Progressive changes of white matter integrity in schizophrenia revealed by diffusion tensor imaging

Recent magnetic resonance imaging (MRI) studies using diffusion tensor imaging (DTI) have suggested reduced fractional anisotropy (FA) in the white matter (WM) of the brain in patients with schizophrenia. We tried to examine whether such reduction in FA exists and whether such changes in FA progress in an age-dependent manner in a Japanese sample of chronic schizophrenia. FA values were compared between 42 patients with chronic schizophrenia and 42 controls matched for age and gender, by using DTI with voxel-by-voxel and region-of-interest analyses. Correlations of FA values with age and duration of illness were examined. Patients with schizophrenia showed lower FA values, compared to controls, in the widespread WM areas including the uncinate fasciculi and cingulum bundles. A significant group-by-age interaction was found for FA in the WM, i.e., age-related reduction of FA was more pronounced in schizophrenics than in controls. A significant negative correlation between FA and duration of illness was also found in the WM. Our data confirmed decreased FA in schizophrenics, compared to controls in the widespread WM areas. Such decreased FA values in schizophrenia might be attributable, at least in part, to progressive changes after the onset of the illness.     

White matter changes associated with cognitive visual dysfunctions in children with cerebral palsy: A diffusion tensor imaging study

Children with cerebral palsy often present with cognitive‐visual dysfunctions characterized by visuo‐perceptual and/or visuo‐spatial deficits associated with a malfunctioning of visual‐associative areas. The neurofunctional model of this condition remains poorly understood due to the lack of a clear correlation between cognitive‐visual deficit and morphological brain anomalies. The aim of our study was to quantify the pattern of white matter abnormalities within the whole brain in children with cerebral palsy, and to identify white matter tracts sub‐serving cognitive‐visual functions, in order to better understand the basis of cognitive‐visual processing. Nine subjects (three males, mean age 8 years 9 months) with cerebral palsy underwent a visual and cognitive‐visual evaluation. Conventional brain MRI and diffusion tensor imaging were performed. The fractional anisotropy maps were calculated for every child and compared with data from 13 (four males, mean age 10 years 7 months) healthy children. Children with cerebral palsy showed decreased fractional anisotropy (a marker of white matter integrity) in corticospinal tract bilaterally, left superior longitudinal fasciculus and bilateral hippocampus. Focusing on the superior longitudinal fasciculus, the mean fractional anisotropy values were significantly lower in children affected by cerebral palsy with cognitive‐visual deficits than in those without cognitive‐visual deficits. Our findings reveal an association between cognitive‐visual profile and the superior longitudinal fasciculus integrity in children with cerebral palsy, supporting the hypothesis that visuo‐associative deficits are related to changes in fibers connecting the occipital cortex with the parietal‐frontal cortices. Decreased fractional anisotropy within the superior longitudinal fasciculus could be considered a biomarker for cognitive‐visual dysfunctions.     

不接受/禁忌思维亚型强迫障碍患者的脑白质磁共振弥散张量成像研究

目的:运用磁共振扩散张量成像技术探讨未经治疗的不接受/禁忌思维亚型强迫障碍(OCD)患者脑白质的变化及与临床症状之间的相关性。方法:对26例不接受/禁忌思维亚型OCD患者和28名性别、年龄、受教育程度相匹配的健康对照者进行弥散张量成像(DTI)扫描,采用耶鲁-布朗强迫量表(Y-BOCS)、17项汉密尔顿抑郁量表(HAMD-17)、汉密尔顿焦虑量表(HAMA)等评估临床症状,采用基于纤维束空间统计分析(TBSS)等方法比较两组全脑DTI的各向异性分数(FA),得出有差异脑区,并分析患者组脑白质改变与临床症状严重程度之间的关系。结果:和正常对照组相比,患者组的大脑胼胝体、右侧上纵束、右侧下额-枕束、右侧丘脑后辐射(视辐射部)等部位的FA值显著降低;未发现任何脑区的FA值与临床行为学量表之间的相关性。结论:多个脑白质区的结构异常可能构成不接受/禁忌思维亚型OCD患者的病理生理基础,这些脑白质区的变化可能是此亚型OCD的特征标志。     

