Device and algorithm for oxygenation quantification in the brain

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Oxygenation, a measure of oxygen carried in the blood, is an important biomarker because brain activity**induces local changes in it. Thus, it reflects brain energy metabolism and is widely used in animal models to**monitor neuronal activity and to investigate neurovascular coupling, the relationship between electrical and**vascular activity. Radiological methods to measure oxygenation, e.g. functional magnetic resonance imaging**(fMRI) and positron emission tomography (PET), are costly and require animals to be restricted or**anesthetized, greatly limiting the scope of studies. Optical methods like near-infrared spectroscopy (NIRS) and**intrinsic optical signal imaging (IOSI), have reduced spatial resolution or limited depth penetration.**This research aims to develop optical techniques and a device for quantifying oxygenation from a**highly-localized volume in the deep brain structures of freely-moving rodents. We propose using reflectance**spectroscopy with a single fiber probe to deliver and collect light in the brain area of interest. Depth penetration**is achieved by stereotaxically implanting the fiber probe. We will select a few illumination wavelengths which**optimize the separation between chromophores and provide optimized sensitivity to functional changes. A**lock-in amplifier along with frequency-modulated multi-wavelength illumination will be used to reconstruct**spectral information of the reflected light. An empirical model based on Monte Carlo simulations will be used**to extract the oxygenation and other hemodynamic parameters from the spectra. The system will be**characterized and verified in a custom designed optical phantom.**The proposed study will create a new device enabling oxygenation measurements in a very localized volume**over time at any depth in freely-moving animals. It will allow functional monitoring of hemodynamics when**the animal is in a more natural state, compared to restrained or anesthetized. When combined with other optical**monitoring modalities, e.g., fiber photometry, the proposed system can be used to correct for hemodynamic**artifacts, which can corrupt other optical signals.