An efficient framework to assess the predictive value of 4D ultrasound-based wall motion indices for abdominal aortic aneurysm rupture risk stratification

Clinical assessment of abdominal aortic aneurysm (AAA) rupture risk relies on diameter criteria, which are often insufficient. Validating non-invasive biomarkers against experimental ground truth is a crucial prerequisite before conducting large-scale clinical trials. We hypothesize that Wall Motion Indices (WMI), derived from 4D ultrasound (4D-US) strain imaging, capture the functionally compromised mechanical state of the aneurysm wall. This study introduces a validation framework using patient-specific, experimental ground truth metrics. For nine AAA patients, the Normalized Experimental Rupture Potential (NERP) was established. The NERP, a normalized ratio of physiological loading to failure capacity, combined finite element analysis (FEA)-estimated wall tension with ex vivo rupture strength from harvested tissue. To ensure strict data separation, patient-specific ground truths (NERP and rupture strength) were correlated with pre-operative WMI exclusively at the documented harvest location. While maximum diameter showed no significant association with NERP or rupture strength, specific WMI quantifying kinematic anisotropy and local strain concentrations demonstrated notable correlations. Strain ratios, identifying local hotspots relative to background deformation, correlated with different structural integrity metrics. Principal strain ratio correlated significantly with intrinsic ex vivo rupture strength (r=-0.711,p=0.032), whereas the macroscopic anatomical strain ratio correlated with the computationally derived NERP (r=0.833,p=0.005). This study demonstrates an efficient validation framework for biomechanical biomarkers in small cohorts. The findings suggest that disparity-based WMI are promising, non-invasive indicators of AAA wall integrity that warrant further investigation. Statement of Significance This study addresses the critical need for reliable rupture risk assessment in abdominal aortic aneurysms (AAA), moving beyond simple diameter measurements. We introduce a multi-modal validation framework that serves as a crucial, mechanistically-informed precursor to large-scale clinical trials. By correlating non-invasive, 4D ultrasound-based wall motion biomarkers with patient-specific, experimental "ground truth" data (tissue strength and stress) from the exact same anatomical location, this approach establishes the necessary biomechanical plausibility of predictive metrics before clinical scaling. Our findings reveal that while traditional clinical parameters fail to predict wall integrity, disparity indices quantifying the mechanical disorganization (anisotropy of heterogeneity) of the aneurysm wall correlate strongly with structural vulnerability. This work establishes an efficient tool for evaluating biomechanical markers in small cohorts and highlights strain disparity-based Wall Motion Indices as promising candidates for a more refined, patient-specific risk stratification.