Longitudinal reliability of tract‐based spatial statistics in diffusion tensor imaging

Relatively little is known about reliability of longitudinal diffusion‐tensor imaging (DTI) measurements despite growing interest in using DTI to track change in white matter structure. The purpose of this study is to quantify within‐ and between session scan‐rescan reliability of DTI‐derived measures that are commonly used to describe the characteristics of neural white matter in the context of neural plasticity research. DTI data were acquired from 16 cognitively healthy older adults (mean age 68.4). We used the Tract‐Based Spatial Statistics (TBSS) approach implemented in FSL, evaluating how different DTI preprocessing choices affect reliability indices. Test‐Retest reliability, quantified as ICC averaged across the voxels of the TBSS skeleton, ranged from 0.524 to 0.798 depending on the specific DTI‐derived measure and the applied preprocessing steps. The two main preprocessing steps that we found to improve TBSS reliability were (a) the use of a common individual template and (b) smoothing DTI data using a 1‐voxel median filter. Overall our data indicate that small choices in the preprocessing pipeline have a significant effect on test‐retest reliability, therefore influencing the power to detect change within a longitudinal study. Furthermore, differences in the data processing pipeline limit the comparability of results across studies. Hum Brain Mapp 35:4544–4555, 2014. © 2014 Wiley Periodicals, Inc.     

A diffusion tensor imaging study of white matter in obsessive-compulsive disorder

Our objective was to test for differences between subjects with obsessive-compulsive disorder (OCD) and healthy controls with respect to white matter architecture within the cingulum bundle (CB) and anterior limb of the internal capsule (ALIC). We studied eight subjects with active OCD and 10 matched healthy controls using diffusion tensor magnetic resonance imaging (DT-MRI) at 1.5 T (Tesla). Fractional anisotropy (FA) was evaluated in both CB and ALIC. Both voxelwise and region-of-interest methods of analysis were employed. Within both the left CB and the left ALIC, subjects with OCD exhibited significantly greater FA than healthy controls. In the right CB, subjects with OCD exhibited significantly decreased FA versus healthy control subjects. Additionally, the OCD group exhibited abnormal asymmetry (left > right) of FA in the CB. These results provide preliminary evidence for abnormal architecture within the CB and ALIC in OCD. FA differences in these areas are consistent with the presence of abnormal connections between the nodes linked by these tracts. This could explain why surgically severing these tracts is therapeutic. Additional studies are needed to replicate these findings and to clarify their pathological and clinical significance.     

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.     

精神分裂症首次发病患者的磁共振弥散张量显像研究

目的探讨从未用过药的精神分裂症首次发病(以下简称首发)患者的重要白质及部分灰质区的磁共振弥散张量显像(DTI)的特点。方法选取9例首发精神分裂症患者(患者组)及9名年龄、性别、受教育程度与患者组相配对的健康者,应用DTI成像技术检测脑额颞交界处、内囊等白质区和颞中回灰质、中央前回、中央后回等灰质区的各向异性(FA)、表观扩散系数(ADC)及双侧海马体积。结果患者组及对照组组内左右两侧兴趣区FA值及ADC值的差异无统计学意义(P>0.05);患者组与对照组各感兴趣区FA值差异无统计学意义(P>0.05),但患者组颞中回灰质(8.655×10-9)、中央前回(7.816×10-9)、中央后回(7.855×10-9)ADC值高于对照组(分别为7.428×10-9,6.921×10-9,7.013×10-9;P=0.049,0.009,0.005);两组内及组间双侧海马体积比较,差异均无统计学意义(P>0.05)。结论首发精神分裂症患者与健康者DTI参数之间没有明显区别。     

Combined brain voxel-based morphometry and diffusion tensor imaging study in idiopathic Restless Legs Syndrome patients

Background and purpose: The aim of this study was to evaluate the presence of abnormalities in the brain of patients with restless legs syndrome (RLS) using voxel‐based morphometry and diffusion tensor imaging (DTI). Methods: Twenty patients and twenty controls were studied. Voxel‐based morphometry analysis was performed using statistical parametric mapping (SPM8) and FSL‐VBM software tools. For voxel‐wise analysis of DTI, tract‐based spatial statistics (TBSS) and SPM8 were used. Results: Applying an appropriate threshold of probability, no significant results were found either in comparison or in correlation analyses. Conclusions: Our data argue against clear structural or microstructural abnormalities in the brain of patients with idiopathic RLS, suggesting a prevalent role of functional or metabolic impairment.     

Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis: Revisited

Voxel‐based analyses (VBA) are increasingly being used to detect white matter abnormalities with diffusion tensor imaging (DTI) in different types of pathologies. However, the validity, specificity, and sensitivity of statistical inferences of group differences to a large extent depend on the quality of the spatial normalization of the DTI images. Using high‐dimensional nonrigid coregistration techniques that are able to align both the spatial and orientational diffusion information and incorporate appropriate templates that contain this complete DT information may improve this quality. Alternatively, a hybrid technique such as tract‐based spatial statistics (TBSS) may improve the reliability of the statistical results by generating voxel‐wise statistics without the need for perfect image alignment and spatial smoothing. In this study, we have used (1) a coregistration algorithm that was optimized for coregistration of DTI data and (2) a population‐based DTI atlas to reanalyze our previously published VBA, which compared the fractional anisotropy and mean diffusivity maps of patients with amyotrophic lateral sclerosis (ALS) with those of healthy controls. Additionally, we performed a complementary TBSS analysis to improve our understanding and interpretation of the VBA results. We demonstrate that, as the overall variance of the diffusion properties is lowered after normalizing the DTI data with such recently developed techniques (VBA using our own optimized high‐dimensional nonrigid coregistration and TBSS), more reliable voxel‐wise statistical results can be obtained than had previously been possible, with our VBA and TBSS yielding very similar results. This study provides support for the view of ALS as a multisystem disease, in which the entire frontotemporal lobe is implicated. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Altered white matter microstructural integrity revealed by voxel-wise analysis of diffusion tensor imaging in welders with manganese exposure

Chronic exposure to manganese (Mn), which can be an occupational hazard or can result from liver failure, is associated with adverse motor and cognitive outcomes. Evidence from previous neuroimaging and magnetic resonance spectroscopy studies suggested alteration of function in Mn-exposed brains. However, the effect of chronic exposure of the human brain to Mn on white matter (WM) structure has not yet been determined. In the present study, we used diffusion tensor imaging (DTI) to investigate whether welders exposed to Mn demonstrate differences in WM integrity, compared with control subjects. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on a voxel-wise basis in 30 male welders with exposure to Mn and in 19 age- and gender-matched control subjects. Direct comparison between welders and controls using investigator-independent Statistical Parametric Mapping (SPM) voxel-wise analysis of DTI metrics revealed a reduction of FA in the corpus callosum (CC) and frontal WM in Mn-exposed welders. Further, marked increases in RD and negligible changes in AD suggested that the microstructural changes in the CC and frontal WM result from compromised radial directionality of fibers in these areas, caused primarily by demyelination. Correlation analysis with neurobehavioral performance also suggested that the microstructural abnormalities were associated with subtle motor and cognitive differences in welders.     

Effects of androgenization on the white matter microstructure of female-to-male transsexuals. A diffusion tensor imaging study

Diffusion tensor imaging (DTI) can sensitively detect white matter sex differences and the effects of pharmacological treatments. Before cross-sex hormone treatment, the white matter microstructure of several brain bundles in female-to-male transsexuals (FtMs) differs from those in females but not from that in males. The purpose of this study was to investigate whether cross-sex hormone treatment (androgenization) affects the brain white matter microstructure. Using a Siemens 3 T Trio Tim Magneton, DTI was performed twice, before and during cross-sex hormonal treatment with testosterone in 15 FtMs scanned. Fractional anisotropy (FA) was analyzed on white matter of the whole brain, and the latter was spatially analyzed using Tract-Based Spatial Statistics. Before each scan the subjects were assessed for serum testosterone, sex hormone binding globulin level (SHBG), and their free testosterone index. After at least seven months of cross-gender hormonal treatment, FA values increased in the right superior longitudinal fasciculus (SLF) and the right corticospinal tract (CST) in FtMs compared to their pre-treatment values. Hierarchical regression analyses showed that the increments in the FA values in the SLF and CST are predicted by the free testosterone index before hormonal treatment. All these observations suggest that testosterone treatment changes white matter microstructure in FtMs.     

