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检测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，以产生子宫内正常人脑生长的第一个3D和4D地图，并识别脑室扩大（VM）中的早期皮质折叠异常，这是最常见的胎儿脑异常。这些发现提出了一个问题，即组织微观结构中的可测量扰动是否可能沿着这些较大尺度的解剖学差异。这种变化可以提供一个更清晰的指标，皮质损伤比简单的折叠单独。因此，在本次更新中，我们建议开发新技术，允许在未镇静的胎儿研究中普遍使用弥散MRI方法。这些方法，以前用于成人和儿童，可以提供一个独特的新窗口到胎儿脑组织的微观结构特性。然而，该技术对于实际的全脑胎儿成像具有重要的限制：它利用重复采集，其中MR信号的细微变化提供感兴趣的测量。由于解剖结构和扫描仪之间的关系发生变化，扫描仪内的胎儿头部运动可能会干扰测量位置、方向和信号水平。我们的第一个目标是开发一种新的统一的框架，可以利用图像采集物理扩散加权成像的信号水平和测量几何校正。然后，我们将开发互补的分析工具，可以解释不同的空间和时间的样本密度的功能和扩散数据所产生的胎儿头部运动。我们将使用这些技术来成像正常胎儿的横截面，并构建一个规范的时空图集的组合结构和微结构测量胎儿大脑覆盖的关键年龄的第一次临床MRI扫描和以下时期的皮质折叠。最后，我们将使用相同的技术来成像和分析来自脑室扩大胎儿临床组的数据，目的是检测与我们先前在表现VM的胎儿中的皮质发现相关的早期微结构差异。该项目作为一个整体有许多更广泛的应用超出了这种常见的条件，并将是一个重要的一步，了解如何在大脑皮层功能专业化与大脑解剖在胎儿和早产儿。

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.