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PET AND PET/CT IN ISCHEMIC HEART DISEASE

PET AND PET/CT IN ISCHEMIC HEART DISEASE. Miguel Hernandez Pampaloni, M.D., Ph.D. Chief, Nuclear Medicine Assistant Professor of Radiology. Agenda. Myocardial perfusion imaging SPECT Perfusion PET Metabolic PET (Viability) Hybrid Imaging (PET/CT).

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PET AND PET/CT IN ISCHEMIC HEART DISEASE

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  1. PET AND PET/CT IN ISCHEMIC HEART DISEASE Miguel Hernandez Pampaloni, M.D., Ph.D. Chief, Nuclear Medicine Assistant Professor of Radiology

  2. Agenda • Myocardial perfusion imaging SPECT Perfusion PET • Metabolic PET (Viability) • Hybrid Imaging (PET/CT)

  3. Myocardial Perfusion ImagingSPECT • Indications • Detects presence/location/extent of myocardial ischemia in patients with R/O ACS. • Risk stratification after ACS. • Identify fixed defects, evaluate EF and viability. • CP with abnormal EKG’s. • Equivocal ETT. • Inability to exercise (pharmacological stress).

  4. SPECT Radiotracers • Isotopes • Thallium-201 or Technetium-99m compounds. • Both assess LV function and ischemia • Isotopes taken up by viable myocardial cells in quantities proportional to perfusion. • Well perfused regions appear brighter.

  5. Myocardial Perfusion ImagingExercise SPECT

  6. Stress Protocols • Exercise • Pt walks on treadmill with increasing speed/incline. • Goal = increase myocardial oxygen demand (MVO2) • CAD: the increased demand exceeds supply = ischemia • Advantages: flexible protocols. • Disadvantages: pt must be able to achieve 85% of maximal HR. • Pharmacologic • dobutamine = increases HR, BP, contractility; mimics exercise. • Coronary vasodilators – dipyridamole and adenosine. • Flow mismatch; diseased dilated arteries get less flow • Sensitivities and specificities comparable to exercise stress.

  7. SPECT Myocardial Perfusion Imaging • Strengths • Extensively validated, useful for cost-effective risk stratification & patient management. • Widely available – outpatient settings. • Standardized protocols. • Excellent procedural and clinical utilization guidelines published by professional medical societies. • 27 accepted clinical indications.

  8. Relationship between Extent of Ischemia and Cardiac Events 60 40 Cardiac Event Rate (%) 20 0 0 2 4 6 Reversible Defects (Number) Ladenheim Ml et al. J Am CollCardiol. 1986;7:464.

  9. 6 5 * Medical Rx 4 log Hazard Ratio 3 * Revasc 2 1 0 0 12.5% 25% 32.5% 50% % Total Myocardium Ischemic SPECT Magnitude of Jeopardized Myocardium *P < 0.001 Hachamovitch R et al. Circulation. 2003;107:2900-2907.

  10. Why PET Perfusion? • Obesity and poor quality studies, SPECT. • Dosing • Attenuation correction • Image clarity. • Improved diagnostic accuracy, lower false positive. • Identification of multivessel ischemia. • Rapid acquisition: impaired patients. • Lower radiation burden.

  11. Energy: 78-140 KeV Attenuation correction: sometimes Stress: exercise, pharmacologic Protocol, start to finish: 2–2/12 hours Ventricular function: post-stress, rest 511 KeV Attenuation correction: always Stress: pharmacologic, exercise in future (F-18) Protocol, start to finish:30–45 minutes Ventricular function: stress, rest SPECT vs PET Perfusion SPECT PET

  12. Myocardial Perfusion PET in Patients with a Non-Diagnostic SPECT 2% (5 pts!!) Non-Diagnostic 233 consecutive pts with a nondiagnostic SPECT followed by MP PET <90 days Abnormal 25% Normal 73% 64% were women Mean BMI 32 Mean age 62 yrs        Bateman. Circ 2003;108:IV-454.

