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.     

Temporal characteristics of tract-specific anisotropy abnormalities in schizophrenia

White matter abnormalities have been detected using diffusion tensor imaging in a variety of locations in the brains of patients with schizophrenia. Studies that included first-episode patients report less severe or no abnormalities but more pronounced deficits in chronic patients. Here, we investigated these abnormalities in a very large group of patients with schizophrenia who had both large ranges in age and in duration of illness. A highly reproducible diffusion tensor imaging tractography technique was used to quantify the fractional anisotropy of the genu and splenium of the corpus callosum as well as the bilateral pyramidal tracts. We found a decline in fractional anisotropy that correlated with the duration of illness in the genu and splenium of the corpus callosum but not in the pyramidal tracts. The findings suggest that there are white matter tract-specific degenerative mechanisms that may be present at the point of illness onset and may progress throughout the illness.     

A voxel-based diffusion tensor imaging study of temporal white matter in patients with schizophrenia

Diffusion tensor imaging (DTI) is a relatively new technique used to detect changes in the anisotropic diffusion of white matter. The study of the disruption of brain connectivity may increase our understanding of cognitive deficits associated with schizophrenia. Here we analysed DTI data in 25 patients with DSM-IV schizophrenia and 24 healthy controls. Two complementary measures, fractional anisotropy (FA) and the apparent diffusion coefficient (ADC), were considered and analysed using voxel-based morphometry. Declarative memory functions were also investigated and their associations with DTI data were analysed. FA was significantly reduced, and the ADC increased in the left sub-gyral white matter of the temporal lobe, which involves the posterior part of the fornix. In the schizophrenic group, females had lower FA than males in the genu of the corpus callosum. Memory functions correlate with FA values. These data provide further evidence for the disruption of white matter connectivity in the left medial temporal lobe, and for its contribution to the declarative memory deficit 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 imaging in early Alzheimer's disease

Our aim was to investigate the extent of white matter tissue damage in patients with early Alzheimer disease (AD) using diffusion tensor magnetic resonance imaging (DTI). Although AD pathology mainly affects cortical grey matter, previous magnetic resonance imaging (MRI) studies showed that changes also exist in the white matter (WM). However, the nature of AD-associated WM damage is still unclear. Conventional and DTI examinations (b=1000 s/mm(2), 25 directions) were obtained from 12 patients with early AD (Mini Mental State Examination [MMSE] score=27, Grober and Buschke test score=33.2, digit span score=5.6) and 12 sex- and age-matched volunteers. The right and left mean diffusivity (MD) and fractional anisotropy (FA) of several WM regions were pooled in each patient and control, and compared between the two groups. Volumes of the whole brain and degree of atrophy of the temporal lobe were compared between the two groups. In AD, MD was increased in the splenium of the corpus callosum and in the WM in the frontal and parietal lobes. FA was bilaterally decreased in the WM of the temporal lobe, the frontal lobe and the splenium compared with corresponding regions in controls. Values in other areas (occipital area, superior temporal area, cingulum, internal capsule, and genu of the corpus callosum) were not different between patients and controls. No correlations were found between the MMSE score and the anisotropy indices. Findings of DTI reveal abnormalities in the frontal and temporal WM in early AD patients. These changes are compatible with early temporal-to-frontal disconnections.     

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.     

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.     

Reduced white matter fractional anisotropy and clinical symptoms in schizophrenia: a voxel-based diffusion tensor imaging study

Although not consistently replicated, diffusion tensor imaging (DTI) studies in schizophrenia have revealed lower fractional anisotropy (FA) in various white matter regions, a finding consistent with the disruption of white matter integrity. In this study, we used voxel-based DTI to investigate possible whole-brain differences in the white matter FA values between 58 schizophrenia patients and 58 healthy controls. We also explored the association between FA values and clinical symptoms in schizophrenia. Compared with the controls, the schizophrenia patients showed significant FA reductions in bilateral superior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus, and genu of right internal capsule. Furthermore, in the patient group, the FA value of the anterior part of the corpus callosum was negatively correlated with the avolition score on the Scale for the Assessment of Negative Symptoms. These findings suggest widespread disruption of white matter integrity in schizophrenia, which could partly explain the severity of negative symptomatology.     

