Alterations of the cerebral microstructure in patients with noise-induced hearing loss: A diffusion tensor imaging study.

OBJECTIVE: To explore the changes in the cerebral microstructure of patients with noise-induced hearing loss (NIHL) using diffusion tensor imaging (DTI). METHOD: Overall, 122 patients with NIHL (mild [MP, n = 79], relatively severe patients [including moderate and severe; RSP, n = 32], and undetermined [lost to follow-up, n = 11]) and 84 healthy controls (HCs) were enrolled. All clinical data, including age, education level, hearing threshold, occupation type, noise exposure time, and some scale scores (including the Mini-Mental State Examination [MMSE], tinnitus handicap inventory [THI], and Hamilton Anxiety Scale [HAMA]), were collected and analyzed. All participants underwent T1WI3DFSPGR and DTI, and tract-based spatial statistics and region of interest (ROI) analysis were used for assessment. RESULTS: The final sample included 71 MP, 28 RSP, and 75 HCs. The HAMA scores of the three groups were significantly different (p < .05). The noise exposure times, hearing thresholds, and HAMA scores of the MP and RSP were significantly different (p < .05). The noise exposure time was positively correlated with the hearing threshold and negatively correlated with the HAMA scores (p < .05), whereas the THI scores were positively correlated with the hearing threshold (p < .05). DTI analysis showed that all DTI parameters (fractional anisotropy [FA], axial diffusivity [AD], mean diffusivity [MD], and radial diffusivity [RD]) were significantly different in the left inferior longitudinal fasciculus (ILF) and left inferior fronto-occipital fasciculus (IFOF) for the three groups (p < .05). In addition, the FA values were significantly lower in the bilateral corticospinal tract (CST), right fronto-pontine tract (FPT), right forceps major, left superior longitudinal fasciculus (temporal part) (SLF), and left cingulum (hippocampus) (C-H) of the MP and RSP than in those of the HCs (p < .05); the AD values showed diverse changes in the bilateral CST, left IFOF, right anterior thalamic radiation, right external capsule (EC), right SLF, and right superior cerebellar peduncle (SCP) of the MP and RSP relative to those of the HC (p < .05). However, there were no significant differences among the bilateral auditory cortex ROIs of the three groups (p > .05). There was a significant negative correlation between the FA and HAMA scores for the left IFOF/ILF, right FPT, left SLF, and left C-H for the three groups (p < .05). There was a significant positive correlation between the AD and HAMA scores for the left IFOF/ILF and right EC of the three groups (p < .05). There were significantly positive correlations between the RD/MD and HAMA scores in the left IFOF/ILF of the three groups (p < .05). There was a significant negative correlation between the AD in the right SCP and noise exposure time of the MP and RSP groups (p < .05). The AD, MD, and RD in the left ROI were significantly positively correlated with hearing threshold in the MP and RSP groups (p < .05), whereas FA in the right ROI was significantly positively correlated with the HAMA scores for the three groups (p < .05). CONCLUSION: The changes in the white matter (WM) microstructure may be related to hearing loss caused by noise exposure, and the WM structural abnormalities in patients with NIHL were mainly located in the syndesmotic fibers of the temporooccipital region, which affected the auditory and language pathways. This confirmed that the auditory pathways have abnormal structural connectivity in patients with NIHL.

Childhood trauma is associated with altered white matter microstructural organization in schizophrenia.

It has been reported that childhood trauma (CT) is associated with reductions in fractional anisotropy (FA) in individuals with schizophrenia (SZ). Here, we hypothesized that SZ with high levels of CT will show the greatest reductions in FA in frontolimbic and frontoparietal regions compared to healthy controls (HC) with high trauma levels and participants with no/low levels of CT. Thirty-seven SZ and 129 HC with CT experience were dichotomized into groups of 'none/low' or 'high' levels. Participants underwent diffusion-weighted MRI, and Tract-based spatial statistics were employed to assess the main effect of diagnosis, main effect of CT severity irrespective of diagnosis, and interaction between diagnosis and CT severity. SZ showed FA reductions in the corpus callosum and corona radiata compared to HC. Irrespective of a diagnosis, high CT levels (n = 48) were related to FA reductions in frontolimbic and frontoparietal regions compared to those with none/low levels of CT (n = 118). However, no significant interaction between diagnosis and high levels of CT was found (n = 13). Across all participants, we observed effects of CT on late developing frontolimbic and frontoparietal regions, suggesting that the effects of CT severity on white matter organization may be independent of schizophrenia.

