Prediction of seizure lateralization and postoperative outcome through the use of deep learning applied to multi-site MRI/DTI data: An ENIGMA-Epilepsy study

摘要 癫痫是一种毁灭性的神经系统疾病，影响全球6500万人。约 三分之一的患者对抗癫痫药物治疗没有反应，需要进行彻底的诊断。 检查结构神经影像学在局灶性脑梗死患者的诊断评价中起着关键作用。 癫痫，在许多患者中识别出与癫痫发作病灶一致的可见病变。然而，20- 40%的患者MRI表现正常，而且这个数字似乎还在增长。结果是 对非侵入性、定量和非侵入性的识别细微的灰色和白色物质网络变化的兴趣增加 MRI，包括结构MRI（sMRI）和扩散张量成像（DTI），可以帮助描绘 癫痫网络不幸的是，从患者的sMRI/DTI数据中选择最佳特征的方法 能够解决这些临床挑战的癫痫患者尚未开发。至少有两 限制这一领域进展的主要障碍。首先，样本量不足， 局灶性癫痫患者的可靠分类算法，导致可重复的结果。的 高成本的数据收集--很少有研究扫描超过50-60名患者--导致研究的效力不足 他们的发现往往无法复制，不能充分模拟混淆。二、高计算性 以前的需求限制了使用复杂的特征选择（即，机 学习; ML）算法在临床环境中的应用。 一项新的大规模数据倡议（即，ENIGMA-癫痫）从全球24个地点获得， 消除这些障碍，并允许开发和验证创新的数据驱动方法 旨在优化MRI数据在癫痫评估中的使用。在这项资助中，我们将利用数据 通过ENIGMA-Epilepsy收集-一种新的，具有成本效益的，创新的全球方法， 通过整合领先的癫痫中心的资源、数据、资本基础设施和人才， 来自全球14个国家（2，149名患者和1，727名健康对照MRI/DTI数据集）。我们将 还利用ML的新发展（即，深度学习）和基于网络的建模（即，连接体 的方法），并测试这些新的方法是否提高了分类精度相对于 更简单、用户驱动的模型。我们的主要目标是测试我们的深度学习方法的能力（即， 致密神经网络）以偏侧化癫痫发作病灶。在一个探索性的目标，我们将测试我们的能力， 模型来预测术后癫痫发作的结果。ENIGMA的协调方法将使我们能够测试我们的 在超过24个数据集中，不同的年龄，种族，发病年龄，癫痫持续时间和手术结果。 这项R-21申请通过引入一种高度- 动力设计，并直接与NINDS的2014年癫痫基准，鼓励 鉴定用于评估或预测癫痫患者的治疗反应的生物标志物。

ABSTRACT Epilepsy is a devastating neurological illness that affects 65 million people worldwide. Approximately one-third of patients affected do not respond to antiepileptic drug therapy and require a thorough diagnostic work-up. Structural neuroimaging plays a pivotal role in the diagnostic evaluation of patients with focal epilepsy, identifying visible lesions in many patients that often coincide with the seizure focus. However, 20- 40% of patients have normal-appearing MRIs and this number appears to be growing. As a result, there is increased interest in identifying subtle gray and white matter network changes on non-invasive, quantitative MRI, including structural MRI (sMRI) and diffusion tensor imaging (DTI), that can help to delineate the epileptogenic network. Unfortunately, methods for selecting optimal features from sMRI/DTI data in patients with epilepsy that can address these clinical challenges have not been developed. There are at least two major barriers that have limited progress in this field. First, sample sizes have been insufficient to develop reliable classification algorithms in patients with focal epilepsy that lead to reproducible findings. The high cost of data collection - few studies scan more than 50-60 patients - has led to underpowered studies whose findings often fail to replicate and cannot adequately model confounds. Second, high computational demands have previously limited the feasibility of using sophisticated, feature-selection (i.e., Machine Learning; ML) algorithms in clinical settings. A new, large-scale data initiative (i.e., ENIGMA-epilepsy) acquired from 24 sites world-wide is now lifting these barriers and allowing for the development and validation of innovative data-driven approaches aimed at optimizing the use of MRI data in the evaluation of epilepsy. In this grant, we will leverage data collected through ENIGMA-Epilepsy—a new, cost-effective, innovative global approach that unblocks the power logjam by merging resources, data, capital infrastructure and talents of leading epilepsy centers from 14 countries across the world (2,149 patient and 1,727 healthy control MRI/DTI datasets). We will also leverage new developments in ML (i.e., deep learning) and network-based modeling (i.e., connectome- based approaches) and test whether these novel approaches improve upon classification accuracy relative to simpler, user-driven models. Our primary aim will be to test the ability of our deep learning approach (i.e., dense neural networks) to lateralize the seizure focus. In an exploratory aim, we will test the ability of our model to predict post-operative seizure outcomes. ENIGMA's harmonized approach will allow us to test our approach in over 24 datasets, diverse in age, ethnicity, age of onset, epilepsy duration, and surgical outcomes. This R-21 application addresses NIH's call for more reproducible studies by introducing a highly- powered design, and is directly aligned with NINDS's 2014 Epilepsy Benchmarks, which encourage the identification of biomarkers for assessing or predicting treatment response in patients with epilepsy.