Pediatric TBI and DAI: Normal Appearing Brain is Not Normal

描述(申请人提供)：创伤性脑损伤(TBI)是导致儿童死亡和残疾的主要原因。弥漫性轴索损伤(DAI)合并出血性/非出血性剪切性损害是公认的颅脑损伤的后果，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低估了这些损伤的程度。我们的总体假设是，两种新的MR技术，磁化率加权成像(SWI)和质子磁共振波谱成像(MRSI)，能够在常规MRI显示正常的区域检测DAI，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，对检测出血性DAI病变的敏感性是常规MRI的6倍。MRSI检测到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上也是正常的。这项应用提出了一项前瞻性、对照、纵向研究，以评估90名中到重度(GCS&lt；13)脑损伤儿童(4-16岁)的11个脑区的3D SWI/MRSI，伤后7-14天，以及90名年龄匹配的非颅脑损伤对照组。选择这些年龄是为了促进标准化的NP测试。测量结果将按区域、全球(所有区域合并)和3个汇集的大脑区域(皮质、皮质下和后颅窝)进行比较。其具体目的是：1)确定SWI是否能检测到常规MRI看不到的出血性DAI病变的数量/体积的增加，并将更好地预测3个月和12个月的NL和全球NP(即智商、记忆力、注意力)的结果；2)确定脑损伤后是否存在以初始MRSI代谢物变化衡量的重大损伤；3)确定单独或联合应用SWI和MRSI数据更能预测NL/NP的预后，以及4)在损伤后12个月重复SWI/MRSI，以便通过与功能长期结果比率的间隔变化来分类神经元变性、恢复和可塑性的区域模式。这些先进的磁共振技术通过显著提高损伤的检测和对康复的了解，有望成为新的护理标准。这将对脑外伤的诊断和治疗管理非常重要，特别是在儿童中，他们的损伤被低估、未被识别和未得到治疗。

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.