Validation of Combined PET-MR Quantitative Parameters for Cardiac Applications
Phase: NA
Conditions: Cardiac Disease
Sponsor: University of California, San Francisco

 
Validation of PET/MRI integrated system acquisition for cardiac applications  
 
NCT02062008 
 
Document Date: December 12, 2016  
 

 
Study Application (Version 1.5) 
 
1.0 
General Information 
2.0 
Add Department(s) 
2.1 List the departments associated with this study. The Principal Investigator's department 
should be Primary.: 
 
3.0 
List the key study personnel: (Note: external and affiliated collaborators who 
are not in the UCSF directory can be identified later in the Qualifications of 
Key Study Personnel section at the end of the form) 
3.1 *Please add a Principal Investigator for the study: 
Hernandez Pampaloni, Jose Miguel MD, MD 
Select if applicable 
 Department Chair 
  Resident 
 Fellow 
If the Principal Investigator is a Fellow, the name of the Faculty Advisor must be supplied below. 
3.2 If applicable, please select the Research Staff personnel: 
A) Additional Investigators 
Acevedo-Bolton, Gabriel, PhD 
Other Investigator 
Bacharach, Stephen 
Other Investigator 
Behr, Spencer C 
Other Investigator 
Botvinick, Elias H 
Other Investigator 
*Enter the full title of your study: 
Validation of PET/MRI integrated system acquisition for cardiac applications 
*Enter the study number or study alias 
Validation of cardiac PET MR 
* This field allows you to enter an abbreviated version of the Study Title to quickly identify this 
study. 
Primary 
Dept? 
Department Name 
◆ UCSF - 147100 - M_Radiology 

Dae, Michael W 
Other Investigator 
Gerstenfeld, Edward P M.D. 
Other Investigator 
Guccione, Julius M Ph.D. 
Other Investigator 
Haraldsson, Henrik 
Other Investigator 
Hernandez Pampaloni, Jose Miguel MD, MD 
Co-Principal Investigator 
Hope, Michael D 
Other Investigator 
Hope, Thomas A, MD 
Other Investigator 
Kanaya, Alka M 
Other Investigator 
Liu, Jing PhD 
Other Investigator 
Mukai, Kanae 
Other Investigator 
Mukai, Kanae 
Other Investigator 
Naeger, David M 
Other Investigator 
Ordovas, Karen G MD, MAS, MD 
Co-Principal Investigator 
Saloner, David A Ph.D., PhD 
Other Investigator 
Yeghiazarians, Yerem 
Other Investigator 
B) Research Support Staff 
Gao, Kenneth T 
Research Assistant 
Lorca, Maria Clara 
Research Assistant 
Tao, Dora H 
Research Assistant 
Verdin, Emily F 
Research Assistant 
Wong, Samantha A 
Research Assistant 
3.3 *Please add a Study Contact: 
Hernandez Pampaloni, Jose Miguel MD, MD 
Ordovas, Karen G MD, MAS, MD 
The Study Contact(s) will receive all important system notifications along with the Principal 
Investigator. (e.g. The project contact(s) are typically either the Study Coordinator or the Principal 
Investigator themselves). 
3.4 If applicable, please add a Faculty Advisor/Mentor: 

3.5 If applicable, please select the Designated Department Approval(s): 
 
 
 
Add the name of the individual authorized to approve and sign off on this protocol from your 
Department (e.g. the Department Chair or Dean). 
 
4.0 
Qualifications of Key Study Personnel 
 
4.1 November, 2015 - NEW Definition of Key Study Personnel and CITI Training 
Requirements: 
UCSF Key Study Personnel include the Principal Investigator, other investigators and research 
personnel who are directly involved in conducting research with study participants or who are directly 
involved in using study participants’ identifiable private information  during  the  course  of  the 
research. Key Personnel also include faculty mentors/advisors who provide direct oversight to 
Postdoctoral Fellows, Residents and Clinical Fellows serving as PI on the IRB application. 
The 
IRB requires that all Key Study Personnel complete Human Subjects Protection 
Training through CITI prior to approval of a new study, or a modification in 
which KSP are being added. More information on the CITI training requirement 
can be found on our website. 
List the study responsibilities and qualifications of any individuals who qualify as Key Study 
Personnel (KSP) at UCSF and affiliated sites ONLY by clicking the "Add a new row" button. This 
information is required and your application will be considered incomplete without it. 
 
 
KSP Name 
Description of Study 
Responsibilities 
Qualifications 
Dr. Ordovas, Karen G MD, MD 
Co-Principal Investigator, 
 
Radiologist with large 
expertise in MRI cardiac 
applications 
Dr. Saloner, David, PhD 
Other Investigator, 
 
PhD Physiscit. Expert in MRI 
applications in the 
cardiovascular system. 
Lorca, Maria Clara 
Research Assistant 
 
Post- Doctoral Fellowship 
 
Hernandez Pampaloni, Jose MD, 
PhD, MD, PhD 
Co-Principal Investigator 
 
Radiologist. Chief of Nuclear 
Medicine at UCSF with 
extensive published work in 
cardiovasular PET imaging. 
Behr, Spencer, MD 
Other Investigator, 
 
Radiologist with expertise in 
cross-sectional imaging 
Botvinick, Elias H 
Other Investigator, 
 
Cardiologist. Expert in Nuclear 
Cardiology 
Liu, Jing PhD, PhD 
Other Investigator, 
 
PhD, Physicist. Expertise in 
cross-sectional physics 
Dae, Michael W 
Other Investigator, 
 
Radiologist. Expert in nuclear 
cardiology 
Acevedo-Bolton, Gabriel, PhD 
Other Investigator, 
PhD 
Dr. Guccione, Julius, PhD 
Other Investigator, 
Bioengineer 
Dr. Hope, Michael MD, MD 
Other Investigator, 
Chest Radiologist with 

 
5.0 
Initial Screening Questions - Updated 9/13 
(Note: You must answer every question on this page to proceed). 
If you are converting to the new form, check questions 5.4, 5.6, 5.7, 5.8 
and 5.10 before saving and continuing to the next section. 
5.1 * Application type: 
 Full Committee 
 Expedited 
 Exempt 
5.2 * Risk level (Help Text updated 9/13): 
 Minimal risk 
 Greater than minimal risk 
5.3 * Subject contact: 
 Yes (including phone, email or web contact) 
 No (limited to medical records review, biological specimen analysis, and/or data analysis) 
5.4 * Funding (past or present): 
 Funded or will be funded (external sponsor, gift, program or specific internal or departmental funds) 
 Unfunded (no specific funds earmarked for this project) 
 
expertise in MRI applications 
in the cardiovascular field 
Naeger, David M 
Other Investigator, 
 
Chest Radiologist. Expertise in 
PET imaging and cross- 
sectional imaging of the chest. 
Dr. Yeghiazarians, Yerem MD, 
1995 
Other investigator 
 
Cardiologist. Interventional 
Cardiologist 
Dr. Kanaya, Alka MD 
Other investigator 
 
Cardiologist 
 
Hope, Thomas A, MD 
Other investigator 
 
Radiologist with experience in 
PET and cross-sectional 
imaging 
Dr. Gerstenfeld, Edward P M.D. 
, MD 
Other investigator 
 
Cardiologist. Chief of cardiac 
electrophysiology 
Dr. Haraldsson, Henrik PhD 
Other investigator 
 
Physicist 
 
Bacharach, Stephen 
Other Investigator 
 
Physicist. Extensive 
experience in applications of 
PET imaging in cardiovascular 
disorders, including 
quantification of myocardial 
blood flow 
Mukai, Kanae 
Other investigator 
 
Advanced Cardiac Imaging 
fellow 

 Unfunded student project 
5.5 * The Principal Investigator and/or one or more of the key study personnel has financial interests 
related to this study: 
  Yes   
   No 
If Yes, the Conflict of Interest Advisory Committee (COIAC) office may contact you for additional 
information. 
5.6 * This is an investigator-initiated study: 
 Yes   
 No 
5.7 * This study ONLY involves retrospective records review and/or identifiable biospecimen analysis: 
  Yes   
   No 
5.8 * This is a clinical trial: 
 Yes   
 No 
Clinical Trial Registration 
"NCT" number for this trial: 
NCT02062008 
5.9 * This is a multicenter study: 
  Yes   
   No 
5.10 * This application involves the study of unapproved or approved drugs, devices, biologics or in vitro 
diagnostics: 
 Yes   
 No 
5.11 * This application involves a Humanitarian Use Device: 
 No 
 Yes, and it includes a research component 
 Yes, and it involves clinical care ONLY 
5.12 * This study involves human stem cells (including iPS cells and adult stem cells), gametes or 
embryos: 
 No 
 Yes, and requires CHR and GESCR review 
 Yes, and requires GESCR review, but NOT CHR review 
5.13 * This is a CIRB study (e.g. the NCI CIRB will be the IRB of record): 
  Yes   
   No 
 

5.14 * This application includes a request to rely on another IRB (other than NCI CIRB): 
 
Yes 
No 
 
Note: If this request is approved, the CHR will NOT review and approve this study. Another institution will 
be the IRB of record. 
 
