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

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Presentation on theme: "PET AND PET/CT IN ISCHEMIC HEART DISEASE Miguel Hernandez Pampaloni, M.D., Ph.D. Chief, Nuclear Medicine Assistant Professor of Radiology."— Presentation transcript:

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

3 Agenda Myocardial perfusion imagingMyocardial perfusion imaging SPECT SPECT Perfusion PET Perfusion PET Metabolic PET (Viability)Metabolic PET (Viability) Hybrid Imaging (PET/CT)Hybrid Imaging (PET/CT)

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

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

6 Myocardial Perfusion Imaging Exercise SPECT

7 Exercise Exercise Pt walks on treadmill with increasing speed/incline.Pt walks on treadmill with increasing speed/incline. Goal = increase myocardial oxygen demand (MVO 2 )Goal = increase myocardial oxygen demand (MVO 2 ) –CAD: the increased demand exceeds supply = ischemia Advantages: flexible protocols.Advantages: flexible protocols. Disadvantages: pt must be able to achieve 85% of maximal HR.Disadvantages: pt must be able to achieve 85% of maximal HR. Pharmacologic Pharmacologic dobutamine = increases HR, BP, contractility; mimics exercise.dobutamine = increases HR, BP, contractility; mimics exercise. Coronary vasodilators – dipyridamole and adenosine.Coronary vasodilators – dipyridamole and adenosine. »Flow mismatch; diseased dilated arteries get less flow Sensitivities and specificities comparable to exercise stress.Sensitivities and specificities comparable to exercise stress. Stress Protocols

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

9 Relationship between Extent of Ischemia and Cardiac Events Ladenheim Ml et al. J Am Coll Cardiol. 1986;7: Reversible Defects (Number) Cardiac Event Rate (%)

10 *P < Hachamovitch R et al. Circulation. 2003;107: Magnitude of Jeopardized Myocardium

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

12 SPECT vs PET Perfusion Energy: KeVEnergy: KeV Attenuation correction: sometimesAttenuation correction: sometimes Stress: exercise, pharmacologicStress: exercise, pharmacologic Protocol, start to finish: 2–2/12 hoursProtocol, start to finish: 2–2/12 hours Ventricular function: post- stress, restVentricular function: post- stress, rest 511 KeV511 KeV Attenuation correction: alwaysAttenuation correction: always Stress: pharmacologic, exercise in future (F-18)Stress: pharmacologic, exercise in future (F-18) Protocol, start to finish:30–45 minutesProtocol, start to finish:30–45 minutes Ventricular function: stress, restVentricular function: stress, rest SPECT PET

13 Normal73% Abnormal25% 2% (5 pts!!) Non- Diagnostic Myocardial Perfusion PET in Patients with a Non-Diagnostic SPECT 64% were women Mean BMI 32 Mean age 62 yrs 233 consecutive pts with a nondiagnostic SPECT followed by MP PET <90 days Bateman. Circ 2003;108:IV-454. Bateman. Circ 2003;108:IV-454.

14 Prevalence of Artifacts: PET vs SPECT SPECTPET P value No artifact 19 (17%) 49 (44%) Minor artifact 26 (23%) 28 (25%) 0.75 Significant artifact 64 (57%) 33 (29%) Major artifact 3 (3%) 2 (2%) 0.32 No GI uptake 45 (40%) 100 (89%) <0.001 Minor GI uptake 19 (17%) 5 (4%) Significant GI uptake 46 (41%) 6 (5%) <0.001 Major GI uptake 2 (2%) 1 (1%) 0.32 Bateman TM et al. J Nucl Cardiol. 2006;13(1):24-33.

15 Radiation Exposure (mSv) PET vs SPECT

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

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18 Myocardial Blood Flow and Radiotracer Uptake

19 PET Cardiac Radiotracers

20 PET Perfusion for Detecting Myocardial Ischemia AuthorSensitivitySpecificity # Patients Gould95%100%50 Demer94%95%193 Go93%78%202 Schelbert97%100%45 Yonekura93%100%49 Williams98%93%146 Stewart84%88%319 Weighted Avg. 93% +/- 8 92% +/

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

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

23 N13-Ammonia PET Images

24 Characteristics of an Abnormal Myocardial Perfusion PET Study Decrease in regional tracer uptake at peak stressDecrease in regional tracer uptake at peak stress LV cavity at peak stress larger than at restLV cavity at peak stress larger than at rest Frequent regional contraction abnormality (stunning) at peak stressFrequent regional contraction abnormality (stunning) at peak stress Peak stress LVEF < rest LVEFPeak stress LVEF < rest LVEF

25 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% ostial stenosis

26 Multivessel Disease Ischemia + Transient Dilatation

27 PET Perfusion/Metabolic Imaging Protocols Transm. RestExercisePharm.Stress DipyridamoleAdenosineDobutamine 13 N-ammonia 82 Rb 82 Rb 13 N-ammonia 82 Rb 82 Rb 18 F-FDG MetabolicImaging

28 Quantification of Myocardial Blood Flow Rest Stress LAO RAO

29 Arterial Tracer Input Function and Changes in Myocardial Tracer Concentration ActivityConcentration (cts / pixel / sec) ActivityConcentration MyocardiumMyocardium Time (sec) Arterial Blood

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

31 SDSD NSNS P <0.05 Percent Increase RPPRPP BaselineBaseline On Treat Off Treat MBFMBF P <0.05 BaselineBaseline On Treat Off Treat Clinical Value Long Term Known Therapy MBF Changes in Insulin Resistance Clinical Value Long Term Known Therapy MBF Changes in Insulin Resistance Quinones et al, Ann Int Med 2004:140:

