Myocardial Perfusion CT : Focused on Results from a Multicenter Registry in Korea Dong Hyun Yang, MD

Transcription

1 Myocardial Perfusion CT : Focused on Results from a Multicenter Registry in Korea Dong Hyun Yang, MD Department of Radiology, Research Institute of Radiology, Cardiac Imaging Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

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3 Diagnostic Accuracy > 50% stenosis, Per-segment analysis CAD FP FN Sensitivity Specificity PPV NPV Small diameter prevalence of artery, poor image quality, and high calcium Diameter, mm are cause of inaccuracy! > <1.5 Image quality Good Moderate Poor Calcium None Moderate High % 77% 45% 89% 84% 86% 78% 92% 95% 90% 91% 96% 94% 85% 78% 97% 81% 47% 49% 20% 29% 58% 40% 30% 54% 49% 38% 99% 99% 98% 99% 98% 98% 99% 98% 97% Sensitivity decreased with vessel diameter and increased with high calcium. Specificity decreased with poor image quality and severe calcification. Meijboom W.B. JACC 2008;52:

4 CTA for Prediction of FFR FFR < 0.80 (n=31) Sensitivity Specificity Accuracy CTA, Visual score CTA, Quantitative measurement CAG, Visual score CAG, Quantitative measurement The anatomical assessment of the hemodynamic significance of coronary stenosis determined by CT and CAG does not correlate well with the functional assessment of FFR Meijboom W.B. JACC 2008;52:636-43

5 Ischemia-guided Revascularization Paradigm shift to functional angioplasty based on objective myocardial ischemia Non-invasive prediction of myocardial ischemia is important to guide revascularization strategy! Tonino et al. FAME NEJM 2009 Kim YH et al. JACC 2012 Park SJ Circulation

6 First Article of CTP, 2005 Summary 16-ch CT (GE, LightSpeed 16) 12 patients Reference: Thallium SPECT Population: suspected CAD Sensitivity (per-vessel): 90% Specificity (per-vessel): 79% First article Kurata A. Mochizuki T. et al Cir J 69:

7 Early Result of CTP: Visual Analysis Per-vessel, CAD (QCA, 50%) CTP SPECT Sensitivity Specificity PPV NPV C-statistic No difference! CT perfusion vs. SPECT Comparable diagnostic accuracy! Blankstein et al JACC 54:

8 TPR: semi-quantitative method First quantification on static CTP! Summary 64-ch CT or 256-ch CT (Toshiba) Stress first protocol 27 patients Reference: QCA plus SPECT Population: Abnormal SPECT Sensitivity (per-vessel): 79% Specificity (per-vessel): 91% Transmural perfusion ratio (TPR) TPR = Subendocardial Density Subepicardial Density 1. Acceptable diagnostic accuracy of CTA/CTP combination. 2. Quantification of static CTP may be useful. George RT et al Circulation CV Img 2:

9 TPR: semi-quantitative method Per-vessel territories CTP vs. SPECT CTA (>50%) vs. SPECT CTP vs. CTA + SPECT Sensitivity Specificity PPV NPV AUC CTP was a better predictor! Summary 320-ch CT (Toshiba) Rest first protocol 50 patients Reference: SPECT or CAG (50% >) + SPECT Population: Suspected CAD who underwent SPECT Sensitivity (per-vessel): 50% Specificity (per-vessel): 89% CTP was a better predictor George RT et al Circulation CV Img 5:

10 CTP-Visual analysis vs. FFR CTA 50% CTP (+) CTA 50% & CTP(+) CTA 50% OR CTP(+) QCA 50% Sensitivity Specificity PPV NPV Accuracy CTA 50% & CTP(+) was 98% specific for ischemia. CTA < 50% and normal CTP was 100% specific for ischemia. Ko BS et al Eur Heart J 33:67-77

11 CORE320 Study: CT perfusion Multicenter studies (n=391) Validation of CT perfusion using QCA / SPECT as a reference standard Rochitte CE, et al. Eur Heart J 2013

12 First CT Perfusion Case at My Institution (2011) /F

13 Perfusion CT Protocols Delayed phase vs. Not Dynamic vs. Static (Single-shot) Exercise vs. Adenosine vs. Dipyridamole vs. Regadenosone vs. Dobutamine Stress perfusion CT 2 x 2 x 2 x 5 x 3 x 2 = 240 Retrospective vs. Prospective protocols vs. High-pitch mode Stress- vs. Rest-first Dual- vs. Singleenergy

