Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study

OBJECTIVES: Diffusion tensor imaging (DTI), a technique capable of examining water diffusion in different tissues and the organisation of white matter tracts, was used to investigate the neuropathology of the corpus callosum in vivo in patients with schizophrenia. METHODS: Diffusion tensor imaging was performed in 20 schizophrenic patients and 25 healthy controls. Two complementary measures, mean diffusivity and fractional anisotropy, which are considered to be sensitive indices of axonal integrity, were obtained from regions of interest in the genu (anterior) and splenium (posterior) of the corpus callosum. RESULTS: Mean diffusivity was significantly increased and fractional anisotropy significantly reduced in the splenium but not the genu of the corpus callosum in the schizophrenic group compared with controls. There were no significant sex differences in the DTI measures for either the schizophrenic or control group. Clinical variables such as age, duration of illness, dose of antipsychotic medication, and schizophrenic symptoms did not predict the DTI changes in the schizophrenic patients. CONCLUSIONS: The presence of DTI changes in the splenium but not the genu of the corpus callosum suggests that there may be a focal disruption of commisural connectivity in schizophrenia. However, these findings do not exclude the possibility of abnormalities in other areas of the corpus callosum or other regions of white matter and further research using different methods of analysis may enable us to clarify this. Diffusion tensor imaging is a valuable tool in investigating the structure of white matter in schizophrenia.     

The corpus callosum in first episode schizophrenia: a diffusion tensor imaging study

BACKGROUND: Neuropathological and imaging studies suggest that corpus callosum abnormalities (CC) are present in schizophrenia, but it remains to be determined whether these abnormalities are present at illness onset. Diffusion tensor imaging (DTI), which is more sensitive than conventional magnetic resonance imaging (MRI) in detecting subtle structural changes in the organisation and integrity of white matter tracts, is an ideal tool to investigate this question. OBJECTIVE: To determine whether CC abnormalities are present at illness onset in schizophrenia. METHODS: Twenty patients (14 men, six women) with first episode schizophrenia and 29 controls (11 men, 18 women) were studied. Both high resolution volumetric T1-weighted images and DTI were acquired. Regions of interest (ROI) were placed in the splenium and genu of the CC and fractional anisotropy (FA) and diffusivity (D) measured. RESULTS: No differences in FA or D were detected in these regions between patients and controls. In women, irrespective of group membership, FA was significantly lower and there was a trend for D to be higher than in men, indicating less barriers to diffusion in females. CONCLUSION: The negative findings of this study suggest that in the early stages of schizophrenia there is no disruption to the integrity of the CC and raise the possibility that the neuropathological abnormalities may appear later and be progressive, at least in some patients.     

Diffusion tensor-based imaging reveals occult abnormalities in adrenomyeloneuropathy

"Pure" adrenomyeloneuropathy (AMN) is the noninflammatory myeloneuropathic variant of X-linked adrenoleukodystrophy, where the disease process appears to be restricted to spinal cord tracts and peripheral nerves. The absence of obvious brain involvement makes it distinct from the inflammatory cerebral phenotypes of X-linked adrenoleukodystrophy. However, some pure AMN patients later experience development of cerebral demyelination, but little is known about the extent of brain involvement in pure AMN patients who have normal brain magnetic resonance imaging. We used diffusion tensor imaging to investigate possible occult cerebral abnormalities in such pure AMN patients. Fractional anisotropy and trace were studied in three-dimensional reconstructions of white matter tracts commonly involved in cerebral phenotypes of X-linked adrenoleukodystrophy. Results demonstrated reduced fractional anisotropy and increased trace in bilateral corticospinal tracts and genu of corpus callosum (p < 0.05). Diffusion tensor imaging-based three-dimensional fiber tracking showed occult tract-specific cerebral microstructural abnormalities in pure AMN patients who had a normal conventional brain magnetic resonance image. Corticospinal tract abnormalities could reflect a centripetal extension of spinal cord long-tract distal axonopathy. Accompanying abnormalities in genu of corpus callosum indicate that the disease pathology in pure AMN may not be limited to spinal cord long tracts alone, although the involvement of the latter is most prominent and severe.     

Characteristics of diffusion-tensor imaging for healthy adult rhesus monkey brains

Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional ani- sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus callosum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, semioval center, thalamus, and corpus callosum （splenium and genu） as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy rhesus monkeys aged 4-8 years. Results showed no laterality dif- ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of cau- date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the sple- nium of corpus callosum in the white matter, followed by genu of the corpus callosum and the pos- terior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4-8-year-old rhesus monkeys are similar to those of healthy young people.     

