Cardiac Radionuclide Imaging and Cost

Effectiveness

May 1982

NTIS order #PB82-239989
THE IMPLICATIONS OF

COST-EFFECTIVENESS

ANALYSIS OF

MEDICAL TECHNOLOGY

MAY 1982

BACKGROUND PAPER #2: CASE STUDIES OF

MEDICAL TECHNOLOGIES

CASE STUDY #13: CARDIAC RADIONUCLIDE IMAGING

AND COST EFFECTIVENESS

William B. Stason, M. D., S.M.

Associate Professor of Health Policy and Management

Center for the Analysis of Health Practices

Harvard School of Public Health

and

Director of Health Services Research

VA Outpatient Clinic

Boston, Mass.

Eric Fortess, M. P. H., S.M.

Center for the Analysis of Health Practices

Harvard School of Public Health

Boston, Mass.

OTA Background Papers are documents that contain information believed to be

useful to various parties. The information under-girds formal OTA assessments or is

an outcome of internal exploratory planning and evaluation. The material is usually

not of immediate policy interest such as is contained in an OTA Report or Technical

Memorandum, nor does it present options for Congress to consider.

CONGRESS OF THE UNITED STATES

Office of Technology Assessment

Washington, D C 20510
Library of Congress Catalog Card Number 80-600161

For sale by the Superintendent of Documents,

U.S. Government Printing Office, Washington, D.C. 20402
This case study is one of 17 studies comprising Background Paper #2 for OTA’s

assessment, The Implications of Cost-Effectiveness Analysis of Medical Technology.

That assessment analyzes the feasibility, implications, and value of using cost-effectiveness and cost-benefit analysis (CEA/CBA) in health care decisionmaking. The major, policy-oriented report of the assessment was published in August 1980, In addition

to Background Paper #2, there are four other background papers being published in

conjunction with the assessment: 1) a document which addresses methodological

issues and reviews the CEA/CBA literature, published in September 1980; 2) a case

study of the efficacy and cost-effectiveness of psychotherapy, published in October

1980; 3) a case study of four common diagnostic X-ray procedures, published in April

1982; and 4) a review of international experience in managing medical technology,

published in October 1980. Another related report was published in September of 1979:

A Review of Selected Federal Vaccine and Immunization Policies.

The case studies in Background Paper #,2: Case Studies of Medical Technologies

are being published individually. They were commissioned by OTA both to provide

information on the specific technologies and to gain lessons that

the broader policy aspects of the use of CEA/CBA. Several of the

cally requested by the Senate Committee on Finance.

Drafts of each case study were reviewed by OTA staff; by

could be applied to

studies were specifimembers of the advisory panel to the overall assessment, chaired by Dr. John Hogness; by members of

the Health Program Advisory Committee, chaired by Dr. Frederick Robbins; and by

numerous other experts in clinical medicine, health policy, Government, and economics. We are grateful for their assistance. However, responsibility for the case studies remains with the authors.

Directo r
Cost= Effectiveness Analysis of Medical Technology

John R. Hogness, Panel Chairman

President, Association of Academic Health Centers

Stuart H. Altman

Dean

Florence Heller School

Brandeis University

James L. Bennington

Chairman

Department of Anatomic Pathology and

Clinical Laboratories

Children's Hospital of San Francisco

John D. Chase

Associate Dean for Clinical Affairs

University of Washington School of Medicine

Joseph Fletcher

Visiting Scholar

Medical Ethics

SChool of Medicine

University of Virginia

Clark C. Havighurst

Professor of Law

School of Law

Duke University

Sheldon Leonard

Manager

Regulatory Affairs

General Electric Co.

Barbara J. McNeil

Department of Radiology

Peter Bent Brigham Hospital

Robert H. Moser

Executive Vice President

American College of Physicians

Frederick Mosteller

Chairman

Department of Biostatistics

Harvard University

Robert M. Sigmond

Advisor 0)1 Hospital Affairs

Blue Cross and Blue Shield Associations

Jane Sisk Willems

VA Scholar

Veterans Administration

.
Joyce C. Lashof* and H. David Banta, ** Assistant Director,

Health and Life Sciences Division, OTA

H. David Banta* and Clyde J. Behney, ** Health Program Manager

Clyde J. Behney, Project Director

Kerry Britten Kemp, *** Editor

Virginia Cwalina, Research Assistant

Shirley Ann Gayheart, Secretary

Nancy L. Kenney, Secretary

Martha Finney, * * * Assistant Editor

Other Contributing Staff

Bryan R. Luce Lawrence Miike Michael A. Riddiough

Leonard Saxe Chester Strobel***

OTA Publishing Staff

John C. Holmes, Publishing Officer

John Bergling Kathie S. Boss Debra M, Datcher Joe Henson

‘Untd December 1981.

“ ‘From December 1981.

● ” “OTA contract personnel
This case study is one of 17 that comprise

Background Paper #2 to the OTA project on the

lmplications of Cost-Effectiveness Analysis of

Medical Technology. * The overall project was

requested by the Senate Committee on Labor

and Human Resources. In all, 19 case studies of

technological applications were commissioned

as part of that project. Three of the 19 were specifically requested by the Senate Committee on

Finance: psychotherapy, which was issued separately as Background Paper #3; diagnostic Xray, issued as Background Paper #5; and respiratory therapies. The other 16 case studies were

selected by OTA staff.

In order to select those 16 case studies, OTA,

in consultation with the advisory panel to the

overall project, developed a set of selection

criteria. Those criteria were designed to ensure

that as a group the case studies would provide:

●

●

●

●

●

●

●

examples of types of technologies by function (preventive, diagnostic, therapeutic,

and rehabilitative);

examples of types of technologies by physical nature (drugs, devices, and procedures);

examples of technologies in different stages

of development and diffusion (new, emerging, and established);

examples from different areas of medicine

(such as general medical practice, pediatrics, radiology, and surgery);

examples addressing medical problems that

are important because of their high frequency or significant impacts (such as

cost);

examples of technologies with associated

high costs either because of high volume

(for low-cost technologies) or high individual costs;

examples that could provide informative

material relating to the broader policy and

methodological issues of cost-effectiveness

or cost-benefit analysis (CEA/CBA); and

● examples with sufficient evaluable literature.

On the basis of these criteria and recommendations by panel members and other experts,

OTA staff selected the other case studies. These

16 plus the respiratory therapy case study requested by the Finance Committee make up the

17 studies in this background paper.

All case studies were commissioned by OTA

and performed under contract by experts in academia. They are authored studies. OTA subjected each case study to an extensive review

process. Initial drafts of cases were reviewed by

OTA staff and by members of the advisory

panel to the project. Comments were provided

to authors, along with OTA’s suggestions for

revisions. Subsequent drafts were sent by OTA

to numerous experts for review and comment.

Each case was seen by at least 20, and some by

40 or more, outside reviewers. These reviewers

were from relevant Government agencies, professional societies, consumer and public interest

groups, medical practice, and academic medicine. Academicians such as economists and decision analysts also reviewed the cases. In all,

over 400 separate individuals or organizations

reviewed one or more case studies. Although all

these reviewers cannot be acknowledged individually, OTA is very grateful for their comments and advice. In addition, the authors of

the case studies themselves often sent drafts to

reviewers and incorporated their comments.

‘Office of Technology Assessment, U.S. Cc>ngress, T/Ic fttlpl/cLJti(l)]s of C(>st-Eff(JctIIIe~1(Ts5 AtIu/ym of i$4dIcL?/ T(Y/Imd(>~y GPO

stock N(). 052-003 -0076 S-7 ( Washington, D. c.: U.S. Governrnen t

[’rlntlng of}]ce, August 1980).

vii
The case studies were selected and designed to

fulfill two functions. The first, and primary,

purpose was to provide OTA with specific information that could be used in formulating.

general conclusions regarding the feasibility and

implications of applying CEA/CBA in health

care. By examining the 19 cases as a group and

looking for common problems or strengths in

the techniques of CEA/CBA, OTA was able to

better analyze the potential contribution that

these techniques might make to the management

of medical technologies and health care costs

and quality. The second function of the cases

was to provide useful information on the specific technologies covered. However, this was

not the major intent of the cases, and

Some of the case studies are formal CEAs or

CBAs; most are not. Some are primarily concerned with analysis of costs; others are more

concerned with analysis of efficacy or effectiveness. Some, such as the study on end-stage

renal disease, examine the role that formal

analysis of costs and benefits can play in policy

formulation. Others, such as the one on breast

cancer surgery, illustrate how influences other

than costs can determine the patterns of use of a

technology. In other words, each looks at evaluation of the costs and the benefits of medical

technologies from a slightly different perspec

j

tives in order to gain a feeling for the potential

role that CEA/CBA can or cannot play in health

care and to better understand the difficulties and

complexities involved in applying CEA/CBA to

specific medical technologies.

The 17 case studies comprising Background

Paper #2 (short titles) and their authors are:

Artificial Heart: Deborah P. Lubeck and John P.

Bunker

Automated Multichannel Chemistry Analyzers:

Milton C. Weinstein and Laurie A, Pearlman

Bone Marrow Transplants: Stuart O. Schweitzer and C. C. Scalzi

Breast Cancer Surgery: Karen Schachter and

Duncan Neuhauser

Cervical Cancer Screening: Bryan R. Luce

Cimetidine and Peptic Ulcer Disease: Harvey V.

Fineberg and Laurie A. Pearlman

Colon Cancer Screening: David M. Eddy

CT Scanning: Judith L. Wagner

Elective Hysterectomy: Carol Korenbrot, Ann

B. Flood, Michael Higgins, Noralou Roos,

and John P. Bunker

End-Stage Renal Disease: Richard A. Rettig

Gastrointestinal Endoscopy: Jonathan A. Showstack and Steven A. Schroeder

Neonatal Intensive Care: Peter Budetti, Peggy

McManus, Nancy Barrand, and Lu Ann

Heinen

Nurse Practitioners: Lauren LeRoy and Sharon

Solkowitz

Orthopedic Joint Prosthetic Implants: Judith D.

Bentkover and Philip G. Drew

Periodontal Disease Interventions: Richard M.

Scheffler and Sheldon Rovin

Selected Respiratory Therapies: Richard M.

Scheffler and Morgan Delaney

These studies will be available for sale by the

Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402.

Call OTA’s Publishing Office (224-8996) for

availability and ordering information.
Case Study #13

Cardiac Radionuclide Imaging

and Cost Effectiveness

William B. Stason, M. D., S.M.

Associate Professor of Health Policy and Management

Center for the Analysis of Health Practices

Harvard School of Public Health

and

Director of Health Services Research

VA Outpatient Clinic

Boston, Mass.

Eric Fortess, M. P. H., S.M.

Center for the Analysis of Health Practices

Harvard School of Public Health

Boston, Mass.

AUTHORS’ ACKNOWLEDGMENTS

The authors wish to thank the many physician experts and users of radionuclide

imaging and employees of the companies cited in this case study for the information

they provided through interviews and questionnaires. We also thank Helen Oskin,

Leslie Stein, and Laurie Pearlman for their expert assistance in manuscript preparation.

94-351 0 - 82 - 2
Contents

Page

Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Cardiac Radionuclide Imaging–A New Technology

in Need of Scrutiny. . . . . . . . . . . . . . . . . . . . . . . . . . . 4

The Technology—Past, Present, and Future . . . . . . . . . . 5

Past . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Present . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Future . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

The Market and the Industry . . . . . . . . . . . . . . . . . . . . . . . 12

The Market . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

The Industry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

The Producers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Users and Uses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Data Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Users . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Clinical Indications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Potential Target Populations for Cardiac Imaging. . . 17

Potential Demand for Cardiac Imaging. . . . . . . . . . . . 18

Costs and Charges. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Costs of a Radionuclide Laboratory . . . . . . . . . . . . . . 19

Unit Costs of Cardiac Imaging Procedures . . . . . . . . . . 23

Current Charges for Cardiac Imaging Procedures. . . . 25

Clinical Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Medical Literature: Overview. . . . . . . . . . . . . . . . . . . 27

Diagnostic Information. . . . . . . . . . . . . . . . . . . . . . . . . . 28

Cardiac Imaging Procedures: Review of the

Medical Literature . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Technical Challenges and Interobserver Variability.. 37

Potential Risks From Cardiac Imaging . . . . . . . . . . . . 37

Cost-Effectiveness Analysis. . . . . . . . . . . . . . . . . . . . . . 39

Framework for Analysis. . . . . . . . . . . . . . . . . . . . . . . . . 39

Cost Effectiveness of Cardiac Radionuclide Imaging. 41

Policy Implications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

Appendix A.—Glossary of Terms. . . . . . . . . . . . . . . . . . . 48

Appendix B.—Manufacturers of Cardiac

Radionuclide Imaging Equipment and Supplies . . . . . 49

References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

LIST OF TABLES

Table No. Page

l. Cardiac Radionuclide Imaging Techniques. . . . . . . . 7

2. Estimated Markets for Nuclear Imaging Equipment. 12

3. Ranks and Market Shares of Producers of

Nuclear Imaging Equipment . . . . . . . . . . . . . . . . . . . 14

4. Clinical Indications for Cardiac Radionuclide

Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

5. Deaths From Coronary Artery Disease, 1970-77. . . 17

6. Death Rates From Coronary Artery Disease,

1970-77. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

7. Prevalence and Morbidity Data for Coronary

Artery Disease, 1972. . . . . . . . . . . . . . . . . . . . . . . . . . . 18

8. Hospital Discharges for Coronary Artery

Disease, 1969-77. . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

9. Projected ’’Demand’’ for Cardiac Imaging. . . . . . . . 19

Table No. Page

10. List Prices of Selected Equipment Suitable

for Cardiac Radionuclide Imaging . . . . . . . . . . . . . . 20

11. Estimated Annual Fixed Costs of Operating

a Radionuclide Imaging Laboratory. . . . 21

12. List Prices of Radionuclides and Cold Product Kits. 22

13. Production Capacity for Cardiac Imaging

Procedures . . . . . . . 23

14. Personnel Time Required for Different Cardiac

Imaging Procedures and Estimated Cost

Equivalents . . . . . . . . . . . 24

15. Unit Costs of Cardiac Imaging Procedures

Assuming Maximal Production Efficiency. . . . 24

16. Suggested Fee Schedules for Cardiac Imaging

Procedures. . . . . . . . . . 26

17. Breakeven Points for Laboratory Operation . . . . . . . 26

18. Thallium-201 Perfusion Scans in the Diagnosis of

19

20

21

22.

23.

24,

25.

26,

27,

28.

29,

30.

Coronary Artery Disease. . . . . . . 32

Technetium-99m Radionuclide Angiography in

the Diagnosis of Coronary Artery Disease. . . 33

Technetium-99m Stannous Pyrophosphate and

Thallium-201 Perfusion Scans in the Diagnosis

of Acute Myocardial Infarction. 35

Thallium-201 Perfusion Scans in the Evaluation

of Coronary Artery Bypass Surgery Results. 36

Technetium-99m Pyrophosphate Scans in

Patients Who Have Had Coronary Artery

Bypass Surgery . . . . . . . . . . . . . . . . . . . 37

Radiation Exposure From Cardiac Radionuclide

Imaging and Selected Radiodiagnostic Procedures. 38

Effectiveness of Alternative Strategies Employing

Cardiac Imaging and Exercise Tolerance Testing To

Diagnose Surgically Treatable Coronary Artery

Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Costs of Alternative Strategies to Diagnose

Surgically Treatable Coronary Disease . . . . . . . . . . . 44

Costs and Effectiveness of Alternative Strategies

To Diagnose Surgically Treatable Coronary Disease 44

Cost Effectiveness of Alternative Diagnostic

Strategies . . . . . . . . . . . . . 45

Cost-Effectiveness Comparisons Between

Alternative Diagnostic Strategies. . 45

Costs and Effectiveness of Alternative Strategies

Employing Cardiac Imaging To Diagnose Surgically

Treatable Coronary Artery Disease in Population

Subgroups . . . . . . . . . . . . . . . . . . . . . . . . . 46

Cost-Effectiveness Comparisons Across Population

Subgroups . . . . . . . . . . . 46

FIGURE

Figure No. Page

1. Schematic Diagram of a Radionuclide Imaging

System . . . . 6
Cardiac Radionuclide Imaging

and Cost Effectiveness

William B. Stason, M. D., S.M.

Associate Professor of Health Policy and Management

Center for the Analysis of Health Practices

Harvard School of Public Health

and

Director of Health Services Research

VA Outpatient Clinic

Boston, Mass.

Eric Fortess, M. P. H., S.M.

Center for the Analysis of Health Practices

Harvard School of Public Health

Boston, Mass.

SUMMARY

Cardiac radionuclide imaging is a new and

rapidly expanding diagnostic technology that

promises to make significant contributions to

the diagnosis and management of heart disease.

Dynamic changes are occurring in the technology at the same time diffusion is taking place.

The combination of diffusion and technological

development creates an imperative for careful

evaluation and prospective planning.

Clinical applications of cardiac imaging include the diagnosis of coronary artery disease,

evaluation of cardiac function abnormalities,

verification of the diagnosis of acute myocardial

infarction (heart attack), and monitoring of patients under treatment for establishing cardiac

disease. * In 1978, an estimated 227,000 cardiac

scans were performed, and expenditures for nuclear imaging equipment and radionuclides were

$225 million. About $100 million of these expenditures can be ascribed to cardiac imaging.

Projected figures for 1981 are for 1.5 million cardiac scans and total of about $425 million. The

potential target population for cardiac imaging

‘Definitions of some of the medical terms used in this case study

are provided in app. A .

in the United States includes 12 million persons

with suspected or established coronary artery

disease and an additional 80 million asymptomatic adults 40 years of age or older who might

become candidates for coronary disease screening programs.

The nuclear imaging equipment industry is

highly competitive. The same is generally true of

the radiopharmaceutical industry, the exception

being the existence of a virtual monopoly for the

production of one widely used radioisotope

(thallium-201).

Capital costs to establish a radionuclide laboratory range from $100,000 to well over

$500,000. Certificate-of-need determination can

be avoided by establishing a laboratory stepwise, and it is doubtful whether the “new service” rule would apply. The resource costs of individual scanning procedures range from $72 to

$258; recommended charges range from $155 to

$405. This apparent discrepancy between costs

and charges deserves further exploration.

The efficacy of cardiac imaging techniques in

identifying physiologically significant coronary

disease appears to be at least equal to, and prob3
ably greater than, the efficacy of the exercise tolerance test. Furthermore, for assessing ventricular function, the radionuclide ventriculogram is

comparable to the more invasive ventricular angiogram.

Before imaging techniques are widely applied

to individuals with suspected or established cardiac disease, however, several important questions need to be answered. First, their performance in nonselected populations needs to be determined. Most studies to date have been done in

patients with significant heart disease referred

for cardiac catheterization. In patients who have

minimal or no symptoms, sensitivities and specificities may well be lower. Second, the effectiveness and safety of imaging techniques when used

in everyday practice by physicians need to be

evaluated, It is not at all certain that results obtainable by the experts who publish their results

will be obtainable by average physicians. Third,

important questions remain about how information from these tests will be used to benefit the

patient. Test information is of little value unless

it leads to better treatment decisions. Finally,

important policy questions arise over utilization

and quality control, reimbursement, and future

research priorities. What means, if any, should

be implemented to avoid excessive utilization?

How can quality control, including avoidance of

radiation hazards, be maintained in the face of

rapid diffusion? Should standard policies concerning reimbursement be developed, and could

these policies be used to influence utilization? To

what extent should the further development of

existing and new technologies be encouraged?

All of these questions deserve careful examination by the medical profession and by the

Federal Government.

CARDIAC RADIONUCLIDE IMAGING–A NEW

TECHNOLOGY IN NEED OF SCRUTINY

Cardiac radionuclide imaging encompasses a

variety of techniques designed to provide information of value in detecting the presence and extent of cardiac disease. All of these techniques

are noninvasive and relatively risk free. All entail the injection of a radiopharmaceutical, its

distribution to the myocardium (heart muscle)

or throughout the blood pool, and the external

detection of radioactivity by means of a gamma

scintillation camera. Cardiac radionuclide imaging techniques represent additions to the cardiologist’s already extensive diagnostic armamentarium, which includes the medical history and

physical examination, resting electrocardiogram

(EKG), chest X-ray, exercise tolerance test, echocardiography, and cardiac catheterization with

coronary angiography.

The ultimate value of cardiac radionuclide imaging will have to be evaluated in terms of the

information the technology can provide to the

diagnosis and treatment of patients with heart

disease. Questions of cost, long-term risks of

low-level radiation exposure, and the ability of

radionuclide techniques to substitute for existing

diagnostic modalities all need to be examined.

Why is evaluation of this technology important and timely? First, cardiac radionuclide imaging is experiencing an extraordinary rapid diffusion. An estimated 227,000 cardiac scans were

performed in 1978, and 1.5 million scans were

projected for 1981 (21). Commensurate growth

is occurring in the domestic market for radionuclide imaging equipment and radiopharmaceuticals. In 1978, this market was $225

million. It was estimated that by 1981, with a

projected annual growth rate of 25 percent, the

market would reach $425 million. Cardiac imaging provides by far the major impetus for this

growth.

Second, diffusion of this technology is occurring at a time when the virtues and limitations of

the various radionuclide imaging procedures

have been evaluated only in highly selected patient populations. Major questions remain to be

answered. For example, are current estimates of
the sensitivity and specificity of these tests obtained in patients referred for cardiac catheterization applicable to asymptomatic patients

being screened for possible coronary disease?

Can private practitioners duplicate the results

obtained by experts in tertiary medical centers?

What is the most appropriate diagnostic strategy

for each set of diagnostic challenges?

Third, technological change within radionuclide imaging is proceeding at a dizzying pace,

both through improvements in existing techniques and through the development of new

techniques that promise to provide information

at the level of cellular function, as well as at the

level of organ perfusion and function. Today’s

technology is sure to be outdated tomorrow,

and evaluations done today may quickly become outdated. Ongoing monitoring of the technology will be essential.

Finally, the potential target population for

cardiac radionuclide imaging, in the extreme,

could include 80 million Americans over the age

of 40. Cardiac imaging could, conceivably, replace the EKG as the baseline technique for evaluating the heart. Implications for the cost of

diagnostic services and for the identification of

increased numbers of patients who then would

be offered medical or surgical treatment are

enormous.

There is little question that cardiac radionuclide imaging will play an increasingly important role in the diagnosis of heart disease.

challenge is to define that role in a way

maximizes benefits while controlling risks

costs.

The

that

and

In the next part of this case study, we describe

the dimensions of the technology of cardiac radionuclide imaging. In the four parts that follow, we summarize information on the industry

producing radionuclide imaging equipment, on

clinical applications of technology, and on the

costs and efficacies of the various techniques.

Finally, we present our formulation of some of

the issues involved in the assessment of the technology’s cost effectiveness. Information for this

case study was obtained from a variety of

sources: from a review of the medical literature,

from interviews with industry representatives,

and from experts and users of the technology.

Our ambitions have far exceeded our resources

in performing this study. Though we believe the

information presented to be reliable, we acknowledge that in some respects the report is less

than complete.

THE TECHNOLOGY–PAST, PRESENT, AND FUTURE

Past

Radioactive tracers were first used to study

the heart in 1927, by Blumgart and Weiss. These

investigators used radium as the tracer and a

cloud chamber as a detector (s). In 1954, accumulation of radioactive potassium and its

analogs in the myocardium was demonstrated

(37), and in 1962, rubidium and cesium were applied in myocardial imaging (16). Since that

time, a number of radionuclides and a variety of

techniques have been developed.

Present

General Description of the Technology

Required components for cardiac radionuclide

imaging include a radiopharmaceutical (usually

a gamma emitter), a detector, photomultiplier

tubes and amplifiers, a cathode ray tube for

visualizing the image of the heart, and a computer system to permit storage and analysis of

acquired count information. Figure 1 depicts

these components schematically.

In a typical study, a radiopharmaceutical is

injected into a resting or exercising patient and

distributed to the heart and other tissues according to its chemical and physical characteristics.

