Pediatric TBI and DAI: Normal Appearing Brain is Not Normal

描述（由申请人提供）：创伤性脑损伤（TBI）是儿童死亡和残疾的主要原因。弥漫性轴索损伤（DAI）伴出血性/非出血性剪切损伤被普遍认为是TBI的结果，导致长期神经系统（NL）和神经心理（NP）缺陷。目前，由于传统的CT和MRI低估了这些病变的程度，损伤可能无法被识别和治疗。我们的总体假设是，两种新的MR技术，即敏感性加权成像（SWI）和质子磁共振光谱成像（MRSI），能够在常规MRI上显示正常的区域检测到DAI，并可以预测长期预后。SWI是一种3d高分辨率梯度回声MRI技术，检测出血性DAI病变的灵敏度是传统MRI的6倍。核磁共振成像检测反映神经元损伤的代谢物变化（n -乙酰天冬氨酸还原），并提供了超过60%的大脑弥漫性损伤的证据，即使在SWI中也表现正常。本应用程序提出了一项前瞻性、对照、纵向研究，以评估90名（4-16岁）中度至重度（GCS< 13） TBI儿童（损伤后7-14天）和90名非头部损伤年龄匹配的对照组的11个脑区域的3D SWI/MRSI。选择这些年龄是为了方便标准化NP测试。测量结果将进行区域、全局（所有区域合并）和3个脑区（皮质、皮质下和后窝）的比较。具体目的是：1)确定SWI是否能检测到常规MRI无法检测到的出血性DAI病变数量/体积的增加，并更好地预测3个月和12个月的NL和整体NP（即智商、记忆、注意力）结果；2)确定TBI后外观正常的大脑是否存在通过初始MRSI代谢物变化测量的显著损伤；3)确定SWI和MRSI数据是否单独或联合更能预测NL/NP结局；4)在损伤后12个月重复SWI/MRSI，以便通过与功能长期预后比值的间隔变化来分类神经元变性、恢复和可塑性的区域模式。这些先进的核磁共振技术有望通过显著提高损伤检测和对康复的理解，成为新的护理标准。这将对TBI的诊断和治疗管理具有重要意义，特别是对那些损伤被低估、未被识别和未得到治疗的儿童。

DESCRIPTION (provided by applicant): 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.