Group‐specific regional white matter abnormality revealed in diffusion tensor imaging of medial temporal lobe epilepsy without hippocampal sclerosis

Purpose: In comparison to temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (TLE‐HS), TLE patients without HS (TLE‐NH) have a similar clinical course but may result in worse surgical outcome. We investigated whether the clinical features related to the lack of HS in TLE patients (TLE‐NH) can be explained by water diffusion abnormalities throughout diffusion tensor imaging (DTI) by voxel‐based analysis. Methods: Nineteen patients with TLE‐HS (left/right TLE 12:7), 18 patients with TLE‐NH (left/right TLE 10:8), and 20 controls were included in the study. By statistical parametric mapping (SPM2), the diffusion properties specific to disease characteristics (TLE‐HS vs. TLE‐NH) were analyzed. Results: In TLE‐HS, we found the areas of increased mean diffusivity (MD) in their ipsilateral temporal and extratemporal areas including the hippocampus, parahippocampal, and frontoparietal regions. Left TLE‐HS showed a characteristic MD increase in the ipsilateral posterior cingulum, isthmus of corpus callosum, and contralateral occipital and temporal regions, which was not observed in right TLE‐HS group. In left TLE‐NH, two regions of increased MD were observed in the ipsilateral posterior fornix (within fusiform gyrus) and posterior cingulum. Right TLE‐NH did not show any increased MD. Discussion: In left TLE‐NH, we could find the water diffusion change along the posterior cingulum, which was quite different from the extensive abnormality from TLE‐HS. In addition, there was a lesion‐side–specific distribution (left predominant) of pathology in mesial TLE. This provides a possibility that TLE‐NH is a heterogenous or entity different from TLE‐HS.     

Longitudinal diffusion tensor imaging after pediatric traumatic brain injury: Impact of age at injury and time since injury on pathway integrity

Following pediatric traumatic brain injury (TBI), longitudinal diffusion tensor imaging may characterize alterations in initial recovery and subsequent trajectory of white matter development. Our primary aim examined effects of age at injury and time since injury on pathway microstructure in children ages 6–15 scanned 3 and 24 months after TBI. Microstructural values generated using tract‐based spatial statistics extracted from core association, limbic, and projection pathways were analyzed using general linear mixed models. Relative to children with orthopedic injury, the TBI group had lower fractional anisotropy (FA) bilaterally in all seven pathways. In left‐hemisphere association pathways, school‐aged children with TBI had the lowest initial pathway integrity and showed the greatest increase in FA over time suggesting continued development despite incomplete recovery. Adolescents showed limited change in FA and radial diffusivity and had the greatest residual deficit suggesting relatively arrested development. Radial diffusivity was persistently elevated in the TBI group, implicating dysmyelination as a core contributor to chronic post‐traumatic neurodegenerative changes. The secondary aim compared FA values over time in the total sample, including participants contributing either one or two scans to the analysis, to the longitudinal cases contributing two scans. For each pathway, FA values and effect sizes were very similar and indicated extremely small differences in measurement of change over time in the total and longitudinal samples. Statistical approaches incorporating missing data may reliably estimate the effects of TBI and provide increased power to identify whether pathways show neurodegeneration, arrested development, or continued growth following pediatric TBI. Hum Brain Mapp 37:3929–3945, 2016. © 2016 Wiley Periodicals, Inc.     

