In the United States alone, 76,000 lives are claimed by liver disease every year. Transplantation is currently the only established treatment, but there is a critical shortage of donor organs. More than 60% of candidates wait over a year to receive a transplant, the majority becoming too ill to tolerate the procedure. These numbers could be improved dramatically by expanding the available donor pool through the rescue of disqualified donor organs; conservatively estimated at 6,000 livers per year. We and others have shown experimentally that machine perfusion, an artificial body and blood supply for isolated donor organs, is a powerful methodology capable of administering treatment and significantly increasing viability. However, unlike tightly-controlled experimental livers, there is a large degre of variability that characterizes human donor organs, from a range of pre-existing comorbidities to the circumstances of death and the duration of warm and cold ischemia experienced during procurement and transportation. There is currently no way to objectively assess the status and therefore likelihood of recovery of individual organs, which also prevents the development of organ-specific treatment regimens to be administered during machine perfusion. Machine perfusion is therefore currently being conducted blindly, inhibiting its true clinical potential an vertical advancement of the field. Our long-term goal is to minimize deaths due to organ shortages by engineering robust strategies to enhance the availability of whole organ- and cell-based therapies. The objective of the proposed study is to validate an innovative imaging approach for qualitative and quantitative evaluation of donor organs at the time of procurement and during perfusion. The work described here is expected to produce novel metrics of organ viability enabling accurate diagnosis of ischemia and real-time evaluation of organ recovery. Future consequences of this work will be its expansion to other systemic disease states, guidance of real-time, organ- specific interventions during perfusion, and the prediction of time to optimal recovery. These developments will facilitate the clinical translation of machine perfusion as a dynamic preservation system for all donor organs.
Public Health Relevance Statement: Public Health Relevance: About thirty million people in the U.S. suffer from a liver disorder and about 76,000 deaths are registered annually due to liver disease. The organ shortage limits transplantation to only 30% of the wait-listed candidates and renders cell-based therapies an unmet need. This project will identify and then recover those disqualified human donor livers amenable to machine perfusion resuscitation, rendering them suitable for the provision of high quality cells or transplantation, thus expanding treatment availability and reducing the number of deaths due to liver diseases significantly.
Project Terms: Acoustics; acute liver disease; Adoption; attenuation; base; Biological Preservation; Biomedical Technology; Biopsy; Cardiac Death; Cell Separation; Cell Therapy; Cell Transplantation; Cell Volumes; Cells; Cessation of life; Clinical; Comorbidity; cost effective; Cryopreservation; Data; Data Analyses; Decision Making; Development; Diagnosis; Diagnostic; Engineering; Ensure; Evaluation; experience; Family suidae; Focused Ultrasound Therapy; Future; Goals; Gold; Government; Hour; Human; Image; improved; indexing; Individual; Injury; innovation; Intervention; Ischemia; Liver; Liver diseases; Measurable; Measures; meetings; Methodology; Metric; Modeling; Monitor; novel; Organ; Organ Donor; Organ Preservation; Organ Viability; Pathology; Perfusion; Persons; pre-clinical; prevent; Procedures; Process; prognostic; Property; public health relevance; Publications; Qualifying; Qualitative Evaluations; Quantitative Evaluations; Recovery; Research; Research Personnel; Resuscitation; Severities; Signal Transduction; Staging; success; System; Systemic disease; Techniques; Testing; Therapeutic; Time; Tissues; tool; Translating; Translations; Transplantation; Transportation; Treatment Protocols; trend; Ultrasonography; Uncertainty; United States; Vascular blood supply; Waiting Lists; Warm Ischemia; Work