Gamma radiation emitted by the radionuclide is

detected externally by either: 1) a scintillation

probe; 2) a rectilinear scanner; or 3) a scintillation camera. For all three detector types, the

operating principle is the same. A photon of

gamma radiation enters the detector and collides

with one or more crystals of sodium iodide. This
Figure 1 .-Schematic Diagram of a Radionuclide Imaging System

collision causes a tiny flash of light which is

sensed by a photomultiplier tube and converted

to an electronic signal. The electronic signal, in

turn, passes to amplifiers and through logic electronics which determine the point of origin within the patient’s body. The readout device displays an image of the heart constructed from

many thousands of these radiation photons, or

“counts. ” This image can be preserved on film or

by feeding the count data to a computer for

mathematical manipulation, analysis, and storage on a magnetic tape or disk.

The three classes of detectors—scintillation

probes, rectilinear scanners, and scintillation

cameras—vary in sensitivity to gamma emissions and ability to achieve spatial resolution.

The tradeoff between sensitivity and resolution

for any given gamma detector can be adjusted

by use of different collimators. (A collimator,

basically, is a device used to control the incoming gamma photons, very much in the same way

that the aperture is used to control the amount

of light entering a camera. It will decrease the

sensitivity of the detector by decreasing the

number of photons that are permitted to reach

the sodium iodide crystal. At the same time,

however, the origin of the photons that do pass

through can be more accurately localized within

the body. ) The scintillation probe is usually used

with a flat field collimator which provides very

high sensitivity to photons anywhere within its

field of view. The rectilinear scanner uses a

focused collimator, which lowers sensitivity.

The scintillation camera is the least sensitive of

the three detectors, but does offer the best spatial resolution. With or without a computer, this

is the most commonly used

radionuclide studies.

Imaging Techniques

Table 1 summarizes the

detector for cardiac

currently available

imaging techniques and indicates the types of information each provides. These techniques are

described below.

Thallium-201 (T1-201) Perfusion Images.—

Thallium chloride (T1-201) is a radionuclide that,

when injected intravenously, behaves as an analog of potassium. It has a half-life of 74 hours

and must be generated by a cyclotron or linear

accelerator. Initial distribution within the body

is related to regional perfusion and to the

cellular extraction efficiency of the various

organs. The myocardium (heart muscle) has a

very high extraction efficiency (85 percent).

Thus, initial distribution is very closely related

to blood flow. Areas of the myocardium that are

well perfused will have a high concentration of

thallium ion, while areas that are less well perfused will have lower concentrations. It is this

relation of accumulation to perfusion that provides the clinical utility of cardiac radionuclide

imaging with thallium. Thallium images can be

performed at rest or during exercise as separate
Table 1 .—Cardiac Radionuclide Imaging Techniques

Technique Information content Identifies

Thallium (TI-201) perfusion studies

Resting Perfusion defects at rest Severe ischemia at rest

Old or recent infarct

Exercise Perfusion defects under Transient ischemia

stress Old or recent infarct

Rest-exercise (2-dose) Both of the above Differentiate transient

ischemia from infarct

Exercise-redistribution Both oft he above Same as rest-exercise

Technetium (Tc-99m) ventriculographic studies

First-pass: resting and

exercise Blood transit times Ventricular function

Ejection fraction abnormalityies

Chamber volumes Wall motion abnormalities

Wall motion Ventricular aneurysms

Multiple-gated acquisition Valvular regurgitation

(MUGA): resting and Intracardiac shunts

exercise Same Same except shunts not

Infarct (“hot spot”) identifiable

imaging Acutely damaged myocardium Acute myocardial infarcTomographic methods

Single-photon emission tomography

Single-photon gated blood pool tomography

Positron emission transaxial tomography (PETT)

Computed axial tomography (CAT)

studies, or in combination in so-called exerciseredistribution studies.

In a resting study, the patient is injected with 1

to 2 mCi of thallium, and 10 to 15 minutes later,

counting is begun. Two or three separate views

are obtained with the camera in different positions relative to the heart, each requiring 10 to

15 minutes counting time to obtain a high-quality image. Perfusion “defects” on images taken

with the patient at rest represent areas of myocardial damage (old or recent infarctions) or severe ischemia.

Exercise is usually required, however, to induce the transient ischemia that has its clinical

equivalent in angina pectoris. In an exercise

study, the thallium dose is injected during stress,

and the image is obtained immediately thereafter. The stress is provided by exercise on a

bicycle ergometer or treadmill or by pharmacological means with a vasodilator (e.g., dipyridamole). A disadvantage of obtaining an exercise

thallium scan alone is that no distinction can be

made between perfusion defects caused by infarction from those due to transient ischemia.

Comparison of the rest and exercise images, on

the other hand, helps make this distinction between fixed and transient defects. A patient with

tion (after 24 hours)

transient ischemia will have a normal resting

scan but show detectable defects on the exercise

scan. A patient with a myocardial infarction will

show a defect on the resting scan and show new

or enlarged defects with exercise if transient

ischemia is produced.

The exercise-redistribution study allows one

to obtain both rest and exercise information

with a single dose of thallium. The patient is exercised, injected with thallium, and scanned as

in an exercise study. Two to four hours later, a

second image is obtained (without further administration of thallium) while the patient is at

rest. A patient with transient ischemia will show

defects on the exercise image but reduced or no

defects after “redistribution” occurs. A patient

with infarcted tissue only will show similar defects on both images. The physiologic explanation for the redistribution of thallium is not completely understood, but may relate to residual

thallium activity in the blood, greater cellular

extraction of thallium by ischemic tissue as the

ischemia resolves during rest, and/or to decreased loss of thallium from the ischemic area.

Technetium (Tc99m) Studies.—Technetium is

used in combination with a variety of chemical
and physiological substrates to assess cardiac

function abnormalities. It is marketed in the

form of a molybdenum technetium generator,

containing molybdenum-99m on an alumina

column; technetium-99m is eluted when sterile

saline is passed through the column. Molybdenum has a half-life of 67 hours, requiring

weekly replacement of the generator, and the

eluted technetium has a half-life of only 6 hours.

The radionuclide may also be supplied as “instant technetium, ” which must be delivered

daily.

Unlike thallium, which is injected directly as

the chloride salt, technetium must be used in

conjunction with a “cold mix” or “cold imaging

agent”-a compound whose biological behavior

in the patient’s body will cause the radionuclide

to be carried to the desired organ sites. In the

case of cardiac studies, the “cold mix” causes the

technetium to become attached to red blood cells

or albumin and hence to remain the blood pool.

Technetium studies assess cardiac function

and infer from observed abnormalities the underlying cause and extent of disease. Parameters

measured include global and regional ejection

fractions (the amount of blood ejected during a

heart beat), abnormalities in myocardial contractility (wall motion abnormalities), cardiac

output and transit times, and the presence of intracardiac shunts. Studies may be performed

during exercise to uncover abnormalities not

present at rest. At rest, for example, a patient’s

ejection fraction may be normal; during exercise, though, a normal person’s ejection fraction

will rise, while that of a person with heart disease may remain unchanged or even fall.

As a group, the technetium studies discussed

below require much more sophisticated computer and software capabilities than do thallium

studies.

First-pass studies, —In 1969, Mullins demonstrated the passage of a radionuclide through the

heart synchronized with an EKG. Counts from

several cycles at end-diastole and several at endsystole were summed, and the resultant images

were used to calculate heart chamber volumes

(49). More recently, methods have been developed to calculate ejection fraction directly from

the count activity in the chambers using a multicrystal scintillation camera and a computer

(11,68,75,87).

A first-pass study is performed by rapidly injecting a small bolus of technetium-labeled imaging agent (technetium pertechnetate) and scanning the patient as this material passes through

the heart. Because only the first passage of the

radionuclide through the heart is recorded, scanning can be performed in as little time as 1

minute. Several complete cardiac cycles are

summed to create a “typical” cycle with enough

counts to produce a well-resolved image. Both

right and left ventricles can be evaluated from

separate activity curves. If, in addition, the

regional wall motion of the ventricles is to be

assessed for abnormalities in contraction, multiple views of the heart maybe required. The brief

duration of the first-pass study allows only one

viewing angle per injection. Thus, a second or

even third injection of radionuclide is required

to obtain the additional views. These can be obtained readily at a single sitting, however,

because technetium pertechnetate is rapidly

cleared from the blood pool.

Multiple-gated acquisition (MUGA) studies.

—Instead of gathering data on the first pass of

technetium through the heart, a MUGA study

measures activity of the radionuclide after it has

equilibrated in the pool of circulating blood. The

word “gated” refers to the synchronization of

the scintillation camera computer system with

the R wave of EKG. Counts obtained during different phases of the cardiac cycle are summed

over many beats, permitting generation of a

high-resolution image of a moving organ. The

same measures of cardiac function are calculated

in MUGA studies as in first-pass studies, except

that intracardiac shunts cannot be derived.

The MUGA study technique requires the patient to be injected with pyrophosphate, followed 15 minutes later by a saline solution containing 20 to 25 mCi of technetium-99m. One or

more views are then obtained, depending on the

purpose of the study; each view requires 5 to 10

minutes of counting time. With appropriate instructions for “area of interest” determination

and background subtraction, the computer cal-
culates desired measurements. In addition, the

data from summed “representative” beats can be

played as a motion picture of the contracting

heart to estimate wall motion abnormalities.

Again, studies can be done at rest and during exercise to examine the effect of stress on ejection

fraction and regional wall motion.

Infarct (“hot spot”) imaging, —This technique

depends on the affinity of certain substances for

recently damaged areas of myocardium and can

be used to facilitate the diagnosis of acute myocardial infarction. Mercury-203-labeled chlormeridin (17), Tc-99m tetracycline (40), and,

most recently, Tc-99m pyrophosphate (29) have

all been used for this purpose.

The radiopharmaceutical is injected, and

scanning is performed 2 to 3 hours later. Both

the location and area of an infarct can be estimated. For maximal sensitivity, scans should be

performed at least 24 hours after an infarction.

The major applications of the technique appear

to be to provide information useful to guide

treatment decisions in patients admitted with

suspected myocardial infarctions (e. g., early

transfer from the coronary care unit).

Tomographic Methods.—The studies discussed to this point provide data in a two-dimensional format. Tomographic methods, discussed briefly below, address the need for a

three-dimensional perspective.

The output of tomographic methods is a set of

“slices” through the volume of the heart. If a

thread were drawn vertically from top to bottom of the heart through the center of its volume

to form an “axis,” the tomograph would produce slices perpendicular to this axis (hence the

derivation of the adjective “transaxial”). Each

slice is rotated 900 to place it in the plane of the

screen or photograph, and ordered so that the

viewer is able to examine contiguous cross-sections of the heart.

The tomographic methods discussed briefly

below are: 1) techniques using single-photon

gamma radiation emiters; 2) a technique using a

two-photon emitter called positron emission tomography; and 3) an X-ray technique, computed-axial tomography (CAT) scanning. In

general, these techniques either have had less extensive clinical evaluations than the perfusion

and blood pool studies described above or are in

experimental phases. They are important, however, because they represent probable future

directions for the technology.

Single-photon emission tomography. —There

are two variants of this. One method uses a multiple-pinhole collimator in conjunction with a

standard single-crystal gamma camera to obtain

tomograms of the heart. With this technique,

using thallium as the radionuclide, greatly increased sensitivity in detecting significant coronary artery obstruction has been reported (80).

The second variant employs a “radionuclide

body function imager” which has 10 detectors

mounted on ring-shaped gantry into which the

patient is placed. The multiple-detector array

permits rapid imaging (20 to 30 minutes for a

complete set of images). Early results suggest

that this technique, again using thallium-201,

produces images superior to those of nontomographic techniques (32).

Single-photon gated blood pool tomography

with technetium is in an early stage of development, but appears to have considerable potential.

Positron emission tomography. —Doublephoton emission tomography, or positron-emision transaxial tomography (PETT), uses radionuclides characterized by a short half-life, which

emit positrons or anti-electrons. When a positron combines with an electron in its immediate

environment, “annihilation” occurs, and a pair

of gamma rays is generated, each of which travels outward from the origin in an opposite direction from the other. Very accurate localization is

achieved by “coincidence counting” on two

detector plates 180° apart. Only those events

that produce gamma rays that strike both detectors at the same time are counted and used to

build up tomographic images. Radionuclides are

incorporated into biologically active elements

and compounds, which can then be used to

evaluate myocardial perfusion and metabolism.

Carbon-n-labeled palmitate, a physiological

substrate of the myocardium, for example, can
be used to image infarcts as tomographic “cold

spots” (72), and nitrogen-13-labeled ammonia

has been reported as highly sensitive to perfusion abnormalities (25).

The half-lives of positron-emitting radiopharmaceuticals are extremely short: 2 minutes for

oxygen-15, 10 minutes for nitrogen-13, and 20

minutes for carbon-n. These short half-lives

greatly reduce the radiation dose to the patient

and allow repeat scans in the same patient every

20 to 30 minutes. However, they require that

centers performing positron scanning have onsite access to a cyclotron, which is required to

produce most of the radio-labeled compounds.

The first two operational PETT instruments

were installed in 1974, one at the Massachusetts

General Hospital in Boston and one at Washington University in St. Louis, Mo. Since then, between 12 and 20 centers in the United States

have acquired units. All of these are used primarily in research activities.

Computed-axial tomography (CAT).–CAT

scanning is a radiologic rather than a radionuclide method. The scanner rotates about the

patient’s body to produce a tomographic slice

that is based on the varying X-ray densities of

the body organs and their components. Recent

technologic improvements have reduced required scanning times to fractions of seconds

and permitted electrocardiographic gating for

longer duration CAT scanning of the heart. Efforts to detect and size infarcts thus far have indicated that CAT scanning tends to underestimate the size of infarcts (27,70). Concomitant

use of contrast material may improve resolution. However, a device called the dynamic spatial reconstructor, recently installed at the Mayo

Clinic, permits a slice to be obtained in onehundredth of a second and creates the potential

for much more sophisticated studies. The dynamic spatial reconstructor was built at a cost of

about $3 million.

The existence in the United States of over

1,100 CAT scanners suggests that there will be

ample incentive to press forward with cardiac

applications.

Future

Future development of cardiac radionuclide

imaging will involve improvements in each of

the components of present scanning systems—

the camera, the computer, and the radionuclide.

In addition, positron emission tomography,

single-photon emission tomography, and CAT

scanning undoubtedly will undergo further technological development and extensive clinical

evaluations.

Camera

Improved counting efficiency and the resulting improved spatial resolution are major goals.

At present, only the multicrystal camera has a

counting efficiency sufficient for good resolution

on first-pass studies. The more commonly used

single-crystal (Anger) camera, with an efficiency

of only 1 percent (50,000 to 100,000 counts per

second), has proven very marginal on first-pass

studies. Changes in the camera, coupled with the

application of multiple-aperture pinhole tomography, may help to resolve these deficiencies.

The possibility of new types of detectors, such as

those having a digital solid-state design, is also

being explored.

Computer Hardware and Software

The development of computers will continue

to follow two divergent trends. One trend is toward large central processing units capable of

accumulating, manipulating, and storing large

amounts of data. The other is toward small remote computers, coupled with a scintillation

camera, for data acquisition and limited manipulation or input into a central processing unit.

Computers will increase in specialization, become more operator-oriented, and require less

technical knowledge to operate. The trend toward more expensive installations will be fostered by the desire for greater capability to do

highly sophisticated quantitative studies, while

the impetus toward development of small, easyto-operate units will be led by industry’s interest

in cultivating the broader market represented by

physicians’ offices and community hospitals.
Progress is being and will continue to be made

in improving the software packages needed for

cardiac radionuclide studies. Similarly, the

quantification and successful application of the

radioisotopic tomographic techniques and gated

CAT scanning will depend on the development

of highly sophisticated computer algorithms.

Better methods for background subtraction,

count smoothing, color images keyed to count

density, automatic chamber border definition,

and arrhythmia discarding are among the features that are being developed.

Radionuclides

An ideal radionuclide would have the following

●

●

●

●

●

●

No

properties:

gamma photon energy in the 100 to 300

KeV range to minimize attenuation by surrounding tissue;

absence of beta or beta-like radiation;

a physical half-life (T1⁄2) of 1 to 30 minutes

to permit multiple views with a single injection, while minimizing the total radiation

dose;

generator systems (similar to technetium)

having long-lived parent elements to obviate the need for onsite cyclotrons or linear

accelerators;

a high target-organ-to-background ratio;

and

low cost and wide availability.

ideal isotope currently exists, but several

possibilities are-being investigated. Among these

are germanium (parent) -gallium (T1⁄2 = 1 hour)

and strontium (T% = 25 days)-rubidium 82 (T1⁄2

= 75 seconds).

Emerging Technologies

The technetium gated blood pool (MUGA)

study will improve in sensitivity, specificity, and

information content. Advocates believe that

MUGA studies may supplant the standard thallium perfusion studies on the basis of their greater

information content, less expensive radionuclide, and reduced patient radiation dose. Thallium perfusion study advocates do not agree.

In the near future, single-photon tomographic

methods will compete with radionuclide ventriculography and may well supplant standard perfusion techniques. It is not clear which of the

two single-photon methods will have wider use.

The seven-pinhole tomographic method is attractive, because it can be used with standard

scintillation cameras and computers, with the

addition of only a seven-pinhole collimator and

software packages (available for about $11,000).

The software for gated blood pool tomography

also is being developed. The revolving-head,

single-photon tomographic imager may produce

even better resolution than seven-pinhole tomography, but it is more expensive (current cost

about $400,000).

In the more distant future, PETT (positronemission transaxial tomography) may play a

large role in cardiac diagnosis because of its ability to provide information on cardiac structure,

function, and metabolism. The requirements for

an onsite cyclotron and for sophisticated hardware result in a startup cost of $1.5 to $2 million.

The general opinion expressed by experts is that

PETT’s dissemination will be limited to selected

tertiary medical centers. However, there is evidence that the size, cost, and complexity of the

technology will be reduced. For example, a Japanese-produced “desk top” cyclotron and positron camera are being marketed by Atomic Energy of Canada in Montreal at a cost of about

$600,000 for the cyclotron and $350,000 for the

camera. If the trend toward lower cost continues, wider dissemination might be anticipated.

The CAT scanner recently installed at the

Mayo Clinic—the dynamic spatial reconstructor

(Raytheon)—has yet to be evaluated. Zeugmatography (nuclear magnetic resonance imaging)

and Fourier rnultiaperture emission tomography

(62) are also in early phases of evaluation. Each

of these technologies merits careful monitoring.
THE MARKET AND THE INDUSTRY

The Market

Nuclear imaging is among the fastest growing

areas in the marketplace for medical equipment.

Within imaging, cardiac procedures lead the

way as the major stimulus for growth. In 1978, it

was estimated that 6.5 million nuclear studies

were performed, of which 227,000 were of the

cardiac system. Projections for 1981 were for a

total of 9.7 million studies (12-percent annual

growth rate), of which 1.5 million would be cardiac scans (71-percent annual growth rate) (21). *

The market for cardiac imaging equipment

has been assessed traditionally in terms of the

number of hospitals that have departments of

nuclear medicine. At present, about half of the

7,100 hospitals in the United States have such

departments. However, large hospitals probably

constitute only a small part of the potential market; small community hospitals and independent

physicians’ practices are increasingly expressing

interest in being able to perform radionuclide

studies. A significant trend in the industry, in

fact, has been to satisfy this burgeoning market

with equipment that is smaller, simpler to operate, and less expensive.

The Industry

The industry can be divided into producers of:

1) gamma scintillation cameras; 2) computers; 3)

radiopharmaceuticals; and 4) ancillary equipment used in conjunction with nuclear medicine

systems. Table 2 summarizes estimated 1978 and

projected 1981 and 1984 unit sales and dollar

volumes for the first three of these market segments (21).

The fastest growing segment of the market is

computer systems, where the major impetus for

growth has been provided by the rapid increase

in cardiac imaging. Nuclear medicine computer

systems, consisting of a minicomputer or microprocessor, memory, storage, CRT display and/

or CRT terminal, retail for $50,000 to $120,000

(1978 prices).

● Another projection, by Market Measures Inc. (1980), was for

650,000 to 830,000 cardiac scans in 1981.

Table 2.—Estimated Markets for

Nuclear Imaging Equipment

Type of equipment 1978Ea

1981 E 1984E

Scintillation camerasb

Number of units in service . . . . 8,000 9,500 11,000

Annual unit sales. . . . . . . . . . . . 800 1,100 1,400

Annual dollar sales (millions). . $85 $150 $225

Computer systems

Number of units in service . . . . 1,000 2,200 4,000

Annual unit sales. . . . . . . . . . . . 275 450 700

Annual dollar sales (millions). . $20 $40 $70

Radiopharmaceuticals

(millions)b

Technetium sales, . . . . . . . . . . $35 $45 –

Cold product kit sales. . . . . . . . 40 80 –

Thallium sales. . . . . . . . . . . . . . 7 35 —

Other sales. . . . . . . . . . . . . . . . . 38 75 —

Total (millions). . . . . . . . . . $225 $425 $295

aE~tlmate~ for Ig78 by IMS, Inc (1979) d!ffer substantially: technetium, $30 rnll”

lion; cold product kits, $18 million; thallium, $7 million; and “other,” $23 roll.

lion; corresponding estimates for 1981 are $42 million, $26 m!lllon, $35 million,

band $30 million respectively,

Includes rectilinear scanners,

SOURCE: F Eberstadt & Co., Inc , 1978,

The camera segment of the market is characterized by expansion in the number of medical

facilities doing imaging, by the upgrading of existing equipment, and by expansion of existing

nuclear medicine laboratories to include more

than one camera/computer unit. Gamma scintillation cameras are being bought to replace rectilinear scanners, and large-field-of-view

cameras (required for multiple-pinhole tomography) are being bought to replace small-fieldof-view cameras. Mobile gamma camera units

are being bought to serve patients who cannot

be transported conveniently to a central nuclear

medicine facility (e. g., patients in emergency

rooms, coronary care units, and operating or

surgical intensive care units). The average price

of a gamma camera in 1978 was $100,000 to

$110,000 . New England Nuclear’s introduction in December 1977 of thallium-201 for cardiac perfusion studies was perhaps the most significant development in the radiopharmaceutical industry.

Of cardiac images done in 1978, nearly half used

thallium. Because thallium perfusion studies do

not require sophisticated computer software,
their growth in the short term will, in all likelihood, keep pace with or exceed the growth of

MUGA technetium studies. With the rapid

growth projected for cardiac images, the thallium market looks robust. Growth in the market

for technetium and cold product kits probably

will be less dramatic, because the frequency of

brain scans using technetium is decreasing and

because other uses of technetium outside cardiology are not rapidly expanding. Between thallium and technetium, there exists a considerable

per-dose price differential. The list price for a

1.65 mCi dose of thallium was recently raised to

over $100, whereas comparable prices per dose

of technetium are in the $8 to $10 range.

The Producers

Producers can be categorized as manufacturers of: 1) scintillation cameras and integrated

systems; 2) computer hardware and software;

and 3) radiopharmaceuticals. Rankings and estimates of percentage of market share of major

producers are presented in table 3. Detailed descriptions of products, manufacturers’ sales,

strategies, and projected future directions are

provided in appendix B.

Data Sources

Data on producers were collected for this case

study from telephone and personal interviews

with company executives (usually the director of

marketing or technical director), from producers’ brochures and annual reports, and from

advertisements in professional and trade journals. Thus, the results presented below reflect

our own interpretations of data from multiple

sources and should not be taken to be official

opinions of the firms concerned. Information

was particularly difficult to obtain on sales and

profits. Unfortunately, the annual reports of

larger companies do not present sales information in sufficient detail to allow the extraction of

information related to nuclear medicine equipment. The rankings of companies within an industry sement that are presented in this case

study, therefore, reflect respondents’ perceptions of national sales. Furthermore, it should be

noted that large variations in sales patterns may

occur between geographic regions. In the radionuclide market, for example, almost all of the

technetium used on the east coast is generatorproduced by the three major generator manufacturers, while in California, a sizable number of

users prefer “instant technetium” delivered daily

by Medi + Physics and smaller radiopharmaceutical producers.

Major Findings

The nuclear medicine industry is a very competitive one, except in the thallium production

segment. In the camera segment, the acknowledged leaders are Searle, Ohio Nuclear, Picker,

and General Electric. The competition is sufficiently keen that the leader, Searle, allegedly lost

several million dollars on its camera business in

1978. The mobile camera represents a major

growth area. Here Ohio Nuclear, with its small,

maneuverable, and reliable “Moon Buggy, ” is

the acknowledged leader, having perhaps twothirds of the market.

