Hybrid PET/CT Cardiac Imaging
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1 Hybrid PET/CT Cardiac Imaging Antti Saraste, MD, PhD Cardiologist, Associate Professor and Heart Center Turku University Hospital and University of Turku Helsinborg
2 Detection of coronary artery disease by PET-CT hybrid imaging Hybrid device: PET/SPECT + 64-rowCT CTA 15-O-water PET Adenosine stress Comprehensive evaluation of anatomy and function Gaemperli,Saraste,Knuuti. Eur Heart J Cardiovasc Imaging 2012
3 Non-invasive coronary CT angiography: Exclusion of obstructive CAD LAD 64-row CT Prospective gating Radiation dose: 3-5 msv RCA LCX
4 Multi Center Trials ACCURACY Trial Multi-Center Study in 230 subjects, 16 sites Sens. Spec. PPV NPV Prevalence PER PATIENT > 50% Stenosis 95% 83% 64% 99% 24% > 70% Stenosis 94% 83% 48% 99% 14% PER VESSEL > 50% Stenosis 84% 90% 51% 99% 10% > 70% Stenosis 84% 92% 36%. 99% 4% Budoff et al, JACC 2008
5 Increased utilization of diagnostic tests/ invasive coronary angiography after CTA Metaanalysis of CCTA in chest pain in the ED UC = Usual care Hulten E J Am Coll Cardiol 2013
6 Challenges for CT angiography Irregular heart rate and extensive calcifications Overestimation of stenosis Schroeder EHJ 2008, Taylor JACC 2010
7 Challenges for coronary angiography: Anatomy vs. Functional Significance 1.0 Pressure-derived FFR N = Angiographic Diameter Stenosis (%) Wijns, de Bruyne, Vanhoenacker, JNC 2007;93: FFR = Fractional flow reserve invasive measurement of the pressure gradient during adenosine infusion Hybrid imaging?
8 Impact of functional significance on prognosis after PCI Tonino et al. FAME
9 Revascularization and ischemic burden Circulation 2003; 107:
10 PET: Accuracy in the detection of significant CAD McArdle, J Am Coll Cardiol 2013 Saraste and Knuuti, J Nucl Cardiol 2012
11 PET flow quantification = measurement of myocardial perfusion in absolute terms (ml/g/min) Dynamic imaging Kinetic modeling MBF in ml/g/min SPECT Technical improvements Count rate performance Data handling Computing power Moody et al J Nucl Cardiol 2015 Combination with clinical protocols
12 Analysis of PET 15-O-water study Carimas TM free software developed in Software packages for myocardial flow quantification: - Cardiac Vuer - Munich Heart - PMOD - FlowQuant - Carimas - Syngo - Hoquto - QPET - UW-QPP - ImagenQ - Corridor 4DM
13 The cross-comparison biplots of 10 software packages When using 1-TCM, the agreement by any SW is good Complex mathematical modeling, accurate measurement of tracer input and myocardial activity
14 PET Tracers for Perfusion Quantifiaction 6 15 O-water 5 Tracer uptake F-flurpiridaz 13 N-ammonia 82 Rb 99m Tc-SPECT tracers (Nekolla Circulation 2009) (Lortie EJNMMI 2007, Lautamäki EJNMMI 2009, El Fakhri JNM 2009) Absolute flow (ml/g/min) Saraste and Knuuti, J Nucl Cardiol 2012
15 New F-18 labeled PET perfusion tracer (Flurpiridaz) 3C-model Nekolla et al. Circulation 2009 Good kinetics, image quality and safety Berman et al. JACC 2013 Phase III trial
16 What is normal myocardial blood flow? Stress 6 5 Range in absolute flow image Range in tracer uptake Measured/modelled flow Abnormal Absolute flow Normal Tracer uptake Absolute flow (ml/g/min)
17 Optimal MBF cut-off for the detection of significant epicardial CAD? 330 patients with suspected CAD and O-15 water PET Optimal cutoff for O-15-water Stress MBF <2.3 ml/g/min CFR <2.5 (Turku, Amsterdam, Uppsala) ICA + FFR in all intermediate (30-90%) stenoses Danad et al JACC with obstructive CAD Heart Centre
18 Accuracy of quantitative PET perfusion Absolute flow is as good as flow reserve Danad et al JACC 2014 Heart Centre
