Diffuse Optics for Pediatric Hydrocephalus Management

摘要 脑积水是一种脑脊液(CSF)生理紊乱，导致进行性脑积水扩张 脑室和颅内压升高。每1000名活产儿中就有1-2人感染它，使其成为 在美国，由儿科神经外科医生治疗的最常见疾病。通常的治疗方法是神经外科分流术。 放置以转移脑脊液和减轻升高的颅内压。关于何时以及是否干预的决策主要是 基于脑室扩大的影像证据和临床判断。然而，脑室大小是一个 颅内压升高和脑缺血的次佳替代物。事实上，大约15%的经历颅内压升高的患者 没有脑室增大的CT影像证据。国际比较研究与国际比较的不一致关系 脑室大小增加了长期颅内高压、脑缺血和继发性脑损伤的风险。 发生在外科治疗之前。 该方案的主要目标是：(1)开发和验证一种新的漫反射光学方法，用于非 有创性检测颅内压升高和脑缺血；以及(2)使用多模式纵向漫反射光学 测量脑血流动力学以确定导致颅内压升高的危险因素。漫反射光学 技术提供了丰富的多模式脑血流动力学数据，连续、非侵入性地 在床边。具体地说，漫反射光学技术可以测量脑血流量(CBF)、氧合指数 萃取率(OEF)和氧代谢(CMRO2)。首席调查员(PI)也开创了 一种新的评估颅内压升高的光学方法。该方法是基于对大脑的测量 具有近红外光强度关联的临界关闭压力(CrCP)。Crcp是icp和active的总和。 小动脉壁张力，它的名字反映了当动脉供血时小动脉关闭和脑血流量停止的概念 压力降至CRCP阈值以下。 这项建议将使用漫反射光学来测量脑生理过程中的纵向血流动力学 大量儿童的进行性脑室扩大(目标1)。多模式数据将与 侵入性的术中颅内压测量：(1)确定术前颅内压升高的危险因素； (2)CRCP升高作为颅内压升高的指标的有效性。漫反射光学神经监测将进一步 建立儿童高颅压模型与侵入性神经监测的比较 脑缺血和颅内压升高的光学生物标志物(目标2)。在目标3中，漫反射光学将转换为 诊断较大儿童的分流失败，40%的患者在2岁内发生分流失败。 该提案的物理科学家和临床医生组成的跨学科团队提供了弥漫领域的领先专业知识 光学、仔猪模型研究和脑积水护理。最终，通过允许手术干预的时机 为了针对每个患者进行优化和个性化，漫反射光学系统有望显著减少或防止 脑积水造成的继发性脑损伤。

ABSTRACT Hydrocephalus is a disorder of cerebral spinal fluid (CSF) physiology that results in progressive expansion of cerebral ventricles and elevated intracranial pressure (ICP). It affects 1-2 of every 1000 live births, making it the most common disease treated by pediatric neurosurgeons in the US. The usual treatment is neurosurgical shunt placement to divert CSF and relieve elevated ICP. Decision-making about when and if to intervene is mostly based on imaging evidence of enlarged ventricular size and clinical judgement. Ventricular size, however, is a suboptimal surrogate of elevated ICP and ischemia. Indeed, roughly 15% of patients experiencing elevated ICP do not have CT imaging evidence of increased ventricle size. The inconsistent relationship between ICP and ventricular size increases the risk of prolonged intracranial hypertension, ischemia, and secondary brain damage occurring prior to surgical treatment. The primary goals of this proposal are to: (1) develop and validate a novel diffuse optical approach for non- invasive detection of elevated ICP and cerebral ischemia; and (2) use multimodal longitudinal diffuse optical measures of cerebral hemodynamics to identify risk factors for the development of elevated ICP. Diffuse optics techniques provide a wealth of multimodal cerebral hemodynamic data continuously, non-invasively, and at the bedside. Specifically, diffuse optics technology can measure indices of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and oxygen metabolism (CMRO2). The principal investigator (PI) has also pioneered a novel optical approach for assessment of elevated ICP. The approach is based on measurement of cerebral critical closing pressure (CrCP) with near-infrared light intensity correlations. CrCP is the sum of ICP and active arteriolar wall tension, and its name reflects the notion that arterioles close and CBF ceases when arterial blood pressure falls below the CrCP threshold. This proposal will use diffuse optics to measure longitudinal hemodynamics of brain physiology during progressive ventricular enlargement in a large group of children (Aim 1). The multimodal data will be related to invasive intraoperative ICP measurements for: (1) identification of preoperative risk factors of elevated ICP; and (2) validation of elevated CrCP as a metric of elevated ICP. Diffuse optical neuro-monitoring will further be compared to invasive neuro-monitoring in a pediatric piglet model of intracranial hypertension to develop optical biomarkers of ischemia and elevated ICP (Aim 2). In Aim 3, diffuse optics will be translated for diagnosing shunt failure in older children, which occurs in 40% of patients within 2 years of age. The proposal’s interdisciplinary team of physical scientists and clinicians provides leading expertise in diffuse optics, piglet model research, and hydrocephalus care. Ultimately, by allowing the timing of surgical intervention to be optimized and individualized for each patient, diffuse optics promises to substantially reduce or prevent secondary brain damage from hydrocephalus.