PET MYOCARDIAL PERFUSION AND QUANTIFICATION OF FLOW

Transcription

1 PET MYOCARDIAL PERFUSION AND QUANTIFICATION OF FLOW Robert Bober, MD, FACC Director of Nuclear Cardiology and Molecular Imaging John Ochsner Heart and Vascular Institute The Ochsner Clinical School University of Queensland Ochsner Medical Center, New Orleans, LA

2 Disclosures Bracco research support, consultant Off-label discussions - None

3 Learning Objectives 1. Discuss the basics of positron emission tomography (PET) imaging and how PET differs from standard single-photon emission computed tomography (SPECT) 2. Discuss evaluation of coronary flow reserve, myocardial perfusion, and absolute myocardial flow by PET imaging and their value in the assessment and management of coronary artery disease (CAD) 3. Introduce the concept of coronary flow capacity and its potential impact on patient care 4. Use cardiac PET imaging to help identify patients for whom revascularization procedures may reduce coronary events

4 Program Agenda PET Instrumentation and how it differs from SPECT Using PET and Flow to Guide Revascularization Measurements of Myocardial Flow Kinetic Models Cases Self Assessment Module

5 PET Instrumentation

6 Conventional SPECT Limited count sensitivity Limited energy resolution Limited spatial and contrast resolution Limited accuracy of measuring uptake without AC Garcia EV, et al. Cardiol Clin. 2009;27(2):

7 PET Instrumentation Line of Response P N N P P P N N B + P 0-5 mm Annihilation 511 KeV γ γ 511 KeV B + Coincidence Event Detected in Ring PET Scanner Cardiac PET. In: Heller GV, Hendel RC. Handbook of Nuclear Cardiology. 1st ed. London, UK: Springer; Turkington TG. J Nucl Med Technol. 2001;29(1):4-11.

8 2D vs 3D Acquisition 2D Turkington TG. J Nucl Med Technol. 2001;29(1):4-11. Multi-ring PET Acquisition Modes 3D

9 Camera Specifications PET 511 KeV photons LIST mode (most) >3 million counts/sec ~35 M counts/study Sensitivity (detection of emitted photons) 2%-15% Spatial resolution < 2-3 mm SPECT Photon energies <140KeV Binned mode (most) counts/sec 7-10 M counts/study Sensitivity 2-3x s less than PETàlonger acquisition Spatial resolution mm Wackers, JACC. 2010;55(18) GB Saha, Basics of Pet Imaging Gould, State of the Art PET 2013, supplement Salerno, Circ Imaging. 2009;2:

10 Attenuation Correction Photon attenuation results from emitted radiation interacting with tissue. For PET, the path length represents the LOR, along which the dually emitted photons travel. Therefore, attenuation is independent of the point of origin along the LOR. For SPECT, due to its single-photon emission nature, attenuation changes depending on the point of emission. LOR, line of response.

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12 Courtesy K. Lance Gould, MD.

13 Courtesy K. Lance Gould, MD.

14 How PET Differs From SPECT

15 Higher Accuracy Current literature supports a high diagnostic accuracy for cardiac PET perfusion imaging, due to: Robust attenuation correction High count densities (improved image quality and interpretation) Tracers that follow MBF in a more linear fashion than current SPECT tracers MBF, myocardial blood flow

16 SROC Curves for Diagnostic Accuracy of Rb-82 PET and Tc-99m SPECT With ECG-Gating and Attenuation Correction Sensi*vity 85% Specificity 85% Sensi*vity 90% Specificity 88% N = 1755 N = 1344 AUC, area under the curve; Q, Cochran Q statistic; SROC, summary receiver-operating characteristic. Mc Ardle BA, et al. J Am Coll Cardiol. 2012;60(18):

17 Summary ROC Curves for SPECT and PET MPI N = 11,862 patients MPI, myocardial perfusion imaging; ROC, receiver operating characteristic Parker MW, et al. Circ Cardiovasc Imaging. 2012;5(6):

18 Overall Diagnostic Accuracy for PET and SPECT: 70% Stenosis Threshold P = 0.02 P = 0.03 Sensi1vity Specificity Accuracy SPECT PET Bateman TM, et al. J Nucl Cardiol. 2006;13(1):24-33.

