Neurometabolic Assessment of Obstructive Sleep Apnea by MRI

描述（由申请人提供）：阻塞性睡眠呼吸暂停（OSA）是一种由于睡眠期间上呼吸道无法保持通畅而导致的疾病。OSA与广泛的合并症相关，包括高血压、心血管疾病和中风，以及显著的认知功能障碍。这种疾病的心脏和神经血管后果被认为是由周期性的夜间缺氧-复氧循环引起的。虽然对自主呼吸暂停（屏气）的正常生理反应通过降低心输出量、外周血管收缩和中枢血管舒张维持脑氧输送，但在OSA中，继发于反复夜间呼吸暂停事件期间经历的慢性间歇性缺氧的这种反应变得迟钝。 基于我们最近开发的定量脑氧代谢率（CMRO 2）研究脑氧代谢的技术，我们建议进一步开发和应用一种新的MRI方法来研究OSA的神经代谢-神经血管后果。该方法的关键是通过测量磁化率来量化静脉血氧饱和度，磁化率与脱氧血红蛋白浓度成比例，并且沿着脑血流量，产生CMRO 2。由于呼吸暂停是一种混合的高碳酸血症/缺氧刺激，没有达到稳态，捕捉生理反应需要高的时间分辨率。为了满足这一需求，研究人员开发了一种大大加速的CMRO 2测量技术，并显示了其在3 T下解决健康受试者中CMRO 2响应于自主呼吸暂停的动态变化的能力，并在宽口径1.5T系统上证明了其在OSA患者中的可行性。我们认为屏气模式是一个合适的模型，以评估神经血管反应的阻塞性睡眠呼吸暂停，因为它反映了间歇性缺氧的睡眠呼吸暂停。在这个项目中，我们假设OSA患者的神经代谢谱受损，包括基线时较低的CMRO 2和对屏气挑战的迟钝的神经代谢反应。此外，我们假设持续气道正压通气（CPAP）治疗将减轻这种异常反应。这些假设将在四个具体目标中得到解决，包括：（1）进一步开发和验证该方法;（2）应用于OSA患者及其对照组的队列;（3）评估CPAP在OSA患者中的作用。 目标2的队列;以及（4）在一个患者子集中进行探索性睡眠研究，以比较清醒的意志性和自发性夜间呼吸暂停的神经代谢作用。提出的神经代谢MRI测量方法最终可用于识别OSA神经认知和神经血管后遗症风险最大的患者，并预测CPAP治疗的疗效。此外，该方法可以允许将OSA患者分类为更具侵入性的治疗方法，并为受这种日益流行的疾病影响的患者提供改进的风险评估手段。

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is a disorder resulting from failure of the upper airway to maintain patency during sleep. OSA is associated with extensive comorbidities, including hypertension, cardiovascular disease and stroke, as well as with significant cognitive dysfunction. The cardio- and neurovascular consequences of the disease are believed to result from periodic nocturnal hypoxia-reoxygenation cycles. While the normal physiologic response to volitional apnea (breath-holding) maintains cerebral oxygen delivery via reduced cardiac output, peripheral vasoconstriction, and central vasodilation, this response becomes blunted in OSA secondary to chronic intermittent hypoxia experienced during repeated nocturnal apneic events. Building on our recent work in developing techniques for quantifying the cerebral metabolic rate of oxygen consumption (CMRO2) to investigate brain oxygen metabolism, we propose to further develop and apply a new MRI method to study the neurometabolic-neurovascular consequences of OSA. Key to the method is the quantification of venous blood oxygen saturation from a measurement of magnetic susceptibility, which scales with deoxyhemoglobin concentration and which, along with cerebral blood flow, yields CMRO2. Since apnea represents a mixed hypercapnic/hypoxic stimulus for which no steady-state is reached, capturing the physiologic response requires high temporal resolution. Responding to this need, the investigators have developed a vastly accelerated CMRO2 measurement technique and shown its ability to resolve dynamic changes in CMRO2 in response to volitional apnea in healthy subjects at 3T and demonstrated its feasibility in OSA patients on a wide-bore 1.5T system. We posit that the breath-hold paradigm is a suitable model to evaluate the neurovascular response in OSA as it reflects the intermittent hypoxia experienced by apneics during sleep. In this project we hypothesize that the neurometabolic profiles in patients with OSA are impaired, including lower CMRO2 at baseline and blunted neurometabolic response to a breath-hold challenge. Further, we hypothesize that continuous positive airway pressure (CPAP) treatment will alleviate this abnormal response. These hypotheses will be addressed in four specific aims, comprising: (1) further development and validation of the method; (2) application to a cohort of OSA patients and their controls; (3) evaluation of the effect of CPAP in the cohort of Aim 2; and (4) an exploratory sleep study in a subset of patients to compare the neurometabolic effects of wakeful volitional and spontaneous nocturnal apnea. The proposed neurometabolic MRI measures could ultimately serve to identify patients at greatest risk of the neurocognitive and neurovascular sequelae from OSA, and to predict the efficacy of CPAP therapy. Further, the method could allow triaging of OSA patients to more invasive treatment approaches and provide an improved means for risk assessment in those affected by this increasingly prevalent disorder.