Motion Robust Mapping of Human Brain Microstructure and Macrostructure In-Utero

描述（由申请人提供）：准确绘制胎儿和早产儿大脑发育的正常和异常模式是早期发现发育障碍以及了解外部因素如何影响早期大脑发育的关键因素。在我们之前的资助期间，我们开发并应用了新的胎儿MRI运动校正和重建技术，以生成子宫内正常人脑生长的第一张3D和4D图，并识别脑室肿大（VM）的早期皮质折叠异常，这是最常见的胎儿大脑异常。这些发现提出了一个问题，即组织微观结构中是否存在可测量的扰动，以及这些更大规模的解剖差异。这种变化可以提供比单纯折叠更清晰的皮质损伤指标。因此，在这项更新中，我们建议开发新技术，允许在非镇静胎儿研究中普遍使用弥散MRI方法。这些以前用于成人和儿童的方法，可以为胎儿脑组织的微观结构特性提供一个独特的新窗口。然而，该技术对实际的全脑胎儿成像有一个重要的限制：它使用重复采集，在磁共振信号的细微变化中提供感兴趣的测量。胎儿头部在扫描仪内的运动，由于解剖结构和扫描仪之间关系的变化，会干扰测量位置、方向和信号水平。我们的第一个目标是开发一种新的统一框架，可以利用图像采集物理来校正扩散加权成像中的信号电平和测量几何形状。然后，我们将开发互补的分析工具，可以解释胎儿头部运动引起的功能和扩散数据中不同的空间和时间样本密度。我们将使用这些技术对正常胎儿的横切面进行成像，并构建胎儿大脑结构和微观结构测量的规范时空图谱，涵盖首次临床MRI扫描的关键年龄和随后的皮质折叠时期。最后，我们将使用相同的技术对脑室肿大胎儿临床组的数据进行成像和分析，目的是检测早期微观结构差异，这些差异与我们之前在脑室肿大胎儿中发现的皮质结果有关。这个项目作为一个整体，除了这种常见的情况外，还有许多更广泛的应用，这将是理解大脑皮层功能专业化与胎儿和早产儿大脑解剖结构之间关系的重要一步。

DESCRIPTION (provided by applicant): Accurate mapping of normal and abnormal patterns of brain development in fetuses and premature neonates is a key factor in early detection of developmental disorders as well as understanding how external factors can influence early brain growth. In our previous funding period we developed and applied novel fetal MRI motion correction and reconstruction techniques to produce the first 3D and 4D maps of normal human brain growth in-utero and to identify early cortical folding abnormalities in ventriculomegaly (VM), the most commonly identified fetal brain abnormality. These findings pose the question of whether measureable perturbations in tissue microstructure may be present along with these larger scale anatomical differences. Such changes could provide a clearer indicator of cortical damage than simply folding alone. In this renewal we therefore propose to develop new techniques that allow the general use diffusion MRI methods in un-sedated fetal studies. These methods, previously used in adults and children, can provide a unique new window into microstructural properties of fetal brain tissue. However, the technique has an important limitation for practical whole brain fetal imaging: it makes use of repeated acquisitions where subtle changes in MR signal provide the measure of interest. Fetal head motion within the scanner can perturb measurement location, orientation and signal level due to the changing relationship between the anatomy and scanner. Our first aim is to develop a novel unified framework that can make use of image acquisition physics for correction of both signal level and measurement geometry in diffusion weighted imaging. We will then develop complementary analysis tools that can account for the varying spatial and temporal sample density in the functional and diffusion data arising from fetal head motion. We will use these techniques to image a cross-section of normal fetuses and construct a normative spatio-temporal atlas of combined structural and micro-structural measurements in the fetal brain covering the critical age of first clinical MRI scan and the following period of cortical folding. Finally, we will use te same techniques to image and analyze data from a clinical group of fetuses with ventriculomegaly with the aim of detecting early micro-structural differences that are related to our previous cortical findings in fetuses exhibiting VM. The project as a whole has many wider applications beyond this common condition and would be a major step in understanding how functional specialization in the cortex relates to brain anatomy in both fetuses and premature neonates.