19 Diagnostic Accuracy for Localizing Disease to Individual Coronary Arteries: 70% Threshold P = P = P = Sensi1vity Specificity Accuracy SPECT PET Bateman TM, et al. J Nucl Cardiol.2006;13:24-33.

20 Body Habitus and Gender Results from studies by Bateman and colleagues demonstrate superior accuracy of PET, independent of both body habitus and gender Bateman TM, et al. J Nucl Cardiol. 2006;13(1):24-33.

21 Diagnostic Accuracy Men 69% 84% *P=0.05 Women 67% 88% *P=0.01 BMI<30 70% 87% *P=0.05 BMI>30 67% 85% *P=0.02 MVD Sensi1vity 48% 71% *P= MVD, multivessel disease. Based on data from Bateman TM, et al. J Nucl Cardiol. 2006;13(1): SPECT PET

22 Risk Stratification SPECT has a wealth of data on risk stratification. More data are emerging for cardiac PET risk stratification. For PET, risk stratification is based on: Size and severity of perfusion abnormalities Decreased ejection fraction at stress Overall ventricular function Coronary flow reserve (CFR)

23 Unadjusted Hazard of Events by % Myocardium Abnormal on Vasodilator Stress Rb-82 PET All-cause Death Cardiac Death Dorbala S, et al. J Am Coll Cardiol. 2013;61(2):

24 Downstream Testing Because of improved image quality, reader confidence is increased. The downstream effect is referral to catheterization for consideration for potential revascularization, NOT to confirm diagnosis. Studies have demonstrated fewer catheterizations following PET compared with SPECT studies.

25 CAD Intervention Utilization Rates vs CAD Management Costs CAD Management Costs in Pts Studied with SPECT vs PET MPI Utilization Rates of Diagnostic Coronary Arteriography, PTCI, and CABG in Pts Studied with SPECT vs PET MPI 50% CABG, coronary artery bypass graft; CAD, coronary artery disease; PTCI, percutaneous transluminal coronary intervention Merhige ME, et al. J Nucl Med. 2007;48(7): % 50%

26 Radiation Exposure Radiation exposure reduction has become an import consideration when selecting a test. ASNC recommended target dose <9 msv for a routine study (recommended to be implemented by 2014). PET flow tracers have been examined, and it has been demonstrated that patient exposure is below that recommended by ASNC. ASNC, American Society of Nuclear Cardiology Cerqueira MD, et al. J Nucl Cardiol. 2010; 17(4):

27 Typical Effective Doses From Cardiac Imaging Procedures Einstein AJ. J Am Coll Cardiol. 2012;59(6):

28 Protocol Patient Convenience Rest/stress Rb-82 protocols can be accomplished in minutes. Rb mci Pharmacologic stress* Rb mci CT transmission Gated rest Gated stress CT transmission sec sec Approx 1 min Approx 7 min Approx 6 min Approx 7 min Approx 1 min *Dipyridamole, adenosine, or dobutamine

29 USING PET AND FLOW TO GUIDE REVASCULARIZATION

30 Current Revascularization Practice LHC (angiogram) gold standard See and fix approach based on % stenosis Current guidelines: 50% LM and 70% for revascularization FFR/stress intermediate lesions 1 FFR used in 6% of patients 2 LHC, left heart catheterization; LM, left main; FFR, fractional flow reserve 1. Levine GN, et al. J Am Coll Cardiol. 2011;58(24):e44-e Dattilo PB, et al. J Am Coll Cardiol. 2012;60(22):

31 Revascularization guided by % stenosis will lead to better outcomes DATA???

32 COURAGE and STICH Revascularization based on % stenosis Stress testing NOT mandatory Decisions to guide revascularization based on judgment of angiographer FFR not utilized Boden WE, et al. N Engl J Med. 2007;356(15): Velazquez EJ, et al. N Engl J Med. 2011;364(17): COURAGE, Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; STICH, Surgical Treatment for Ischemic Heart Failure.

