A Hybrid Hierarchical Framework for Quantifying Mechanical Markers in Atherosclerotic Disease Progression: A New...

Atherosclerosis is the primary pathological basis for cardiovascular diseases. Despite advances in diagnosis and treatment, current methods primarily focus on late-stage intervention, missing critical opportunities for early detection. Recently, the dynamic mechanical properties of arterial tissue have been recognized as a novel approach for assessing vascular status, and offer an opportunity to employ the mechanical properties of atherosclerotic lesions for evaluating disease status and monitoring disease progression. Here, we employed a Hybrid Hierarchical theory-Microrheology (HHM) framework to quantify multiscale mechanical markers during lesion progression. The results revealed a two-stage power-law rheology, with short- and long-timescale exponents (α_short, α_long) as key mechanical markers of lesion composition and mechanical gradients. We further applied a self-similar hierarchical framework to capture plaque heterogeneity across cytoplasmic, cellular, and tissue scales, yielding additional mechanical markers (e.g., E₁, η, E₂, E₃) from subcellular to tissue scales. Based on these markers, we built a multiparametric diagnostic model that outperforms traditional elastic modulus criterion. This model captures stage- and region-specific trajectories, coupling mechanical signatures with histology for improved staging and risk assessment, establishing an operational framework for enhanced prediction and diagnosis of atherosclerosis.