White matter abnormalities in bipolar disorder and schizophrenia detected using diffusion tensor magnetic resonance imaging

Objectives:  Strong qualitative and quantitative evidence exists of white matter abnormalities in both schizophrenia and bipolar disorder (BD). Diffusion tensor imaging (DTI) studies suggest altered connectivity in both disorders. We aim to address the diagnostic specificity of white matter abnormalities in these disorders.
Methods:  DTI was used to assess white matter integrity in clinically stable patients with familial BD (n = 42) and familial schizophrenia (n = 28), and in controls (n = 38). Differences in fractional anisotropy (FA) were measured using voxel-based morphometry and automated region of interest analysis.
Results:  Reduced FA was found in the anterior limb of the internal capsule (ALIC), anterior thalamic radiation (ATR), and in the region of the uncinate fasciculus in patients with BD and those with schizophrenia compared with controls. A direct comparison between patient groups found no significant differences in these regions. None of the findings were associated with psychotropic medication.
Conclusions:  Reduced integrity of the ALIC, uncinate fasciculus, and ATR regions is common to both schizophrenia and BD. These results imply an overlap in white matter pathology, possibly relating to risk factors common to both disorders.     

Microstructural abnormalities of white matter differentiate pediatric and adult-onset bipolar disorder

Lu LH, Zhou XJ, Fitzgerald J, Keedy SK, Reilly JL, Passarotti AM, Sweeney JA, Pavuluri M. Microstructural abnormalities of white matter differentiate pediatric and adult onset bipolar disorder. Bipolar Disord 2012: 14: 597–606. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: White‐matter microstructure, known to undergo significant developmental transformation, is abnormal in bipolar disorder (BD). Available evidence suggests that white‐matter deviation may be more pronounced in pediatric than adult‐onset BD. The present study aimed to examine how white‐matter microstructure deviates from a typical maturational trajectory in BD. Methods: Fractional anisotropy (FA) was measured in 35 individuals presenting with first episode BD (type I) and 46 healthy controls (HC) (aged 9–42) using diffusion tensor imaging (DTI). Patients were medication free and close to illness onset at the time of the DTI scans. Tract‐based spatial statistics were used to examine the center of white‐matter tracts, and FA was extracted from nine tracts of interest. Axial, radial, and mean diffusivity were examined in post‐hoc analyses. Results: The left anterior limb of the internal capsule (ALIC) showed significantly lower FA in pediatric than adult‐onset BD. The lower FA in BD was due primarily to greater radial, rather than decreased axial, diffusivity. Conclusions: The ALIC connects the frontal lobes with archistriatum, thalamus, and medial temporal regions, and alteration in these pathways may contribute to mood dysregulation in BD. Abnormalities in this pathway appear to be associated with an earlier onset of illness and thus may reflect a greater susceptibility to illness.     

Microstructural Changes of Anterior Corona Radiata in Bipolar Depression

Objective

In bipolar disorder, dysregulation of mood may result from white matter abnormalities that change fiber tract length and fiber density. There are few studies evaluating the white matter microstructural changes in bipolar I patients (BD) with depressive episodes. The present study aimed to evaluate anterior corona radiata in BD patients with depressive episode using Diffusion Tensor Imaging (DTI).

Methods

Twenty-one patients with bipolar depression and 19 healthy controls were investigated and groups were matched for age and gender. Diffusion-weighted echoplanar brain images (DW-EPI) were obtained using a 1.5 T MRI scanner. Regions of interest (ROIs) were manually placed on directional maps based on principal anisotropy. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of white matter were measured in the anterior corona radiata (ACR) bilaterally by diffusion tensor imaging.

Results

There was not a significant difference between groups of age and gender (p>0.05). Significantly lower FA was observed in bilateral ACR in bipolar patients with depression compared with healthy individuals. And there is significantly higher ADC values in the left frontal corona radiate in bipolar patients.

Conclusion

White matter abnormalities can be detected in patients with BD using DTI. The neuropathology of these abnormalities is unclear, but neuronal and axonal loss, myelin abnormalities and reduced white matter fiber density are likely to be relevant.     