33 Rates of Survival and Freedom From Major Cardiovascular Events The BARI 2D Study Group. N Engl J Med. 2009;360(24):

34 Revascularization Guided by % Stenosis Will Lead to Better Outcomes DATA Revasculariza1on guided by % stenosis will lead to beter outcomes

35 Repe11on of Error Does Not Cons1tute Experience Edmund Tramont, MD 1999ish

36 FAME I and II FFR-guided revascularization I - FFR vs angiography II - FFR vs optimal medical therapy Pijls N, et al. J Am Coll Cardiol. 2010;56(3): De Bruyne B, et al. N Engl J Med. 2012;367(11): FAME, Fractional Flow Reserve versus Angiography for Multivessel Evaluation; MACE, major adverse cardiac events; PCI, percutaneous coronary intervention

37 Herzog BA, et al. J Am Coll Cardiol. 2009;54(2): Ziadi MC, et al. J Am Coll Cardiol. 2011;58(7): Murthy VL, et al. Circulation. 2011;124(20): MFR, myocardial flow reserve; SSS, summed stress score.

38 Introduction to Coronary Blood Flow Ischemia myocardial O 2 supply vs demand Adequate supply is maintained with ability to increase CBF 2 major resistances to flow Epicardial arteries (>350 µm) Arterioles and capillaries (microvasculature) Resting microvascular (R 2 ) >>> epicardial (R 1 ) Normally regulation occurs at level of microvasculature CBF increases automatically to increase O 2 demands Exercise Pharmacologic stress Neurohormonal CBF, coronary blood flow

39 Epicardial Vessels and the Microvasculature

40 Pathologic Conditions R 1 > R 2 Coronary stenosis and diffuse disease à Flow impaired at level of epicardial artery R 2 > R 1 Autoregulation impaired à Flow impaired within microvasculature

41 Coronary Flow Reserve = 2.9 Baseline flow remains stable up to ~83% stenosis. Hyperemic flow starts diminishing ~40% stenosis. Gould KL, et al. Am J Cardiol. 1974;33(1):87-94.

42 A Brief Word on FFR FFR = fractional flow reserve Pressure-derived flow surrogate Stress test of an artery in the cath lab Distal coronary pressure FFR = Proximal coronary pressure During Maximal Hyperemia

43 Relationships of CFR, FFR, and Absolute Flow Danad I, et al. J Am Coll Cardiol. 2014;64(14): Johnson NP, et al. JACC Cardiovasc Imaging. 2012;5(2):

44 Relationships of CFR, FFR, and Absolute Flow Johnson NP, et al. JACC Cardiovasc Imaging. 2012;5(2):

45 Invasive CFR vs % Stenosis CFR, coronary flow reserve; LAD, left anterior descending artery White CW, et al. N Engl J Med. 1984;310(13):

46 % Stenosis vs FFR Tonino PA, et al. J Am Coll Cardiol. 2010;55(25):

47 Why is there a huge disparity between flow and anatomy?

48 Flow Dynamics Dependent on lesion length Dependent on lesion diameter to the 4th power A small decrease in diameter or increase in length has a profound effect on flow Gould KL. Circ Res. 1985;57(3):

49 Limitations of Anatomic Measures of Stenosis Severity by Angiogram or IVUS Blood Flow No stenosis CFR = % stenosis CFR = % stenosis CFR = 3.4 Diffuse no stenosis IVUS 38% CFR = 1.4 Diffuse + 60% Artgm IVUS 75% CFR = 1.0 Diffuse + 62% Artgm IVUS 75% & adaptive remodeling CFR = 3.5 IVUS, intravascular ultrasound; Artgm, arteriogram Gould KL. JACC Cardiovasc Imaging. 2009;2(8):

50 Flow vs Stenosis Paradox Flow is determined by a combination of Stenosis Diffuse disease Arterial remodeling Microvascular function Impossible to visually determine the physiologic impact of aggregate disease

