1. PET vs. SPECT: An MPI Case Review
“Cardiac PET MPI is a well-established and highly accurate technique for detecting hemodynamically significant CAD. The ability to reduce attenuation artifact is useful in all patients, but particularly the obese.” 7
7. ASNC Model Coverage Policy: Cardiac positron emission tomographic imaging. J Nucl Cardiol 2013; 20:916-47

2. Legal Disclaimers
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3. Purpose
Present published data comparing the image quality and diagnostic accuracy of PET myocardial perfusion imaging (MPI) to SPECT MPI in similarly matched patient types
Report on Rb-82 PET MPI event-free survival and prognosis
Demonstrate, through patient case studies, the effect of better image quality in the treatment of patients
Gender bias
Body mass index (BMI)
Multi-vessel disease (MVD)

4. Image Quality: PET MPI vs. SPECT MPI
This was a study published in the Journal of Nuclear Cardiology by Bateman and colleagues comparing the image quality of SPECT MPI to PET MPI in similarly matched patient types.
As you can see, there was markedly improved image quality for PET vs. SPECT, and the results were statistically significant.
Even for the gated scans, there was a trend towards better image quality for PET. What’s not illustrated here is that PET also provides peak stress information, due to the timing of when the images are acquired, which SPECT can not provide. Peak Stress functional information can be a very useful additional indicator of disease, especially for MVD patients.
Figure 1. Image quality scores for PET and SPECT perfusion and ECG-gated scans
1. Bateman, et. al. J Nucl Cardiol 2006 Jan-Feb; 13(1):24-33

5. Why is the Image Quality with PET Better than SPECT?
Improved image quality for PET vs. SPECT due to:1-4,6
Higher count rates (240% increase over SPECT)
Improved spatial resolution: 3mm PET vs. 6mm SPECT
Routine and robust attenuation correction on all scans
Better detection of MVD
Bateman, et. al. J Nucl Cardiol 2006 Jan-Feb; 13(1):24-33
Merhige, et al. J Nucl Med 2007; 48:1069–1076
Yoshinaga, et al. J Amer Coll Cardiol 2006; 48(5):
Chow, et al. J Nucl Med 2005; 46:1095–101
6. Dorbala et al. J Nucl Med 2007; 48(3):

6. Diagnostic Accuracy: PET vs. SPECT
BY GENDER
BY BMI
69%
84%
*P = 0.55
67%
88%
*P = 0.009
70%
87%
67%
85%
*P = 0.05
*P = 0.02
BMI<30
BMI>30
MVD SENSITIVITY
48%
71%
*P = 0.03
MVD
MEN
WOMEN
This slide illustrates some additional data points from the Journal of Nuclear Cardiology study mentioned earlier. These charts compare the diagnostic accuracy between PET and SPECT for three subcategories. Regardless of the patient’s gender, BMI, or extent of multi-vessel disease, PET outperformed SPECT (with statistical significance).
SPECT
PET
Bateman, et. al. J Nucl Cardiol 2006 Jan-Feb; 13(1):24-33

7. PET MPI: Improved Interpretive Certainty vs. SPECT MPI
The literature suggests that PET MPI images can be read with 96% interpretive certainty vs. 82% with SPECT.
Figure 2. Comparison of degrees of interpretive certainty of SPECT and PET studies
Bateman, et. al. J Nucl Cardiol 2006 Jan-Feb; 13(1):24-33

8. Rb-82 PET vs. Gated AC Tc-99m SPECT
Tc-99m SPECT SROC*
Rb-82 PET SROC*
SPECT:
Pooled Sensitivity = 85%
Pooled Specificity = 85%
PET:
Pooled Sensitivity = 90%
Pooled Specificity = 88% *
AUC: 0.95
Q ():
AUC: 0.909
Q (): 0.841
Prognstic value already shown
*SROC: summary receiver operating characteristic curve
*P < 0.01 for Rb-82 PET vs. gated AC SPECT
5. McArdle et al. J Am Coll Cardiol 2012; 60(18):