Analytical Development Associates Corp.

(ADAC) Laboratories and Medical Data Systems appear to be the front runners in computer

systems. ADAC’s strategy is to promote sales of

moderately priced units to small arid middlesized hospitals and to private physicians’ offices.

Twenty-five percent of sales in 1979 involved

second units to hospitals. Medical Data Systems, on the other hand, though interested in the

same market, takes pride in its more sophisticated hardware and software.

Competition among producers of technetium99m and its associated cold product kits is at

least as intense as that among producers of cameras and computers. Mallinckrodt, Squibb, and

New England Nuclear are the leaders, each with

its advocates and detractors. The possibility for

generator production of the isotope from a longlived parent, coupled with competitive pressure,

keeps the price of radioisotope per study down.

On the other hand, the only current producer of

thallium is New England Nuclear, though Mallinckrodt has received the Food and Drug Administration’s approval to sell in this country. It

is difficult to predict how much effect Mallinckrodt’s entry into the market will have on the

future prices of thallium. Nor is it possible to
predict what effect New England Nuclear’s linear greater efficiency will permit a reduction in

accelerator will have when it comes on line and price.

is used to produce thallium. Presumably, its

Table 3.—Ranks and Market Shares of Producers of Nuclear Imaging Equipment”

Current survey

Market segment and company 12345 6 Comments

Scintillation cameras

Searle Radiographic. . . . . . . . . . . . . . . . . . .

Ohio Nuclear. . . . . . . . . . . . . . . . . . . . . . . . . .

Picker. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

General Electric . . . . . . . . . . . . . . . . . . . . . . .

Raytheon . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Baird Atomic . . . . . . . . . . . . . . . . . . . . . . . . . .

Union Carbide . . . . . . . . . . . . . . . . . . . . . . . . .

Toshiba . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Elscint . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Pfizer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Computer systems

ADAC Laboratories. . . . . . . . . . . . . . . . . . . . .

Medical Data Systems . . . . . . . . . . . . . . . . . .

Digital Equipment. . . . . . . . . . . . . . . . . . . . . .

Ohio Nuclear. . . . . . . . . . . . . . . . . . . . . . . . . .

Informatek. . . . . . . . . . . . . . . . . . . . . . . . . . . .

Searle Radiographic. . . . . . . . . . . . . . . . . . .

Data General . . . . . . . . . . . . . . . . . . . . . . . . . .

Keronix. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Radionuclides

Thallium

New England Nuclear. . . . . . . . . . . . . . . . .

Mallinckrodt Nuclear . . . . . . . . . . . . . . . . .

Technetium

Mallinckrodt Nuclear . . . . . . . . . . . . . . . . .

Squibb . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

New England Nuclear. . . . . . . . . . . . . . . . .

Union Carbide. . . . . . . . . . . . . . . . . . . . . . .

Medi + Physics . . . . . . . . . . . . . . . . . . . . .

 Cardiac cold mix

Union Carbide.. . . . . . . . . . . . . . . . . . . . . .

Squibb . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Mallinckrodt Nuclear . . . . . . . . . . . . . . . . .

New England Nuclear . . . . . . . . . . . . . . . .

Procter and Gamble . . . . . . . . . . . . . . . . . .

Ackerman Nuclear . . . . . . . . . . . . . . . . . . .

Ancillaries

Harshaw Chemical Co.

Meal-X, inc.

Eastman Kodak

5

2

1

1

1

4

3

1

1

1

6 1

2 3

1 2

1

1 1

1

1

1

2 3

1

1

1

1

2

1 2

1

1 1

1

1

1

1

1

2

1 2

1

Searle = 1—50-60% b

Ohio Nuclear = 2—20-25%

Picker = 3

General Electric = 4

ADAC = 1—25-30%b

Medical Data Systems = 1—25-30%

Digital Equipment = 3—15-200/o

Ohio Nuclear = 4—10-150/o

1 Informatek = 5—5.10%

New England Nuclear is sole source as of 1979.

Mallinckrodt recently received FDA approval.

Very competitive market

Small subset of the hundreds of companies

involved. No ranks assigned.

aDetermlned from ,ntewlew~ of company repre~entatlve~ Each company interviewed was asked to rank producers In its market segment from 1 to 6. %me respondents

awarded tle rankings. Others failed to rank all major producers. Example: Fwe persons ranked Searle first among producers of sc!ntlllatlon cameras and one each

ranked it third and fourth.

b Market shares as repo~ed by F, Eberstadt and CO , Inc., 1978
USERS AND USES

Data Sources

Information on users and uses of cardiac radionuclide imaging was obtained for this case

study from questionnaires distributed to selected

institutions performing cardiac radionuclide imaging, from informal interviews with other physicians and technologists, from the medical literature (which primarily represents the opinions

and practices of experts), and from health statistics prepared by the National Center for Health

Statistics (NCHS). Projections of the potential

utilization of imaging procedures, though based

on the best available prevalence data, must be

considered speculative, especially in the face of

the rapid evolution that the technology is

undergoing.

Users

Nearly all of the existing 3,500 departments of

nuclear medicine in the United States now have

the ability to perform one or more types of cardiac radionuclide imaging procedures. In these

institutions, nuclear medicine experts are responsible for purchasing and maintaining hardware and test performance. Referrals come from

cardiologists and internists, and only rarely are

criteria to guide utilization specified.

Radionuclide imaging units are also being sold

to hospitals without departments of nuclear

medicine. These hospitals, through their departments of radiology or cardiology, represent major targets of the industry’s promotional efforts.

Similarly, group practices and private physicians are acquiring the capability to perform

scans. The extent of penetration into these markets is difficult to quantify at the present time.

Of the nonrandom sample of 13 institutions

we surveyed, 7 were tertiary medical centers and

6 were community hospitals. Of the seven referral centers, five favored technetium studies over

thallium studies (all performed both, however);

four had multicrystal cameras capable of performing first-pass studies; five had both mobile

and stationary scintillation cameras; and the

average number of cameras owned was 2.6. In

the six community hospitals, thallium perfusion

studies predominated. Only two had the computer hardware capable of performing MUGA

technetium studies, and three had mobile

camera units.

The estimated number of cardiac studies performed in the 13 institutions surveyed ranged

from 3 per week in one community hospital to

over 50 per week in two tertiary centers. Rest

and exercise studies were about equally represented. In the community hospitals, cardiac images, on average, constituted about 30 percent

of all radionuclide studies performed. In the referral centers, there was a greater tendency for

some equipment to be totally dedicated to cardiac uses.

Each institution surveyed indicated more or

less well-defined plans for updating or enlarging

its capability to perform cardiac studies within

the next year or two. Referral centers indicated

particular interest in tomographic techniques

(single-photon emission tomography and gated

CAT scanning) and in positron emission tomography. Several of the community hospitals interviewed favored seven-pinhole tomography.

Experts in cardiac radionuclide imaging appear to divide themselves into three groups: advocates of first-pass or MUGA technetium studies; equally vociferous defenders of thallium perfusion studies; and those who believe that these

two types of studies are complementary, each

contributing valuable independent information.

Advocates of technetium studies point to their

greater information content (cardiac output,

ejection fractions, transit times, in addition to

wall motion abnormalities), while perfusion

study supporters believe that this type of imaging is more sensitive in detecting coronary artery

disease.

Clinical Indications

Clinical indications for cardiac radionuclide

imaging cover the entire spectrum of cardiac disease. At one end, some experts point to the technology’s potential for routine screening for coro-
nary disease in asymptomatic individuals. In this

case, it might supplement or substitute for the

routine resting EKG. At the other end of the

spectrum, cardiac radionuclide imaging is used

to monitor the effects of drug therapy or surgery

in patients with established heart disease. In between are the applications most widely reported

in the medical literature: evaluation of suspected

coronary disease (e. g., chest pain of uncertain

cause); determination of the extent of disease

prior to coronary angiography or surgery in patients with established disease; and the diagnosis

of acute myocardial infarction. Table 4 lists major indications, the type of test used for each indication, the type of information yielded, and

the potential action(s) to be taken if the test

result is abnormal.

We were unable to obtain any information to

quantify the extent to which cardiac radionuclide imaging is being used as a primary screening procedure. Furthermore, no information is

available in the medical literature to document

the sensitivity and specificity of scanning in

unselected asymptomatic patients. In the

absence of data, the implications of a widespread policy to screen such individuals can only

be speculated upon.

In patients with established coronary disease,

imaging procedures at present appear to be used

primarily as adjuncts to other diagnostic tests,

especially exercise tolerance tests and coronary

angiography. A substitutive role has yet to be

defined. Some cardiologists believe that some

Table 4.—Clinical Indications for Cardiac Radionuclide Imaging

Indication Test Derived information Actions

Screening for CAD in

asymptomatic patient

Suspected CAD

. asymptomatic with positive ETT

. chest pain, ? etiology

● abnormal EKG precluding ETT

Probable or definite angina pectoris

Suspected acute Ml

● within 24 hr

. 24-72 hr

TI-201 (R &/or E)

First-pass or MUGA

(R &/or E)

Same as above

TI-201 (R & E or E-R)

MUGA or first-pass (R &/or E)

TI-201 or MUGA (R)

Tc-99m pyrophosphate

(“Hot spot”)

Recovery from Ml TI-201 (R & E or E-R)

MUGA or first-pass (R

Congestive heart failure MUGA or first-pass (R

Patients undergoing CABS TI-201 (R & E or E-R)

MUGA or first-pass

(R & E)

Monitor drug therapy (nitroglycerin, TI-201 (R & E or E-R)

& E)

&/or E)

propranolol, adriamycin, etc.) MUGA or first-pass (R+ E)

Congenital heart disease—shunts First-pass (R &/or E)

Valvular insufficiency First-pass or MUGA (R &/or E)

Perfusion defect

Wall motion or EF

abnormality y

Same as above

Perfusion defects

Wall motion or EF abnormality

Same as above

Identify extent & location

of Ml

Perfusion defect(s) enlarge

with exercise

Wall motion or EF abnormality

Wall motion or EF

abnormality

Response to surgery

Extent of perfusion defects

Wall motion or EF

abnormalities

Quantification of shunts

Valve regurgitation

ETT

Coronary angiography

Coronary angiography

Coronary angiography

Admit to CCU?

Continue in CCU?

Activity prescript ion

Coronary angiography

Surgery for left

ventricular aneurysm?

Activity prescription

Adjust medical therapy

Adjust medical therapy

Cardiac catheterization

Cardiac catheterization

CAD = coronary artery disease Tc-99m = technetium perfusion study

ETT

E-R = exercise redistribution

= exercise tolerance test TI-201 = thallium perfusion study

EKG

ETT = exercise tolerance test

= electrocardiogram first-pass = first-pass technetium study

Ml

EF = cardiac ejection fraction

= myocardial Infarction MUGA = multiple-gated acquisition

CABS

CCU = coronary care unit

= coronary artery bypass technetium study

surgery R = rest

CHF = congest we heart failure E = exercise
coronary angiographies will be avoided by normal or minimally abnormal radionuclide studies

in patients with chest pain syndromes. Others

point to the potential of radionuclide studies to

obviate the need for coronary angiography in

patients with congestive heart failure who have

findings that would not be amenable to surgery

(e.g., diffuse myocardial contraction abnormalities).

In the only systematic study of the role played

by cardiac imaging in physician decisionmaking,

58 percent of 171 consecutive studies met established criteria for ordering, usefulness, and interpretation, but only 12 percent were considered

to contribute to appropriate changes in therapy

(24). Clearly, much remains to be learned of the

real contribution that cardiac radionuclide imaging can make to the clinical management of patients with heart disease.

Potential Target Populations for

Cardiac Imaging

Selected statistics will provide a framework

for speculation regarding the ultimate extent of

diffusion of cardiac radionuclide imaging. We

summarize current information on heart disease

mortality and morbidity below. Then we present implications of these data for the potential

number of studies that might be performed under different assumptions.

Heart disease constitutes the leading cause of

mortality and morbidity in the United States. In

1977, it killed almost 719,000 Americans, with

638,000 dying as a result of ischemic heart disease (50). An additional 1,465,000 hospital discharges were attributed to ischemic heart disease

(59). By comparison, cancer, the second leading

cause of death, resulted in 377,000 deaths (1976

data (60)). Mortality data for ICDA codes related to coronary artery disease, presented in

tables 5 and 6, show that the number of deaths

and age-adjusted mortality rates from all heart

diseases and from acute myocardial infarction

decreased between 1970 and 1977. During this

same period, death rates from chronic ischemic

heart disease failed to show any clear trend.

Morbidity data provide further documentation of the enormous impact of coronary artery

Table 5.—Deaths From Coronary Artery Disease, 1970-77

ICDA codea

1970 1971 1972 1973 1974 1975 1976 1977

410-413 Ischemic heart disease. . . . .

410 Acute Ml . . . . . . . . . . . . . .

411 Other acute. . . . . . . . . . . .

412 Chronic . . . . . . . . . . . . . . .

413 Angina pectoris . . . . . . . .

390-398

}

402,404, All diseases of the heartb

410-429

666,665 674,242 684,424 684,066 664,854 642,719 696,673 638,427

357,241 357,714 357,844 351,662 334,196 324,652 319,477 306,398

4,246 4,027 4,528 4,503 4,418 4,069 4,008 3,993

304,962 312,301 321,884 327,722 326,065 313,847 302,362 327,830

216 200 168 179 175 151 186 206

735,542 743,368 755,864 757,075 738,171 715,318 723,878 718,850

aElghth R~Vi~l~” of International Classification of Diseases, adopted 1965.

blncludes cjlseases other than coronary artery disease.

SOURCE: National Center for Health Statistics, Hyattsville, Md., personal communication, 1979.

Table 6.—Death Rates From Coronary Artery Disease, 1970-77 (per 100,000 population)

ICDA codea

1970 1971 1972 1973 1974 1975 1976 1977

410-413 Ischemic heart disease. . . . . 328.1 327.1 328.8 326.0 314.5 301.7 301.0 295.0

410 Acute Ml . . . . . . . . . . . . . . 175.8 173.5 171.9 167.6 158.1 152.4 148.8 141.6

411 Other acute. . . . . . . . . . . . 2.1 2.0 2.2 2.1 2.1 1.9 1.9 1.8

412 Chronic . . . . . . . . . . . . . . . 150.1 151.5 154.6 156.2 154.2 147.3 150.2 151.5

413 Angina pectoris . . . . . . . . 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1

390-398,

)

402,404, All diseases of the heartb

362.0 360.5 363.0 360.8 349.2 336.2 337.2 332.3

410-429

aEighth Revlslon of International Classification of Diseases, adopted 1%5.

blncludes d{seases other than coronary artery disease.

SOURCE National Center for Health Statlstlcs, Hyattsvllle, Md., personal communication, 1979
disease. As shown in table 7, in 1972, the Health

Interview Survey of NCHS found 3,307,000 persons who reported coronary artery disease in its

various clinical manifestations. Of these persons, 31.8 percent attributed 1 or more days of

bed-disability per year to the condition, and 23

percent attributed more than 1 week. Nearly 58

percent claimed to be bothered somewhat or a

great deal by related symptoms. Over 12 million

physician visits were attributed to coronary

artery disease. In contrast to mortality, data

from the Professional Activities Survey, in table

8, show a steady increase in live hospital discharges for coronary artery disease between

1969 and 1977. Inferences from these data must

be qualified by the fact that the trends may

reflect changes in reporting, increases in the

population at risk, or changing patterns of coronary artery disease.

Table 7.—Prevalence and Morbidity

Potential Demand for Cardiac Imaging

Table 9 summarizes the potential future demand for cardiac radionuclide imaging by different target populations. Admittedly, these

projections are highly speculative and, in all

probability, represent upper bound estimates.

Access to imaging facilities and patient or physician attitudes regarding the value of imaging will

heavily influence actual utilization.

If all asymptomatic persons 40 years of age

and older were studied yearly, the estimated demand from this category alone would be 70.8

million scans per year. Restriction of imaging to

persons with suspected or established coronary

heart disease leads to estimates of 11.7 million

scans per year. These figures do not include

scans performed for types of heart disease other

than coronary disease (e.g., congenital heart disData for Coronary Artery Disease, 1972

Prevalence

All ages < 4 5 45-64 65 plus

In thousands. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3,307 167 1,466 1,674

Per 1,000 persons. . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.4 1.2 34.7 84.0

Bed disability days for the condition

Bed-disability days in past year (percent in category)

Prevalence (000’s) None 1-7 8-14 15-30 31-180 >180

3,307 68.2% 8.8% 5.170 7.2% 7.7 % 2.30/o

Discomfort from the condition (percent in category)

Great deal Some Very little Other Not bothered

27.2% 30.7% 15.3% 3.3% 22.8%

Physician visits

Physician visits in past year (percent in category)

Prevalence (000’s) None 1 2-4 5 or more Unknown

12,271 16.40/. 21 .8% 32.7% 26.2% 2.9%

SOURCES: National Center for Health Statistics, “1976 Summary: National Ambulatory Medical Care Survey: Advance Data,” in Vital and Health Statistics, series 30

(Hyattsville, Md.: NCHS, 1978); National Center for Health Statistics, “Prevalence of Chronic Circulatory Conditions, United States, 1972,” in Vital and Health

Statistics, series 10, No. 94 (Hyattsville, Md.: NCHS, 1974).

Table 8.—Hospital Discharges for Coronary Artery Disease, 1969-77 (in thousands)

ICDA codea

Age group 1969 1970 1971 1972 1973 1974 1975 1976 1977

410 . . . . . . . . . . . . . . 40-59 144 137 147 156 154 162 157 163 172

411-413 . . . . . . . . . . . 40-59 189 197 230 256 286 298 340 348

410 . . . . . . . . . . . . . . 60-64 57 50 60 55 55 62 63 70 68

411-413 . . . . . . . . . . . 60-64 79 76 88 78 107 106 122 131 125

410 . . . . . . . . . . . . . . All ages 402 390 413 428 423 455 451 481 488

411-413 . . . . . . . . . . . All ages 712 706 792 849 903 903 921 983 977

Total. . . . . . . . . All ages 1,114 1,096 1,205 1,277 1,326 1,358 1,372 1,464 1,465

aEighth Revision of International Classification of Diseases, adopted 1965. see tables 5 and 6

SOURCE: Professional Activities Survey, Chicago Ill., personal communication, 1979.
Table 9.—Projected “Demand” for Cardiac Imaging

Number of

persons (in Number of Number of scans

Indication millions) scans/person/year a

(in millions)

Screen, asymptomaticb adults . . . . . . 70.8 1 70.8

Suspected CADC. . . . . . . . . . . . . . . . . . 3.1 1.25 3.9

Definite CADd. . . . . . . . . . . . . . . . . . . . 3.9 1.5 5.8

Monitor drug therapy in CADe. . . . . . . 0.6 2 1.2

Monitor CABS patientsf. . . . . . . . . . . 0.4 2 0.8

Total projected scans . . . . . . . . . . . — — 82.5

Excluding routine screening. . . . . . — . 11.7

CAD = coronary artery disease

CABS = coronary artery bypass surgery

Assumptions:

aThe number of scans per Year estimates are entirely arbitrary In principle they represent YeadY Screen lng for all Cate90rleS Of

patients with either Increased frecluency or more than one type of scanning procedure per patient for the more complex cateb~~~~~sated u .S population 40 years and older for 1976 minus the estimated number of Patients with suspected or deflnw

CAD

cRate of suspected CAD in adults (2.2 percent) determined in the 1960-62 National Health Examination survey awdied to the

estimated 1976 adult population.

dsame as (c) for definite CAD (rate 2.8 percent); includes aCtJte rnYmarcJlal Infarctions.

ef.JatlOnal Health InteWiew suwey (52) estimated that 79 percent of patients Wflo ac~rlowledge CAD have a treatment prescribed. It is assumed that 20 percent of these might require periodic monitoring of drug effect (0.2 xO.79 x3.9 = 0.6x 10*).

flt is estimat~ that loo,~ persons receive cABs per year. Assuming an average survival of 4 years, there will be 400,000

prevalent patients with CABS (well may be underestimated).

ease, rheumatic heart disease, myocardio- If only one out of four office visits generated a

pathies, and unclassified types of heart disease). scan, or, alternatively, if one of every two EKGs

Another method for projecting numbers of were replaced by a scan, then 13.5 million scans

or 9.5 million scans, respectively, would be

cardiac scans involves the use of ambulatory generated from the ambulatory care sector care data (51). These data indicate that in 1976

there were over 54 million office visits for dis- alone. No matter what assumptions one makes

eases of the circulatory system (ICDA 390-458)

nor what techniques one employs, the potential

demand for cardiac imaging is enormous. and that over 19 million EKGs were performed.

COSTS AND CHARGES

Costs of a Radionuclide Laboratory

To perform a cost analysis of a constantly

changing and expanding technological area such

as cardiac radionuclide imaging is risky. Today’s

calculations may be out of date tomorrow. Furthermore, radionuclide imaging laboratories

vary widely. A large teaching hospital may have

a nuclear medicine department occupying an entire floor or wing, with several technologists,

numerous physicians, five scintillation cameras,

several computers, and elaborate ancillaries. At

the other end of the spectrum, a small rural hospital may provide cardiac imaging services once

a month by contracting on a per-scan basis with

a mobile imaging service. Most community hospitals fall somewhere between these two extremes, with one or two cameras, a small computer, and a technologist.

Analysis is further complicated by the fact

that discounts from list prices of up to 40 percent

are available on many items of equipment and

on some radionuclides. Producers may even give

new equipment to prestigious institutions or investigators at no charge to promote the equipment through subsequent publication of research results. Finally, most radionuclide laboratories are not fully dedicated to cardiac studies.

Under these circumstances, the proportion of

costs attributable to cardiac scans must be estimated. Given the rapid expansion of cardiac imaging, this proportion is ever changing.
In the following analysis, costs are assessed

for a hypothetical laboratory with one scintillation camera and one small computer. It is assumed that the laboratory is fully dedicated to

cardiac imaging and that maximum production

capacity of the laboratory is realized. To the extent that economies of scale might be realized in

larger laboratories through more efficient use of

personnel or through purchase of computers capable of handling the inputs from two cameras,

our costs estimates will be high. To the extent

that larger laboratories will purchase more expensive equipment (e.g., a computer capable of

handling dual inputs or more elaborate accessories), however, these economies of scale

will be counterbalanced. It should be noted that

any unit cost estimates that assume maximal efficiency of production are bound to be optimistic.

Equipment downtime, illness of key personnel,

uneven demand for services, and scheduling

problems all militate against achieving optimal

productivity.

Many different schema are available to categorize the costs of production of a service. We

use the following nomenclature:

1.

2.

Direct nonlabor costs. —Fixed, including

equipment and service contracts or maintenance; and variable, including radionuclides and other disposable.

Direct labor costs. —Fixed or variable, depending on whether alternative uses of time

and skill exist when personnel are not doing

cardiac imaging. Personnel for a radionuclide laboratory typically include a technologist, a physician, and a secretary/

receptionist.

3. Indirect costs. —Overhead costs (administration, space, utilities); training costs.

Direct Nonlabor Costs: Fixed

The single most expensive item of equipment

is the scintillation camera. The price varies with

the characteristics of the camera itself, accessories obtained with it, and size of discount available. Table 10 summarizes 1979 list prices of current models from several producers. The average base price is $90,000, with a range from

$78,000 to $110,000. Accessories can increase

these prices by 30 to 70 percent.

The second major equipment item is the computer. Although a computer is not essential for

qualitative analysis of thallium perfusion studies, it is required for calculation of transit times,

for ventricular function studies that include calculation of ejection fractions, and for tomographic studies. List prices of basic units range

from $40,000 to $54,000 (and up for more sophisticated multipurpose systems), with an average of $49,000.

Accessories for the camera and computer, including collimators, visual display, and software

packages, are estimated for purposes of this

analysis to amount to 25 percent of the base

price. Their cost can be considerably greater.

