Aims
Standard manual analysis of IVUS to study the impact of anti-atherosclerotic therapies on the coronary vessel wall is done by a core laboratory (CL), the ground truth (GT). Automatic segmentation of IVUS with a machine learning (ML) algorithm has the potential to replace manual readings with an unbiased and reproducible method. The aim is to determine if results from a CL can be replicated with ML methods.

Methods
This is a post-hoc, comparative analysis of the IBIS-4 (Integrated Biomarkers and Imaging Study-4) study (NCT00962416). The GT baseline and 13-month follow-up measurements of lumen and vessel area and percent atheroma volume (PAV) after statin induction were repeated by the ML algorithm.

Results
The primary endpoint was change in PAV. PAV as measured by GT was 43.95 % at baseline and 43.02 % at follow-up with a change of −0.90 % (p = 0.007) while the ML algorithm measured 43.69 % and 42.41 % for baseline and follow-up, respectively, with a change of −1.28 % (p < 0.001). Along the most diseased 10 mm segments, GT-PAV was 52.31 % at baseline and 49.42 % at follow-up, with a change of −2.94 % (p < 0.001). The same segments measured by the ML algorithm resulted in PAV of 51.55 % at baseline and 47.81 % at follow-up with a change of −3.74 % (p < 0.001).

Conclusions
PAV, the most used endpoint in clinical trials, analyzed by the CL is closely replicated by the ML algorithm. ML automatic segmentation of lumen, vessel and plaque effectively reproduces GT and may be used in future clinical trials as the standard.

Abbreviations
CADcoronary artery diseaseCLcore laboratoryCNNconvolutional neural networkGTground truthIBIS-4integrated biomarker imaging studyIRAinfarct-related arteriesIVUSintravascular ultrasoundMFCNNmulti-frame convolutional neural networkMLmachine learningPAVpercent atheroma volumePCIpercutaneous coronary interventionROIregion of interest