Profusa Inc., South San Francisco, CA, USA.
Kaiser Permanente Medical Center, Honolulu, HI, USA.
Microvasc Res. 2019 Jul;124:6-18. doi: 10.1016/j.mvr.2019.02.002. Epub 2019 Feb 8.
Measurements of regional tissue oxygen serve as a proxy to monitor local perfusion and have the potential to guide therapeutic decisions in multiple clinical disciplines. Transcutaneous oximetry (tcpO) is a commercially available noninvasive technique that uses an electrode to warm underlying skin tissue and measure the resulting oxygen tension at the skin surface. A novel approach is to directly measure interstitial tissue oxygen using subcutaneous oxygen microsensors composed of a biocompatible hydrogel carrier platform with embedded oxygen sensing molecules. After initial injection of the hydrogel into subcutaneous tissue, noninvasive optical measurements of phosphorescence-based emissions at the skin surface are used to sense oxygen in the subcutaneous interstitial space. The object of the present study was to characterize the in vivo performance of subcutaneous microsensors and compare with transcutaneous oximetry (tcpO). Vascular occlusion tests were performed on the arms of 7 healthy volunteers, with repeated tests occurring 1 to 10 weeks after sensor injection, yielding 95 total tests for analysis. Comparative analysis characterized the response of both devices to decreases in tissue oxygen during occlusion and to increases in tissue oxygen following release of the occlusion. Results indicated: (I) time traces returned by microsensors and tcpO were highly correlated, with the median (interquartile range) correlation coefficient of r = 0.93 (0.10); (II) both microsensors and tcpO sensed a statistically significant decrease in normalized oxygen during occlusion (p < 0.001 for each device); (III) microsensors detected faster rates change (p < 0.001) and detected overshoot during recovery more frequently (38% vs. 4% of tests); (IV) inter-measurement analysis showed no correlation of baseline values between microsensors and tcpO (r = 0.03), but comparison of integrated oxygen dynamics showed similar variation in the normalized response to occlusion between devices (p = 0.06), (V) intra-measurement analysis revealed that microsensors detect greater physiological fluctuations than tcpO (p < 0.001) and may provide enhanced sensitivity to processes such as vasomotion. Additionally, the functional response of microsensors was not significantly different across time groupings (per month) post-injection (p = 0.61). Although the compared devices have differences in the mechanisms used to sense oxygen, these findings demonstrate that subcutaneous oxygen microsensors measure changes in interstitial tissue oxygen in human subjects in vivo.
组织氧测量可作为监测局部灌注的替代指标，具有指导多个临床学科治疗决策的潜力。经皮氧饱和度（tcpO）是一种商业上可用的非侵入性技术，它使用电极加热皮下组织，并测量皮肤表面的氧分压。一种新方法是使用由生物相容性水凝胶载体平台组成的皮下氧微传感器直接测量间质组织氧，该平台嵌入了氧传感分子。在将水凝胶最初注入皮下组织后，使用皮肤表面基于磷光的发射的非侵入性光学测量来感测皮下间质空间中的氧。本研究的目的是描述皮下微传感器的体内性能，并与经皮氧饱和度（tcpO）进行比较。对 7 名健康志愿者的手臂进行血管闭塞测试，在传感器注射后 1 至 10 周重复进行测试，共分析了 95 次测试。比较分析的特点是两种设备对组织氧减少的反应以及对闭塞释放后组织氧增加的反应。结果表明：（I）微传感器和 tcpO 的时间轨迹高度相关，中位数（四分位距）相关系数 r=0.93（0.10）；（II）微传感器和 tcpO 均检测到组织氧在闭塞过程中显著下降（每种设备的 p<0.001）；（III）微传感器检测到更快的速率变化（p<0.001），并且更频繁地检测到恢复过程中的过冲（38%比测试的 4%）；（IV）测量间分析显示微传感器和 tcpO 之间的基线值没有相关性（r=0.03），但比较设备之间对闭塞的归一化响应的综合氧动力学显示出相似的变化（p=0.06）；（V）测量内分析表明，微传感器比 tcpO 检测到更大的生理波动（p<0.001），并且可能对血管运动等过程提供更高的灵敏度。此外，微传感器的功能响应在注射后（每个月）不同时间分组（p=0.61）之间没有显著差异。尽管比较的设备在用于感测氧的机制上存在差异，但这些发现表明，皮下氧微传感器在体内测量人类受试者间质组织氧的变化。