Other equipment items required to perform

scans include an examination table, bicycle ergometer for exercise studies, radiation counters

Table 10.—List Prices of Selected Equipment Suitable for

Cardiac Radionuclide Imaginga

Equipment item Producer Model List price

Camera. . . . . . . . . . . . . . . Picker DynaCamera 4/15-61 $110,000+

DynaCamera 4/15-37 $96,000 +

GE MaxiCamera 11 $80,000-$120,000

Searle Pho/Gamma V $78,000-$150,000

Ohio Nuclear Sigma 410 S $85,000-$100,000

Computer. . . . . . . . . . . . . ADAC Clinical Acquisition Module II $40,000 +

MDS A

2

$53,000 +

Searle Scintiview $49,000 +

Digital Gamma 11-1134 $54,000

System. . . . . . . . . . . . . . . Baird System 77 $99,500-$170,000

%nly the most recent model is listed for each product of a given type of equipment. The range for a given item is accounted

for by accessories that can be purchased with the basic equipment.
and badges, Polaroid film, magnetic tapes or

disks for data storage, etc. The costs of this

“other” category are difficult to estimate. The

figure of $10,000 that we adopt in this analysis

was provided by one laboratory director.

The aforementioned capital expenditures

(camera, computer, accessories, “other”), which

are annualized in this analysis by amortization

over a 7-year period at a real interest rate of 5

percent (above inflation), are shown in table 11.

The choice of the period of amortization depends on the physical and technological lifetimes

of the equipment, as well as on the accounting

practices of the institution. Scintillation cameras

10 years old are still in use, and many are capable of being updated as technological developments occur. Computer technology, on the

other hand, is evolving more rapidly. Even

though the physical life of a computer may well

be 7 years, its technological life maybe considerably shorter; 5 years was proposed by some experts. Our choice of 7 years is a compromise that

probably errs on the side of underestimating annual costs of a radionuclide laboratory. At the

extreme, for example, a laboratory director

might propose annual or biannual updating or

replacement of equipment to retain state-of-theart scanning capability. In fact, it is the desire on

the part of some institutions to remain current

that helps to fuel markets for both new and used

equipment. The international market for used

equipment allows less wealthy facilities to perform cardiac radionuclide scans at reduced cost.

The costs of maintenance must be added to

capital expenditures. Most producers offer service contracts, most commonly at an annual cost

of 10 percent of the basic purchase price. As

shown in table 11, for purposes of this analysis,

the annual cost of a service contract is estimated

to be $14,000.

Table 11 .—Estimated Annual Fixed Costs of Operating

a Radionuclide Imaging Laboratorya

Average purchase

Direct nonlabor costs (fixed) price Annual costs

Equipment

Camera/computer/accessories b

. . . . . . . . . . $174,000 $30,000

Other c 

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10,000 1,700

Serviced. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14,000 14,000

Subtotal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . — $45,700

Annual salary Full-time

Direct labor costse

(plus 20% fringe) equivalent Annual cost

Technologist . . . . . . . . . . . . . . . . $24,000 1.0 $24,000

Physician . . . . . . . . . . . . . . . . . . . 84,000 0.2 16,800

Secretary/receptionist. . . . . . . . . 12,000 0.3 3,600

Subtotal . . . . . . . . . . . . . . . . . . — — $44,400

Indirect costs Average cost Annual cost

Overhead f

. . . . . . . . . . . . . . . . . . . . . . . . . .

$5,000

$22,500

Technologist trainingg

. . . . . . . . . . . . . . . 1,200

Subtotal . . . . . . . . . . . . . . . . . . . . . . . . . — $23,700

Total annual cost. . . . . . . . . . . . . . . . — $113,800

calculations assume a single cameralcomputer system. Some economies of scale might be achieved in laboratories having

more than one system

bAverage list price of basic equipment plus 25 percent for accessories. Average prices: camera $90,000; COrnputer $49,000. Annual costs assume a 7-year amortization period at a 5-percent real interest rate. CFor eXa~lnatjon tables, eXercjSe equipment, EKG m~hlnes,r~iationcounters, etc. Estimated to total $10,000. Annual cost

again assumes a 7-year period and a 5-percent Interest rate.

dusual sewice contract is 10 percent of base price per year (0,10 x $139,000 = $13,9~/year

eAnn@l sala~es repre=nt current full.time equivalent estimatesbased on interviews with the personnel Of several laboratories

scaled down to requirements of a laboratory with a single scanning system.

fEstlmated as 25 percent of total direct COStS (48).

gcould range from zero If a fully trained technologist is hired to as high as $10,OOO if an untrained person is trained on the job.

The assumption of $5,000 is a compromise, Annual cost considers a 5-year duration of employment and a 5-percent real

Interest on the investment In training.
Direct Nonlabor Costs: Variable

The major variable nonlabor cost is for radiopharmaceuticals. Table 12 presents list prices for

thallium-20l and for the technetium-99m generators and cold product kits provided by New

England Nuclear. Several factors must be considered. First, 30- to 50-percent discounts are

available for technetium generators and cold

product kits; however, the price for thallium is

relatively fixed, because New England Nuclear is

the sole producer. Second, the radioactive halflife of the isotope is a major consideration in estimating costs. Thallium is supplied by the dose,

has a 74-hour half-life, and is generally used

within 24 hours of delivery; the necessity for

thrice-weekly deliveries, at $16 per delivery,

adds to the already high cost. Technetium, on

the other hand, is supplied weekly in the form of

generators of variable specific activity. The

molybdenum parent has a half-life of 67 hours,

while the half-life of technetium-99m is 6 hours.

Therefore, greater efficiency is achieved by

scheduling patients for examination early in the

week after Saturday deliveries. Technetium-99m

must be produced from the generator daily for

immediate use. Again, scheduling is critical.

Third, unit dose costs for technetium depend on

congruence between the size of the generator

and the number of patients examined. Any excess capacity of a generator will be wasted.

Direct Labor Costs

Labor costs may be fixed or variable, depending on whether or not the personnel involved

have responsibilities other than cardiac imaging.

Most laboratories have the following personnel:

1) a technologist, usually fully dedicated to radionuclide imaging, though often performing

scans other than cardiac scans; 2) a physician (or

nuclear medicine expert plus consulting cardiologists and internist) who supervises operation of

the laboratory, evaluates patients, places intracaths when required, monitors exercise, supervises data analysis, and interprets the results of

the study; and 3) a secretary/receptionist who

schedules appointments, greets patients, and

types reports. (Except in large laboratories, the

secretary/receptionist has responsibilities other

than cardiac imaging. )

Table 12.—List Prices of Radionuclides (Thallium-201, Technetium-99m) and Cold Product Kitsa

Thallium-201 b

Amount shipped Price/dose Usual dose Comment

1.65 mc $93.50 1.5-2.0 mCi Calibrated for day of delivery.

Must add $16 delivery charge per order.

Technetium-99m generators

Amount

New scale Old scale Price Usual dose Comment

225 50 mc $169 15-25 mCi New scale represents radioactivity at time of

450 100 224 delivery.

675 150 279 Old scale is radioactivity remaining on Friday after

900 200 334 a Saturday delivery.

1,350 300 445 Must add a $22 delivery charge per generator.

1,800 400 555

2,250 500 666

2,640 600 776

Cold product kitsd

Amount Price/kit Price/vial Comment

1-4 kits $92 $18.40 Each kit contains 5 vials.

5-9 86 17.20 Each vial is sufficient for 2 doses.

10 or more 69 13.80

aLl~t ~rlC.a are thO~e ~uOted bY N~W E“~la”d Nuclear @JEN), NEN IS the sole sources for tflalllurn. sfnall discounts (10 to IS percent) are Qivwl for large orders. List

prices of other producers of technetium and cold product kits are competitive; 35-50 percent discounts are available for Tc-99m.

bT 1A Of T1-2Crl is 74 hours.

CT 1A of molybdenum parent is 67 hours; T 1/2 of Tc.99m Is 6 hours.

dshelf life 1 year; therefore, large purchase feasible even if volume Is relatively IOW.
Full-time equivalent (FTE) salaries of personnel, of course, vary from institution to institution. Estimated average salaries, including

20-percent fringe benefits, are:

Technologist: $24,000 (base salary $20,000)

Physician: $84,000 (base salary $70,000)

Secretary: $12,000 (base salary $10,000)

A tradeoff exists between employing a technologist who is less qualified than one represented by

a $20,000 base salary and increased physician

time spent in supervising activities of the laboratory. Our assumptions, we believe, are fiscally

conservative.

Annual salaries, estimated FTEs for a laboratory of the size being evaluated, and annual direct labor costs are summarized in table 11.

Indirect Costs

Indirect costs fall into two categories: 1) overhead expenses for administration, space, and

utilities; and 2) costs of technologist training.

Overhead costs are estimated to be 25 percent of

total annual direct costs (nonlabor and labor)

(48), or $22,500 (see table 11). Technologist

training could range from zero, if a fully trained

person were hired, to perhaps $10,000 if an inexperienced person were trained on the job by the

supervising physician. Our chosen figure is

$5,000, which is annualized by amortization

over an expected 5-year period of employment

at a 5-percent real interest rate.

Total Annual Fixed Costs

As shown in table 11, estimated total annual

fixed costs of our model radionuclide laboratory

are $113,800. To this figure must be added the

variable costs of radiopharmaceuticals and disposable. Enlargement of this laboratory to accommodate increased demand for scans would,

in essence, involve the stepwise addition of

similar units at comparable costs, or at somewhat reduced costs if efficiencies of scale were

realized.

Unit Costs of Cardiac Imaging

Procedures

The unit costs of different types of cardiac imaging procedures are calculated by summing annual nonlabor costs prorated over the number of

procedures of a given type that a laboratory

could perform in 1 year, estimated labor costs

per procedure, and the cost of radionuclides and

other disposable.

Prorated annual nonlabor costs are obtained

from estimates of the daily production capacity

of a laboratory if it were totally dedicated to one

type of procedure (see table 13) the number of

workdays per year (250 days), and the annual

nonlabor costs (direct plus indirect). Nonlabor

costs range from $27.76 to $92.53 per test.

Labor inputs in time (minutes) and dollar

equivalents are summarized in table 14. Estimates for technologist and physician times were

obtained from several laboratory directors and

checked by a time-motion study in one laboratory; those for secretarial inputs are the

authors’. Time estimates varied widely from one

laboratory to another, probably because of the

differences in the amount of responsibility delegated to the technologist, or the varying sophistication of available computer software and

resulting differences in the time required for data

analysis. Values chosen represent approximate

medians. *

*An alternative method for estimating labor costs per procedure

would be simply to divide annual direct labor costs by the number

of procedures performed per year by the laboratory. This method

assumes that all labor costs should be ascribed to individual procedures. Labor costs estimated by using this method range from

$17.76 for first-pass studies (rest) to $59.20 for thallium perfusion

studies (exercise-redistribution).

Table 13.—Production Capacity for

Cardiac Imaging Procedures

Procedure Number per day

Thallium-201 perfusion studies

Rest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Exercise-redistribution . . . . . . . . . . . . . 3

Technetium-99m studies

First-pass studies

Rest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Exercise . . . . . . . . . . . . . . . . . . . . . . . . . 6

MUGA studies

Rest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Exercise . . . . . . . . . . . . . . . . . . . . . . . . . 5

Infarct imaging (“Hot spot”) . . . . . . . . . 8

aAssumes that an 8-hour workday IS totally devoted to a gwen type of test

Estimates were obtatned from dwcusslons with laboratory directors
Table 14.—Personnel Time Required for Different Cardiac Imaging Procedures

and Estimated Cost Equivalentsab

Technologist Physician Secretary Total

Procedure Time $ Time $ Time $ $

Thallium-201 perfusion studies

Rest. . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 $11.40 10 $8.00 10 $1.15 $20.55

Exercise . . . . . . . . . . . . . . . . . . . . . . . . 80 18.30 40 32.00 10 1.15 51.45

Exercise-redistribution . . . . . . . . . . . 120 27.40 50 40.00 20 2.30 69.70

Technetium-99m studies

First-pass studies

Rest. . . . . . . . . . . . . . . . . . . . . . . . . . 40 9.10 30 24.00 15 1.70 34.80

Exercise . . . . . . . . . . . . . . . . . . . . . . 70 16.00 60 48.00 15 1.70 65.70

MUGA studies

Rest . . . . . . . . . . . . . . . . . . . . . . . . . . 60 13.70 30 24.00 15 1.70 39.40

Exercise . . . . . . . . . . . . . . . . . . . . . . 90 20.55 60 48.00 15 1.70 70.25

Infarct imaging (’’Hotshot”) . . . . . . . 60 13.70 10 8.00 10 1.15 22.85

aTjme ~~~imate~ are the ~edlan~ of figures quoted by several laboratory directors, Estimates vary widely from one laboratory to mother, In part, at least, In relatlOrl to

the degree of responslblllty delegated to the technologist. bDollar equlvalent~ are based on annual ~alary plus fringe e~t,nl~tes (table 11) and an assumed 1,750 Work hours per year (250 workdays x 7 hours Of work/day, ex.

eluding lunch and breaks) Hourly rates: technologist $13.70; M D. $48.00, secretary $690

Costs of radionuclides plus disposable per because rest studies avoid both the extra time retest are estimated to be $95.50 per dose for thal- quired for exercise (20 to 30 minutes) and the

lium studies and from $15.53 to $18.66 for tech- need for physician supervision. Thallium studies

netium studies. are more costly than technetium studies because

of the greater cost of the isotope. First-pass

Unit costs calculated as the sum of these sev- studies are less expensive than MUGA (multipleeral components are presented in table 15. Rest gated acquisition) studies, because first-pass

studies are less costly than exercise studies, studies require less imaging time.

Table 15.—Unit Costs of Cardiac Imaging Procedures Assuming Maximal Production Efficiency

Non labor costs

Procedure Fixeda Variable b

Labor costs Total costs

Thallium-201 C perfusion studies

Rest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $34.70 $95.50 $20.55 $150.75

Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55.42 95.50 51.45 202.37

Exercise-redistribution . . . . . . . . . . . . . . . . . . . . . 92.53 95.50 69.70 257.73

Technetium-99m studiesd e

First-pass studies

Rest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.76 15.53 34.80 78.09

Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46.27 16.73 65.70 128.70

MUGA studies

Rest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.70 15.98 39.40 90.08

Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55.52 18.66 70.25 144.43

Infarct imaging (“Hot spot”) . . . . . . . . . . . . . . . . . 34.70 15.98 22.85 73.53

aAssumes 25CI workdays per year and production capacities as estimated in table 13.

bEstlnlated costs per dose for radionuclldes and cold product kits, If required, plus $3 for other dwposables (syringes, etc ).

cThe cost for thalllum assumes Ilst price plus a delivery charge per dose Of $2.00 ($93 SO + $2.00 = $gs.so).

dThe cost for technetlunlassumes that the rnedlarltest in a week IS done after one radioactivity half -l!fe, a dose Of 20 mc, a 40-percent discount Off llSt prlCe, and a $22

delivery charge per generator

No tests per week Requ/red mc Generator size requ!red D/scountedcost + $22 Cost/dose

50 1,000 2,250

40 800

$421.60

1,800

$8.43

30

355.00

600

8.88

1,350

25

289.00

500 1,350

963

289.00

~he cost for the stannous pyrophosphate cold product kits used with gated blood pool and “hot spot” scans assumes purchase of a 1 year’s supply, 2 doses per wal,

11.56

and a 40-percent discount (price = $4.10 per dose).
Our cost estimates must be interpreted with

certain caveats. First, it is unlikely that any laboratory would devote itself totally to one type of

test. If more than one type of test were performed, the weighted production capacity might

increase or decrease, thus affecting costs. For example, more efficient scheduling might be possible with shorter studies interdigitated with

longer ones. On the other hand, greater expertise of personnel with a particular type of test

would probably enhance efficiency. Numerous

tradeoffs can be imagined. Second, it is unlikely

that any laboratory would live up to its production capacity day in and day out. To the extent

that production capacity is not realized, our

results will underestimate true unit costs. On

balance, however, we believe that the calculated

unit costs are reasonable.

Current Charges for Cardiac Imaging

Procedures

There is enormous variation both in the

nomenclature on which charges for imaging procedures are based and in the charges themselves.

In some regions of the country, a single fee is

charged for procedures categorized very much

as we have categorized them. In other regions,

each view (e. g., left anterior oblique, anterior) is

charged for separately, and charges vary depending on the extent of data analysis performed. Fragmentation of charges into those

ascribed to the nuclear medicine department, to

the exercise laboratory, and to the physician is

another common practice that tends to increase

total charges.

Anecdotal reports from several physicians active in cardiac imaging suggest that actual

charges for a thallium perfusion study at rest

and during exercise range from as low as $300 to

as high as $1,000. Similar ranges apply to technetium (first-pass and MUGA) studies. Clearly,

standardization of nomenclature and equitable

determination of costs (and hence reimbursements) are issues that are only now beginning to

be confronted.

Third-Party Reimbursements

A recent survey performed by the National

Blue Cross and Blue Shield Association indicated wide variations in the reimbursement formulas being employed by member plans. Two

different approaches to the problem of achieving

better standardization of policies are represented

by the activities of Blue Cross/Blue Shield of

Greater New York and Blue Cross/Blue Shield

of Massachusetts. *

In New York, concerns have developed over

rapid increases in the volume of scanning by independent as well as hospital laboratories and

the ill-defined nomenclature which permits fragmentation of charges. Efforts are being directed

to consolidate the number of codes for which

reimbursements will be provided and to define

an equitable global fee schedule. Reimbursement

is (and apparently will continue to be) provided

whether the procedure is performed in a hospital

laboratory or an independent laboratory.

In Massachusetts, a different approach has

been taken. Here, Blue Shield has defined codes

(very similar to our own classification) and,

with the help of an advisory committee, has

established basic benefits and interim customary

scales that are limited to the professional component. Since Blue Cross covers the basic service

component only for scans performed in hospital

laboratories, this decision by Blue Shield has, in

effect, limited the ability of independent laboratories to perform scans.

Suggested Fee Schedules

Global fee schedules suggested by three

laboratory directors are presented in table 16.

As can be seen, fees for rest studies of all types

are about $250, whereas those for studies that

involve exercise or exercise combined with rest

range from $350 to $405. The range of proposed

fees is considerable, especially for exercise

studies. These suggested fees are not necessarily

representative of the United States at large. It is

probable that the true range of charges is in fact

much greater.

Comparison of the information in tables 1 5

and 16 indicates that unit costs for thallium stud-

● Massachusetts: Dr. James Young, Medical Director, Massachusetts Blue Shield, Boston, Mass., personal communication, 1979.
Table 16.—Suggested Fee Schedules for Cardiac Imaging Proceduresa

Procedure Charge (range) Midpoint of range

Thallium-201 perfusion studies

Rest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $245-$250 $248

Exercise. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315-420 368

Exercise-redistribution . . . . . . . . . . . . . . . . 315-495 405

Technetium-99m studies

First-pass studies

Rest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260-275 268

Rest and exercise . . . . . . . . . . . . . . . . . . . . 315-475 395

MUGA studies

Rest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225-260 243

Rest and exercise . . . . . . . . . . . . . . . . . . . . 315-385 350

Infarct imaging (“Hot spot”) . . . . . . . . . . . . 150-160 155

aprOvided by tfl~~e laboratory directors. pflysician proportions estimated to be between so and do PerCent Of total Chwm

ies average about 60 percent of proposed fees

(range 56 to 65 percent); and unit costs for resting first-pass studies, resting MUGA studies, and

infarct imaging are 29, 37, and 47 percent of proposed fees, respectively. Comparisons could not

be drawn for exercise studies done alone, since

fee schedules address exercise studies only when

they are performed in conjunction with their

resting counterparts.

Another way to examine suggested fee schedules is to calculate the volume of testing required

to defray the costs of laboratory operations. Table 17 presents these results under the assumption that the laboratory is totally devoted to the

production of one type of test only. Breakeven

volumes represent between 18 percent (resting

first-pass studies) and 49 percent (exerciseredistribution thallium studies) of projected full

production capacities. Volumes above these levels would represent profit to the institution.

Differences found between resource costs and

charges may be due to underestimation of unit

costs or to the fact that substantial profit margins are built into proposed fee schedules. Arguments can be made on both sides of this issue.

Quite clearly, this problem warrants further exploration.

Table 17.—Breakeven Points for Laboratory Operationa

Production capacity- Breakeven volume

Procedure (per year) (per year) Percent of capacity

Thallium-201 perfusion studies

Rest. . . . . . . . . . . . . . . . . . . . 2,000 746 370/0

Exercise . . . . . . . . . . . . . . . . 1,250 418 33

Exercise-redistribution . . . 750 368 49

Technetium-99m studies

First-pass studies

Rest. . . . . . . . . . . . . . . . . . 2,500 451 18

Rest and exercise. . . . . . . — b — —

MUGA studies

Rest. . . . . . . . . . . . . . . . . . 2,000 501 25

Rest and exercise. . . . . . . —b — —

Infarct imaging (“Hot

spot “). . . . . . . . . . . . . . . . 2,000 819 41

calculations use estimated annual fixed costs of laboratory operations (table 11), variable costs for radiopharmaceuticals

(table 15), and midpoints of suggested fees for different cardiac imaging procedures (table 16). bNOt estimable because production capacities were estimated on the basis of exercise tests done alon% while suggested fee

schedules were for exercise studies only when done in conjunction with rest studies.
CLINICAL EFFICACY

In the broadest sense, a diagnostic test should

be evaluated in terms of its ability to improve

the medical outcomes of patients to whom it is

applied; earlier and more effective treatment

regimens should result. However, most diagnostic tests serve only as elements in the physician’s

decisionmaking process, which also involves inputs from multiple sources, including the patient’s history of symptoms, the presence of risk

factors, and findings on the physical examination. Furthermore, the relation between management decisions and patient outcome is not always clear. For these reasons, the evaluation of

a diagnostic test is usually limited to its information content, while resultant patient benefits are

implied. Each of these limitations applies to the

evaluation of the efficacy of cardiac radionuclide imaging.

Medical Literature: Overview

Early papers describing the development of

the current generation of cardiac imaging procedures appeared in the 1960’s and early 1970’s,

and an explosion of clinical investigations began

in 1977.

Several generalizations will facilitate interpretation of the medical literature. First, most studies have been conducted in a small number of

medical centers in the United States. Second, almost all studies have been performed in highly

selected populations. Subjects have been patients with chest pain who have been referred to

the hospital for evaluation and cardiac catheterization or patients admitted with suspected or

proven myocardial infarction. “Normal” patients have been those found to have either minimal or no coronary artery disease on coronary

angiography or, in a few instances, have been

hospital controls or normal volunteers. No information is currently available from an unselected population.

Third, the “gold standards” against which radionuclide procedures have been judged are: 1)

the coronary angiogram for the diagnosis of coronary artery disease; 2) the left ventricular angiogram for the assessment of left ventricular

function; and 3) a combination of clinical, enzymatic, and electrocardiographic findings for the

diagnosis of acute myocardial infarction. Each

of these “gold standards” has very definite limitations. The coronary angiogram provides an

anatomic demonstration of coronary disease,

but the correlation between anatomic disease

and impaired blood supply to the myocardium

(the root cause of angina pectoris and myocardial infarction) is only approximate. Two problems exist. On the one hand, interpretation of

the degree of vessel narrowing from a coronary

angiogram is highly subjective; interobserver

variability of between 15 and 35 percent for different coronary arteries was noted in one carefully performed study (88). On the other hand,

even accurate determination of the degree of

coronary artery narrowing will not necessarily

correlate with degree of reduced blood flow or

the risk of an untoward myocardial event; the

length, nature, and location of the obstruction

and the existence of collateral blood supply are

also important. Coronary arteriography is an

imperfect indicator of physiologically significant

disease, but it is indispensable to the selection of

patients for coronary artery bypass surgery. The

left ventricular angiogram is also an imperfect

standard. Interobserver variability in the interpretation of wall motion abnormalities has been

reported to be as high as 42 percent. The diagnosis of acute myocardial infarction is, at present, made on the basis of composite information

from the clinical history, changes in the EKG,

and increased levels of certain cardiac enzymes

(SGOT, CPK, MB-CPK). False-negative results

are indicated by the identification of the pathological changes of myocardial necrosis on postmortem examination in patients with ischemic

disease who do not evidence infarction by the

above criteria during life (58). False-positive

results are probably rare if stringent criteria are

employed.

Finally, it is important to note that all of the

information in the medical literature on cardiac

radionuclide imaging has been generated by experts in nuclear radiology and cardiology. Since

performance of imaging procedures is technical-
ly exacting, data analysis difficult, and interpretation to a large extent subjective, results

presented below are likely to represent the best

achievable with the technology existing at the

time the studies were conducted. As diffusion

occurs, the technical quality of scans that are

performed may decline. At the same time, the

procedures may be applied to populations very

different from those in which currently available

information was obtained. These factors, coupled with the rapid changes that are occurring in

the state of the technology, make it very difficult

to predict the true clinical effectiveness of cardiac scans in widespread applications.