 
6.0 
Funding 
 
6.1 
Identify all sponsors and provide the funding details. If funding comes from a Subcontract, please list 
only  the Prime Sponsor: 
Note: we require only a P Number OR an A Number for 
funding coming through UCSF. Please avoid these common errors in funding 
documentation: 
DO NOT add the A Number if a P Number was already provided OR update 
the A Number field when a new funding cycle begins. The IRB does NOT 
use this information or want these changes made. 
DO NOT add a grant continuation as a new funding source. 
 
 
External Sponsor: 
 
View 
Details 
Sponsor Name 
Sponsor Type 
Awardee 
Institution 
Contract 
Type: 
UCSF RAS 
"P 
number" 
or 
eProposal 
number 
UCSF 
RAS 
System 
Award 
Number 
("A" + 
6 
digits) 
 
GE Medical Systems 
04 
UCSF 
Grant 
P0501481 
Sponsor Name: 
GE Medical Systems 
Sponsor Type: 
04 
Sponsor Role: 
Funding 
CFDA Number: 
Grant/Contract Number: 
CA-0050676 
Awardee Institution: 
UCSF 
Is Institution the Primary Grant 
Holder: 
Yes 
Contract Type: 
Grant 
UCSF RAS "P number" or 
eProposal number: 
P0501481 
UCSF RAS System Award Number 
("A" + 6 digits): 
Grant Number for Studies Not 
Funded thru UCSF: 
Grant Title: 
PI Name: 
(If PI is not the same as identified 
on the study.) 
Significant Discrepancy: 

Gift, Program, or Internal Funding (check all that apply): 
 Funded by gift (specify source below) 
 Funded by UCSF or UC-wide program (specify source below) 
 Specific departmental funding (specify source below, if applicable) 
List the gift, program, or departmental funding source: 
6.2 
If you tried to add a sponsor in the question above and it was not in the list, follow these steps: 
If funding has already been awarded or the contract is being processed by the Office of 
Sponsored Research (OSR) or Industry Contracts Division (ICD), your sponsor is already in the 
system and the project has an eProposal Proposal or Award number. Check with your 
department's OSR Staff or ICD Officer to ask how the sponsor is listed in the UC sponsor list 
and what the Proposal or Award number is. Click here to find your OSR staff and here to find 
your ICD staff. 
If your sponsor is not yet in the list, enter it in the box below. 
 Sponsor not in list 
Only if your sponsor is not yet in the list, type the sponsor's name: 
 
If the funding is administered by the UCSF Office of Sponsored Research, your study will not 
receive CHR approval until the sponsor and funding details have been added to your 
application. 
6.3 * This study is currently supported in whole or in part by Federal funding OR has received ANY 
Federal funding in the past (Help Text updated 9/13): 
  Yes   
   No 
If yes, indicate which portion of your grant you will be attaching: 
 The Research Plan, including the Human Subjects Section of your NIH grant or subcontract 
 For other federal proposals (contracts or grants), the section of the proposal describing human 
subjects work 
 The section of your progress report if it provides the most current information about your human 
subjects work 
 The grant is not attached. The study is funded by an award that does not describe specific plans for 
human subjects, such as career development awards (K awards), cooperative agreements, program 
projects, and training grants (T32 awards) OR UCSF (or the affiliate institution) is not the prime 
recipient of the award 
7.0 
Sites 
7.1 Institutions (check all that apply): 
 UCSF 
 China Basin 
 Helen Diller Family Comprehensive Cancer Center 
 Mission Bay 
 Mount Zion 
 San Francisco General Hospital (SFGH) 
 SF VA Medical Center (SF VAMC) 
 Blood Centers of the Pacific (BCP) 
 

 Blood Systems Research Institute (BSRI) 
 Fresno (Community Medical Center) 
 Gallo 
 Gladstone 
 Institute on Aging (IOA) 
 Jewish Home 
 SF Dept of Public Health (DPH) 
7.2 Check all the other types of sites not affiliated with UCSF with which you are cooperating or 
collaborating on this project (Help Text updated 9/13): 
 Other UC Campus 
 Other institution 
 Other community-based site 
 Foreign Country 
List the foreign country/ies: 
7.3 Check any research programs this study is associated with: 
 Cancer Center 
 Center for AIDS Prevention Sciences (CAPS) 
 Global Health Sciences 
 Immune Tolerance Network (ITN) 
 Neurosciences Clinical Research Unit (NCRU) 
 Osher Center 
 Positive Health Program 
8.0 
Study Design 
8.1 * Study design (Help Text updated 9/13): 
The goal of this study is to understand how simultaneous PET/MR acquisition can provide novel qualitative 
and quantitative information to guide clinical intervention and predict prognosis of patients with risk 
factors for the development of coronary artery disease, or with diagnosis of cardiovascular ischemic or 
inflamatory disorders. 
Patients required to have a clinical cardiac FDG PET or PET/CT imaging study as part of standard of care, 
to detect myocardial viability or a cardiac inflammatory process will be enrolled in the study. After the 
initial acquisition of the clinical study patients will be immediately imaged in the PET/MRI system, with no 
additional administration of any radiopharmaceutical. The main purpose of the study would then be to 
compare the infomration proveided form the clinical PET/CT with the one from the simultaneous cardiac 
PET/MRI. 
8.2 If this is a clinical trial, check the applicable phase(s) (Help Text updated 9/13): 
 Phase I 
 Phase II 
 Phase III 
 Phase IV 
9.0 
Scientific Considerations 

9.1 Hypothesis (Help Text updated 9/13): 
This study has a hypothesis: 
 Yes   
 No 
If yes, state the hypothesis or hypotheses: 
We hypothesize that simultatenous acquisition of cardiac PET/MRI can could provide some other benefits 
in comparison to stand alone scanners. 
– In a hybrid system, real-time MR-based motion detection and correction could be applied since cardiac 
and respiratory gating can be image-based without external sensors. This could allow partial-volume 
correction and event-based correction of patient motion during the PET acquisition. 
-Combined metabolic information provided by FDG and structural information offered by MRI can help to 
better define the extent , location and siginficance of infarcted myocardium or viable tissue, with special 
significance for non-transmural or transmural lesions. 
– The lack of exposure to ionizing radiation and iodinated contrast agents makes hybrid PET/MRI attractive 
when compared with PET/CT. 
– Both cardiac MRI and PET examinations can be rather time consuming. Thus, improvements in patient 
compliance as a result of reduced scan time could be significant, particularly in patients with dyspnea due 
to heart failure who have difficulty holding their breath during MRI acquisitions. 
– Increased patient throughout based on reduced scan times is also likely to be cost-effective. 
9.2 * List the specific aims: 
· 
To compare regional myocardial uptake of FDG on images obtained on a standard PET camera with 
the new PET/MR camera, in patients with and without overt diagnosis of ischemic coronary artery disease. 
· 
To compare viability maps obtained with cardiac MR images and FDG-PET for delineation of 
myocardial infarct core and border zone, in patients with coronary artery disease. 
· 
To correlate MRI myocardial strain with relative myocardial FDG uptake in patients with a previous 
myocardial infarction, referred for a clinical myocardial viability study. 
· 
To interrogate if simultaneous acquisition of cardiac PET and viability cardiac MR differ from 
acquisitions obtained independently, with special focus on attenuation correction methods. 
· 
To combined MRI scar map with FDG-PET uptake in patients with cardiac sarcoidosis and myocarditis. 
· 
To evaluate cardiac strain and myocardial scar burden in obese patients with and without diabetes. 
9.3 Statistical analysis: 
Correlation coefficient and Bland Altman plots will be applied to evaluate the agreement between linear 
variables obtained from PET and cardiac MRI. 
9.4 If this study has undergone scientific or scholarly review, please indicate which entity performed the 
review: 
 Cancer Center Protocol Review Committee (PRC) (Full approval is required prior to final CHR approval 
for cancer-related protocols.) 
 CTSI Clinical Research Center (CRC) advisory committee 
 Departmental scientific review 
 Other: 
Specify Other: 
 

