Fluorescence Imaging and PBPK Modeling of Liver Viability during Normothermic Machine Perfusion

Project Summary:

End-stage liver disease (ESLD) is the eighth leading cause of death in Wisconsin, contributing to more than 900 deaths annually and over $130 million in healthcare costs each year. Liver transplantation (LT) is the only curative treatment for ESLD, yet a critical shortage of donor organs persists. While the number of LTs in Wisconsin has increased by nearly 200% since 1995, waitlist mortality has risen by more than 500%, reflecting a widening gap between need and organ availability. In 2023, only 61% of the 293 patients listed for LT in Wisconsin received transplants. Despite this demand, many recovered donor livers are discarded because of uncertainty about their functional viability, and approximately 10% of transplanted grafts fail after surgery. A major unmet need is the absence of a reliable, quantitative method to assess organ viability during preservation. Current assessments rely on subjective indices such as bile output or lactate release, which provide limited predictive value. This project will establish an integrated fluorescence imaging and computational modeling platform for the quantitative assessment of donor liver viability during normothermic machine perfusion (NMP)—a clinical preservation method that maintains the organ's physiological metabolism. The approach will combine real-time optical imaging with physiologically based pharmacokinetic computational modeling to dynamically measure hepatocellular transport and metabolic activity. By defining objective, mechanistic biomarkers of viability, the project will improve donor organ utilization, reduce discard rates, and expand the pool of transplantable livers in Wisconsin. Furthermore, the platform will lay the foundation for extending fluorescence-based functional assessment to other perfused organs affected by ischemia–reperfusion injury and other stressors, establishing a scalable precision tool for organ preservation science and positioning the team for future multi-investigator NIH funding.