Lisa R. Karam

Chief, Ionizing Radiation Division

National Institute of Standards and Technology

301-975-5561

lisa.karam@nist.gov

NIST Standards for RadiationBased Medical Imaging:

toward harmonization
Where NIST Fits In

• Long history in

– Methods development

– Standards and calibrations 

(radionuclides, X-ray beams)

– Tech transfer and support

• Expanding applications

– Budget initiative in 2007, plans 

beyond

– Physical measurements for 

bio/med

Providing critical measurement 

infrastructure for biological imaging
Radiation Physics

Theoretical dosimetry

Codes and models

Measurements for dosimetry

Brachytherapy

X-ray calibrations

Standards for mammography

Radionuclide metrology

Radionuclide standardization

Standard Reference Materials

Calibrations

NIST Measurement Standards 

Health Care
Metrology for Diagnostics

• Mammography

• Conventional x rays

• Spiral CT

• Theoretical Dosimetry

• Imaging radionuclides, 

etc.

• 1992 Law requires proficiency testing of mammography 

instruments

• NIST and FDA developed necessary calibration facilities

• 4 manufacturers and FDA now meet the legal requirements

• 3 AAPM Accredited Dosimetry Calibration Labs

Instrument Calibrations Required by 

Mammography Quality Standards Act

Conformal radiation therapy

CT and conventional plan
Partners in Measurement Standards

Together Towards Harmonization

• Medical Applications 

Subcommittee CIRMS 

• Radiation Therapy 

Committee AAPM

• Industry (manufacturers)

• Academia

• FDA CDRH

• NIH (NIBIB, NCI)

• Other community groups 

(PCF, ATA, ISCD, SNM, 

RSNA, etc.)

16th Annual Meeting

COUNCIL ON IONIZING 

RADIATION 

MEASUREMENTS AND 

STANDARDS

CIRMS

2007

Measurements and 

Standards for 

Radiation-Based 

Imaging

October 22-24, 2007
Proposed Chain of Measurements

NIST

Radiopharmacy

Source Supplier

Clinic

Uncertainty

1 %

3 %

10 %

Secondary Lab

Sources

Dose Calibrators

Collaborations with Stakeholders

Reducing Uncertainties

• Development of primary standards

• Development of transfer standards and calibration 

factors

• Protocol development for instrumentation, procedures

• Measurement assurance programs for traceability
Why Now

NIST asked by representatives of the drug 

industry, the NCI, the medical imaging industry, 

and various professional organizations such as 

the Radiological Society of North America to 

provide***:

• Physical standards and calibration tools for 

quantitative imaging and change measurements in 

therapy:

– PET/CT/MRI, spiral CT, bone health, optical imaging

• Standards for image generation, transmission, 

archival storage and dissemination to researchers

***2006 Workshop, Imaging as a Biomarker: Standards for 

Change Measurements in Therapy.......NIH, RSNA, PhRMA, 

FDA, et al.
Quantitative imaging needed for 

treatment planning, patient 

evaluation, drug development, 

clinical trials

Technical Opportunity

Where standards enable the technology

Do you see it? What is it? Where is it? 

Has it changed? What’s it up to? 

Just how much radiation do I have to get???
• Usefulness depends on consistent subject data (time 

and distance)

• Persistent variability in results from PET/CT images 

(in addition to subject variability)

– Between clinical sites

• Activity calibration (injected or in phantom)

• Conversion of image intensity to activity

• Protocols for acquisition, reconstruction, analysis

– Between scanners

• Conversion of image intensity to activity

• Different reconstruction algorithms

– Between scans

• Activity calibration (injected or in phantom)

• Conversion of image intensity to activity

Quantitative PET/CT

Seeing the same thing the same way

Calibration traceable to national standards for 

more quantitative results in patient assessment, drug 

development, and treatment planning
Progress with CT

Size and Dimension

• Recognized need for length standard

– Tumor definition

– Tumor size

– Cheap, portable

• NIST-designed “pocket-phantom”

– Very inexpensive

– Robust

– Good contrast 

• Status

– Dimensional accuracy NIST-traceable

– LEGO® pieces about 0 H.U.

– Teflon balls about +800 H.U. (±25%)

– Difference estimated at ±100 H.U.

– Positive feedback from stakeholders

– Redesigned CT phantom (looking to 

evaluate in clinical trial using CT)

3D visualization 

reconstructed 

from CT images 
Progress with CT

Density and Contrast

• Need for tissue contrast

– Particular in lung imaging

– H.U. variability across tumor 

dimension

• NIST evaluated “foam”

– NIST-standard x-ray beam

– Good contrast

– Wide density range

• Status

– Foam densities visible at 

various thresholds

– Good separation (23 H.U. 

steps)

– Paper published, appears to 

be in use

PMMA cylindrical 

vial (for PET 

solution) half filled 

with water

1 2

3 4

air

water

5 cm

X-ray transmission 

images of foam 

samples

-955 -932

-886 -863 -840 -817

-794 -771 -748 -725

-978 -909
Progress with PET

Traceability Despite 2-hour Half-Life

• Input from stakeholders show 

needs

– Traceability for instrument 

calibration

– Longer-lived

– Phantom variety

– Protocols for use, training

• Ge-68 (t1/2 271 d)

– National standard

– Calibration for different geometries 

(syringe, phantoms)

