The invisible becomes quantifiable in coronary computed tomography angiography exams with CT-FFR

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The invisible becomes quantifiable in coronary computed tomography angiography exams with CT-FFR Moti Freiman Global Advanced Technology, CT/AMI, Philips 06-Mar-2018

Coronary Artery Disease (CAD) 2 Image source: http://www.nhlbi.nih.gov/health/health-topics/topics/cad/signs

Evaluating CAD by Coronary Computed Tomography angiography Image source: https://www.health.harvard.edu/heartdisease-overview/cardiac-exercise-stress-testing-whatit-can-and-cannot-tell-you 3

Evaluating chest pain by Coronary Computed Tomography angiography (CCTA) Coronary CTA has a high sensitivity and high negative predictive value for diagnosis of obstructive CAD by detecting anatomical narrowing in the coronaries 4 Soft plaque (darker) Calcified plaque (brighter)

Quantifying coronary artery disease by CCTA Stenosis percentage: different clinical definitions Recently demonstrated high accuracy: 1 lumen cross sectional area vessel cross sectional area Healthy vessel: ~ 0.0 Vessel with CAD: ~ 0.8 5

Anatomical assessment of intermediate disease with CCTA is not enough >50% of lesions with greater than 50% diameter stenosis by CCTA were not functionally significant Image source: Meijboom et al. J Am CollCardiol 2008;52:636 43 6

Anatomical assessment of intermediate disease with CCTA is not enough >50% of lesions with greater than 50% diameter stenosis by CCTA were not functionally significant Too many unnecessary invasive coronary angiography Image source: Meijboom et al. J Am CollCardiol 2008;52:636 43 7

CAD functional significance: Fractional Flow Reserve (FFR) FFR = Pd/Pa FFR: measured through invasive cathlab procedure through a pressure wire 8

Transforming CCTA from anatomical to functional imaging modality with CT-FFR CT-FFR: Non-invasive FFR measurement from a routine cardiac CTA scan using a biophysical model CT-FFR 9

CT-FFR application pipeline CCTA data Tree extraction Vessel by vessel segmentation Flow simulation 3D model Goal: to improve CCTA specificity by enabling non-invasive CCTA-based functional characterization of coronary stenosis 10

CT-FFR application pipeline CCTA data Tree extraction Vessel by vessel segmentation Flow simulation 3D model Goal: to improve CCTA specificity by enabling non-invasive CCTA-based functional characterization of coronary stenosis 11

Machine-learning based coronary segmentation algorithm Input: Machine-learning based likelihood + PV detection Regularization function E v = φ(v) v + v p,v q Ω ψ(v p, v q ) F cut B 12 Freiman et al, Medical Physics 2016

Approximate K nearest neighbor (L2) likelihood estimation Lumen likelihood function: P lumen x p : R N R N Defined as: P lumen x p = σk k=1 w I x p, I x k S x k σk k=1 where: x p : ray to assign likelihood to x k : similar ray from the database I: ray HU profile S: ray expert segmentation w: weighting function (L2) w I x p, I x k DB: Test : 0 0 0 0 1 2 3 4 4 4 4 4 5 5 5

Accounting for partial volume effect (PVE) in small vessels Small radius with PVE No PVE 14 Freiman et al, Medical Physics 2016

Simultaneous lumen and wall segmentation using hierarchical graph L1=Wall log(p x i L1 ) TBD Lumen Wall Background log(p x i Bkg ) 1 L2=Lumen log(p x i L2 ) log(p x i L1 ) 0

Simultaneous lumen and wall segmentation using hierarchical graph: solution L1=Wall log(p x i L1 ) Lumen Wall Background log(p x i Bkg ) 1 L2=Lumen log(p x i L2 ) log(p x i L1 ) 0

Database optimization DB N : function that create sampled database from the full one according to the parameters N Find N = N i i=1 5 that maximize the CT-FFR AUC: Optimization strategy: DB N = arg max AUC FFR CT DB N, FFR GT N Optimize FFR-CT AUC over the parameters: N using the BOBYQA algorithm (Powell, M. J. D. 2009) For each iter.: 1. Build a sparsely sampled database for the full database by sampling N percent samples to the database from each class 2. Perform lumen segmentation 3. Calculate FFR-CT values. Freiman et al, PATCH-MI, MICCAI 2017

Representative vessel segmentation results Red: lumen Blue: wall

Lumen segmentation evaluation on the MICCAI 2012 database Evaluate the impact of database sampling using the publicly available MICCAI 2012 challenge framework Website: http://coronary.bigr.nl/stenoses/ Papers: Medical Image Analysis, 2013 Summary statistics of coronary lumen segmentation accuracy using the MICCAI 2012 challenge evaluation framework for the training datasets with provided centerlines (18 cases, 78 coronary segments). Method Dice (%) MSD (mm) MAX SD (mm) Healthy Disease Healthy Disease Healthy Disease Mohr et al. 0.75 0.73 0.45 0.29 3.73 1.87 Ours 0.69 0.74 0.49 0.28 1.69 1.22

CT-FFR results: non significant lesion Stenosis: ~40% 20

CT-FFR results: significant lesion Stenosis: ~50% 21

CT-FFR results: automatic segmentation vs. manual Invasive FFR 22

Summary CT-FFR enables on-site non-invasive functional assessment of coronary lesions Potential to reduce substantially unnecessary invasive coronary angiography exams Automatic coronary segmentation can achieve almost humanlevel performance by means of CT-FFR accuracy 23

Participants Haifa (CT Global Advanced Technology - GAT) Liran Goshen, Moti Freiman Philips Research Hamburg: Hannes Nickisch, Sven Prevrhal, Holger Schmitt Cleveland, OH (CT Clinical Science) Mani Vembar