The Development of a Thin-Filmed, Non-Invasive Tissue Perfusion Sensor to Quantify Capillary Pressure Occlusion of Explanted Organs

ABSTRACT

A new thin-filmed perfusion sensor was developed using a heat flux gauge, thin-film thermocouple, and a heating element. This sensor, termed “CHFT+”, is an enhancement of the previously established CHFT (combined heat flux – temperature) sensor technology predominately used to quantify the severity of burns [1]. The CHFT+ sensor was uniquely designed to measure tissue perfusion on explanted organs destined for transplantation, but could be functionalized and used in a wide variety of other biomedical applications. Exploiting the thin and semi-flexible nature of the new CHFT+ sensor assembly, perfusion measurements can be made from the underside of the organ – providing a quantitative, indirect measure of capillary pressure occlusion. Results from a live tissue test demonstrated, for the first time, the effects of pressure occlusion on an explanted porcine kidney. CHFT+ sensors were placed on top of and underneath 18 kidneys to measure and compare perfusion at perfusate temperatures of 5˚C and 20˚C. The data collected shows greater perfusion on the topside than the underside of the specimen for the length of the experiment. This indicates that pressure occlusion is truly affecting the perfusion and thus, the overall preservation of explanted organs. Moreover, the results demonstrate the effect of preservation temperature on the tissue vasculature. Focusing on the topside perfusion only, the 20˚C perfusion was greater than the 5˚C perfusion, likely due to the vasoconstrictive response at the lower perfusion temperatures.

INTRODUCTION

Since the first kidney transplant in the early 1950s, improvements in surgical techniques and the use of immunosuppressive medications have resulted in better overall outcomes of transplant procedures. A workable technology, hypothermic static cold storage (SCS) has been the preferred method of organ preservation mainly because it is a simple, low-cost method with predictable results. However, it is not necessarily optimum for organ preservation. SCS does not provide any sensing or measurements of explanted organ condition during the storage interval (termed “cold ischemia interval”) that predict organ quality or suitability for implantation, forcing transplant surgeons to rely on gross organ appearance, a small biopsy, and consideration of donor and recipient characteristics in deciding whether or not to transplant. While hypothermic preservation has proven satisfactory for renal preservation (24-36 hrs.), the time frame from initial procurement to implantation is still much too short for other organs such as livers and hearts (6-12 hrs.). According to the Organ Procurement and Transplant Network (OPTN), there are approximately 120,005 people currently in need of a life-saving organ transplant. Typically, fewer than 20% of wait list candidates have received a transplant. More than 2,600 kidneys are discarded annually (prior to transplantation) due to severe anatomical anomalies such as glomerulosclerosis, tubular atrophy, interstitial fibrosis, inflammation, cortical necrosis, vascular pathology, and prolonged cold and warm ischemic intervals [2]. In 2014, a total of 17,107 renal transplants were performed, the most ever reported in a single year and nearly a 1.3% increase from the previous year. In 2015, there was a 4.8% decrease in the number of renal transplants compared to 2014. While the demand for organs increases every year, the consistent shortage in supply is disconcerting. The organ supply deficit can be attributed to several factors including insufficient donation to meet the needs, discarding of organs prior to transplantation due to quality concerns, inability to transplant in a timely manner, and problems occurring during surgery. Fig. 1 illustrates this large disparity for transplantable organs from 1988 through 2015.

CONCLUSION

This work illustrated the use of a novel, perfusion-sensing technology and exploited its unique qualities to measure and evaluate the perfusion of explanted porcine kidneys from both their top and underside for the first time. The performance of the CHFT+ sensor was demonstrated in a controlled phantom tissue setting, where the sensor displayed good repeatability and sensitivity. The results of the live tissue testing indicate that the pressure due to the weight of the organ creates an additional resistance to capillary perfusion on the underside of an explanted organ. Although progress has been made in the development of machine perfusion devices, no one has yet considered the potential deleterious effect pressure occlusion could have on an explanted organ resting on a dense surface.

This sensor could potentially influence the way organ preservation systems are designed, perhaps by incorporating more anatomical cassette designs or other pressure-relieving technologies. Also, while these sensors were employed towards the study of pressure occlusion experienced by explanted organs, there are many other biomedical concerns where they can be applied.