Actualités et Avenir de la Cardiologie Nucléaire
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1 Actualités et Avenir de la Cardiologie Nucléaire Doumit Daou, MD, PhD Département de Médecine Nucléaire, Hôpital Cochin, APHP Paris, France
2 Nuclear Cardiology
3 Future of Nuclear Cardiology
4 Future of Nuclear Cardiology Clinical Cardiology: Progress in molecular biology and genetics Patient specific mechanistic approach underlying the disease Leading to patient specific treatment Directly impact Future of Nuclear Cardiology
5 Future of Nuclear Cardiology Basic / Clinical Cardiology: Moreover, cardiology is steadily moving towards earlier detection and treatment of disease. This requires radically new imaging methods to be implemented: Atherosclerosis: Concept: endothelial dysfunction, vulnerable plaque (patient) Heart failure: Concept: MMP activity Gene therapy
6 Future of Nuclear Cardiology Nuclear Cardiology is well armed to meet this Molecular Imaging challenges (radiotracers): Angiogenesis Hypoxia Metabolism Neurotransmission Apoptosis Myocardial inflammation Vulnerable atherosclerotic lesions Gene products Nuclear Cardiology is progressing in parallel with basic/clinical cardiology
7 Future of Nuclear Cardiology
8 Future of Nuclear Cardiology
9 Lessons from the Past/Present CCTA: Indication: To rule out CAD Challenged recently by a publication in the NEJM 2008: NPV=83%! Correlation of quantitative stenosis vs invasive CA: r=0.6 (and lower if calcifications) Nissen SE J Limitations of computed tomography coronary angiography. J Am Coll Cardiol 2008; 52:
10 Lessons from the Past/Present Ca scoring: Risk stratification Recently, Erbel et al reported NS value for risk stratification at 5 years in low risk and high risk patients (prospective study). It reached statistical significance in intermediate risk patients Erbel et al ACC 2009
11 Future of Nuclear Cardiology Nuclear cardiology may sometimes compete with or complement other technologies: This may lead to the development of hybrid imaging technology (PET/CT, SPECT/CT, or MRI): Strength Limitations
12 Future of Nuclear Cardiology Multimodality imaging with PET/CCTA (or SPECT/CCTA): Coronary plaque detection: anatomy Physiologic significance of plaques Increase in sensitivity and specificity of the PET/CCTA hybrid method as compared to each alone Increase in prognostic value of combining CCTA and MPI data Schiujf et al ESC 2007 Joutsiniemi et al ESC 2008
13 Future of Nuclear Cardiology Metabolic syndrome Tahara N et al JACC 2007;49:1533-9
14 Future of Nuclear Cardiology Davies JR et al J Nucl Cardiol 2005;12:234-46
15 Future of Nuclear Cardiology Inflammation was visualized by FDG PET imaging in 30% of patients with documented carotid atherosclerosis Tahara N et al Eur Heart J 2007;28:2243-8
16 Future of Nuclear Cardiology Tahara N et al JACC 2006;48:
17 Future of Nuclear Cardiology Wykrzykowska J et al J Nucl Med 2009;50:563-8
18 Future of Nuclear Cardiology
19 Future of Nuclear Cardiology
20 Future of Nuclear Cardiology
21 Lessons from the Past/Present Patient population Validation studies Clinicians expertise Guidelines Imaging center expertise
22 Lessons from the Past/Present MPS withstood the test of time versus: Exercise stress test Stress echocardiography Coronary angiography
23 Lessons from the Past/Present MPS strength: Stress test: physiological exercise or pharmacologic Implicating cardiologists Highly reproducible Easily exportable to non-academic centers Wide availability of SPECT Availability Tc-99m based tracers (generators) Coupling function to perfusion
24 Lessons from the Past/Present MPS SPECT strength: Abundant validating literature in CAD: Diagnosis Prognosis Suggestion of treatment strategy Evaluation of treatment efficacy: medical, PTCA, CABG