Disruption of white matter integrity and its relationship with cognitive function in non-severe traumatic brain injury.

Background: Impairment in cognitive function is a recognized outcome of traumatic brain injury (TBI). However, the degree of impairment has variable relationship with TBI severity and time post injury. The underlying pathology is often due to diffuse axonal injury that has been found even in mild TBI. In this study, we examine the state of white matter putative connectivity in patients with non-severe TBI in the subacute phase, i.e., within 10 weeks of injury and determine its relationship with neuropsychological scores. Methods: We conducted a case-control prospective study involving 11 male adult patients with non-severe TBI and an age-matched control group of 11 adult male volunteers. Diffusion MRI scanning and neuropsychological tests were administered within 10 weeks post injury. The difference in fractional anisotropy (FA) values between the patient and control groups was examined using tract-based spatial statistics. The FA values that were significantly different between patients and controls were then correlated with neuropsychological tests in the patient group. Results: Several clusters with peak voxels of significant FA reductions (p < 0.05) in the white matter skeleton were seen in patients compared to the control group. These clusters were located in the superior fronto-occipital fasciculus, superior longitudinal fasciculus, uncinate fasciculus, and cingulum, as well as white matter fibers in the area of genu of corpus callosum, anterior corona radiata, superior corona radiata, anterior thalamic radiation and part of inferior frontal gyrus. Mean global FA magnitude correlated significantly with MAVLT immediate recall scores while matrix reasoning scores correlated positively with FA values in the area of right superior fronto-occipital fasciculus and left anterior corona radiata. Conclusion: The non-severe TBI patients had abnormally reduced FA values in multiple regions compared to controls that correlated with several measures of executive function during the sub-acute phase of TBI.

A Diffusion Tensor Imaging Study on the White Matter Structures Related to the Phonology in Cantonese-Mandarin Bilinguals.

Cantonese and Mandarin are logographic languages, and the phonology is the main difference between the two languages. It is unclear whether the long-term experience of Cantonese-Mandarin bilingualism will shape different brain white matter structures related to phonological processing. A total of 30 Cantonese-Mandarin bilinguals and 30 Mandarin monolinguals completed diffusion-weighted imaging scan and phonological processing tasks. The tractography and tract-based spatial statistics were used to investigate the structural differences in the bilateral superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), and inferior fronto-occipital fasciculus (IFOF) between Cantonese-Mandarin bilinguals and Mandarin monolinguals. The post-hoc correlation analysis was conducted to investigate the relationship between the different structures with phonological processing skills. Compared to the Mandarin monolinguals, the Cantonese-Mandarin bilinguals had higher fractional anisotropy (FA) along the left ILFs higher mean diffusivity (MD) along the right IFOF and the temporoparietal segment of SLF (tSLF), higher axial diffusivity (AD) in the right IFOF and left ILF, and lower number of streamlines in the bilateral tSLF. The mean AD of the different voxels in the right IFOF and the mean FA of the different voxels in the left ILF were positively correlated with the inverse efficiency score (IES) of the Cantonese auditory and Mandarin visual rhyming judgment tasks, respectively, within the bilingual group. The correlation between FA and IES was different among the groups. The long-term experience of Cantonese-Mandarin bilinguals shapes the different brain white matter structures in tSLF, IFOF, and ILF. Compared to the monolinguals, the bilinguals' white matter showed higher diffusivity, especially in the axonal direction. These changes were related to bilinguals' phonological processing.

