Concise biomarker for spatial–temporal change in three-dimensional ultrasound measurement of carotid vessel wall and plaque thickness based on a graph-based random walk framework: Towards sensitive evaluation of response to therapy

Rapid progression in total plaque area and volume measured from ultrasound images has been shown to be associated with an elevated risk of cardiovascular events. Since atherosclerosis is focal and predominantly occurring at the bifurcation, biomarkers that are able to quantify the spatial distribution of vessel-wall-plus-plaque thickness (VWT) change may allow for more sensitive detection of treatment effect. The goal of this paper is to develop simple and sensitive biomarkers to quantify the responsiveness to therapies based on the spatial distribution of VWT-Change on the entire 2D carotid standardized map previously described. Point-wise VWT-Changes computed for each patient were reordered lexicographically to a high-dimensional data node in a graph. A graph-based random walk framework was applied with the novel Weighted Cosine (WCos) similarity function introduced, which was tailored for quantification of responsiveness to therapy. The converging probability of each data node to the VWT regression template in the random walk process served as a scalar descriptor for VWT responsiveness to treatment. The WCos-based biomarker was 14 times more sensitive than the mean VWT-Change in discriminating responsive and unresponsive subjects based on the p-values obtained in T-tests. The proposed framework was extended to quantify where VWT-Change occurred by including multiple VWT-Change distribution templates representing focal changes at different regions. Experimental results show that the framework was effective in classifying carotid arteries with focal VWT-Change at different locations and may facilitate future investigations to correlate risk of cardiovascular events with the location where focal VWT-Change occurs.