• Status

– Calibration transferred to NIST 

Secondary Standard Ionization 

Chamber (routine future 

calibrations)

– Calibrated 68Ge phantoms (same 

tech – epoxy - as mock syringes)

96.86 % β+ (633.5 keV)

3.14 % EC

18F

(1.83 h)

18O

(stable)

68Ge

(270.95 d)

68Ga

(1.130 h)

100 % EC

68Zn

(stable)

1.2% β+

1.79% EC

87.94% β+ (1899.1 keV)

8.70% EC

1077 keV
Progress with PET

Determination of response factor 18F relative to 68Ge

Total of 5 mock syringes + 1 NIST 

ampoule gravimetrically prepared 

from [18F]DG 

Activity conc. determined from 

ampoule (traceable to National 

Standard)

Activity in each syringe calculated; 

each source measured in 

ionization chambers.

Response of 18F at different 

calibration factors compared with 

liquid and solid 68Ge sources.

Measured rel. resp. = 1.054 ± 0.020; 

Monte Carlo predicts 1.053

18F Primary 

Standard

68Ge 

Primary 

Standard

68Ge Syringe

Mock Standard

18F 

Syringe

18F Phantom 68Ge Phantom

RF = 1.054

RF =

?

uc = 0.61 %

uc = 0.34 %

uc = 0.52 % uc = 0.83 %

Goal: uc < 1 % uc = 0.7 %

• Traceable 68Ge mock-syringes sent to 3 

clinical sites (40+ dose calibrators)

• Measurements made at manufacturerrecommended settings for 18F

• Comparison with NIST traceable activity 

value for 18F (from relative response 

factor)

• Total of 31 independent measurements

• Results were all 5-6 % high 

Measurement Error Uncovered for 18F
Collaboration Opportunities

Harmonization across the community

• Planned expansion (DXA, PET/MRI, change 

analysis, and personalized nuclear medicine)

• Interactions with other agencies and 

stakeholders to address clinical needs (FDA, 

NIH, NCI, CIRMS)

• Established and growing laboratory facilities for

– Guest researcher opportunities (visiting scientist)

– Technical discussions, combined “problem solving”

– Cooperative research (“CRADA”)

– Measurement traceability and SRMs in-place

– Pending acquisition of PET/CT scanner

• Long-standing international interactions “closing the loop”

radioactivity contrast

Measurement foundation to enable standardization among 

centers:

Quantitative imaging traceable to National standards
For further information contact:

Lisa Karam, Ionizing Radiation Division

Physics Laboratory, NIST

100 Bureau Dr. MS 8460

Gaithersburg, MD 20899-8460

301-975-5561 (tel.)

301-869-7682 (Fax)

lisa.karam@nist.gov

http://physics.nist.gov/Divisions/Div846/div846.html

Contact Information
• Problem: Better assessment of bone health

• Today: Uncoordinated approach using 

manufacturer-developed phantoms to calibrate 

system-specific instrumentation

• Goal: Absolute, well-characterized phantoms, 

traceable to National standards, for confidence in 

calibration for a range of instruments/systems 

• Success: Reduced variability among 

instruments due to system-specific technical and 

engineering issues. 

• Impact: Reduction in bone disease impact, 

including fracture, for an aging population. 

• Why NIST? Unique expertise in physical 

metrology and recognized role as “honest broker” 

for industry

Metrology for X-Ray-Based 

Bone-Density Measurements

Acquisition

vs.

Interpretation

bone bone

fat fat

LMT

Personalized

bon

e
• Problem: No phantoms for combined PETMRI available (on the rise)

• Today: No institution working on 

development of calibrated dual-modality 

phantoms

• Goal: Quantification of medical images in 

terms of spatial dimension and 

contrast/positron emission intensity

• Success: Appropriate standard phantoms 

and their adoption in practice 

• Impact: Ability to calibrate PET-MRI 

scanners traceable to National standards 

• Why NIST? National standards for physical 

quantities (esp. radioactivity, dose, and 

length) crucial to medical imaging and patient 

safety

Standards for Quantitative 

PET-MRI

bon

e

“closing the loop”

radioactivity contrast
• Problem: Current guideline based on 

clinical data and assumptions

• Today: Estimations based on internal 

dosimetry models

• Goal: Development of new standards for 

patient-based quantitative nuclear 

medicine imaging

• Success: Development and adoption of 

appropriate standards 

• Impact: Safer and more effective 

treatment for the over 1.4 million US 

patients diagnosed with cancer each year 

• Why NIST? Unique neutral position to 

objectively compare current 

methodologies

bonPersonalized Nuclear Medicine

e
• Problem: Imaging currently limited by ability to discern 

only large changes in size/metabolism as a direct 

consequence to lack of standards to monitor equipment 

performance

• Today: No institution working to address intrinsic 

variability due to difference in scanner performance and 

lack of calibration

• Goal: Development of calibration standards, 

implementation of proficiency testing scheme, work with 

clinicians, drug and instrument manufacturers to assess 

needs

• Success: Standards adoption in practice, and 

participation in proficiency tests by major clinical centers 

• Impact: Billions of dollars saved by drug companies 

• Why NIST? Neutrality allows NIST to play a unique role 

in administering proficiency tests

Standards and Methods for Change 

Analysis

bon

e

SIENA