A tract-based spatial statistics study of white matter integrity in epilepsy.

OBJECTIVE: To explore the changes of cerebral white matter diffusion tensor in epilepsy. METHODS: This study was a retrospective study based on diffusion tensor imaging (DTI). Twenty-six epileptic patients and 42 normal controls matched for sex, age and handedness were enrolled in our research. Based on the method of tract-based spatial statistics (TBSS), we analyzed the changes of each relevant parameter index of DTI in white matter of the brain in all subjects, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). RESULTS: In comparison with the control group, epileptic patients had decreased FA and elevated MD, AD, and RD in the anterior thalamic radiation, corticospinal tract, forceps major, forceps minor, cingulum, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus and uncinate fasciculus (P < 0.05). CONCLUSION: Widespread white matter integrity was observed in epileptic patients, which may be the structural basis for the development of affective disorders, impaired cognition, and motor abnormalities.

Brain White Matter Abnormality Induced by Chronic Spinal Cord Injury in the Pediatric Population: A Preliminary Tract-based Spatial Statistic Study.

Objectives: Tract-based spatial statistics (TBSS) is a diffusion tensor imaging (DTI)-based processing technique that aims to improve the objectivity and interpretability of analysis of multisubject diffusion imaging studies. This study used TBSS to measure quantitative changes in brain white matter structures following spinal cord injury (SCI). Methods: Eighteen SCI subjects aged 8-20 years old (mean age, 16.5 years) were scanned using a conventional single-shot EPI DTI protocol using a 3.0T Siemens MR scanner. All participants underwent a complete International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination to determine the level and severity of injury. Five participants were classified as American Spinal Injury Association Impairment Scale (AIS) A, nine as AIS B, and four as AIS C/D. Imaging parameters used for data collection were as follows: 20 directions, b = 1000 s/mm2, voxel size = 1.8 mm x 1.8 mm, slice thickness = 5 mm, TE = 95 ms, TR = 4300 ms, slices = 30, TA = 4:45 min. To generate TBSS, nonparametric permutation tests were used for voxel-wise statistical analysis of the fractional anisotropy (FA) skeletons between AIS groups. A two-tailed t test was applied to extract voxels with significant differences at p < .05. Results: Notable significant changes occurred throughout the corticospinal, spinothalamic, and dorsal column/medial lemniscus tracts. Altered regions in the temporal, occipital, and parietal lobes were also identified. Conclusion: These results suggest that white matter structures are altered differently between people with different AIS classifications. TBSS has the potential to serve as a screening tool to identify white matter changes in regions of interest.

Diffusion Tensor Imaging Before and 3 Months After Concentrated Exposure Response Prevention in Obsessive-Compulsive Disorder.

Background: Subtle differences in white matter microstructure have been found in obsessive-compulsive disorder (OCD) compared to controls using diffusion tensor imaging (DTI), but it is unclear if and how this change after treatment. The primary aim of this pre-registered study was to investigate white matter integrity between OCD patients and controls and changes after concentrated exposure and response prevention (ERP). Methods: Fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) and mean diffusivity (MD) were estimated using FMRIB Software Library (FSL). The images were registered to a study-specific template using a longitudinal pipeline based on full tensor information in DTI-TK. Voxel-based analysis was performed using tract-based spatial statistics (TBSS). Using SPSS, we compared the integrity in three bilateral regions of interest (ROI), the sagittal stratum, posterior thalamic radiation and cingulum, in 32 OCD patients and 30 matched healthy controls at baseline. Patients received a four-day concentrated ERP format. We investigated longitudinal changes in 26 OCD patients and 22 healthy controls at 3months follow-up using repeated-measures ANOVA. Exploratory t-tests were conducted for AD and MD. Secondary hypothesis used linear regression to investigate if baseline FA predict treatment outcome 3 months later, and if patients with illness onset before 18 years of age would show lower FA in sagittal stratum. Finally, we performed sensitivity analysis on medication and comorbidity influences on FA. Results: Three months after treatment, 77% of the patients were in remission. Contrary to our hypotheses, we did not find any significant differences in FA, RD, AD or MD between the groups before treatment, nor significant group by time effects in any of the ROI. None of the baseline FA measures significantly predicted treatment outcome. Illness onset before 18 years of age did not significantly predict FA in the sagittal stratum. Adjusting for medication or comorbid anxiety or mood disorder did not influence the results. Conclusions: Although concentrated ERP in OCD lead to high remission, we did not find significant long-term changes by DTI. Future studies will benefit from using larger sample sizes and multi-shell diffusion-weighted imaging when investigating white matter microstructure in OCD and underlying neurobiological mechanisms of treatment.