25 Future of Nuclear Cardiology MPS SPECT strength Hachamovitch R et al Circulation 2003;107:2900-7
26 Lessons from the Past/Present MPS limitations: Radiotracers: not ideal for perfusion Artifacts : affecting its PPV» Inferior» Breast attenuation Underestimation of CAD:» particularly 3-vessel and left main CAD Duration of the overall exam Radiation exposure Low spatial resolution (cold-spot) SPECT low tracer-detection-sensitivity
27 Future of Nuclear Cardiology
28 Future of Nuclear Cardiology NM SPECT: CT: 1990 s : ECG gating: coupling function to perfusion Tc-99m tracers SPECT: large FOV! Limited amelioration in software and hardware 1998: 4 slices 2009: 320 slices
29 Present: New Imaging Systems
30 Present: New Imaging Systems SPECT / CT (PET / CT)
31 SPECT Quantification and Attenuation correction Garcia E J Nucl Cardiol 2007;14:16-24
32 No More Inferior Wall Attenuation Bybel B et al Radiographics 2008;28:
33 Incremental Diagnostic Accuracy for CAD ASNC and SNM joint statement J Nucl Med 2002;43:273-80
34 Incremental Diagnostic Accuracy for CAD Garcia E J Nucl Cardiol 2007;14:16-24
35 Incremental Diagnostic Accuracy for CAD Links JM et al J Nucl Cardiol 2000;7:414-25
36 Incremental Diagnostic Accuracy for CAD Links JM et al J Nucl Cardiol 2000;7:414-25
37 Incremental Diagnostic Accuracy for CAD Links JM et al J Nucl Cardiol 2000;7:414-25
38 Incremental Diagnostic Accuracy for CAD Links JM et al J Nucl Cardiol 2000;7:414-25
39 Incremental Diagnostic Accuracy for CAD Links JM et al J Nucl Cardiol 2000;7:414-25
40 Prognostic value of AC in CAD Baghdasarian SB et al J Nucl Cardiol 2009;16:533-9
41 Attenuation Correction Well established: Higher specificity / higher normalcy rate diaphragmatic and breast attenuation over-correction of inferior wall attenuation Similar sensitivity (without decline!) Increased observer confidence for the presence or absence of image normalcy Substantial improvement in specificity for right coronary, but a slight loss of sensitivity in right coronary and LAD coronary artery Improved uniformity in the mean and variance maps of normal database (body habitus, gender)
42 Future of Nuclear Cardiology False positive Mrs S C AC FBP
43 Future of Nuclear Cardiology False positive Mr L G AC FBP
44 Future of Nuclear Cardiology Inferior MI Mr I Y AC FBP
45 Future of Nuclear Cardiology Inferior MI Mr Z Y AC FBP
46 Future of Nuclear Cardiology Infero-lateral ischemia Mr G J AC FBP
47 Future of Nuclear Cardiology Infero-lateral ischemia Mr G M AC FBP
48 Future of Nuclear Cardiology Ant + Lat ischemia Mr P H AC FBP
49 Future of Nuclear Cardiology Normal Mr M M AC FBP
50 DM2, dyslip, smoker Diabetic neuropathy Lower limb arteritis Asymptomatic Mr C J Stress: Exercise (90 W, 76% THR) + Dip (0.84 mg/kg): Clinically negative ECG positive: 1 mm V4-V6
51 Mr C J Myoview : Exercise + Dip vs rest Stress Rest FBP
52 IR + AC Stress Rest Mr C J
53 Mr C J SPECT / CT with CT done for attenuation correction: Coronary Calcium Heavy LAD and LCx Calcifications
54 Present: New Imaging Systems Address the main limitations of actual SPECT systems: Changing the gamma camera system conception: Changing the detector geometry Optimizing tomographic sampling of the FOV for cardiac imaging Improving the detector material and collimator design Optimizing the image reconstruction algorithms
55 Conventional gspect Acquisition
56 Present: New Imaging Systems Different systems designed to: Increase sensitivity Increase spatial and temporal resolution Allow dynamic SPECT acquisitions without having to rotate the heads of gamma-camera Allow simultaneously AC, scatter, RR, and dealing with noise Potentially, it is technically possible to realize positron detection!