Diagnostic Information

The value of diagnostic information lies in the

contribution that it makes to diagnosing a disease or to documenting the extent of disease or

its response to treatment. Underlying this criterion is the assumption that increased knowledge somehow confers benefits to the patient.

Diagnosis of a Disease

Diagnosis implies that one has a clear definition of what constitutes a disease. This is not

always simple, Many diseases represent a point

on a continuum of a physiologic or pathologic

phenomenon, rather than a discrete entity. Coronary artery disease is an example. Furthermore,

most diagnostic tests are less than perfect indicators of a disease, no matter how it is defined.

The likelihood that a disease exists is increased

by a “positive” result and decreased by a “negative” result, but in neither case is the diagnosis

“certain. ” Under these circumstances, the usefulness of a test to the clinician will depend on

several factors:

● the probability that disease exists given the

characteristics of the patient tested;

● the change in disease probability that can be

attributed to the test result; and

● the threshold probability level that must be

reached for the physician to make the next

diagnostic or therapeutic decision, i.e., to

proceed with further tests or with treatments if the likelihood of the disease is sufficiently high or to stop testing if it is sufficiently low. This threshold, in turn, should

depend on the clinical implications of falsely diagnosing a disease that is not present

(false positive) or missing the diagnosis of a

disease that is present (false negative).

The principles involved in this decision process are summarized by Bayes’ theorem, which

relates the probability of the disease if a test is

positive to the probability of disease prior to the

test and to test sensitivity and specificity, such

that:

P(D+ IT+) = P(T+ ID+) X P(D+)

P(T+ ID+) X P(D+) + P(T+ID–) X P(D–)

where: P(D+ I T+ ) is the posterior probability of the disease

P(T+ I D + ) is the sensitivity of the test

P(D+ ) is the prior probability or prevalence of the

disease

P(T +ID – ) is the false-positive rate, which in turn is 1

minus the specificity of the test or [1– (T – ID – )]

P(D – ) is the prior probability that the disease is absent

or [1 –P(D+ )]

Vecchio (77) and McNeil, et al. (46) discuss the

assessment of diagnostic information in general,

and Diamond and Forrester (20) relate these concepts to the diagnosis of coronary artery disease

in particular.

As discussed below, the application of Bayes’

theorem to clinical decisionmaking requires

careful definition of several parameters: 1) what

is meant by disease presence or absence; 2) the

criterion for test positivity, and how this relates

to sensitivity and specificity; and 3) the characteristics of the population being tested as they

relate to the prevalence of disease (prior probability) and to test sensitivity and specificity.

Disease Presence or Absence. —Disease can be

defined by pathologic, anatomic, or physiologic

criteria. The criterion chosen will have important implications for the sensitivity and specificity of a diagnostic test and for disease prevalence

in the population. The point on the continuum

of pathophysiologic abnormalities one uses to

define the presence of disease also will have important implications. Development of the pathologic lesions of coronary artery disease begins

early and progresses throughout life. Clinical

consequences may include sudden death, myocardial infarction, angina pectoris, and congestive heart failure.
Pathologically, coronary artery disease is

defined by the presence of arterial lesions or by

changes in the myocardium consistent with ischemic damage. The continuum is from minimal

to extensive changes. Assessment of cardiac imaging techniques according to pathologic findings has relied on post mortem examinations,

biopsies done at the time of coronary artery

bypass surgery, and, in one study, transvenous

myocardial biopsies (36), In general, practical

difficulties in obtaining pathologic material have

limited applications of this criterion.

Anatomic manifestations of coronary artery

disease are usually assessed by coronary arteriography. The risks and costs of this procedure

limit its application to patients in whom coronary artery disease is strongly suspected. Hence,

it will be difficult or impossible to use coronary

arteriography in a general population to evaluate cardiac imaging techniques. The presence of

disease by coronary arteriography is defined by

the percentage reduction in luminal diameter of

a vessel. Criteria vary, but narrowing of greater

than 70 percent is the most common definition

of “significant” disease. Additional criteria relate

to the number of vessels involved, the location

of lesions, and the extent of involvement (local

or diffuse). That obstruction of less than 70 percent may be designated “nondisease” is an obvious dilemma.

Physiologic expressions of coronary artery

disease include typical symptoms of angina pectoris, abnormal electrocardiographic changes

during exercise, and measurement of enzymes

released from damaged tissue (CPK) or metabolizes released from an ischemic myocardium (lactate). From many points of view, physiologic

criteria should be the most useful of all clinically. For myocardial infarction, a combination of

physiologic changes is, in fact, the “gold standard. ”

Criterion for Test Positivity.—Test sensitivity, test specificity, and false-positive and falsenegative rates all depend on the criterion selected to identify a positive test. For thallium

perfusion scans, for example, detection of a defect depends on the extent of count rate deviation from normal patterns. The effects of the

choice of cutoff criterion on sensitivity and the

false-positive rate can be depicted in a receiver

operating curve as shown in the following figure.

Truepositive

rate

(sensitiv ‘)

0

0.5

0.8

0.9

0.1 0.3 0.5 1.0

False-positive rate

If a 25-percent reduction in count rate were

specified (point A), the sensitivity might be 0.85

and the false-positive rate 0.20. If a lesser reduction were chosen, a larger proportion of true

positives would be identified, at the cost of a

higher false-positive rate (point B). The converse

would occur if a more stringent criterion were

chosen (point C).

When quantitative analysis of data is performed, a 20- to 25-percent reduction in count

rates is usually selected. When subjective interpretations are made, the criterion is a qualitative

one based on the identification of a definite or

probable defect. Even with standardization in

the technical performance of a procedure, variations in interpretation between observers and

between laboratories will have important effects

on the comparability of results.

Disease Prevalence. —Finally, the value of a

test can be assessed only if the prior probability

of the disease in the patient is known. Considerable data are available that relate the independent contributions of sex, age, and the characteristics of chest pain to the likelihood of coronary

artery disease (20,85). For example, the likelihood of disease in asymptomatic persons ranges

from 0.3 percent in women 30 to 39 years of age

to 12.3 percent in men 60 to 69 years of age. If

typical angina is present, comparable figures are

25.8 percent and 94.3 percent, respectively. In-
formation from prior diagnostic tests, such as a

resting EKG or exercise tolerance test, would

modify probabilities based on age, sex, and

chest pain.

Not only will the prior probability of disease

in a population have an important effect on the

posterior probability, but it also may have an effect on the sensitivity and specificity of a particular diagnostic test. This phenomenon has been

demonstrated clearly in the case of exercise tolerance testing. Chaitman, et al. (19), for example, studied 200 patients with suspected coronary disease prior to cardiac catheterization. All

had normal resting EKGs. Eighty-six percent of

87 men with typical angina, 65 percent of 64

men with atypical angina, and 28 percent of 49

men with nonspecific chest pain were found to

have coronary artery stenoses (of at least 70 percent). In patients with typical angina, the sensitivity of exercise tolerance testing was 87 percent

and the specificity was 100 percent; in patients

with atypical angina, corresponding figures

were 64 and 83 percent. Weiner, et al. (85)

verified these findings in a large prospective

study of coronary artery disease. The sensitivity

of the exercise tolerance test in that study ranged

from 85 percent in patients with definite angina

to 53 percent in patients with nonischemic pain;

corresponding values for specificity were 67 and

77 percent. In women with definite angina, sensitivity was 85 percent and specificity only 49

percent; however, the number of women with

nonischemic pain was too small to permit meaningful estimates. Clearly, the sensitivity and specificity of cardiac imaging procedures must be

examined in various population subgroups before one can extrapolate with confidence from

studies currently available.

The relevant parameters having been defined,

Bayes’ theorem can be applied to assess the relation between prior and posterior probabilities of

disease and hence the value of diagnostic information. This relation can be displayed as shown

in the figure that follows.

The shapes of the curves for abnormal and

normal results are determined by the specificity

and sensitivity of the test in question. The hypothetical example shown portrays a test with a

Posttest

likelihood

of disease

0.6

o.4t0.2

0.2 0.4 0.6 0.8 1.0

Pretest likelihood of disease

specificity of about 85 percent and a sensitivity

of about 70 percent. If the pretest probability

were 0.4, then the posttest probability would be

about 0.8 if the test were abnormal and 0.2 if the

test were normal, probability differences of 0.4

and 0.2, respectively. If the physician’s threshold for proceeding to the next diagnostic step

(e.g., cardiac catheterization) were 0.8, the test

results would allow that decision. If the posterior probability in the face of a positive test were

lower than the threshold for decisionmaking,

however, the value of the test would be dubious.

Other decisions or other physicians might have

different thresholds. The effectiveness of a test,

therefore, depends both on the posterior probability of disease achieved and on the influence

that the probability would have on a physician’s

choice of further diagnostic or therapeutic actions.

Physician thresholds for action in the face of

the need to make decisions with less than perfect

data have not been evaluated systematically. Information from such studies could make important contributions to physician education as well

as to the evaluation of physician performance

and the utilization of medical technology.

Cardiac Imaging Procedures:

Review of the Medical Literature

Our review of the literature addresses each of

the major clinical uses of cardiac imaging procedures: 1) diagnosis of coronary artery disease; 2)

diagnosis of acute myocardial infarction; 3) assessment of ventricular function; and 4) follow-
up of patients undergoing coronary artery bypass operations. Also discussed are problems of

interobserver variability in the interpretation of

scans and questions of safety.

Diagnosis of Coronary Artery Disease

Medical Decisions Affected.—Determination

of the cause of chest pain has important implications for prognosis and for the choice of treatment. In patients in whom the diagnosis of coronary artery disease is strongly suspected, the

major alternatives are to offer a trial of medical

treatment or to proceed to coronary angiography with the view that coronary artery bypass

surgery would be recommended if the results of

this study revealed “operable” disease. Some experts argue that high-risk, though asymptomatic, patients should also be evaluated because of

the increased risk of “sudden death” in these individuals. To date, however, the value of medical or surgical treatments in this group has not

been demonstrated convincingly.

Techniques.—Thallium-20l perfusion studies

and technetium-99m ventriculographic techniques have both been used to diagnose coronary artery disease. As discussed earlier, coronary artery disease appears as perfusion defects

in the former technique and as wall motion abnormalities or abnormalities in regional or global ejection fractions in the latter. Results are

summarized for thallium-201 studies in table 18

and for technetium-99m studies in table 19.

Definition of Disease.—The “gold standard”

for defining the presence of coronary artery disease is the coronary arteriogram. Limitations of

this procedure were discussed previously. As indicated in tables 18 and 19, the criterion for diagnosis may range from roughly 50-percent to at

least 75-percent obstruction of one or more coronary arteries. This range may in part represent

the use of different nomenclatures, 50-percent

diameter narrowing being equivalent to about

75-percent reduction in luminal area. To the extent that real differences in criteria exist, test

results will be difficult to compare among studies.

Populations Studied.—Essentially all studies

have been performed in patients with suspected

coronary artery disease who have undergone

coronary arteriography. Most have chest pain of

some type; many have had prior myocardial infarctions. Specification of the proportion of patients with typical or atypical angina pectoris is

presented in a minority of studies (1,4,18,45,47,

54,71,78). Disease prevalence ranges from 50 to

82 percent.

Results.—The overall sensitivity of thallium-201 studies for the detection of coronary

artery disease ranges from 75 percent (81) to 100

percent (73), with an average of 86 percent,

while specificity ranges from 56 percent (73) to

100 percent (1,81), with an average of 89 percent. In general, sensitivity seems to be greater

in studies having a larger proportion of subjects

with prior myocardial infarctions. No relation

of sensitivity to the criterion chosen for definition of the disease was apparent in the one study

that examined this directly (54). The single study

that used seven-pinhole tomography (81) reported by far the highest sensitivity (97 percent),

with a specificity of 100 percent. Direct comparison of tomography to the standard perfusion

scan in this study suggested the greater sensitivity of the tomographic methods. Further validation of the superiority of this technique is

needed, however.

Comparison of thallium scan results to exercise tolerance tests poses a special problem, because, while the latter detect only myocardial ischemia sufficient to depress the ST segment a

prescribed amount, exercise or exercise-redistribution scans detect both fixed perfusion defects

(usually reflecting areas of myocardial scar) and

transient defects occurring during exercise. The

proper comparison, therefore, depends on

whether the desired endpoint is the detection of

any coronary artery disease (CAD) or the detection of transient ischemia only.

Average unweighed results from studies that

compare the thallium scan and exercise tolerance

test (ETT) in the same population

Thallium

Sens. Spec.

Any CAD (N=14), ., 8370 86%

Ischemia (N=4) . . . . . 7070 8570

show:

ETT

Sens. Spec.

6370 80%

60% 8570
Table 18.—ThalIium-201 Perfusion Scans in the Diagnosis of Coronary Artery Disease

—

Subjects Test results

Disease Disease

Author

Selection Prior defi- prevaYear criterion Total AP Atyp Other Mla nition b Ience R/RD Ex Overall ETT Comments

27 S = 95% — — Segmental analysis performed.

21

48

Lenears, et al. 1977 Admitted for CA 70 — —

(34)

Ritchie, et al. 1977 Suspected CAD 101 — —

(64) Admitted for CA

Bailey, et al. (1) 1977 CA proven 83 40 3

CAD (63 pts);

normal (17)

Turner, et al. (76) 1978 Chest pain but 66 — —

no prior Ml

—

—

—

—

2

6

4

0

—

—

—

o

—

—

—

—

—

—

—

5 0 %

7 0 %

Sp = 93%

75% S = 29% S = 66% S = 76% S = 45%

SP = 96% SP = 96% SP = 92% SP = 84%

76% S = 49% S= 56% S = 75% S = 38% S of ETT= 54% if endpoints of ST

Sp = 100% SP = 100% SP = 1OO% SP = 100% depression and chest pain are

combined.

5370 — S = 68% — S = 71% Excluded from study were patients

— Sp = 97% — Sp = 79% with prior Ml, patients unsuitable for

ETT or if predicted submaximal

heart rates not achieved, Also excluded were patients with coronary

artery obstruction > 50%, but

<757..

59% — S = 79% — S = 88% Ett results exclude 26 patients with

SP = 97% — Sp = 62% nondiagnostic results (on medications or 85% predicted rate not

achieved).

71% — S = 87% — S = 54% ETT results include 27 patients in

Sp = 100% — Sp = 75% whom results were equivocal.

67% S = 390/. S = 69% S = 84% S = 92% Calculations exclude 3 rest and 2

Sp = 80% Sp = 60% Sp = 600/0 Sp = 71% exercise scans that were technically unsatisfactory.

78% S = 40% S = 73% S = 86% S = 85% 18 of 49 ETTs were nondiagnostic

Sp = 91 O/. Sp = 90% Sp = 90% Sp = 75% and are excluded,

o 75%

Veroni, et al, (78) 1978 Suspected CAD 82 53 26

with CA

4 — 5 0 %

Carrillo, et al. 1978 Suspected CAD 55 32 17

(18) with CA

Okada, et al. (54) 1978 Suspected CAD 49 36 9

with CA

22

10

7 5 %

7 0 %

5 0 %

Blood, et al. (4) 1978 Suspected 7 0 %

CAD with CA

71% Rest

S = 32% S = 90% S = 93% S = 660/0 Redistribution scans were more

Sp = 92% Sp = 84% Sp = 76% Sp = 86% sensitive than rest scans.

RD

S = 56% S = 890/. S = 93%

SP = 880/0 Sp = 80% Sp = 76%

63% — — S = 85% S = 67% ETT calculations exclude patients

— — Sp = 92”/. Sp = 63% with equivocal results.

65% — S= 74% Standard —

}

7-pinhole tomography compared with

— SP = 96% — standard scintigraphy.

87 68 –

65 – –

65 — –

39 – –

27 15 12

78 – –

36 – –

95 – –

128 – –

39 – –

52 — –

227 – –

32

Botvinick, et al. 1978 Chest pain with

(13) CA

Vogel, et al, (81) 1979 CAD with CA

19

—

75%

70%

82% S = 69% S = 94% S = 975 7.pinhole Redistribution of > 20%

Sp = 100% Sp = 100%Sp = 1007 —

O Sp = 93% Sp = 850/. Sp = 85°/0 Sp = 60% ETT uninterpretable in 3 patients.

—

Meller, et al. 1979 Chest pain with —

(47) normal CA

Massie, et al. 1979 Chest pain with

(43) CA

33 — S= 89Y0 — Sensitivity of TI-201 scans for

— Sp = 93% — regional perfusion abnormalities

evaluated. Seventy of stenosis

highly correlated with sensitivity of

scan.

— S = 100% S = 44%. Uses processed-lesion enhancement.

— S = 56% Sp = 89% Without processing S = 85%,

Sp = 56%. ETT calculations count

11 indeterminate results as not

abnormal

— S = 75% S = 56% With asynergy on LV angiogram as

Sp = 91% Sp = 860/0 the endpoint TI.201 sensitivity

= 93%.

S = 87% — S= 88% 60 patients on propranolol.

S P = 85% — Sp = 85% ETT calculations are for

diagnostically adequate tests.

——

——

—

—

——

——

—

Sonnemaker, et 1979 Referred for CA

al. (73)

—

Bodenheimer, et 1979 Chest discomal. (8) fort with CA

—

McCarthy, et al. 1979 Known or 43

(45) suspected

CAD with CA

S= 81% — Nondiagnostic ETTs occurred in 39

S P = 69% — patients. TI-201 stress abnormal if a

new or enlarged defect was noted

compared to the redistribution scan.

S = 83% — S = 55% New or enlarged defect on stress

S P = 94% — Sp = 82% TI-201 scan

Calculations excluded 6 patients with

equivocal scans or ETT results.

— S = 87% S = 63% Propranolol therapy associated with

— Sp= 75% Sp = 77% a decrease of sensitivity of TI-201

scans from 90% to 76% and specificity from 82% to 53%,

—

—

—

Stolzenberg, et 1979 CA

al. (74)

Pohost, et al, 1979 CA

(57) —

CA = coronary arteriogram s = sensitivity R/RD = rest or redistribution

CAD = coronary artery disease Sp = specificity EF

Ml

= cardiac ejection fraction

= myocardial infarction ETT = exercise tolerance test H R = heart rate

AP = angina pectoris Ex = exercise LV = left ventricular

Atyp = atypical angina pectoris

af+istory and/or Q waves.

bpercent obstruction of at least one coronary artery.
Table 19.—Technetium-99m Radionuclide Angiography in the Diagnosis of Coronary Artery Disease

— Subjects

—

Test results

Selection

Author Year criterion Total AP Atyp Other

Disease Disease

Prior defi- preva- Technetium-99m TI.201 —

Ml a nition b Ience R Overall Overall ETT Comments

First-pass studies

— S = 27% S = 83%*

S = 97?...

Sp = 100%

— 760/. S = 67% S =91%.

SP = 84% SP = 840/.

— S= 82% —

(and LV Sp = 100 ”/0 —

asynergy)

—

Rerych, et al

(63)

1977 30 normals

30 with CAD

60 – –

129 — —

44 — —

● Criterion for abnormality: abnormal

wall motion; ● ● rise in ejection

Isometric handgrip exercise

Criterion for abnormality is decreased relative regional EF

Rest only. Criterion for abnormality IS

abnormal segmental wall motion

—

—

—

—

—

—

——

——

——

Bodenheimer

et al (7)

1978 Chest pain

with CA

—

Bodenheimer

et al (9)

1978 Suspected CAD

with CA —

——

Slutsky, et al

(71 )

197932 normal

volunteers, 48

with chest pain

and CA

80 48 – 60% S = 96% —

Sp = 100 ”/0 —

Rest only. Single crystal camera

First-third EF (NL =

— —

0.29 ± 0.04) IS criterion for abnormality, Sensitivity of global EF at

rest = 35%.

75% — S = 82% S = 82% S = 58% Q waves in 15 patients Combined

Sp = 79% Sp = 890/. Sp = 840/. sensitivity of all tests = 960/.

Bodenheimer

et al (6)

1979 Chest pain

with CA

75 — –

MUGA studies

Borer, et al (12) 1979 Suspected CAD

with CA

84 – – 75 ”/0 s = 54% s = 94% ● — — “Regional dysfunction with exercise.

— Sp = 100% — —

— S =89”/0“• ● ● Global EF c normal

— Sp = 100%

82% S = 93% S = 85% —

Sp = 54 ”/0 Sp = 100% —

Caldwell, et al

(15)

1979 CA 52 – –

NL = normal level - —

CA = coronary arteriogram ETT = exercise tolerance test

CAD = coronary artery disease Ex = exercise

Ml = myocardial infarction R/RD = rest or redistribution

AP = angina pectoris EF = cardiac ejection fraction

Atyp = atypical angina pectoris HR = heart rate

s = sensitivity LV = left ventricular

Sp = specificity

aHlstory and/or Q waves

bpercent obstruction of at least one coronarY arterY

The results for exercise tolerance tests must be

interpreted with caution because of varying

practices in counting equivocal results and the

inability of some patients to attain adequate exercise levels. The highest sensitivities were obtained in studies that excluded indeterminate

results (45,54,76,78). Nonetheless, thallium perfusion studies appear to be at least as sensitive

and specific as the exercise tolerance test in

detecting myocardial ischemia. Treatment with

propranolol for angina pectoris or for hypertension at the time of testing appears to decrease the

sensitivity and specificity of thallium studies (57)

and to decrease the number of patients able to

attain 85 percent of the predicted maximal heart

rate on exercise tolerance tests.

Fewer studies have evaluated the effectiveness

of radionuclide ventriculography in diagnosing

coronary artery disease (6,7,9,12,15,63,71).

Studies employing regional wall motion abnormalities as the criterion for a positive test indicate an average sensitivity of 89 percent and an

average specificity of 88 percent (table 19). Two

studies comparing radionuclide ventriculography to the thallium-201 perfusion in the same

patient population demonstrate similar sensitivity estimates but lower specificity for ventriculography (6,15). Abnormalities in the response

of ejection fractions to exercise and measurement of the first one-third of ejection fraction at

rest also appear to be promising criteria for the

diagnosis of coronary artery disease (7,71).

Diagnosis of Acute Myocardial Infarction

Medical Decisions Affected .—Between 20 and

50 percent of patients admitted to coronary care

units with chest pain syndromes ultimately

prove not to have had an acute myocardial infarction. Care at home or less intensive care in

the hospital may suffice for patients with chest

pain but no infarction. Hence, early and accurate exclusion of myocardial infarction may

obviate unnecessary admissions, with consequent savings in patient inconvenience and cost.
Current indices of infarction—clinical history,

EKG, or enzyme elevations—are either insufficiently sensitive or specific or may not confirm

the diagnosis for several days. Better tests are

needed.

Techniques. —Two radionuclide techniques

have been applied to the diagnosis of acute myocardial infarction: thallium-201 and technetium99m pyrophosphate infarct imaging. The former

identifies an infarcted area as a perfusion defect

(“cold spot”); the latter isotope concentrates in

the infarcted area and creates a “hot spot.” The

technetium pyrophosphate technique has several

drawbacks. First, a study may be falsely negative if circulation to an infarcted area is completely obstructed. At least limited perfusion is

required to allow the radionuclide to reach the

infarcted area. Second, the test does not become

maximally sensitive until 24 hours after the onset

of symptoms. Hence, it is of limited value in

helping to decide whether to admit a patient to

the hospital. Finally, a small but significant

number of patients remain positive for several

months after an infarction, thus creating the

potential for false-positve results. Thallium

studies, on the other hand, are most sensitive

during the first 24 hours, but cannot distinguish

new from old infarctions.

Definition of Disease. -Invariably, acute

myocardial infarction is defined in terms of the

clinical history and the electrocardiographic and

enzymatic changes that are observed over a

number of days of hospitalization.

Populations Studied. —Most studies have

been performed on patients admitted to coronary care units or on patients with documented

myocardial infarctions.

Results.—Results for technetium-99m and

thallium-201 studies are summarized in table 20.

Sensitivity for technetium-99m studies ranged

from 74 to 100 percent and averaged 93 percent

for studies done 24 or more hours after admission. False-negative results related primarily to

small or nontransmural myocardial infarctions.

