Frequency domain shortwave infrared spectroscopy (FD-SWIRS) for volume status monitoring during hemodialysis in end stage kidney disease

项目总结 慢性肾脏疾病(CKD)，或肾功能的逐渐丧失，是世界上第九大主要死亡原因。 并造成了天文数字的医疗负担。慢性肾脏病最终导致终末期肾病(ESKD)， 需要血液透析治疗(HD)或肾脏移植才能存活。HD是去除多余的过程 患者血液中的水、溶质和毒素，因为肾脏不能再执行这些自然功能。 2017年，有746,557名美国人患有ESKD，其中70%是HD患者。患有ESKD的患者 在HD会话之间积累液体，清除液体是HD的一项典型功能。体液不足 去除HD会导致容量超负荷，从而导致高血压、心力衰竭和最终的心血管疾病 死亡率。过多的液体排出会导致低血压、肌肉痉挛，并影响HD后的活力。因此， 在CKD患者中，保持干体重或体重而不过量液体是至关重要的。尽管核心重要性 在维持ESKD患者的容量内稳方面，目前还没有量化标准 监测HD患者的容量状态。HD患者的容量评估仍然是 肾内科实践中最具挑战性的方面。该项目旨在开发频域短波 红外线光谱(FD-SWIRS)在未满足临床需要的高血压患者HD容量状态监测中的应用 ESKD。与SWIR波段相比，SWIR波段(也称为NIR II)对水和脂肪更敏感 可见或近红外波段，并有可能提供更深层次的组织测量。FD-SWIRS将提供 宽波长范围内绝对吸收系数和折合散射系数的测量 (900-1310 nm)。FD-SWIR将代表一种新技术，据我们所知，没有类似的 高清监控技术已被用于高清监控。FD-SWIRS将提供三个独特的无标签来源 HD监测的对比：1)根据宽带(900-1310)计算组织摩尔水分浓度的变化 Nm)吸收系数(µa)，2)宽带减少散射(µS‘)，以及3)结合水指数(BWi)，其 利用与水分子与组织中蛋白质结合相关的微妙光谱变化。我们假设 这些对比源将准确地揭示音量状态，并提供一个非侵入性指标 细胞外与细胞内的水，这已被证明是重要的容量评估。我们会 首先开发了FD-SWIRS系统，并通过严格的系统测试验证了系统的性能。一个多层的 将开发反模型来提取深部组织的光学特性。然后我们将执行Pre、POST和 假设会有变化的50次透析中的FD-SWIRS测量 在HD前后时间点的FD-SWIRS信号中。此外，我们假设FD-SWIRS信号将 在整个透析过程中会发生变化，可能与透析相关的并发症同时发生或先于透析相关并发症发生。成功 这一试点项目的完成将是第一个将FD-SWIRS新技术应用于重要临床 在HD患者中的问题，并将指导后续的R01规模资金。

PROJECT SUMMARY Chronic kidney disease (CKD), or the gradual loss of kidney function, is the ninth leading cause of death in the US and poses an astronomical healthcare burden. CKD eventually leads to end-stage kidney disease (ESKD), requiring hemodialysis treatment (HD) or kidney transplant for survival. HD is the process of removing excess water, solutes, and toxins from the blood in patients, as kidneys can no longer perform these natural functions. In 2017 there were 746,557 Americans with ESKD, and 70% of these were on HD. Patients with ESKD accumulate fluid in between HD sessions, whose removal is a quintessential function of HD. Insufficient fluid removal on HD results in volume overload contributing to hypertension, heart failure and eventual cardiovascular mortality. Excess fluid removal results in hypotension, muscle cramps and compromises vitality after HD. Thus, it is critical to maintain dry weight, or weight without excess fluid in CKD patients. Despite the central importance of maintaining volume homeostasis in patients with ESKD, there are currently no quantitative standards for monitoring volume status of patients undergoing HD. The volume assessment of patients on HD remains the most challenging aspect of nephrology practice. This project aims to develop frequency-domain shortwave infrared spectroscopy (FD-SWIRS) for the unmet clinical need of HD volume status monitoring in patients with ESKD. The SWIR wavelength band (also called NIR II) is more sensitive to water and lipids compared to the visible or NIR bands, and can potentially provide deeper tissue measurements. FD-SWIRS will provide measurements of the absolute absorption and reduced scattering coefficients over a broad wavelength range (900-1310 nm). FD-SWIRS would represent a new technology, and to the best of our knowledge, no similar technologies have been used for HD monitoring. FD-SWIRS will provide three unique sources of label-free contrast for HD monitoring: 1) tissue molar water concentration changes calculated from broadband (900-1310 nm) absorption coefficients (µa), 2) broadband reduced scattering (µs′), and 3) bound water index (BWI), which utilizes subtle spectral shifts related to the binding of water molecules to proteins in tissue. We hypothesize that that these sources of contrast will accurately reveal volume status and provide a non-invasive indicator of extracellular versus intracellular water, which has been shown to be important for volume assessment. We will first develop an FD-SWIRS system and validate performance through rigorous system testing. A multi-layer inverse model will be developed to extract deep tissue optical properties. We will then perform pre, post and intradialytic measurements of FD-SWIRS in 50 dialysis sessions with the hypothesis that there will be alteration in FD-SWIRS signal between pre and post-HD time points. In addition, we posit that FD-SWIRS signal will change throughout dialysis session and may coincide or precede the dialysis-related complications. Successful completion of this pilot project will be the first to apply a novel technique FD-SWIRS to an important clinical problem in patients on HD, and will guide subsequent R01-scale funding.