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

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

34 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 powerCoronary 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 PETSmall 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 begunChanges in PET perfusion can be seen in 40–90 days after intense risk factor treatment is begun Gould KL. J Nucl Cardiol. 2005;12:

35 Viability PET Study Chronic LVEF Dysfunction Traditionally the gold standard Traditionally the gold standard Two sets of resting images to detect viable and hibernating myocardium: Two sets of resting images to detect viable and hibernating myocardium: Perfusion image (usually with N-13 ammonia or rubidium-82) Perfusion image (usually with N-13 ammonia or rubidium-82) Glucose metabolic image (with F-18 fluorodeoxyglucose = FDG) Glucose metabolic image (with F-18 fluorodeoxyglucose = FDG) OH HO HOHO 18 F

36 Myocyte FDG Uptake Normal Myocyte Ischemic Myocyte Glucose 6-phosphatase Hexokinase G6P D- Glucose D- Glucose Glycolytic Pathway D- Glucose D- Glucose X FFA Glucose 6-phosphatase Hexokinase FDG-6-P G6P Glycolytic Pathway D- Glucose D- Glucose X FDGFDG FDG-6-P FDGFDGFDG FDGFDG FDGFDG FDG FDG FDG FDG FDGFDG FDG FFAFFA FFAFFAFFA FFA FFA FFAFFAFFA FFAFFA FFAFFA

37 FixedFixed FixedFixed Partially Reversible MatchMatch MismatchMismatch StressStress RestRest FDGFDG NH 3 MatchMatch MismatchMismatch PET Myocardial Viability

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

39 PET viable (%) Delta METS (%) r=0.54 P= PET vs Dobutamine Echo Improved Exercise Tolerance Marwick T et al: J Am Coll Cardiol 33:750, 1999 DE viable (%) Multivessel CAD, mean LVEF = 27 7% 59% NYHA III or IV r=0.005 P=

40 Beeres, S. L.M.A. et al. J Am Coll Cardiol 2007;49: The Next Thing is…. Tracking of Genetically Labeled Progenitor Cells by PET

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

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

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

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

45 SPECT Underestimates Disease Burden: Stable CAD Calcium score: 890

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

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

48 StudyEffective Radiation (mSv) PET F-18 FDG (370 MBq)7.0 N-13 NH3 rest/stress (2X 550 MBq)2.2 Rb82 rest/stress (2 x 740 MBq)3.6 H2O-15 rest/stress (2 x 740 MBq)1.4 Transmission Ge-68 rod source MSCT Calcium Scoring CT angiography CT based PET attenuation correction Effective Radiation Dose for Cardiac PET/CT Studies

49 Relationship of Stress-Induced Ischemia and Atherosclerosis (CAC) Berman DS et al. J Am Coll Cardiol. 2004;44: Distribution of the normal MPS studies (N=1,119) Distribution of the ischemic MPS studies (N=76) CAC score 5% 0 % 7 % 20 % 29 % 39 % 22% 4 % 18 % 25 % 20 % 11 %

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

51 Kajander, S. et al. Circulation 2010;122: Hybrid PET/CTA: Myocardial Perfusion and Function

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

53 Discordance Between Noninvasively Determined Anatomic and Functional Measures of Atherosclerosis Percent stenosis a moderate descriptor of coronary resistancePercent stenosis a moderate descriptor of coronary resistance –Stenosis difficult to estimate with soft plaque Coronary vasodilator reserve integrates coronary epicardial and microvascular functionCoronary vasodilator reserve integrates coronary epicardial and microvascular function Balanced ischemia (MPI)Balanced ischemia (MPI) Artifacts (MPI)Artifacts (MPI) Noncoronary causes of myocardial damageNoncoronary causes of myocardial damage

54 PETCTADiagnosis Potential Strategy Normal No CADDischarge NormalAbnormalNon-significant CAD Medical Tx & Follow-up Abnormal Significant CADMedical Tx & Consider Cath AbnormalNormalCoronary microvascular dysfunction Risk Profile Modification & Consider Antianginal Tx Scenarios in Cardiac PET/CT imaging for (suspected) Coronary Artery Disease

55 Lautamaki, R. et al. Circ Cardiovasc Imaging 2009;2: Infarct size measurement

56 Changes Coming With Hybrid Imaging Nuclear Cardiology Evolution PET-CT:PET-CT: Comprehensive evaluation of CAD Comprehensive evaluation of CAD Perfusion Perfusion Function Function Viability Viability Vulnerable Plaque Assessment (FDG ?) Vulnerable Plaque Assessment (FDG ?)

57 Take Home Message Information derived from CT and PET is complementary for the evaluation of CAD.Information derived from CT and PET is complementary for the evaluation of CAD. Promising new 18 F-labelled myocardial perfusion tracers are under development and will likely increase use cardiac PET as a routine diagnostic tool. Promising new 18 F-labelled myocardial perfusion tracers are under development and will likely increase use cardiac PET as a routine diagnostic tool. Absolute quantification of myocardial blood flow by dynamic PET has contributed to an improved understanding of the pathophysiology of CAD. It characterizes patients without evidence of regional, visually detectable perfusion heterogeneity. Absolute quantification of myocardial blood flow by dynamic PET has contributed to an improved understanding of the pathophysiology of CAD. It characterizes patients without evidence of regional, visually detectable perfusion heterogeneity. The potential of PET to introduce tracers targeting biologic and molecular mechanisms relevant to cardiac disease and therapy is basically unlimited. PET has the potential to take a central role as a diagnostic tool in personalised, molecular cardiovascular medicine of the future. The potential of PET to introduce tracers targeting biologic and molecular mechanisms relevant to cardiac disease and therapy is basically unlimited. PET has the potential to take a central role as a diagnostic tool in personalised, molecular cardiovascular medicine of the future.


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