Use of Hypoxic Respiratory Challenge for Differentiating Alzheimer's Disease and Wild-Type Mice Non-Invasively: A Diffuse Optical Spectroscopy Study.

Alzheimer's disease is one of the most critical brain diseases. The prevalence of the disease keeps rising due to increasing life spans. This study aims to examine the use of hemodynamic signals during hypoxic respiratory challenge for the differentiation of Alzheimer's disease (AD) and wild-type (WT) mice. Diffuse optical spectroscopy, an optical system that can non-invasively monitor transient changes in deoxygenated (ΔRHb) and oxygenated (ΔOHb) hemoglobin concentrations, was used to monitor hemodynamic reactivity during hypoxic respiratory challenges in an animal model. From the acquired signals, 13 hemodynamic features were extracted from each of ΔRHb and -ΔOHb (26 features total) for more in-depth analyses of the differences between AD and WT. The hemodynamic features were statistically analyzed and tested to explore the possibility of using machine learning (ML) to differentiate AD and WT. Among the twenty-six features, two features of ΔRHb and one feature of -ΔOHb showed statistically significant differences between AD and WT. Among ML techniques, a naive Bayes algorithm achieved the best accuracy of 84.3% when whole hemodynamic features were used for differentiation. While further works are required to improve the approach, the suggested approach has the potential to be an alternative method for the differentiation of AD and WT.

Blood flow estimation via numerical integration of temporal autocorrelation function in diffuse correlation spectroscopy.

BACKGROUND AND OBJECTIVE: Diffuse correlation spectroscopy (DCS) is an optical technique widely used to monitor blood flow. Recently, efforts have been made to derive new signal processing methods to minimize the systems used and shorten the signal processing time. Herein, we propose alternative approaches to obtain blood flow information via DCS by numerically integrating the temporal autocorrelation curves. METHODS: We use the following methods: the inverse of K2 (IK2)-based on the framework of diffuse speckle contrast analysis-and the inverse of the numerical integration of squared g1 (INISg1) which, based on the normalized electric field autocorrelation curve, is more simplified than IK2. In addition, g1 thresholding is introduced to further reduce computational time and make the suggested methods comparable to the conventional nonlinear fitting approach. To validate the feasibility of the suggested methods, studies using simulation, liquid phantom, and in vivo settings were performed. In the meantime, the suggested methods were implemented and tested on three types of Arduino (Arduino Due, Arduino Nano 33 BLE Sense, and Portenta H7) to demonstrate the possibility of miniaturizing the DCS systems using microcotrollers for signal processing. RESULTS: The simulation and experimental results confirm that both IK2 and INISg1 are sufficiently relevant to capture the changes in blood flow information. More interestingly, when g1 thresholding was applied, our results showed that INISg1 outperformed IK2. It was further confirmed that INISg1 with g1 thresholding implemented on a PC and Portenta H7, an advanced Arduino board, performed faster than did the deep learning-based, state-of-the-art processing method. CONCLUSION: Our findings strongly indicate that INISg1 with g1 thresholding could be an alternative approach to derive relative blood flow information via DCS, which may contribute to the simplification of DCS methodologies.

Changes in Cytochrome C Oxidase Redox State and Hemoglobin Concentration in Rat Brain During 810 nm Irradiation Measured by Broadband Near-Infrared Spectroscopy.

Objective: The effects of 810 nm light-emitting diode (LED) photobiomodulation (PBM) on cerebral metabolism and cerebral hemodynamic were investigated by using a broadband near-infrared spectroscopy (bb-NIRS) under anesthesia conditions with isoflurane. Background data: PBM was supposed to increase cerebral hemodynamic and cerebral metabolism. There has been no study about the effect of 810 nm LED stimulation on cerebral hemodynamic and cerebral metabolism in vivo by using bb-NIRS measurement. Methods: PBM was applied to seven Sprague-Dawley rats at 50 mW/cm2 power density. The changes in hemoglobin concentration (ΔHbO2 and ΔHHb) and oxidized cytochrome c oxidase (CCO) concentration (ΔoxCCO) were measured using a bb-NIRS. The total hemoglobin and the difference in hemoglobin concentration changes were calculated by summation and difference of ΔHbO2 and ΔHHb, respectively. Results: PBM evoked the gradual increases of ΔHbO2 (+7.7 µM vs. baseline, p = 0.008), ΔHbT (+9.5 µM vs. baseline, p = 0.0044), and ΔHbD (+5.9 µM vs. baseline, p > 0.05) during light stimulation. Meanwhile, ΔoxCCO (-3.5 µM vs. baseline, p = 0.0019) was significantly decreased right after the onset of stimulation. Conclusions: PBM with 810 nm LED (50 mW/cm2) increased cerebral oxygenation and blood volume as expected. However, oxidized CCO concentration was decreased, which was contrary to most previous studies. The two pathways of PBM effects on mitochondria and the inhibition of complex I by isoflurane were suggested to explain the decreased ΔoxCCO during PBM, but further study is required for the verification.