Neurocognitive and neuroimaging correlates of pediatric traumatic brain injury: a diffusion tensor imaging (DTI) study.

This study examined the sensitivity of diffusion tensor imaging (DTI) to microstructural white matter (WM) damage in mild and moderate pediatric traumatic brain injury (TBI). Fourteen children with TBI and 14 controls ages 10-18 had DTI scans and neurocognitive evaluations at 6-12 months post-injury. Groups did not differ in intelligence, but children with TBI showed slower processing speed, working memory and executive deficits, and greater behavioral dysregulation. The TBI group had lower fractional anisotropy (FA) in three WM regions: inferior frontal, superior frontal, and supracallosal. There were no group differences in corpus callosum. FA in the frontal and supracallosal regions was correlated with executive functioning. Supracallosal FA was also correlated with motor speed. Behavior ratings showed correlations with supracallosal FA. Parent-reported executive deficits were inversely correlated with FA. Results suggest that DTI measures are sensitive to long-term WM changes and associated with cognitive functioning following pediatric TBI.     

Diffusion tensor imaging detects axonal injury in a mouse model of repetitive closed-skull traumatic brain injury

Mild traumatic brain injuries (TBI) are common in athletes, military personnel, and the elderly, and increasing evidence indicates that these injuries have long-term health effects. However, the difficulty in detecting these mild injuries in vivo is a significant impediment to understanding the underlying pathology and treating mild TBI. In the following experiments, we present the results of diffusion tensor imaging (DTI) and histological analysis of a model of mild repetitive closed-skull brain injury in mouse. Histological markers used included silver staining and amyloid precursor protein (APP) immunohistochemistry to detect axonal injury, and Iba-1 immunohistochemistry to assess microglial activation. At 24h post-injury, before silver staining or microglial abnormalities were apparent by histology, no significant changes in any of the DTI parameters were observed within white matter. At 7 days post-injury we observed a reduction in axial and mean diffusivity. Relative anisotropy at 7 days correlated strongly with the degree of silver staining. Interestingly, APP was not observed at any timepoint examined. In addition to the white matter alterations, mean diffusivity was elevated in ipsilateral cortex at 24h but returned to sham levels by 7 days. Altogether, this demonstrates that DTI is a sensitive method for detecting axonal injury despite a lack of conventional APP pathology. Further, this reflects a need to better understand the histological basis for DTI signal changes in mild TBI.     

Changes in working memory after traumatic brain injury in children

The impact of traumatic brain injury (TBI) on working memory (WM) was studied in 144 children (79 with mild, 23 with moderate, and 42 with severe injuries) who underwent magnetic resonance imaging (MRI) at 3 months and were tested at baseline and at 3, 6, 12, and 24 months postinjury. An n-back WM task for letter identity was administered with memory load ranging from 1- to 3-back and a 0-back condition. A TBI Severity x Quadratic Tune interaction showed that net percentage correct (correct detections of targets minus false alarms) was significantly lower in severe than in mild TBI groups. The Left Frontal Lesions x Age interaction approached significance. Mechanisms mediating late decline in WM and the effects of left frontal lesions are discussed.     

Longitudinal diffusion tensor imaging in a rat brain glioma model

In order to investigate the properties of water motion within and around brain tumors as a function of tumor growth, longitudinal diffusion tensor imaging (DTI) was carried out in a rat brain glioma (C6) model. As tumors grew in size, significant anisotropy of water diffusion was seen both within and around the tumor. The tissue water surrounding the tumor exhibited high planar anisotropy, as opposed to the linear anisotropy normally seen in white matter, indicating that cells were experiencing stress in a direction normal to the tumor border. When tumors were sufficiently large, significant anisotropy was also seen within the tumor because of longer-range organization of cancer cells within the tumor borders. These findings have important implications for diffusion-weighted MRI experiments examining tumor growth and response to therapy. Copyright (c) 2008 John Wiley & Sons, Ltd.     