Microstructural White Matter Alterations in Cognitively Impaired Patients at Early Stages of Multiple Sclerosis.

PURPOSE: As conventional quantitative magnetic resonance imaging (MRI) parameters are weakly associated with cognitive impairment (CI) in early multiple sclerosis (MS), we explored microstructural white matter alterations in early MS or clinically isolated syndrome (CIS) comparing patients with or without CI. METHODS: Based on a preceding tract-based spatial statistics analysis (3 Tesla MRI) which contrasted 106 patients with early MS or CIS and 49 healthy controls, diffusion metrics (fractional anisotropy, FA, mean diffusivity, MD) were extracted from significant clusters using an atlas-based approach. The FA and MD were compared between patients with (Ci_P n = 14) and without (Cp_P n = 81) cognitive impairment in a subset of patients who underwent CI screening. RESULTS: The FA was reduced in Ci_P compared to Cp_P in the splenium of corpus callosum (p = 0.001), right parahippocampal cingulum (p = 0.002) and fornix cres./stria terminalis (0.042), left posterior corona radiata (p = 0.012), bilateral cerebral peduncles, medial lemniscus and in cerebellar tracts. Increased MD was detected in the splenium of corpus callosum (p = 0.01). The CI-related localizations overlapped only partially with MS lesions. CONCLUSION: Microstructural white matter alterations at disease onset were detectable in Ci_P compared to Cp_P in known cognitively relevant fiber tracts, indicating the relevance of early treatment initiation in MS and CIS.

[Abnormalities of white matter differentiate the Parkinson variant of multiple system atrophy from Parkinson's disease].

Objective: To identify objective markers between the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD). Methods: Retrospective analysis was performed on 10 patients with MSA-P, 15 patients with PD, and 15 healthy control group during the period from August 2016 to February 2019 in Baoshan Branch of Shanghai First People's Hospital.We combined the novel tract based spatial statistics (TBSS) and region of interest (ROI) analyses for the first time to investigate three groups with diffusion tensor imaging. By TBSS, we performed pairwise comparisons of mean diffusivity and fractional anisotropy (FA) maps. The clusters with significant differences between MSA-P and PD were used as ROIs for further analyses. Results: FA values in the left anterior thalamic radiation(ATR) (ROI values were 0.371(0.287-0.535), 0.472(0.390-0.594), 0.473(0.388-0.555); P values were 0.008, 0.008) and left superior longitudinal fasciculus (SLF)(ROI values were 0.397(0.291-0.469), 0.456(0.338-0.560), 0.473(0.427-0.530); P values were 0.013,<0.001) were significantly decreased in MSA-P compared with PD or controls, and significantly correlated with clinical data((r =-0.807, P =0.005),(r =-0.455, P =0.022)). Conclusion: Our findings indicate the abnormalities of left ATR and left SLF as specific biomarkers for differential diagnosis.

Structural MRI research in patients with nasopharyngeal carcinoma following radiotherapy: A DTI and VBM study.