9. Left Ventricular EF Reserve and Magnitude of Jeopardized Myocardium
Left ventricular ejection fraction (LVEF) reserve (%)
In a moment, I will be showing you a case that highlights the value of obtaining peak stress functional information along with the perfusion images, but I first wanted to review some relevant data. In a study published in the Journal of Nuc Med by Dorbala et al. from Harvard, LV ejection fraction reserve (Stress EF – Rest EF) was shown to have incremental value above and beyond the perfusion images alone. That is because normal patients should have an increase between rest & stress EF. Patients with left main or 3-vessel disease have a decrease in EF from rest to stress.
Coronary angiogram results
6. Dorbala et al. J Nucl Med 2007; 48(3): 9

10. Rb-82 PET MPI: Event-Free Survival
Summed Stress Score, Total Cardiac Events
0.70
0.75
0.80
0.85
0.90
0.95
1.00
Normal
Mild
Adjusted Event Free Survival
Log-rank p=0.001
Moderate - Severe
Prognostic value in a recent series
0.5 1
1.5 2
2.5 3
3.5 4
Follow up (years)
3. Yoshinaga K, et al. J Am Coll Cardiol 2006; 48:

11. Results from a Multicenter Observational Registry
Rb-82 PET MPI: Prognosis
Prognostic Value of Stress Myocardial Perfusion Positron Emission Tomography:
Results from a Multicenter Observational Registry
Cardiac death (N = 6,037)
All-cause death (N = 7,061)
Unadjusted Hazard of Cardiac Death (A, 6, 037 patients, N= 169 cardiac deaths)
and All-cause Death (B, 7,061 patients, N=570 all-cause deaths) by the % Abnormal Myocardium in and Undergoing Pharmacologic Stress Myocardial Perfusion Rb-82 PET.
7. Dorbala et al. J Am Coll Cardiol 2013 Jan; 61(2):176-8

12. CASE STUDIES

13. Case #1 Patient Profile Demographics: 77-year-old female
Body Habitus: Wt: 160 lbs; Ht: 61 inches; BMI: 31
Risk Factor: hypertension
Reason for Test: atypical chest pain
ECG: normal sinus rhythm and nonspecific T-wave abnormalities
Meds: atenolol, famotidine, aspirin, anticoagulant
Following are images of a patient who underwent a SPECT MPI and a PET MPI study 2 weeks apart at Harvard/Brigham & Women’s Hospital in Boston, MA. The case and study all images courtesy of Marcelo DiCarli, MD (Harvard/Brigham & Women’s Hospital).

14. Case #1: SPECT Images
Since the SPECT images shown here could not be read with confidence, the patient was subsequently referred for a PET scan.

15. Case #1: Rb-82 PET Images
The PET images demonstrated normal myocardial perfusion with interpretive certainty.

16. Case #1: SPECT and PET Images
Tc-99m
Rb-82
The PET images demonstrated normal myocardial perfusion with interpretive certainty.

17. Case #1: Summary
Protocol
SPECT
PET
Mode of Stress
Adenosine (4 min)
Dipyridamole (4 min)
Clinical Response
Non-ischemic
BP Response
Normal
ECG Response
Negative
Radiopharmaceutical
Tc-99m sestamibi
Rubidium-82
Rest / Stress Dose
11mCi / 33mCi
60mCi / 60mCi
Gated
Yes
Cardiac catheterization was not performed because the PET MPI study was normal.

18. Case #2 Patient Profile Demographics: 59-year-old female
Body Habitus: Wt: 140 lbs, H: 65 inches, BMI: 23.5
Reason for Test: evaluation of atypical chest pain and dyspnea
Meds: metoprolol, amlodipine, captopril, furosemide, aspirin, simvastatin, bupropion
Following are images of a patient who underwent a underwent a SPECT MPI and a PET MPI study 12 days apart at Harvard/Brigham & Women’s Hospital in Boston, MA. The case and all study images courtesy of Marcelo DiCarli, MD and Sharmila Dorbala, MBBS (Harvard/Brigham & Women’s Hospital).

19. Case #2: SPECT Images SPECT MPI Report
There was a small defect of moderate intensity in the mid to apical anterior wall that remained fixed on the rest images and most likely is due to breast attenuation artifact; however a non-transmural myocardial scar cannot be excluded.