10.0 
Background 
10.1 Background: 
Background 
Magnetic resonance (MR) imaging and positron emission tomography (PET) have been clinically available 
for more than 20 years and have evolved into highly valuable and versatile tools in diagnostic imaging. 
Since their first introduction, both imaging modalities have undergone a largely independent evolution in 
regard to technological development and clinical application. Nevertheless, since the first implementation 
of these inherently different imaging modalities, the idea of combining both into hybrid systems to 
complement each other has emerged. 
Simultateous acquisition of cardiac MRI and PET images has multiple potential clinical applications, 
particularly in patients with coronary artery disease and cardiomyopathies. While cardiac MRI provides 
high spatial resolution, and precise characterization of flow and function, PET imaging adds metabolic 
information that can be coregistered with MRI images. 
The importance of identification and quantification of the border zone of an infarct has been emphasize in 
recent cardiac imaging publications. The extent of border zone is a strong predictor of adverse left 
ventricular remodeling and lethal arrhythmias after an MI. In addition, it has been described that residual 
ischemia after MI is a strong predictor of adverse outcomes. However, the relationship between ischemia 
and border zone is not clearly understood. We have previously demonstrated the potential of chronic low 
dose vasodilator therapy to decrease the volume of border zone over time, a finding that suggests a 
potential role of combined high resolution scar and perfusion mapping in predicting response to specific 
treatment strategies in ischemic heart disease. In addition, combined PET MR acquisition may allow for 
assessment of any associations between border zone ischemia and myocardial strain, which may enhance 
our understanding of myocardial hybernation, and provide potential goals for treatment strategies. 
Compared to PET, MR has the ability to assess whether a region of ischemia and scar is transmural or not, 
and to map areas of core and border zone infarct. The relationship between ischemia and border zone may 
be an important consideration in determining whether tissue in the border zone can be salvaged. 
In patients with cardiac sarcoidosis and myocarditis, it is well established that abnormal cardiac MR 
delayed enhancement and FDG uptake are important features for diagnosis, prognosis and for guiding 
therapy. However, the mismatch between these abnormalities has not been interrogated. Quantification of 
delayed enhancement areas that do not correspond to FDG uptake could be a novel biomarker for 
quiescent or chronic disease, and may have important role in patient management. 
Another area of potential application for combined PET-MR imaging is metabolic diseases and obesity. MRI 
has the ability to quantify myocardial strain and vessel wall abnormalities, which can be combined with 
PET information on cardiac metabolism and vessel wall information to aid on characterization of obesity- 
related organ damage. Combined FDG-PET acquisition with morphologic characterization of atherosclerotic 
plaque can also be combined with morphologic markers of inflammation, including atherosclerotic plaque 
components, and contrast enhancement with ferumoxytol, a marker of vessel wall inflammation. 
10.2 Preliminary studies: 
Positron emission tomography (PET) has contributed significantly to the advances in our understanding of 
cardiac physiology and pathophysiology for more than 20 years. In addition to being a powerful research 
tool in cardiology, recent technical development and improved availability facilitated also its routine clinical 
use in cardiology. PET is the most reliable non-invasive tool for the identification of 
myocardial viability and also allows accurate assessment of myocardial perfusion and coronary artery 
disease (CAD), which is known to be the leading cause of mortality in adults. Imaging of myocardial 
viability with PET has been shown to identify heart failure patients who are at increased risk of death, 
which can be effectively reduced by surgical treatment. 
Magnetic resonance imaging (MRI) has rapidly developed into a versatile tool for investigating 
cardiovascular diseases, especially for the evaluation of cardiac structure, assessment of ventricular 
function, and detection of myocardial infarction.Therefore, the combination of this technique without 
ionizing 
radiation with PET is attractive in many applications. 
To perform a combined analysis of sequential MRI and PET studies, images must be aligned accurately in 
the spatial domain. However, a particular challenge in cardiac 
studies is that the three spatial dimensions must be supplemented with a time dimension in order to 
correct for continuous motion during respiratory and cardiac 
cycles. Cardiac gating is routine in MRI and also possible in PET. Moreover, the integration of respiratory 
triggering is achieved using “navigators” (MRI) or list-mode acquisitions (PET). However, variable 
acquisition times between PET and MRI cause additional problems for exact timing of events. MRI scans 
are typically performed within few seconds during breath-holds while PET scans have a 

minimum duration of 5 min. However, spatial co-registration is rarely addressed in studies using separate, 
sequential MRI and PET scans. Misalignment is mostly caused by significant patient motion, respiration, 
and cardiac contraction. The first two are very challenging, as they are involuntary and can produce 
irregular patterns. In their review, Mäkela et al. summarized the co-registration accuracy for intra- and 
intermodal cardiac applications. For alignment of repeated MRI acquisitions accuracies of 1.5–3.0 mm were 
reported. Co-registration 
accuracy of repeated PET studies was on the order of 1.0– 2.5 mm. Finally, alignment of gated PET with 
gated MRI images showed an accuracy of 2.0±1.6 mm. In another study a misalignment of 2.8±0.5 mm 
was calculated using 
thorax and lung surfaces. Co-registration of any data not acquired 
simultaneously is therefore a major problem in inter- and intra-modal 
examinations. 
Assessment of heart failure 
Ventricular function 
Determination of LV function in gated PET studies is based on the use of partial volume effects. As the 
effective spatial resolution in clinical cardiac PET scans is approximately 6– 10 mm FWHM (full-width at 
half-maximum), changes in 
wall thickness can be estimated in terms of changes in regional count rates during cardiac contraction. 
Using algorithm-dependent assumptions, such as homogeneous 
tracer distribution over the myocardial wall, geometrical models can be used to estimate endo- and 
epicardial borders. This approach has been extensively implemented and validated in SPECT imaging and 
has also been 
used in comparative MRI and PET studies. However, while being technically feasible, the accuracy of the 
assessment of global and regional LV function by PET 
is limited by the low resolution of the PET compared to that of MRI. Here, MRI is clearly the modality-of- 
choice to quantitate cardiac function, such as volumes, mass, ejection fraction and regional wall 
thickening. Determination of LV function is essential for the diagnosis of heart failure and its prognostic 
value is well established. Therefore, its combination with any other imaging parameter is likely to provide 
incremental information. 
Myocardial viability 
Ischemic myocardium that is dysfunctional but viable has the potential for recovery of contractile function 
after revascularization. Evaluation of myocardial glucose utilization with 18F-FDG PET is considered as the 
most reliable tool to assess myocardial viability. Its quantitative nature allows assessment of the amount 
of viable tissue as a continuum from fully viable, through partially viable in the 
areas of non-transmural infarction, to non-viable scar. Contrast-enhanced MRI appears to be a promising 
alternative capable of visualizing transmural distribution of viable and infarcted myocardium with excellent 
spatial resolution. Contrast-enhanced MRI of myocardial infarction is based on the delayed-enhancement 
technique using inversion-recovery prepared T1-weighted gradient-echo pulse 
sequences after intravenous administration of Gd-DTPA. Infarcted myocardium appears enhanced relative 
to normal myocardium when imaged with a delay (typically 5–20 min) after intravenous injection of the 
contrast agent due to 
different wash-out kinetics. A comparison of delayed-enhancement MRI with 18FFDG PET and 13NH3 in 31 
patients with ischemic heart failure revealed that the location and extent of infarct scarring as delineated 
by delayed enhancement correlated very well with the non-viable segments from PET. The main source of 
difference between the methods was related to the presence of non-transmural 
enhancement in regions that were viable on PET. This can be explained by the higher spatial resolution of 
MRI compared with nuclear imaging methods that makes delayed-enhancement suitable for the detection 
of small areas of subendocardial infarcts. An improved contractile performance after intervention is 
commonly considered as the gold standard for assessing myocardial viability, 
although benefits of revascularization do not appear to be limited to improved function. In an initial study 
by Kim et al. in 41 patients with chronic ischaemic heart disease, dysfunctional segments with less than 
25% of delayed enhancement were likely to recover after complete revascularization. In contrast, 
segments with more than 50% of delayed enhancement had a low probability (<10%) of 
functional improvement. Comparable positive predictive values (73%) for functional recovery 6 months 
after revascularization were found for the lack of delayed enhancement (cut-off value less than 50% 
transmural scar) and the presence of preserved 18F-FDG uptake (cut-off value more than 50% of normal 
myocardium) as assessed by PET as the reference method to detect viable vs. nonviable myocardium. A 
recent meta-analysis of diagnostic studies indicated 
that 18F-FDG PET has a higher sensitivity than delayed enhancement MRI (92% vs. 84%) in predicting 
functional recovery upon revascularization, while specificities were comparable (63%). The relatively low 
specificity of the techniques indicates that a substantial percentage of segments that are classified as 
viable by the imaging 
techniques do not improve after revascularization. Although there are limited data on their combined use, 
adjunctive PET and MRI markers of viability, such as reduced 
diastolic wall thickness, lack of contractile response to inotropic stimulation with a low dose of dobutamine, 
preserved epicardial rim of viable myocardium, and 
preserved perfusion have been proposed to help refine the classification of dysfunctional segments as 
clinically viable or non-viable. 