White matter reduced streamline coherence in young men with autism and mental retardation

Background and purpose:  It has been proposed that white matter alterations might play a role in autistic disorders; however, published data are mainly limited to high-functioning autism. The goal of this study was to apply diffusion tensor imaging (DTI) and fiber tractography (FT) to study white matter in low-functioning autism and the relationship between white matter and cognitive impairment.
Methods:  Ten low-functioning males with autism (mean age: 19.7 ± 2.83 years) and 10 age-matched healthy males (mean age: 19.9 ± 2.64 years) underwent DTI-MRI scanning. fractional anisotropy (FA) maps were analyzed with whole brain voxel-wise and tract-of-interest statistics. Using FT algorithms, white matter tracts connecting the orbitofrontal cortex (OFC) with other brain regions were identified and compared between the two groups. FA mean values of the autistic group were correlated with intelligence quotient (IQ) scores.
Results:  Low-functioning autistic subjects showed a reduced tract volume and lower mean FA values in the left OFC network compared with controls. In the autistic group, lower FA values were associated with lower IQ scores.
Conclusions:  We showed evidence of OFC white matter network abnormalities in low-functioning autistic individuals. Our results point to a relationship between the severity of the intellectual impairment and the extent of white matter alterations.     

Diffusion tensor imaging abnormalities in focal cortical dysplasia

PURPOSE: Focal cortical dysplasia (FCD) is one of the most common underlying pathologic substrates in patients with medically intractable epilepsy. While magnetic resonance imaging (MRI) evidence of FCD is an important predictor of good surgical outcome, conventional MRI is not sensitive enough to detect all lesions. Previous reports of diffusion tensor imaging (DTI) abnormalities in FCD suggest the potential of DTI in the detection of FCD. The purpose of this study was to study subcortical white matter underlying small lesions of FCD using DTI. METHODS: Five patients with medically intractable epilepsy and FCD were investigated. Diffusion tensor imaging images were acquired (20 contiguous 3 mm thick axial slices) with maps of fractional anisotropy (FA), trace apparent diffusion coefficient (trace/3 ADC), and principal eigenvalues (ADC parallel and ADC perpendicular to white matter tracts) being calculated for each slice. Region of interest analysis was used to compare subcortical white matter ipsilateral and contralateral to the lesion. RESULTS: Three subjects with FCD associated with underlying white matter hyperintensities on T2 weighted MRI were observed to have increased trace/3 ADC, reduced fractional anisotropy and increased perpendicular water diffusivity which was greater than the relative increase in the parallel diffusivity. No DTI abnormalities were identified in two patients with FCD without white matter hyperintensities on conventional T2-weighted MRI. CONCLUSIONS: While DTI abnormalities in FCD with obvious white matter involvement are consistent with micro-structural degradation of the underlying subcortical white matter, DTI changes were not identified in FCD lesions with normal appearing white matter.     

Diffusion tensor imaging findings and their correlation with neuropsychological deficits in patients with temporal lobe epilepsy and interictal psychosis

PURPOSE: To examine frontotemporal white-matter integrity in patients with temporal lobe epilepsy (TLE) and interictal psychosis. METHOD: Patients with TLE and interictal psychosis (IP; n = 20) were compared with age-matched TLE patients without psychosis (NIP; n = 20). Patients had either no focal lesions or hippocampal sclerosis on conventional MRI. Complete diffusion tensor imaging (DTI) data were available in 18 IP and 20 NIP patients. A region-of-interest (ROI) approach was used to determine the DTI measures, fractional anisotropy (FA) and mean diffusivity (MD), in the middle frontal and middle temporal gyri. The relation between the DTI measures and neuropsychological tests previously identified as impaired in the IP group was examined. RESULTS: The IP group had significantly lower FA values in both frontal and temporal regions and significantly higher MD in bilateral frontal regions. We found that performance on some neuropsychological tests was significantly related to frontotemporal FA reductions. CONCLUSIONS: Our findings suggest that subtle abnormalities in the frontotemporal white matter of patients with interictal psychosis may be undetectable on conventional MRI. These abnormalities may contribute to the cognitive deficits detected in these patients.     

