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

干涉、声光调制漫相关光谱 @ 1064 nm (AOM-iDCS) 实现更高灵敏度、非侵入性脑血流测量

• 批准号: 10065091
• 负责人: Mitchell Robinson
• 金额: $ 4.55万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10065091
• 关键词: Adoption; Adult; Anesthesia procedures; Biological; Blood flow; Brain; Brain Injuries; Cardiovascular Surgical Procedures; Cerebrovascular Circulation; Cerebrum; Clinic; Clinical; Coma; Communication; Coupled; Critical Care; Custom; Data; Detection; Development; Devices; Diffuse; Discrimination; Effectiveness; Erythrocytes; Fiber; Frequencies; Goals; Gold; Hemoglobin; Individual; Infant; Institution; Intensive Care Units; Ischemia; Lasers; Length; Light; Location; Manuscripts; Measurement; Measures; Mentors; Methods; Modality; Monitor; Morbidity - disease rate; Near-Infrared Spectroscopy; Neurologic Examination; Neurological outcome; Operative Surgical Procedures; Optics; Patients; Penetration; Performance; Perfusion; Perioperative; Photons; Physicians; Physiologic Monitoring; Physiologic pulse; Physiology; Population; Procedures; Process; Professional Competence; Records; Research; Research Assistant; Resources; Risk; Role; Sampling; Scalp structure; Scanning; Signal Transduction; Source; Spectrum Analysis; Speed; Stroke; Students; System; Technical Expertise; Techniques; Technology; Theoretical model; Thick; Time; Tissues; Training; Transducers; Translating; Ultrasonic Transducer; Ultrasonic wave; Ultrasonography; Work; arm; attenuation; base; blood flow measurement; brain surgery; clinical translation; cost; design; health care settings; heterodyning; high risk; hypoperfusion; improved; indexing; innovation; lens; light intensity; mortality; neurovascular; new technology; non-invasive monitor; novel; novel strategies; operation; personalized medicine; photon-counting detector; pressure; prototype; skills; symposium; synergism; temporal measurement

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.

持续的床边监测有神经血管并发症风险的患者的脑血流 有可能降低发病率和死亡率。例如，据估计，围术期中风发生在 大约10%接受高危心血管或脑部手术的患者。这些病人是 通常由麻醉后难以唤醒来识别，但这一体征不是特异性的，可能是 由于持续的麻醉。虽然系统生理学的测量可以用来推断脑血流灌注，但 需要直接和连续测量脑血流量(CBF)的技术来正确管理 治疗。漫反射相关光谱(DCS)是一种成熟的光学技术，它使连续、 无创、直接测量脑血流量。分布式控制系统在测量CBF方面的有效性受到阻碍 成年人对脑外污染和有限的深度敏感。这项建议旨在延长 通过开发一种称为声光调制的新技术， 1064 nm处的干涉漫相关光谱(AOM-IDCS)，它将增强CBF的灵敏度和 减少脑外污染。首先，我们将展示与传统移动相比，移动到1064 nm的效用 近红外波长(680-850 nm)，得益于更大的光子穿透深度以及 探测到的光子总数，~15到20倍。为了克服1064 nm处的单光子探测器的缺点， 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的分布式控制系统，以提高血流测量的灵敏度 更深层次的流动。我们将优化应用超声的压力分布，以最大限度地提高对CBF的敏感度， 建立从调制信号中提取血流的理论模型，并证明 深度敏感性和选择性。最后，我们将结合这两种技术来演示AOM-IDDC， 不仅受益于各自技术的长处，而且还得益于它们之间的协同效应。通过调制 超声频率处的参考臂、标记的光信号将被频率解调，并且 未标记的光将被转移到超声波频率，然后可以通过低通滤光器去除。这个 拟议的研究表明，在对脑血流的敏感性和脑外排斥反应方面都有显著改善 污染。我们相信，这项研究的成功完成将导致一种易于翻译的设备 管理神经科危重病人的诊所。拟议的培训计划提供了以下机会 通过开发AOM-IDC，发展理论和硬件相关事项的技术技能； 科学沟通技能，通过书面作品和 在会议上发言；专业上，通过在会议上建立网络以及利用许多 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，参与审稿。