20. Case #2: Rb-82 PET Images
As you can see, there is a significant improvement in the image quality with PET. Again, this is the same patient who received both SPECT & PET. The images are very bright and clear here, and the patient has an obviously normal scan.
PET MPI Report
There were no regional perfusion defects seen on the stress or rest images. The patient’s PET/CT test results are normal and suggest no evidence of flow-limiting CAD. The results suggest that the previously described fixed anterior wall defect (her prior SPECT study) is likely to represent an attenuation artifact.

21. Case #2: SPECT and PET Images
Tc-99m
Rb-82
As you can see, there is a significant improvement in the image quality with PET. Again, this is the same patient who received both SPECT & PET. The images are very bright and clear here, and the patient has an obviously normal scan.
PET MPI Report
There were no regional perfusion defects seen on the stress or rest images. The patient’s PET/CT test results are normal and suggest no evidence of flow-limiting CAD. The results suggest that the previously described fixed anterior wall defect (her prior SPECT study) is likely to represent an attenuation artifact.

22. Case #2: Summary
Protocol
SPECT
PET
Mode of Stress
Adenosine (4 min)
Dipyridamole (4 min)
Clinical Response
Non-ischemic
BP Response
Normal
ECG Response
Negative*
Radiopharmaceutical
Tc-99m sestamibi
Rubidium-82
Rest / Stress Dose
12mCi / 30mCi
36mCi / 36mCi
Gated
Yes
*Patient had normal sinus rhythm and non-specific ST-T wave abnormalities on the resting ECG prior to the MPI studies.

23. Case #2: Report Comparison
SPECT MPI Report
There was a small defect of moderate intensity in the mid to apical anterior wall that remained fixed on the rest images and most likely is due to breast attenuation artifact; however, a non-transmural myocardial scar cannot be excluded.
PET MPI Report
There were no regional perfusion defects seen on the stress or rest images. The patient’s PET/CT test results are normal and suggest no evidence of flow-limiting CAD. The results suggest that the previously described fixed anterior wall defect (her prior SPECT study) is likely to represent an attenuation artifact.
Cardiac catheterization was not performed because the PET MPI study was normal.

24. Case #3 Patient Profile Demographics: 82-year-old male
Body Habitus: Wt: 210 lbs; Ht: 70 inches; BMI: 30.1
Risk Factor: hypertension
Reason for Test: preoperative cardiac evaluation prior to hip replacement surgery
Meds: aspirin, bisoprolol
Following are images of a patient who underwent a SPECT MPI and a PET MPI study 2 weeks apart at University Hospitals Case Medical Center in Cleveland, OH. The case and all images are courtesy of Jim O’Donnell, MD (University Hospitals Case Medical Center, Cleveland, OH).

25. Case #3: SPECT Images SPECT Report
At a BMI of 30, this patient is just over the line for being considered obese and turns out to present a challenge for SPECT during this pharm stress study.
SPECT Report
Fixed defect is noted at the apex, which does not move or thicken appropriately and likely represents a scar. There is no SPECT evidence of ischemia. LV ejection fraction of 40 percent (normal above 45 percent).

26. Case #3: Rb-82 PET Images PET Report
The PET images demonstrate the above-described apical scar pattern but also demonstrate a mild to moderate anterior ischemic pattern involving the distal half of the anterior segment. This is suggestive of mild peri-infarct ischemia. The LV ejection fraction in the PET study is 53% at rest rising to 57% with pharmacologic stress (normal left ventricular function). Statistically, the likelihood of a perioperative event is still fairly low. Even though this patient received pre-op clearance for hip surgery, the detection of ischemia on the PET study provided prognostically useful information to assist in the management of this patient’s progressive CAD.
Case courtesy of Jim O’Donnell, MD, University Hospitals Health System, Cleveland, OH

27. Case #3: SPECT and PET Images
Tc-99m
Rb-82
PET Report
The PET images demonstrate the above-described apical scar pattern but also demonstrate a mild to moderate anterior ischemic pattern involving the distal half of the anterior segment. This is suggestive of mild peri-infarct ischemia. The LV ejection fraction in the PET study is 53% at rest rising to 57% with pharmacologic stress (normal left ventricular function). Statistically, the likelihood of a perioperative event is still fairly low. Even though this patient received pre-op clearance for hip surgery, the detection of ischemia on the PET study provided prognostically useful information to assist in the management of this patient’s progressive CAD.