The role of diffusion tensor imaging in the evaluation of ischemic brain injury - a review

Water diffusion in brain tissue is affected by the presence of barriers to translational motion such as cell membranes and myelin fibers. The measured water apparent diffusion coefficient (ADC) value is therefore frequently anisotropic and varies depending upon the orientation of restricting barriers (such as white matter tracts) relative to the diffusion-sensitive-gradient direction. Anisotropic water diffusion can be specified using indices of diffusion anisotropy [e.g. standard deviation of the individual ADC values, fractional anisotropy (FA), lattice index (LI)], which are derived from measurements of the full diffusion tensor. The rotationally invariant nature of particular diffusion anisotropy indices (e.g. FA, LI) allows orientation-independent comparisons of these parameters between different subjects. Pathophysiological processes (such as cerebral ischemia) that modify the integrity of the tissue microstructure result in significant alterations in tissue anisotropy and make this metric a useful endpoint for characterizing the temporal evolution of the disease. Diffusion-tensor imaging (DTI) studies of both experimental and human stroke suggest that DTI may provide additional information about the evolution of the disease that is not available from diffusion-weighted MRI (DWI) alone. Acute reductions in the average diffusivity [ = (lambda(1) + lambda(2) + lambda(3))/3 where lambda(1), lambda(2), and lambda(3) are the eigenvalues of the diffusion tensor] following the onset of cerebral ischemia are often accompanied by increases in diffusion anisotropy. In the transition from acute to sub-acute and chronic stroke, renormalizes and subsequently increases whereas diffusion anisotropy measures (e.g. FA) decline and remained reduced in chronic infarcts. Overall isotropic ADC changes during infarct evolution have been observed to be greater in white matter (WM) than in gray matter (GM) lesions (although there have been conflicting reports on this issue) and GM lesions tend to renormalize prior to WM lesions as the infarct evolves. Ischemic WM exhibits a significant decrease in diffusion anisotropy (relative to normal WM) during ischemic evolution whereas that of ischemic GM remains statistically unchanged. Furthermore, the percentage decrease in ischemic WM is largely determined by reductions in lambda(1), the eigenvalue that coincides with the long axis of the WM fiber tract. Variations in unidirectional ADC or over the ischemic time course limit the usefulness of this parameter alone as a predictor of ischemic injury. Consequently, ADC information has been combined with that of other MR parameters (including DTI) to unambiguously stage and predict ischemic brain injury over its entire temporal evolution. Combined and diffusion anisotropy measurements have identified three phases of diffusion abnormality: (1) reduced and elevated anisotropy; (2) reduced and reduced anisotropy; and (3) elevated and reduced anisotropy. However, variations in the differential patterns of and diffusion anisotropy evolution have been observed by a number of investigators and more work is needed to clarify the role of these measurements in characterizing the severity of the ischemic insult as well as the potential outcome in response to the initial ischemic injury. The use of DTI, in combination with more sophisticated analysis methods for performing multiparametric segmentation, such as multispectral analysis, may enhance the use of MRI for accurate diagnosis and prognosis of stroke. Furthermore, these techniques may also play an important role in the clinical evaluation of new stroke treatments.     

Brain imaging correlates of verbal working memory in children following traumatic brain injury

Neural correlates of working memory (WM) based on the Sternberg Item Recognition Task (SIRT) were assessed in 40 children with moderate-to-severe traumatic brain injury (TBI) compared to 41 demographically-comparable children with orthopedic injury (OI). Multiple magnetic resonance imaging (MRI) methods assessed structural and functional brain correlates of WM, including volumetric and cortical thickness measures on all children; functional MRI (fMRI) and diffusion tensor imaging (DTI) were performed on a subset of children. Confirming previous findings, children with TBI had decreased cortical thickness and volume as compared to the OI group. Although the findings did not confirm the predicted relation of decreased frontal lobe cortical thickness and volume to SIRT performance, left parietal volume was negatively related to reaction time (RT). In contrast, cortical thickness was positively related to SIRT accuracy and RT in the OI group, particularly in aspects of the frontal and parietal lobes, but these relationships were less robust in the TBI group. We attribute these findings to disrupted fronto-parietal functioning in attention and WM. fMRI results from a subsample demonstrated fronto-temporal activation in the OI group, and parietal activation in the TBI group, and DTI findings reflected multiple differences in white matter tracts that engage fronto-parietal networks. Diminished white matter integrity of the frontal lobes and cingulum bundle as measured by DTI was associated with longer RT on the SIRT. Across modalities, the cingulate emerged as a common structure related to performance after TBI. These results are discussed in terms of how different imaging modalities tap different types of pathologic correlates of brain injury and their relationship with WM.     

