White Matter Cytoarchitecture in Preterm Infants

描述(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活体磁共振成像(MRI)方法，该方法代表了一种新的3D探测器，可以探测无髓早产儿大脑皮质下白质(WM)发育中的细胞结构。这一工具的发明可以提供一种独特的、非侵入性的微结构监测，既可以监测正常的WM纤维束发育，也可以监测神经元对损伤的反应。早产儿的初步结果清楚地表明了基本方法及其对西医损伤的敏感性。该方法需要定量测定WM内的3D脉动细胞外流场(EFF)，如使用快速MRI所观察到的。值得注意的是，它的应用是独一无二的早期早产儿组胎龄(GA)约&lt；36周，这包含了相对较大的细胞外空间的无髓WM，并不是现在实际观察从密集的髓鞘白质约40周或成人GA。观察到的搏动性EFF是由心脏(大脑的动脉搏动)强迫的，这是研究人员利用的一种理想的内源性生理标记。该方法通过对快速回波平面动态磁共振序列中的每个元音信号进行傅立叶(频率)分析，使用带通滤波来区分心脏跳动的影响。通过该方法，每个元音内的EFF的主轴和大小将通过沿每个垂直方向记录的MRI时间序列的计算来确定。本研究假设EFF主流轴与局部体素内WM纤维对齐轴线平行，EFF流量值是WM纤维密度和髓鞘程度的函数，即EFF直接揭示了WM细胞构筑的亚体素特征。目前还没有已知的非侵入性活体技术可以提供如此特定的定量血流信息，注意到扩散张量成像结合细胞外水包含几种不同的信号贡献。这项研究开发的新方法将应用于获取和分析15名早产儿和2名足月儿在两年中每年的3D MRI数据，并生成每个病例的3D EFF的3D可视化。结果将结合3D DT-MRI结果和每个病例的分割结果进行分析，以证明EFF揭示了WM细胞结构的定量细节的假设。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.