Diffuse Optics for Pediatric Hydrocephalus Management

摘要 脑积水是一种脑脊髓液（CSF）生理学障碍，导致脑组织进行性扩张， 脑室和颅内压升高（ICP）。它影响每1000个活产中的1 - 2个，使其成为世界上 在美国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CSF并缓解升高的ICP。关于何时以及是否进行干预的决策主要是 基于脑室扩大的影像学证据和临床判断。然而，心室大小是 ICP升高和局部缺血的次优替代物。事实上，大约15%的ICP升高患者 没有脑室增大的CT成像证据。国际比较方案与 脑室大小增加了长期颅内高压、缺血和继发性脑损伤的风险 发生在手术治疗之前。 该方案的主要目标是：（1）开发和验证一种新的漫射光学方法， ICP升高和脑缺血的侵入性检测;和（2）使用多模式纵向扩散光学 测量脑血流动力学，以确定颅内压升高的危险因素。漫射光学 技术提供了丰富的多模态脑血流动力学数据连续，非侵入性，并在 床边具体地，漫射光学技术可以测量脑血流量（CBF）、氧含量、脑血流速度、脑血流速度等指标。 提取分数（OEF）和氧代谢（CMRO 2）。首席研究员（PI）也开创了 一种新的光学方法来评估颅内压升高。该方法是基于测量大脑 临界关闭压力（CrCP）与近红外光强度的相关性。CrCP是ICP和活性的总和 小动脉壁张力，其名称反映了当动脉血 压力福尔斯降至CrCP阈值以下。 该建议将使用漫射光学来测量脑生理学的纵向血流动力学， 在一个大的儿童群体中进行性心室扩大（目标1）。多模态数据将与 有创术中ICP测量：（1）识别ICP升高的术前风险因素;以及 (2)验证升高的CrCP作为升高的ICP的度量。扩散光学神经监测将进一步 与有创神经监测相比，在小儿颅内高压仔猪模型中， 缺血和ICP升高的光学生物标志物（目的2）。在目标3中，漫射光学将被转换为 诊断年龄较大儿童的分流失败，2岁以内的患者中有40%发生分流失败。 该提案的物理科学家和临床医生的跨学科团队提供了扩散方面的领先专业知识 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，漫射光学有望大大减少或防止 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.