精神分裂症首次发病患者的脑扩散张量成像研究

目的 利用磁共振扩散张量成像(DTI)技术研究未经药物治疗的精神分裂症首次发病(以下简称首发)患者主要脑区白质纤维束的异常.方法 选取26例首发精神分裂症患者(患者组)和20名健康志愿者(对照组)行脑DTI扫描(两组均为右利手),测量胼胝体膝部、压部、双侧额叶白质、扣带束前部及海马头的部分各向异性(FA)值.结果 (1)对照组左侧扣带束FA值(0.428±0.067)大于右侧(0.375±0.079;P＜0.05).(2)患者组两侧相对应感兴趣区FA值差异均无统计学意义(P＞0.05).(3)患者组左右侧胼胝体压部FA值(均为0.734±0.085)、左右侧扣带束前部FA值(0.300±0.068和0.306 4±0.062)均低于对照组(0.785±0.045,0.428±0.067,0.375±0.079;均P＜0.05).结论 首发精神分裂症患者存在双侧扣带束、胼胝体压部白质纤维束的受损,支持脑内连接异常假说.     

Abnormal brain white matter in schizophrenia: a diffusion tensor imaging study.

Fractional anisotropy and the mean diffusion coefficient were measured in the cerebral volume in 20 schizophrenic and 24 healthy subjects, men and women, using diffusion tensor imaging. In addition, 3D SPGR was used for segmentation of brain tissue into grey and white matter and cerebrospinal fluid. In schizophrenic patients, fractional anisotropy was reduced in the splenium of the corpus callosum and in adjacent occipital white matter. The segmentation revealed no tissue deficits in the volume of reduced fractional anisotropy. The mean diffusion was increased in the total white and grey matter volume of the schizophrenic patients compared with the healthy subjects. The findings support the view that global and regional white matter abnormalities occur in chronic schizophrenia.     

A diffusion tensor imaging study of fasciculi in schizophrenia

OBJECTIVE: Cognitive models propose that the symptoms and psychological impairments associated with schizophrenia arise as a consequence of impaired communication between brain regions, especially the prefrontal cortex and the temporal and parietal lobes. Functional imaging and electrophysiological data have provided evidence of functional dysconnectivity, but it is unclear whether this reflects an underlying problem with anatomical connectivity. This study used diffusion tensor imaging to examine the integrity of the major white matter fasciculi, which connects the frontal and temporal-parietal cortices, and the corpus callosum in patients with schizophrenia. METHOD: A 1.5-T magnetic resonance scanner was used to acquire diffusion tensor images giving whole brain coverage at an isotropic 2.5-mm voxel size. Fractional anisotropy was measured in 33 patients with schizophrenia and 40 healthy comparison subjects with an automated voxel-based method of analysis. RESULTS: There was reduced fractional anisotropy in patients with schizophrenia in regions corresponding to the superior longitudinal fasciculi bilaterally and in the genu of the corpus callosum. However, within the patient group, the propensity to experience auditory hallucinations was associated with relatively increased fractional anisotropy in superior longitudinal fasciculi and in the anterior cingulum. CONCLUSIONS: Schizophrenia is associated with altered white matter integrity in the tracts connecting the frontal cortex with the temporal and parietal cortices and with the contralateral frontal and temporal lobes. The severity of these changes may vary with the pattern of symptoms associated with the disorder.     

Diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease: a review

PURPOSE OF REVIEW: To provide a comprehensive review of diffusion tensor imaging in evaluating microstructural changes in the spectrum of cognitive decline from ageing to Alzheimer's disease, in particular focusing on mild cognitive impairment. RECENT FINDINGS: Mild cognitive impairment represents a transition phase between normal ageing and early Alzheimer's disease. Diffusion tensor imaging has emerged as a useful imaging modality that provides information about the structural integrity of tissue. In healthy ageing, diffusion tensor imaging abnormalities occur in the frontal regions, specifically the frontal white matter, anterior cingulum and the genu of the corpus callosum. Some studies report an anterior-posterior gradient change with greater abnormalities in the genu than the splenium of the corpus callosum and in the frontal than parietal white matter. In Alzheimer's disease, diffusion tensor imaging abnormalities are concentrated in the posterior regions: the parahippocampal gyrus, temporal white matter, splenium of corpus callosum and posterior cingulum. In mild cognitive impairment, changes seem to parallel those in Alzheimer's disease, with similar posterior regions showing abnormalities. SUMMARY: Due to the similarities in diffusion tensor imaging findings in both mild cognitive impairment and Alzheimer's disease, it is likely that diffusion tensor imaging has the potential to emerge as a useful clinical tool for early detection and monitoring of disease progression and treatment response in mild cognitive impairment/Alzheimer's disease patients.     

Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study

OBJECTIVE: Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. METHOD: Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. RESULTS: Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. CONCLUSIONS: These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.     

Anatomical brain connectivity and positive symptoms of schizophrenia: A diffusion tensor imaging study

Structural brain changes in schizophrenia are well documented in the neuroimaging literature. The classical morphometric analyses of magnetic resonance imaging (MRI) data have recently been supplemented by diffusion tensor imaging (DTI), which mainly assesses changes in white matter (WM). DTI increasingly provides evidence for abnormal anatomical connectivity in schizophrenia, most often using fractional anisotropy (FA) as an indicator of the integrity of WM tracts. To better understand the clinical significance of such anatomical changes, we studied FA values in a whole-brain analysis comparing paranoid schizophrenic patients with a history of auditory hallucinations and matched healthy controls. The relationship of WM changes to psychopathology was assessed by correlating FA values with PANSS scores (positive symptoms and severity of auditory hallucinations) and with illness duration. Schizophrenic patients showed FA reductions indicating WM integrity disturbance in the prefrontal regions, external capsule, pyramidal tract, occipitofrontal fasciculus, superior and inferior longitudinal fasciculi, and corpus callosum. The arcuate fasciculus was the only tract which showed increased FA values in patients. Increased FA values in this region correlated with increased severity of auditory hallucinations and length of illness. Our results suggest that local changes in anatomical integrity of WM tracts in schizophrenia may be related to patients' clinical presentation.     

Complementary diffusion tensor imaging study of the corpus callosum in patients with first-episode and chronic schizophrenia

Background

Abnormalities in the corpus callosum have long been implicated in schizophrenia. Previous diffusion tensor imaging (DTI) studies in patients with different durations of schizophrenia yielded inconsistent results. By comparing patients with different durations of schizophrenia, we investigated if white matter abnormalities of the corpus callosum emerge at an early stage in the illness or result from pathological progression.

Methods

We recruited patients with first-episode schizophrenia, patients with chronic schizophrenia and age-, sex-and handedness-matched healthy controls. We used 2 DTI techniques (voxel-based and fibre-tracking DTI) to investigate differences in corpus callosum integrity among the 3 groups.

Results

With both DTI techniques, significantly decreased fractional anisotropy values were identified in the genu of corpus callosum in patients with chronic schizophrenia, but not first-episode schizophrenia, compared with healthy controls.

Limitations

This study was cross-sectional, and the sample size was relatively small.

Conclusion

Abnormalities in the genu of the corpus callosum might be a progressive process in schizophrenia, perhaps related to disease severity and prognosis.     

Evaluation of white matter changes in agyria-pachygyria complex using diffusion tensor imaging

Associated abnormalities of the white matter in patients with agyria-pachygyria complex have rarely been investigated using new imaging modalities like diffusion tensor imaging. The present study evaluated the white matter changes of 9 children with agyria-pachygyria complex using diffusion tensor imaging. Regions of interest were placed in 17 white matter tracts. Compared with normal controls, the axial diffusivity of the genu of the corpus callosum, corticospinal tract, and fornix in patients with agyria-pachygyria complex was decreased. In the subcortical white matter without changes in T2-weighted image, there were significant decreases in fractional anisotropy and axial diffusivity and increases in radial diffusivity, indicating significant alterations of the white matter. Since axial diffusivity and radial diffusivity reflect changes in the axon and myelin, respectively, the findings here indicate disturbance in both axonal and myelin development in agyria-pachygyria complex.     

Bilateral white matter diffusion changes persist after epilepsy surgery

PURPOSE: Bilateral white matter diffusion tensor imaging (DTI) abnormalities have been reported in patients with temporal lobe epilepsy (TLE) and unilateral mesial temporal sclerosis (MTS), but it is unknown whether these are functional or structural changes. We performed a longitudinal study in patients with unilateral MTS who were seizure-free for 1 year after surgery to determine whether the observed presurgical white matter diffusion abnormalities were reversible. METHODS: Eight TLE patients with unilateral MTS who were seizure-free after anterior temporal resection and 22 healthy subjects were recruited. DTI was performed before surgery and at 1-year follow-up. Tractography and region-of-interest (ROI) analyses were performed in the fornix, cingulum, genu, and splenium of the corpus callosum and external capsules. Diffusion tensor parameters were compared between groups and before and after surgery in the patient group. RESULTS: The fornix, cingulum, and external capsules showed preoperative bilateral abnormal diffusion parameters (i.e., decreased diffusion anisotropy and increased mean and perpendicular diffusivities). The fornix and cingulum ipsilateral to the resected mesial temporal structures showed signs of wallerian degeneration at 1-year follow-up. The contralateral tracts of the fornix, cingulum, and external capsules, as well as the genu of the corpus callosum, failed to show a normalization of their diffusion parameters. CONCLUSIONS: The irreversibility of the white matter DTI abnormalities on seizure freedom suggests underlying structural abnormalities (e.g., axonal/myelin degradation) as opposed to functional changes (e.g., fluid shifts due to seizures) in the white matter.     