The aim of the present study was to investigate the microstructural characteristics of the brain lobes following radiotherapy (RT) for patients with nasopharyngeal carcinoma (NPC) at distinct times. Diffusion tensor imaging (DTI) and 3D-T1-weighted imaging was performed in 70 age- and sex-matched subjects, 24 of whom were pre-treatment patients. The patients were divided into three groups, according to the time following completion of RT. Fractional anisotropy (FA) and gray matter (GM) volume were determined. The DTI data were analyzed using tract-based spatial statistics and the GM volume was analyzed using voxel-based morphometry (VBM). Compared with the pre-RT group, the mean FA values in the left parietal lobe white matter (WM) and right cerebellum decreased significantly in the post-RT 0-6 month group (P<0.05). In addition, the mean FA values in the right parietal lobe WM decreased significantly in the post-RT 6-12 month group (P<0.05), compared with the pre-RT group. The FA level in the right temporal lobe remained significantly decreased, compared with that in the pre-RT group (P<0.05) for 1 year after RT. Furthermore, compared with pre-RT group, the GM volume in the bilateral frontal lobe, right occipital lobe, left parietal lobe, right temporal lobe and left cerebellum decreased significantly in the post-RT 0-6 month group (P<0.05), and in the bilateral temporal lobe, parietal lobe, right frontal lobe and left cerebellum, the GM volume decreased significantly in the post-RT 6-12 month group (P<0.05). The GM volume in the right temporal lobe, bilateral frontal lobe and bilateral cerebellum remained significantly decreased compared with that in the pre-RT group (P<0.05) for 1 year after RT. A combination of DTI and VBM may be used to determine radiation-induced brain injury in patients treated for NPC.

Longitudinal assessment of fractional anisotropy alterations caused by simian immunodeficiency virus infection: a preliminary diffusion tensor imaging study.

Previous diffusion tensor imaging (DTI) studies found that human immunodeficiency virus (HIV) infection led to white matter (WM) microstructure degeneration. Most of the DTI studies were cross-sectional and thus merely investigated only one specific point in the disease. In order to systematically study the WM impairments caused by HIV infection, more longitudinal studies are needed. However, longitudinal studies on HIV patients are very difficult to conduct. To address this question, we employed the simian immunodeficiency virus (SIV)-infected rhesus monkeys model to carry out a longitudinal DTI study. We aimed to longitudinally access the WM abnormalities of SIV-infected rhesus monkeys by studying the fractional anisotropy (FA) alterations with Tract Based Spatial Statistic (TBSS) analysis. Four rhesus monkeys inoculated intravenously with SIVmac239 were utilized in the study. DTI scans and peripheral blood CD4(+) and CD8(+) T cell counts were acquired prior to virus inoculation (as the baseline) and in the 12th and 24th week postvirus inoculation. Significant FA alterations were found in the two areas of the inferotemporal regions (iTE), respectively located in the ventral subregion of posterior iTE (iTEpv) and the dorsal subregion of iTE (iTEpd). The decreased FA values in iTEpd were found significantly negatively correlated with the elevated peripheral blood CD4(+)/CD8(+) ratios. It might suggest that WM in iTEpd was still impaired even though the immune dysfunction alleviated temporally.

Adverse childhood experiences influence white matter microstructure in patients with schizophrenia.

Integrity of brain white matter (WM) tracts in adulthood could be detrimentally affected by exposure to adverse childhood experiences (ACE). Changes of diffusion tensor imaging (DTI) measures suggesting WM disruption have been reported in patients with schizophrenia together with a history of childhood maltreatment. We therefore hypothesized that ACE could be associated with altered DTI measures of WM integrity in patients with schizophrenia. We tested this hypothesis in 83 schizophrenia patients using whole brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial, radial, and mean diffusivity (MD), and fractional anisotropy (FA). We observed an inverse correlation between severity of ACE and DTI measures of FA, and a positive correlation with MD in several WM tracts including corona radiata, thalamic radiations, corpus callosum, cingulum bundle, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus. Lower FA and higher MD are indexes of a reduction in fibre coherence and integrity. The association of ACE to reduced FA and increased MD in key WM tracts contributing to the functional integrity of the brain suggests that ACE might contribute to the pathophysiology of schizophrenia through a detrimental action on structural connectivity in critical cortico-limbic networks.

