Right lateralized white matter abnormalities in first-episode,drug-naive paranoid schizophrenia

Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia.     

Spatiotemporal microstructural white matter changes in diffusion tensor imaging after transient focal ischemic stroke in rats

Structural reorganization in white matter (WM) after stroke is a potential contributor to substitute or to newly establish the functional field on the injured brain in nature. Diffusion tensor imaging (DTI) is an imaging modality that can be used to evaluate damage and recovery within the brain. This method of imaging allows for in vivo assessment of the restricted movements of water molecules in WM and provides a detailed look at structural connectivity in the brain. For longitudinal DTI studies after a stroke, the conventional region of interest method and voxel‐based analysis are highly dependent on the user‐hypothesis and parameter settings for implementation. In contrast, tract‐based spatial statistics (TBSS) allows for reliable voxel‐wise analysis via the projection of diffusion‐derived parameters onto an alignment‐invariant WM skeleton. In this study, spatiotemporal WM changes were examined with DTI‐derived parameters (fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, DA; radial diffusivity, RD) using TBSS 2 h to 6 weeks after experimental focal ischemic stroke in rats (N = 6). FA values remained unchanged 2–4 h after the stroke, followed by a continuous decrease in the ipsilesional hemisphere from 24 h to 2 weeks post‐stroke and gradual recovery from the ipsilesional corpus callosum to the external capsule until 6 weeks post‐stroke. In particular, the fibers in these areas were extended toward the striatum of the ischemic boundary region at 6 weeks on tractography. The alterations of the other parameters in the ipsilesional hemisphere showed patterns of a decrease at the early stage, a subsequent pseudo‐normalization of MD and DA, a rapid reduction of RD, and a progressive increase in MD, DA and RD with a decreased extent in the injured area at later stages. The findings of this study may reflect the ongoing processes on tissue damage and spontaneous recovery after stroke.     

Multiple DTI index analysis in normal aging, amnestic MCI and AD. Relationship with neuropsychological performance

White matter (WM) damage has been reported in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) in diffusion tensor imaging (DTI) studies. It is, however, unknown how the investigation of multiple tensor indexes in the same patients, can differentiate them from normal aging or relate to patients cognition. Forty-six individuals (15 healthy, 16 a-MCI and 15 AD) were included. Voxel-based tract based spatial-statistics (TBSS) was used to obtain whole-brain maps of main WM bundles for fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA) and mean diffusivity (MD). FA reductions were evidenced among AD patients with posterior predominance. A-MCI patients displayed reduced mean FA in these critical regions, compared to healthy elders. MD increases were widespread in both groups of patients. Interestingly, a-MCI patients exhibited DR increases in overlapping areas of FA shrinkages in AD, whereas DA increases were only observed in AD. Gray matter atrophy explained most DTI differences, except those regarding MD in both groups as well as DR increases in posterior associative pathways among a-MCI cases. FA values were the only DTI measure significantly related to memory performance among patients. Present findings suggest that most DTI-derived changes in AD and a-MCI are largely secondary to gray matter atrophy. Notably however, specific DR signal increases in posterior parts of the inferior fronto-occipital and longitudinal fasciculi may reflect early WM compromise in preclinical dementia, which is independent of atrophy. Finally, global measures of integrity, particularly orientation coherence (FA) of diffusion, appear to be more closely related to the cognitive profile of our patients than indexes reflecting water movement parallel (DA) and perpendicular (DR) to the primary diffusion direction.     

User‐independent diffusion tensor imaging analysis pipelines in a rat model presenting ventriculomegalia: A comparison study

Automated analysis of diffusion tensor imaging (DTI) data is an appealing way to process large datasets in an unbiased manner. However, automation can sometimes be linked to a lack of interpretability. Two whole‐brain, automated and voxelwise methods exist: voxel‐based analysis (VBA) and tract‐based spatial statistics (TBSS). In VBA, the amount of smoothing has been shown to influence the results. TBSS is free of this step, but a projection procedure is introduced to correct for residual misalignments. This projection assigns the local highest fractional anisotropy (FA) value to the mean FA skeleton, which represents white matter tract centers. For both methods, the normalization procedure has a major impact. These issues are well documented in humans but, to our knowledge, not in rodents. In this study, we assessed the quality of three different registration algorithms (ANTs SyN, DTI‐TK and FNIRT) using study‐specific templates and their impact on automated analysis methods (VBA and TBSS) in a rat pup model of diffuse white matter injury presenting large unilateral deformations. VBA and TBSS results were stable and anatomically coherent across the three pipelines. For VBA, in regions around the large deformations, interpretability was limited because of the increased partial volume effect. With TBSS, two of the three pipelines found a significant decrease in axial diffusivity (AD) at the known injury site. These results demonstrate that automated voxelwise analyses can be used in an animal model with large deformations.     

