1. PET In Cardiology; Metabolic Imaging with 18-FDG

2. Introduction to Metabolic Cardiac Imaging
Patients with severe left ventricular dysfunction and heart failure may have reduced cardiac performance due to irreversible (myocardial infarction or scarring), or reversible causes.
Definitions:
Infarction – artery blocked - heart attack
Stenosis – narrowing of the blood vessel
Ischemia – restriction in blood supply
Perfusion – blood flow
Akinesis – lack of wall motion in a myocardial segment
Tachycardia – abnormal, rapid heart beat
CABG – coronary artery bypass graft
CHF – congestive heart failure

3. Myocardial Metabolism
Resting aerobic conditions: myocardium predominantly utilizes free fatty acids (FFA) as energy substrate.
Glucose loading: insulin released by glucose loading downregulates FFA use, and increases glucose utilization.
Chronic ischemia: FFA utilization suppressed; anaerobic glycolysis preferred. glucose utilization normal.
Acute ischemia: FFA suppressed, enhanced glucose utilization to supranormal levels.

4. Reversible Causes of Global and Regional Myocardial Dysfunction
Stunned myocardium: episode of severe ischemia causes acute cell injury, disruption of architecture, and transient myocardial dysfunction. Residual severe stenosis with patent artery.
Hibernating myocardium: severe stenosis causes chronically ischemic myocardium. Contractility sacrificed for cell integrity.

5. Myocardial Viability and PET Imaging
Viable Myocardium> myocardium which exhibits regional dysfunction due to injury or ischemia and severely reduced blood flow (perfusion), but which is intact metabolically, and can achieve normal or near-normal contractility with revascularization.
Goal of PET Imaging > Identify myocardial segments with poor contractility and severely reduced perfusion, which are intact metabolically (viable).

6. Why 18-Fluorodeoxyglucose Is A Good Cardiac Tracer
Glucose analogue with Fl-18 substituting for hydroxyl group. Trapped in glucose-pyruvate anaerobic glycolysis.
On site synthesis not required. With a 110 min. half-life, off- site synthesis and delivery available.
Studies performed in the non-fasting state, with oral glucose loading and insulin injection.

7. FDG Protocols
Resting perfusion imaging performed as previously described.
18-FDG administered intravenously
Oral glucose loading
One hour given for equilibration
Fingerstick glucose assessed
Insulin administered if necessary
20 minute static acquisition

8. Analysis of Perfusion/Metabolism PET Images
Compare perfusion (Rb-82) with metabolic activity (18-FDG) in each myocardial segment.
Evaluate for regions of mismatch between perfusion and metabolism, relate to wall motion.

9. Perfusion/Metabolism Pattern I
Perfusion metabolism match: severely reduced perfusion, with matching reduction in FDG uptake. This is consistent with low probability of viable myocardium
The following slide shows a severe perfusion defect of the lateral and inferolateral walls (upper panels), with a matching severe metabolic defect in the lower panels. This is consistent with a low probability of viable myocardium in those regions.
This patient would not benefit from an invasive revascularization procedure and would be treated medically.

10. Perfusion Metabolism Match
Rb-82
Severe perfusion defect of the lateral and inferolateral walls (upper panels), with a matching severe metabolic defect in the lower panels
FDG

11. Perfusion/Metabolism Pattern II
Perfusion metabolism mismatch: severely reduced perfusion. FDG uptake normal or near normal. Consistent with high probability of viable myocardium.
The following slide shows a patient with a severe perfusion defect of the lateral wall (RB-82, upper panel). Metabolic study shows intact 18-FDG uptake in the lateral wall (lower panel), indicative of viable myocardium.
Therefore, this patient would benefit from revascularization.

12. Perfusion Metabolism Mismatch
Rb-82
Severe perfusion defect of the lateral wall (RB-82, upper panel).
Metabolic study shows intact 18-FDG uptake in the lateral wall (lower panel),
FDG

13. Perfusion/Metabolism Pattern III
Enhanced FDG uptake: severely reduced perfusion. FDG uptake increased, with downscaling of FDG uptake in other segments. Consistent with viable myocardium and resting silent ischemia.
The following slide shows a patient with a severe perfusion defect of the lateral and inferolateral walls (upper two panels, NH3). Metabolic imaging (lower panel) shows hyper intense uptake of 18-FDG in the lateral and inferolateral walls, with relative downscaling of FDG uptake in other segments. This pattern is consistent with viable myocardium, and resting ischemia.
Therefore, the patient would be treated??????

