Separating Intensity Change from Atrophy in Serial MRI

该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，如多序列序列MRI研究所观察到的。具体来说，它旨在研究血管性痴呆和慢性酒精滥用导致的退行性疾病，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声序列MRI中量化。所提出的方法利用基于配准的方法的新发展来估计连续MRI随时间的组织体积损失，作为几何变换。我们建议这些方法可以用来分离组织损失的宏观结构效应和组织强度变化，允许敏感和自动检测组织强度随时间变化的模式。具体来说，这种来自高空间分辨率MRI的几何变换估计可以用作萎缩校正变换，将在较晚时间点获得的多序列MRI数据映射回较早时间点，以创建组织一致的解剖图像对。这些校正后的图像之间的MRI强度差异将提供直接和敏感的高分辨率地图，仅代表组织完整性的区域变化，独立于萎缩（即新的对比图像）。以这一基本处理步骤为基础，我们建议开发一种方法来调查多受试者强度变化模式与适当临床变量变化之间的统计关系。我们还将研究与组织强度变化模式共同分析区域组织损失的方法，以检查白质高强度与皮层、皮层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影像学研究中获得的数据。这些应用旨在帮助区分血管性疾病和其他痴呆症，并更好地了解酒精对大脑的慢性影响和恢复的生物学机制。

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.