MRI study of white matter diffusion anisotropy in schizophrenia

Diffusion tensor imaging (DTI) can provide information about brain white matter integrity. The results of DTI studies in schizophrenia are somewhat variable and could benefit from standardized image processing methods. Fourteen patients with schizophrenia or schizoaffective disorder and 14 healthy volunteers underwent DTI. Scans were analyzed using a rigorous voxelwise approach. The key dependent variable, fractional anisotropy, was lower for patients in the corpus callosum, left superior temporal gyrus, parahippocampal gyri, middle temporal gyri, inferior parietal gyri, medial occipital lobe, and the deep frontal perigenual region. Regions showing reduced white matter fractional anisotropy are known to be abnormal in schizophrenia. The voxelwise method used in the current study can provide the basis for hypothesis-driven research.     

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.     

创伤后应激障碍患者扣带束及胼胝体纤维束FA值的初步研究

目的探讨创伤后应激障碍患者(PTSD)是否存在连合纤维束胼胝体及联络纤维扣带纤维束的超微结构异常。方法1.5T的MR成像仪下对12例PTSD患者及12名正常对照进行磁共振弥散张量成像(DTI),测量受试者胼胝体膝部、体部、压部、及双侧扣带水平部、后部等感兴趣区内主要白质纤维束的各向异性分数(FA)值,并进行组间比较。结果患者组双侧(左侧、右侧)扣带束水平部、胼胝体压部的FA值较对照组明显降低,差异均有统计学意义(t分别为3.26、-4.13、2.84,P均小于0.05)。结论PTSD患者的边缘系统纤维束可能存在结构异常。     

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。     

Extratemporal white matter abnormalities in mesial temporal lobe epilepsy demonstrated with diffusion tensor imaging

PURPOSE: Recent studies have demonstrated bilateral white matter abnormalities in temporal lobe epilepsy (TLE) patients with unilateral mesial temporal sclerosis (MTS). The purpose of this project was to determine whether abnormalities of water diffusion are seen in extratemporal white matter of patients with TLE and pathologically confirmed MTS and to determine whether these findings are associated with worse surgical outcome. METHODS: Eleven patients with TLE and unilateral MTS confirmed in surgical specimens and 14 controls were studied by using cerebrospinal fluid-suppressed diffusion tensor imaging (DTI) and T2 relaxometry. RESULTS: Hippocampal T2 signal for patients was significantly elevated both ipsilateral (p<0.001) and contralateral (p=0.006) to MTS. DTI demonstrated reduced fractional anisotropy of the genu of the corpus callosum (p=0.003) and external capsule (p=0.02) and elevated mean diffusivity of the genu (p=0.005), splenium (p=0.03), and external capsule (p<0.001). For both the genu and external capsule, parallel diffusion of patients was not different from that of controls (genu, p=0.81; external capsule, p=0.45), whereas perpendicular diffusion was elevated (genu, p=0.001; external capsule, p<0.001). With mean postsurgical follow-up of 18.5 months, eight of 11 patients were entirely seizure free and the remaining three had all experienced a worthwhile reduction in seizure frequency. CONCLUSIONS: Our findings suggest that although patients with TLE and MTS have extensive bilateral and extratemporal pathology, these findings may not be associated with a worse postsurgical outcome.     

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.     

弥漫性轴索损伤早期磁共振弥散张量成像检测与恢复期注意力障碍的相关性研究

目的应用磁共振弥散张量成像技术研究患者早期弥漫性轴索损伤(DAI)与恢复期时注意力障碍之间的关系。方法分别对12例DAI患者(伤后4.1±1.7d)和10例健康志愿者(正常对照组)进行MRI弥散张量成像(DTI)检查及神经心理测评量表评估。使用感兴趣区域方法对两组DTI图像的下纵束、上纵束、胼胝体膝部和胼胝体压部的FA值进行比较;分别对恢复期的DAI患者(20.9±7.3 M)与健康志愿者行认知量表评估,并对DAI组的FA值与神经心理测评量表的总分行pearson直线相关分析。结果与健康对照组相比,DAI患者全部感兴趣区的FA值显著降低(P<0.05)、注意力功能显著降低(P<0.05)。DAI患者中的上纵束和下纵束与注意力量表总分呈负性相关(P<0.05),胼胝体膝部和胼胝体压部与注意力量表总分无相关性(P>0.05)。结论利用DTI技术检测早期白质纤维束的损伤可以预测DAI患者在恢复期中的注意力功能障碍,为临床上DAI患者的认知障碍的诊断提供一定的科学依据。     

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.     

