Presentation on theme: "PET AND PET/CT IN ISCHEMIC HEART DISEASE"— Presentation transcript:
1PET AND PET/CT IN ISCHEMIC HEART DISEASE Miguel Hernandez Pampaloni, M.D., Ph.D.Chief, Nuclear MedicineAssistant Professor of Radiology
2Agenda Myocardial perfusion imaging SPECT Perfusion PET Metabolic PET (Viability)Hybrid Imaging (PET/CT)
3Myocardial Perfusion Imaging SPECT IndicationsDetects 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).
4SPECT Radiotracers Isotopes Thallium-201 or Technetium-99m compounds.Both assess LV function and ischemiaIsotopes taken up by viable myocardial cells in quantities proportional to perfusion.Well perfused regions appear brighter.
6Stress Protocols Exercise Pharmacologic Pt walks on treadmill with increasing speed/incline.Goal = increase myocardial oxygen demand (MVO2)CAD: the increased demand exceeds supply = ischemiaAdvantages: flexible protocols.Disadvantages: pt must be able to achieve 85% of maximal HR.Pharmacologicdobutamine = increases HR, BP, contractility; mimics exercise.Coronary vasodilators – dipyridamole and adenosine.Flow mismatch; diseased dilated arteries get less flowSensitivities and specificities comparable to exercise stress.
7SPECT Myocardial Perfusion Imaging StrengthsExtensively 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.
8Relationship between Extent of Ischemia and Cardiac Events 6040Cardiac Event Rate (%)20246Reversible Defects (Number)Ladenheim Ml et al. J Am Coll Cardiol. 1986;7:464.
9Magnitude of Jeopardized Myocardium log Hazard Ratio123456% Total Myocardium Ischemic SPECT12.5%25%32.5%50%Medical RxRevasc**P < 0.001Hachamovitch R et al. Circulation. 2003;107:
10Why PET Perfusion? Obesity and poor quality studies, SPECT. DosingAttenuation correctionImage clarity.Improved diagnostic accuracy, lower false positive.Identification of multivessel ischemia.Rapid acquisition: impaired patients.Lower radiation burden.
11SPECT vs PET Perfusion SPECT PET Energy: 78-140 KeV Attenuation correction: sometimesStress: exercise, pharmacologicProtocol, start to finish: 2–2/12 hoursVentricular function: post-stress, rest511 KeVAttenuation correction: alwaysStress: pharmacologic, exercise in future (F-18)Protocol, start to finish:30–45 minutesVentricular function: stress, rest
12Myocardial Perfusion PET in Patients with a Non-Diagnostic SPECT 2% (5 pts!!) Non-Diagnostic233 consecutive pts with a nondiagnostic SPECT followed by MP PET <90 daysAbnormal25%Put in the comparison differencesNormal73%64% were womenMean BMI 32Mean age 62 yrs Bateman. Circ 2003;108:IV-454.
13Prevalence of Artifacts: PET vs SPECT P valueNo artifact19 (17%)49 (44%)0.0001Minor artifact26 (23%)28 (25%)0.75Significant artifact64 (57%)33 (29%)0.0003Major artifact3 (3%)2 (2%)0.32No GI uptake45 (40%)100 (89%)<0.001Minor GI uptake5 (4%)0.0002Significant GI uptake46 (41%)6 (5%)Major GI uptake1 (1%)Bateman TM et al. J Nucl Cardiol. 2006;13(1):24-33.
15Perfusion PET Advantages High spatial and temporal resolution.Excellent sensitivity.Accurate depth-independent attenuation correction.High contrast resolution.Quantitative imaging capabilities.At the end
19PET Perfusion for Detecting Myocardial Ischemia AuthorSensitivitySpecificity# PatientsGould95%100%50Demer94%193Go93%78%202Schelbert97%45Yonekura49Williams98%146Stewart84%88%319Weighted Avg.93% +/- 892% +/- 5766This sensitivity & specificity chart is a compilation of studies from various authors using both Rb-82 & N-13 Ammonia.22. Nuclear Medicine Self-Study Program III: Nuclear Medicine Cardiology. Botvinik, EH, Ed. 1998: Society of Nuclear Medicine, Reston, VA.
20Yoshinaga K et al. J Am Coll Cardiol. 2006;48:1029. Freedom From Any Cardiac Events Following Rb-82 Myocardial Perfusion PETYoshinaga K et al. J Am Coll Cardiol. 2006;48:1029.
21Characteristics of a Normal Myocardial Perfusion PET Study Uniform distribution of tracer, independent of genderLV cavity at peak stress equal to/smaller than at restUniform and normal wall thickness and thickeningUniform and normal regional wall motionPeak stress LVEF > rest LVEFThis slide enumerates the important descriptors of a normal ECG-gated rest and peak stress Rb-82 PET scan after dipyridamole stress.