In addition to improved detection of viability, multimodal imaging approaches could contribute to the 
clarification of the complex pathophysiological basis underlying 
the LV dysfunction in ischemic heart failure. Non-invasive detection of viable myocardium in chronic LV 
dysfunction associated with CAD has important clinical 
implications for the treatment of patients. Although limited by the lack of large randomized clinical trials, a 
metaanalysis of retrospective data has indicated that such patients are also at substantial risk of death, 
which can be 
effectively reduced by successful revascularization. Furthermore, pre-operative assessment of viability may 
identify patients who are at low risk of serious perioperative complications. The prognostic significance of 
myocardial 
scars detected by delayed enhancement is currently under investigation. Among 159 patients with clinical 
suspicion of CAD but without a history of myocardial 
infarction, the presence of even small amounts of delayed enhancement was associated with a high risk of 
major adverse clinical events (hazard ratio 8.29 for death, acute myocardial infarction or unstable angina 
pectoris, hospitalization 
for heart failure, and life-threatening arrhythmias requiring defibrillation) and cardiac death (hazard ratio 
10.9) during a follow-up period of 16 months [50]. 
It is important to emphasize that delayed-enhancement MRI is specific for either acute myocardial 
infarction or scar of old infarction, but not for hibernating myocardium. Plain infarct size carries well- 
established prognostic value 
that is also expected to apply to MRI. However, in contrast, 
the prognostic value of PET relies on the relative comparison of flow and glucose uptake (mismatch), which 
has been shown experimentally and clinically to reflect 
viable, but jeopardized myocardium. Several studies have indicated that there is an association between 
PET “mismatch” and adverse clinical outcome [3]. There is a 
need for prospective clinical trials comparing measures of infarction and either hibernation or stunning 
obtained with MRI and PET to obtain prognostic data to better understand whether they provide 
complementary clinical value. 
Our research team has high level of expertise in advanced cardiac MRI and cardiac PET imaging techniques 
and clinical applications. Dr Ordovas has multiple prior publications on viability and functional imaging and 
its applications in ischemic and non-ischemic heart disease. She has a previous work on border zone 
response to chronic vasodilator therapy. Dr Pampaloni has studied and published cardiac PET applications 
for perfusion and viability, with special focus on quantitative imaging. 
Dr Saloner has extensive experience with cardiac MR techniques for myocardial strain imaging, and 
multiple publications on the topic. 
Dr Michael Hope has previous publications on aortic imaging and 4d flow MR techniques for flow 
characterization of patients with bicuspid aortic valve. 
10.3 References: 
References 
Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, 
Berman DS, et al. ACC/AHA/ASNC guidelines for the clinical 
use of cardiac radionuclide imaging – executive summary: a 
report of the American College of Cardiology/American Heart 
Association Task Force on Practice Guidelines (ACC/AHA/ 
ASNC Committee to Revise the 1995 Guidelines for the Clinical 
Use of Cardiac Radionuclide Imaging). J Am Coll Cardiol 
2003;42:1318–33. 
Eisner RL, Patterson RE. Attenuation correction for stress and rest 
PET 82Rb myocardial perfusion images. J Nucl Med 2007; 
48:1912–3. 
Allman KC, Shaw LJ, Hachamovitch R, Udelson JE. Myocardial 
viability testing and impact of revascularization on prognosis in 
patients with coronary artery disease and left ventricular dysfunction: 
a meta-analysis. J Am Coll Cardiol 2002;39:1151–8. 
Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda 
M, et al. Guidelines for the diagnosis and treatment of chronic 
heart failure: executive summary (update 2005): The Task Force 

for the Diagnosis and Treatment of Chronic Heart Failure of the 
European Society of Cardiology. Eur Heart J 2005;26:1115–40. 
Martinez-Moller A, Zikic D, Botnar RM, Bundschuh RA, Howe 
W, Ziegler SI, et al. Dual cardiac-respiratory gated PET: 
implementation and results from a feasibility study. Eur J Nucl 
Med Mol Imaging 2007;34:1447–54. 
Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, 
Laskey WK, et al. Standardized myocardial segmentation and 
nomenclature for tomographic imaging of the heart. A statement 
for healthcare professionals from the Cardiac Imaging Committee 
of the Council on Clinical Cardiology of the American Heart 
Association. Int J Cardiovasc Imaging 2002;18:539–42. 
Sinha S, Sinha U, Czernin J, Porenta G, Schelbert HR. 
Noninvasive assessment of myocardial perfusion and metabolism: 
feasibility of registering gated MR and PET images. AJR Am J 
Roentgenol 1995;164:301–7. 
Mäkela T, Clarysse P, Lötjönen J, Sipilä O, Lauerma K, Hänninen 
H, et al. A new method for the registration of cardiac PET and MR 
images using deformable model based segmentation of the main 
thorax structures. In: Niessen W, Viergever M, editors. Medical 
image computing and computer-assisted intervention – MICCAI 
2001. Lecture Notes in Computer Science, vol. 2208. 4th 
International Conference, Utrecht, The Netherlands, October 14– 
17, 2001. Heidelberg: Springer; 2001. p. 557–64. 
Martinez-Moller A, Souvatzoglou M, Navab N, Schwaiger M, 
Nekolla SG. Artifacts from misaligned CT in cardiac perfusion 
PET/CT studies: frequency, effects, and potential solutions. J Nucl 
Med 2007;48:188–93. 
Gould KL, Pan T, Loghin C, Johnson NP, Guha A, Sdringola S. 
Frequent diagnostic errors in cardiac PET/CT due to misregistration 
of CT attenuation and emission PET images: a definitive 
analysis of causes, consequences, and corrections. J Nucl Med 
2007;48:1112–21. 
Souvatzoglou M, Bengel F, Busch R, Kruschke C, Fernolendt H, 
Lee D, et al. Attenuation correction in cardiac PET/CT with three 
different CT protocols: a comparison with conventional PET. Eur 
J Nucl Med Mol Imaging 2007;34:1991–2000. 
Bluemke DA, Achenbach S, Budoff M, Gerber TC, Gersh B, 
Hillis LD, et al. Noninvasive coronary artery imaging: magnetic 
resonance angiography and multidetector computed tomography 
angiography: a scientific statement from the american heart 
association committee on cardiovascular imaging and intervention 
of the council on cardiovascular radiology and intervention, and 
the councils on clinical cardiology and cardiovascular disease in 
the young. Circulation 2008;118:586–606. 
Khorsand A, Graf S, Frank H, Kletter K, Sochor H, Maurer G, et 
al. Model-based analysis of electrocardiography-gated cardiac 
(18)F-FDG PET images to assess left ventricular geometry and 
contractile function. J Nucl Med 2003;44:1741–6. 
Schaefer WM, Lipke CS, Nowak B, Kaiser HJ, Reinartz P, 
Buecker A, et al. Validation of QGS and 4D-MSPECT for 
quantification of left ventricular volumes and ejection fraction 
from gated 18F-FDG PET: comparison with cardiac MRI. J Nucl 
Med 2004;45:74–9. 
Bellenger NG, Davies LC, Francis JM, Coats AJ, Pennell DJ. 
Reduction in sample size for studies of remodeling in heart failure 
by the use of cardiovascular magnetic resonance. J Cardiovasc 
Magn Reson 2000;2:271–8. 

