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

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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.