PEDIATRIC TBI AND DAI: NORMAL APPEARING BRAIN IN NOT NORMAL

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 创伤性脑损伤（TBI）是儿科人群死亡和残疾的主要原因。弥漫性轴索损伤（DAI）伴出血性/非出血性剪切性病变被普遍认为是TBI的结果，可导致长期的神经（NL）和神经心理（NP）缺陷。目前，损伤可能无法识别和治疗，因为传统的CT和MRI低估了这些病变的范围。我们的总体假设是，两种新的MR技术，磁共振加权成像（SWI）和质子磁共振波谱成像（MRSI），能够检测DAI在常规MRI上显示正常的区域，并可以预测长期结果。SWI是一种3D高分辨率梯度回波MRI技术，检测出血性DAI病变的灵敏度是常规MRI的6倍。MRSI检测反映神经元损伤的代谢物变化（N-乙酰天冬氨酸减少），并提供了超过60%的大脑弥漫性损伤的证据，即使在SWI上也表现正常。本申请提出了一项前瞻性、对照性、纵向研究，以评估90名中度至重度（GCS< 13）TBI儿童（4-16岁）在受伤后7-14天和90名非头部受伤年龄匹配对照者的11个脑区中的3D SWI/MRSI。选择这些年龄是为了方便标准化NP测试。将在区域、全球（所有区域合并）和3个合并脑区域（皮质、皮质下和后颅窝）对测量值进行比较。具体目标是：1）确定SWI是否将检测到传统MRI不可见的出血性DAI病变的数量/体积增加，并更好地预测3个月和12个月NL和总体NP（即智商、记忆力、注意力）结果; 2）确定TBI后外观正常的大脑中是否存在通过初始MRSI代谢物变化测量的显着损伤; 3）确定SWI和MRSI数据单独或组合是否更能预测NL/NP结果，以及4）在损伤后12个月重复SWI/MRSI，以便对神经元变性的区域模式进行分类，恢复和可塑性，通过与功能性长期结果的比率的间隔变化来测量。这些先进的磁共振技术有望成为新的护理标准，显着提高损伤的检测和恢复的理解。这对创伤性脑损伤的诊断和治疗管理非常重要，特别是在那些损伤被低估、未被识别和未得到治疗的儿童中。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Traumatic brain injury (TBI) is the leading cause of death and disability in the pediatric population. Diffuse axonal injury (DAI) with hemorrhagic/non-hemorrhagic shearing lesions is universally recognized as a consequence of TBI that results in long-term neurologic (NL) and neuropsychological (NP) deficits. Currently, injury may go unrecognized and untreated because conventional CT and MRI underestimate the extent of these lesions. Our overall hypothesis is that 2 new MR techniques, susceptibility-weighted imaging (SWI) and proton magnetic resonance spectroscopic imaging (MRSI), are capable of detecting DAI in areas that appear normal on conventional MRI and can predict long-term outcome. SWI is a 3D-high-resolution gradient echo MRI technique that is 6 times more sensitive for detecting hemorrhagic DAI lesions than conventional MRI. MRSI detects metabolite changes (reduced N-acetylaspartate) that reflect neuronal injury and has provided evidence of diffuse damage in over 60% of brain that appears normal even on SWI. This application proposes a prospective, controlled, longitudinal study to evaluate 3D SWI/MRSI in 11 brain regions in 90 children (4-16 years) with moderate to severe (GCS< 13) TBI, 7-14 days after injury and 90 non-head injured age-matched controls. These ages were selected to facilitate standardized NP testing. Measurements will be compared regionally, globally (all regions combined) and as 3 pooled brain regions (cortical, subcortical, and posterior fossa). The specific aims are: 1) to determine if SWI will detect an increased number/volume of hemorrhagic DAI lesions not visible with conventional MRI and will better predict 3 and 12 month NL and global NP (i.e. IQ, memory, attention) outcomes; 2) to determine if significant injury measured by initial MRSI metabolite changes is present in normal-appearing brain following TBI; 3) to determine if SWI and MRSI data individually or combined are more predictive of NL/NP outcomes and 4) to repeat SWI/MRSI at 12 months after injury in order to categorize regional patterns of neuronal degeneration, recovery and plasticity as measured by interval changes of ratios with functional long-term outcome. These advanced MR techniques hold promise of becoming new standards of care by significantly improving detection of injury and understanding of recovery. This will be of importance to diagnostic and therapeutic management of TBI, particularly in children in whom injury is underestimated, unrecognized and untreated.