Specificity, where measurable, averaged 78 percent. False-positive results occurred especially

when diffuse uptake and minimal focal uptake

were included in the criterion for an abnormal

test. In three studies that directly compared thallium-201 and technetium-99m techniques, sensitivities were approximately equal (3,69,83).

Assessment of Ventricular Function

Medical Decisions Affected. —Objective evaluation of left ventricular function is needed in at

least four clinical circumstances. First, in patients with heart failure of uncertain cause, it is

needed to identify surgically treatable disease

(e.g., left ventricular aneurysm). Second, it may

serve to exclude from cardiac catheterization

and surgery patients who would be untreatable

surgically or who would have an unacceptably

high risk associated with surgery (e.g., patients

with cardiomyopathy). Third, objective evaluation of ventricular function may help guide

medical treatment aimed to improve symptomatic heart disease or to monitor unwanted side

effects of certain drugs on the heart (e. g., those

of the anticancer agent, adriamycin). Finally,

ventricular function studies in patients with lung

disease may help to establish whether shortness

of breath is pulmonary or cardiac in origin;

treatment will vary accordingly.

Techniques. —The technetium-99m radionuclide ventriculographic techniques described

earlier can be used to determine the several parameters of right and left ventricular function.

Definition of Disease.—The medical history,

physical examination, and routine laboratory

studies may be insufficient to determine the

cause of ventricular failure. Cardiac catheterization and the contrast ventricular angiogram typically are used in situations where ambiguity exists. Disease is defined in terms of abnormalities

in pressures, blood flows, and myocardial contractility observed at rest and during exercise.

Populations Studied.—Patients with various

types of heart disease who have been studied by

cardiac catheterization.

Results.—Agreement between radionuclide

and contrast ventriculograms in the evaluation

of ventricular function has been excellent. Correlation coefficients for left ventricular ejection

fraction comparing first-pass studies to contrast

studies average 0.90 (range 0.80 to 0.95) (9,23,

42,61). Comparisons of MUGA studies to con-
Table 20.—Technetium.99m Stannous Pyrophosphate (“Hot spot”) and Thallium.201 Perfusion Scans

in the Diagnosis of Acute Myocardial Infarctiona

Test results

--

No of

subjects

23

200

20

100

31

78

38

26

80

114

52

Prevalence of

disease

65%

100%

1 00%

590/0

48%

1000/0

53°4

100%

100%

65%

600/0

Tc-99m

s = 1000/0 ;Sp = 1000/0

s = 500/0

TI-201 Comments

‘Good correlation with EKG

Iocalization of Ml in all patients with positive scans

Defect size decreased in

first 24 hr in patients with

repeat scans

Author

Parkey, et al (56)

Year Select Ion criterion

1974 Admission to CCU

Time from Ml to test

1-5 days in 19

7-10 days in 4

Wackers, et al (84) 1976 Documented Ml c 6 hr in 44

<24 hr in 96

24-48 hr in 36

3-10 days in 68

at 1 mo in 18

at 9 mo in 18

1-6 days

s = 100 ”/0

S = 94%

S = 58%

S = 79%

———

S = 830/0

S =61%

s = 17%

s = 100 ”/0

SP = 520/.

Mann, et al (41)

Holman, et al (31)

1978 Documented Ml

1978 Admissions to CCU

Persistently positive scans

detract from value of Tc99m to diagnose acute Ml.

False positives occurred

with diffuse or slight focal

uptake especially in patients with unstable

AP. S = 1000/.

with intense focal or

massive uptake

Focal uptake the criterion

for abnormality 2/16 patients with unstable AP

had focal uptake.

Of patients with I Ml 38°A

showed RV Involvement

Criterion for positivity was

“definite uptake “

4-8 hr

24 hr

s = 73 ”/0

s = 100%

Sp= 88%

Holman, et al (30) 1978 Admissions to CCU

Wackers, et al (83)

Hoilund-Carlsen,

et al (28)

Sharpe, et al (69)

1978 Patients with

Inferior Ml

1978 20 patients with Ml

18 without Ml

1978 Acute TM Ml

S = 82% s = 100 ”/0

s = 100%

SP = 83%

s = 100% s = 100%

Berger, et al (3) 1978 55 patients with TM s =91%

Ml and 25 with

NTM Ml

1979 31 with NTM Ml,

43 with TM Ml,

40 with stable AP

2-12 days

1-5 days

s = 950/0 Excellent correlation with

EKG localization of MI.

Massie et al (44) Overall. S = 74 ”/0

TM: S =91%

NTM: S = 52%

Overall. Sp = 90°/0

4 false positives in patients

with AP had diffuse uptake Diffuse uptake nonspecific, discrete uptake

highly specific but insensitive in NTM Ml

All 12 false positives in

patients with unstable or

stable AP had pathological

evidence of multifocal

necrosis or fibrosis

——

Poliner, et al (58) 1979 59 studies in 52 ?

patients who later

had post mortem

examinations or

surgical myocardial biopsies

s = 94%

SP = 57%

—

CCU = coronary care unit AP =

Ml = myocardial infarction s .

TM Ml = transmural Ml Sp =

angina pectoris

sensitivity

specificity

NTM Ml = nontransmural Ml RV = right ventricular

IMI = inferior Ml

aln all cases, the dlagnosts of acute M I was established by history, EKG changes, and enzyme elevations.

trast studies average 0.88 (range 0.84 to 0.93) gestive heart failure,

(22,23,61,79,82), and those comparing first-pass tricular dysfunction

similar patterns of left venby contrast and radionuto MUGA studies average 0.93 (range 0.87 to

0.94 (23,61,82).

elide techniques were demonstrated in 34 of 36

patients (53). This paper also reported that of 82

patients studied, 4 patients were scheduled for

cardiac catheterization because scans disclosed

potentially operable left ventricular aneurysms,

and 20 patients were excluded from catheterization because of extensive ventricular dysfunction that would effectively preclude surgery.

This is the only study reviewed that directly addressed the question of the potential of radionuclide studies to substitute for cardiac catheterization.

Evaluations of regional ejection fraction abnormalities by radionuclide techniques have

been fewer, in part because of the need for

sophisticated computer programs, Available

results show excellent agreement with contrast

ventriculography, both for the localization of

dysynergic (poorly contracting) areas and for

quantification of the degree of impaired contractility (9,22,79). In a study of patients with con-
Evaluation of the Results of Coronary

Artery Bypass Surgery

Medical Decisions Affected.—Evaluations of

patients who undergo coronary artery bypass

operations aim to determine the etiology of residual chest pain and to permit more judicious

prescriptions for physical activity and medical

treatments.

Techniques. —Thallium-201 studies have been

used to evaluate improvements in pre-existing

perfusion defects following surgery, while technetium-99m pyrophosphate studies help to determine the incidence of postsurgical myocardial

infarctions.

Populations Studied. —Patients who have undergone coronary artery bypass operations,

most of whom were studied by radionuclide

techniques, as well as by coronary arteriography

and contrast ventriculography, preoperatively.

Results.—Tables 21 and 22 summarize selected studies using thallium-201 and technetium-99m infarct imaging scans, respectively.

Postoperative exercise thallium scans show improved perfusion in 70 to 80 percent of patients.

Excellent correlation with graft patency was

shown in the two studies in which postoperative

scans and coronary arteriograms were systematically compared (26,65). The resolution of persistent as well as transient (exercise) defects has

raised questions about the interpretation that

resting thallium defects represent old myocardial

infarctions (2). The limited number of technetium-99m studies reviewed suggest that this

technique is more specific than either enzymes or

the EKG in identifying postoperative myocardial

infarctions.

Table 21.—Thallium-201 Perfusion Scans in the Evaluation of Coronary Artery Bypass Surgery Results

Number of

Author Year Select ion criterion subjects Results

Ritchie, et al. (65) 1977 Imaging before and after 20 Exercise perfusion improved in 7 of 11

CABS patients. In 13 of 20, there were no new

or enlarged defects postop; graft patency in these was 87°/0. In 7 of 20 with

new defects, graft patency was 54°/0.

Veroni, et al. (79) 1978 Imaging before and after 23 Exercise scans improved in 19 patients

CABS but become normal only in 9.

Greenberg, et al. (26) 1978 Imaging after CABS 27 Postop catheterization in all patients: 17

with recurrent chest pain; 10 because

MD wanted information on graft patency. Cath criterion Z 75% obstruction.

Exercise tolerance test: sensitivity 60%,

specificity 86°/0; equivocal results in 6

patients. Scintigram: sensitivity 67°/0,

specificity 100°/0. In 7 patients with

preop and postop scintigrams who had

postop caths, correlation with successful revascularization was excellent.

1978 Imaging before and after 36 21 patients had no evidence of ischemia

CABS on TI-201 scan postop; all symptom

free. 15 patients had unchanged or

decreased ischemia; 8 had angina.

Perioperative myocardial damage noted

in 8 patients.

1979 Triple vessel CAD: 30 One-half of abnormal preop scintigrams

20 with CABS resolved. TI-201 stress/reperfusion

imaging correlated “well” with complete revascularization.

Berger, et al. (2) 1979 Imaging before and after 22 37 of 48 transient defects (77%) resolved

CABS postop; as did 13 of 18 “persistant”

defects.

CABS = coronary artery bypass surgery

CAD = coronary artery disease

Robinson, et al. (67)

Leppo, et al. (35)
Table 22.—Technetium-99m Pyrophosphate Scans in

Patients Who Have Had Coronary Artery Bypass Surgery

Lowenthal, et al. (38) 1977

Roberts, et al. (66) 1979

44

27

Author Year Number of subjects Results

Klausner, et al. (33) 1977 51 10 of 51 patients had positive

scintigrams postoperatively; in 8,

EKG and enzymes were also positive;

in 2, enzymes were positive.

29 patients developed abnormal

enzymes or EKG postoperatively. 2

had positive scans. Scintigrams the

most specific criterion.

Tc-99m glucoheptonate. Of 7 patients

with positive postop scintigrams, 4

had abnormal EKGs and enzymes

and 3 had abnormal enzymes only.

Technical Challenges and

Interobserver Variability

The technical aspects of radionuclide studies—patient evaluation, proper injection of the

required quantity of radionuclide, adequate exercise during exercise studies, proper positioning

of the scintillation camera, choice of count

times, and important analytic factors such as

background subtraction and edge detection–all

are vital to achieving optimal results. That problems arise is exemplified by Okada, et al. (55),

who reported that 5 of 98 studies were technically unsatisfactory. Additional references to scans

that were uninterpretable or of marginal quality

were frequent. Furthermore, the laboratory directors who were interviewed indicated that as

many as 5 percent of studies had to be repeated

because of technical inadequacies.

The interpretation of radionuclide studies involves considerable subjectivity and, even in the

hands of experts, may result in important interobserver and intraobserver variations. Blood (4)

indicated interobserver disagreements in 8 percent of studies, and Massie (43) found interobserver disagreement for 13 percent of myocardial regions and intraobserver differences in 10

percent of images.

Careful evaluation of MUGA imaging in one

institution (55) revealed interobserver variances

for the estimation of ejection fraction of 6.0 to

8.8 percent in resting studies and 9.6 to 14.0 percent in exercise studies. These variances were

comparable to those for left ventricular angiograms (11.6 percent). Intraobserver variances

were of the same order of magnitude. To increase confidence in results, the authors advocated an average of at least two determinations

for calculations of exercise-induced changes in

ejection fractions.

It is important to re-emphasize that results

reported in the medical literature represent the

best that can be obtained by current technology.

Authors of these papers are experts, and often

the innovators, in nuclear medicine. They have,

by and large, the best equipment that is available, perform studies meticulously, and take

great care in data analysis and interpretation. As

diffusion occurs, technical problems and interobserver variations are almost certainly going to

increase.

Potential Risks From Cardiac Imaging

Potential risks from cardiac imaging fall into

two categories: risks due to exposure to radiation and nonradiation risks.

Nonradiation risks relate to emotional or

physical trauma to the patient as a result of the

cardiac imaging procedure. Anxiety precipitated

by the procedure’s results—needless anxiety if

the results are falsely positive or inadequately

explained—may be significant. Pain, development of a hematoma or infection at the site of injection, and the small but definite risk of a cardiac arrest or myocardial infarction during an

exercise test are the physical effects to be considered. These potential adverse effects must all
be weighed against the benefits of the information to be derived from the procedure. Information with which to quantify these nonradiation

risks does not appear in the literature.

The risks of exposure to radiation may be of

greater concern. Populations that are exposed

include not only the patients, but also producers

of radionuclides, transport workers, users, and

persons involved in the disposal of radioactive

wastes. Despite the importance of broader environmental and economic issues related to the use

of radionuclides, attention in this case study is

limited to the risks incurred by the users and patients.

Actual radiation exposures experienced by

technologists, physicians, and other hospital

employees working in or around radionuclide

laboratories were not determined. Radiation

safety regulations require staff members to wear

film badges that monitor radiation exposure. We

assume (perhaps optimistically) that these regulations are observed and that any unusual exposures would be detected before significant risk

was incurred. Radionuclide exposure to these

personnel, other than spillage onto skin or clothing, would be through the walls of the container.

Because electron energies of less than 150 keV,

the levels of technetium and thallium, barely

penetrate glass or plastic, the risk is probably

minimal.

At greater risk is the patient, and especially

the patient who undergoes repetitive scans over

a period of years for purposes of screening or for

monitoring treatment of an established disease.

Typical whole-body and selected organ radiation doses for cardiac radionuclide procedures

and for chest X-ray and mammography are

shown in table 23. Factors that determine organ

exposure include radionuclide dose per test; radiation half-life (6 hours for technetium-99m

and 74 hours for thallium-201); the affinity of

the organ for the particular chemical form of radionuclide employed; excretory route; and the

number of tests performed. The total body exposure from radionuclide scans is similar to that for

mammography and is well within radiation exposure guidelines. Judging from the recent controversy over the potential risk from yearly

breast cancer screening with mammography,

however, care needs to be taken in evaluating

the potential long-term effects of repeated lowdose radiation exposure. Too little is known at

the present time.

Table 23.—Radiation Exposure From Cardiac Radionuclide Imaging and Selected Radiodiagnostic Procedures

Procedure and radiation exposure (millirads)

Tc-99m Tc-99m

Irradiation site TI-201a pyrophosphate b

pertechnetate c Chest X-rayd e Mammography

Total body . . . . . . . . . . . . . . . . .

Skeleton. . . . . . . . . . . . . . . . . . .

Bone marrow . . . . . . . . . . . . . . .

Kidneys . . . . . .’. . . . . . . . . . . . .

Bladder: 2 hour void . . . . . . . . .

4.8 hour void . . . . . . . .

Skin. . . . . . . . . . . . . . . . . . . . . . .

Testes: 2 hour void . . . . . . . . . . 

4.8 hour void. . . . . . . . .

Ovaries: 3 hour void. . . . . . . . . .

4.8 hour void . . . . . . . . )

Heart: normal. . . . . . . . . . . . . . .

impaired . . . . . . . . . . . . . )

360

—

510

2,200

—

—

—

810

850

510

130

590

420

2,100

1,460

3,450

—

150

230

140

230

110

220

320

—

—

2,400

—

270

370

790

3.3 —

—

—

—

59

—

100 —

—

—

—

2,000

—

—

—

aEstimated absorbed radiation dose to a 70-kg patient fOllOWing injection of 15 MCI of TI-201.

bEstimated absorbed radlatlon from an ,ntravenou~ injection of 15 mci of Tc.99m.labeled stannous pyrophosphate Into a 70-kg patient undergoing bone Or cardiac

(“hot spot”) imaging. About half the dose is retained In the skeleton, and half IS excreted Into the bladder, The skeletal area of highest Intake may receive up to 5,900

millirads

CE~timated ~b80~~ r~iation oneha[f hour after an intravenous Injection of 20 mcl of Tc-99m-labeled sodium pertechnetate into 70-kg patient undergoing MUGA

Imaging.

dpersonal communication from Dr. Jacob Shapiro, Cambridge, Mass.

eposterior.anterior and lateral.
COST= EFFECTIVENESS ANALYSIS

How can available information be used to

evaluate the cost effectiveness of cardiac radionuclide imaging procedures? What are the alternative diagnostic strategies to which radionuclide imaging should be compared? For what

specified populations? What are the limitations

of cost-effectiveness analysis (CEA) for diagnostic procedures in general and for cardiac radionuclide imaging procedures in particular? What

additional information is needed to evaluate the

potential benefits and costs of radionuclide imaging? These are the questions to be addressed in

the discussion below.

Framework for Analysis

Who Is the Decisionmaker?

To be most useful, CEA must be tailored to

the perspective of the particular decisionmaker.

One decisionmaker’s cost and benefit priorities

may differ from those of another decisionmaker.

Our own analysis takes the perspective of a

Congress interested in allocating limited public

dollars to medical care in such a way as to

achieve maximal medical benefits. Nonmedical

costs and benefits are ignored. This perspective

differs, of course, from that of the patient who is

interested primarily in out-of-pocket costs compared to medical benefits, or the physician interested in his or her own net income and professional satisfaction, as well as in the patient.

Health maintenance organizations and thirdparty reimbursers will have still other sets of

priorities.

Measures of Cost

Costs to be considered are the total of incremental or marginal costs that can be attributed

directly to the performance of the test. These include the following:

●

●

Direct cost of the tests. For our decisionmaker, these costs would be the reimbursements to be provided out of tax

dollars for tests done on Medicare and

Medicaid patients.

Cost of any tests that need to be repeated

because of technically inadequate results.

●

●

●

●

Cost of induced tests (tests that would not

have been performed had the test in question not been used). Tests may be induced

either by abnormal test results or by normal

results if the latter are unexpected.

Cost of tests saved when one test is

substituted for another. For example, cardiac radionuclide scanning may substitute

in some cases for the exercise tolerance test

and/or the coronary arteriogram.

Cost of treating any adverse effects attributable to the diagnostic test or induced

tests.

Cost of subsequent treatment that can be attributed directly to the availability of the

diagnostic test. An example would be the

cost of coronary artery bypass surgery in

asymptomatic patients with coronary artery disease who would not have been identified had cardiac imaging not been performed. The cost of treatment includes not

only its direct cost, but also costs of the

treatment of any complications and any

savings from the prevention of future morbid events.

Calculation of the net marginal costs of a new

diagnostic technology, therefore, requires information on:

1. the direct cost of the new diagnostic test;

2. the direct cost of each diagnostic test that

might be substituted for or induced;

3. the direct cost of treatments that might be

induced;

4. the indirect cost of each of the above;

5. the likelihood, in each population to which

the test would be applied, that additional

diagnostic tests or treatments would be induced.

The direct costs of tests are usually readily

available or calculable. Indirect costs usually

have to be estimated, often from inadequate information. Probabilities of induction or substitution are the most difficult data to obtain and

usually become available relatively late during

the diffusion of a new technology.
Measures of Effectiveness

Conceptually, the effectiveness of a diagnostic

test lies in its information content and in the

ability of that information to affect subsequent

medical decisions in ways that benefit the patient. As with its costs, a new test’s effectiveness

must be determined in marginal terms, either in

direct comparison with an existing technology

that it may replace or as an add-on to existing

diagnostic strategies. For technologies with multiple uses and multiple potential target populations, marginal effectiveness should be aggregated over all uses and all populations. Analyses

that focus on only a single use or population will

not fully describe the technology.

Effectiveness can be assessed at several levels,

depending on the availability of data:

●

●

●

The

actual health benefit in terms of life-years or

quality-adjusted life-years gained;

treatments affected—with projections of expected health benefits from these; and

diagnostic information gained—with projections of expected treatment changes and

resultant health benefits.

closer the analysis can come to direct estimates of health benefits, the more conclusive it

will be. This is especially true in view of the tenuous relationship that frequently exists between

diagnostic information and medical care decisions, and between treatments and subsequent

health benefits.

However, very useful C2EAS of diagnostic

technologies can rest solely on careful assessment of diagnostic information alone, provided:

1) there is reasonable evidence linking the availability of this diagnostic information to treatment decisions and resultant health benefits; 2)

decisions that might be affected are made explicit; and 3) physician thresholds for diagnostic

or therapeutic decisions are established. When

these conditions are met, the value of diagnostic

information will depend on the prior probability

of the disease given the patient’s characteristics

and the results of any prior diagnostic tests; the

sensitivity and specificity of the diagnostic test;

and the relationship of the resultant posterior

probability of disease, given positive or negative

results on the test, to a threshold for a specific

decision. The measure of effectiveness, then,

becomes the ability of the test to effect an action—the choice of a more definitive diagnostic

test or a better treatment.

Example.—A hypothetical example will serve

to demonstrate the aforementioned approach.

Assume a patient (or homogeneous group of

patients) with specified characteristics and a certain prior probability (Po) of a disease and a disease defined in terms of a generally accepted criterion for offering a specified beneficial treatment (e.g., surgery). The relation between the

prior probability (Po) of the disease and the posterior probability (PP), given the results of a test

with known sensitivity and specificity, is provided by Bayes’ theorem and is shown graphically for an abnormal test result in the figure

below. *

1.0

0.8

PP 0.6

0.4

0.2

0.2 0.4 0.6 0.8 1.0

Po

Thre

for

deci

sho 

sio

l d

n

Assume that the threshold for proceeding to a

definitive, though more risky, diagnostic procedure that must precede the beneficial treatment

is 0.8. If the Po were 0.1 and an abnormal result

were obtained, the PP would be 0.4, a value not

sufficiently high to effect an action. If the Po, on

the other hand, were 0.85, a normal result

would lower the PP only to about 0.7. It is dubious whether such a finding would dissuade the

physician from doing the more definitive study.

In this case, the test would be superfluous. Final-

*See previous discussion of Bayes’ theorem in the section of this

case study on diagnostic information.
ly, a Po between 0.4 and 0.6, if the test result

were abnormal, would lead to a PP in excess of

the threshold for action, unequivocally valuable

information. Patients with Pos in this range

would benefit most from the test.

Cost Effectiveness of Cardiac

Radionuclide Imaging

costs

Information is available on the direct costs of

radionuclide imaging procedures (see unit costs

in table 15 and suggested fee schedules in table

16) and the direct costs of the coronary arteriogram and exercise tolerance test. In Boston, the

usual charge for a coronary arteriogram (including 2 days of hospitalization) is about $1,500,

and the charge for an exercise tolerance test is

$110.

The costs of treating occasional cardiac arrests

and myocardial infarctions precipitated by exercise tolerance tests and a variety of complications from coronary arteriograms can only be

speculated upon, and we made no attempt to

quantify them for our analysis. Furthermore, no

information exists on the extent to which cardiac

radionuclide scans substitute for or induce other

tests. The most likely substitutions would be for

exercise tolerance testing in the diagnosis of

chest pain syndromes and for coronary arteriography in the selection of patients who might be

candidates for cardiac surgery.

The potential to induce additional testing and

treatments would relate primarily to the widespread use of imaging to screen asymptomatic

populations for coronary disease. Abnormal

screening results would undoubtedly lead to coronary arteriograms in some patients who otherwise would not receive them and to surgery in

some patients with “significant” and “surgically

correctable” lesions. No evidence exists at present to document the effectiveness of coronary

artery bypass surgery in asymptomatic populations; nonetheless, there might be a tendency to

extrapolate results from symptomatic groups, in

which enhanced survival has been demonstrated, and to offer surgery to such patients.

Effectiveness

On the effectiveness side of the equation, cardiac radionuclide imaging can be judged at present only in terms of the diagnostic information it

provides. Effects on treatment decisions and on

ultimate health benefits have yet to be evaluated. Even estimates of information content

must be considered to be tentative because of the

highly selected natures of the populations in

which test sensitivity and specificity have been

evaluated. Whether comparable results will be

obtained in more heterogeneous populations

and by average users of the technology remains

to be seen.

For purposes of our analysis, we do not distinguish among the various radionuclide procedures. On the average, thallium perfusion,

MUGA, and first-pass studies appear to have

comparable sensitivities and specificities for the

presence of coronary artery disease, though the

radionuclide ventriculogram techniques have

the advantage of providing additional information on ventricular function not provided by

thallium-201 perfusion studies. We also assume

that the sensitivity and specificity of scans are

not dependent on the prevalence of coronary

disease in the population being tested nor on

other patient characteristics (an assumption that

may well overestimate the value of imaging).

