Diffusion tensor imaging in mild traumatic brain injury litigation

A growing body of literature addresses the application of diffusion tensor imaging (DTI) to traumatic brain injury (TBI). Most TBIs are of mild severity, and their diagnosis and prognosis are often challenging. These challenges may be exacerbated in medicolegal contexts, where plaintiffs seek to present objective evidence that supports a clinical diagnosis of mild (m)TBI. Because DTI permits quantification of white matter integrity and because TBI frequently involves white matter injury, DTI represents a conceptually appealing method of demonstrating white matter pathology attributable to mTBI. However, alterations in white matter integrity are not specific to TBI, and their presence does not necessarily confirm a diagnosis of mTBI. Guided by rules of evidence shaped by Daubert v. Merrell Dow Pharmaceuticals, Inc., we reviewed and analyzed the literature describing DTI findings in mTBI and related neuropsychiatric disorders. Based on this review, we suggest that expert testimony regarding DTI findings will seldom be appropriate in legal proceedings focused on mTBI.     

Diffusion kurtosis imaging in mild traumatic brain injury and postconcussional syndrome

Aims of this study were to investigate white matter (WM) and thalamus microstructure 72 hr and 3 months after mild traumatic brain injury (TBI) with diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI), and to relate DKI and DTI findings to postconcussional syndrome (PCS). Twenty-five patients (72 hr = 24; 3 months = 23) and 22 healthy controls were recruited, and DKI and DTI data were analyzed with Tract-Based Spatial Statistics (TBSS) and a region-of-interest (ROI) approach. Patients were categorized into PCS or non-PCS 3 months after injury according to the ICD-10 research criteria for PCS. In TBSS analysis, significant differences between patients and controls were seen in WM, both in the acute stage and 3 months after injury. Fractional anisotropy (FA) reductions were more widespread than kurtosis fractional anisotropy (KFA) reductions in the acute stage, while KFA reductions were more widespread than the FA reductions at 3 months, indicating the complementary roles of DKI and DTI. When comparing patients with PCS (n = 9), without PCS (n = 16), and healthy controls, in the ROI analyses, no differences were found in the acute DKI and DTI metrics. However, near-significant differences were observed for several DKI metrics obtained in WM and thalamus concurrently with symptom assessment (3 months after injury). Our findings indicate a combined utility of DKI and DTI in detecting WM microstructural alterations after mild TBI. Moreover, PCS may be associated with evolving alterations in brain microstructure, and DKI may be a promising tool to detect such changes.     

轻中型颅脑损伤后认知功能障碍的DTI研究

目的应用弥散张量成像(diffusion tensor imaging,DTI)技术探讨轻中型颅脑损伤病人不同部位脑白质微结构改变与其认知功能障碍的相关性。方法分析127例轻中型颅脑损伤病人的临床资料,伤后10 d采用蒙特利尔认知评估量表(Mo CA)评定有无认知功能障碍,并常规行头颅MRI检查,采集DTI数据,测量两侧额叶、颞叶内侧、顶叶,胼胝体膝部和压部,中脑部位的感兴趣区各向异性分数(FA值)、表观弥散系数(ADC值),并与Mo CA评估结果进行相关性分析。结果以Mo CA量表为标准评定,无认知功能障碍41例(32.28%,无认知障碍组),存在认知功能障碍86例(67.72%,认知障碍组),主要表现为视空间与执行功能、注意力和计算力、语言、抽象能力、延迟记忆的障碍。与无认知障碍的病人相比,认知障碍的病人两侧额叶、颞叶内侧、胼胝体膝部FA值降低,ADC值增加,差异具有统计学意义(P0.01)。结论轻中型颅脑损伤病人早期存在显著认知功能障碍,以视空间与执行功能、注意力和计算力、语言、抽象能力、延迟记忆障碍为主。颅脑损伤后早期认知功能障碍与病人额叶、颞叶、胼胝体白质受损密切相关。     

