Enhanced recovery of disqualified donor organs using image-guided machine perfusion

描述（由申请人提供）：仅在美国，每年就有76，000人死于肝病。移植是目前唯一确定的治疗方法，但 捐献器官严重短缺超过60%的候选人等待一年以上才接受移植，大多数人病情严重，无法忍受手术。通过挽救不合格的供体器官来扩大可用的供体库，这些数字可以大大提高;保守估计每年有6，000个肝脏。我们和其他人已经通过实验证明，机器灌注，一种人造身体和血液供应的孤立供体器官，是一种强大的方法，能够管理治疗和显着提高生存能力。然而，与严格控制的实验肝脏不同，人类供体器官具有很大程度的可变性，从一系列预先存在的合并症到死亡情况以及在采购和运输过程中经历的热缺血和冷缺血的持续时间。目前没有办法客观地评估单个器官的状态以及因此恢复的可能性，这也阻碍了在机器灌注期间要施用的器官特异性治疗方案的开发。因此，机器灌注目前正在盲目进行，抑制了其真正的临床潜力和该领域的垂直发展。我们的长期目标是通过设计强有力的策略来提高整个器官和细胞治疗的可用性，从而最大限度地减少因器官短缺而导致的死亡。拟议研究的目的是验证一种创新的成像方法，用于在采购时和灌注期间对供体器官进行定性和定量评价。本文所述的工作有望产生新的器官活力指标，从而能够准确诊断缺血和实时评估器官恢复。这项工作的未来结果将是其扩展到其他全身性疾病状态，指导灌注期间的实时器官特异性干预，以及预测最佳恢复时间。这些发展将促进机器灌注作为所有供体器官的动态保存系统的临床翻译。

DESCRIPTION (provided by applicant): 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.