14 Perfusion CT Protocols Delayed phase vs. Not Exercise vs. Adenosine vs. Dipyridamole vs. Regadenosone vs. Dobutamine Dynamic vs. Static (Single-shot) Stress perfusion CT Stress- vs. Rest-first Retrospective vs. Prospective vs. High-pitch mode Dual- vs. Singleenergy

15 Static (Single Shot) vs. Dynamic Scan Koo HJ, Yang DH et al. In submission

16 Increase of (a) Dynamic Scan (b) 40 / M Effort chest pain for 1 month (c) (d) Koo HJ, Yang DH et al. In revision

17 Static (Single shot) Scan Contrast enhancement: Static Koo HJ, Yang DH et al. In revision Motion Dynamic (Retrospective ECG-gating)

18 Static vs. Dynamic Scan Static perfusion Dynamic perfusion Pros Cons Cine CT Static scan Low radiation dose Easy to perform - Same with CCTA Wall motion abnormality No quantification of blood flow Suboptimal enhancement time low lesion detectability Blood flow map Dynamic scan Pros Cons Blood flow quantification Better detectability (not validated) High radiation dose Hard to perform - Need high-end CT machine - Long breath hold time (30 s) Systolic phase only

19 Dynamic vs. Single-shot CT Perfusion Imaging Single-shot scan Dynamic scan Parameter Sensitivity Specificity Single-shot Dynamic Peak enhancement 34 HU Myocardial blood flow 1.64 ml/g/min Perform dynamic CT scan Peak enhancement vs. Myocardial blood flow Huber et al. Radiology P=0.27

20 Perfusion CT Protocols Delayed phase vs. Not Dynamic vs. Single-shot Exercise vs. Adenosine vs. Dipyridamole vs. Regadenosone vs. Dobutamine Stress perfusion CT Stress- vs. Rest-first Retrospective vs. Prospective vs. High-pitch mode Dual- vs. Singleenergy

21 Old Infarction: Limitation of CTP RCA occlusion Stress Rest 58/M

22 Old Infarction: Limitation of CTP CT Stress MRI 58/M

23 Delayed Phase of CT CT MRI 34/M HCMP

24 Incremental Value of DE-CT?? DE MRI for detection of significant DE CAD. CT 105 pts FFR reference standard CT-MRI comparison - DE-CT has low sensitivity for detection of both scar and ischemia. - DE-CT dose not have incremental value over CTP Sensitivity Specificity Accuracy Vs. MRI Vs. FFR Vs. FFR Vs. FFR DE-CT DE-CT CTA + CTP CTA + CTP + DE-CT Bettencourt et al. JACC img

25 Perfusion CT Protocols Delayed phase vs. Not Dynamic vs. Single-shot Exercise vs. Adenosine vs. Dipyridamole vs. Regadenosone vs. Dobutamine Stress perfusion CT Stress- vs. Rest-first Retrospective vs. Prospective vs. High-pitch mode Dual- vs. Singleenergy

26 Stress-First vs. Rest-First Advantages Disadvantages Stress Rest Rest Stress Better sensitivity of stress scan (ability to detect ischemia) Better CTA quality by giving pre-medication Ability to stop protocol after rest phase Better sensitivity of rest scan (ability to detect infarct) Contrast contamination (decreased sensitivity for infarct) Contrast contamination (decreased sensitivity for ischemia) Beta-blocker given during first scan can underestimate myocardial ischemia Techasith et al. JACC img

27 CTP/CTA protocol at AMC 128-ch dual source CT or 64-ch dual source CT Siemens, Definition (FLASH) Static protocol, single energy Stress-first No beta-blocker Nitroglycerin: 2 min. before rest CTP (CTA) 100 kv for reduce radiation dose Tube current modulation and ECG-pulsing Bolus triggering method (NOT test bolus) NO Delayed enhancement scan