Conditions of the Effectiveness Analysis. —

1.

2.

Definition of coronary artery disease

(CAD): anatomic evidence of at least

70-percent obstruction of one or more coronary arteries.

Decision affected: to perform coronary arteriography as a precondition to selecting

patients for coronary artery bypass surgery. Patients with “definite angina” are

considered to meet the criterion for surgery

if one or more coronary arteries are diseased. Patients with “probable angina” or

“nonischemic pain” are candidates only if

they have multivessel disease (MVD). The

rationale for these assumptions is based on

evidence suggesting that coronary surgery

is clearly superior to medical treatment in
3.

4.

5.

6.

7.

relieving angina, regardless of the number

of vessels involved, and prolongs life if two

or more vessels are diseased.

Threshold probability for the decision to

perform coronary arteriography: posterior

probability of disease 0.80 or greater.

Type of chest pain and the prior probabilities of coronary artery disease (20,85):

prevalence of CAD

Type of chest pain CAD + MVD +

Definite angina men 89% 68%

women 62 39

Probable angina men 70 40

women 40 22

Nonischemic pain men 22 6

women 5 1

No pain both 4 (1)a

CAD = any coronary artery obstruction of 70 percent or

more.

MVD = obstruction of two or more coronary arteries.

aAssumed value.

Population tested: 200 patients (100 men

and 100 women) in each of the four chest

pain groups. Total number of patients is

800.

Sensitivity and specificity of tests for the

presence of coronary artery disease: unweighed average figures from the efficacy

studies reviewed earlier:

Sensitivity Specificity

Cardiac scans (thallium

and technetium). 8770 8970

Excercise tolerance test. 63% 80%

Neither type of test has been shown to differentiate reliably between single-vessel

and multivessel disease.

Diagnostic strategies: A variety of diagnostic strategies could be conceived that would

involve the simultaneous or sequential application of the various tests used to diagnose coronary artery disease (EKG, exercise tolerence test, radionuclide scans, echocardiography, coronary angiography).

Strategies would vary, no doubt, with the entry characteristics of the patient. The logical

comparison would be between the optimal (or

usual) strategy without the new technology and

the optimal (or usual) strategy employing the

new technology. The difference in effectiveness

between these two strategies would be in the

number of surgical candidates correctly identified (true positives), the number of surgical candidates missed (false negatives), and the number

of patients needlessly subjected to the risks of

coronary arteriography (false positives).

Alternative diagnostic strategies to be considered in our analysis are:

Strategy A: Cardiac radionuclide imaging in all

patients; coronary arteriograms in positives;

no further tests in negatives.

Strategy B: Cardiac radionuclide imaging in

subgroups of patients whose posterior probabilities (PPs) of disease in the face of an abnormal response would be at least 0.80; coronary

arteriograms in positives; no further tests in

negatives. Coronary arteriography without

prior radionuclide imaging in subgroups of

patients whose prior probabilities (Pos) of

disease are at least 0.80.

Strategy C: Same as A but with exercise tolerance testing.

Strategy D: Same as B but with exercise tolerance testing.

Results of Effectiveness Analysis.—The r e -

sults of calculations performed under the assumptions specified above serve to emphasize

several points (see table 24). First, diagnostic

strategies B and D lead to fewer coronary arteriograms, fewer false-positive examinations, and

fewer false-negative results than their counterparts, strategies A and C, with no loss in truepositive examinations. Hence, a decision rule

based on a threshold cutoff probability to guide

the use of diagnostic tests appears to be more effective than a blanket-testing decision rule,

Second, the strategies employing cardiac radionuclide imaging (A and B) result in the identification of more patients requiring surgery and

fewer missed surgical candidates than the strategies using exercise tolerance testing (C and D).

These advantages are partially offset for strategy

B, however, by the fact that a greater number of

patients are needlessly subjected to the risks of

coronary arteriography.

Finally, several clinical subgroups have calculated posterior probabilities of disease close to,

but not reaching, the threshold of 0.8. Proba-
Table 24.—Effectiveness of Alternative Strategies Employing Cardiac Imaging and Exercise

Tolerance Testing To Diagnose Surgically Treatable Coronary Artery Disease

Patient characteristics Results for alternative strategies

No.

No. CA No. TP No. FP No. FN

Symptom Po with PP/ A B A B A B A B

Strategy category Sex No. CAD CAD Abnl S CAD S CAD S CAD S CAD S CAD S CAD

Cardiac Definite angina M 100 0.89 89

imaging F 100 0.62 62

(strategies

A&B)

Probable angina M 100 0.70

F 100 0.40

Nonischemic pain M 100 0.22

F 100 0.05

No pain Both 200 0.04

Totals 800

70

40

22

5

8

296

0.98 78 100 77 77 89 89 1 1 11 11 12 12 0 0

0.93 58 58 54 54 54 54 4 4 4 4 8 8 8 8

0.95 64 64 35 61 35 61 29 3 29 3 5 9 5 9

0.84 42 42 19 35 19 35 23 7 23 7 3 5 3 5

0.69 28 0 5 19 0 0 23 900 1 3 6 22

0.29 14 0 1 4 0 0 13 10 0 0 0 1 1 5

0.25 28 0 2 7 0 0 26 21 0 0 0 1 2 8

312 264193 257197 239119 55 67 25 29 39 25 57

C D C D c D c D

Exercise

test

(strategies

C&D)

Definite angina M

F

Probable angina M

F

Nonischemic pain M

F

No pain Both

‘Totals

100 0.89

100 0.62

100 0.70

100 0.40

100 0.22

100 0.05

200 0.04

800

89

62

70

40

22

5

8

296

S CAD S CAD S CAD S CAD S CAD S CAD

0.96 58 100 56 56 89 89 2 2 11 11 33 33 0 0

0.84 47 47 39 39 39 39 8 8 8 8 23 23 23 23

0.88 50 50 25 44 25 44 25 6 25 6 15 26 15 26

0.68 37 0 14 25 0 0 23 12 0 0 8 15 22 40

0.47 30 0 4 14 0 0 26 16 0 0 2 8 6 22

0.14 22 0 1 3 0 0 21 19 0 0 0 2 1 5

0.12 43 0 1 5 0 0 42 38 0 0 1 3 1 8

287 197140 186153 172147 101 44 25 82 110 68 124

Assumptions

(1) The clinical population studied IS composed of 100 men and 100 women

with each of the four types of chest pain for a total population of 800 patients

(2) Health benefits accrue only to patients who subsequently receive coronary

artery bypass surgery, while all patients are subjected to the risks of the

diagnostic tests employed. Potential health benefits other than those

from surgery (e g , better medical treatment) are ignored

(3) patient S with definite angina receive surgery if any coronary artery IS Z 70%

obstructed, while patients with other types of chest pain or not chest pain

receive surgery only if multivessel disease IS present (2 or more coronary

arteries obstructed s 70% )

(4) Prior probabilities of CAD, the sensitivity and specificity of cardiac imaging

and exercise tolerance test, and the diagnostic strategies (A,B,C,D) are as

stated in the text

bilities at these levels, though not sufficient to

sway the decision to do coronary arteriography,

might well be sufficient to cause the physician to

perform some other noninvasive test. In this

case, serial likelihood estimation, in which the

previous posterior probability becomes the subsequent prior probability, might be employed in

order to reach the threshold for coronary arteriography. This technique, however, requires that

the results of different diagnostic tests be independent, a requirement that to date has not

been demonstrated convincingly.

Cost-Effectiveness Analysis

The limited CEA of cardiac imaging that is

possible provides some useful insights. Our analysis uses charges for laboratory examinations on

Abbreviations:

s —

CAD =

Po ——

PP/Abnl =

No. CA =

No. TP =

No. FP =

No. FN =

surgery

coronary artery disease

prior probability

posterior probability if the test is abnormal

number of coronary arteriograms done

number true positives cathed and found to meet criterion

for surgery

number of false positives: cathed and found not to meet

criterion for surgery

number of false negatives. not cathed and would have met

criterion for surgery

the cost side and effectiveness estimates presented in table 24. Costs and effectiveness for

each of the alternative diagnostic strategies A, B,

C, and D are calculated, and the marginal costs

and marginal yields of nondominated strategies

are derived.

Discounting is not used since all costs, risks,

and benefits (availability of diagnostic information) are immediate. If future benefits from surgery (improved survival, reduced angina) were

considered, discounting would be required.

Total costs of alternative diagnostic strategies

A, B, C, and D are shown in table 25, and costs

are presented with effectiveness estimates in table 26. To rank all strategies by a single cost-effectiveness criterion would require weighting the
Table 25.—Costs of Alternative Strategies To Diagnose

Surgically Treatable Coronary Disease”

Non invasive

Coronary arteriograms diagnostic tests Total cost

Strategy Number ($000’s) Number ($000’s) ($000’s)

Cardiac imaging

A (test all). . . . . . . . . . . . . . . . 312 $468 800 $280 $748

B (test threshold. . . . . . . . . . 264 396 300 105 501

Exercise test

C (test all). . . . . . . . . . . . . . . . 287 431 800 88 519

D (test threshold). . . . . . . . . . 197 296 200 22 318

aunlt ~fla~~~~ RadlOnUCllde scan—$sso (average recommended fee for rest and exercise Study)

Exercise test–$1 10 (local Blue Cross/Blue Shield rate).

Coronary arteriogram-$1,500 (local hospital rate in 1978),

Table 26.—Costs and Effectiveness of Alternative

Strategies To Diagnose Surgically

Treatable Coronary Disease

Effectiveness a

Strategy Cost ($000’s) TP FP FN

Cardiac imaging

A (test all). . . . . . . . . $748 193 119 29

B (test threshold). . . 501 197 67 25

Exercise test

C (test all). . . . . . . . . 519 140 147 82

D (test threshold). . . 318 153 44 68

TP = true positive, FP = false positive, FN = false negative

awith regpect to diagnosing surgically treatable coronary arte~ disease.

different measures of effectiveness so that they

could be combined. The weights, in turn, would

depend on the relation between the risk to a patient with surgically treatable coronary artery

disease who is not identified (false negative), the

risk of coronary arteriography in a patient who

does not have surgically treatable disease (false

positive), and the net benefits from coronary

arteriography and surgery (benefits minus risks)

in true positives. Such a weighting scheme

would be tenuous and is not attempted.

Instead, two other approaches are taken. In

one, the assumption is made that a correct diagnosis (true positive) has sufficient value that the

negative effects of false positives and false negatives can be ignored. In the second, no such assumption is made, and the strategies are compared qualitatively. Cost-effectiveness comparisons are presented in tables 27 and 28.

In table 27, strategies are ranked from least to

most costly, and the incremental costs and benefits are calculated relative to the next less costly

strategy. Comparison of strategy B to strategy D

reveals that 44 additional true positives cost

$183,000, or $4,200 per true positive. Strategy C

is dominated by B, in that C is both more expensive and less effective. Strategy A is also dominated by B. The average cost per true positive is

lowest for D. Whether a decisionmaker would

choose strategy D or B would depend on his or

her willingness to spend an additional $4,200 per

additional surgical candidate identified.

Qualitative comparisons between strategies

are presented in table 28, and these are also interesting. First, strategy A is effectively dominated by B, since A is both more costly and less

effective by all three measures of effectiveness.

Strategy C is similarly dominated by B. Comparison of B and D (threshold strategies for

radionuclide imaging and exercise tolerance testing, respectively) indicates that B buys additional true positives, at a cost, but also results in

fewer false negatives and more false positives. If

false negatives were in some sense considered to

be worse than false positives, the net benefits

from B relative to D would be increased further,

and the cost-effectiveness ratio for B would become more favorable.

In conclusion, decision strategies based on

threshold cutoff probabilities of disease (B and

D) are more cost effective than blanket-testing
Table 27 .—Cost Effectiveness of Alternative Diagnostic Strategies”

Marginal cost/TP

Strategy — ($000’s) — —

D . . . . . . . ... ..- —

B . . . . . . . . . . . . . . $183 44 $4-2

c . . . . . . . . . . . . . . 18 –57

A . . . . . . . . . . . . . . 229 53 4.3

A1 247 – 4

Average cost/TP

- ($000’s)

.

$2.1

2.5

3.7

3.9

aA~~um~s that the values of false-positive and false-negative results are inconsequential compared to true positives Marginal costs and benefits are calculated relative to the next less costly strategy. Because C is more costly and less effective

that B, it is dominated Similarly, A is dominated relative to B (labeled Al).

Table 28.—Cost-Effectiveness Comparisons Between

Alternative Diagnostic Strategiesa

Comparison

—

TP FP FN -

A-B -$247

-.

– 4 52 4 - ”

C-D. ., . . . . 201 – 13 103 15

A-C. ... 229 53 – 2 8 - 5 5

B-D . . . . . 183 44 23 – 44

A-D. ., ... 430 40 75 –40

C-B . 18 –57 80 59

.

aNo “SSuM~t,~n ,S made “bout th-e-rejatlw values of different Outcomes.

strategies. Furthermore, use of cardiac imaging

appears to identify additional surgical candidates at reasonable cost when compared to exercise tolerance testing. How reasonable these

additional costs are will ultimately depend on

the incremental health benefits achieved by coronary artery bypass surgery.

Sensitivity Analysis

Variables upon which our CEA depend include:

• the characteristics of the patient population

tested;

● the costs of tests employed;

● the threshold probability for decisionmaking;

Ž the sensitivity and specificity of scanning in

different population subgroups; and

● the diagnostic strategies compared.

Sensitivity analysis can be used to determine

the effects on the analysis of changes in assumed

values for each of these variables. Here we examine only the importance of the characteristics

of the population tested. Evaluation of the other

variables will be the subject of future research.

In our analysis in the previous section, the

four diagnostic strategies A, B, C, and D were

applied to a mixed population consisting of

equal numbers of males and females and equal

numbers of patients of each sex with definite angina, probable angina, nonischemic pain, and

no pain. A very important policy question,

however, relates to the need to define the optimal approach to diagnosis in different target

populations. To address that need, strategies A

and B (respectively, the test all and threshold

strategies for cardiac radionuclide imaging) are

evaluated in population subgroups defined by

sex and by symptom category. Table 29 summarizes the cost and effectiveness estimates, and

table 30 presents cost-effectiveness comparisons.

Strategy A leads to testing in all subpopulations, while by strategy B, testing is performed

only in patients with probable or definite angina

because of the 0.8 probability threshold required
Table 29.—Costs and Effectiveness of Alternative Strategies Employing Cardiac Imaging

To Diagnose Surgically Treatable Coronary Artery Disease in Population Subgroups

Strategy

A (test all) B (test threshold)

costs Effectiveness costs Effectiveness

Population tested (by symptom) Sex ($000’s) TP FP FN ($000’s) TP FP FN

Definite angina . . . . . . . . . . . . . . . . . . . . . . M $152 77 1 12 $150 89 11 0

F 122 54 4 8 122 54 4 8

Probable angina . . . . . . . . . . . . . . . . . . . . . M 131 35 29 5 131 35 29 5

F 98 19 23 3 98 19 23 3

Nonischemic pain . . . . . . . . . . . . . . . . . . . M 77 5 23 1 0 0 0 6

F 56 1 13 0 0 0 0 1

No paina . . . . . . . . . . . . . . . . . . . . . . . . . . . M 56 1 13 0 0 0 0 1

F 56 1 13 0 0 0 0 1

aDlstrlbutlons of costs and effectiveness assumed to be equal in M and F

Table 30.—Cost-Effectiveness Comparisons Across Population Subgroupsa

Strategy

A (test all) B (test threshold)

Average AC Average

Ac AE AE AE AE cost/TP

Population tested (by symptom) Sex ($000’s) (TP) ($000’s/TP)($000’s) ($000’s) (TP) ($000's/TP) ($000’s)

Nonischemic pain . . . . . . . . . . . . . . . . . . . Fb

$56.0 – – – –

Nonischemic pain . . . . . . . . . . . . . . . . . . . M $21.0 4 $5.2 15.4 — — —

Probable angina . . . . . . . . . . . . . . . . . . . . . F 21.0 1.5 5.2 $5-2

Definite angina . . . . . . . . . . . . . . . . . . . . . . F 24.0 35 0.7 2.3 $24.0 35 $0.7 2.3

Probable angina. . . . . . . . . . . . . . . . . . . . . 9.0 – 19 3.7 9 – 2 0 3.7

Probable angina. . . . . . . . . . . . . . . . . . . . . M

C

33.0 16 2.1 - 33 16 2.1 -

Definite angina . . . . . . . . . . . . . . . . . . . . . . M 21.0 42 0.5 2.0 19 54 0.4 1.7

aA~sumption is made that the values of false-positive and false-negative results are inconsequential compared to true positives

bcosts and effectiveness the same as in the no pain group for M and F

CCompared t. probable angina in F.

to proceed to coronary arteriography. Cost estimates are affected accordingly (see table 29).

Cost effectiveness is examined both by marginal analysis and by average cost-effectiveness

ratios (see table 30). Marginal analysis ranks

population subgroups tested from least to most

costly and calculates incremental costs and benefits relative to the next less costly subgroup.

Such analysis shows that as one progresses from

the testing of asymptomatic persons and females

with nonischemic pain to subgroups with higher

prevalence of surgically correctable coronary

artery disease, incremental costs per true positive for both strategies A and B fall. Average

cost-effectiveness ratios indicate a cost per true

positive of no more than $5,200 for patients with

probable or definite angina, but a considerably

higher ratio than this for patients with nonischemic pain or no pain ($56,000 per true positive

in females with nonischemic pain, in both sexes

in the absence of pain). Clearly, the characteristics of the population tested have important implications for the cost effectiveness of diagnostic

strategies. Cardiac imaging does not appear to

be cost effective in the routine testing of asymptomatic patients or patients with atypical chest

pain syndromes.
POLICY IMPLICATIONS

Cardiac radionuclide imaging is a new, rapidly expanding, and relatively expensive technology with the potential for extremely broad application in the diagnosis and evaluation of heart

disease. The major challenges are to define the

limits of its potential, to ensure proper use

within those limits, and to maintain quality control. Physicians, the government, and thirdparty carriers all will need to participate in meeting these challenges.

Physicians are in the best position to define

clinical indications and to ensure quality control. Since physicians stand to benefit monetarily and professionally from the performance of

cardiac scans, however, they need to be counterbalanced by others who have a societywide

perspective. Among the issues that require contributions from outside the medical profession

are utilization control, prevention of possible

low-dose radiation risks, and planning for future

R&D.

Policy questions stimulated by the present

study

1.

2.

3.

4.

include the following:

Under what circumstances does cardiac

imaging serve a useful role in cardiac diagnosis and evaluation, and what is the potential of cardiac imaging to obviate the

need for other diagnostic modalities?

Should the diffusion of cardiac imaging

capability be limited to hospitals with

demonstrated nuclear medicine expertise,

or should commercial laboratories and

private practices perform scans?

Could certificate-of-need legislation be

used to limit diffusion? Does scanning

constitute a new service? Since cardiac imaging may be performed with existing

equipment, it seems unlikely that the

capital expenditure limit of the certificateof-need legislation will be applicable except to positron emission tomography and

new types of CAT equipment.

Should a group of experts be asked to define clinical indications for imaging? How

would the standards be updated to accommodate improvements in the technology?

5.

6.

7.

8.

9.

10.

11

Most

How could utilization be limited to these

indications? Could reimbursement policies under Medicare and Medicaid be

adapted to this end?

At present, there are wide differences in

third-party reimbursement policies in different parts of the United States. Would

standardization of policies and rates by

Medicare/Medicaid and Blue Cross/Blue

Shield be desirable? If the twofold discrepancy between the resource costs of

scans and fee schedules were verified,

should reimbursement schedules be adjusted?

How can safety in the use and disposal of

radionuclides in cardiac imaging be assured?

How should the quality of laboratory results be monitored? Would a mechanism

of quality control similar to that used by

clinical chemistry laboratories be feasible?

Should R&D in new radionuclide imaging

techniques be encouraged? With what objectives?

What further evaluation of the clinical effectiveness and cost effectiveness of radionuclide imaging needs be done? Should

the use of scans by practicing physicians

be monitored to document the effects on

clinical decisions and patient benefits?

Should the sensitivity and specificity of

these techniques in population subgroups

be further evaluated?

Would a National Institutes of Health

consensus conference serve as a useful

stimulus to develop policy concerning cardiac radionuclide imaging and to increase

awareness of the medical profession of the

benefits and limitations of imaging?

of these questions are generic ones that

need to be addressed for any- new technology

and for many existing technologies, as well. Implementation of a uniform policy for evaluating

medical technologies would serve, in the long

run, to benefit the public and the medical profession alike.
Angina pectoris: a condition characterized by severe

transient chest pains, typically precipitated by

exertion or excitement and relieved by rest.

Arrhythmia: any variation from the normal rhythm

of the heart beat.

Arteriography: the radiologic (X-ray) visualization

of the blood vessels following the injection of a

contrast dye.

Cardiac catheterization: passage of a small catheter

through a vein or artery into the heart for purposes of securing blood samples, determining intracardiac pressures, and detecting cardiac

anomalies.

Cardiac ejection fraction: the amount of blood

ejected during a heart beat.

Cardiac radionuclide imaging: the imaging of the

heart by the detection of radioactivity in the

heart muscle or heart chambers following the injection of a radionuclide or radiopharmaceutical.

Coronary arteries: arteries that supply blood to the

heart.

Coronary arteriography (coronary angiography): arteriography of the coronary arteries.

Coronary artery disease (coronary heart disease):

narrowing or blockage of the coronary arteries,

usually which results in reduced blood flow to

the heart muscle.

Coronary artery bypass surgery: a surgical procedure in which a vein or an artery is used to bypass a constricted portion of one or more coronary arteries. This procedure has become the primary surgical approach to the treatment of coronary artery disease.

Echocardiography: a method of imaging the heart

walls and internal structures of the heart by the

echo obtained from beams of ultrasonic waves

directed through the heart wall.

Effectiveness: same as efficacy (see below) except that

it refers to “average conditions of use. ”

Efficacy: benefit achieved in a defined population

from a medical technology applied for a given

medical problem under ideal conditions of use.

Electrocardiogram (EKG): a graphic tracing of the

changes of electrical potential of the heart occurring during each heartbeat; usually performed

with the patient supine and at rest.

Exercise tolerance testing (exercise stress testing):

testing the response of the heart to exercise while

observing the EKG and other physiological functions of the heart.

Half-life: the time required for the activity of a given

quantity of radioactive material to decay to half

its initial value.

Infarct: an area of necrosis (death) of tissue resulting

from the obstruction of blood supply.

Intracardiac shunt: an abnormality of blood flow between the sides of the heart.

Ischemia: insufficient blood supply to meet the full

physiologic needs of the tissue for oxygen (but

short of the degree of ischemia that results in necrosis).

Ischemic heart disease: coronary artery disease of

sufficient severity to result in angina pectoris or

myocardial infarction.

Myocardial infarction: necrosis (death) of tissue in

the myocardium (heart muscle) that results from

insufficient blood supply to the heart. A transmural myocardial infarction involves the entire

thickness of the myocardium, while a nontransmural infarction involves only part of the wall.

Myocardium: muscle of the heart.

Nonischemic heart disease: heart disease from causes

other than coronary artery disease (e. g., congenital heart disease, rheumatic heart disease, myocardiopathy).

Posterior probability of a disease: the probability

that a disease exists after the results of a given

test are known.

Prior probability of a disease: the probability that a

disease exists before the results of a given test are

known.

Radionuclide or radiopharmaceutical: a radioactive

substance.

Radionuclide ventriculogram: an image of the chambers (ventricles) of the heart obtained by detection of radioactivity following the injection of a

radionuclide or radiopharmaceutical.

Sensitivity of a diagnostic test: proportion of all persons with a given disease whose tests results are

positive (true-positive rate).

Specificity of a diagnostic test: proportion of all persons without a given disease whose results are

negative (true-negative rate).

Ventricle: chamber of the heart.

Ventricular angiogram: a radiologic image of the

ventricles of the heart obtained following the injection of a contrast dye.

Ventriculography: imaging of the ventricles of the

heart.

48
RADIONUCLIDE IMAGING EQUIPMENT AND SUPPLIES

Picker

Northford, Corm.

(Head office in Cleveland, Ohio)

Background.—Picker is a subsidiary of CIT Corporation. It is one of the oldest companies in the nuclear medicine field and has produced gamma cameras since 1970.