51 Measurements of Myocardial Flow Kinetic Models

52 Analogy of Kinetic Modeling Problem: measure height of a tree Solutions Chop it down Sun + shadow + trigonometry Photograph tree and yard stick; scaling All methods are valid and should yield similar results

53 How Is Flow Calculated? Kinetic modeling (various models) Basic principles Flow = (myocardial activity) (time activity of arterial blood pool) (extraction coefficient) PET is capable of measuring myocardial activity (M) and activity blood pool (A). Extraction coefficient of Rb-82 and N-13 calculated experimentally. F = M/(1 e -( F/F) )(A) for Rb-82. Different kinetic models have different assumptions for extraction coefficient and measurements of A. Yoshida K, et al. J Nucl Med. 1996;37(10):

54 Relative Imaging Activity Myocardial Activity Time (s)

55 Time-Activity Curves, Rb-82 Blood Pool Activity Activity Myocardial Activity Time (s)

56 For Each Site Percent with Optimal Arterial Input (highest arterial input without spillover) Vasquez AF, et al. JACC Cardiovasc Imaging. 2013;6(5):

57 Arterial Input Function (Ao) Most SP automated selection typically at basal plane of LV and LA Some SP allows manual choice Best Ao could differ between stress and rest LA, left atrium; LV, left ventricle; SP, software package

58 2D vs 3D 3D >10Mcps (~30 mci, 1100 MBq), decline in accuracy and increased image noise from high randoms and dead-time factors At higher activities, the random rate becomes prohibitive in 3D Reduced dose of isotope required to obtain accurate input function Reduced dose reduces myocardial count density

59 Technical Requirements of Flow? Register attenuation/emission images 2D - Linear count recovery up to 3M cps 3D - Linear count recovery up to 12M cps and avoid scanner saturation from 1 st pass bolus (need for internal QC on all images) Selection and QC of input function Confirm not in or on LV LV, left ventricle; QC, quality control Gould KL, et al. J Am Coll Cardiol. 2013;62(18):

60 CFR in 1674 Rest Dipyridamole Quantitative PET Perfusion Images Based on data from Sdringola S, et al. JACC Cardiovasc Imaging. 2011;4(4): Courtesy of K. Lance Gould, MD.

61 Is My Software Correct? (assuming technical requirements are met) Sample 20 NORMAL patients. Young, no risk factors, no tobacco, screen for caffeine Resting flows should all be <1 cc/min/gm AND Stress flows should all be ~3.5 cc/min/gm CFR ~>4.3 Something is wrong if you do not get these values!

62 Is My Software Correct? (assuming technical requirements are met) Sample 20 ABNORMAL patients with definite ischemia (classic angina, perfusion abnormality, and cath-correlated disease) Low stress in ischemic zone should be <0.9 cc/min/gm with low CFR <1.74 Occluded vessels CFR <1.0 Something is wrong if you do not get these values!

63 25 patients with low-to-intermediate probability of CAD 26 patients with known CAD 3 different software applications GE Discovery VCT PET/CT (2D mode, FBP) Tahari AK, et al. Eur J Nucl Med Mol Imaging. 2014;(1):

64 Tahari AK, et al. Eur J Nucl Med Mol Imaging. 2014;(1):

65 Tahari AK, et al. Eur J Nucl Med Mol Imaging. 2014;(1):

66 Measurement of Absolute Flow Requires blood pool and myocardial activity Extraction coefficient and kinetic modeling software Results typically in cc/min/g of myocardium Absolute flow measured at rest and stress (rmbf and smbf)

67 We Can Measure Flow Now What? What is normal? Is there a point where flow drops below metabolic demand? Is there a flow threshold that is associated with angina or ST depression? Is CFR or stress flow more important? CFR, coronary flow reserve

68 Conceptual Thresholds of Flow Causing Ischemia Percent or Number of Cases Flow Value(s)?? FLOW Stents/CABG Medical Therapy Courtesy of K. Lance Gould, MD.