A comparative study of bone marrow mesenchymal stem cell functionality in C57BL and mdx mice

Abnormalities of the white matter (WM) tracts integrity in brain areas involved in emotional regulation have been postulated in major depressive disorder (MDD). However, there is no diffusion tensor imaging (DTI) study in patients with treatment-responsive MDD at present. DTI scans were performed on 22 patients with treatment-responsive MDD and 19 well-matched healthy subjects. Tract-based spatial statistics (TBSS) approach was employed to analyze the scans. Voxel-wise statistics revealed four brain WM tracts with lower fractional anisotropy (FA) in patients compared to healthy subjects: the bilateral internal capsule, the genu of corpus callosum, the bilateral anterior corona radiata, and the right external capsule. FA values were nowhere higher in patients compared to healthy subjects. Our findings demonstrate that the abnormalities of the WM tracts, major in the projection fibers and corpus callosum, may contribute to the pathogenesis of treatment-responsive MDD.     

Structural brain alterations in bipolar disorder II: A combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) study

Background

Brain structural changes have been described in bipolar disorder (BP), but usually studies focused on both I and II subtypes indiscriminately and investigated changes in either brain volume or white matter (WM) integrity. We used combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis to track changes in the grey matter (GM) and WM in the brains of patients affected by BPII, as compared to healthy controls.

Methods

Using VBM and DTI, we scanned 20 DSM-IV-TR BPII patients in their euthymic phase and 21 healthy, age- and gender-matched volunteers with no psychiatric history.

Results

VBM showed decreases in GM of BPII patients, compared to controls, which were diffuse in nature and most prominent in the right middle frontal gyrus and in the right superior temporal gurus. DTI showed significant and widespread FA reduction in BPII patients in all major WM tracts, including cortico-cortical association tracts.

Limitations

The small sample size limits the generalisability of our findings.

Conclusions

Reduced GM volumes and WM integrity changes in BPII patients are not prominent like those previously reported in bipolar disorder type-I and involve cortical structures and their related association tracts.     

Diffusion tensor imaging and Tract-Based Spatial Statistics in Alzheimer's disease and mild cognitive impairment

We aimed to explore the changes in fractional anisotropy (FA) in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD) by analyzing diffusion tensor imaging (DTI) data using the Tract-Based Spatial Statistics (TBSS). DTI data were collected from 17 AD patients, 27 MCI subjects and 19 healthy controls. Voxel-based analysis with TBSS was used to compare FA among the three groups. Additionally, guided by TBSS findings, a region of interest (ROI)-based analysis along the TBSS skeleton was performed on group-level and the accuracy of the method was assessed by the back-projection of ROIs to the native space FA. Neurofiber tracts with decreased FA included: the parahippocampal white matter, cingulum, uncinate fasciculus, inferior and superior longitudinal fasciculus, corpus callosum, fornix, tracts in brain stem, and cerebellar tracts. Quantitative ROI-analysis further demonstrated the significant decrease on FA values in AD patients relative to controls whereas FA values of MCI patients were found in between the controls and AD patients. We conclude that TBSS is a promising method in examining the degeneration of neurofiber tracts in MCI and AD patients.     

Major depressive disorder and white matter abnormalities: A diffusion tensor imaging study with tract-based spatial statistics