Schinkel AF, Poldermans D, Elhendy A, Bax JJ. Assessment of 
myocardial viability in patients with heart failure. J Nucl Med 
2007;48:1135–46. 
Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, 
et al. Relationship of MRI delayed contrast enhancement to 
irreversible injury, infarct age, and contractile function. Circulation 
1999;100:1992–2002. 
Klein C, Schmal TR, Nekolla SG, Schnackenburg B, Fleck E, 
Nagel E. Mechanism of late gadolinium enhancement in patients 
with acute myocardial infarction. J Cardiovasc Magn Reson 
2007;9:653–8. 
Klein C, Nekolla SG, Bengel FM, Momose M, Sammer A, Haas 
F, et al. Assessment of myocardial viability with contrastenhanced 
magnetic resonance imaging: comparison with positron 
emission tomography. Circulation 2002;105:162–7. 
Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, et 
al. The use of contrast-enhanced magnetic resonance imaging to 
identify reversible myocardial dysfunction. N Engl J Med 
2000;343:1445–53. 
Kuhl HP, Lipke CS, Krombach GA, Katoh M, Battenberg TF, 
Nowak B, et al. Assessment of reversible myocardial dysfunction 
in chronic ischaemic heart disease: comparison of contrastenhanced 
cardiovascular magnetic resonance and a combined 
positron emission tomography–single photon emission computed 
tomography imaging protocol. Eur Heart J 2006;27:846–53. 
Gerber BL, Rochitte CE, Bluemke DA, Melin JA, Crosille P, 
Becker LC, et al. Relation between Gd-DTPA contrast enhancement 
and regional inotropic response in the periphery and center 
of myocardial infarction. Circulation 2001;104:998–1004. 
Schmidt M, Voth E, Schneider CA, Theissen P, Wagner R, Baer 
FM, et al. F-18-FDG uptake is a reliable predictory of functional 
recovery of akinetic but viable infarct regions as defined by 
magnetic resonance imaging before and after revascularization. 
Magn Reson Imaging 2004;22:229–36. 
Higuchi T, Nekolla SG, Jankaukas A, Weber AW, Huisman MC, 
Reder S, et al. Characterization of normal and infarcted rat 
myocardium using a combination of small-animal PET and 
clinical MRI. J Nucl Med 2007;48:288–94. 
Haas F, Haehnel CJ, Picker W, Nekolla S, Martinoff S, Meisner H, 
et al. Preoperative positron emission tomographic viability assessment 
and perioperative and postoperative risk in patients with advanced 
ischemic heart disease. J Am Coll Cardiol 1997;30:1693–700. 
Kwong RY, Chan AK, Brown KA, Chan CW, Reynolds HG, 
Tsang S, et al. Impact of unrecognized myocardial scar detected 
by cardiac magnetic resonance imaging on event-free survival in 
patients presenting with signs or symptoms of coronary artery 
disease. Circulation 2006;113:2733–43. 
Muzzarelli S, Ordovas KG, Cannavale G, Naeger 
D, Michaels AD, Higgins CB. Potential of Delayed Gadolinium 
Enhancement Magnetic Resonance Imaing for Quantification of Reverse 
Remodeling of the Peri-Infarct Zone in Patients with Ischemic Cardiomyopathy Treated 
with Chronic Vasodilator Therapy: Initial Experience. J Thoracic Imaging 2011 33(6): 1440-6. 
Akhtar M, Ordovás KG, Martin A, Higgins CB, Michaels AD. Effect of 
Chronic Sustained-Release Dipyridamole on Myocardial Blood Flow and Left Ventricular 
Function in Patients with Ischemic Cardiomyopathy. Congestive Heart Failure 2007, 13: 130-135. 
Ordovas KG, Higgins CB. Delayed contrast enhancement on MR images of myocardium: 
past, present, future. Radiology. 2011 Nov;261(2):358-74. 

Moraes GL, Higgins CB, Ordovas KG. Delayed enhancement magnetic resonance imaging in 
nonischemic myocardial disease. J Thorac Imaging. 2013 Mar;28(2):84-92. 
Ordovás KG, Reddy GP, Higgins CB. MRI in Non-ischemic Acquired Heart Disease. JMRI 2008;27(6):1195- 
213. 
Reddy GP, Pujadas S, Ordovás KG, Higgins CB. MR Imaging of Ischemic Heart Disease. 
Magn Reson Imaging Clin N Am. 2008;16(2):201-12. 
Muzzareli S, Ordovas KG, Higgins CB. Cardiovascular Magnetic Resonance Imaging for the 
Assessment of Heart Failure: Focus on clinical management and prognosis. JMRI 2011; 33(2): 275-86. 
Muzzareli S, Ordovas KG, Meadows A, Higgins CB. Impact of Excursion of the Interventricular 
Septum on Left Ventricular Systolic Function and Fibrosis after Surgical Repair of Tetralogy of Fallot. 
Radiology 2011; 259(2): 375-83. 
Karen G. Ordovas, Marcus Carlsson, Katy E. Lease, Elyse Foster, Alison K. Meadows, Alastair 
J. Martin, Michael Hope, Loi Do, Charles B. Higgins, Maythem Saeed, PhD. Impaired Regional Left 
Ventricular 
Strain After Repair of Tetralogy of Fallot. JMRI 2012; 35(1): 79-85. 
Peral V, Vilacosta I, de la Pena A, San Roman JA, Fernandez C, 
Hernandez M, Batlle E, Carreras JL, Bethencourt A, "Thallium-201 Scintigraphy 
and Dobutamine Echocardiography in the Assessment of Myocardial Viability," 
Rev Clin Esp. 201: 5-15, 2001. 
Hernandez-Pampaloni M, Keng FY, Kudo T, Sayre J, Schelbert HR, 
"Abnormal Longitudinal Base to Apex Myocardial Perfusion Gradient by 
Quantitative Blood Flow Measurements in Patients with Coronary Risk Factors," 
Circulation 104: 522-526, 2001. 
Peral V, Vilacosta I, Fernandez C, Hernandez-Pampaloni M, San Roman JA, 
Battle E, Merono E, Carreras JL, Bethencourt A, "Comparison of Dobutamine Echocardiography 
and 201-Thallium Imaging Tomography in the Assessment of Viability Considering Positron Emission 
Tomography as Gold Standard," Rev Esp Cardiol, 54: 1394-1405, 2001. 
Campisi R, Nathan L, Hernandez Pampaloni M, Schoder H, Sayre J, Chaudhuri G, Schelbert H, 
"Coronary Microcirculatory Function in Postmenopausal Women Following Acute and Chronic 
Estrogen Administration," Circulation 105: 425-430, 2002 
Hernandez-Pampaloni M, Allada V, Fishbein MC, Schelbert HR, "Assessment of Myocardial 
Perfusion and Viability in Infants and Children with Suspected Coronary Abnormalities by Positron 
Emission Tomography: Correlation with Coronary Angiography and Histopathology," J Am Coll Cardiol 
41: 618-626, 2002. 
Hernandez-Pampaloni M, Peral V, Fernandez C, Carreras JL, Merono E, 
Sanchez-Harguindey L, Vilacosta I. "Biphasic Dobutamine Echocardiographic 
Response Predicts Improvement of Left Ventricular Dysfunction After Surgical Revascularization. 
Comparison with positron Emission and Rest-Redistribution Tl Tomography," I 
ntl J Cardi Imaging 19;519-528,2003. 
Quinones M, Hernandez-Pampaloni M, Jimenez X, Chun Y, De La Rosa R, 
Modelevsky T, Castellani L, Elashoff R, Schelbert H, Hsueh WA. "Coronary V 
asomotion Dysfunction in Early Resistance: Normalization by Ppar-Gamma 
Agonists," Annals Int Med 140: 700-708, 2004. 
M Hernandez-Pampaloni, J Bax, K Morita, D Dutka, PG Camici. "Incidence of 
stunned, hibernating and scarred myocardium in patients with ischemic cardiomyopathy". 
Eur J Nucl & Mol Imag, 32(3):314-321, 2005. 
JO Prior, A Facta, M Hernandez-Pampaloni, TH Schindler, JW Sayre, 
WA Hsueh, M Quinones, HR Schelbert. "Coronary circulatory dysfunction i 
n insulin resistance, impaired glucose tolerance and type 2 diabetes". Circulation,111;18:2291-2298, 2005. 
Botvinick EH, Perini R, Bural G, Chen W, Chryssikos T, Houseni M, Hernandez-Pampaloni M, 
Torigian DA, Alavi A. "The aging of the heart and blood vessels: a consideration of anatomy and physiology 
in the era of computed tomography, magnetic resonance imaging, and positron emission tomographic 
imaging 
methods with special consideration of atherogenesis. "Semin Nucl Med, 37:2;120-143, 2007. 