69 Ischemic Thresholds for Flow CFR < CFR < CFR, coronary flow reserve Johnson NP, et al. JACC Cardiovasc Imaging. 2011;4(9):

70 Conceptual Thresholds of Flow Causing Ischemia Percent or Number of Cases Stress flow 0.9 cc/min/g and CFR of 1.7 FLOW Stents/CABG Medical Therapy Courtesy of K. Lance Gould, MD.

71 Coronary Flow Capacity Johnson NP, et al. JACC Cardiovasc Imaging. 2012;5(4):

72 Invasive Coronary Flow Capacity Map van de Hoef TP, et al. JACC Cardiovasc Interv. 2015;8(13):

73 Scatter Plot of Invasive Flow Data Across the Coronary Flow Capacity Concept van de Hoef TP, et al. JACC Cardiovasc Interv. 2015;8(13):

74 Scatter Plots of Fractional Flow Reserve Across Map of Coronary Flow Capacity van de Hoef TP, et al. JACC Cardiovasc Interv. 2015;8(13):

75 Risk of Major Adverse Cardiac Events According to Coronary Flow Capacity Strata van de Hoef TP, et al. JACC Cardiovasc Interv. 2015;8(13):

76 Left Ventricular Quadrants in Cardiac PET Johnson NP, et al. JACC Cardiovasc Imaging. 2011;5(4):

77 Case 1 49-year-old female admitted for chest pain Diabetes mellitus, hypertension, and tobacco use BP 173/109 mm Hg Troponin negative ECG sinus rhythm, no acute ST changes

78 Case 1 AV, atrioventricular; D1, first diagonal branch; D2, second diagonal branch; LAD, left anterior descending artery; LCx, left circumflex artery; LV, left ventricular; OM1, first obtuse marginal branch; OM2, second obtuse marginal branch; PDA, posterior descending artery; RI, ramus intermedius

79 Case 1

80 Case 1

81 Case 5 65-year-old woman with chest pain in ED BP 170/110 mm Hg Tobacco use, hypertension, unknown lipids, denies diabetes mellitus ECG left ventricular hypertrophy with strain Troponin borderline ED, emergency department.

82 Case 5

83 Case 5

84 Case 5

85 Case 6 44-year-old woman transferred for TMR for lifestyle-limiting angina h/o: >5 PCIs, 5-vessel CABG, 4/5 grafts occluded Known RCA and LCX occlusion Patent SVG jump to OM1-OM2 Patient arrived and PCI of LAD was performed Angina walking to bathroom later that PM CABG, coronary artery bypass graft; TMR, transmyocardial revascularization; LAD, left anterior descending artery; SVG, saphenous vein graft.

86 Case 6

87 Case 6

88 Case 6

89 Case 7 87-year-old man with chest pain and SOB Found to be in atrial fibrillation with RVR Hypertension, hyperlipidemia, diabetes mellitus Troponin 3.5 Beta-blockers à converted to sinus LHC occluded RCA and 3VD referred for CABG PET requested for 2nd opinion by patient RVR, rapid ventricular response; 3VD, three-vessel disease.

90 Case 7

91 Case 7

92 Case 7

93 Defect, Interven1on No Defect, Interven1on No Defect, No Interven1on Increased 0.6±0.7 cc/min/g (1.2±0.4 vs 1.7±0.8, p<0.001). smbf no change (1.7±0.3 vs 1.5±0.4 cc/min/g, p=0.16) smbf no change (2.0±0.6 vs 1.9±0.7 cc/min/g, p=0.7). Bober, R, The Effect of Coronary Revascularization on Regional Myocardial Blood Flow. J Nucl Cardiol. 2016

94 Cardiac PET With Flow Reserve Measuring the Effects of Revascularization 65-year-old man History of HTN, DM, CAD s/p CABG LIMA to LAD, SVG to PLB, and SVG to OM2 PET to assess symptoms of exertional dyspnea Angiogram with 2-vessel PCI performed No change in symptoms Repeat PET PET, positron emission tomography; HTN, hypertension; DM, diabetes mellitus; CAD, coronary artery disease; s/p, status post; CABG, coronary artery bypass graft; LIMA, left internal mammary artery; LAD, left anterior descending artery; SVG, saphenous vein graft; PLB, posterolateral branch; OM2, second obtuse marginal branch; PCI, percutaneous coronary intervention.