Diffusion tensor imaging: tract based spatial statistics study in essential tremor

IntroductionEssential tremor (ET) is a common movement disorder with motor and non-motor symptoms. We aimed to investigate the neurodegenerative changes in the brain white matter of patients with ET using Diffusion Tensor Imaging (DTI).MethodsClinical and MRI data from 20 patients (5 women and 15 men; age-38.2 ± 16.5 yrs) with ET and 17 controls (3 women and 14 men; age-40.7 ± 16.5 yrs) were collected prospectively. The DTI data were analyzed using tract based spatial statistics (TBSS) software for tract wise analysis. Further region of interest (ROI) analysis was carried out in the genu of corpus callosum, anterior limb of internal capsule (ALIC), corticospinal tract (CS), and cerebellar peduncles. Effect of tremor severity, disease duration and age of onset on DTI metrics was also studied.ResultsPatients with ET in comparison to controls showed significant (P_corrected < 0.05) increase of mean diffusivityand radial diffusivity in right frontoparietal white matter. Axial diffusivity increase was seen in bilateral cerebral hemispheres, thalamus, brainstem and cerebellar hemisphere white matter. No significant change in fractional anisotropy of the white matter was seen. ROI analysis also revealed abnormalities in the ALIC and cerebellar peduncles. There was no correlation between the severity of white matter changes and clinical tremor severity score as well as disease duration.ConclusionsThis study provides in vivo evidence for axonal disintegration of the cerebral and cerebellar white matter fibres in patients with ET.     

Microstructural white matter changes in euthymic bipolar patients: a whole-brain diffusion tensor imaging study

Objectives:  Brain structures of a distributed ventral-limbic and dorsal brain network have been associated with altered mood states and emotion regulation in affective disorders. So far, diffusion tensor imaging studies in bipolar patients have focused on frontal/prefrontal brain regions and found alterations in white matter integrity in manic, depressed, and euthymic bipolar patients, observed as changes in fractional anisotropy and mean diffusivity. To extend previous findings, we investigated whole-brain modifications in white matter integrity in euthymic bipolar patients with minimal manic and depressive symptoms.
Methods:  Twenty-two patients with a DSM-IV-TR diagnosis of bipolar I and II disorder in remission, with no lifetime or present comorbidities of substance abuse, and 21 sex- and age-matched healthy controls underwent diffusion tensor imaging with diffusion gradients applied along 41 directions. Fractional anisotropy and mean diffusivity group differences were explored using two voxel-based, whole-brain analyses that differ in their normalization approaches.
Results:  Fractional anisotropy was significantly increased in bipolar patients relative to healthy controls in medial frontal, precentral, inferior parietal, and occipital white matter. No group differences in mean diffusivity were found.
Conclusions:  The result of increased fractional anisotropy in euthymic bipolar patients in the present study suggests increased directional coherence of white matter fibers in bipolar patients during remission.     

Reduced white matter integrity and verbal fluency impairment in young adults with bipolar disorder: A diffusion tensor imaging study

BackgroundClinical evidence shows that bipolar disorder (BD) is characterized by white matter (WM) microstructural abnormalities. However, little is known about the biological mechanisms associated with these abnormalities and their relationship with cognitive functioning.Methods49 adult BD patients ((M ± SD): 29.27 ± 7.92 years; 17 males, 32 females; 34 BD-I, 10 BD-II, and 5 BD-NOS) and 28 age-matched normal subjects ((M ± SD): 29.19 ± 7.35 years; 10 males and 18 females) underwent diffusion tensor imaging (DTI) imaging. DTI metrics were computed using whole-brain tract-based spatial statistics (TBSS) as part of the FMRIB Software Library. Measures of WM coherence (fractional anisotropy - FA) and axonal structure (mean, axial and radial diffusivity – MD, AD and RD) were employed to characterize the microstructural alterations in the limbic, commissural, association and projection fiber tracts. All participants performed the Brief Assessment of Cognition for Affective disorders (BAC-A).ResultsBD patients performed poorly on verbal fluency tasks and exhibited large clusters of altered FA, RD and MD values within the retrolenticular part of the internal capsule, the superior and anterior corona radiata, and the corpus callosum. Increased FA values in the left IFOF and the forceps minor correlated positively with verbal fluency scores. Altered RD parameters in the corticospinal tract and the forceps minor were associated with reduced visuomotor abilities.ConclusionsThe reported verbal fluency deficits and FA, RD and MD alterations in WM structures are potential cognitive and neural markers of BD. Abnormal RD values may be associated with progressive demyelination.     