19 Accuracy of quantitative PET perfusion High negative predictive value Danad et al JACC 2014 Heart Centre
20 Case 1 LAD >50% Case RE LCX RCA IM >50% CT Acquisition: Premedication: Metoprolol 12 mg i.v. HR 60/min Acquisition: Prospective step-andshoot protocol 750 ma, 120 kv Contrast: Iomeron 400mg/ml 90 ml Radiation dose 8 msv, Finland
21 Cardiac CTA + PET perfusion protocol PET- 64 row CT Scouts Calcium score CTA CTAC Stress perfusion CT scan PET scan Tracer injection Contrast injection PET H 2 O Adenosine Time (min)
22 Fusion of CTA and PET perfusion? Carimas TM free software developed by Nesterov et al EJNMMI 2009
23 Case 1 CTA and O 15 -water stress perfusion image fusion Case RE 2.3 ml/g/min Anterior view Posterior view Evaluation of haemodynamic significance of stenoses PET Acquisition: Injected Dose: 1100 MBq O-15-water Stress: Adenosine 140 µg/min/kg for 6.5 min Acquisition: Dynamic 4.5 min Radiation dose 0.9 msv, Finland
24 Case 1 Case LCXRE Left coronary artery RCA LAD Invasive angiography, Finland
25 Hybrid PET/CT for CAD diagnosis Figure 2b: Vessel Analysis against ICA+FFR Sensitivity (%) Specificity (%) PPV (%) NPV (%) Accuracy (%) MDCT PET MDCT-PET hybrid MDCT PET MDCT-PET hybrid 107 patients with intermediate probability of CAD Kajander et al Circulation 2010, Finland
26 Challenges and solutions of perfusion imaging Challenge Balanced 3 vessel disease Multivessel disease LM disease Anatomical location Non-obstructive CAD Microvascular disease Solution Hybrid imaging/quantitation Hybrid imaging/quantitation Hybrid imaging Hybrid imaging Hybrid imaging Hybrid imaging/quantitation Impact of hybrid imaging in clinical practice?
27 Advantages of hybrid imaging: Detection of multivessel disease Adenosine stress O 15 -water PET perfusion % ml/g/min Relative scale Absolute scale (0-3.5 ml/g/min) 52-year old female, atypical chest pain
28 Diffusely reduced stress MBF and 3-vessel obstructive CAD RCA LAD LCX CTA + Adenosine stress O 15 - water PET perfusion
29 Example: Different severity of ischemia after quantification with 82 Rb PET Ziadi MC, et al J Nucl Cardiol Heart Centre
30 Relative analysis vs. quantification in patients with multivessel disease Regional analysis in patients with intermediate likelihood of CAD, n=104 PET perfusion with O 15 -water during adenosine stress - Balanced 3-VD missed in 2 (2%) patients - Underestimated in 13 (12%) other patients 24 patients with multivessel CAD (QCA and FFR) Kajander S et al Circ Cardiovasc Im 2011 Heart Centre
31 Advantages of hybrid imaging: Localization of culprit vessel Posterior view Ischemia in the RCA territory Small LCX
32 Incremental prognostic value of hybrid CTA-perfusion MSCT - MPI - MSCT - MPI + MSCT + MPI - MSCT + MPI + Van Werkhoven J Am Coll Cardiol 2009
33 Baseline statin therapy and nonobstructive CAD on coronary CTA Plaque on CTA No plaque on CTA Chow ATVB 2014
34 Advantages of hybrid imaging: Differentiation of epicardial and microvascular dysfunction Fusion image of 3D coronary anatomy (CTA) and O 15 -water PET perfusion during adenosine stress 2.3 ml/g/min anterior posterior 65-y old male, risk factors for CAD (smoking, family history), atypical chest pain, >2 mm ST-depression
35 Hybrid imaging: Differentation of Epicardial and microvascular disease O 15 -water PET during adenosine stress.5 ml/g/min CFR = 1.8 ml/g/min Rest flow: ~ 0.9 ml/g/min Stress flow: ~ 1.6 ml/g/min
36 Heart Centre 2783 patients with suspected CAD, Rb 82 rest-stress PET Circulation 2011 CFR <1.5 CFR >2.0 Ischemia (% of LV) Prognostic implications of CFR