Diffusion tensor imaging studies of mild traumatic brain injury: a meta-analysis

Objectives To assess the possibility that diffusion tensor imaging (DTI) can detect white matter damage in mild traumatic brain injury (mTBI) patients via systematic review and meta-analysis. Methods DTI studies that compared mTBI patients and controls were searched using MEDLINE, Web of Science, and EMBASE, (1980 through April 2012). Results A comprehensive literature search identified 28 DTI studies, of which 13 independent DTI studies of mTBI patients were eligible for the meta-analysis. Random effect model demonstrated significant fractional anisotropy (FA) reduction in the corpus callosum (CC) (p=0.023, 95% CIs -0.466 to -0.035, 280 mTBIs and 244 controls) with no publication bias and minimum heterogeneity, and a significant increase in mean diffusivity (MD) (p=0.015, 95% CIs 0.062 to 0.581, 154 mTBIs and 100 controls). Meta-analyses of the subregions of the CC demonstrated in the splenium FA was significantly reduced (p=0.025, 95% CIs -0.689 to -0.046) and MD was significantly increased (p=0.013, 95% CIs 0.113 to 0.950). FA was marginally reduced in the midbody (p=0.099, 95% CIs -0.404 to 0.034), and no significant change in FA (p=0.421, 95% CIs -0.537 to 0.224) and MD (p=0.264, 95% CIs -0.120 to 0.438) in the genu of the CC. Conclusions Our meta-analysis revealed the posterior part of the CC was more vulnerable to mTBI compared with the anterior part, and suggested the potential utility of DTI to detect white matter damage in the CC of mTBI patients.     

Diffusion tensor imaging studies on corticospinal tract injury following traumatic brain injury: a review

The corticospinal tract (CST) is the most important neural tract for motor function in the human brain. Therefore, clarification of CST injury would be an important topic in traumatic brain injury (TBI) rehabilitation. In this review, I reviewed diffusion tensor imaging (DTI) studies on CST injuries in terms of etiology and recovery in patients with TBI. Although DTI has several unique advantages for research on CST injury in TBI, only a dozen DTI studies on this topic have been reported: etiology of CST injury (9 studies), recovery of CST injury (3 studies). As for the etiology of CST injury in TBI, the previous studies have demonstrated the usefulness of DTI in diagnosis of CST injury in cases of diffuse axonal injury, transtentorial herniation, cerebral hemorrhage, and cortical contusion; moreover, according to the severity of TBI. The three studies on recovery of CST injury focused on recovery of a CST injured by diffuse axonal injury. In the future, we suggest an increase in the total number of DTI studies on this topic. In particular, research on recovery of CST injury should be encouraged. Moreover, studies of the various recovery mechanisms related to the CST are necessary.     

Metabolic imaging of mild traumatic brain injury

Traumatic brain injury results in a metabolic cascade of changes that occur at the molecular level, invisible to conventional imaging methods such as computed tomography or magnetic resonance imaging. Non-invasive metabolic imaging tools such as single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance spectroscopy (MRS) are the ideal methods for providing insight to these changes by measuring regional cerebral blood flow, glucose metabolism, and brain metabolite concentrations, respectively, after mild traumatic brain injury (mTBI). The purpose of this review is to provide an overview of the different methodologies and provide an up-to-date summary of recent findings with SPECT, PET, and MRS technologies, specifically after mTBI, as defined by standardized criteria. Given that the different physiological and pathological responses are heterogeneous, efforts will be made to separate studies at different time points after injury (acute, subacute, and chronic stages) as well as to the different types of mTBI such sports-related head injury where repetitive head injuries are much more common and may present a unique signature.     