Products.—Scintillation cameras, CAT scanner.

Current Models.—

Year List

introduced price

DynaCamera 4/15-61 (15” field, 1979 $110,000+

61 photomultiplier tubes, scintillation camera)

DynaCamera 4 15-37 (15” field, 1976 $96,000-

37 tubes, scintillation camera) 100,000 +

DynaCamera 4/11-37 (11” field, 1976 $90,000

37 tubes, scintillation camera)

DynaMO (motorized mobile 1976? $100,000

scintillation camera, a 4/11-37 avg.

on wheels)

DynaCamera 4 (19 tubes) 1974 Discontinued

Market Share.—Claims independent survey of June

1978 to June 1979 sales of scintillation cameras gives

Picker 35- to 38-percent market share and first-place

ranking.

Customers.—1) Hospitals (ranked: radiology,

nuclear medicine, pathology, internal medicine, cardiology); and 2) physicians’ offices.

Sales Strategy .—Company prefers to be conservative and tries to maximize the number of standard

features, while minimizing add-on accessories. Emphasis on quality control in production raises cost of

products. Sales from network of 1 national, 4

regional, and 120 district offices. Advertisements are

aimed at physicians. Works with major computer

manufacturers to maximize ease of interface.

Future Directions for Company.—In 1979, introduced 7-pinhole tomography with 4/15-61 camera. Predicts that future products will be less expensive, yet will offer better resolution scans. Also researching positron emission tomography, but unsure

of economic feasibility.

Future Directions for Radionuclide Imaging.—Features will include higher performance digital computers, better resolution and lower cost. Emphasis will

be on improving resolution and sensitivity, better

service, and lower price in that order. Respondent

sees organizational trend in hospitals toward departments of medical imaging to consolidate administratively nuclear medicine, X-ray, ultrasound, C A T

scanning, and other imaging technologies.

General Electric (GE)

Waukesha, Wis.

Background.—GE entered the nuclear medicine

field in 1972 as a distributor for the Elscint wholebody scanner. In 1975, it bought Nuclear Data,

which had just developed the first mobile scintillation

camera.

Products.—Scintillation cameras.

Current Models.—

Year

introduced

MaxiCamera 2 System (large- 1978

field (16”) scintillation camera

system, 37 tubes)

MaxiCamera 535 (large-field 1978?

(24”) scintillation camera, 64

tubes)

MaxiCamera 400T (large-field 1979?

(24’ ) scintillation camera, 67

tubes, for 7-pinhole

tomography)

DataCamera (motor-powered, 1977

small-field mobile camera, 37

tubes)

PortaCamera 2C (manually 1977?

moved, small-field mobile scintillation camera, 37 tubes)

(MaxiCamera 1) 1977

(MaxiCamera) 1976

List

price

$80,000-

$120,000

$80,000-

$120,000

$65,000

Discontinued

Discontinued

Market Share.—Claimed 26 percent of scintillation

camera market in fiscal year 1978.

Customers.—1) Hospitals (ranked: nuclear medicine, radiology, internal medicine, cardiology); and

2) physicians’ offices.

Sales Strategy .—Broad range of models, including

PortaCamera 2C for the “van trade” (physicians and

technologists who bring the cameras in vans to remote hospitals). Field sales force includes 20 nuclear

medicine specialists and 300 X-ray salesmen. Advertising is aimed at physicians through professional

journals and medical conventions.

Future Directions for Company.—GE is developing single-photon emission tomography and positron

emission tomography equipment.

Future Directions for Radionuclide Imaging.—Respondent foresees more expensive equipment, especially more sophisticated computers. Scintillation

cameras will become digital solid-state detectors.

Trend toward positron emission tomography and the

assessment of cardiac metabolism. Sees organizational trend toward hospital departments of diagnostic imaging, consolidating all imaging functions.
Searle Radiographic

2000 Nuclear Drive

Des Plaines, Ill.

Background.—Searle was formed when G. D.

Searle, a pharmaceutical manufacturer, bought Nuclear Chicago in the 1960’s. First company to manufacture scintillation cameras. Still appears to have

largest installed base and largest market share.

Products.—Scintillation cameras,

CAT scanner.

Current Models.—

Year

introduced

Pho/Gamma 5 (scintillation 1977

camera system)

Scintiview (microprocessor) –

Gamma/COR (cardiac probe) 1977

Pho/Gamma LFOV (large-field- 1976

of-view scintillation camera)

Pho/Gamma LEM (low energy, 1976

mobile scintillation camera)

Pho/Con-Emission 1975

Tomographic Scanner (updated

1979)

Pho/Gamma 37 GP Camera

(update) 1974

minicomputer,

List

price

$78,000-

$150,000 ‘

$49,000

$15,000

$90,000 (avg.

depending on

collimator(s))

$85,000

($106,500

w/ADAC

computer)

?

Market Share.—Claimed 1978 market share of 46

percent for scintillation cameras.

Customers.—1) Hospitals (ranked: radiology, internal medicine, pathology, cardiology); 2) clinics;

3) physicians’ offices; and 4) commercia l

laboratories.

Sales Strategy .—Company prefers to wait and introduce well-developed equipment, not to do continual updates. Uses direct sales from main office. Advertising aimed at doctors through professional and

trade journals and medical conventions.

Future Directions for Company .—Currently developing lines of single-photon and positron emission

tomography in Europe, where cost regulation is said

to be less than in the United States. Conducting

research on solid-state crystals for photon detection.

Future Directions for Radionuclide Imaging.—

Cardiac imaging will continue to increase, especially

techniques using technetium. Thallium use will also

increase, but more slowly because it is too expensive.

Positron emission tomography will increase greatly if

prices drop or Government cost controls ease. R e -

spondent sees trend toward easier to use, less expensive equipment.

Ohio Nuclear

29100 Aurora Road

Solon, Ohio 44139

Background.—*

Products.—Scintillation cameras,

CAT scanner.

Current Models.—

Year

introduced

Sigma 400 Camera ?

(standard field of view)

Sigma 4105 Camera ?

(large field of view)

Sigma 420 Mobile Camera ?

Market Share.—Outside estimate

minicomputer,

List

price

?

$85,000-

$100,000

$125,000

of 1978 market

share is 20 to 25 percent (scintillation cameras and

systems). Inside estimate is that Ohio Nuclear has

two-thirds of the mobile camera market; 122 units

sold in fiscal year 1979. Picker and Searle are the

competition for mobile cameras. For fixed cameras,

Ohio Nuclear has 15 percent of the market.

Customers.—1) Hospitals.

Sales Strategy .—Push mobile cameras. The

“Moon Buggy” is the most mobile and reliable mobile

unit and is battery powered. Ohio Nuclear software

is better than ADAC.

Future Directions for Company.—

Future Directions for Radionuclide Imaging.—Efficiency and resolution of cameras will be improved

twofold to threefold.

Raytheon

70 Ryan Street

Stamford, Corm. 06907

Background.—Raytheon is a large corporation

that appears to be about the fifth largest scintillation

camera manufacturer.

Products.—Scintillation cameras, minicomputer.

Current Models.—

Year List

introduced price

Step 1 (scintillation camera) 1978 Step 1 and

Step 2 (formatter/microproc- 1978 Step 2

essor/CRT) together sell

for $100,000

to $115,000

XL 91 (large-field-of-view 1976

scintillation camera)

Market Share.—Proprietary.

*Data Incomplete No literature received from company
Customers.—1) Hospitals (ranked: radiology, cardiology); and 2) physicians’ offices (only a few radiologists and cardiologists).

Sales Strategy .—Company uses its own field sales

force. Advertising is aimed at physicians through

professional and trade journals and through business

magazines.

Future Directions for Company .—Future products

will be more dedicated to specific cardiac imaging

uses and less general purpose.

Future Directions for Radionuclide Imaging.—Respondent feels market for cardiac imaging is “growing by leaps and bounds. ” Sees future products easier

to use, less expensive to purchase, less expensive to

operate, and more dedicated to thallium and technetium cardiac studies.

Baird Corp.

Cordis Nuclear Medical

125 Middlesex Turnpike

Bedford, Mass. 01730

Background.—Baird was the

Systems

second company to

manufacture scintillation cameras (beginning in

1965) and an early developer of the multicrystal

camera (about 1972). Company has not been able to

capitalize on the market share advantage provided

by its early entry into the field. There are 100 systems

in the field at present, but only 12 were sold in 1978.

Products.—Scintillation camera system,

Current Models.—

Year List

introduced price

System 77 (scintillation camera 1972 $99,500-

system with Keronix com- $190,000

puter

Market Share.—Proprietary. Only producer of

multicrystal camera for “first-pass” studies.

Customers.—Hospitals (ranked: radiology, nuclear medicine)

Sales Strategy .–Refined single model distributed

by Cordis.

Future Directions for Company .—Will continue to

produce the System 77 with updates.

Future Directions for Radionuclide Imaging.—

Opinion not expressed.

Union Carbide

Medical Imaging Division

333 Providence Highway

Norward, Mass. 02062

Background.—Union Carbide is a large corporation that entered the nuclear medicine field in 1976

when it purchased Cleon, a company that had just

developed a CAT scanner.

Products .—Scintillation

single-photon tomographic

Current Models.—

Union Carbide Cleon 711

(radionuclide body function

imager for single-photon

tomography)

Union Carbide Cleon 720

(large-field gamma camera)

Union Carbide Cleon 110

(image processor,

minicomputer)

camera, minicomputer,

imager.

Year List

introduced price

1979 $398,000

1977 $70,000

1977 $50,000

Market Share.—Proprietary, but claims Union

Carbide is in fifth place in scintillation camera and

systems sales.

Customers.—1) Hospitals (ranked: nuclear medicine, radiology); 2) physicians’ offices (few); and 3)

clinics (few).

Sales Strategy .—Union Carbide uses its own

regionally based sales force. Advertising is aimed at

physicians through professional trade journals and

meetings.

Future Directions for Company .—Into singlephoton tomography market. Will continue research

and explore new markets.

Future Directions for Radionclide Imaging.—

There will be new capabilities in cardiac imaging,

especially from improved data processing. Resolution of scans will not increase much, as cameras are

operating at their limits of resolution (about 1/10”)

now. The Anger-type scintillation camera will continue in use for about 5 years. The present market is

mature, with stable prices through competition and

comparable products. The use of CAT scanning in

cardiac diagnosis will increase during the next 5

years.

ADAC (Analytical Development

Associates Corp.) Laboratories

255 San Geronimo Way

Sunnyvale, Calif. 94086

Background.—ADAC Laboratories is a California

company that has been manufacturing computers for

medical use since the mid-1970’s. ADAC is perhaps

the leader in computers for nuclear cardiology.

Products.—Minicomputers for nuclear imaging.

Current Models.—

Year List

introduced price

Clinical Acquisition Module 11 ? $40,000

(mobile minicomputer for (base)
imaging data collection and $50,000

manipulation) (avg. )

Clinical Acquisition Module 1976?

(mobile minicomputer for imaging data collection)

Clinical Data System 1976 $50,000

(stationary minicomputer) (base)

$75,000

(avg. )

Also: a Remote Terminal, a Modem to transmit data

over telephone lines, a Multiformat Camera to transfer

images or curves to X-ray film, a high-speed Disk

Drive, a Fortran IV compiler on which users can write

their own software, and a number of software packages including 7-pinhole tomography.

Market Share.—Proprietary, but claims to and appears to be ranked first in sales for minicomputers,

though may be tied with Medical Data Systems.

Customers.—1) Hospitals (ranked: radiology and

cardiology); and 2) private radiology and cardiology

laboratories and practices.

Sales Strategy .—Not described. Company advertises in professional journals and at conventions.

Future Directions for Company .—Continue research. Nuclear cardiology is company’s biggest application. Developing software for 7-pinhole tomography. Also developing software for 7-pinhole gated

blood pool tomography.

Future Directions for Radionuclide Imaging.—Not

discussed.

Medical Data Systems (MDS)

Division of Medronic, Inc.

2311 Green Road

Ann Arbor, Mich. 48105

Background. —MDS is an established leader in the

computer segment that maintains its software capabilities are second to none. The company pioneered

MUGA (multiple-gated-acquisition) studies.

Products.—Computer systems.

Current Models.—

Year List

introduced price

Modumed 1972

AZ 1972 $53,000

Market Share.—400 Modumed systems in the

field, and 60 A2 units sold since January 1979. Has

production problems and a current 90- to 120-day delay in meeting orders. Major competition is ADAC.

Virtues of the A2 model include a hard disc and minicomputer (versus ADAC’s floppy disc and microprocessor) and the ability to acquire and process

more than one study simultaneously.

Customers.—1) Hospitals; and 2) physicians’ offices.

Future Directions for Company .—Improved software and trend toward larger central processing

units.

Digital Equipment

Marlborough, Mass.

Background.—Digital Equipment is a large minicomputer firm producing computers for nuclear medicine applications.

Products.—Minicomputers for nuclear medicine

data applications.

Current Models.—

Year List

introduced price

Gamma 11-1134 Processor* 1976 $54,000

(minicomputer for use with

scintillation cameras)

MDA-11 (mobile unit) ? ?

● Includes 128 Kiloword memory, DEC terminal, video terminal, Anger camera interface color video ability, operating

system, softward, installation, operator training, 90-day’s service.

Market Share.—Proprietary, but claims to be

leader in nuclear medicine computers worldwide,

with more than 500 systems installed, man y in

research institutions.

Customers,—1) Hospitals (ranked: radiology, nuclear medicine, cardiology); and 2) clinics.

Sales Strategy. —Not discussed. Advertisements in

professional journals aimed at physicians.

Future Directions for Company .—Continued research to develop hardware and software for present

and new cardiac imaging technologies.

Future Directions for Radionuclide Imaging.—Respondent sees two diverging trends in hardware: 1)

use of large central computers to process input from

one or more small remote computers; and 2) increasing use of portable self-contained units. Thinks future belongs to tomography, but not sure which tomographic technique. Seven-pinhole is the easiest to

perform, but the new revolving-head cameras for

radionuclide tomography (Searle Pho/Con, GE,

Union Carbide) will compete.

Mallinckrodt Nuclear

675 Brown Road

Hazelwood, Mi. 63042

Background.—Mallinckrodt is a large chemical

producer that has been involved in nuclear medicine

for many years. The company sold contrast media

before buying Nuclear Consultants in about 1965. It

then started making and selling its own line of radiochemicals.
Products.—Technetium generators, gallium, thallium (introduction imminent), cold mix agents.

Current Models.—

Year List

introduced price

Ultratechnical Tc99m Generator 1965 $160-$500

(in 8 steps of increasing (depending

radiation specific activity on specific

from 250 mCi to 3 Ci) activity

Techniscan (pyrophosphate cold $71 .50/kit

mix)

Gallium generators

Market Share.—Proprietary. Respondent claims

Mallinckrodt and Squibb are tied for first place in

sales of technetium generators and that Mallinckrodt

sells over 1,000 generators per week, Mallinckrodt is

first overall in radiopharmaceuticals.

Customers.—Hospitals (ranked: radiology, nuclear medicine).

Sales Strategy .—Not discussed. Advertisements

are aimed at physicians through professional journals.

Future Directions for Company .—Mallinckrodt

will soon introduce thallium and a kit to determine

cardiac enzyme (CPK) levels to diagnose acute myocardial infarctions. Thallium will probably be produced in Holland initially and transported to distribution centers in the United States,

Future Directions for Radionuclide Imaging.—Not

discussed.

Squibb

Hospital Division

P.O. Box 4000

Princeton, N. J. 08540

Background.—Squibb is a large pharmaceutical

firm that has produced radionuclides since about

1963.

Products.—Technetium generators, cold mixes.

Current Models.—

Year List

introduced price

Technethium-99m Molybdenum 1963 $100-$300

Generator (in 6 steps of in- (depending

creasing radiation specific on specific

activity from 220 mCi to activity)

2.2 Ci)

Phosphotec (pyrophosphate for

labeling with Tc-99m)

Macrotec (albumin for labeling with Tc-99m)

Market Share.—Respondent claims Squibb is

leader in generator and cold mix sales, with 50 percent of the market.

Customers.—1) Hospitals (ranked: radiology, cardiology, pathology, internal medicine); and 2) physicians’ offices (radiologists, cardiologists).

Sales Strategy .—Squibb employs its own field

sales force. Production facilities are on both coasts of

the United States, in New Brunswick, N. J., and in

Los Angeles, Calif. Advertising is aimed at physicians and hospital administrators in medical, professional, and trade journals.

Future Directions for Company. —Seeking approval to introduce thallium.

Future Directions for Radionuclide Imaging.—

Market is still growing. Respondent thinks technetium will replace the cyclotron-produced thallium, as

it replaced cyclotron-produced fluoride in bone imaging. Reasons are the lower cost and lower radiation

dose of technetium compared to thallium.

New England Nuclear (N EN)

Medical Diagnostics Division

Bedford, Mass.

Background.—NEN has been a producer of isotopes and radiopharmaceuticals since 1956. The company owns four cyclotrons and is the sole source of

thallium approved for human use in the United

States.

Products.—Thalluim, technetium generators, cold

mixes, other radioisotopes.

Current Models.—

Year List

introduced price

Thallous Chloride-201 (1.65 1977 $93.50 (dose)

mCi, thallium for cardiac

scanning)

Technetium Generator (in 8 1967 $169-$776

steps of increasing radiation (depending

specific activity from 225 mCi on amount)

to 2.7 Ci)

Pyrolite (“hot spot” imaging 19777 $483

agent for labeling with (30 vials)

technetium

Cardiolite (human serum 1977? —

albumin imaging agent for

labeling with technetium; not

FDA approved for human use)

Market Share .—100 percent of market for thallium

(sole U.S. source). Respondent claims that NEN is

even with Mallinckrodt and Squibb in technetium

generator sales, with each company having one-third

of the market. In cardiac cold kits, these companies

are all tied for second position behind Union Carbide.

Customers.—1) Hospitals (ranked: radiology, internal medicine, cardiology, pathology); and 2)

physicians’ offices (increasing).
Sales Strategy. —NEN employs an international

field sales force in the United States, Japan, South

America, Europe, India. Salespersons coordinate cardiologists and nuclear medicine specialists with the

supplier. Advertising in professional journals and at

conventions.

Future Directions for Company .—NEN is evaluating radionuclides with improved energy characteristics and reduced radiation dose.

Future Directions for Radionuclide Imaging.—Respondent predicts considerable growth in use of thallium for the nexts years. Predicts considerable future

use of positron emission tomography due to its desirable scanning characteristics and reduced radiation

dose. Active research into development of new isotopes with long-lived parents and short-lived (1 to 30

minutes) products of appropriate energy.

Medi + Physics

(a subsidiary of Roche

Pharmaceuticals)

Emeryville, Calif.

This company markets “instant technetium,” a

ready-to-use form for labeling cold mix imaging

agents. The 6-hour half-life of the isotope necessitates

same-day delivery to users. This form is popular on

the west coast, where it is provided by Medi +

Physics and a number of smaller radiopharmacies.

Procter and Gamble

Cincinnati, Ohio

This company manufacturers one product for use

in radionuclide scanning, “Osteoscan,” a cold mix

agent used for bone imaging but also approved for

“hot spot” myocardial infarction imaging.

Union Carbide

Clinical Diagnostics Division

Tuxedo, N. . Y

Background.— Union Carbide is a large, diversified chemical company that was able to enter the

radionuclide market through possession of a reactor

for economic production.

Products.—Technetium generators, cold imaging

agents.

Current Models.—

Year List

introduced price

CintiChem Moly-99m- 1972 $180-$360

Technetium-99m Generator (in (depending

5 steps of increasing radiation on amount)

specific activity from 500 mCi

to 2.5 Ci)

CintiChem HSA (human serum 1972 —

albumin imaging agent for

labeling with technetium)

Market Share. —Respondent states that Union

Carbide is ranked third in sales of technetium generators (after Mallinckrodt and New England Nuclear)

with 20 percent of the market.

Customers.–1) Hospitals (ranked: radiology); 2)

physicians’ offices (a few radiologists); 3) clinics

(radiologists); and 4) radiopharmacies,

Sales Strategy. —Union Carbide employs its own

field sales force from regional offices, and orders can

be made directly to the main office as well. Advertising is aimed at physicians through professional journals and at conventions.

Future Directions for Company .—Not discussed.

Future Directions for Radionuclide Imaging.—

Not discussed.

Ancillary Equipment Producers

The following three companies are included to

describe the range of products in this segment. They

are not intended to be a representative sample of the

hundreds of ancillary equipment producers.

Harshaw Chemical Company

Crystal and Electronic Products

Division

6801 Cochran Road

Solon, Ohio 44139

This company is a manufacturer of components

for scintillation cameras. It produces the detectors

and sells them to the camera producers. Its main customer is Searle; companies in the second rank of Harshaw clients are Picker, Pfizer, Ohio Nuclear, GE,

and Raytheon. The company began producing scanner parts in 1955-60. Respondent considers that

radionuclide imaging in the future will be characterized by equipment that is more technician-oriented,

easer to use, capable of faster scans with better

resolution, and exposes the patient to a lower wholebody radiation dose.

Med-X, Inc.

Palatine, Ill.

This company specializes in servicing and upgrading older Searle scintillation cameras. It makes and

installs two models of improved detectors, the X-7

and the X-37 Super Resolution. These detectors improve resolution from 3/16” to about 1/10” or better.
The new detectors cost from $19,000 to $25,000, including 1 year of service. Meal-X was started by

former Searle employees and has been making updates since 1975. The firm’s largest customers are

hospital purchasers of used scintillation cameras.

Meal-X also performs scanning for rural hospitals on

a per-scan charge basis. The respondent predicts that

the future of medical imaging will be a competition

among competing modalities, with scanning, ultrasound, and other technologies all improving constantly.

Eastman Kodak

Health Sciences Division

State Street

Rochester, N.Y.

This large photographic and chemical company

makes X-ray and other sheet film to produce the hard

copy of selected images from cardiac radionuclide

studies. From one to many pictures up to 8“ x 10”

may be taken during each study for viewing by physicians and/or for the patient’s record.
1.

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4.

5.

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10.

11.

12.

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Perfusion Imaging at Rest and During Exercise,”

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at Rest in Patients With Stable and Unstable Angina and The Effect of Coronary Artery Bypass

Surgery, “ Circulation 60:1114, 1979.

Berger, H. J., et al., “Dual Radionuclide Study of

Acute Myocardial Infarction: Comparison of

ThalIium-201 and Technetium-99m Stannous Pyrophosphate Imaging in Man, ” Ann. Znt. Med.

88:145, 1978.

Blood, D. K., et al., “Comparison of Single-Dose

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1979.

“Detection of Coronary Heart Disease

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“Extent and Severity of Coronary Heart

Diseas~: Determinations by Thallous Chloride

T1-201 Myocardial Perfusion Scanning and Comparison With Stress Electro Cardiography,”

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Botvinick, E. H., et al., “Thallium-201 Myocardial Perfusion Scintigraphy for the Clinical Clarification of Normal, Abnormal and Equivocal

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Carrillo, A. D., et al., “Correlation of Exercise

201-Thallium Myocardial Scan With Coronary

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Exercise Test Results: The Role of Multiple-Lead

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Gould, K. L., et al., “Noninvasive Assessment of

Coronary Stenoses With Myocardial Perfusion

Imaging During Pharmacologic Coronary Vasodilation,” Am. ~. Card. 43:200, 1979

Greenberg, B. H., et al., “Thallium-201 Myocar56
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dial Perfusion Scintigraphy To Evaluate Patients

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1979.

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Myoca~dial Infarct Scintigraphy With 99m-Tc

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Radionuclide Infarct Scintigraphy To Diagnose

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59:714, 1979.

Losse, B., et al., “Exercise Thallium-201 Myocardial Perfusion Imaging in Patients With Normal

Coronary Angiogram and Ventriculogram, ” Circulation 59-60 (Suppl. 11):148, 1979.

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Massie, B. M., et al., “Correlations of Thallium-201 Scintigrams With Coronary Anatomy:

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McCarthy, D. M., et al., “Single Dose Myocardial Perfusion Imaging With Thallium-2C)l: Application in Patients With Non-Diagnostic Electro Cardiographic Stress Tests, ” Am. ]. Card.

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“Observer Variance in the Quantitative

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187:449, 1978.

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