Carotid Plaque Calcification Attenuation Characteristics are Associated with Intraplaque Hemorrhage Volumes: A 3D Segmentation-Based Analysis

Background and Purpose Despite the high prevalence of plaque calcifications in carotid atherosclerosis, the association between morphologic and attenuation features of calcifications and intraplaque hemorrhage (IPH) remains unclear.

Carotid bifurcation calcific plaques were identified on neck CTAs from patients with unilateral anterior circulation ischemic stroke consistent with embolic stroke of undetermined source. Plaque calcifications were manually segmented using 3D Slicer to measure volume, surface area, shape, and attenuation (Hounsfield Units (HU)) characteristics. IPH volume (IPHvol) was quantified using a semi-automated software. A linear mixed regression model evaluated associations between calcification features and IPHvol, adjusting for sex, age, and cardiovascular risk factors. An interaction term between calcification volume and attenuation was included after dichotomizing attenuation (>924HU) and volume (>30mm3) as high versus low based on median values.

From 70 patients (median age 68 years, 50% female), 116 calcific plaques containing 269 plaque calcifications were analyzed. Adjusting for age, cardiovascular risk factors and plaque calcification features, being female showed lower IPHvols compared to males (mean ratio 0.34, p=0.002). A significant interaction between calcification volume and attenuation emerged (p=0.042). Among plaques with low volumes (<30mm3) of plaque calcifications, plaques with low-attenuation (924HU), plaques with high volumes of these calcifications showed 4.40 times higher IPHvols compared to low-volumes of high-attenuation calcifications (p=0.011).

Plaque calcification attenuation characteristics are associated with IPHvols. Beyond presence or volumes of plaque calcifications, calcification attenuation characteristics should be considered when evaluating unstable plaque components. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study was funded by the National Science Foundation Graduate Research Fellowship (DGE-2236662), American Heart Association (938082) and NIH/NIBIB T-32 grant (EB004311). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The institutional review board at the University of Pennsylvania gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Grant Support: JR is supported by the National Science Foundation Graduate Research Fellowship DGE-2236662. JWS is supported by the AHA (938082). YS is supported by NIH/NIBIB T-32 grant (EB004311). A typographical error in the grants acknowledgement was updated from NINIB to NIBIB. Data Availability All data produced in the present study are available upon reasonable request to the authors.