Diffusion tensor tractography characteristics of axonal injury in concussion/mild traumatic brain injury

The main advantage of diffusion tensor tractography is that it allows the entire neural tract to be evaluated.In addition,configurational analysis of reconstructed neural tracts can indicate abnormalities such as tearing,narrowing,or discontinuations,which have been used to identify axonal injury of neural tracts in concussion patients.This review focuses on the characteristic features of axonal injury in concussion or mild traumatic brain injury(m TBI)patients through the use of diffusion tensor tractography.Axonal injury in concussion(m TBI)patients is characterized by their occurrence in long neural tracts and multiple injuries,and these characteristics are common in patients with diffuse axonal injury and in concussion(m TBI)patients with axonal injury.However,the discontinuation of the corticospinal tract is mostly observed in diffuse axonal injury,and partial tearing and narrowing in the subcortical white matter are frequently observed in concussion(m TBI)patients with axonal injury.This difference appears to be attributed to the observation that axonal injury in concussion(m TBI)patients is the result of weaker forces than those producing diffuse axonal injuries.In addition,regarding the fornix,in diffuse axonal injury,discontinuation of the fornical crus has been frequently reported,but in concussion(m TBI)patients,many collateral branches form in the fornix in addition to these findings in many case studies.It is presumed that the impact on the brain in TBI is relatively weaker than that in diffuse axonal injury,and that the formation of collateral branches occurs during the fornix recovery process.Although the occurrence of axonal injury in multiple areas of the brain is an important feature of diffuse axonal injury,case studies in concussion(m TBI)have shown that axonal injury occurs in multiple neural tracts.Because axonal injury lesions in m TBI patients may persist for approximately 10 years after injury onset,the characteristics of axonal injury in concussion(m TBI)patients,which are reviewed and categorized in this review,are expected to serve as useful supplementary information in the diagnosis of axonal injury in concussion(m TBI)patients.     

Diffusion tensor imaging changes following mild,moderate and severe adult traumatic brain injury: a meta-analysis

Diffusion tensor imaging quantifies the asymmetry (fractional anisotropy; FA) and amount of water diffusion (mean diffusivity/apparent diffusion coefficient; MD/ADC) and has been used to assess white matter damage following traumatic brain injury (TBI). In healthy brains, diffusion is constrained by the organization of axons, resulting in high FA and low MD/ADC. Following a TBI, diffusion may be altered; however the exact nature of these changes has yet to be determined. A meta-analysis was therefore conducted to determine the location and extent of changes in DTI following adult TBI. The data from 44 studies that compared the FA and/or MD/ADC data from TBI and Control participants in different regions of interest (ROIs) were analyzed. The impact of injury severity, post-injury interval (acute: ≤ 1 week, subacute: 1 week-3 months, chronic: > 3 months), scanner details and acquisition parameters were investigated in subgroup analyses, with the findings indicating that mild TBI should be examined separately to that of moderate to severe injuries. Lower FA values were found in 88% of brain regions following mild TBI and 92% following moderate-severe TBI, compared to Controls. MD/ADC was higher in 95% and 100% of brain regions following mild and moderate-severe TBI, respectively. Moderate to severe TBI resulted in larger changes in FA and MD/ADC than mild TBI. Overall, changes to FA and MD/ADC were widespread, reflecting more symmetric and a higher amount of diffusion, indicative of white matter damage.     

Functional magnetic resonance imaging of mild traumatic brain injury

Functional magnetic resonance imaging (fMRI) offers great promise for elucidating the neuropathology associated with a single or repetitive mild traumatic brain injury (mTBI). The current review discusses the physiological underpinnings of the blood-oxygen level dependent response and how trauma affects the signal. Methodological challenges associated with fMRI data analyses are considered next, followed by a review of current mTBI findings. The majority of evoked studies have examined working memory and attentional functioning, with results suggesting a complex relationship between cognitive load/attentional demand and neuronal activation. Researchers have more recently investigated how brain trauma affects functional connectivity, and the benefits/drawbacks of evoked and functional connectivity studies are also discussed. The review concludes by discussing the major clinical challenges associated with fMRI studies of brain-injured patients, including patient heterogeneity and variations in scan-time post-injury. We conclude that the fMRI signal represents a complex filter through which researchers can measure the physiological correlates of concussive symptoms, an important goal for the burgeoning field of mTBI research.     