28 CT Perfusion Protocol at AMC AMC protocol (30 minutes) Second degeneration dual-source CT 10 min. interval Calcium scoring Adenosine infusion Stress perfusion Sublingual NTG Rest perfusion (CTA) Scan range 5 min Retrospective ECG-gating 2 min. before Retrospective ECG-gating Option 1. Static perfusion 2. Dynamic perfusion Option 1. Retrospective mode 2. Prospective mode 3. High-pitch mode

29 CT Perfusion Analysis: Qualitative Very smooth kernel (B10f) reconstruction Multiphase image (0% ~ 90% of R-R interval, 10% increment) 10-mm thick MPR image with narrow window setting Diagnostic clue of perfusion defect Low density lesion conforming coronary territory Persistent lesion on cine image DDx) Transient motion or beam-hardening artifact Complementary regional wall motion abnormality on cine image Stress phase Stress phase cine image

30 Tips to Distinguish Artifacts Motion Dose not correspond to a vascular territory Dose not persist different phases of the cardiac cycle Beam-hardening Same as motion artifact above An artifact in the basal inferolateral wall due to the proximity of the dense spine and contrast in the descending aorta Triangular shape artifact originating from the region of high attenuation in the proximity Techasith et al. JACC img

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32 CT Perfusion Analysis: Quantitative Diastolic phase with the least motion artifact Customized software Classification of whole myocardium into 16 segments and into three myocardial layers Assignment of myocardial segments to vessel territories (LAD, LCX, RCA) Evaluation parameters CT density on stress / rest CT (Density stress / Density rest, HU) Transmural perfusion ratio (TPR) Density endocardial /Density epicardial Myocardial perfusion reserve index (MPRI),% (Density stress Density rest )/Density rest * 100 Yang DH, Kim YH et al. Radiology :715-23

33 Heavily calcified plaque 69/M, Effort chest pain Which lesion is true stenosis? RCA vs. LAD RCA LAD RCA LAD Reversible perfusion defect in RCA territory

34 Borderline Coronary Stenosis: FFR 0.75

35 42/M, Effort chest pain Positive TMT, stage 4 (II, III, avf, V4-6) Others CT virtual angioscopy LCA RCA LAD Aorta PA PA Aorta RCA Commissure Compression of RCA prox. PA RCA Aorta Aberrant origin of RCA from left coronary sinus with interarterial course

36 42/M, Effort chest pain Positive TMT, stage 4 (II, III, avf, V4-6) + Reversible perfusion defect in RCA territory Stress Rest Aberrant origin of RCA from left coronary sinus with interarterial course

37 Executive Committee (EC) PERFUSE Registry Prospective Evaluation of StRess Coronary PerFUSion CT REgistry PERFUSE registry PI: Young-Hak Kim Co-PI: Dong Hyun Yang DSMB Chair: PI Co-chair: co-pi Cardiologist: total 3 Radiologist: total 3 Core Laboratory Statistical Department Data Coordinating Department (DCD) Steering Committee (SC) Angiography CT Statistician Research nurses CRF producer DB manager Each site: 1 cardiologist 1 radiologist > 1300 cases ( )

38 Early Results Prospective CTP registry (262 patients) Previous PCI (58 patients) or CABG (7 patients) No invasive angiography (122 patients) Angiography with stenosis 20~90% but, no FFR (10 patients, 15 vessels) CTP with invasive angiography (75 patients, 210 vessels) FFR Measured (45 patients, 81 vessels) FFR Non-measured (62 patients, 129 vessels) FFR 0.80 (24 pts, 28 ves) FFR > 0.80 (34 pts, 53 ves) Stenosis < 20% (45 pts, 71 ves) Stenosis 90% or TIMI flow < grade 2 (43 pts, 58 ves) Yang DH, Kim YH et al. Radiology :715-23

39 Early Results: CTP visual assessment CTP CTA CTP / CTA Integration QCA, DS 50% True positive False positive True negative False negative Sensitivity,% Specificity,% PPV,% NPV,% Kappa statistic Accuracy Yang DH, Kim YH et al. Radiology :715-23

40 Subgroup Analysis High Agastone calcium score > 400 (N=63) Multivessel disease (N=56) Sensitivity Specificity IDI index Sensitivity Specificity IDI index CTP visual assessment * CTA, DS 50% Integration of CTP and CTA * QCA, DS 50% IDI, integrated discrimination improvement Yang DH, Kim YH et al. Radiology :715-23