White matter abnormalities observed in bipolar disorder: a diffusion tensor imaging study

OBJECTIVES: An increased incidence in white matter abnormalities is among the most frequently reported brain change in patients with bipolar disorder. The objective of the present study was to examine white matter tract integrity, using diffusion tensor imaging (DTI), in bipolar patients and healthy comparison subjects. METHODS: Eleven DSM-IV bipolar I patients and 10 healthy age- and sex-matched controls were studied. DTI data were acquired on a 1.5 Tesla scanner. Fractional anisotropy (FA) and diffusivity (trace) were determined from axial images using region of interest (ROI) analyses. The ROIs were manually placed in the midline and forward projecting arms of the genu (anterior) and the midline of the splenium (posterior) of the corpus callosum. RESULTS: Bipolar patients had significantly higher FA in the midline of the genu compared with healthy controls. Regional white matter differences were also observed, with significantly lower FA in the genu than forward projecting regions in both groups and lower FA in the genu than the splenium in controls. CONCLUSIONS: Diffusion tensor imaging revealed significant microstructural differences in the genu, as measured by elevated FA in bipolar patients compared with healthy controls. These preliminary findings further support the hypothesis that anomalous frontal brain mechanisms may be associated with bipolar disorder.     

轻微型肝性脑病磁共振扩散加权成像和扩散张量成像的定量研究

目的通过磁共振扩散加权成像(DWI)和扩散张量成像(DTI)定量分析轻微型肝性脑病(MHE)患者脑功能的异常改变,探讨DWI和DTI在MHE中的应用价值。方法30例肝硬化患者经神经心理测试评分量表测试后,分为MHE组16例和无MHE单纯肝硬化组14例,同时选取15例健康志愿者为正常对照组。所有受试者均行DWI与DTI扫描,选取脑内8个部位为感兴趣区,计算各部位的表观扩散系数(ADC)值和各向异性分数(FA)值。结果18例肝硬化患者于T1WI图像上可见到双侧内囊、苍白球对称性高信号。额叶、枕叶白质、胼胝体膝部、胼胝体压部、内囊前肢、内囊后肢、尾状核头部由正常组、单纯肝硬化组至MHE组ADC值逐渐增加,且MHE组的ADC值较肝硬化组和正常组增加,差异有统计学意义(P<0.05);胼胝体膝部和压部的FA值由正常组、单纯肝硬化组至MHE组逐渐降低,差异有统计学意义(P<0.05)。结论DWI与DTI联合应用能够预测肝硬化患者MHE的进展程度,具有潜在的临床价值。     

Callosal dysfunction in amyotrophic lateral sclerosis correlates with diffusion tensor imaging of the central motor system

We investigated the frequency and functional relevance of corpus callosum degeneration in amyotrophic lateral sclerosis (ALS). A total of 22 ALS patients and 29 healthy controls performed the newly developed Contralateral Co-Movement Test as indicator of callosal dysfunction. Diffusion tensor imaging was applied to determine fractional anisotropy values in the callosal area containing the crossing motor fibers and in the pyramidal tracts in 13 subjects of each group. ALS patients had more than twice the amount of co-movements as compared to healthy subjects. Contralateral co-movements correlated with fractional anisotropy values of the corpus callosum motor region as did ALS Functional Rating Scale as measure of disease progression. In both groups, contralateral co-movements correlated with the central motor index (ratio of the mean of fractional anisotropy values of both pyramidal tracts and corpus callosum motor region). Neuropsychological test results failed to show correlations with functional or morphological parameters. Combining Contralateral Co-Movement Test and diffusion tensor imaging in ALS revealed the close relation between functional and morphological impairment in the degenerating central motor-neuronal network. The Contralateral Co-Movement Test delivers simple means of symptom quantification, independent of ALS Functional Rating Scale, for future neuroprotective trials.     