Photosensitivity as a symptom of maladapive plasticity in a patient with traumatic brain injury: Diffusion tensor imaging study

We report on a patient with traumatic brain injury who had photosensitivity as the presenting visual symptom and demonstrated axonal injury of the left optic radiation using diffusion tensor imaging. A 41-year-old man with traumatic brain injury began to complain of photosensitivity about 4 months after head trauma. The ophthalmic evaluation, including visual evoked potential study and conventional brain MRI, did not exhibit a pathologic basis for his photosensitivity. However, we did detect axonal injury in the left optic radiation on a diffusion tensor imaging study 36 months after onset. This lesion was almost recovered on 76-month diffusion tensor imaging study, however, the photosensitivity had continued. We suggest that the photosensitivity in this patient was caused by axonal injury of the left optic radiation and it seems to be a symptom of maladaptive plasticity that occurs during the recovery of the axonal injury of the left optic radiation.     

Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Traumatic axonal injury (TAI) is thought to be a major contributor to cognitive dysfunction following traumatic brain injury (TBI), however TAI is difficult to diagnose or characterize non-invasively. Diffusion tensor imaging (DTI) has shown promise in detecting TAI, but direct comparison to histologically-confirmed axonal injury has not been performed. In the current study, mice were imaged with DTI, subjected to a moderate cortical controlled impact injury, and re-imaged 4-6 h and 24 h post-injury. Axonal injury was detected by amyloid beta precursor protein (APP) and neurofilament immunohistochemistry in pericontusional white matter tracts. The severity of axonal injury was quantified using stereological methods from APP stained histological sections. Two DTI parameters - axial diffusivity and relative anisotropy - were significantly reduced in the injured, pericontusional corpus callosum and external capsule, while no significant changes were seen with conventional MRI in these regions. The contusion was easily detectable on all MRI sequences. Significant correlations were found between changes in relative anisotropy and the density of APP stained axons across mice and across subregions spanning the spatial gradient of injury. The predictive value of DTI was tested using a region with DTI changes (hippocampal commissure) and a region without DTI changes (anterior commissure). Consistent with DTI predictions, there was histological detection of axonal injury in the hippocampal commissure and none in the anterior commissure. These results demonstrate that DTI is able to detect axonal injury, and support the hypothesis that DTI may be more sensitive than conventional imaging methods for this purpose.     

Optic radiation injury following traumatic epidural hematoma: Diffusion tensor imaging study

Little is known about optic radiation (OR) injury in patients with traumatic brain injury (TBI). We report on a patient who showed an OR injury on diffusion tensor imaging (DTI) following traumatic epidural hematoma (EDH). A 38 year-old man with TBI and 7 age-matched normal subjects were enrolled in this study. The patient had fallen down stairs while in an alcohol intoxicated state. He underwent a craniotomy following diagnosis of traumatic EDH in the left temporo-parietal lobe on brain CT. He complained of right bilateral homonymous hemianopsia, which was confirmed on the Humphrey visual field test. No lesion on the left OR was observed during brain MRI. We were not able to reconstruct the fiber tractography for the left OR in this patient. We found that the left OR had been injured most severely around the midportion between the lateral geniculate body and occipital pole. We determined that DTI would be a useful technique for detection of an OR injury in patients with TBI. Therefore, we believe that DTI should be performed along with conventional brain MRI for patients with visual field defects following TBI.     

缺血缺氧后5周大脑损伤患者的神经纤维束损伤：弥散张量成像证据

Hypoxic-ischemic brain injury (HI-BI) is one of the most common causes of severe neurological disability. Some studies have reported diffusion tensor imaging (DTI) findings of neonatal patients with HI-BI. However, very little is known about DTI in the adult brain. The present study reports on a 15-year-old male patient with HI-BI, who exhibited no specific focal lesions on conventional brain MRI at 5 weeks. However, neural tract injuries were revealed by DTI. Seven control subjects were also evaluated. The patient suffered from cardiac arrest due to ventricular fibrillation for a period of 10-15 minutes. At 4 weeks after onset of cardiac arrest, although he was conscious and alert, he exhibited mild quadriparesis and severe cognitive dysfunction. DTI was acquired at 5 weeks after HI-BI onset. Decreased fractional anisotropy or voxel number of neural tracts suggested partial injury of the corticospinal tract, fornix, and cingulum. Disruptions of the fornix and cingulum on DTI confirmed neural tract injury. DTI could serve as a useful tool for evaluating the state of neural tracts in patients with HI-BI.     