28. Case #3: Summary Protocol SPECT PET Mode of Stress Dipyridamole
Clinical Response
Non-ischemic
BP Response
Normal
ECG Response
Negative
Radiopharmaceutical
Tc-99m sestamibi
Rubidium-82
Rest / Stress Dose
10mCi / 33mCi
47mCi / 47mCi
Gated
Yes
Length of Time
2.5 hours
40 minutes

29. Case #3: Report Comparison
SPECT MPI Report
Fixed defect is noted at the apex, which does not move or thicken appropriately and likely represents a scar. There is no SPECT evidence of ischemia. LV ejection fraction of 40% (normal  45%).
PET MPI Report
The PET images demonstrate the above-described apical scar pattern but also demonstrate a mild to moderate anterior ischemic pattern involving the distal half of the anterior segment. This is suggestive of mild peri-infarct ischemia. The LV ejection fraction in the PET study is 53% at rest rising to 57% with pharmacologic stress (normal left ventricular function). Statistically, the likelihood of a perioperative event is still fairly low.

30. Case #3: Final Note
Even though this patient received pre-operative clearance for hip surgery, the detection of ischemia on the PET study provided prognostically useful information to assist in the management of this patient’s progressive CAD.

31. Case #4 Patient Profile Demographics: 69-year-old female
Risk Factor: hyperlipidemia, hypertension, Type II DM
Reason for Test: admitted to hospital after a CVA; found to be in atrial fibrillation with small increase in troponin-I; abnormal ECG
Meds: coumadin, lovenox, toprol XL, lipitor, altace (over the last 24 hrs. prior to imaging per rest/stress dipyridamole cardiogen-82 PET report)
This female with serum-marker documented coronary disease, clinically stable after her acute event, warrants myocardial perfusion imaging for risk-stratification purposes. Either SPECT or PET would be acceptable choices. In this case, PET was selected because the patient was female and because of the CVA required pharmacologic stress. Rubidium-82 PET can be especially useful compared to SPECT in such cases, because attenuation correction will obviate the potential for challenging interpretations due to breast attenuation artifacts, and because Rubidium-82 has minimal liver or bowel uptake after pharmacologic stress, a common finding with SPECT that can make interpretation of the inferior wall difficult.
Following are images of a patient who underwent a rest/dipyridamole stress Rb-82 myocardial perfusion PET study. The case and all images are courtesy of Tim Bateman, MD (Cardiovascular Consultants, Kansas City, MO).

32. Case #4: Rb-82 PET Images
Transient Ischemic Dilation (TID) Ratio: 1.63 (normal = 1.0)
STRESS
REST
A larger cavity size on stress images can indicate a near-balanced flow reduction.
The most distinctive finding in these images is the much larger left ventricular cavity at peak stress than at rest. The transient ischemic dilation (TID) ratio was measured at In both image sets, there appears to be relatively uniform distribution of tracer. However, on closer inspection, it is noted that the entire apical portion of the left ventricle is relatively under-perfused in the peak stress images. The perfusion pattern suggests CAD; the marked TID suggests prognostically important CAD.

33. Case #4: Rb-82 PET Functional Images
PEAK STRESS
LVEF 50%
A lower EF during exercise vs. rest is considered an abnormal compensatory response at a time of increased demand.
REST
LVEF 61%
Although the peak stress images show normal and uniform thickening and motion, the end-systolic dimension is larger at peak stress than at rest, and LVEF is 50% at peak stress compared to 61% at rest. This is a highly abnormal finding, and suggests global LV insult in response to hyperemic stress. This would only be expected in the presence of prognostically important CAD.