23Characteristics of an Abnormal Myocardial Perfusion PET Study Decrease in regional tracer uptake at peak stressLV cavity at peak stress larger than at restFrequent regional contraction abnormality (stunning) at peak stressPeak stress LVEF < rest LVEFThis slide enumerates the important descriptors of a normal ECG-gated rest and peak stress Rb-82 PET scan after dipyridamole stress.
24Abnormal 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
25Ischemia + Transient Dilatation Multivessel DiseaseIschemia + Transient DilatationThe peak stress images show a uniform distribution of Rb-82 to all regions except for the inferior and inferolateral walls. That region shows a severe defect with normalized uptake in the rest images.Note that the LV cavity is larger at peak stress than at rest; the TID ratio is quantitated at This is frequently observed with PET in the presence of ischemia, even when this involves only a single coronary territory. With SPECT, TID is seen infrequently, and usually indicates multivessel CAD. The difference presumably is because PET stress images are acquired during hyperemia, while SPECT images are acquired late after hyperemia has resolved.The reversible perfusion defect is severe in its intensity, and involves a moderately large amount of contiguous lateral and inferior myocardium extending from the base of the left ventricle to the apex. Because the anterolateral wall is spared, this defect is most likely in the distribution of a large obtuse marginal vessel, rather than the proximal left circumflex itself.
27Quantification of Myocardial Blood Flow RestLAOStressRAO
28Arterial Tracer Input Function and Changes in Myocardial Tracer Concentration543ActivityConcentration(cts / pixel / sec)Myocardium21Arterial Blood20406080100120Time (sec)
29Clinical Value Long Term Known MBF in Kawasaki Diseasep = 0.01500400300Myocardial Blood Flow(ml/100g/min)200100RestAdenosineRestAdenosineControln = 10Kawasakin = 10Muzik et al, J ACC Vol 28; 3:757-62, 1996
30Clinical Value Long Term Known Therapy MBF Changes in Insulin ResistanceRPPMBFNSP <0.05P <0.05SDPercent IncreaseBaselineOn TreatOff TreatBaselineOn TreatOff TreatQuinones et al, Ann Int Med 2004:140:
31Long Term Prognostic Value PET Perfusion Added Value of Coronary Flow ReserveHerzog et al. JACC 2009;54:
32Clinical Role of Quantitative PET Conditions which cannot be evaluated by "relative" imaging modalitiesExtent and significance of multivessel diseasePharmacologic therapy and life style modificationsDetection of preclinical and early CADMicrovascular disease (endothelial disfunction)Evaluation of procedural outcome (PTCA)Hemodynamic significance of CAD (coronary steal syndrome, collaterals)Myocardial regenerationVentricular remodeling (the discussion of which would require two more hours)Limitations of quantitative PETUnpredictable hyperemic response (what is "normal"?)Computational demands
33Why Is PET More Suitable to Follow Pro/Regression of CAD Coronary blood flow is a function of the arterial radius raised to the fourth powerSmall changes in diameter not measurable by anatomic imaging are magnified into much larger changes in blood flow that are readily quantifiable by PETChanges in PET perfusion can be seen in 40–90 days after intense risk factor treatment is begunGould KL. J Nucl Cardiol. 2005;12:
34Viability PET Study Chronic LVEF Dysfunction Traditionally the gold standardTwo 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 integrityGlucose metabolismOHHO18F
35Myocyte FDG Uptake Normal Myocyte Ischemic Myocyte X X Hexokinase Glucose 6-phosphataseGlucose 6-phosphataseXXFDG-6-PFDGFDGFDG-6-PFFAGlycolytic PathwayGlycolytic PathwayHexokinaseHexokinaseFFAFFAG6PD- GlucoseD- GlucoseG6PD- GlucoseD- GlucoseGlucose 6-phosphataseGlucose 6-phosphatase
37Improved symptoms of CHF PET ViabilityImproved symptoms of CHFExtent mismatch (%LV)r=0.87,SEE=10.8P<0.001Improvement(%)Multivessel CADMean LVEF = 28±6%18%Di Carli M et al, Circulation 1995;92:
38PET vs Dobutamine Echo Improved Exercise Tolerance Delta METS (%) 8020-20-40-6040608020-20-404060Delta METS (%)r=0.54P=0.0001r=0.005P=0.92PET viable (%)DE viable (%)Multivessel CAD, mean LVEF = 277% 59% NYHA III or IVMarwick T et al: J Am Coll Cardiol 33:750, 1999
39The Next Thing is….Tracking of Genetically Labeled Progenitor Cells by PET3 x 106 endothelial progenitor cells transfected with the sodiumiodide symporter gene were injected intramyocardially in a healthy rat. After injection of N-13 ammonia, homogeneous myocardial perfusion is shown in grayscale on the top. Perfusion images are overlayed with images of reporter-gene expression (bottom). obtained after injection of I-124 sodiumiodide (red/yellow). Regional accumulation of the reporter probe depicts presence of viable transplanted cells at the injection site in the lateral wall. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.Beeres, S. L.M.A. et al. J Am Coll Cardiol 2007;49:
40Hybrid PET/CTA: Myocardial Perfusion and Function Concurrent Rest & Peak Stress FunctionCardiac PerfusionCoronary Calcium AssessmentCTA
41Progression of Atherosclerosis CT Coronary angiographySPECTPETEndothelial dysfunctionSevere ischemiaAdapted from Abrams J. N Engl J Med. 2005;352:
42Why Now? Availability of PET cameras: oncology Availability of RadiopharmaceuticalImprovement in acquisition protocolsImprovement in cardiac processingAbility to do ECG-gated imagingImprovement in cardiac display
43PET/CT scan protocol Spiral CT Corrections: scatter attenuation (1-8 min total)Fused PET/CTCTPETCTPETWhole-body PET(6-40 min total)Reconstruction:FORE + OSEMCTPET
45Why 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.