Diffusion tensor imaging and white matter lesions at the subacute stage in mild traumatic brain injury with persistent neurobehavioral impairment

Mild traumatic brain injury (mTBI) can induce long‐term behavioral and cognitive disorders. Although the exact origin of these mTBI‐related disorders is not known, they may be the consequence of diffuse axonal injury (DAI). Here, we investigated whether MRI at the subacute stage can detect lesions that are associated with poor functional outcome in mTBI by using anatomical images (T₁) and diffusion tensor imaging (DTI). Twenty‐three patients with mTBI were investigated and compared with 23 healthy volunteers. All patients underwent an MRI investigation and clinical tests between 7 and 28 days (D15) and between 3 and 4 months (M3) after injury. Patients were divided in two groups of poor outcome (PO) and good outcome (GO), based on their complaints at M3. Groupwise differences in gray matter partial volume between PO patients, GO patients and controls were analyzed using Voxel‐Based Morphometry (VBM) from T₁ data at D15. Differences in microstructural architecture were investigated using Tract‐Based Spatial Statistics (TBSS) and the diffusion images obtained from DTI data at D15. Permutation‐based non‐parametric testing was used to assess cluster significance at p < 0.05, corrected for multiple comparisons. Twelve GO patients and 11 PO patients were identified on the basis of their complaints. In PO patients, gray matter partial volume was significantly lower in several cortical and subcortical regions compared with controls, but did not differ from that of GO patients. No difference in diffusion variables was found between GO and controls. PO patients showed significantly higher mean diffusivity values than both controls and GO patients in the corpus callosum, the right anterior thalamic radiations and the superior longitudinal fasciculus, the inferior longitudinal fasciculus and the fronto‐occipital fasciculus bilaterally. In conclusion, PO patients differed from GO patients by the presence of diffusion changes in long association white matter fiber tracts but not by gray matter partial volume. These results suggest that DTI at the subacute stage may be a predictive marker of poor outcome in mTBI. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Diffusion imaging in brain tumors

Diffusion-weighted imaging is of limited value in the MR imaging diagnosis of various tumor pathologies, except in differentiating between dermoids/epidermoids and arachnoid cysts. Diffusion tractography, on the other hand, allows accurate depiction of important white-matter tracts adjacent to brain tumors. This technique uses data derived from diffusion tensor imaging.     

Diffusion imaging in brain infections

Diffusion-weighted magnetic resonance imaging (DWI) provides image contrasts that are different from conventional magnetic resonance techniques. DWI is particularly sensitive for detecting acute ischemic stroke, but it also has many other clinical applications, including the evaluation of central nervous system (CNS) infections. This article addresses the role of DWI in the differential diagnosis of CNS infections, and discusses the most common DWI findings for each type of infection.     

MR imaging in the detection of diffuse axonal injury with mild traumatic brain injury

Abstract

Purpose: To evaluate the occurrence and distribution of mild traumatic brain injury (MTBI) caused by diffuse axonal injury (DAI) using magnetic resonance (MR) imaging and to attempt to correlate MR findings with post-concussion symptoms (PCS).

Patients and methods: Forty MTBI patients (mean age: 32.5 years) with normal cranial computed tomography (CT) findings were examined with standard MR protocol including T₁-weighted, T₂-weighted, fluid attenuated inversion recovery (FLAIR), gradient echo (GRE) and diffusion-weighted (DW) sequences. MR imaging was performed within 24 hours of injury. The lesions were classified as DAI based on their location and morphologic appearance.

Results: In MR imaging of five (12.5%) of the patients, the lesions compatible with DAI were observed. Four patients (10%) had the foci of low signal intensity compatible with hemorrhagic shear injury on the GRE sequence, and five (12.5%) patients had high signal intensity on FLAIR and DW sequence.

Conclusion: MR imaging can be helpful in revealing DAI lesions in patients with normal CT scan findings after MTBI. FLAIR, GRE and DW sequences are superior to conventional spin-echo images in detecting DAI lesions.