57 Present: New Imaging Systems
58 CardiArc SPECT-HD
59 D-SPECT
60 Discovery 530 NM Discovery NM 530c Discovery NM /CT 530c
61 Discovery 530 NM Multipinhole collimator design An array of Cadmium Zinc Telluride (CZT) pixilated detectors Gives complete and consistent angular data to allow real dynamic SPECT acquisitions: Detectors and collimators do not move All LOR are acquired simultaneously Garcia E et al J Nucl Cardiol 2008;15:S3
62 Discovery 530 NM MAP iterative reconstruction adapted to the camera geometry As compared to the Ventri Camera: 1.65-fold improvement in energy resolution Energy resolution: 5.7% fold improvement in spatial resolution Spatial resolution: mm 5-7-fold improvement in sensitivity Garcia E et al J Nucl Cardiol 2008;15:S3
63 New Imaging Systems This will impact favorably: Energy resolution Spatial resolution Temporal resolution Image quality Acquisition time Radiation dose Patient comfort Patient motion Lab throughput Imaging feasible with Old and New tracers
64 New Imaging Systems This will impact favorably: Total exam time (stress-rest) Claustrophobic patients Potential acquisition of ED perfusion images Potential respiratory gating Amelioration in image quality and temporal resolution of gated SPECT and GBPSPECT Render practical SPECT acquisitions at rest and under stress with dobutamine for GSPECT Render practical SPECT acquisitions at rest and under stress with dobutamine for GBPSPECT
65 New Imaging Systems This will impact favorably: Real dynamic cardiac SPECT
66 Respiratory Motion
67 Respiratory Motion
68 Perspectives: Respiratory Gating
69 Respiratory Motion
70 Respiratory Motion Tidal respiration Respiratory motion amplitude Cranio-caudal axis (mm) Diaphragm 12 ± 7 Liver 22 ± 10 Heart * 10.5 ± 5 Kidneys 17 ± 2.5 Spleen 13 ± 0.6 * : D CC > 5 mm (100% sujets) D CC > 12 mm (50% sujets)
71 New Imaging Systems Real dynamic cardiac SPECT: calculate absolute CFR : Teboroxime may come back! Gullberg GT et al J Nucl cardiol 2001;8:620-5 Sugihara H et al J Nucl cardiol 2001;8:575-9 Chiao P-C et al J Nucl med 1994;35: Serafini AN et al J Nucl Med 1992;33:
72 Future of Nuclear Cardiology Di Rocco RJ et al J Nucl Med 1992;33:1152-9
73 New Imaging Systems Real dynamic cardiac SPECT:
74 New Imaging Systems Real dynamic cardiac SPECT: Extract kinetic parameters of compartment models: Defect contrast is better evaluated with wash-in parameters obtained with Tl-201 and Tc-99m- Teboroxime than with static perfusion imaging. The estimation of kinetic parameters yields greater dynamic range than the mapping of flow that is based on intensity uptake of the tracer as usually done with Tl-201 Khare HS et al IEEE Trans Nucl Sci 2001;48:774-9 Di Bella EVR et al Inv Radiol 2001;36:178-85
75 New Imaging Systems Gambhir SS et al J Nucl Med 2009;50:635-43
76 New Imaging Systems Gambhir SS et al J Nucl Med 2009;50:635-43
77 New Imaging Systems Gambhir SS et al J Nucl Med 2009;50:635-43
78 New Imaging Systems Seo Y et al Sem Nucl Med 2008;38:177-98
79 New Imaging Systems Gambhir SS et al J Nucl Med 2009;50:635-43
80 New Imaging Systems Mettre icono nouvelle machines vs FBP Gambhir SS et al J Nucl Med 2009;50:635-43
81 New Imaging Systems Gambhir SS et al J Nucl Med 2009;50:635-43
82 New Imaging Systems Gambhir SS et al J Nucl Med 2009;50:635-43
83 New Imaging Systems These new imaging devices will push to explore new frontiers in SPECT imaging: - Hardware - Radiopharmaceuticals - Pharmacologic stress - Processing methods