46Rest-Stress PET Rubidium-82 and CTA Protocol 0:00 min0:30 min
47Effective Radiation Dose for Cardiac PET/CT Studies StudyEffective Radiation (mSv)PETF-18 FDG (370 MBq)7.0N-13 NH3 rest/stress (2X 550 MBq)2.2Rb82 rest/stress (2 x 740 MBq)3.6H2O-15 rest/stress (2 x 740 MBq)1.4Transmission Ge-68 rod sourceMSCTCalcium ScoringCT angiographyCT based PET attenuation correction
48Relationship of Stress-Induced Ischemia and Atherosclerosis (CAC) Distribution of the normal MPS studies (N=1,119)1-910-991000Distribution of the ischemic MPS studies (N=76)CAC score5%0 %7 %20 %29 %39 %22%4 %18 %25 %20 %11 %Berman DS et al. J Am Coll Cardiol. 2004;44:
49Prognosis of Cardiac Events by PET-CT Added Value of CACSchenker, M. P. et al. Circulation 2008;117:
50Hybrid PET/CTA: Myocardial Perfusion and Function A 57-year-old man with atypical chest pain during exertion. A, CT reconstructions show significant stenoses in the LAD, RCA, and a small intermediate branch (IM). LCx was nonstenosed. Yellow dotted line denotes motion artifacts in the RCA. B, Hybrid volume-rendered image. Stress myocardial perfusion was reduced only in the area supplied by the LAD. C, ICA with quantitative analysis showed significant 73% luminal narrowing in the LAD. Other vessels were not stenosed.A 63-year-old man with positive family history. Good performance, atypical chest pain, and 2-mm ST depression in the ECG at the exercise test. In hybrid images, stress myocardial perfusion was reduced in most regions (green and blue). However, both CT and ICA showed normal coronary arteries, indicating possible microvascular disease.Kajander, S. et al. Circulation 2010;122:
51PET and CTA Complement Each Other Calcium (blooming)StentsLimited spatial resolution, <1.5-mm vesselsOverestimation of stenosisPositive predictive value MDCT ~50%Clinical outcomes dataPreclinical diseaseAbnormal CT Angiography: Limited Positive Predictive Value
52Discordance Between Noninvasively Determined Anatomic and Functional Measures of Atherosclerosis Percent stenosis a moderate descriptor of coronary resistanceStenosis difficult to estimate with soft plaqueCoronary vasodilator reserve integrates coronary epicardial and microvascular functionBalanced ischemia (MPI)Artifacts (MPI)Noncoronary causes of myocardial damage
54Infarct size measurement Representative midventricular short-axis slices of CT delayed enhancement (left), resting PET perfusion (measured by N-13 ammonia, NH3) and metabolism (measured by FDG) (right), and PET-CT fusion (middle) in animals studied in the chronic and acute phasesRepresentative midventricular short-axis slices of CT delayed enhancement (left), resting PET perfusion (measured by N-13 ammonia, NH3) and metabolism (measured by FDG) (right), and PET-CT fusion (middle) in animals studied in the chronic and acute phases after myocardial infarction. Images of chronic infarction show transmural delayed enhancement in anteroseptal wall, associated with a perfusion/metabolism matched defect on PET. Images of acute infarction show a no-reflow phenomenon in anteroseptal wall, associated with reduced perfusion but enhanced metabolism (mismatch) on PET.Lautamaki, R. et al. Circ Cardiovasc Imaging 2009;2:
55Changes Coming With Hybrid Imaging Nuclear Cardiology Evolution PET-CT:Comprehensive evaluation of CADPerfusionFunctionViabilityVulnerable Plaque Assessment (FDG ?)
56Take Home MessageInformation derived from CT and PET is complementary for the evaluation of CAD.Promising new 18F-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.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.