Cortical and subcortical white matter abnormalities in adults with remitted first‐episode mania revealed by Tract‐Based Spatial Statistics

Chan W‐Y, Yang G‐L, Chia M‐Y, Woon P‐S, Lee J, Keefe R, Sitoh Y‐Y, Nowinski WL, Sim K. Cortical and subcortical white matter abnormalities in adults with remitted first‐episode mania revealed by Tract‐Based Spatial Statistics.
Bipolar Disord 2010: 12: 383–389. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Abnormalities of brain white matter have been noted in structural magnetic resonance imaging and diffusion tensor imaging (DTI) studies of bipolar disorder, but there are fewer investigations specifically examining white matter integrity early in the course of illness. In this study, we employed DTI to elucidate white matter changes in adult patients with remitted first‐episode mania and hypothesized that first‐episode mania was associated with decreased fractional anisotropy in cortical (frontal) and subcortical (thalamus, striatum) white matter as well as white matter tracts (cingulum, corpus callosum). Methods: Diffusion tensor images were acquired from 16 patients with remitted first‐episode mania and 16 healthy controls matched for age, gender, handedness, and years of education. Fractional anisotropy and radial and axial diffusivities were analyzed using Tract‐Based Spatial Statistics. Results: Patients had lower fractional anisotropy and higher radial diffusivity in the left anterior frontal white matter, right posterior thalamic radiation, left cingulum, and bilateral sagittal striatum. In addition, increased radial diffusivity was found in the left corpus callosum. Conclusion: Our findings highlighted that white matter abnormalities were present by the time of remission of first‐episode mania. The widespread occurrence of these white matter abnormalities both in first‐episode mania and chronic bipolar disorder suggested that disruption of white matter cortical‐subcortical networks as well as projection, associative, and commissural tracts is a hallmark of the illness.     

Quantification of age- and gender-related changes in diffusion tensor imaging indices in deep grey matter of the normal human brain

This study aimed to demonstrate age-related and gender-related changes in diffusion tensor imaging (DTI) indices of deep grey matter (GM) nuclei of the normal human brain. DTI was performed on 142 subjects (age: 10-52 years). Regions of interest were placed on the caudate nucleus (CN), putamen, globus pallidus, frontal white matter (WM), occipital WM, anterior and posterior limb of internal capsule, genu of the corpus callosum and splenium in all participants. The quadratic regression model was used to describe age-related and gender-related changes in DTI indices for GM and WM. We observed increased fractional anisotropy (FA) values with age up to adulthood in GM, and a rise up to the third decade of life followed by a decrease in FA for WM. We observed higher FA values in males compared to females in CN and all WM regions. Decreased mean diffusivity with age was observed in GM and WM irrespective of gender. This normative data may be valuable in the diagnosis of neurodegenerative diseases.     

Reduced frontal white matter integrity in early-onset schizophrenia: a preliminary study.

BACKGROUND: Research suggests that brain frontal white matter (WM) might be qualitatively altered in adolescents with early onset schizophrenia (EOS). Diffusion tensor imaging provides a relatively new approach for quantifying possible connectivity of WM in vivo. METHODS: Diffusion tensor imaging was used to examine the WM integrity of frontal regions at seven levels from 25 mm above to 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. Three other regions were examined: the occipital region at the AC-PC plane and the genu and splenium of the corpus callosum. Fractional anisotropy was compared between 12 adolescents (nine male, 3 female) with EOS (onset of psychotic symptoms by age 18 years) and nine age-similar healthy comparison subjects (six male, 3 female). RESULTS: Adolescents with EOS had significantly reduced fractional anisotropy in the frontal WM at the AC-PC plane in both hemispheres and in the occipital WM at the AC-PC plane in the right hemisphere. CONCLUSIONS: These preliminary data support a hypothesis that alterations in brain WM integrity occur in adolescents with EOS. Abnormalities found in this study were similar to those reported in adults with chronic schizophrenia. Additional studies are needed to assess whether there is progression of WM abnormalities in schizophrenia.