84 Future of Nuclear Cardiology
85 New Stressors:Vasodilators Regadenoson (A 2A adenosine receptor agonist): Body-weight independent one dose IV Bolus injection in 10 sec of 400 microgrammes Inject the radiotracer sec later: Teboroxime Acquire for 5 minutes in list mode Get the absolute CFR
86 New Horizons: Combining New Vasodilators and New Imaging Systems Combining Regadenoson and new imaging systems: Body-weight independent one dose IV Bolus injection in 10 sec of 400 microgrammes Inject the radiotracer 20 to 30 sec later: Thallium or Teboroxime Acquire for 5 minutes in list mode Get the absolute CFR Iida H et al Eur J Nucl Med Mol Imaging 2008
87 Future of Nuclear Cardiology
88 Future of Nuclear Cardiology Nuclear Cardiology is well armed to meet this Molecular Imaging challenges (radiotracers): Angiogenesis Hypoxia Metabolism Neurotransmission Apoptosis Myocardial inflammation Vulnerable atherosclerotic lesions Gene products Nuclear Cardiology is progressing in parallel to basic/clinical cardiology
89 Future of Nuclear Cardiology
90 Metabolic Myocardial Imaging
91 Metabolic Myocardial Imaging FA Fasting conditions Insuline Catecholamines Workload Hypoxia ischemia Glucose Pyruvate Lactate Ketones Amino acids
92 Metabolic Myocardial Imaging Opie LH et al Eur J Clin Invest 1973;3: Neely JR Circ res 1975;37: Schelbert HR et al Am Heart J 1982;103: Schelbert HR et al Am Heart J 1982;103: Schwaiger M et al J Am Coll Cardiol 1985;6: Camici P et al Circulation 1986;74:81-8 Marwick TH et al Am J Cardiol 1992;69:854-9 Abramson BL et al J Nucl Cardiol 2000;7: McNulty PH et al Circulation 2000;101: Araujo LI et al J Nucl Cardiol 2001;8: McFalls EO et al Am J Physiol Heart Circ Physiol 2002;282:H205 11
93 Metabolic Myocardial Imaging Camici P et al Circulation 1986;74:81-8 Araujo LI et al Am J Cardiol 1987;60:26H-30H Fudo T et al Am J Cardiol 1988;61: Yonekura Y et al Am J cardiac Imaging 1988;2: Schwaiger M et al J Am Coll Cardiol 1989;13: Marwick TH et al Am J Cardiol 1992;69:854-9 McNulty PH et al J Clin Invest 1996;98:62-9 Abramson BL et al J Nucl Cardiol 2000;7: McNulty PH et al Circulation 2000;101: Araujo LI et al J Nucl Cardiol 2001;8: McFalls EO et al Am J Physiol Heart Circ Physiol 2002;282:H205 11
94 Metabolic Myocardial Imaging Glucose and FA utilization: Under aerobic fasting conditions, the heart primarily utilizes FA for metabolism During ischemia, myocardial metabolism switches to glucose utilization supplying ATP through anaerobic glycolysis
95 Metabolic Myocardial Imaging Metabolic signature of ischemic myocardium: Decreased FA uptake: cold spot Increased glucose uptake: hot spot This has been known for quite some time now but primarily used for viability assessment
96 Metabolic Myocardial Imaging Rb rest Rb stress Rb post stress FDG post stress Camici P et al Circulation 1986;74:81-8
97 Metabolic Myocardial Imaging Basics : Exercise ischemia Prompt metabolic switch to stress ischemia: Decrease FA metabolism Increase in glucose metabolism Prolonged recovery phase with recovery of metabolism lagging behind perfusion for 24-30h or more. Therefore extending the imaging time-window of myocardial ischemia far beyond that of perfusion imaging
98 Metabolic Myocardial Imaging ONLY NOW it is appreciated that simultaneous assessment of perfusion and metabolism : Can enhance the detection of myocardial ischemia Perhaps detect its extent better than with conventional perfusion imaging alone
