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克)和低出生体重(LBW；1500-2499克)婴儿患长期脑病的风险增加。在美国每年出生的6.3万名极低出生体重婴儿中，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着重要作用。不幸的是，低出生体重儿和极低出生体重儿的脑血管系统维持充足脑血流的能力尚不清楚。虽然使用经典的Kty-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、具有挑衅性的临床研究，但目前还没有简单、重复和非侵入性地监测或测量LBW或VLBW婴儿脑循环充分性的技术。我们的初创公司NONINVISH Six最近在极低出生体重和低出生体重婴儿身上展示了光声技术可以通过开放的前颧门轻松、准确、直接地无创测量上矢状窦(SSSSO2)的脑静脉血氧饱和度。SSSSO2衡量的是脑血流量满足脑氧量的能力；在成人创伤性脑损伤患者中，脑静脉血饱和度低于50%，提示脑血流量不满足脑氧量，具有不祥的预后意义。在建立了新生儿光声SSS监测的概念验证后，我们现在建议在第一阶段应用中改进这项技术，作为实现新生儿脑血流间歇测量和连续监测设备商业化的重要一步。在这个第一阶段的提案中，基于我们的实验室原型，NoninvSix将与德克萨斯大学医学分部以及工程设计公司库珀咨询服务公司(CCS)合作，迭代地设计和构建临床原型新生儿界面和用户界面，并在分娩后的新生儿中进行测试。我们将通过以下具体目标来生产和测试临床原型(图1在创新部分)：具体目标1.为我们的非侵入性光声监测仪开发一个临床原型患者界面，该界面将准确地测定新生儿中的SSSSO2。具体目的2.为我们的非侵入性光声监测仪开发一个临床用户界面，以便于在新生儿重症监护病房间歇性或连续地快速评估新生儿的SSSSO2。具体目的3.在新生儿体内初步建立不同体重的婴儿(10-12 LBW和10-12 VLBW)预计的SSSSO2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).