Polarimetry reveals reduced collagen signature in CCTA-defined high-risk coronary plaques

Background High-risk plaque (HRP) features on coronary computed tomography angiography (CCTA)—including positive remodeling, low-attenuation plaque (LAP), the napkin-ring sign (NRS), and spotty calcification—are associated with future coronary events, yet the in vivo microstructural substrate that underpins these radiologic signatures remains incompletely defined. Polarization-sensitive (PS) optical frequency domain imaging (OFDI) enables intracoronary quantification of collagen organization (birefringence) and lipid/inflammatory-related signal randomness (depolarization), offering a potential bridge between CT morphology and plaque tissue architecture. Purpose To evaluate whether PS-OFDI–derived polarimetric signatures are linked to CCTA-defined HRP features and to explore quantitative relationships between polarimetric measures and CT plaque metrics. Methods From a prospective intracoronary PS-OFDI registry, we identified 32 patients (53 lesions) who underwent CCTA prior to hospitalization and subsequently received OFDI-guided percutaneous coronary intervention. HRP was defined as the presence of ≥2 CCTA features (positive remodeling, LAP, NRS, spotty calcification). Conventional OFDI findings (qualitative and quantitative) and polarimetric properties (birefringence and depolarization) were compared between HRP and non-HRP lesions. Plaque-level birefringence and depolarization were computed across the segmented plaque volume, and associations between polarimetric measures and CCTA quantitative parameters (including LAP volume) were explored using unadjusted linear regression. Results We analyzed 53 lesions from 32 patients (median age 74 years; 81% male), with HRP present in 26 lesions (49%). Birefringence was significantly lower in HRP versus non-HRP lesions [0.45 (0.42–0.49)×10⁻³ vs 0.51 (0.48–0.55)×10⁻³; p=0.011], consistent with reduced collagen organization or altered fibrous architecture in HRP. Depolarization did not differ significantly between groups [0.13 (0.11–0.16) vs 0.12 (0.11–0.15); p=0.323; log-transformed −2.05 (−2.18 to −1.79) vs −2.14 (−2.25 to −1.90); p=0.323], although values trended higher in HRP. In unadjusted quantitative analyses, birefringence was inversely associated with LAP volume (β −0.35; 95% CI −19.848 to −2.261; p=0.015), supporting a link between increasing lipid-rich/low-attenuation burden and loss of organized fibrous structure (Figure). Conclusion Intracoronary polarimetry with PS-OFDI identifies a microstructural signature associated with CCTA-defined HRP. Lower birefringence in HRP lesions supports reduced collagen organization as a plausible substrate of CT vulnerability markers, suggesting PS-OFDI may complement CCTA by linking plaque morphology to in vivo tissue architecture and pathobiology.