99 Metabolic Myocardial Imaging I-123 BMIPP: Rest ischemic metabolic memory: Unstable angina: Meta-analysis BMIPP» Sv=86% Sp=95% Stress myocardial ischemia Rest BMIPP imaging > 20 hours after exercise stress had the same sensitivity for CAD detection as early Tl-201 stress perfusion imaging. Dilsizian V et al Circulation 2005;112:
100 Metabolic Myocardial Imaging FDG: In prior data (animals, humans), it was shown that the up-regulation of glucose uptake by the ischemic myocardium may persist for hours to days even after a brief episode of ischemia. Schelbert HR et al Am Heart J 1982;103: Camici P et al Circulation 1986;74:81-8 Marwick TH et al Am J Cardiol 1992;69:854-9 Abramson BL et al J Nucl Cardiol 2000;7: McNulty PH et al Circulation 2000;101: Araujo LI et al J Nucl Cardiol 2001;8: McFalls EO et al Am J Physiol Heart Circ Physiol 2002;282:H205 11
101 Metabolic Myocardial Imaging Dual isotope exercise MIBI / FDG simultaneous-injection-and-acquisition SPECT: Prompt metabolic switch from FA to glucose use occurs when myocardial ischemia is induced during exercise Exercise-induced metabolic switch to glucose may persist for 24 h despite restoration of blood flow at rest Potential superiority of exercise F18-FDG/MPI over exercise/rest MPI for the detection of CAD He ZX et al Circulation 2003;108: Dou K-F et al J Nucl Med 2008;49:
102 Metabolic Myocardial Imaging FDG: Camici P et al showed in 1986 that stressinduced ischemia in patients with stable CAD can increase glucose uptake well after symptoms and ECG changes have resolved. McNulty et al showed that enhanced glucose uptake may persist for 24 hours or more after a brief period of ischemia Camici P et al Circulation 1986;74:81-8 McNulty PH et al Circulation 2000;101: McNulty PH et al Am J Physiol 1995;268:H McNulty PH et al J Clin Invest 1996;98:62-9
103 Metabolic Myocardial Imaging Combining the 2 studies: N=42 pts with CAD: Abnormal Ex MPI : 29/42 pts = 69% Abnormal Ex FDG 35/42 pts = 83% N=90 vascular territory D stenosis >50%: Abnormal Ex MPI : 37/90 = 41% Abnormal Ex FDG: 56/90 = 62% He ZX et al Circulation 2003;108: Dou K-F et al J Nucl Med 2008;49:
104 Metabolic Myocardial Imaging Normal MIBI FDG He ZX et al Circulation 2003;108:
105 Metabolic Myocardial Imaging 3-Vessels: LAD (70%) + LCx (60%) + RC (60%) MIBI FDG He ZX et al Circulation 2003;108:
106 Metabolic Myocardial Imaging 2-Vessels: LAD (80%) + LCx (100%) MIBI FDG He ZX et al Circulation 2003;108:
107 Metabolic Myocardial Imaging 2-Vessels: LAD (50%) + RC (100%) MIBI FDG He ZX et al Circulation 2003;108:
108 Metabolic Myocardial Imaging 2-Vessels: LCx (80%) + RC (100%) MIBI FDG He ZX et al Circulation 2003;108:
109 Metabolic Myocardial Imaging Significant ST-segment depression at 6 minutes without chest pain. At angiography, she had a significant stenosis in the proximal LAD. Abramson BL et al J Nucl Cardiol 2000;7:205-12
110 Metabolic Myocardial Imaging Pharmacologic stress test?
111 Metabolic Myocardial Imaging Pharmacological stress also increase FDG uptake for metabolic ischemia imaging! Adenosine/Dipyridamole: Law WR et al Am J Physiol 1988;254:H970-5 Brosius FC III et al Am J Cardiol 1997;80:77A-84A Araujo LI et al J Nucl Cardiol 2001;8: Α-adrenoreceptors Eigert S et al Circ res 1999;84:
112 Metabolic Myocardial Imaging Inverse relationship between vasodilatory capacity and FDG uptake Araujo LI et al J Nucl Cardiol 2001;8:339-46