White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study

Diffuse white matter pallor is the most frequent neuropathological feature of HIV-1 infection and has been found to be particularly prominent in the advanced stages of the disease. The purpose of this study was to determine whether subtle white matter abnormalities can be detected in medically stable, ambulatory HIV-1 patients, in vivo, using diffusion tensor imaging (DTI). DTI is a magnetic resonance imaging (MRI) technique that is uniquely suited for the study of subtle white matter abnormalities. DTI was performed in six HIV-1 patients and nine controls. The two groups were similar in age. Abnormal fractional anisotropy was found in the white matter of the frontal lobes and internal capsules of the HIV-1 patients, in the absence of group differences in mean diffusivity, computed proton density, and computed T2. DTI may be more sensitive than conventional MRI methods for detecting subtle white matter disruptions in HIV-1 disease.     

A Comparative Multimodal Meta-analysis of Anisotropy and Volume Abnormalities in White Matter in People Suffering From Bipolar Disorder or Schizophrenia

Schizophrenia (SZ) and bipolar disorder (BD) share some similarities in terms of genetic-risk genes and abnormalities of gray-matter structure in the brain, but white matter (WM) abnormalities have not been studied in depth. We undertook a comparative multimodal meta-analysis to identify common and disorder-specific abnormalities in WM structure between SZ and BD. Anisotropic effect size-signed differential mapping software was used to conduct a comparative meta-analysis of 68 diffusion tensor imaging (DTI) and 34 voxel-based morphometry (VBM) studies comparing fractional anisotropy (FA) and white matter volume (WMV), respectively, between patients with SZ (DTI: N = 1543; VBM: N = 1068) and BD (DTI: N = 983; VBM: N = 518) and healthy controls (HCs). The bilateral corpus callosum (extending to the anterior and superior corona radiata) showed shared decreased WMV and FA in SZ and BD. Compared with BD patients, SZ patients showed remarkable disorder-specific WM abnormalities: decreased FA and increased WMV in the left cingulum, and increased FA plus decreased WMV in the right anterior limb of the internal capsule. SZ patients showed more extensive alterations in WM than BD cases, which may be the pathophysiological basis for the clinical continuity of both disorders. The disorder-specific regions in the left cingulum and right anterior limb of the internal capsule provided novel insights into both disorders. Our study adds value to further understanding of the pathophysiology, classification, and differential diagnosis of SZ and BD.     

Cerebral white matter abnormalities in patients with charcot‐marie‐tooth disease

Here, we report the structural evidence of cerebral white matter abnormalities in Charcot‐Marie‐Tooth (CMT) patients and the relationship between these abnormalities and clinical disability. Brain diffusion tensor imaging (DTI) was performed in CMT patients with demyelinating (CMT1A/CMT1E), axonal (CMT2A/CMT2E), or intermediate (CMTX1/DI‐CMT) peripheral neuropathy. Although all patients had normal brain magnetic resonance imaging, all genetic subgroups except CMT1A had abnormal DTI findings indicative of significant cerebral white matter abnormalities: decreased fractional anisotropy and axial diffusivity, and increased radial diffusivity. DTI abnormalities were correlated with clinical disability, suggesting that there is comorbidity of central nervous system damage with peripheral neuropathy in CMT patients. ANN NEUROL 2017;81:147–151     

Leukoencephalopathy with vanishing white matter: serial MRI of the brain and spinal cord including diffusion tensor imaging

