Photoacoustic Tomography Tracks Vascular Remodeling and Functional Recovery in Liver Regeneration

Objective: This study aims to longitudinally monitor hepatic vascular remodeling and functional recovery during liver regeneration in mice using 3-dimensional panoramic photoacoustic computed tomography (3D-PanoPACT). Impact Statement: By enabling noninvasive, whole-organ spatiotemporal tracking within the same animal, this work establishes a novel imaging framework for staging organ regeneration and mapping vascular dynamics. Introduction: Hepatic vascular remodeling is critical for successful liver regeneration; however, existing imaging modalities lack the capacity for noninvasive, longitudinal, 3D characterization at the whole-organ scale. Methods: Male nude mice under isoflurane anesthesia underwent 70% partial hepatectomy or served as controls. A custom 3D-PanoPACT system performed continuous whole-organ imaging over 16 d. Quantitative vascular parameters, contrast clearance kinetics, and histological validation via hematoxylin and eosin and CD31 staining were assessed. Serum biochemical analyses independently evaluated hepatobiliary functional recovery. Results: 3D-PanoPACT delineated 3 temporally distinct vascular remodeling phases: proliferative (days 2 to 4), recovery (days 5 to 9), and remodeling (days 10 to 16). By day 16, regenerated livers exhibited no significant differences from normal controls in vascular volume, vessel length, mean diameter, or branching density, which was further confirmed by CD31 evaluation. While functional imaging showed a slightly delayed early peak enhancement, long-term metabolic clearance remained similar to that of normal controls. This functional recovery was independently corroborated by normal-like serum biochemical profiles at day 16. Conclusion: 3D-PanoPACT enables noninvasive, longitudinal tracking of hepatic regeneration. By delineating distinct morphological phases and complementing them with metabolic and biochemical validations, this framework effectively maps macroscopic vascular remodeling and confirms adequate functional recovery by day 16.