34. Case #4: Report The combined test findings indicate the following:
Virtually diagnostic for the presence of CAD
Apical ischemia probably in the distribution of the left anterior descending coronary artery
Severe transient ventricular dilation, suggesting possible near-balanced flow reduction in multiple coronary territories
Normal left ventricular function at rest (LVEF 61%)
Significant drop in LVEF in response to pharmacologic stress
Prognostically concerning scan, with numerous markers of high-risk for major adverse coronary events
REST/STRESS DIPYRIDAMOLE CardioGen-82 (Rubidium Rb-82 Generator) POSITRON EMISSION TOMOGRAPHY REPORT
PATIENT: XXXXXXX TEST DATE: 7/18/2002
GENDER: Female AGE: 69
DOB: XXXXXXX LOCATION: PET/CT Plaza
CHART #: XXXXXXX INPATIENT: Yes
REFERRING PHYSICIAN: XXXXXXXX
SUPERVISING PHYSICIAN: XXXXXXXX
MEDICATIONS:
1. Past 24 Hours: Coumadin, Lovenox, Toprol XL, Lipitor, Altace, Multi Vitamin
2. Held: N/A
HOURS SINCE LAST CAFFEINE INTAKE: 24
INDICATIONS FOR TEST: Myocardial infarction, Hyperlipidemia, Hypertension, Type II DM, Abnormal ECG
PROCEDURAL NOTE: An intravenous line was inserted and an infusion of normal saline was started. A positioning scan was acquired This was followed by an infusion of 53.9 mCi of Rb-82, 60 to 100 seconds after which resting perfusion images were acquired. Following the first set of rest images, an infusion of 38.8 mCi of Rb-82 was given, 60 to 100 seconds after which ECG-gated rest images were acquired. Then 60 mg of Dipyridamole was infused over 4.0 minutes. At three minutes following the infusion, 53.4 mCi of Rb-82 was infused, with the peak stress perfusion images acquired beginning approximately 60 to 100 seconds later. Immediately following the first set of stress images 38.6 mCi of Rb-82 was infused. ECG-gated peak stress images were acquired beginning approximately 60 to seconds later. Aminophylline 100 mg was given intravenously two minutes after the stress scans were completed.
CLINICAL RESPONSE: The heart rate at rest was 57 beats per minute. This increased to 63 beats per minute in response to dipyridamole. The blood pressure at baseline was 126/72 mmHg, and was 115/62 mmHg after dipyridamole infusion. The patient experienced the following symptoms during the test: chest pain.
ELECTROCARDIOGRAPHIC FINDINGS: The resting ECG showed atrial fibrillation, LVH, associated ST/T wave abnormalities. Significant changes did not occur with dipyridamole.
SCINTIGRAPHIC FINDINGS: The rest images were completely normal, with respect to both perfusion and function. Rest LVEF was 61%. The peak-stress images showed a perfusion defect at the apex. In addition, the left ventricular cavity was much larger at peak-stress than at rest, with a TID ratio of Peak stress LVEF was lower than at rest, quantitated at 50%.
IN SUMMARY, the clinical, electrocardiographic, and scintigraphic findings in this 69-year-old female being evaluated for risk stratification after non-STEMI using dipyridamole are as follows:
1) Clinical response: Non-Diagnostic (dipyridamole)
2) Electrocardiographic response: Non-Ischemic
3) Scintigraphic response: Ischemic
The combined test findings indicate the following:
1. Virtually diagnostic for the presence of CAD.
2. Apical ischemia probably in the distribution of the left anterior descending coronary artery
3. Severe transient ventricular dilation, suggesting possible near-balanced flow reduction in multiple coronary territories
4. Normal left ventricular function at rest (LVEF 61%).
5. Significant drop in LVEF in response to pharmacologic stress.
6. Prognostically concerning scan, with numerous markers of high-risk for major adverse coronary events.
Special Comments: Results communicated verbally at time of dictation.
XXXXXXX, MD
Phone: XXXXXXXX
Fax: XXXXXXXX
D: XXXXXXXX 7/18/2002
T: VM 7/22/2002 4:57:20 PM

35. Case #4: Catherization Correlation
The combined test findings indicate the following:
Coronary angiography showed a 75% left main stenosis, a 90% stenosis of the mid LAD and a 70% right coronary artery stenosis
CABG surgery was performed after recovery from the CVA