41 Intermediate stenosis Quantitative Analysis Density map Syngo, Siemens TPR map Home-made, AMC Yang DH, Kim YH et al. Radiology :715-23

42 Quantitative Analysis Parameter AUC Cut off Sensitivity Specificity All patients (n=75) TPR Density stress, HU Density rest, HU MPRI, % Quantitative composite of TPR, Density stress, or MPRI * Combination of visual and quantitative composite ** Multivessel disease group (n=20) TPR Density stress Density rest MPRI, % Quantitative composite of TPR, Density stress, or MPRI * Combination of visual and quantitative composite ** Yang DH, Kim YH et al. Radiology : TPR: transmural perfusion ratio MPRI: myocardial perfusion reserve index

43 Case: Assistance with Density Quantitation Step 1 Visual Assessment Low density lesion conforming coronary territories in both systolic and diastolic phases Cine Diastole Systole LCX (+) LAD (-)

44 Case: Assistance with Density Quantitation Step 2 Density quantitation Positive quantitative parameters in Two or more consecutive myocardial segments LAD (-) visual assessment TPR map LCX (+) LAD (+)

45 Case: Assistance with Density Quantitation Angiography & FFR FFR=0.68 LCX (+) LAD (+)

46 Quantitative Analysis of CTP: Potential Role Improvement of diagnostic accuracy Intermediate lesion Multi-vessel disease (balanced ischemia) Quantification of ischemic burden Vascular territory assignment

47 Coronary artery based myocardial segmentation (CAMS) method LAD LCX Final result of CAMS method RCA Step Step Dimensional Coronary Artery Voronoi Myocardial Algorithm Segmentation Step (CAMS) - Gradually 1 Area growing methods of coronary 3D-space around arteries three coronary arteries - Projection Density Included of more as divided than coronary 3D space 200HU artery depends territory on each coronary artery onto area of myocardium - Stop Generation growing LAD of when mask it files encounters following preoccupied LCX CAMS methods space RCA - Semi-automated extraction of coronary arteries

48 CAMS Animal Validation Chung MS, Yang DH, Kim YH, 2015 in submission

49 CAMS vs. Specimen Chung MS, Yang DH, Kim YH, 2015 in submission

50 Case: LAD Territory Ischemia Tight stenosis in proximal 52/M LAD Reversible perfusion defect Tight stenosis in LAD territory, larger than conventional in proximal myocardial segmentation LAD than apical area

51 Ischemic Area: 42% of LV myocardium LCX LCX LAD RCA RCA LAD Ischemia area

52 Randomized Clinical Trial (on-going) NCT , Clinicaltrials.gov

53 Conclusion Cardiac Perfusion CT / CTA protocol is promising one-stop shop modality for predicting hemodynamically significant coronary stenosis. However some issues should be investigated in future study. Imaging: dynamic vs. static, stress- or rest first, CT- FFR vs. CT perfusion Clinical issue: prognostication, treatment guidance

54 Thank you!

55 Cardiac CT: One Stop Shop Imaging Target Conventional Technique Limitation of CT 1. Coronary artery stenosis CAG 2. Plaque evaluation IVUS, OCT 3. Ventricular function ECHO, MRI 4. Myocardial ischemia (CT perfusion) 5. Fractional flow reserve (CT-FFR) 6. Valve, Structural abnormality SPECT, MRI Invasive FFR ECHO, MRI Temporal resolution Spatial resolution Radiation exposure Use of contrast material Blooming artifact from calcified plaque

56 Perfusion CT Protocols Delayed phase vs. Not Dynamic vs. Single-shot Exercise vs. Adenosine vs. Dipyridamole vs. Regadenosone vs. Dobutamine Stress perfusion CT Stress- vs. Rest-first Retrospective vs. Prospective vs. High-pitch mode Dual- vs. Singleenergy

57 CT Perfusion Protocol at AMC AMC protocol (25 minutes) Second degeneration dual-source CT 10 min. interval Calcium scoring Adenosine infusion Stress perfusion Sublingual NTG Rest perfusion (CTA) Scan range 4 min. 30 sec Retrospective ECG-gating 2 min. before Retrospective ECG-gating Option 1. Static perfusion 2. Dynamic perfusion Option 1. Retrospective mode 2. Prospective mode 3. High-pitch mode