Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA.
Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.
Artif Organs. 2024 Dec;48(12):1536-1548. doi: 10.1111/aor.14840. Epub 2024 Aug 27.
Ex vivo perfusion of transplant-declined human organs has emerged as a promising platform to study the response of an organ to novel therapeutic strategies. However, to fully realize the capability of this platform for performing translational research in human organ pathophysiology, there is a need for robust assays to assess organ function and disease. State-of-the-art research methods rely on analyses of biopsies taken during perfusion, which both damages the organ and only provides localized information. Developing non-invasive, whole organ methods of assessment is critical to the further development of this research platform.
We use ex vivo cold infusion scanning (EXCIS) with contrast-enhanced computed tomography (CT) to quantify perfusion in kidneys preserved ex vivo. EXCIS-CT computes three complementary metrics for whole organ assessment: a dynamic assessment of contrast filling, a measure of vascular network anatomical structure, and a static assessment of perfusion heterogeneity.
These metrics were applied to a series of six transplant-declined human kidneys, which demonstrated a range of anatomies and perfusion. Lastly, two transplant-declined human kidneys were imaged before and after a 1-h period of ex vivo normothermic perfusion (NMP). We found variable responses to NMP, with one kidney maintaining the vascular network and hemodynamics and the other showing significant changes in vessel size and spatial perfusion profile.
EXCIS-CT provides metrics that can be used to characterize whole organ perfusion and vascular function.
离体灌注移植失败的人体器官已成为研究器官对新型治疗策略反应的有前途的平台。然而，为了充分发挥该平台在人体器官病理生理学方面进行转化研究的能力，需要有强大的检测方法来评估器官功能和疾病。最先进的研究方法依赖于在灌注过程中进行的活检分析，这既损害了器官，又只能提供局部信息。开发非侵入性的、整个器官的评估方法对于该研究平台的进一步发展至关重要。
我们使用离体冷灌注扫描（EXCIS）与对比增强计算机断层扫描（CT）来量化离体保存的肾脏灌注。EXCIS-CT 计算了三种用于整体器官评估的互补指标：对比剂填充的动态评估、血管网络解剖结构的测量，以及灌注异质性的静态评估。
这些指标应用于一系列 6 例移植失败的人类肾脏，这些肾脏表现出不同的解剖结构和灌注情况。最后，对 2 例移植失败的人类肾脏进行了离体常温灌注（NMP）前和 1 小时后的成像。我们发现 NMP 的反应各不相同，一个肾脏保持血管网络和血液动力学，另一个肾脏显示出血管大小和空间灌注分布的显著变化。
EXCIS-CT 提供了可用于描述整个器官灌注和血管功能的指标。