Well, DS, Meier JM, Mahne A, Houseni M, Hernandez-Pampaloni M, Mong A, 
Mishra S, Zhuge Y, Souza A, Udupa JK, Alavi A, Torigian DA. "Detection of age-related 
changes in thoracic structure and function by computed tomography, magnetic resonance 
imaging, and positron emission tomography." Semin Nucl Med. 37:2;103-119, 2007. 
Brothers JA, McBride MG, Seliem MA, Marino BS, Tomlinson RS, Pampaloni MH, 
Gaynor JW, Spray TL, Parison, SM. Evaluation of myocardial ischemia after surgical 
repair of anomalous aortic origin of a coronary artery in a series of pediatric patients. 
J Am Coll Cardiol. 2007; 50(21):2078-82. 
Takalkar A, Hernandez-Pampaloni M, Cheng G, Zhuang H, Alavi A. 
Pediatric cardiac PET imaging. PET Clinics. 2008, Volume 3:4; 587-596. 
Hope MD, Meadows AK, Hope TA, Ordovás KG, Reddy GP, Alley MT, Higgins CB. 
Images in cardiovascular medicine. Evaluation of bicuspid aortic valve and aortic 
coarctation with 4D flow magnetic resonance imaging. Circulation 2008;27:117(21):2818-9. 
Hope MD, Hope TA, Meadows AK, Ordovás KG, Urbania TH, Alley MT, 
Higgins CB. Clinical Evaluation of Aortic Coarctation with 4D Flow MR Imaging. 
JMRI 2010; 31(3):711-18. 
If you have a separate bibliography, attach it to the submission with your other study documents. 
11.0 
Sample Size and Eligibility 
11.1 Number of subjects that will be enrolled at UCSF and affiliated institutions: 
 
60 
11.2 Total number of subjects that will be enrolled at all sites (Help Text updated 9/13): 
 
60 
11.3 Estimated number of people that you will need to consent and screen here (but not necessarily 
enroll) to get the needed subjects: 
 
120 
11.4 Explain how and why the number of subjects was chosen (Help Text updated 9/13): 
This is a pilot study and we anticipate a number of 50 patients to obtain data to generate a formal sample 
size calculation for a larger trial. 
11.5 * Eligible age range(s): 
 0-6 years 
 7-12 years 
 13-17 years 
 18+ years 
 

11.6 Inclusion criteria: 
Subjects with ischemic and non-ischemic cardiac disease referred for cardiac PET for viability imaging. 
11.7 Exclusion criteria: 
Contraindications for MRI, including cardiac pacemaker, claustrophobia, retained metallic foreign body, 
cochlear implant, Aneurysm clip in the brain, pregnancy and eGFR less than 45%. 
11.8 There are inclusion or exclusion criteria based on gender, race or ethnicity: 
  Yes   
   No 
If yes, please explain the nature and rationale for the restrictions: 
12.0 
Drugs and Devices 
12.1 * Investigational drugs or biologics will be used OR approved drugs or biologics will be studied 
under this application: 
 Yes   
 No 
12.2 * Investigational medical devices or in vitro diagnostics will be used OR approved medical devices or 
in vitro diagnostics will be studied under this application: 
 Yes   
 No 
12.3 * A Non-Significant Risk (NSR) determination is being requested for an investigational device: 
 Yes   
 No 
12.4 Verification of IND/IDE numbers: If the sponsor’s protocol does not list the IND/IDE number, you 
must submit documentation from the sponsor or FDA identifying the IND/IDE number for this study. 
Attach this documentation in the Other Study Documents section of the Initial Review Submission 
Packet. 
13.0 
Study Drug Details 
13.1 List the drugs or biologics that will be studied: 
 
 
View 
Details 
Drug Name 
FDA Approved 
A new drug or a 
new use of 
approved drug: 
IND Number 
Trade Drug Gadavist 
Name: 
Generic Drug Gadobutrol 
Name: 
Investigational 
Drug Name: 
Yes 
No 
Trade Drug Name: 
Gadavist 
Generic Drug Name: 
Gadobutrol 

Investigational Drug Name: 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic: 
Is the drug supplied at no cost? 
No 
Is the Drug FDA Approved: 
Yes 
Is this a new drug or a new use of 
an already approved drug 
No 
Is an IND necessary 
No 
IND Number 
Who holds the IND: 
N/A 
IND details: 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption: 
This drug is currently used in MRI exams. 
Are you currently using this IND 
in another research project? 
No 
If yes, list the IRB Number(s): 
Will the investigational pharmacy 
be dispensing? 
No 
If the source is not a FDA licensed 
facility, provide details regarding 
the purity, quality, stability and 
sterility of the investigational drug 
/biologic: 
 
 
14.0 
Study Device Details 
 
14.1 
List the medical devices or in vitro diagnostics to be studied or used and attach any FDA or sponsor 
correspondence relating to the device to the application in the Study Documents section: (Note: 
Device category descriptions added to the Help link December, 2014) 
 
 
View 
Details 
Device Name 
Is the Device FDA 
Approved 
Is this a new 
device or a new 
use of an already 
approved device 
IDE Number 
 
GE PET/MRI 
No 
Yes 
Manufacturer/Supplier of Device 
Medicare Category 
A 
B 
Where will the Devices Be Stored 
Will Devices be supplied at no Cost Yes 
Is this a HUD (HDE) 
No 
HDE Number 
Is the Device FDA Approved 
No 
Is this a new device or a new use 
of an already approved device 
Yes 
Is an IDE necessary 
No 
IDE Number 
Who holds the IDE 
N/A 

15.0 
Non-Significant Risk Determination for an 
Investigational Device 
15.1 Explain why the use of the device in this study poses non-significant risk: 
The PET/MRI study device is classified as non-significant risk in accordance with the definition of a 
significant risk device provided in 21 CFR Part 812.3(m): 
It is not intended as an implant; 2) is not purported or represented to be for a use in supporting or 
sustaining human life; 3) is not for a use of substantial importance in diagnosing, curing, mitigating, or 
treating disease, or otherwise preventing impairment of human health; 4) and it does not otherwise 
present a potential for serious risk to the health, safety, or welfare of a subject (refer to additional study 
controls below). 
Additional study controls: 
For parameters besides Specific Absorption Rate (SAR), the study will comply with the non- 
significant risk limits described in the guidance ‘Criteria for Significant Risk Investigations of 
Magnetic Resonance Diagnostic Devices’, dated July 14, 2003. For SAR parameters, the device 
within the study will be tested and required to comply with the risk limits identified in IEC 60601- 
2-33 Ed. 3.0 Medical electrical equipment – Part 2-33: Particular requirements for the basic safety 
and essential performance of magnetic resonance equipment for medical diagnosis, which is a FDA 
Recognized Consensus standard. 
Attach any supporting documentation (e.g. any reports of prior investigations) at the end of the 
application. 
16.0 
Other Approvals and Registrations 
16.1 * Do any study activities take place on patient care units: 
  Yes   
   No 
If Yes, attach a letter of support for the study from the involved patient care manager(s). 
16.2 * Does your protocol involve any radiation exposure to patients/subjects? The UCSF Radiation 
Safety Committee requires review of your protocol if it includes administration of radiation as part of 
standard of care OR research exposures: 
  Yes   
   No 
16.3 * This study may generate genetic data that may be broadly shared (e.g. submitted to NIH for 
Genome-Wide Association Studies (GWAS) in dbGaP, TCGA, etc): 
  Yes   
   No 
16.4 * This study involves administration of vaccines produced using recombinant DNA technologies to 
human subjects: 
  Yes   
   No 
16.5 * This study involves human gene transfer (NOTE: Requires NIH Recombinant DNA Advisory 
 
IDE Details 
In the opinion of the sponsor, 
select the level of risk associated 
with this device 
No Significant Risk 

Committee (RAC) review prior to CHR approval): 
  Yes   
   No 
16.6 This study involves other regulated materials and requires approval and/or authorization from the 
following regulatory committees: 
 Institutional Biological Safety Committee (IBC) 
Specify BUA #: 
 Institutional Animal Care and Use Committee (IACUC) 
Specify IACUC #: 
 Radiation Safety Committee 
Specify RUA #: 
 Radioactive Drug Research Committee (RDRC) 
Specify RDRC #: 
 
 Controlled Substances 
17.0 
Procedures 
17.1 * Procedures/Methods (Help Text updated 9/13) For clinical research list all study procedures, test 
and treatments required for this study, including when and how often they will be performed. If 
there are no clinical procedures, describe the Methods: 
The subjects will undergo PET/MR for study purposes after they have finished their clinically 
indicated PET/CT, with no additional venipuncture to the patients. 
We propose to use 5D MR imaging (3D in space, in time through the cardiac cycle, and in time 
through the respiratory cycle) to provide improved information on the location of the signal 
source during PET acquisition. 
Dynamic and static PET data will be acquired in list mode and retrospectively rebinned according 
to predicted location from MR data. 
Accelerated MR methods (including compressed sensing) will be used to give rapid assessment 
of volumes over time. 
Additional MR imaging sequences will include strain mapping and VEC-MRI for flow imaging. In 
addition gadolium delayed enhancement will be obtained for myocardial tissue characterization 
with MRI. 
If you have a procedure table, attach it to the submission with your other study documents. 
17.2 Interviews, questionnaires, and/or surveys will be administered or focus groups will be conducted: 
 

