Validation of CT Perfusion Imaging Against Invasive Angiography and FFR on a 320-MDCT Scanner

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Validation of CT Perfusion Imaging Against Invasive Angiography and FFR on a 320-MDCT Scanner Zhen Qian, Gustavo Vasquez, Sarah Rinehart, Parag Joshi, Eric Krivitsky, Anna Kalynych, Dimitri Karmpaliotis, Szilard Voros Piedmont Heart Institute, Atlanta, GA Disclosures Study funding ATLANTA II www.clinicaltrials.gov (NCT00817102) Abbott Vascular, Volcano Therapeutics Inc. Principal Investigators Szilard Voros, MD, FACC, FSCCT Grant Funding: Abbott Vascular, Abbott Pharmaceuticals, Volcano Therapeutics Inc, Toshiba, Vital Images, Merck, Cardiogenesis Zhen Qian, PhD: No disclosures

Background Previous Work on CT perfusion Stress CT perfusion ² imaging¹ has been reported on 64- and 256-MDCT single and dual source scanners Validation was done against stress nuclear test and invasive angiography Limitation: Not a hemodynamic measurement Visual comparison of myocardial intensity in stress and rest¹ and transmural perfusion ratio² were used to quantify myocardial perfusion Limitation: Not a standalone absolute measurement. Difficult to handle homogeneous myocardial perfusion defect. 1. Blankstein R, Shturman LD, Rogers IS, et al. Adenosine-induced stress myocardial perfusion imaging using dual-source cardiac computed tomography. J Am Coll Cardiol 2009; 54: 1072-1084. 2. George RT, Arbab-Zadeh A, Miller JM, et al. Adenosine stress 64- and 256-row detector computed tomography angiography and perfusion imaging: a pilot study evaluating the transmural extent of perfusion abnormalities to predict atherosclerosis causing myocardial ischemia. Circ Cardiovasc Imaging 2009; 2(3):174-82. Background CT perfusion on 320-MDCT CT perfusion on 320-MDCT has not been published 320-MDCT s potentials and limitations: Whole heart scan in a single heart beat: better contrast homogeneity. Lower temporal resolution than dual source CT, but improved temporal uniformity Lower overall contrast media Lower overall radiation dose

Purpose Investigate 320-multi-detector row vasodilator stress and rest volumetric CT s ability of myocardial perfusion quantification Investigate the feasibility of a blood poolnormalized measurement to quantify myocardial perfusion Investigate the feasibility of a refined reference standard that uses both morphological and hemodynamic measurements Methods Rest and Stress CT Perfusion Protocol Flowchart Beta-blockade 70cc Contrast Rest CTP 10 min 45 sec Regadenosone 70cc Contrast Stress CTP CT imaging protocols for both rest and stress CTP: 320-MDCT with prospectively triggered, single-beat, volumetric acquisition; detector width 0.5 mm, voltage 120 kv, current 200-550 ma. Reconstruction at 65-75% R-R.

Methods Angiography and FFR Protocol XRA: 70% stenosis was abnormal Visual assessment After standard XRA, FFR was measured after intracoronary injection of adenosine in all 3 vessels with angiographically severe or moderate lesions 3 independent FFR measurements were averaged for each lesion FFR 0.75 was considered abnormal CAD was defined as: XRA: 70% or FFR 0.75 Methods Study Design - Arterial territories AHA 17-segment model * Territories supplied by LAD, LCx, and RCA LAD: 1, 2, 7, 8, 13, 14, 17 LCx: 5, 6, 11, 12, 16 RCA: 3, 4, 9, 10, 15 * AHA Scientific Statement Standardized Myocardial Segmentation and Nomenclature for Tomographic Imaging of the Heart, A Statement for Healthcare Professionals From the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association, American Heart Association Writing Group on Myocardial Segmentation and Registration for Cardiac Imaging. Circulation. 2002;105:539

Methods Study Design Myocardial Intensity Quantification Reconstruction: 0.5 mm slices Average 3 measurements in each segment (in HU) Normalization to blood pool intensity: Segment / Blood Pool Basal { Mid { Apical { Apex - Methods Statistical Analysis In each arterial territory, we calculated the mean intensity value (absolute value), and the normalized value (divided by the average blood pool intensity) t-test was done between territories with obstructive arterial disease, and without obstructive disease. p 0.05 considered significant. ROC analysis was performed to predict perfusion defect. Sensitivity, specificity, AUC were calculated.

Results Patient information 8 patients Gender M: 3; F: 5 Age 61.3±9.6 136 myocardial segments, and 24 arterial territories. 11 of the 32 arteries had CAD (based on XRA and FFR) 11 of the 24 arterial territories were supplied by artery with obstructive CAD Results Visual Comparison Stress Rest X-ray Angiography

Results Comparison of myocardial territories with and without CAD Rest Stress S/R Ratio t-test CAD No CAD p-value Stress (ABS) 119.4±32.9 123.4±30.2 0.76 Rest (ABS) 91.0±22.0 97.6±17.1 0.42 S/R Ratio (ABS) 1.36±0.27 1.28±0.16 0.44 Stress (Norm) 0.27±0.03 0.32±0.05 0.01 Rest (Norm) 0.16±0.04 0.19±0.03 0.05 S/R Ratio (Norm) 1.88±0.47 1.87±0.43 0.94 Results ROC Analysis ROC Analysis Stress (ABS) Rest (ABS) Stress (Norm) Rest (Norm) AUC Sensitivity Specificity 0.58 0.67 0.58 0.60 0.65 0.5 0.79 0.67 1 0.73 0.67 0.75

Discussion Comparison with previous work Predictive performance of normalized stress CT perfusion is comparable to previous studies Sensitivity Specificity AUC Blankstein et al In Jacc 2009 0.75 0.87 0.80 George et al * In Circ Cardiovascular imaging 2009 0.91 0.91 0.90 Our Method 0.67 1 0.79 * The predictive performance was based on the combination of CTA and CTP. Discussion Predictive measurements for CT perfusion Normalized myocardial intensity is a good absolute measurement for perfusion study Stress perfusion (AUC=0.79) outperformed rest perfusion (AUC=0.73) When specificity fixed at 90%, sensitivity increased from 40% to 67% by using stress perfusion Rest perfusion is predictive (t-test p=0.05, ROC AUC = 0.73). It may contain additive value to conventional CTA analysis. Data not shown, but decreased rest perfusion correlated with FFR before the injection of adenosine In this sample, stress/rest ratio did not predict CAD. More investigation is needed.

Unique aspects One of the first myocardial perfusion studies with 320-MDCT Utilizes regadenosone Quantification was performed by normalizing to the blood pool One of the first studies to use FFR as part of the reference standard Limitations Limited patient number We have a CT perfusion study currently being carried out in our lab that will enroll 60 patients Arterial territory is a coarse atlas We are developing a patient-specific polar map based on the vessel geometry from CTA Didn t consider beam hardening

Conclusions 320-MDCT can detect perfusion defect when compared with invasive angiography and fractional flow reserve Myocardial intensity normalized by the LV blood pool intensity both at stress and rest are absolute measurements that are predictive of perfusion defect