## 1 Introduction
### Super-Continuum Infrared Spectroscopy  
To noninvasively interrogate the redox state of the CCO enzyme as well as blood oxygenation, we developed a SCISCCO system that uses an all-fiber integrated super-continuum light source. Our novel SCL can provide almost an order of magnitude improvement in brightness compared with the tungsten-halogen lamps typically employed for CCO measurements. The signal-to-noise ratio (SNR) for the measurements using the SCL is not only enhanced by the increase in NIR light brightness, but it can be further enhanced because the SCL is pulsed, and the detection system can be synchronized to the SCL (improvements we plan on adding in the near future). For example, the SNR may further obtain improvement of \(\sim\)30 times which arises from time-gated detection of the pulsed SCL light, and change detection (i.e., subtracting SCL on from SCL off) further improves the SNR by subtracting the background light. The high-brightness fiber delivery of our SCL NIR light will permit clinical applications through deeper brain penetration and a higher SNR, which will help to distinguish the CCO signal from clutter or interference from hemoglobin and other chemicals in the brain or organs, as well as scattered light from the scalp, skull, or environment. The diagnostic instrument prototype integrates theSCL with a two-arm differential set-up and receivers, and laboratory tests quantify the sensitivity and selectivity of CCO measurements.  
Following the introduction, the remainder of the paper is organized as follows. Section 2 describes the set-up and results for the laboratory measurements of CCO, particularly the optical spectra for CCO. Then, in Section 3, the modification of the set-up for human testing is explained. Three sets of human tests are conducted. In Section 3.1, the experimental results for the blood pressure test are presented, showing that we obtain similar results to those in published literature on CCO. In Section 3.2, the breath-holding tests are described, confirming that our measurements for hemoglobin correlate with the measurements when using an fNIRS commercial system. Then, in Section 3.3, attention tests are conducted on 25 healthy human participants, which is the key pilot human study reported in this paper. Section 4 provides a detailed analysis of the results from the healthy human attention tests, and a hypothesis is derived from the experiments. A discussion in Section 4 also explains the basis of the hypothesis that the redox state of CCO decreases during the attention test periods. Then, a comparison is made between our results and those reported in the literature. Although other reports in the literature were unable to draw a conclusion on the change in CCO during attention test procedures, our results appear to have a higher SNR and are more definitive in showing that the redox state of CCO decreases during the attention test period, which is qualitatively consistent with the reported behavior of CCO in mitochondria.  
Having shown the efficacy of the laboratory-based SCISCCO system, Section 5 describes a cart-based SCISCCO prototype, which is a stand-alone unit that includes the SCL, optical system, electronics, and processing computer. The hardware and software are integrated so the cart-based prototype can be used in laboratory or hospital settings as well as transported to remote locations, such as from the University of Michigan in Ann Arbor to the Northwestern University medical campus in Chicago. To validate the instrument's measurements, and to show that it can be used in the context of existing protocols, Section 6 describes the cart-based SCISCCO prototype being applied to swine animal models undergoing induction of hemorrhagic shock followed by different treatment modalities, including pREBOA and VPA. The data verify that the measured HbO and HbR concentration changes across different clinical phases are consistent with the expectations based on physiological principles.