Frequency domain diffuse optical spectroscopy and diffuse correlation spectroscopy for assessing inspiratory muscle metabolism in mechanically ventilated patients

项目总结 机械通气(MV)用于帮助或取代危重患者的自主呼吸， 2010年，美国的医疗支出达到270亿美元，占所有医院成本的12%。同年，在那里 每1000人中有2.7次MV，突显了这一程序的巨大重要性。这个 新冠肺炎大流行大幅增加了这些数字，尽管目前尚不能获得准确的数字。 MV部分用于“卸载”或减少呼吸肌的代谢努力，以改变氧气的方向。 输送到重要器官。随着患者病情的改善，关键的吸气肌(例如横隔膜，鳞状突， 胸乳突骨等。)需要独立于呼吸机进行自主呼吸。这种“重装”是 由于卸货引起的肌肉废用性萎缩而导致的不稳定。这一点由于其他常见的 败血症或心源性休克等情况，可严重限制不依赖肌肉的氧气输送 状态。需要的是一种能够持续监测血液流量和氧气利用的方法学 吸气肌肉，以便在MV过程中持续优化呼吸努力。该项目旨在 开发吸气式综合血流指数、氧合和代谢测量平台 结合宽带频域漫反射光谱(WbDOS)和漫反射的肌肉生理学 相关光谱学(DCS)来解决这一未得到满足的需求。WbDOS是一种新型的全数字频域DOS 在很宽的调制频率带宽上捕获幅度和相位测量的技术 (50-500 MHz)，高速(&gt；100赫兹)。WbDOS和分布式控制系统将协同结合，提供路径长度- 更正了Hb/Mb绝对浓度和血流指数(BFI)的估计，允许提取 组织局部氧代谢率(MRO2i)，这是一个与氧利用直接相关的参数。我们假设 可以并行高速(&gt；10赫兹)同时采集wbDOS和DCS测量 探测和集成电子学。这个速度是捕捉吸气/呼气动力学所必需的。 呼吸频率。此外，我们假设宽带频域DOS测量将提供 与分布式控制系统光学集成时，改进了光学特性、BFI和MRO2I的量化 单频FD-DOS或CW-NIR。我们将通过使用流动通道的严格系统测试来验证这一点 模仿组织的光学模体。为了更好地捕捉吸气，将开发一个多层逆模型。 肌肉新陈代谢通过考虑皮下脂肪厚度和肤色。我们还将扩展我们的 最近在深度神经网络(DNN)处理方面的工作，以开发计算Hb/Mb的高速算法 浓度、StO2(%)、BFI(mm2/S)和MRO2i(10赫兹)。我们将进行一项可行性研究(n=10) 志愿者在呼吸肌加载和卸载过程中评估与预期相比的性能 趋势。预计这些目标的完成将产生新的和全面的血液流动指数， 氧合和代谢测量平台(wbDOS-DCS)，并导致随后的R01规模的资金。

PROJECT SUMMARY Mechanical ventilation (MV), which is used to assist or replace spontaneous breathing in critically ill patients, led to $27 billion in expenditures in the US in 2010, accounting for 12% of all hospital costs. In that same year there were 2.7 episodes of MV per 1000 population, highlighting the enormous importance of this procedure. The COVID-19 pandemic has substantially increased these numbers, although precise rates are not yet available. MV is used, in part, to “unload”, or reduce the metabolic effort of respiratory muscles in order to redirect oxygen delivery to vital organs. As the patients’ conditions improve, key inspiratory muscles (e.g. diaphragm, scalenes, sternomastoid, etc.) need to take over spontaneous breathing independent of the ventilator. This “reloading” is precarious due to muscle disuse atrophy, induced by unloading. This is further complicated by other common conditions such as septic or cardiogenic shock, which can severely limit oxygen delivery independent of muscle status. What’s needed is a methodology that can continuously monitor blood flow and oxygen utilization of inspiratory muscles so that respiratory effort can be continuously optimized during MV. This project aims to develop a comprehensive blood flow index, oxygenation, and metabolic measurement platform for inspiratory muscle physiology by integrating wideband frequency-domain diffuse optical spectroscopy (wbDOS) and diffuse correlation spectroscopy (DCS) to tackle this unmet need. wbDOS is a new all-digital frequency-domain DOS technique that captures amplitude and phase measurements over a wide bandwidth of modulation frequencies (50-500 MHz) at high speeds (>100 Hz). wbDOS and DCS will combine synergistically to provide pathlength- corrected estimates of absolute Hb/Mb concentrations and blood flow index (BFi), allowing for the extraction of tissue regional oxygen metabolic rate (MRO2i), a parameter directly linked to oxygen utilization. We hypothesize that wbDOS and DCS measurements can be acquired simultaneously at high speed (>10 Hz) with parallel detection and integrated electronics. This speed is needed to capture inspiratory/expiratory dynamics at the respiratory rate. Additionally, we hypothesize wideband frequency-domain DOS measurements will provide improved quantification of optical properties, BFi and MRO2i when optically integrated with DCS as compared to single frequency FD-DOS or CW-NIRS. We will validate this through rigorous system testing using flow-channel tissue-mimicking optical phantoms. A multi-layer inverse model will be developed to better capture inspiratory muscle metabolism by accounting for subcutaneous lipid thickness and skin tones. We will also expand on our recent work in Deep Neural Network (DNN) processing to develop high-speed algorithms for calculating Hb/Mb concentrations, StO2 (%), BFi (mm2/s), and MRO2i at 10 Hz. We will conduct a feasibility study (n=10) of healthy volunteers during respiratory muscle loading and unloading to evaluate performance compared to expected trends. It is anticipated that completion of these aims will yield a novel and comprehensive blood flow index, oxygenation, and metabolic measurement platform (wbDOS-DCS) and lead to subsequent R01-scale funding.