Brain Axonal Injury in Obstructive Sleep Apnea

描述(申请人提供)：目的是确定阻塞性睡眠呼吸暂停(OSA)中的白质损伤是由髓鞘损伤还是轴突损伤所致，以及这些变化是处于急性阶段还是慢性阶段。阻塞性睡眠呼吸暂停综合征是一种常见的进行性综合征，伴有严重的心血管、代谢、记忆、情绪和认知障碍，推测是由于间歇性低氧和伴随疾病的血流灌注变化导致的神经过程受损所致。确定髓鞘和轴突损伤的必要性在于神经保护的干预措施，以防止进一步的损伤；髓鞘和轴突保护的具体治疗方案已经存在。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，这是通过仅通过呼吸机支持程序而不是神经保护干预来实现潜在恢复所必需的洞察力。在阻塞性睡眠呼吸暂停综合征中，灰质和白质组织都会受到影响；然而，白质变化的性质尚不清楚，这些白质变化连接着灰质结构。我们将评估整个大脑白质的变化是处于急性阶段还是慢性阶段，以及区域纤维是否显示出髓鞘或轴突的变化。我们还将评估选定纤维束的纤维特征，从其他方面的证据来看，这些纤维束已知有助于OSA中突出的心血管、记忆和影响缺陷。研究将使用最近诊断的、治疗天真的、中度到重度的阻塞性睡眠呼吸暂停患者和年龄和性别匹配的对照组受试者。脑白质损伤的病理分期采用扩散张量成像(DTI)和基于平均弥散张量成像(DKI)的平均峰度指数(DKI)。髓鞘与轴突的变化将通过DTI和基于DKI的轴向扩散系数和轴向峰度以及径向扩散系数和径向峰度的测量来评估，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，因为每个过程都有独特的优势。更详细的髓鞘评估将通过磁化转移成像(MTI)程序进行。最后，纤维数量、平均长度和其他纤维特性将通过纤维束成像进行评估。我们的初步数据表明，OSA的白质损伤主要处于早期阶段，主要是由于髓鞘的变化，尽管在新诊断的患者中也有特定部位的轴突变化。阻塞性睡眠呼吸暂停综合征的心血管和神经心理后遗症很严重，尤其是肥胖、老年男性和绝经后女性。针对潜在病理变化的神经保护将对国家医疗保健做出重大贡献。这些研究有可能确定阻塞性睡眠呼吸暂停综合征的白质病理变化，从而指出最适合阻塞性睡眠呼吸暂停综合征的神经保护和康复的干预措施。]

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.]