  13. Prevalence of Artifacts: PET vs SPECT Bateman TM et al. J NuclCardiol. 2006;13(1):24-33.

  14. Radiation Exposure (mSv) PET vs SPECT

  15. Perfusion PET Advantages • High spatial and temporal resolution. • Excellent sensitivity. • Accurate depth-independent attenuation correction. • High contrast resolution. • Quantitative imaging capabilities.

  16. Myocardial Blood Flow and Radiotracer Uptake

  17. PET Cardiac Radiotracers

  18. PET Perfusion for Detecting Myocardial Ischemia

  19. Freedom From Any Cardiac Events Following Rb-82 Myocardial Perfusion PET Yoshinaga K et al. J Am CollCardiol. 2006;48:1029.

  20. Characteristics of a Normal Myocardial Perfusion PET Study • Uniform distribution of tracer, independent of gender • LV cavity at peak stress equal to/smaller than at rest • Uniform and normal wall thickness and thickening • Uniform and normal regional wall motion • Peak stress LVEF > rest LVEF

  21. Characteristics of an Abnormal Myocardial Perfusion PET Study • Decrease in regional tracer uptake at peak stress • LV cavity at peak stress larger than at rest • Frequent regional contraction abnormality (stunning) at peak stress • Peak stress LVEF < rest LVEF

  22. Abnormal N-13 perfusion study 72 year old man with peripheral vascular disease. Coronary arteriography: •LAD: 60% ostial and 80% mid vessel stenoses •LCX: 90% proximal stenosis and occluded OM •RCA: 90% ostialstenosis

  23. Multivessel Disease • Ischemia + Transient Dilatation

  24. PET Perfusion/Metabolic Imaging Protocols 13N-ammonia 82Rb 13N-ammonia 82Rb 18F-FDG Transm. Rest Exercise Pharm. Stress Metabolic Imaging Dipyridamole Adenosine Dobutamine

  25. Quantification of Myocardial Blood Flow Rest LAO Stress RAO

  26. Arterial Tracer Input Function and Changes in Myocardial Tracer Concentration 5 4 3 Activity Concentration (cts / pixel / sec) Myocardium 2 1 Arterial Blood 0 0 20 40 60 80 100 120 Time (sec)

  27. Clinical Value Long Term Known MBF in Kawasaki Disease p = 0.01 500 400 300 Myocardial Blood Flow (ml/100g/min) 200 100 0 Rest Adenosine Rest Adenosine Control n = 10 Kawasaki n = 10 Muzik et al, J ACC Vol 28; 3:757-62, 1996

  28. Clinical Value Long Term Known Therapy MBF Changes in Insulin Resistance RPP MBF P <0.05 P <0.05 NS SD Percent Increase Baseline On Treat Off Treat Baseline On Treat Off Treat Quinones et al, Ann Int Med 2004:140:700-708

  29. Long Term Prognostic Value PET Perfusion Added Value of Coronary Flow Reserve Herzog et al. JACC 2009;54:150-156.

  30. Clinical Role of Quantitative PET Conditions which cannot be evaluated by "relative" imaging modalities • Extent and significance of multivessel disease • Pharmacologic therapy and life style modifications • Detection of preclinical and early CAD • Microvascular disease (endothelial disfunction) • Evaluation of procedural outcome (PTCA) • Hemodynamic significance of CAD (coronary steal syndrome, collaterals) • Myocardial regeneration • Ventricular remodeling (the discussion of which would require two more hours) Limitations of quantitative PET • Unpredictable hyperemic response (what is "normal"?) • Computational demands

  31. Why Is PET More Suitable to Follow Pro/Regression of CAD • Coronary blood flow is a function of the arterial radius raised to the fourth power • Small changes in diameter not measurable by anatomic imaging are magnified into much larger changes in blood flow that are readily quantifiable by PET • Changes in PET perfusion can be seen in 40–90 days after intense risk factor treatment is begun Gould KL. J Nucl Cardiol. 2005;12:625-638.