113 Metabolic Myocardial Imaging Breast attenuation on MPI: Combining MPI and hot spot imaging?
114 Metabolic Myocardial Imaging Dual hot-spot FDG / cold-spot MPI SPECT in female for the diagnosis of CAD: May potentially overcome the problem of attenuation artifacts in cold-spot MPI Abramson et al: n=19 pts with abnormal MPI (25% were diabetics!!!) Ex (n=8) or Dip (n=11) N=9/19 with CAD (D stenosis >50%): Sv=89% ; Sp=90% Abramson BL et al J Nucl Cardiol 2000;7:205-12
115 Metabolic Myocardial Imaging Efficacy of treatment?
116 Metabolic Myocardial Imaging Potential role for FDG imaging in assessing efficacy of therapy: Araujo LI et al demonstrated that anti-ischemic therapy with nitrates partially normalized FDG uptake values Araujo LI et al Am J Cardiol 1987;60:26H-30H
117 Metabolic Myocardial Imaging Prognostic value?
118 Metabolic Myocardial Imaging Rest BMIPP/Tl-201 in asymptomatic hemodialysis patients: cardiac death-free survival rates at 3 years Nishimura M et al J Am Coll Cardiol 2008;51:139-45
119 Metabolic Myocardial Imaging Myocardial FA metabolism: Prognostic value in hemodialysis patients Nishimura M et al J Am Coll Cardiol 2008;51:139-45
120 Metabolic Myocardial Imaging Myocardial FA metabolism: Prognostic value in hemodialysis patients 3 years 98% 67% Nishimura M et al J Am Coll Cardiol 2008;51:139-45
121 Metabolic Myocardial Imaging Myocardial FA metabolism: Prognostic value in hemodialysis patients Nishimura M et al J Am Coll Cardiol 2008;51:139-45
122 Metabolic Myocardial Imaging Much unresolved issues: BMIPP or FDG: alone or combined to perfusion? Which is better: BMIPP or FDG? Optimal timing of FDG injection! Optimal timing of FDG imaging! FDG imaging : fasting or after glucose loading! Utility of FDG imaging in diabetes PET or SPECT! Interpretation criteria! In conjunction or replacement of MPI! Specificity issues!
123 Metabolic Myocardial Imaging CardioPET : An F-18 labeled, modified fatty acid that provides insight into regions of metabolic insufficiency in myocardium Normal Healthy Volunteer Coronary Artery Disease minutes after CardioPET injection.
124 Future of Nuclear Cardiology PET myocardial perfusion tracers: 18F - BMS (BMS): MIBI-like 18F - BFPET (Fluoro Pharma): dynamic
125 Future of Nuclear Cardiology 18F BMS Yu M et al J Nucl Cardiol 2007;14:789-98
126 Future of Nuclear Cardiology 18F BMS Yu M et al J Nucl Cardiol 2007;14:789-98
127 Future of Nuclear Cardiology Yu M et al J Nucl Cardiol 2007;14:789-98
128 Future of Nuclear Cardiology Yu M et al J Nucl Cardiol 2007;14:789-98
129 Future of Nuclear Cardiology Yu M et al J Nucl Cardiol 2007;14:789-98
130 Future of Nuclear Cardiology Higuchi T et al J Nucl Med 2008;49:
131 Future of Nuclear Cardiology Higuchi T et al J Nucl Med 2008;49:
132 Future of Nuclear Cardiology Higuchi T et al J Nucl Med 2008;49:
133 Future of Nuclear Cardiology F18-BFPET (Fluoro Pharma): blood flow tracer PET images and corresponding time-activity curves after left anterior descending artery ligation in rabbit.
134 Future of Nuclear Cardiology In conclusion, Very promising bright future Too much remain to be done: Development Prospective multicenter trials Cost/effectiveness Exciting task awaiting us
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