脑微损伤的影像学进展

脑微损伤是创伤性脑损伤最常见的类型,然而,其潜在的神经生理机制尚未完全阐明,影响患者的早期诊断、治疗及预后评估。近年来,多项磁共振（MRI）新技术不断地涌现并用于评估脑微损伤,如功能磁共振、灌注MRI、弥散张量成像、定量易感性图谱、T2 mapping等。本研究综述了多模态MRI在脑微损伤中的应用,从不同的角度深入地了解脑微损伤的神经病理机制,有助于提高临床医生对脑微损伤的诊断和治疗。     

磁共振扩散张量成像评价小儿脑病的初步应用

目的应用扩散张量成像（DTI）来进一步评价小儿脑疾病，探讨DTI的诊断价值。方法对15例患各种脑病的小儿进行MRI检查，其中男性10例，女性5例，年龄为生后3天至11岁（平均年龄4．8岁）。采用Philips Intera Achieva 3．0 Tesla的超导MRI仪，用回波平面成像（EPI）的DTI技术，b为800s／mm^2，15个方向。观察彩色分数各向异性（FA）图和三维彩色编码图。结果15例患儿中，发育畸形2例，分别是胼胝体发育不良、巨脑回；脑室旁白质软化（PVL）7例；缺氧缺血性脑病3例；脑软化2例；脑积水1例。在巨脑回病例，常规MRI见右侧脑回发育不良，呈巨脑回畸形，右侧脑室扩大，在DTI上见右侧病变区白质束明显较对侧少。胼胝体发育不良病例在DTI张量图见胼胝体菲薄。在PVL和缺氧缺血性脑病病例均可见白质纤维束在放射冠颜色混杂，方向性混乱。脑软化病例可见白质纤维束部分中断。在脑积水病例可见白质束受压推移。结论DTI能够显示白质束的走向、绕行、交叉及推挤、中断等异常，可能对今后评估小儿脑病的预后转归有帮助。     

磁共振扩散张量成像在评价儿童脑内部分皮质脊髓束发育中的应用

目的 应用磁共振扩散成像技术探讨儿童皮质脊髓束年龄和性别差异及其变化规律。 方法 90例无中枢神经系统症状及体征且颅脑磁共振检查正常的儿童（年龄5d～18岁）。按年龄分为5组: 婴儿组（组1,≤1岁）,幼儿组（组2,＞1～3岁）,学龄前组（组3,＞3～6岁）,学龄组（组4,＞6～12岁）,青春发育期组（组5,＞12～18岁）。每个年龄组内再按性别分为男、女2组。各组儿童分别行头部扩散张量成像, 根据感兴趣法选取皮质脊髓束感兴趣区并重建,测量重建的皮质脊髓束的扩散张量参数并进行统计学分析。 结果 各年龄组的表观扩散系数(ADC)值、分数各向异性(FA)值、纤维示踪平均长度、体积以及示踪的纤维束数量不完全相同（P<0.01）;组间的两两比较间发现,1组与2组间ADC值、FA值及示踪纤维平均长度差异具有统计学意义;2组与3组间FA值差异具有统计学意义;3组与4组间ADC值、FA值、示踪纤维平均长度、纤维束数目及体积差异均具有统计学意义。ADC值与年龄间呈负相关,余参数与年龄间呈正相关。结论 儿童皮质脊髓束发育具有阶段性,且具有阶段性特征;磁共振扩散张量技术可用于观测儿童皮质脊髓束,评价其发育状况。     

Inflicted traumatic brain injury in infants and young children

Abstract This article will discuss the subject of inflicted or abusive head injury in infants and young children. Inflicted neurotrauma is a very common injury and a frequent problem in attempting to distinguish between inflicted and accidental injury. Inflicted head injury occurs usually in the home in the presence of the individual who has inflicted the injury outside the view of unbiased witnesses. Distinguishing between inflicted and accidental injury may be dependent upon the pathological findings and consideration of the circumstances surrounding the injury. The most common finding in an inflicted head injury is the presence of subdural hemorrhage. Subdural hemorrhage may occur in a variety of distributions and appearances. The natural history of subdural bleeding and the anatomy of the "subdural" will be considered. The anatomy of the dura and its attachment to the skull and to the arachnoid determines how subdural bleeding evolves into the cleaved dural border cell layer and as well as how bridging veins are torn and anatomically where bleeding will occur. Different biomechanical mechanisms result in different distributions of subdural blood and these differences will be discussed.     