Vanishing white matter disease (VWM) is one of the most frequent inherited childhood white matter disorders. We present the brain and spinal cord disease progression on serial conventional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) in a 4-year-old boy. Consecutive MRI examinations demonstrated a progression of the signal abnormalities in the cerebral white matter. Globally, apparent diffusion coefficient (ADC) values as well as axial and radial diffusivity increased over time, while fractional anisotropy (FA) values decreased. Involvement of the cervical posterior spinal tracts and mild global spinal cord atrophy was found. In conclusion, serial MRI and DTI studies may help to better understand the selective injury of the myelin and axons in VWM disease. These data may help in monitoring disease progression. Our data also show that complete neuroimaging work-up in VWM should also include the spinal cord.     

Structural white matter abnormalities in patients with idiopathic dystonia

We investigated whether structural white matter abnormalities, in the form of disruption of axonal coherence and integrity as measured with diffusion tensor imaging (DTI), constitute an underlying pathological mechanism of idiopathic dystonia (ID), independent of genotype status. We studied seven subjects with ID: all had cervical dystonia as their main symptom (one patient also had spasmodic dysphonia and two patients had concurrent generalized dystonia, both DYT1‐negative). We compared DTI MR images of patients with 10 controls, evaluating differences in mean diffusivity (MD) and fractional anisotropy (FA). ID was associated with increased FA values in the thalamus and adjacent white matter, and in the white matter underlying the middle frontal gyrus. ID was also associated with increase in MD in adjacent white matter to the pallidum and putamen bilaterally, left caudate, and in subcortical hemispheric regions, including the postcentral gyrus. Abnormal FA and MD in patients with ID indicate that abnormal axonal coherence and integrity contribute to the pathophysiology of dystonia. These findings suggest that ID is not only a functional disorder, but also associated with structural brain changes. Impaired connectivity and disrupted flow of information may contribute to the impairment of motor planning and regulation in dystonia. © 2006 Movement Disorder Society     

Diffusion Tensor and Functional Magnetic Resonance Imaging of Diffuse Axonal Injury and Resulting Language Impairment

Diffuse axonal injury (DAI) is a common aftermath of brain trauma. The diagnosis of DAI is often difficult using conventional magnetic resonance imaging (MRI). We report a diffusion tensor imaging (DTI) study of a patient who sustained DAI presenting with language impairment. Fractional anisotropy (FA) and DTI tractography revealed a reduction of white matter integrity in the left frontal and medial temporal areas. White matter damage identified by DTI was correlated with the patient's language impairment as assessed by functional MRI (fMRI) and a neuropsychological exam. The findings demonstrate the utility of DTI for identifying white matter changes secondary to traumatic brain injury (TBI).     

Abnormal white matter integrity in young children with autism

This study investigated white matter integrity in young children with autism using diffusion tensor imaging (DTI). Twenty-two children with autism, mean age 3:2 years, and 32 controls, mean age 3:4 years, participated in the study. Tract-based spatial statistics (TBSS) revealed white matter abnormalities in several distinct clusters within the genu and body of the corpus callosum (CC), left superior longitudinal fasciculus (SLF) and right and left cingulum (Cg). TBSS-VOIs analysis was performed in the clusters where differences in fractional anisotropy (FA) were detected to investigate the relationship between changes in FA and diffusivity indices. In all VOIs, increase in FA was caused by a decrease in radial diffusivity (Dr), while no changes in axial diffusivity (Da) or mean diffusivity (MD) were observed. Tractography analysis was applied to further study the CC, SLF, and Cg. Witelson parcellation scheme was used for the CC. Significant increase in FA was seen in children with autism in the mid-body of the CC as well as in the left Cg. It is suggested that such abnormal white matter integrity in young children with autism may adversely affect connectivity between different brain regions and may be linked to some of the behavioral impairments apparent in autism.     

