Comparison of 2D and 3D carotid plaque analysis and longitudinal in vivo ultrasound registration using 3D histology

Abstract. Purpose Characterizing carotid plaque specimens based on two-dimensional (2D) “representative” histology sections is considered standard practice in clinics. In comparison, three-dimensional (3D) histology has the potential to provide much more useful, volumetric information about carotid plaques. Despite this, due to the increased requirement for manual labor, 3D histology has been less employed for carotid plaque characterization. Evaluating the representativeness of 2D histology and exploring clinical applications of 3D carotid plaque histology, particularly in the arena of registration to and correlations with in vivo ultrasound, could be insightful. Approach Using 3D carotid plaque histology models, we evaluated the representativeness of 2D histology by comparing the predicted specimen composition based on 2D histology to the actual specimen composition based on 3D histology. We introduced a workflow that properly orients 3D carotid plaque histology based on transverse ultrasound and takes virtual histology slices at an angle to register histology to the longitudinal ultrasound. We correlated 3D histology composition to in vivo ultrasound parameters such as strain and grayscale features. Results The 2D histology successfully predicted specimen composition (to within 3%) for 11 specimens out of 34. The 2D representative slice predictions generally overestimated calcification for more calcified specimens (≳30% calcified). Using 3D histology, we registered virtual histology to in vivo longitudinal ultrasound B-mode and strain. For B-mode, the registrations had higher IoU with respect to the ultrasonographer’s annotations (0.54±0.05) compared with the registrations with conventional 2D histology (0.30±0.08). 3D histology composition was loosely related to all strain indices and grayscale features used in the study. In one of the cases, we note that hemorrhage corresponded to opposing strains. Conclusions 3D histology can be helpful for carotid plaque characterization as it enables a better understanding of plaque composition and better histology to in vivo ultrasound imaging registration.