  Yes   
   No 
List any standard instruments used for this study: 
Attach any non-standard instruments at the end of the application. 
17.3 Conduct of study procedures or tests off-site by non-UCSF personnel: 
  Yes   
   No 
If yes, explain: 
17.4 Sharing of experimental research test results with subjects or their care providers: 
  Yes   
   No 
If yes, explain: 
17.5 * Specimen collection for future research and/or specimen repository/bank administration: 
  Yes   
   No 
17.6 Time commitment (per visit and in total): 
1 hour in the scanner. 
17.7 Locations: 
The cardiac MRI will take place at the China Basin radiology. 
17.8 Describe the resources in place to conduct this study in a way that assures protection of the rights 
and welfare of participants: 
1. The research team will make several efforts to keep the PHI under extreme security, 
including the use of a coded database, password protected computers and locked cabinets, 
which will all be kept inside a locked office at the Parnassus campus. 
2. Patients are screened for prior claustrophobic symptoms using a screening form. Earplugs 
are provided to all patients in order to minimize the discomfort related to the loud noise. 
3. Loose metal objects are not allowed in the MR room. All entrances to the scanners are 
clearly marked with signs warning people not to enter with any metal and by each entrance 
there is a mobile metal detector. 
4. All patients fill up a screening form for any incompatible devices and metallic foreign bodies 
prior to entering the MR scanner room. 
18.0 
Alternatives 
18.1 Study drug or treatment is available off-study: 
 Yes 

 No 
 Not applicable 
18.2 * Is there a standard of care (SOC) or usual care that would be offered to prospective subjects at 
UCSF (or the study site) if they did not participate: 
 Yes   
 No 
If yes, describe the SOC or usual care that patients would receive if they choose not to participate: 
If patients do not participate on the study, they will still receive the standard FDG PET-CT per clinical 
request. 
18.3 Describe other alternatives to study participation that are available to prospective subjects: 
Not to participate. 
19.0 
Risks and Benefits 
19.1 * Risks and discomforts: 
The main risks to subjects for participating in this study are related to breach of confidentiality and 
exposure to the MRI scanner. 
No significant physical, psychological, financial, or legal harm is anticipated in case subject’s confidentiality 
is inadvertently breached. 
Risks associated with the MRI study are stratified based on probability of occurrence and listed below: 
Common: 
MR imaging may cause some discomfort, such as feelings of claustrophobia and discomfort due to loud 
sounds of the MR instrument during the study. 
Uncommon/Rare: 
Another potential hazard of the exam is localized heating of the body due to the radio waves employed. 
MR scanner and the MR probes have been designed to reduce the chance of heating. 
Because the MR scanner attracts iron, there is a small possibility that an iron-containing object could 
accidentally fly into the magnet causing injury to the patient. 
The presence of some metallic implantable devices or foreign bodies represents formal contra-indication to 
MR imaging and exposure to the strong magnetic field may cause malfunction or dislodgement of such 
devices or foreign bodies, potentially harming patients. A cardiac pacemaker is one example. 
Gadolinium is considered to be very safe for most people. Side effects from gadolinium itself are very rare. 
These side effects are usually headache and nausea. There have been a very few people who have had 
allergic reactions to gadolinium. Most people with allergic reactions get hives. Patients with severe kidney 
disease sometimes have a bad reaction to gadolinium contrast. The condition is called nephrogenic 
systemic fibrosis (NSF). It can cause skin to tighten or scar and can damage internal organs. Sometimes it 
can be life threatening. There are no reports of NSF in patients with normal kidney function. 
19.2 Steps taken to minimize risks to subjects: 
1) The research team will make several efforts to keep the PHI under extreme security, including the use 
of a coded database, password protected computers and locked cabinets, which will all be kept inside a 
locked office at the Parnassus campus. 
2) Patients are screened for prior claustrophobic symptoms using a screening form. Earplugs are provided 
to all patients in order to minimize the discomfort related to the loud noise. 
3) Loose metal objects are not allowed in the MR room. All entrances to the scanners are clearly marked 
with signs warning people not to enter with any metal and by each entrance there is a mobile metal 
detector. 
4) All patients fill up a screening form for any incompatible devices and metallic foreign bodies prior to 
entering the MR scanner room. 
5) Gadolinium: There have been a very few people who have had allergic reactions to gadolinium. Most 
people with allergic reactions get hives. These are usually very mild and require no treatment. Sometimes 
people will receive Benadryl to help relieve any itching. Subjects may experience a temporary discomfort 
from the needle stick, bruising, and rarely infection. Before the subject undergo an MRI requiring an 

injection of gadolinium contrast, we will review his medical record for results of a blood test to check the 
renal function. If the subject have not had a recent laboratory test done for that purpose, we will obtain 
that blood test on the day of the study, without the need for an additional puncture. Based on his medical 
history and the results of the test, a doctor will decide whether it is safe for you to undergo the MRI. 
19.3 Benefits to subjects: 
  Yes   
   No 
If yes, describe: 
No direct benefit for the patients; however, future patients could benefit from the combined acquisition of 
PET/MRI for management of their cardiac disease. 
19.4 Benefits to society: 
The combined acquisition of PET/MRI may be a reliable diagnostic and prognostic tool for patients with 
cardiac disease. 
19.5 Explain why the risks to subjects are reasonable: 
MR imaging may cause some discomfort, such as feelings of claustrophobia and discomfort due to loud 
sounds of the MR instrument during the study. These discomfort and risks will be outweighed by the 
possibility of a reliable diagnostic and prognostic tool for patients with cardiac disease. 
20.0 
Data and Safety Monitoring Plan 
20.1 Describe the plan for monitoring data and safety (Help Text updated 9/13): 
One of the study investigators will be present during the study acquisition and will document any possible 
adverse reaction on a log book. Dr Ordovas and Dr Pampaloni will review the log book to confirm absence 
of adverse events once a week. In case of a minor adverse event, CHR will be informed within one week. 
In the unlikely event of a significant adverse event, CHR will be informed within 24 hours. 
20.2 This study requires a Data and Safety Monitoring Board: 
 Yes 
 No or not sure 
If yes, press SAVE and CONTINUE to move to the next section of the application. 
20.3 If No, provide rationale: 
 Social/Behavioral research 
 Phase I trial 
 Treatment IND/Compassionate Use Trial 
 Other (explain below) 
If Other, explain: 
It does not make criteria for the Data and Safety Monitoring Board. 

21.0 
Confidentiality and Privacy 
21.1 Plans for maintaining privacy in the research setting: 
The research team will make several efforts to keep the PHI under extreme security, including the use of a 
coded database, password protected computers and locked cabinets, which will all be kept inside a locked 
office at the Parnassus campus. 
21.2 Possible consequences to subjects resulting from a loss of privacy: 
No significant physical, psychological, financial, or legal harm is anticipated in case subject’s confidentiality 
is inadvertently breached. 
21.3 Study data are: 
 Derived from the Integrated Data Repository (IDR) or The Health Record Data Service (THREDS) at 
SFGH 
 Derived from a medical record (e.g. APeX, OnCore, etc. Identify source below) 
 Added to the hospital or clinical medical record 
 Created or collected as part of health care 
 Used to make health care decisions 
 Obtained from the subject, including interviews, questionnaires 
 Obtained from a foreign country or countries only 
 Obtained from records open to the public 
 Obtained from existing research records 
 None of the above 
If derived from a medical record, identify source: 
21.4 Identifiers may be included in research records: 
 Yes   
 No 
If yes, check all the identifiers that may be included: 
 Names
 Dates 
 Postal addresses 
 Phone numbers 
 Fax numbers 
 Email addresses 
 Social Security Numbers* 
 Medical record numbers 
 Health plan numbers 
 Account numbers 
 License or certificate numbers 
 Vehicle ID numbers 
 Device identifiers or serial numbers 
 Web URLs 
 IP address numbers 
 

 Biometric identifiers 
 Facial photos or other identifiable images 
 Any other unique identifier 
* Required for studies conducted at the VAMC 
21.5 Identifiable information might be disclosed as part of study activities: 
 Yes   
 No 
If yes, indicate to whom identifiable information may be disclosed: 
 The subject's medical record 
 The study sponsor 
 Collaborators 
 The US Food & Drug Administration (FDA) 
 Others (specify below) 
 A Foreign Country or Countries (specify below) 
If Others, specify: 
21.6 Indicate how data are kept secure and protected from improper use and disclosure (check all that 
apply): NOTE: Whenever possible, do not store subject identifiers on laptops, PDAs, or other 
portable devices. If you collect subject identifiers on portable devices, you MUST encrypt the devices. 
 Data are stored securely in My Research 
 Data are coded; data key is destroyed at end of study  
 Data are coded; data key is kept separately and securely 
 Data are kept in a locked file cabinet 
 Data are kept in a locked office or suite 
 Electronic data are protected with a password 
 Data are stored on a secure network 
 Data are collected/stored using REDCap or REDCap Survey 
 Data are securely stored in OnCore 
21.7 Additional measures to assure confidentiality and protect identifiers from improper use and 
disclosure, if any: 
21.8 This study may collect information that State or Federal law requires to be reported to other officials 
or ethically requires action: 
  Yes   
   No 
Explain: 
21.9 This study will be issued a Certificate of Confidentiality: 
  Yes   
   No 
22.0 
Subjects 
 

