Multimodal OCT Biomarkers of Fibrosis and Steatosis in the Regenerating Liver

The liver's regenerative capacity is essential for resection and transplantation, but chronic liver diseases compromise this ability. Conventional preoperative tests poorly predict regeneration in diseased livers, necessitating new intraoperative tools. Optical coherence tomography (OCT) provides real-time high-resolution "optical biopsy" and functional tissue assessment, making it a promising method for evaluating liver regenerative potential. The aim of this study was to identify characteristic criteria derived from MM OCT that could be used intraoperatively to detect the presence and type of pathology, and to assess the reduction in liver regenerative potential in patients. In this study, we used intraoperative multimodal OCT (MM OCT)-combining attenuation mapping and elastography-for real-time, label-free assessment of changes in liver structure, and stiffness during regeneration. MM OCT also provides higher resolution and specificity than conventional clinical imaging. In a rat model, we induced steatosis by high-fat diet and fibrosis by CCl₄ injections, then induced regeneration by 70% partial hepatectomy (PH). MM OCT monitoring was performed on day 0 (pre-PH), day 3, and day 7 (post-PH). Pathologies and regeneration were verified by biochemical blood tests, histological analysis, and real time-PCR for steatosis- and fibrosis-specific genes. As a result, attenuation coefficient and Young's modulus obtained by MM OCT enable real-time assessment of liver tissue changes in steatosis and fibrosis, which vary with regeneration stage. Steatosis showed uniformly high attenuation and low stiffness before and after resection. Fibrosis exhibited heterogeneous attenuation and marked stiffness fluctuations-high pre-resection values dropped at day 3 and rose again by day 7. Attenuation coefficient detects lipid droplets in hepatocytes and identifies high-density hepatocyte zones near collagen septa, distinguishing them from densely packed unaltered cells. Thus, MM OCT identifies pathology type, lipid infiltration and collagen presence-features that serve as indicators of impaired liver regenerative capacity.