  32. HO HO OH HO 18F Viability PET StudyChronic LVEF Dysfunction • Traditionally the gold standard • Two sets of resting images to detect viable and hibernating myocardium: • Perfusion image (usually with N-13 ammonia or rubidium-82) • Glucose metabolic image (with F-18 fluorodeoxyglucose = FDG) Cellular membrance integrity Glucose metabolism

  33. FDG FDG FDG-6-P FDG FDG FDG FDG FDG FDG FFA FFA FDG FDG FFA FFA FDG FDG FFA FFA FDG FDG FFA FFA FDG FDG FFA FFA FFA FFA FFA FFA D-Glucose Myocyte FDG Uptake Normal MyocyteIschemic Myocyte Glucose 6-phosphatase Glucose 6-phosphatase X X FDG-6-P Glycolytic Pathway Glycolytic Pathway Hexokinase Hexokinase FFA G6P D-Glucose D-Glucose D-Glucose G6P Glucose 6-phosphatase Glucose 6-phosphatase

  34. PET Myocardial Viability NH3 FDG Stress Rest Fixed Match Fixed Mismatch Partially Reversible Match Partially Reversible Mismatch

  35. r=0.87, SEE=10.8 P<0.001 18% Extent mismatch (%LV) PET Viability Improved symptoms of CHF Improvement (%) Multivessel CAD Mean LVEF = 28±6% Di Carli M et al, Circulation 1995;92:3436-44.

  36. 80 80 60 60 40 40 20 20 0 0 -20 -20 -40 -40 -60 PET vsDobutamine Echo Improved Exercise Tolerance Delta METS (%) r=0.54 P=0.0001 r=0.005 P=0.92 PET viable (%) DE viable (%) Multivessel CAD, mean LVEF = 277%59% NYHA III or IV Marwick T et al: J Am CollCardiol 33:750, 1999

  37. The Next Thing is…. Tracking of Genetically Labeled Progenitor Cells by PET Beeres, S. L.M.A. et al. J Am CollCardiol 2007;49:1137-1148

  38. Hybrid PET/CTA: Myocardial Perfusion and Function Concurrent Rest & Peak Stress Function Coronary Calcium Assessment Cardiac Perfusion CTA

  39. PET Endothelial dysfunction Severe ischemia SPECT Progression of Atherosclerosis CT Coronary angiography Adapted from Abrams J. N Engl J Med. 2005;352:2524-2533.

  40. Why Now? • Availability of PET cameras: oncology • Availability of Radiopharmaceutical • Improvement in acquisition protocols • Improvement in cardiac processing • Ability to do ECG-gated imaging • Improvement in cardiac display

  41. PET/CT scan protocol • Corrections: • scatter • attenuation Spiral CT (1-8 min total) Fused PET/CT CT PET CT PET Whole-body PET (6-40 min total) • Reconstruction: • FORE + OSEM CT PET

  42. Calcium score: 890 SPECT Underestimates Disease Burden: Stable CAD

  43. Why use PET/CTA ? • Non invasive. • Offer high diagnostic accuracy. • Monitor the course of disease. • Allow quantification of myocardial blood flow and coronary reserve. • Able to detect early functional abnormalities. • Able to monitor consequences of lifestyle modifications.

  44. 0:00 min 0:30 min Rest-Stress PET Rubidium-82 and CTA Protocol

  45. Effective Radiation Dose for Cardiac PET/CT Studies

  46. Distribution of the normal MPS studies (N=1,119) Distribution of the ischemic MPS studies (N=76) CAC score 0 5% 22% 4 % 1-9 0 % 10-99 18 % 7 % 100-399 20 % 25 % 400-999 20 % 29 % 1000 11 % 39 % Relationship of Stress-Induced Ischemia and Atherosclerosis (CAC) Berman DS et al. J Am CollCardiol. 2004;44:923-930.

  47. Prognosis of Cardiac Events by PET-CT Added Value of CAC Schenker, M. P. et al. Circulation 2008;117:1693-1700

  48. Hybrid PET/CTA: Myocardial Perfusion and Function Kajander, S. et al. Circulation 2010;122:603-613

  49. PET and CTA Complement Each Other • Calcium (blooming) • Stents • Limited spatial resolution, <1.5-mm vessels • Overestimation of stenosis • Positive predictive value MDCT ~50% • Clinical outcomes data • Preclinical disease Abnormal CT Angiography: Limited Positive Predictive Value

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