Brain Axonal Injury in Obstructive Sleep Apnea

描述（由申请人提供）：目的是确定阻塞性睡眠呼吸暂停（OSA）的白质损伤是否由髓鞘或轴突损伤引起，以及这些变化是急性期还是慢性期。OSA是一种常见的进行性综合征，伴有严重的心血管、代谢、记忆、情绪和认知缺陷，可能是由于间歇性缺氧和伴随的灌注改变引起的神经过程受损。髓鞘vs轴索损伤的需要取决于干预神经保护以防止进一步损伤；髓鞘与轴突保护之间存在特定的治疗方案。我们还需要知道这些纤维变化是最近发生的，还是已经存在了很长一段时间，这是通过仅呼吸机支持程序而不是神经保护干预来潜在恢复的必要见解。阻塞性睡眠呼吸暂停同时影响灰质和白质组织；然而，连接灰质结构的白质变化的性质尚不清楚。我们将评估整个大脑白质的变化是急性阶段还是慢性阶段，以及局部纤维是否显示髓鞘或轴突的变化。我们还将评估选定纤维束的纤维特性，根据其他证据，这些纤维束已知有助于心血管，记忆和影响OSA突出的缺陷。研究将使用新诊断的、未接受治疗的、中度至重度OSA受试者以及年龄和性别匹配的对照受试者。以弥散张量成像（DTI）和弥散峰度成像（DKI）为基础的平均弥散系数和平均峰度指数检测白质损伤的病理分期。髓鞘与轴突的变化将通过DTI和dki为基础的轴向扩散率和轴向峰度以及径向扩散率和径向峰度来评估，它们分别显示轴突和髓鞘的变化。我们将同时使用DTI和DKI技术，因为每种方法都具有独特的优势。更详细的髓磷脂评估将通过磁化转移成像（MTI）程序进行。最后，纤维束造影将评估纤维的数量、平均长度和其他纤维特性。我们的初步数据表明，OSA患者的白质损伤主要处于早期阶段，主要由髓鞘的改变引起，尽管在新诊断的患者中也出现了特定部位的轴突改变。阻塞性睡眠呼吸暂停的心血管和神经心理后遗症很严重，在肥胖、老年男性和绝经后妇女中表现突出。防止病理背后的神经变化将大大有助于国家卫生保健。这些研究有可能确定OSA的白质病理变化，从而指出最适合该综合征的神经保护和恢复的干预措施。

DESCRIPTION (provided by applicant): The objective is to determine whether the white matter injury in obstructive sleep apnea (OSA) results from myelin or axonal damage, and whether those changes are in acute or chronic stages. OSA is a common and progressive syndrome accompanied by severe cardiovascular, metabolic, memory, emotional, and cognitive deficits, presumably stemming from compromised neural processes induced by intermittent hypoxia and perfusion changes accompanying the condition. The need to determine myelin vs axonal injury rests with interventions for neuroprotection to prevent further injury; specific treatment protocols exist for myelin vs axonal protection. We also need to know whether these fiber changes are recent, or have been in place for long periods, an insight necessary for potential recovery by ventilatory-only support procedures, rather than neural protection intervention. Both gray and white matter tissues are affected in OSA; however, the nature of the white matter changes which interconnect gray matter structures is unknown. We will assess whether the changes in white matter over the entire brain are in acute or chronic stages, and whether regional fibers are showing changes in myelin or axons. We will also assess fiber characteristics of selected fiber bundles which, from evidence of others, are known to contribute to cardiovascular, memory and affect deficits prominent in OSA. Studies will use recently-diagnosed, treatment naive, moderate-to-severe OSA subjects and age- and gender-matched control subjects. The pathological stage of white matter injury will be examined by diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI)-based mean diffusivity and mean kurtosis indices. Myelin vs axonal changes will be assessed by DTI and DKI-based axial diffusivity and axial kurtosis, and radial diffusivity and radial kurtosis measures, which show axonal and myelin changes, respectively. We will use both DTI and DKI techniques, since each procedure offers unique advantages. More detailed myelin evaluation will be performed by magnetization transfer imaging (MTI) procedures. Finally the number of fibers, mean length, and other fiber characteristics will be evaluated by fiber tractography. Our preliminary data suggest that the white matter injury in OSA principally is in an early stage, and largely arise from changes in myelin, although axonal changes also appeared in particular sites in newly-diagnosed patients. The cardiovascular and neuropsychological sequelae of OSA are severe, and are prominent in targets for the condition, obese, older males and post-menopausal women. Protection against the neural changes underlying the pathologies would significantly contribute to national health care. These studies have the potential to determine white matter pathological changes in OSA, and thus point to interventions most appropriate for neural protection and recovery in the syndrome.]