14. Enhanced 18-FDG Uptake
Severe perfusion defect of the lateral and inferolateral walls
Hyper intense uptake of 18-FDG in the lateral and inferolateral walls
Viable Myocardium and Resting Ischemia
(ML Goris, Bretille J. Colour Atlas of Nuclear Cardiology. Chapman and Hall Medical. London p. 216)

15. Use of PET Metabolic Imaging to Guide Revascularization
Revascularization of segments shown “viable” on PET has a high likelihood of improving cardiac function.
Revascularization of nonviable segments is unlikely to improve function.

16. Results of Revascularization in Viable vs. Nonviable Segments
Likelihood of improved wall motion:
Mismatch 82%
Match: 17%
Tillsch J. NEJM (1986) 314:
Tamaki N. Am J Cardiol (1989) 64: 860-5
Von Dahl A. J Nuc Med (1993) 34:23

17. Improvement in LV function with Revascularization Based on PET Metabolic Imaging
The following table lists studies in which PET perfusion and metabolic imaging is used to identify viable myocardium and dictate coronary bypass surgery or angioplasty.
In 109 total patients studied, mean LV ejection fraction rose from 34% to 47% post revascularization.
Schelbert H. Card Clin 1994; 12:

18. PET Viability with 18-FDG
Superior to SPECT: 30% of nonviable segments on Tl-201 are viable by PET FDG
Extent of viability on PET FDG predicts extent of improvement in left ventricular function post- CABG
Prognosis:
Patients with viable myocardium and revascularization < 10% event rate
Patients with viable myocardium, no revascularization > 27% event rate

19. Pitfalls of PET Perfusion/Metabolic Imaging
Early Post-Myocardial Infarction, there is a increased incidence of:
False (+) Positive Studies: (Positive mismatch, but no viable myocardium). Due to increased anaerobic glycolytic uptake by remodeling WBC’s (white blood cells) and macrophages.
False (--) Negative Studies: (Viable myocardium, but local metabolic factors, such as acidosis and lactate, impair glucose and FDG uptake by myocardium).
Gropler R. JACC (1992) 19:989 JACC (1993) 22: Range Effects: ß(+) energy F-18 (0.64 MeV) vs. Rb-82 (3.35 MeV)

20. Case Study #1 Anterior Wall Viability?
History
66 YOM
H/O anterior MI and CHF
Angiogram: 99% stenosis mid-LAD; 50% stenosis LCX; akinesis anterior and apical walls.
PET Findings
Matched severe perfusion and metabolic defects in the mid-distal anterior wall and apex
Low prob. of viable myocardium
Outcome
No indications for revascularization of LAD
Intensive medical treatment.
Rb-82
FDG

21. Case Study #2; Interior and/or Exterior Wall Viability?
History
50 YOM with unstable angina, cardiogenic shock, sustained ventricular tachycardia.
Angiogram: 100% LAD; 80% RCA. Stenoses. LVEF 25% with severe diffuse hypokinesis. IABP placed
PET Findings
Perfusion/metabolism mismatch in the anterior, apical and inferior wall regions.
Indicates viable, hibernating myocardium in the LAD and RCA distributions
Outcome
PCI successfully performed to LAD and RCA. IABP weaned. Patient discharged.
Rest
Rb-82
FDG

22. Case Study #3 Site of Resting Ischemia and Wall Viability?
History
68 YOF
DM: S/P CABG: recurrent angina
SPECT MPI: severe intensity, slightly reversible lateral defect
Angiogram: Patent LIMA. Grafts to LADD and LCX 100%; 100% RCA. Diffuse LV hypokinesis, LVEF 38%.
PET Findings
PET: mod-severe perfusion defect of lateral and inferolateral walls with hyper-intense lateral wall FDG uptake.
Resting lateral wall ischemia
Outcome
PCI of native LCX
Rb-82
FDG

23. Case Study #4 Evidence of viable myocardium in the anterior wall to justify catheterization and PCI?
History
77 YOF
H/O of CHF. ECG reveals delayed R-wave progression suggestive of anterior MI.
Echocardiogram: severe hypokinesis to akinesis of the anterior, septal and apical walls.
PET Findings
Severe perfusion defect of the anterior, apical, septal and inferoapical walls, with matched decrease in 18-FDG uptake in these regions.
Low prob. of viable myocardium
Outcome
Continued medical therapy
Rest
Rb-82
FDG

24. Case Study #5 Jeopardized or Viable Myocardium?
History
68 YOM
H/O anterior MI, S/P CABG, now with unstable angina.
Angiogram: patent LIMA, and patent grafts to RCA and OM. Significant CAD proximal to grafts.
LV gram: severe anterior wall hypokinesis
PET Findings
Anterior wall severe matched defect of perfusion and metabolism
Low probability of viable myocardium.
Moderate defect in the anteroseptum with slightly greater 18-FDG uptake vs. Rb-82 (mild mismatch).
Outcome
Continued medical therapy
Rb-82
FDG
NOTE: Rb-82 uptake in lateral wall is >> 18-FDG. This indicates viable myocardium

