OCT-Derived Index of Plaque Attenuation as a Quantitative Metric for Histological Plaque Vulnerability in Human...

Vulnerable plaque rupture is a major mechanism underlying acute coronary events, but imaging-based risk assessment using individual plaque features remains limited. The histology-derived vulnerability index (VI) integrates multiple plaque components and is associated with adverse cardiovascular outcomes but requires ex vivo assessment. Optical coherence tomography (OCT) enables high-resolution in vivo plaque characterization, and the OCT-derived index of plaque attenuation (IPA) may provide a quantitative measure of integrated plaque vulnerability.

This study aimed to determine the association between OCT-derived IPA and histological VI and to identify the histological plaque components contributing to IPA.

In 240 coronary blocks from 10 human cadaveric hearts, co-registered OCT and histology were performed. IPA was calculated from attenuation images. Histology quantified necrotic core, collagen, α-SMA⁺ area, and macrophages (CD68⁺, CD206⁺). Associations were assessed using correlation and multivariable regression.

IPA at a 9 mm^-1 threshold (IPA₉) correlated with VI (r = 0.714, p < 0.001) and discriminated high-VI blocks (AUC = 0.852). CD68⁺ macrophage area (β = 17.20, p < 0.001) and necrotic core (β = 1.39, p = 0.013) predicted higher IPA, whereas collagen and α-SMA⁺ area were inversely associated. CD206⁺ areas were not independently related with IPA, but the CD206⁺/CD68⁺ ratio significantly improved IPA model performance (ΔR² = 0.023, p = 0.004).

OCT-derived IPA closely corresponds to histological VI and is primarily driven by necrotic core and pro-inflammatory macrophage infiltration. IPA may serve as a clinically obtainable quantitative OCT marker for integrated assessment of inflammation-weighted plaque vulnerability.