基于DTI的胶质瘤患者手术前后脑网络特性分析

目的利用弥散张量成像(diffusion tensor imaging,DTI)技术构建胶质瘤患者手术前后全脑结构网络和半脑结构网络,基于图论知识对脑网络参数进行定量研究及对比分析,探究胶质瘤及肿瘤切除手术对患者脑网络拓扑特性的影响。方法构建健康对照组、胶质瘤患者组手术前后全脑和半脑结构网络,定量分析两组大脑结构网络拓扑特性及网络参数,比较分析手术对患者全脑及半脑网络特性的影响。结果从全脑角度看,患者术后各全局网络参数较正常人均有所降低,但是小世界特性却有所增强,患者各全局参数在术前术后均无显著差异,患者术后的全脑局部参数明显低于术前;在半脑结构网络中,手术前后半脑全局参数无明显差异,而术后半脑全局参数明显低于术前。结论手术使得脑结构网络的局部脑区发生损伤,但并未对患者全脑及半脑全局参数造成显著影响,研究证实了人类大脑的代偿机制以及功能重组。该研究方法可对胶质瘤患者术后的疾病发展状况以及手术治疗效果评价提供帮助。     

健康儿童颈髓磁共振扩散张量成像

目的 应用扩散张量成像技术研究儿童颈髓发育规律。方法 使用单次激发自旋回波平面回波序列对90例健康儿童行颈髓扩散张量成像。在颈髓节段分别测量其表观扩散系数值（ADC）、各向异性分数值（FA）、纤维束平均长度（Ltract）以及纤维束体积（Vtract）。结果 各组的ADC值、FA值、Ltract及Vtract分别如下：0.9747±0.2777、0.8493±0.2236、0.8210±0.1432、0.9198±0.1444、0.9048±0.1676;0.4117±0.0391、0.4712±0.0199、0.4944±0.0439、0.5608±0.0443、0.6169±0.0551;25.61±8.63、24.66±7.14、27.03±7.23、34.93±10.99、37.63±10.22;3.07±1.49、3.00±1.52、3.81±1.33、5.41±2.35、6.64±2.84。各年龄组的FA值、Ltract和Vtract不完全相同（P<0.001）,而ADC值各年龄组的均值差异无统计学意义（F=1.758, P=0.145）。在组间的两两比较中：1、2组间FA值差异具有统计学意义;3、4组间FA值、Ltract和Vtract差异均具有统计学意义;4、5组间FA值差异具有统计学意义。FA值、Ltract和Vtract与年龄呈正相关。
结论 儿童颈髓发育具有阶段性,且具有阶段性特征;磁共振扩散张量技术可用于观测儿童颈髓并评价其发育。     

Relationship between diffusion tensor imaging and brain morphology in patients with myotonic dystrophy

Myotonic dystrophy type 1 (MyD) is a common inherited neuromuscular disorder. In addition to neuromuscular symptoms, many MyD patients show central nervous system neuropathology. This study evaluated whether MyD patients display diffusion tensor (DT) abnormalities associated with regional cortical atrophy and clinical features. Three-dimensional T1-weighted and DT magnetic resonance images of the brain were obtained in 11 MyD patients and 13 age- and sex-matched healthy subjects. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in corpus callosum subregions with DT imaging (DTI) along with volumetric changes, and correlations with clinical features were examined. Differences between MyD patients and healthy subjects were analyzed statistically. Significantly lower FA and higher MD values were found in the genu, rostral body, anterior midbody, posterior midbody and splenium in MyD patients than in control subjects (p < 0.05, corrected; lower FA in the splenium was at a trend level). These corpus callosum subregions were the areas connected to cortical areas where significantly lower volumes were found in MyD patients. No significant decrease in volumes was noted in the parietal cortex, where connecting fibers pass through the isthmus in which DTI abnormalities were not detected in MyD patients. Significant negative correlations to volumes of frontal areas were noted, particularly bilateral motor areas, with cytosine thymine guanidine (CTG) triplet expansion. DTI results in corpus callosum may reflect morphological changes in the connecting cortical areas of MyD patients.     