25. Case Study #6 Viable myocardium sufficient to justify revascularization and mitral valve replacement?
History
Pt. with history of MI. Admitted with CHF and found to have mitral regurgitation. LVF severely reduced on echocardiogram.
PET Findings
Anteroapical perfusion/metabolism mismatch - viable myocardium
Inferior wall severe perfusion defect with matched FDG uptake - low prob. of viable myocardium
Outcome
CABG + MVR
Rb-82
FDG

26. Case Study #7 Is LAD viable?
History
66YOM
S/P anterior MI and stent to the LCX. Now admitted with unstable angina.
Angiogram: 100% stenosis of proximal LAD. 100% stenosis of LCX stent.
LV gram: Severely reduced LVF with anteroapical akinesis. LVEF 25%.
PET Findings
Severe perfusion defect of the anterior, anterolateral and apical walls, with matched 18-FDG uptake in those regions. FDG uptake and perfusion intact in the lateral wall.
Low probability of anterior wall viable myocardium
Outcome
PCI LCX
Rb-82
FDG

27. Case Study #8 Viable myocardium in the LAD?
History
71YOM with abnormal ECG
Angiogram: 100% stenosis of LAD
LV gram: akinesis of the distal anteroapex
PET Findings
Severe perfusion defect in the distal anterior and apical walls, with intact metabolic 18-FDG uptake.
Perfusion/metabolism mismatch - viable myocardium
Outcome
PCI of LAD
Rb-82
FDG

28. Case Study #9 Is Anterior Wall Viable?
History
81YOF with abnormal ECG
H/O stents to the RCA and LCX. Recurrent angina
Angiogram: Patent stents of the LCX. Occluded stent of the RCA. 100% occlusion of the mid LAD
Ventriculogram: moderately reduced LV function with anteroapical akinesis
PET Findings
Perfusion/Metabolism mismatch in the anteroapical, anterolateral and lateral walls, consistent with hibernating, viable myocardium
Outcome
CABG
Rb-82
FDG

29. Case Study #10 Is there viable myocardium in the anterior and lateral walls to justify attempts at revascularization?
History
64 yo male with anterolateral MI, CHF
Angiography: 100% occlusion mid LAD. 100% occlusion mid LCX. RCA nonobstructive
Echocardiogram: severely reduced LV function.. Akinesis of the distal septum and apex. Severe hypokinesis of the lateral wall.
PET Findings
Rb-82 perfusion: Severe perfusion defects distal anterior, apical, lateral walls.
18-FDG Metabolic study: severe defects matching rubidium perfusion uptake. Consistent with low probability of viable myocardium
Outcome
Medical management
Rb-82
FDG

30. Case Study #11 Is there viable myocardium in the anterior wall?
History
79 y.o. male with acute myocardial infarction and cardiogenic shock
Coronary Angiography revealed 100% occlusion of the proximal LAD, and 90% stenosis of the LCX. RCA was non-dominant
Echo revealed severely reduced LV function with anterior, septal and apical akinesis.
PET Findings
PET study shows severe matching perfusion defects in the LAD distribution. Viable myocardium present in the lateral and inferior walls (which was jeopardized on angiogram).
Outcome
PCI LCX
Rb-82
FDG

31. ACC/ASNC Guidelines for PET Imaging
Class I
Adenosine or dipyridamole myocardial perfusion PET in patients in whom an appropriately indicated myocardial perfusion SPECT study has been found to be equivocal for diagnostic or risk stratification purposes. (Level of Evidence: B)

32. ACC/ASNC Guidelines for PET Imaging
Class IIa
Adenosine or dipyridamole myocardial perfusion PET to identify the extent, severity, and location of ischemia as the initial diagnostic test in patients who are unable to exercise. (Level of Evidence: B)
Adenosine or dipyridamole myocardial perfusion PET to identify the extent, severity, and location of ischemia as the initial diagnostic test in patients who are able to exercise but have LBBB or an electronically-paced rhythm. (Level of Evidence: B)

33. ACC/ASNC Guidelines for Viability Imaging

34. Summary
PET MPI: Due to higher energy isotopes, higher resolution and established attenuation correction, PET has superior sensitivity, specificity and accuracy for detecting, and evaluating the significance of CAD.
PET has a unique and central role in diagnosing CAD in patients with prior equivocal or non-diagnostic non-invasive studies.
PET metabolic imaging, with 18-FDG allows identification of high risk CAD patients who may benefit from revascularization.

35. Andrew Van Tosh, M.D. Associate Professor of Medicine
Albert Einstein College of Medicine
Lab Director, Nuclear Cardiology
Beth Israel Medical Center, New York