Mesoscopic Diffusion-based MRI Histology of Epileptic Human Hippocampi

 描述(由申请人提供)：癫痫是美国第四大最常见的神经疾病，每年的成本约为176亿美元。抗癫痫药物在大多数情况下有效，但不足以控制高达40%的癫痫发作 病人。局灶性癫痫患者可以通过非侵入性测试(EEG、成像研究)或侵入性颅内记录显示发生在特定的大脑区域，是手术切除的候选对象。最常见的癫痫切除手术是前颞叶切除术，包括切除海马体。有很好的证据表明存在发作灶，即癫痫发作起源的区域(通常定义手术干预的目标)，但发作的功能解剖也影响下游区域，并受发作灶的输入调节。了解癫痫发作网络，而不仅仅是发作灶(异常处理汇聚到产生不受控制的活动)，将是改进我们的手术干预和对受影响个体的护理的重要进步。然而，目前的方法，如临床MRI或EEG，以及神经病理学不足以解决癫痫网络。因此，我们建议对手术切除的癫痫患者的海马区进行中尺度磁共振成像，以揭示构成癫痫发作网络的解剖学变化。具体地说，我们的目标是：1)进一步发展基于扩散的MR组织学，以更好地区分细胞层和轴突连接；以及2)实现组织切片的三维重建，以验证轨迹成像重建。主要的目标是提供一种方法，能够更好地描述癫痫网络，以提高我们对MTLE的理解，并通过改进鉴别诊断和手术前计划，对接受海马区切除术的患者产生切实的好处。

 DESCRIPTION (provided by applicant): Epilepsy is the fourth most common neurological disorder in the United States with an approximate cost of $17.6 billion per year. Anti-epileptic medication is effective in most cases, but is insufficient to control seizures in as many as 40% of patients. Patients with focal epilepsy that can be shown to arise from a specific brain region, by noninvasive testing (EEG, imaging studies) or invasive intracranial recordings, are candidates for surgical resection. The most common type of resective epilepsy surgery is anterior temporal lobectomy, which includes removal of the hippocampus. There is good evidence that there is an ictal focus, a region where the seizure originates (typically defining the target for surgical intervention), but the functional anatomy of the seizure also affects regions downstream and is modulated by the input to the ictal focus. Understanding the seizure network, rather than merely the ictal focus (where aberrant processing converges to produce uncontrolled activity), will be an important advance to improve our surgical interventions and care for the affected individuals. Nevertheless current approaches such as clinical MRI or EEG, as well as neuropathology are inadequate to resolve the seizure network. We therefore here propose to investigate the use of mesoscale MRI on surgically-resected epileptic hippocampi to uncover anatomical changes that constitute a seizure network. Specificially, we here aim to: 1) further develop diffusion-based MR histology to better distinguish cell layer and axonal connectivity, as well as 2) implementing a 3 dimensional reconstruction of histological sections to validate tractographic reconstructions. The overarching goal is to provide a method that can lead to a better description of the seizure network to improve our understanding of mTLE with a tangible benefit to patients undergoing a hippocampectomy by improving the differential diagnosis, as well as pre-surgical planning