Two-step anomalous diffusion tensor imaging

We extend the formalism of anomalous diffusion imaging to include directional anisotropy of fitted parameters. The resulting technique is termed anomalous diffusion tensor imaging (aDTI), and allows the directional properties of the distributed diffusion coefficient (α) and the anomalous diffusion exponent, (γ) to be analysed using the same analytical techniques as regular diffusion tensor imaging (DTI). Together, these parameters quantify the rate of diffusion (α) and the complexity of the diffusion environment (γ). We generated tensor images for the anomalous exponent tensor (Γ) and distributed diffusivity tensor (A) from in vivo human brain data and present images of eigenvalues, eigenvectors, Trace/3 (Tr), fractional anisotropy (FA) and tensor shape measures. In white matter, A is found to have a median Tr = 0.56 × 10^{? 3}mm²s^{? 1}, FA = 0.58 and Γ Tr = 0.69, FA = 0.13. We observed that white matter shows a similar anisotropic geometry for the distributed diffusion tensor as for the regular diffusion tensor, whereas the anomalous exponent tensor exhibits a different shape characteristic which may be informative of tissue microstructure. Copyright © 2011 John Wiley & Sons, Ltd.     

基于弥散张量成像的脑结构网络参数研究

目的 利用复杂网络参数评估大脑特征,是探明大脑工作机制的新思路。方法 本研究基于弥散张量纤维束追踪和小世界网络理论构建脑结构网络。首先利用自动解剖标定（automated anatomical labeling,AAL）模板对大脑分区,并计算脑区间的纤维连接情况,对正常人的大脑结构进行网络建模。然后分析脑结构网络中节点度、簇系数和节点介数等网络参数,并通过引入小世界网络的介数和损伤性定义人脑结构网络的核心节点位置和特征。结果 脑结构网络具有小世界属性,且网络中存在少量的核心节点,具有较高的节点度和簇系数值。结论 利用弥散张量成像能够客观构建大脑结构网络,而核心节点的存在为揭示脑疾病的病理生理机制提供新的思路。     

A prospective study of short- and long-term neuropsychological outcomes after traumatic brain injury in children

Longitudinal neuropsychological outcomes of traumatic brain injury (TBI) were investigated in 53 children with severe TBI, 56 children with moderate TBI, and 80 children with orthopedic injuries only. Neuropsychological functioning was assessed at baseline, at 6- and 12-month follow-ups, and at an extended follow-up (a mean of 4 years postinjury). Mixed model analyses revealed persistent neuropsychological sequelae of TBI that generally did not vary as a function of time postinjury. Some recovery occurred during the first year postinjury, but recovery reached a plateau after that time, and deficits were still apparent at the extended follow-up. Further recovery was uncommon after the first year postinjury. Family factors did not moderate neuropsychological outcomes, despite their demonstrated influence on behavior and academic achievement after childhood TBI.     

Response inhibition after traumatic brain injury (TBI) in children: impairment and recovery

Children who experience traumatic brain injury (TBI) often show cognitive impairments postinjury, some of which recover over time. We examined the recovery of motor response inhibition immediately following TBI and over 2 years. We assessed the role of injury severity, age at injury, and lesion characteristics on initial impairment and recovery while considering the role of pre-injury psychiatric disorder. Participants were 136 children with TBI aged 5-16 years. Latency of motor response inhibition was measured with the stop-signal task within 1 month of the injury and again at 3, 6, 12, and 24 months. The performance of the TBI participants at each measurement occasion was standardized with 117 children of similar age, but without injury. Residualized latency scores were calculated. Growth curve analyses showed an initial impairment in response inhibition and improvement over the 2 years following injury. Younger TBI patients were initially more impaired although they exhibited greater recovery of response inhibition than did older TBI patients. Longer duration of coma, but not reactivity of pupils or Glasgow Coma Scale score, predicted initial deficit. Lesion characteristics or pre-injury attention deficit hyperactivity disorder did not predict initial impairment or recovery. Replication with longitudinal testing of a comparison group of children sustaining extracranial injury is necessary to confirm our findings.