White Matter Cytoarchitecture in Preterm Infants

描述（由申请人提供）：该项目的主要目标是开发和应用一种创新的非侵入性体内磁共振成像（MRI）方法，该方法代表了一种新的3D探针，用于研究无髓鞘早产儿大脑皮层下白质（WM）发育中的细胞结构。该工具的创建可以为正常WM纤维束发育和神经元对损伤的反应提供独特的、非侵入性的微结构监测。早产儿的初步结果清楚地证明了基本方法及其对WM损伤的敏感性。所提出的方法需要定量测定WM内使用快速MRI观察到的3D脉冲细胞外液流场（EFF）。值得注意的是，它的应用仅适用于胎龄<36周的早期早产儿组的WM，在无髓鞘WM中含有相对较大的细胞外空间，而目前在胎龄约40周的婴儿或成人的致密髓鞘WM中没有实际观察到。观察到的脉动性EFF是由大脑的心脏（动脉）搏动所引起的，这是研究人员利用的一种理想的内源性生理标记。通过这种方法，通过在快速回波平面动态MRI序列的每个单个元音信号的傅里叶（频率）分析中使用带通滤波器来区分心脏搏动的影响。通过所提出的方法，将根据沿每个正交方向记录的MRI时间序列计算确定每个元音内的EFF的主轴和大小。本研究假设EFF主流量轴平行于局部体素内WM纤维对齐轴，EFF流量大小是WM纤维密度和髓鞘形成程度的函数，即EFF直接揭示了WM细胞结构的亚体素特征。目前还没有一种已知的非侵入性体内技术可以提供如此具体的定量血流信息，请注意，弥散张量MRI包含几种不同的信号贡献，并结合细胞外水。本研究开发的新方法将用于获取和分析每两年15名早产儿和2名足月婴儿的3D MRI数据，并在每种情况下生成3D EFF的3D可视化。结果将与每个病例的3D DT-MRI结果和分割结果一起分析，以证明EFF揭示WM细胞结构定量细节的假设。计划进一步改进方法。

DESCRIPTION (provided by applicant): The main goal of this project is the development and application of an innovative non-invasive in vivo magnetic resonance imaging (MRI) method that represents a new 3D probe of the cytoarchitecture of the developing subcortical white matter (WM) of the unmyelinated preterm human infant brain. The creation of this tool can provide a unique, non-invasive microstructural monitor of both normal WM fiber tract development and the neuronal response to injury. The basic method and its sensitivity to WM injury is clearly demonstrated with preliminary results from preterm infants. The proposed method entails the quantitative determination of the 3D pulsatile extracellular fluid flow field (EFF) within the WM as observed using fast MRI. Its application is, notably, unique to the WM of the early preterm infant group gestational age (GA) approximately <36 weeks, that contains relatively larger extracellular space in unmyelinated WM, and is not now practically observable from the dense myelinated WM of infants GA approximately 40 weeks or adults. Observed pulsatile EFF is forced by the cardiac (arterial pulsation of the brain, an ideal endogenous physiological marker that the investigators exploit. By this method, effects of cardiac pulsation are differentiated by employing a bandpass filter in a Fourier (frequency) analysis of each individual vowel's signal from a fast echo planar dynamic MRI series. By the proposed method, the principal axis and magnitude of the EFF within each vowel will be determined from computations based on MRI time series recorded along each orthogonal direction. It is the hypothesis of this proposed study that the EFF principal flow axis is parallel to the localized intra-voxel WM fiber alignment axis, and the EFF flow magnitude is a function of the WM fiber density and extent of myelination, that is, the EFF directly reveals the subvoxel characteristics of the WM cytoarchitecture. No known non-invasive in vivo technique currently can provide such specific quantitative flow information, noting that Diffusion Tensor MRI contains several different signal contributions combined with that of extracellular water. The new method developed in this study will be applied to acquire and analyze 3D MRI data from 15 preterm infants and two term infants in each of two years, and produce a 3D visualization of the 3D EFF in each case. Results will be analyzed in conjunction with 3D DT-MRI results and segmentation results also obtained in each case to prove the hypothesis that EFF reveals quantitative details of WM cytoarchitecture. Further method refinements are planned.