Separating Intensity Change from Atrophy in Serial MRI

这个项目将开发新的方法来灵敏地检测和分析神经退行性疾病的MRI强度变化，正如多序列系列MRI研究所观察到的那样。具体地说，它旨在研究血管性痴呆和慢性酒精滥用所致的退行性疾病，其中白质完整性的变化模式以及相关的白质和灰质体积损失可以在多回波序列MRI中定量。提出的方法利用基于配准的方法的新发展来估计组织体积随时间的损失，作为一种几何变换。我们认为，这些方法可以用来分离组织丢失的宏观结构效应和组织强度变化，从而能够灵敏地和自动地检测组织强度随时间变化的模式。具体地说，从高空间分辨率MRI导出的这种几何变换估计可以被应用为萎缩校正变换，以将在较晚时间点获取的多序列MRI数据映射回较早时间点，以创建组织一致的解剖图像对。这些校正图像之间的MRI强度差异将提供直接和灵敏的高分辨率地图，仅代表组织完整性的局部变化，与萎缩无关(即新的对比度图像)。以这一基本处理步骤为基础，我们建议开发统计方法来研究强度变化的多受试者模式与适当的临床变量变化之间的关系。我们还将研究联合分析局部组织丢失与组织强度变化模式的方法，以检查白质高强度与皮质、皮质下脑和潜在白质萎缩模式之间的关系。在优化方法后，我们将应用这些新技术来分析独立资助的血管性痴呆、慢性酒精滥用及其康复的系列成像研究中获得的数据。这些应用旨在帮助将血管疾病与其他痴呆症区分开来，并更好地了解酒精对大脑的慢性影响和康复的生物学机制。

This project will develop new methodological approaches to the sensitive detection and analysis of MRI intensity change in neurodegenerative diseases, as observed by multi-sequence serial MRI studies. Specifically it is aimed at the study of degenerative conditions as a consequence of vascular dementia and chronic alcohol abuse, in which patterns of change in white matter integrity and associated white and gray matter volume loss are quantifiable in multi-echo serial MRI. The proposed method makes use of new developments in registration-based approaches to estimating tissue volume loss over time from serial MRI, as a geometric transformation. We propose that these methods can be used to separate the macrostructural effects of tissue loss from tissue intensity change, allowing sensitive and automated detection of patterns of tissue intensity change over time. Specifically, such geometric transformation estimates, derived from high spatial resolution MRI, can be applied as an atrophy- correcting transformation to map multi-sequence MRI data acquired at a later time point back to an earlier time point, to create a tissue-consistent pair of anatomical images. MRI intensity differences between these corrected images will then provide a direct and sensitive high resolution map representing solely regional change in tissue integrity, independent of atrophy (i.e. a novel contrast image). Using this fundamental processing step as a basis, we propose to develop methodology to investigate statistically the relationship between multi-subject patterns of intensity change and changes in appropriate clinical variables. We will also investigate methods of co-analyzing regional tissue loss with patterns of tissue intensity, change, to examine the relationship between white matter hyper-intensity and patterns of atrophy in the cortex, subcortical brain, and underlying white matter. After optimizing methodology, we will apply these new techniques to analyze data acquired in independently funded serial imaging studies of vascular dementia, chronic alcohol abuse and recovery thereof. These applications are aimed at helping distinguish vascular disease from other dementias and at a better understanding of the biological mechanisms underlying the chronic effects of alcohol and recovery on the brain.