Novel method for classifying BOLD response mechanisms in focal epilepsy

项目摘要 对于多达93.3万患有顽固性癫痫的美国人来说，神经外科手术是最可行的 解药。这种手术依赖于准确的定位来精确切除癫痫发作的病灶，但目前 方法的成功率仅为~50%-60%。使用了各种方法，但为了提高成功率， 需要改进方法来使这些区域本地化。产生发作间期癫痫的脑区 放电(IED)被称为刺激区，与癫痫的起源有关。简易爆炸装置可以通过脑电检测到， 这是手术前评估的关键临床工具，但仅凭脑电不足以诊断 定位简易爆炸装置原点区域和避免区分实际和图像唯一性问题 虚假的IED诱发电流源。通过在同步记录中结合fMRI和EEG，大脑区域 表现出IED诱发的血氧水平依赖(BOLD)反应，这是神经元的间接指标 激活，可以以高空间分辨率定位，并且建立的标准临床方案使 用这项技术定位癫痫发作灶。然而，一个技术问题限制了这一成本的应用- 有利的、广泛可用的方法。临床EEG-fMRI标测方案的核心是严格的和非 可解释的血流动力学反应函数(HRF)，允许表征局部神经血管 功能磁共振成像的IED依赖回归模型的耦合和表示。目前，HRF计算假定 简易爆炸装置会导致局部脑血流量增加(BOLD激活)，但IED也会引起非典型的BOLD 反应，例如，某些大脑区域的失活，混淆了分析，从而阻碍了有效的脑电- FMRI在许多患者中的应用。为了克服这一障碍并使EEG-fMRI能够更多、更准确地用于 我们的目标是：1)确定IED诱发的BOLD的生物物理机制 癫痫的反应；2)确定它们的细胞底物；3)开发一种自动图像引导 按产地类型对它们进行分类的方法。我们的中心假设，得到我们初步发现的支持，是 这3个机制单独或结合在一起，促成了非典型大胆反应的出现 癫痫脑与经典充血反应区：1)IED介导的意外干扰 静息状态网络；2)血液窃取/泄漏效应；3)局部血管/代谢脱钩。我们的 初步研究结果进一步表明，通过分析来区分大胆反应机制是可行的。 脑电-功能磁共振成像数据，这将允许有效的定位病灶。解决复杂的神经生理学问题 和计算问题，我们建立了一个独特的多学科/机构合作 在佛罗里达国际大学之间。和耶鲁大学。团队，与两家南佛罗里达医院进行互动。我们 将使用一种新的、与翻译相关的大鼠癫痫模型和创新策略来进行EEG-fMRI分析。 验证我们的想法将允许翻译和广泛的、现场推进的成本- 有效/非侵入性脑电-功能磁共振成像方式，改善人类癫痫患者的手术结果。

Project Summary For the up to 933,000 epileptic Americans who have intractable epilepsy, neurosurgery is the most feasible cure. Such surgery relies upon accurate localization for precise resection of seizure-onset foci, but current approaches yield success rates of only ~50-60%. Various methods are used, but to increase success rates, improved approaches are needed for localizing these zones. Brain areas generating interictal epileptic discharges (IEDs), known as irritative zones, are associated with seizure origin. IEDs can be detected by EEG, which is a key clinical tool for pre-surgical evaluation, but EEG alone has insufficient spatial resolution for localizing IED origin zones and image-uniqueness problems that preclude discrimination of actual from spurious IED-evoked current sources. By combining fMRI with EEG in concurrent recordings, brain areas exhibiting IED-evoked blood oxygen level-dependent (BOLD) responses, an indirect indicator of neuronal activation, can be localized with high spatial resolution, and an established standard clinical protocol enables localization of seizure-onset foci by this technique. However, a technical problem limits application of this cost- advantageous, widely-available approach. Central to the clinical EEG-fMRI mapping protocol are rigid and non- interpretable hemodynamic response functions (HRFs) that permit characterization of local neurovascular coupling and representation of fMRI by IED-dependent regressors. Currently, HRF computation assumes that IEDs cause local cerebral blood flow increases (BOLD activations), but IEDs also evoke atypical BOLD responses, e.g. deactivations, in certain brain regions, confounding analysis and thus barring effective EEG- fMRI use in many patients. To overcome this barrier and enable increased, more accurate use of EEG-fMRI for seizure-onset zone mapping, our aims are to: 1) identify the biophysical mechanisms of IED-evoked BOLD responses in epilepsy; 2) determine their cellular substrates; and 3) develop an automated image-guided method for classifying them by origin type. Our central hypothesis, supported by our preliminary findings, is that 3 mechanisms, alone or in combination, contribute to the emergence of atypical BOLD responses in the epileptic brain together with classical hyperemic responding areas: 1) unexpected IED-mediated interruptions of the resting state network; 2) blood stealing/leaking effects; and 3) local vascular/metabolic decoupling. Our preliminary findings further indicate that it is feasible to discriminate BOLD response mechanisms by analyzing EEG-fMRI-derived data, which will permit effective localization of foci. To solve the complex neurophysiological and computational problems involved, we established a unique multi- disciplinary/institutional collaboration between Florida International Univ. and Yale Univ. teams, with interactions with 2 South-Florida hospitals. We will use a novel, translationally-relevant rat epilepsy model and innovative strategies for EEG-fMRI analysis. Validating our ideas will permit translation and widespread, field-advancing clinical implementation of cost- effective/noninvasive EEG-fMRI imaging modality, improving surgical outcomes in human epilepsy patients.