37 Implementation of hybrid imaging? Symptomatic patients with suspected CAD Estimation of pretest probability of CAD using clinical history and exercise ECG when available Low probability (<15%) Intermediate probability (15-85%) High probability (>85%) Hybrid imaging CT angiography to detect disease and localize stenoses CAD - CAD + Ischemia - CAD + Stress imaging (ischemia) Ischemia + CAD + ICA to confirm disease and final decision of revascularization (if necessary with help of FFR) Primary prevention Secondary prevention / Medical therapy Revascularization and medical therapy Knuuti and Saraste Eur Heart J 2013
38 Open questions with hybrid imaging: Benefits vs. incremental radiation dose? Cost effectiveness? Order of anatomy/functional? Clinical implementation? Duration Radiation, msv Perfusion CT SPECT rest and stress imaging 3-4 h 12 - SPECT/CAC rest and stress imaging 3-4 h 12 1 SPECT/CTA rest and stress imaging 3-4 h PET/CTA stress and rest imaging 1 h SPECT/CTA stress only imaging 1.5 h PET/CTA stress only imaging (quantification) 0.5 h Invasive Coronary Angiography (mean 7) msv
39 Molecular imaging of myocardial responses to injury Kiugel et al. Mol Im Biol integrin
40 18 F-Galacto-RGD PET of human MI DeMRI 13 N-ammonia 18 F-gRGD 4-ch 2-ch Relationship to functional recovery? Makowski Eur Heart J 2008
41 PET imaging of coronary atherosclerosis and rupture prone plaque? Biomarker Anatomy PET MDCT
42 Clinical nuclear imaging of atherosclerotic plaque inflammation by 18 F-FDG PET-CT FDG accumulation detected in carotid artery plaques of patients with acute stroke Rudd Circulation 2002
43 Vascular 18 F-FDG uptake associated with future vascular events Vascular event in 15 patients Roeminger JNM cancer patients with prior 18F-FDG PET study Mean of TBRs in aorta, carotid and iliac arteries Prospective trials in non-cancer patients (HRP)
44 Dual gated 18 F-FDG PET/CT of coronary arteries in ACS patients 20 ACS patients Dual-gated FDG PET+ CTA 3 ± 2 days after onset of symptoms 5 before PCI, 15 after PCI Myocardial uptake suppressed by low carbohydrate diet + fasting 19 sufficient for analysis 79% of patients visual coronary FDG uptake Hoppela et al (abstract) ICNC 2011
45 New PET tracers for atherosclerotic plaque imaging [ 18 F] galacto-rgd HE stain Autoradiography [ 18 F] Choline HE stain Autoradiography B A Laitinen, Saraste et al. Circ Cardiovasc Imaging 2009 [18F] EF5 HE stain Autoradiography Hellberg, Saraste et al. EAS 2013 (abstract) [18F] Siglec-9 Silvola, Saraste et al., ATVB 2011 Silvoa et al., manuscript
46 Summary: Hybrid PET/CT Cardiac Imaging CTA: Exclusion of CAD Flow quantification with perfusion PET Hybrid imaging: Evaluation of both coronary anatomy and ischemia Functional significance of intermediate stenosis Localization of culprit vessel Detection of multivessel disease Non-obstructive disease Microvascular disease
47 Acknowledgements Juhani Knuuti, Anne Roivainen, Miikka Tarkia, Virva Saunavaara, Pirjo Nuutila, Riikka Lautamäki, Tommi Kokki, Chunlei Han, Sergei Nesterov, Mika Teräs, Sami Kajander, Tommi Noponen, Olof Solin, Matti Haavisto, Sauli Uotila, Antti Varis, Johanna Silvola, Sanna Hellberg, Max Kiugel, Suvi Puolakkainen, Erika Hoppela, Teemu Maaniitty, Iida Soukka, Valtteri Uusitalo, Xiang Guo-Li, Anu Autio Turku Univeristy Hospital, Cardiac Surgery Timo Savunen, Tommi Vähäsilta, Christoffer Stark, Ville-Veikko Hynninen Turku University Hospital, Heart Center Mikko Pietilä, Juhani Airaksinen, Heikki Ukkonen, Ville Kytö, Marjatta Strandberg University of Turku, Forensic Medicine Prof. Pekka Saukko University of Eastern Finland, Seppo Ylä- Herttuala, Markku Laakso Heart Centre
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