Optoacoustic monitoring of cerebral blood oxygenation

描述（由申请人提供）： 急性、危及生命的神经系统疾病（如严重创伤性脑损伤）的管理可通过准确和持续的脑氧合监测来促进。然而，目前的监测系统是侵入性的，需要颈内静脉球插管或将探针直接插入大脑。近红外光谱法是一种无创的监测脑血氧的方法，很有前途，但尚未得到令人满意的校准，以提供定量测量成人。目前还没有一种准确、无创、连续的脑血氧监测系统。我们提出并进行了一种新型光声技术的体外和体内测试，该技术可直接从上级矢状窦准确连续地测量血氧，该结构由于光声技术的高分辨率而易于定位。光声技术基于通过激光脉冲产生超声波（光声）并通过灵敏的声换能器检测这些波。血氧的光声监测利用了氧合血红蛋白和脱氧血红蛋白在近红外光谱范围内的光学吸收系数的公认差异。在我们目前的NIH R21项目中，根据PA-98-050计划公告（旨在开发包括光声脑监测在内的创新技术），我们设计，建造并测试了一种用于精确监测脑血氧的无创光声系统。我们的体外和体内（绵羊）研究表明：（1）光声波的参数与血氧呈线性相关;（2）使用专门设计的换能器和光声探头，尽管厚骨会导致光学和声学衰减，但仍能进行灵敏检测;（3）该技术可以高精度测量血氧。在这项资助申请中，我们建议在本计划公告下进一步开发这项技术。该项目的具体目标是：（1）修改光声系统，以提供多波长测量，并在尸体上进行系统评价;（2）在志愿者体内进行评价;（3）评价创伤性脑损伤患者的系统性能。到项目结束时，该系统将得到充分的开发，以允许多中心临床试验。

DESCRIPTION (provided by applicant): Management of acute, life-threatening neurologic illnesses, such as severe traumatic brain injury, is facilitated by accurate and continuous monitoring of cerebral oxygenation. However, current monitoring systems are invasive, requiring either cannulation of the internal jugular venous bulb or insertion of a probe directly into the brain. Nearinfrared spectroscopy, a noninvasive method of monitoring cerebral blood oxygenation, is promising, but has yet to be satisfactorily calibrated to provide quantitative measurement in adults. At present there is no system for accurate, noninvasive, and continuous monitoring of cerebral blood oxygenation. We proposed and performed in vitro and in vivo testing of a novel optoacoustic technique that accurately and continuously measures blood oxygenation directly from the superior sagittal sinus, a structure that can easily be localized due to the high resolution of the optoacoustic technique. The optoacoustic technique is based on generation of ultrasonic (optoacoustic) waves by laser pulses and detection of these waves by a sensitive acoustic transducer. Optoacoustic monitoring of blood oxygenation utilizes well-established differences in the optical absorption coefficients of oxy- and deoxyhemoglobin in the nearinfrared spectral range. During our current NIH R21 project supported by an NINDS grant under the Program Announcement PA-98-050 (directed at the development of innovative technologies including photoacoustic brain monitoring), we designed, built, and tested a noninvasive optoacoustic system for accurate monitoring of cerebral blood oxygenation. Our in vitro and in vivo (in sheep) studies demonstrated that: (1) the parameters of the optoacoustic waves are linearly dependent on blood oxygenation; (2) the use of specially designed transducers and optoacoustic probes allows sensitive detection despite optical and acoustic attenuation by thick bone; and (3) this technique can measure blood oxygenation with high accuracy. In this grant application, we propose to further develop this technique under this program announcement. The specific aims of the project are: (1) to modify the optoacoustic system to provide multiwavelength measurements and perform evaluation of the system in cadavers; (2) to evaluate it in vivo in volunteers; and (3) to evaluate the system performance in patients with traumatic brain injury. By the end of the project the system will be developed sufficiently to permit multi-center clinical trials.