Development of quantitative MRI DTI analysis tool for preterm neonate

描述(申请人提供)：我们将建立一种新生儿脑MRI的量化方法来评估早产儿的异常。在美国，大约12%的新生儿是早产(妊娠37周)，其中2%是早产(VPB，妊娠28-32周)。在过去十年中，早产儿的比例一直在上升，部分原因是改善了对早产儿的新生儿护理。然而，大约一半的VPB婴儿可能会发展为临床明显的神经或心理障碍，如果包括细微的功能异常，这个数字可能会更高。早产儿晚期(妊娠33-36周)的神经认知障碍的程度也是未知的。然而，大多数神经认知缺陷在生命的第一年并不容易被发现。为了从早期干预中受益，并开发更具缺陷特异性的干预措施，我们需要在早期阶段检测和量化大脑异常的方法。磁共振成像是检测新生儿脑内微小解剖异常最有前景和最敏感的方法之一。之前的脑核磁共振研究已经发现了几种类型的异常与神经结果之间的一些相关性，但也有报告发现，信号变化与神经结果之间没有关系。因此，目前的知识并不能证明使用MRI进行常规临床评估是合理的。为了优化MRI在新生儿和儿科护理中的有效性，需要基于定量图像分析和功能相关性的系统研究。提出的方法基于两项用于新生儿大脑解剖量化的核心技术：具有详细解剖信息的可变形脑图谱和高度弹性的拓扑保持翘曲方法。这一组合将从176个自动分割的大脑结构中提供多个磁共振参数。该项目的目标是建立一种基于图谱的新生儿大脑自动量化方法，以评估与足月年龄相当的早产儿的详细解剖。总体假设是，我们的DTI引导的定量脑分析将以特定区域的方式敏感地检测早产儿的解剖异常。我们有四个具体目标。在目标1中，我们将创建一个多对比(T1、T2加权和DTI)正常足月新生儿脑图谱，用于定量脑分析，这将是总体的统计表示(“贝叶斯图谱”)。在目标2中，我们将结合贝叶斯地图集和高弹性拓扑保持扭曲(大变形微分度量映射，LDDMM)进行自动脑分割，并测试分割精度。在目标3中，我们将使用贝叶斯图谱和LDDMM的组合来进行足月新生儿脑MRI的T1/T2/DTI量化。在目标4中，我们将该方法应用于足月出生的早产儿(胎龄28-36周)的大脑磁共振成像，并将其与足月儿的磁共振参数进行比较。这项研究将是寻找早产儿解剖脑异常功能结局的非常早期预后指标的第一步。

DESCRIPTION (provided by applicant): We will establish a quantification method for neonatal brain MRI to evaluate the abnormalities of preterm born neonates. In the U.S., approximately 12% of all neonates are born preterm (<37 weeks gestation), with 2% of these being very preterm (VPB, 28-32 weeks gestation). The percentage of preterm births has been increasing over the last ten years, partly due to improved neonatal care for preterm infants. Nevertheless, about half of the VPB infants may develop clinically-evident neurological or psychological disorders and the number could be even higher if subtle functional abnormalities are included. The extent of neurocognitive deficits in the late preterm infants (33-36 weeks gestation) is also unknown. However, most of the neuro- cognitive deficits are not easily detected during the first year of life. To benefit from early intervention and to develop more deficits-specific interventions, we need methods to detect and quantify brain abnormalities at an early stage. MRI is one of the most promising and sensitive methods to detect subtle anatomic abnormalities in the neonatal brain. Previous brain MRI studies have found some correlations between several types of abnormalities and neurological outcomes, but there are also reports that found no relationship between signal alterations and neurological outcomes. Hence, the current knowledge does not justify the use of MRI for routine clinical evaluations. To optimize the usefulness of MRI for neonatal and pediatric care, systematic research, based on quantitative image analysis and functional correlation, is needed. The proposed method is based on two core technologies for the quantification of neonatal brain anatomy: a deformable brain atlas with detailed anatomic information and a highly elastic topology-preserved warping method. The combination will provide multiple MR parameters from 176 automatically segmented brain structures. The goals of this project are to establish an atlas-based, automated quantification method for the neonatal brain, to evaluate the detail anatomy of premature neonates at a term-equivalent age. The overall hypothesis is that our DTI-guided quantitative brain analysis will sensitively detect anatomical abnormalities of preterm born neonates in region- specific manner. We have four specific aims. In Aim 1, we will create a multi-contrast (T1-, T2-weighted, and DTI) normal-term neonatal brain atlas for quantitative brain analysis, which will be a statistical representation of the population ("Bayesian atlas"). In Aim 2, we will combine the Bayesian atlas with highly elastic topology- preserved warping (Large Deformation Diffeomorphic Metric Mapping, LDDMM) for automated brain segmentation and test the segmentation accuracy. In Aim 3, we will use the combination of the Bayesian atlas and LDDMM to perform T1/T2/DTI quantification of term neonatal brain MRIs. In Aim 4, we will apply the method to the brain MRIs from term-equivalent preterm born infants (born at 28-36 weeks gestational age) and compare the MR parameters to those in the term infants. This study will be a first step toward seeking very early prognostic indicators for functional outcomes of the anatomical brain abnormalities in preterm births.