Interferometric, acousto-optic modulated diffuse correlation spectroscopy @ 1064 nm (AOM-iDCS) toward higher sensitivity, non-invasive measurement of cerebral blood flow

对有神经血管并发症风险的患者进行连续床旁脑血流监测， 降低发病率和死亡率的潜力。例如，据估计， 约10%的患者接受高风险心血管或脑部手术。这些患者 通常通过麻醉后难以唤醒来识别，但这种迹象并不特异，可能是 因为持续的麻醉虽然全身生理学的测量可用于推断脑灌注， 需要一种直接和连续测量脑血流量（CBF）的技术， 治疗扩散相关光谱（DCS）是一种成熟的光学技术， 无创和直接测量CBF。DCS测量CBF的有效性受到以下因素的阻碍： 成年人通过脑外污染和有限的深度敏感性。这项建议旨在扩大 通过开发一种新技术，称为声光调制， 在1064 nm处的干涉扩散相关光谱（AOM-iDCS），这将增强CBF灵敏度， 减少脑外污染。首先，我们将展示移动到1064 nm的实用性，与传统的 NIRS波长（680-850 nm），受益于更大的光子穿透深度以及增加的 检测到的光子总数，约15至20倍。为了克服在1064 nm处的单光子检测器的缺点， 我们将利用外差干涉技术来实现散斑信号的相干放大。 第二，我们将开发声光调制DCS，以提高血流测量的灵敏度 更深的流动。我们将优化应用的超声压力分布，以最大限度地提高对CBF的灵敏度， 开发理论模型，用于从调制信号中提取血流，并证明增加 深度灵敏度和选择性。最后，我们将联合收割机与AOM-iDCS技术相结合， 不仅受益于单个技术的优势，还受益于它们之间的协同作用。通过调制 参考臂处于超声频率，标记光信号将被频率解调，并且 未标记的光将被转移到超声频率，然后可以通过低通滤波器去除该超声频率。的 拟议的研究代表了对CBF的敏感性和脑外排斥的显着改善， 污染.我们相信，这项研究的成功完成将导致一个设备很容易翻译， 神经重症监护患者管理诊所。拟议的培训计划提供了机会， 通过AOM-iDCS的开发，在理论和硬件相关问题上发展技术技能; 科学沟通技能，通过书面作品传播拟议的研究，以及 在会议上的演讲;专业地，通过会议上的网络以及利用许多 通过赞助机构（MGH，哈佛-麻省理工学院HST）提供的资源;以及长期职业技能， 通过指导研究助理和硕士生以及参与审稿。

Continuous, bedside monitoring of cerebral blood flow in patients at risk for neurovascular complications has the potential to decrease morbidity and mortality. For example, perioperative stroke has been estimated to occur in approximately 10% of patients undergoing high risk cardiovascular or brain surgeries. These patients are commonly identified by their difficulty to awaken following anesthesia, but this sign is not specific and could be due to lingering anesthesia. While measures of systemic physiology can be used to infer cerebral perfusion, a technology that directly and continuously measures cerebral blood flow (CBF) is needed to properly manage treatment. Diffuse Correlation Spectroscopy (DCS) is an established optical technique that enables continuous, non-invasive, and direct measurements of CBF. The effectiveness of DCS in measuring CBF is hampered in adults by to extracerebral contamination and limited depth sensitivity. This proposal seeks to extend the usefulness of DCS through the development of a new technique, known as acousto-optic modulated, interferometric diffuse correlation spectroscopy (AOM-iDCS) at 1064 nm, which will enhance CBF sensitivity and reduce extracerebral contamination. First, we will show the utility of moving to 1064 nm as compared to traditional NIRS wavelengths (680–850 nm), benefitting from both greater photon penetration depth as well as an increased overall number of detected photons, ~15 to 20x. To overcome single photon detector shortcomings at 1064 nm, we will utilize a heterodyne interferometric technique to enable coherent amplification of the speckle signal. Second, we will develop acousto-optic modulated DCS to increase the sensitivity of blood flow measurements to deeper flows. We will optimize the applied ultrasound pressure distribution to maximize sensitivity to CBF, develop theoretical models for the extraction of blood flow from the modulated signal, and demonstrate increased depth sensitivity and selectivity. Finally, we will combine the two techniques to demonstrate AOM-iDCS, benefitting not only from the individual techniques’ strengths but also synergies between them. By modulating the reference arm at the ultrasound frequency, the tagged light signal will be frequency demodulated, and the untagged light will be shifted to the ultrasound frequency, which can then be removed by a low pass filter. The proposed research represents a significant improvement in both sensitivity to CBF and rejection of extracerebral contamination. We believe the successful completion of this research will lead to a device readily translatable to the clinic for the management of patients in neuro-critical care. The proposed training plan gives opportunities to develop technical skills, both in theoretical and hardware related matters through the development of AOM-iDCS; scientific communication skills, through dissemination of the proposed research through written works as well as presentations at conferences; professionally, through networking at conferences as well as utilizing the many resources available through the sponsoring institutions (MGH, Harvard-MIT HST); and long term career skills, through mentoring of research assistants and master students and participating in manuscript review.