36. Slide References
Bateman TM, Heller GV, McGhie AI, et al. Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99m sestamibi SPECT. J Nucl Cardiol 2006 Jan-Feb; 13(1):24-33
Merhige ME, Breeny WJ, Shelton V, et al. Impact of myocardial perfusion imaging with PET and 82Rb on downstream invasive procedure utilization, costs, and outcomes in coronary disease management. J Nucl Med 2007; 48:1069–1076
Yoshinaga K, Chow B, Williams K, et al. What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography? J Amer Coll Cardiol 2006; 48(5):
Chow BJW, Wong JW, Yoshinaga K, et al. Prognostic significance of dipyridamole-induced ST depression in patients with normal 82Rb PET myocardial perfusion imaging. J Nucl Med 2005; 46:1095–101

37. Slide References
McArdle BA, Dowsley TF, deKemp RA, et al. Does rubidium-82 have superior accuracy to SPECT perfusion imaging for the diagnosis of obstructive coronary disease? J Am Coll Cardiol 2012; 60(18):
Dorbala S, Vangala D, Sampson U, et al. Value of vasodilator left ventricular ejection fraction reserve in evaluating the magnitude of myocardium at risk and the extent of angiographic coronary artery disease: A 82Rb PET/CT study. J Nucl Med 2007; 48(3):
Dorbala S, DiCarli M, Beanlands R, et al. Prognostic value of stress myocardial perfusion positron emission tomography: Results from a multicenter observational registry. J Am Coll Cardiol 2013; 61(2):

38. Additional References
Sherif Iskander and Ami Iskandrian; Risk Assessment Using Single-Photon Emission Computed Tomographic Technetium-99m Sestamibi Imaging. J Am Coll Cardiol. 1998;32:57-62.
Gary Heller and Robert Hendel, Editors: Handbook of Nuclear Cardiology: Cardiac SPECT and Cardiac PET. Springer-Verlag London ©2013
Benjamin J. W. Chow et al, Prognostic Value of PET Myocardial Perfusion Imaging in Obese Patients, JACC Cardiovascular Imaging 2014; 7(3)
Vasken Dilsizian and Jagat Narula, Atlas of Nuclear Cardiology, 3rd Edition, ©2009 Current Medicine Group LLC
Marcelo DiCarli et al, Long Term Survival of Patients with Coronary Artery Disease and Left Ventricular Dysfunction: Implications for the Role of Myocardial Viability Assessment in Management Decisions. J Thorac Cardiovasc Surg 1998; 116(6):

39. Additional References
D’Egidio G, et al. Increasing Benefit From Revascularization is Associated With Increasing Amounts of Myocardial Hibernation; A Substudy of the PARR-2 Trial. JACC Cardiovascular Imaging 2009; 2(9)
2013 ACCF/ACR/ASE/ASNC/SCCT/SCMR Appropriate Utilization of Cardiovascular Imaging in Heart Failure. J Am Coll Cardiol 2013; 61(21)
Ziadi M, et al. Impaired Myocardial Flow Reserve on Rubidium-82 Positron Emission Tomography Imaging Predicts Adverse Outcomes in Patients Assessed for Myocardial Ischemia. J Am Coll Cardiol 2011; 58(7)
Murthy V, et al. Improved Cardiac Risk Assessment with Non-Invasive Measures of Coronary Flow Reserve. Circulation 2011; 124(20):

40. Additional References
Skali H, Schulman A and Dorbala S. 18-F FDG PET/CT for the Assessment of Myocardial Sarcoidosis. Current Cardiology Reports 2013; 15(4):352
Einstein AJ. Effects of Radiation Exposure From Cardiac Imaging: How Good Are the Data? J Am Coll Cardiol 2012; 59(6):
Cerqueira MD, et al. ASNC Information Statement: Recommendations for reducing radiation exposure in myocardial perfusion imaging. J Nucl Cardiol doi: /s Published online 26 May 2010

41. Important Safety Information
Image interpretation errors can occur with PET imaging.
Hypersensitivity reactions, including anaphylaxis, may occur in patients who receive PET radiopharmaceuticals. Emergency resuscitation equipment and personnel should be immediately available.
PET/CT imaging contributes to a patient’s overall long-term cumulative radiation exposure, which may be associated with an increased risk of cancer. Safe handling practices should be used to minimize radiation exposure to the patient and healthcare providers.
Adverse reactions, although uncommon, may occur when using PET radiopharmaceuticals. Always refer to the package insert prior to use.