95 PET Prior to PCI PET 4 weeks after PCI SUCCESS?? Bober R, et al. Progress in Cardiovascular Diseases, 2015;57(6):

96 PET Prior to PCI PET 4 weeks after PCI NO BENEFIT (at best)

97 Case # 65 y/o female presented with NSTEMI Occluded high OM (culprit) PCI, high grade disease in PDA and proximal LAD medically managed CP recurred in ~ 1 week Returned and underwent LHC Prox LAD FFR =.82 Therefore PCI of PDA Continued with angina

98 Case #

99 Case

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102 /1.27= /1.27= /1.27=.57

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104 LE y/o man with HTN, HPL, DM, tobacco use, Hep C, CKD Initial SPECT 5-12 for DOE and CP fixed defect base to mid inferior wall Normal wall motion on gated SPECT and ECHO Interpreted as likely diaphragm attenuation Medically managed Second SPECT 8-14 for DOE and fatigue Fixed defect base to distal inferior wall Abnormal inferior wall motion (low normal LVEF) Interpreted as infarct with peri-infarct ischemia Medically optimized. No LHC as patients sxs improved and no angina

105 LE SPECT

106 LE SPECT

107 LE Was CP free for ~ 3 years however started to develop exertional CP and worsening DOE Opted for repeat stress for risk stratification over LHC. SPECT interpreted as no change since 2014 however, in this patient with angina and a known fixed perfusion abnormality, SPECT scanning with Tc-99 based isotopes can misclassify ischemic tissue as infarction (based on the flow properties of Tc-99 and tissue attenuation) Consider PET stress testing with absolute flow. PET stress flow obtained

108 LE SPECT

109 LE Review of 2014 and 2015 SPECTS

110 Preview of 2014 and 2015 SPECTS

111 LE PET

112 LE PET

113 LE PET Flows

114 LE PET Flow Capacity

115 LE Summary SPECTS All with FIXED (rest and stress) inferior wall defects 2012 thought to be attenuation thought to be secondary to CAD (infarct) PET No resting defect à no infarction Ischemic flows in RCA and LCX territory LAD flows not normal however, not ischemic Presence of disease expected Not flow limiting LHC- High grade disease in OM1 and RCA Mild/moderate distal LAD disease

116 Polling Question When comparing the difference between photons of SPECT and PET tracers, the true statement regarding SPECT photons: a) Are emitted at ~ 511KeV b) Are emitted as single photons c) Attenuation is independent of the point of origin along the Line of Response d) Are higher energy than PET photons GB Saha, Basics of Pet Imaging

117 Polling Question Coronary Flow Reserve (CFR) is: a) Absolute hyperemic flow minus absolute resting flow b) Absolute resting flow minus absolute hyperemic flow c) The ratio of absolute hyperemic flow to absolute resting flow d) The ratio of absolute resting flow to hyperemic flow Gould KL, et al. Am J Cardiol. 1974;33(1):87-94.

118 Polling Question The estimated effective dose of radiation for cardiac PET rest/stress study with Rb-82 is: a) 10 msv b) <5 msv c) msv d) 6-9 msv Einstein AJ. J Am Coll Cardiol. 2012;59(6):

119 Polling Question Under normal conditions, what is the major resistance to coronary flow? a) Myocardial microvasculature b) Sympathetic nervous system c) Epicardial vessel d) Diastolic filling time Gould KL. Circ Res. 1985;57(3):

120 Polling Question Identify the true statement regarding Coronary Flow Capacity a) Is the integration of both CFR and absolute myocardial stress flow due to a combination of discrete, diffuse and microvascular disease. b) Is the ratio of stress to resting myocardial blood flow. c) Is dependent on patient BMI (body mass index). d) Doesn t not fluctuate within an individual. Johnson NP, et al. JACC Cardiovasc Imaging. 2012;5(4):