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) due to dengue virus

A 14-year-old girl presented with encephalopathy, delirium and ophthalmoplegia following a 3 day history of high-grade fever. Brain MRI on day 6 of illness showed diffusion restricted ovoid lesion in the splenium of corpus callosum. Dengue virus encephalitis was diagnosed with positive PCR for dengue virus type-2 in both serum and cerebrospinal fluid. She made a complete recovery from day 10 of illness. Repeat brain MRI on day 12 of illness showed resolution of the splenial lesion. Serial diffusion tensor imaging (DTI) showed normal fractional anisotropy values on resolution of splenial lesion indicating that MERS was likely due to transient interstitial oedema with preservation of white matter tracts. This is the first reported case of MERS following dengue virus infection. It highlights the usefulness of performing serial DTI in understanding the underlying pathogenesis of MERS. Our case report widens the neurological manifestations associated with dengue infection and reiterates that patients with MERS should be managed supportively as the splenial white matter tracts are reversibly involved in MERS.     

White matter loss in the splenium of the corpus callosum in a case of posterior cortical atrophy: a diffusion tensor imaging study

There have been several functional imaging studies using PET and SPECT to investigate posterior cortical atrophy (PCA). These studies have suggested dysfunction of corticocortical connections which is consistent with the occipitoparietal stream. However, there are no reports suggesting disturbance of the white matter that interconnects the temporal, parietal and occipital cortices. We measured fractional anisotropy (FA) in the genu and splenium of the corpus callosum and created color maps using diffusion tensor imaging (DTI), which is a relatively new MRI technique that allows visualization of the directionality of water diffusion, in a patient with PCA and compared these findings with those in 5 typical Alzheimer disease (AD) patients. The PCA patient was a 75-year-old man presenting with progressive complex visual disorder who satisfied the clinical diagnostic criteria for PCA. In 5 typical AD patients, the FA index in the splenium was higher than that in the genu; however, in the PCA patient, the FA index in the splenium was significantly lower than that in the genu. A DTI-based color map of the PCA patient showed reduction of anisotropy and fiber volume in the splenium. These findings suggest that the splenium of the corpus callosum secondarily degenerated due to neuronal degeneration of the temporal, parietal and occipital cortices and suggest that reduction of the FA in the splenium is one of the characteristics of PCA.     

Diffusion tensor imaging of the corpus callosum in addiction

Diffusion tensor imaging, a novel technique with an increased capability of detecting abnormalities in the white matter, has increasingly been employed in the study of the biology of addictions. A comprehensive search from a range of databases was conducted and publications on this topic were selected. Nine reports, eight published and one unpublished, met criteria for inclusion, five on alcoholism, three on cannabis and one on cocaine use. Findings of this review suggest focal disruption of commissural connectivity in the corpus callosum. In alcoholism, the genu and splenium were particularly affected with a different pattern in men and women, and an association with age and duration of substance use. In cocaine dependence, the genu and rostral body showed significant damage. Cannabis consumption may be associated with white matter disruption, but there is not sufficient evidence to support pathological changes in the corpus callosum. The improved detection of white matter pathology with diffusion tensor imaging supports the importance of future research in this field.     

Tract-based spatial statistics of diffusion tensor imaging after corpus callosotomy in relation to seizure recurrence

Purpose

To delineate microstructural changes in transected white matter tracts after corpus callosotomy in relation to seizure recurrence using tract-based spatial statistics of diffusion tensor imaging (DTI-TBSS).

Methods

We retrospectively included 12 total corpus callosotomy patients who had undergone serial pre- and postoperative DTI studies. The first postoperative DTI was performed within 6 months after callosotomy. The second postoperative DTI was performed in five patients with seizure recurrence (symptomatic group) and in seven patients without seizure recurrence (asymptomatic group) after 1 year following surgery. Group comparisons of fractional anisotropy (FA) with age- and sex-matched controls were performed in a whole brain voxel-wise manner using DTI-TBSS.

Results

The first postoperative DTI-TBSS showed a significant FA decrease in the entire corpus callosum in all patients. The second postoperative DTI-TBSS showed that a significant FA decrease remained in the entire corpus callosum in the asymptomatic group. However, in the symptomatic group, no significant decrease of FA was observed in some parts of the posterior body and splenium of the corpus callosum, although there was still a significant FA decrease in the genu of the corpus callosum.

Conclusions

Using DTI-TBSS analysis, we characterized and visualized microstructural white matter changes over time in relation to seizure recurrence in callosotomy patients, suggesting that reorganization of some transected white matter tracts may be related to seizure recurrence. DTI-TBSS analysis can provide reliable and useful information about the state of white matter bundles affected by corpus callosotomy in a noninvasive manner.