Device and algorithm for oxygenation quantification in the brain

氧合作用是衡量血液中携带氧气的指标，是一个重要的生物标志物，因为大脑活动**会引起局部变化。因此，它反映了大脑的能量代谢，并被广泛应用于动物模型，以监测神经元活动和研究神经血管耦合，即电和血管活动之间的关系。测量氧合的放射学方法，如功能磁共振成像**(FMRI)和正电子发射断层扫描(PET)，成本高昂，需要对动物进行限制或**麻醉，极大地限制了研究范围。近红外光谱(NIRS)和本征光学信号成像(IOSI)等光学方法降低了空间分辨率或限制了深度穿透。**本研究旨在开发一种光学技术和设备，用于量化自由活动的啮齿类动物大脑深层结构中**高度局部化的体积的氧合作用。我们建议使用单光纤探头的反射光谱**在感兴趣的大脑区域传输和收集光。深度穿透**是通过立体定向植入光纤探头来实现的。我们将选择一些照明波长来**优化发色团之间的分离，并提供对功能变化的优化敏感度。**锁定放大器和频率调制的多波长照明将用于重建**反射光的**光谱信息。基于蒙特卡罗模拟的经验模型将被用来**从光谱中提取氧合和其他血流动力学参数。该系统将在定制设计的光学模型中进行**表征和验证。**拟议的研究将创建一种新的设备，能够在自由移动的动物体内随时间在任何深度进行非常局部化的体积**的氧合测量。与束缚或麻醉相比，当**动物处于更自然的状态时，它将允许对血流动力学进行功能监测。当与其他光学**监测模式(例如光纤光度法)相结合时，所提出的系统可用于校正血液动力学**伪影，这可能会破坏其他光学信号。

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.