ABSTRACT
We developed a new method to measure voxel-based vessel-wall-plus-plaque volume (VVol). In addition to quantifying the change in local vessel-wall-plus-plaque thickness (VWT), VVol also assesses the local circumferential change stemming from over-compensatory remodeling, evaluation of which is important because it encourages plaque growth by reducing the endothelial shear stress. The vessel wall was segmented from the three-dimensional ultrasound (3DUS) images acquired at baseline and one year after. The vessel wall region was partitioned into small voxels with the percentage difference between the volumes in the corresponding voxels in the baseline and follow-up images for each voxel measured. We refer to the voxel-based volume difference as https://www.w3.org/1998/Math/MathML"> Δ V V o l % https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781003299462/450ced82-5fab-4976-8cb5-8d8f32c870f4/content/math8_1.tif" xmlns:xlink="https://www.w3.org/1999/xlink"/> , the distribution of which was mapped to a 3D carotid atlas for group-wise analysis and visualization. A new patient-based biomarker denoted by https://www.w3.org/1998/Math/MathML"> Δ V V o l % ¯ https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781003299462/450ced82-5fab-4976-8cb5-8d8f32c870f4/content/math8_2.tif" xmlns:xlink="https://www.w3.org/1999/xlink"/> was measured by taking the mean https://www.w3.org/1998/Math/MathML"> Δ V V o l % https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781003299462/450ced82-5fab-4976-8cb5-8d8f32c870f4/content/math8_3.tif" xmlns:xlink="https://www.w3.org/1999/xlink"/> over the left and right arteries for each patient. A statistically significant difference was detected by https://www.w3.org/1998/Math/MathML"> Δ V V o l % ¯ https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781003299462/450ced82-5fab-4976-8cb5-8d8f32c870f4/content/math8_4.tif" xmlns:xlink="https://www.w3.org/1999/xlink"/> between patients randomized to the pomegranate and placebo groups (p = 0.0002). The number of patients required to achieve statistical significance was about one-third of that needed for the corresponding local VWT biomarker. The increase in sensitivity to treatment effect afforded by the new biomarker would improve the cost-effectiveness of clinical trials piloting novel therapies and reduce the time duration that effective treatments are withheld from patients who need them.