Longitudinal diffusion tensor imaging in Huntington's Disease

Serial diffusion tensor imaging scans were collected at baseline and 1 year follow-up to investigate the neurodegenerative profile of white matter (WM) in seven individuals with the Huntington's Disease (HD) gene mutation and seven control subjects matched on age and gender. In the HD subjects, but not controls, a significant reduction of fractional anisotropy (FA), a measure of WM integrity, between baseline and follow-up was evident throughout the brain. In addition, a DTI scalar associated with the stability of axons, axial diffusivity, showed significant longitudinal decreases from year 1 to year 2 in HD subjects, declines that overlapped to greater degree with FA discrepancies than longitudinal increases in radial diffusivity, a DTI variable sensitive to demylinization. These preliminary results provide the first longitudinal DTI evidence of WM degeneration in HD and support the notion that FA abnormalities in HD may be a result of axonal injury or withdrawal. These results suggest that longitudinal FA changes may serve as a neuropathological biomarker in HD.     

Alteration of fractional anisotropy and apparent diffusion coefficient in obsessive-compulsive disorder: a diffusion tensor imaging study

BACKGROUND: Abnormalities of fractional anisotropy (FA) have been reported in previous diffusion tensor imaging (DTI) studies in patients with obsessive-compulsive disorder (OCD). However, there are some inconsistencies in the results and the apparent diffusion coefficient (ADC) has not been investigated. The goal of this study was to investigate white matter abnormalities and water diffusivity, as reflected by FA and ADC, using DTI in patients with OCD. METHODS: Fifteen patients with OCD and 15 healthy volunteers underwent DTI. Voxelwise analysis was used to compare FA in white matter and ADC in gray matter/white matter of the two groups. RESULTS: Compared with healthy volunteers, the patients had higher FA in the bilateral semioval center extending to the subinsular white matter; and a higher ADC in the left medial frontal cortex. There were no areas with a significantly lower FA or ADC in patients compared with healthy volunteers. CONCLUSIONS: A significantly higher FA was found in regions associated with the emotion of disgust and a trend for a higher ADC was found in a region associated with the regulation of emotions. These findings suggest that neurocircuits involved in disgust processing may play an important role in the pathophysiology of OCD.     

Quantitative DTI assessment of periventricular white matter changes in neonatal meningitis

Neonatal meningitis is one of the important causes of infant mortality and morbidity. Periventricular white matter of neonatal brain is known to be vulnerable to oxidative and hypoxic/ischemic injury secondary to neuro-infections. The aim of this study was to assess periventricular white matter damage in neonatal bacterial meningitis using diffusion tensor imaging (DTI). DTI was performed in 7 age/sex matched controls and 14 neonates with proven bacterial meningitis at the time of diagnosis and after 3 weeks of antibiotic treatment. Region of interest were placed on periventricular white matter to quantify fractional anisotropy (FA) and mean diffusivity (MD). Based on the clinical prognosis and conventional MRI, patients were grouped into those with normal and with abnormal outcome. Compared to controls significantly decreased FA values were observed in entire periventricular white matter except for left parietal white matter in patients with abnormal outcome. Even in those with normal outcome significant decrease in FA values were observed in right parietal and bilateral occipital white matter compared to controls. Decreased FA values in the periventricular white matter regions in neonatal meningitis confirm microstructural white matter injury.     

White matter integrity in hair-pulling disorder (trichotillomania)

Hair-pulling disorder (trichotillomania, HPD) is a disabling condition that is characterized by repetitive hair-pulling resulting in hair loss. Although there is evidence of structural grey matter abnormalities in HPD, there is a paucity of data on white matter integrity. The aim of this study was to explore white matter integrity using diffusion tensor imaging (DTI) in subjects with HPD and healthy controls. Sixteen adult female subjects with HPD and 13 healthy female controls underwent DTI. Hair-pulling symptom severity, anxiety and depressive symptoms were also assessed. Tract-based spatial statistics were used to analyze data on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). There were no differences in DTI measures between HPD subjects and healthy controls. However, there were significant associations of increased MD in white matter tracts of the fronto-striatal-thalamic pathway with longer HPD duration and increased HPD severity. Our findings suggest that white matter integrity in fronto-striatal-thalamic pathways in HPD is related to symptom duration and severity. The molecular basis of measures of white matter integrity in HPD deserves further exploration.