首次发病未用药老年抑郁症患者脑白质完整性的弥散张量成像研究

目的 使用弥散张量成像探讨首次发病未用药老年抑郁症患者的脑白质完整性.方法 15例首次发病未用药的老年抑郁症患者和15例正常对照组接受脑弥散张量成像扫描,用基于体素的分析方法对脑内所有体素的各向异性分数(FA)逐一进行组间比较.结果 与正常对照组相比,首次发病未用药老年抑郁症患者左侧前扣带(丛集体积=106体素,t=3.21)、右侧前扣带(丛集体积=60体素,t=2.71)、右侧膝下扣带(丛集体积=63体素,t=3.37)、左侧脑干(丛集体积=62体素,t=3.25)白质FA值显著降低(检验水准为未校正的单侧P＜0.01,体素集阈值＞50体素).结论 老年抑郁症发病早期存在双侧前扣带及右侧膝下扣带白质完整性下降,经由该脑区的神经通路损害可能与老年抑郁症的病理机制有关.     

首次发病未用药老年抑郁症患者脑白质完整性的弥散张量成像研究

Objective To explore the white matter integrity by using diffusion tensor imaging (DTI) in first-episode, medication-naive geriatric patients with major depressive disorder.Methods Fifteen first-episode, medication-naive depressive patients and fifteen healthy controls underwent DTI scan.Fractional anisotropy (FA) of white matter was compared between the two groups using voxel-based approach.Results Compared with healthy controls, geriatric depressive patients showed significantly lower FA in left anterior cingulate (cluster size = 106 voxels, t = 3.21 ), right anterior cingulate ( cluster size =60 voxels, t = 2.71 ), right subgenual cingulate ( cluster size = 63 voxels, t = 3.37 ) and left brainstem ( cluster size = 62 voxels, t = 3.25 ) ( level of significance was uncorrected single-tailed P ＜ 0.01, threshold of cluster size ＞ 50 voxels).Conclusion Decrease of white matter integrity in bilateral anterior cingulate and right subgenual cingulate are present in the early stage of geriatric depression.Lesions of neural pathways by way of these regions may be involved in the pathophysiology of geriatric depression.     

首次发病未用药老年抑郁症患者脑白质完整性的弥散张量成像研究

Objective To explore the white matter integrity by using diffusion tensor imaging (DTI) in first-episode, medication-naive geriatric patients with major depressive disorder.Methods Fifteen first-episode, medication-naive depressive patients and fifteen healthy controls underwent DTI scan.Fractional anisotropy (FA) of white matter was compared between the two groups using voxel-based approach.Results Compared with healthy controls, geriatric depressive patients showed significantly lower FA in left anterior cingulate (cluster size = 106 voxels, t = 3.21 ), right anterior cingulate ( cluster size =60 voxels, t = 2.71 ), right subgenual cingulate ( cluster size = 63 voxels, t = 3.37 ) and left brainstem ( cluster size = 62 voxels, t = 3.25 ) ( level of significance was uncorrected single-tailed P ＜ 0.01, threshold of cluster size ＞ 50 voxels).Conclusion Decrease of white matter integrity in bilateral anterior cingulate and right subgenual cingulate are present in the early stage of geriatric depression.Lesions of neural pathways by way of these regions may be involved in the pathophysiology of geriatric depression.     

Relation between brain lesion location and clinical outcome in patients with severe traumatic brain injury: A diffusion tensor imaging study using voxel‐based approaches

The early prediction of consciousness recovery from traumatic brain injury (TBI) is crucial to make decisions about the appropriate use of prolonged intensive care. Diffusion tensor imaging (DTI) has been proposed as a biomarker of white matter injury that could be used in a classification purpose. Instead of region‐of‐interest‐based approach, we applied voxel‐based approaches (voxel‐based DTI and tract‐based spatial statistics) on 30 patients with TBI to identify, without any prior, the brain regions that were specifically damaged in unfavorable 1‐year outcome group compared to the favorable one. DTI were acquired at mean 23 days (5–53 days) and two DTI‐derived indices, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), were tested. Our results showed that (1) ADC is not a relevant biomarker for early 1‐year outcome prognosis; (2) FA measured in inferior longitudinal fasciculus, in cerebral peduncle, in posterior limb of the internal capsule, and in posterior corpus callosum is specifically decreased in unfavorable outcome group compare to the favorable one; (3) a linear discriminant analysis using the FA measured in these four regions showed good classification performance (sensitivity = 86% and specificity = 86%). These findings confirm the relevance of the use of DTI as biomarkers for consciousness recovery after TBI and support the possible use of these biomarkers for early classification of patients. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.