22.1 Check all types of subjects that may be enrolled: 
 Inpatients
 Outpatients 
 Healthy volunteers 
 Staff of UCSF or affiliated institutions 
22.2 Additional vulnerable populations: 
 Children 
 Subjects unable to consent for themselves 
 Subjects unable to consent for themselves (emergency setting) 
 Subjects with diminished capacity to consent 
 Subjects unable to read, speak or understand English 
 Pregnant women 
 Fetuses
 Neonates
 Prisoners 
 Economically or educationally disadvantaged persons 
 Investigators’ staff 
 Students 
Explain why it is appropriate to include the types of subjects checked above in this particular study: 
Describe the additional safeguards that have been included in the study to protect the rights and welfare 
of these subjects and minimize coercion or undue influence: 
23.0 
Recruitment 
23.1 * Methods (check all that apply): 
 Study investigators (and/or affiliated nurses or staff) recruit their own patients directly in person or by 
phone. 
 Study investigators recruit their own patients by letter. Attach the letter for review. 
 Study investigators send a “Dear Doctor” letter to colleagues asking for referrals of eligible patients. If 
interested, the patient will contact the PI or the PI may directly recruit the patients (with documented 
permission from the patient). Investigators may give the referring physicians a study information 
sheet for the patients. 
 Study investigators provide their colleagues with a “Dear Patient” letter describing the study. This 
letter can be signed by the treating physicians and would inform the patients how to contact the study 
investigators. The study investigators may not have access to patient names and addresses for mailing 
 Advertisements, notices, and/or media used to recruit subjects. Interested subjects initiate contact 
with study investigators. Attach ads, notices, or media text for review. In section below, please explain 
where ads will be posted. 
 Study investigators identify prospective subjects through chart review. (Study investigators request a 
Waiver of Authorization for recruitment purposes.) 
 Large-scale epidemiological studies and/or population-based studies: Prospective subjects are 
identified through a registry or medical records and contacted by someone other than their personal 
physician. (Study investigators request a Waiver of Authorization for recruitment purposes.) 
 Direct contact of potential subjects who have previously given consent to be contacted for participation 
in research. Clinic or program develops a CHR-approved recruitment protocol that asks patients if they 
agree to be contacted for research (a recruitment database) or consent for future contact was 
documented using the consent form for another CHR-approved study. 
 Study investigators list the study on the School of Medicine list of UCSF Clinical Trials website or a 
similarly managed site. Interested subjects initiate contact with investigators. 

 Study investigators recruit potential subjects who are unknown to them through methods such as 
snowball sampling, direct approach, use of social networks, and random digit dialing. 
 Other 
If Other, explain: 
Inpatients and outpatients referred for clinically indicated FGD-PET are going to be invited for participation 
in this study. The investigators will explain in detail the study and will provide the informed consent to the 
potential subject. The investigators will clarify any doubts related to the informed consent and/or the study. 
23.2 * How, when, and by whom eligibility will be determined: 
The patients will be approached (by phone call) by one of the investigators before they arrive at the 
Radiology department for the clinically indicated FGD-PET. 
23.3 * How, when, where and by whom potential subjects will be approached: 
The investigator will look for exclusion criteria of scheduled patients for FGD-PET . The patients will be 
approached by phone call before their scheduled appointment at the Radiology department for the 
clinically indicated FGD-PET. 
23.4 * Protected health information (PHI) will be accessed prior to obtaining consent: 
 Yes   
 No 
24.0 
Waiver of Consent/Authorization for Recruitment 
Purposes 
This section is required when study investigators (and/or affiliated 
nurses or staff) recruit their own patients directly. 
24.1 * Study personnel need to access protected health information (PHI) during the recruitment process 
and it is not practicable to obtain informed consent until potential subjects have been identified: 
 Yes 
If no, a waiver of consent/authorization is NOT needed. 
24.2 * A waiver for screening of health records to identify potential subjects poses no more than minimal 
risk to privacy for participants: 
 Yes 
If no, a waiver of authorization can NOT be granted. 
24.3 * Screening health records prior to obtaining consent will not adversely affect subjects' rights and 
welfare: 
 Yes 
If no, a waiver of authorization can NOT be granted. 
24.4 * Check all the identifiers that will be collected prior to obtaining informed consent: 

 
 Names
 Dates 
 Postal addresses 
 Phone numbers 
 Fax numbers 
 Email addresses 
 Social Security Numbers* 
 Medical record numbers 
 Health plan numbers 
 Account numbers 
 License or certificate numbers 
 Vehicle ID numbers 
 Device identifiers or serial numbers 
 Web URLs 
 IP address numbers 
 Biometric identifiers 
 Facial photos or other identifiable images 
 Any other unique identifier 
 None 
Note: HIPAA rules require that you collect the minimum necessary. 
24.5 * Describe any health information that will be collected prior to obtaining informed consent: 
Name, phone number and presence of contraindications (history of cardiac pacemaker, retained metallic 
foreign body, cochlear implant, aneurysm clip in the brain, claustrophobia, pregnancy and eGFR less than 
45%) to the MR exam. 
Note: HIPAA requires that you collect the minimum necessary. 
24.6 * Describe your plan to destroy the identifiers at the earliest opportunity consistent with the 
research or provide a health or research justification for retaining the identifiers, or indicate and 
explain that retention is required by law: 
As soon as this study is finished, all the data will be destroyed, physically and virtually. 
25.0 
Informed Consent 
25.1 * Methods (check all that apply): 
 Signed consent will be obtained from subjects and/or parents (if subjects are minors) 
 Verbal consent will be obtained from subjects using an information sheet or script 
 Electronic consent will be obtained from subjects via the web or email 
 Implied consent will be obtained via mail, the web or email 
 Signed consent will be obtained from surrogates 
 Emergency waiver of consent is being requested for subjects unable to provide consent 
 Informed consent will not be obtained 
25.2 * Process for obtaining informed consent: 

An investigator will invite potential patients that were referred for clinically indicated FGD-PET for study 
participation before their exam. 
25.3 * How investigators will make sure subjects understand the information provided to them: 
Investigators will talk in a lay language and will be available to clarify any doubts regarding any questions. 
26.0 
Financial Considerations 
26.1 Subjects payment or compensation method (check all that apply): 
Payments will be (check all that apply): 
 Subjects will not be paid 
 Cash
 Check 
 Debit card 
 Gift card 
 Reimbursement for parking and other expenses 
 Other: 
Specify Other: 
26.2 Describe the schedule and amounts of payments, including the total subjects can receive for 
completing the study. If deviating from recommendations in Subject Payment Guidelines, include 
specific justification below. 
Subjects will not be paid. 
26.3 Costs to Subjects: Will subjects or their insurance be charged for any study procedures? 
  Yes   
   No 
If yes, describe those costs below, and compare subjects’ costs to the costs associated with alternative 
care off-study. Finally, explain why it is appropriate to charge those costs to the subjects. 
27.0 
CTSI Screening Questions 
27.1 * This study will be carried out at one of the UCSF Clinical Research Services (CRS) centers or will 
utilize CRS services. CRS centers are at the following sites: 
SFGH Clinical Research Center 
Moffitt Adult Clinical Research Center 
Moffitt Hospital Pediatrics & NCRC 
Mount Zion Hospital Clinical Research Center 
Tenderloin Center 
CHORI Children's Hospital Pediatrics & Adult Clinical Research Center 
Kaiser Oakland Research Unit 
SF VA Medical Center Clinical Research Unit 
Please note: Effective 3/1/14, the CRS form will no longer be completed and submitted in iRIS. The 
CRS budget request form can be found at: https://accelerate.ucsf.edu/files/crs 
/BudgetRequest2015.docx. Follow the instructions on the form to submit. Even if you click 'Yes' to 
this question, the form will no longer proceed to the Clinical Research Services (CRS) Application 
Form section. 
 

  Yes   
   No 
27.2 This project involves community-based research: 
  Yes   
   No 
27.3 This project involves practice-based research: 
  Yes   
   No 
28.0 
End of Study Application 
28.1   End of Study Application Form To continue working on the Study 
Application: Click on the section you need to edit in the left-hand menu. Remember to save 
through the entire Study Application after making changes. If you are done working on the 
Study Application: Click Save and Continue. If this is a new study, you will automatically 
enter the Initial Review Submission Packet form, where you can attach consent forms or 
other study documents. Review the Initial Review Submission Checklist for a list of required 
attachments. Answer all questions and attach all required documents to speed up your 
approval.