White matter differences between multiple system atrophy (parkinsonian type) and Parkinson's disease: A diffusion tensor image study.

The clinical differential diagnosis between the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD) is difficult in early stages. To identify objective markers for differential diagnosis, we combined the novel tract-based spatial statistics (TBSS) and region of interest (ROI) analyses for the first time to investigate three groups (15 MSA-P, 20 PD patients and 20 controls) with diffusion tensor imaging data. By TBSS, we performed pairwise comparisons of fractional anisotropy (FA), mean diffusivity, radial diffusivity (RD) and axial diffusivity maps. The clusters with significant differences between MSA-P and PD were used as ROIs for further analyses. FA/RD values in bilateral corticospinal tract (CST) and left anterior thalamic radiation (ATR) in MSA-P were significantly different from PD or controls, and significantly correlated with clinical data. These findings indicated that the abnormalities of left ATR and bilateral CST were specific for MSA-P relative to PD or controls, and seemed to be promising for differential diagnosis. Furthermore, it may be useful for severity assessment of MSA-P.

Tract based spatial statistics in multiple system atrophy: a comparison between clinical subtypes.

OBJECTIVE: Using a novel method of tract-based spatial statistics (TBSS), this study aimed to investigate micro-structural white matter similarities and differences between the two MSA variants. METHODS: Diffusion tensor image data were acquired from 10 MSA-P, 15 MSA-C patients and 15 controls. Using TBSS, we performed pairwise comparison by examining the fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD) and radial diffusivity (RD) maps of the white matter tract. Clusters showing diffusivity abnormalities were used as region of interests for correlation analysis. RESULTS: Both in MSA-C and MSA-P, we detected significantly decreased FA values in bilateral corticospinal tract (CST) and right anterior thalamic radiation (ATR), increased RD values in bilateral CST, which correlated significantly with clinical severity. Direct comparison of two variants showed higher AD values of superior longitudinal fasciculus (SLF) in MSA-P than in MSA-C. CONCLUSIONS: These findings indicate that patients with MSA-C and MSA-P share similar diffusivity abnormalities in the bilateral CST and right ATR. Higher AD values of SLF in MSA-P than in MSA-C might be a reason for faster functional deterioration in MSA-P than in MSA-C.

White matter abnormalities in patients with focal cortical dysplasia revealed by diffusion tensor imaging analysis in a voxelwise approach.

BACKGROUND: Diffusion tensor imaging (DTI) allows the analysis of changes in microstructure, through the quantification of the spread and direction of water molecules in tissues. We used fractional anisotropy (FA) maps to compare the integrity of WM between patients and controls. The objective of the present study was to investigate WM abnormalities in patients with frontal lobe epilepsy secondary to focal cortical dysplasia (FCD). MATERIALS AND METHODS: We included 31 controls (12 women, 33.1 ± 9.6 years, mean ± SD) and 22 patients (11 women, 30.4 ± 10.0 years), recruited from our outpatient clinic. They had clinical and EEG diagnosis of frontal lobe epilepsy, secondary to FCD detected on MRI. Patients and controls underwent 3T MRI, including the DTI sequence, obtained in 32 directions and b value of 1000 s/mm(2). To process the DTI we used the following softwares: MRIcroN and FSL/TBSS (tract-based spatial statistics). We used a threshold-free cluster enhancement with significance at p < 0.05, fully corrected for multiple comparisons across space. RESULTS: Areas with FA reduction in patients were identified in both hemispheres, mainly in the frontal lobes, cingulum, and forceps minor (p = 0.014), caudate e anterior thalamic radiation (p = 0.034), superior longitudinal fasciculus (p = 0.044), uncinate fasciculus, and inferior fronto-occipital fasciculus (p = 0.042). CONCLUSION: Our results showed a widespread pattern of WM microstructural abnormalities extending beyond the main lesion seen on MRI (frontal lobe), which may be related to frequent seizures or to the extent of MRI-invisible portion of FCD.