Noninvasive, Optoacoustic Monitoring of Cerebral Circulation in Preterm Neonates

描述（由申请人提供）：早产，极低出生体重（VLBW; d1500 g）和低出生体重（LBW; 1500-2499 g）婴儿长期脑病的风险增加。在美国每年出生的63,000名VLBW婴儿中，有25-50%患有严重的长期认知或神经行为缺陷。出生后脑缺血似乎在长期认知后遗症中起重要作用。不幸的是，LBW和VLBW新生儿的脑血管系统维持足够的脑血流量的能力尚不清楚。尽管经典的key - schmidt方法、多普勒超声、正电子发射断层扫描、灌注计算机断层扫描、磁共振成像和近红外光谱进行了重要的临床研究，但目前还没有一种技术可以轻松、重复和无创地监测或测量LBW或VLBW婴儿的脑循环充分性。我们的初创公司Noninvasix最近在VLBW和LBW婴儿中证明，光声技术可以通过开放的前囟门轻松，准确，直接无创地测量上矢状窦（SSSSO2）的脑静脉血氧饱和度。SSSSO2测量脑血流量满足脑氧需求的能力；在创伤性脑损伤的成人中，脑静脉饱和度低于50%，表明脑血流量不能满足脑氧需求，具有不祥的预后意义。在建立了新生儿光声SSS监测的概念验证之后，我们现在建议在这个第一阶段的应用中完善该技术，作为新生儿脑灌注间歇测量和连续监测设备商业化的重要一步。在第一阶段的提案中，基于我们的实验室原型，Noninvasix将与德克萨斯大学医学分部合作，该分部与两名教师共同拥有Noninvasix，他们是该提案的发明者和研究人员，以及库珀咨询服务公司（CCS），一家工程设计公司，反复设计和构建临床原型新生儿界面和用户界面，并在产后新生儿中进行测试。我们将通过以下具体目标来生产和测试临床原型（创新部分图1）：为我们的无创光声监测仪开发临床原型患者界面，以准确测定新生儿的SSSSO2。具体目标2。为我们的无创光声监测仪开发临床用户界面，以促进新生儿重症监护病房间歇性或连续新生儿SSSSO2的快速评估。具体目标3。初步确定不同体重新生儿（10-12 LBW新生儿和10-12 VLBW新生儿）体内SSSSO2的预期范围。

DESCRIPTION (provided by applicant): Premature, very-low-birth-weight (VLBW; d1500 g) and low-birth-weight (LBW; 1500-2499 g) infants are at increased risk for long-term encephalopathy. 25-50% of the 63,000 VLBW infants born annually in the U.S. have major long-term cognitive or neurobehavioral deficits. Postnatal cerebral ischemia appears to play an important role in long-term cognitive sequelae. Unfortunately, the ability of the cerebral vasculature of LBW and VLBW neonates to maintain adequate cerebral blood flow is poorly understood. Although important, provocative clinical studies have been performed with classical Kety-Schmidt methodology, Doppler ultrasound, positron emission tomography, perfusion computed tomography, magnetic resonance imaging and near-infrared spectroscopy, there is currently no technique for easily, repeatedly and noninvasively monitoring or measuring cerebral circulatory adequacy in LBW or VLBW infants. Our start-up company, Noninvasix, recently demonstrated in VLBW and LBW infants that optoacoustic technology permits easy, accurate, direct noninvasive measurement of cerebral venous blood oxygen saturation in the superior sagittal sinus (SSSSO2) through the open anterior fontanelle. SSSSO2 measures the ability of cerebral blood flow to meet cerebral oxygen demand; in adults with traumatic brain injury cerebral venous saturations less than 50%, suggesting that cerebral blood flow does not meet cerebral oxygen demand, have ominous prognostic implications. Having established the proof-of-concept for optoacoustic SSS monitoring of neonates, we now propose in this Phase I application to refine that technique as a major step toward commercialization of a device for intermittent measurements and continuous monitoring of neonatal cerebral perfusion. In this Phase I proposal, based on our laboratory prototype, Noninvasix will collaborate with The University of Texas Medical Branch, which co-owns Noninvasix with two faculty who are inventors and investigators in this proposal, and Cooper Consulting Services (CCS), an engineering design firm, to iteratively design and build a clinical prototype neonatal interface and a user interface and test it in post- delivery neonates. We will produce and test the clinical prototype (Fig. 1 in Innovation section) by progressing through the following specific aims: Specific Aim 1. To develop a clinical prototype patient interface for our noninvasive optoacoustic monitor that will accurately determine SSSSO2 in neonates. Specific Aim 2. To develop a clinical user interface for our noninvasive optoacoustic monitor that will facilitate rapid assessment of SSSSO2 in neonates intermittently or continuously in the Neonatal Intensive Care Unit. Specific Aim 3. Preliminarily establish in vivo in neonates the range of SSSSO2 to be expected in infants of varying body weight (10-12 LBW neonates and 10-12 VLBW neonates).