BackgroundA few diffusion tensor imaging (DTI) studies have shown abnormalities in areas of white matter tracts involved in mood regulation in geriatric depressive patients, using a region-of-interest technique. A voxel-based morphometry DTI study of young depressive patients reported similar results. In this study, we explored the structure of the white matter of the whole brain with DTI in middle-aged major depressive disorder (MDD) patients, using novel tract-based spatial statistics.MethodsSixteen MDD patients and 20 controls underwent DTI. An automated tract-based spatial method (TBSS) was used to analyze the scans.ResultsCompared with controls, the MDD patients showed a trend for lower values of fractional anisotropy (FA) in the left sagittal stratum, and suggestive decreased FA in the right cingulate cortex and posterior body of corpus callosum. Regressing out the duration and severity of disorder in the model did not change the finding in the sagittal stratum, but dissipated the decrease of FA in latter regions.LimitationsPossibly by reason of a relatively small study sample for a TBSS, the results are suggestive, and should be replicated in further studies.ConclusionsA novel observer-independent DTI method showed decreased FA in the middle-aged MDD patients in white matter regions that have previously connected to the emotional regulation. Lower FA might imply underlying structural abnormalities that contribute to the dysfunction detected in the limbic-cortical network of depressive patients.     

首发重症抑郁症的弥散张量成像研究:基于纤维束示踪的空间统计学分析结果

目的:应用基于纤维束示踪的空间统计分析(Tract-Based Spatial Statistics,TBSS)方法,探讨重症抑郁症病患者全脑白质纤维的完整性是否受到损害。方法:对20(8男,12女)例重症抑郁症病患者组和20(8男,12女)例与抑郁症组按性别、年龄、教育程度匹配的正常人进行全脑弥散张量成像扫描。应用TBSS方法来比较两组的各向异性分数。结果:抑郁症组的左侧内囊前肢、右侧海马旁回、左侧后扣带回的各向异性分数显著低于正常组(P<0.05,t>3,校正),患者组内囊前肢的各向异性分数和抑郁症严重程度呈现负相关。结论:白质病变在抑郁症发病早期即已存在,这些病变区域主要涉及前额叶和边缘系统等与认知和情感调节关系较密切的神经环路的纤维束,这些改变可能导致皮层和皮层下连接受损,从而有利于深入了解抑郁症疾病的发病机理。     

White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study

Diffusion tensor imaging (DTI) can detect, in vivo, the directionality of molecular diffusion and estimate the microstructural integrity of white matter (WM) tracts. In this study, we examined WM changes in patients with Alzheimer's disease (AD) and in subjects with amnestic mild cognitive impairment (MCI) who are at greater risk for developing AD. A DTI index of WM integrity, fractional anisotropy (FA), was calculated in 14 patients with probable mild AD, 14 participants with MCI and 21 elderly healthy controls (NC). Voxel-by-voxel comparisons showed significant regional reductions of FA in participants with MCI and AD compared to controls in multiple posterior white matter regions. Moreover, there was substantial overlap of locations of regional decrease in FA in the MCI and AD groups. These data demonstrate that white matter changes occur in MCI, prior to the development of dementia.     

MRSI and DTI: a multimodal approach for improved detection of white matter abnormalities in alcohol and nicotine dependence

Our previous proton magnetic resonance spectroscopic imaging (¹H MRSI) studies showed that the frontal lobe white matter (WM) in smoking recovering alcoholics (sRA) had lower concentrations of N‐acetylaspartate (NAA), a marker for neuron viability, compared to both nonsmoking recovering alcoholics (nsRA) and a control group of nonsmoking light drinkers (nsLD). Using diffusion tensor imaging (DTI) in a similar population, we found lower fractional anistropy (FA), a microstructural measure of WM fiber integrity, in regions of specific fiber bundles within frontal WM of recovering alcoholics compared to light drinkers. In this study, we hypothesized that in these regions of lower FA, NAA concentrations in the alcoholic groups are lower than in non‐alcoholic controls. We hypothesized further that sRA have lower regional NAA concentrations than nsRA. We retrospectively analyzed existing ¹H MRSI data by quantitating metabolite concentrations from voxels that corresponded to previously identified WM regions of lower FA, and from a control region of normal FA in alcoholics. We found significant NAA concentration differences between groups in regions of abnormal FA. In particular, sRA had significantly lower NAA concentration than nsLD, but in no region was NAA significantly lower in nsRA than nsLD. Furthermore, no NAA group differences were detected in a frontal WM region of normal FA. These results indicate regionally localized NAA loss within the frontal WM, and specifically NAA loss in regions of low FA. Compared to our previous lobar analyses, DTI‐guided MRSI analysis allows the selective evaluation of small WM regions with microstructural injury, thereby increasing statistical power to detect relevant pathology and group differences. DTI‐guided MRSI analyses promise to contribute to a better understanding of brain injury in alcohol and nicotine dependence and, by extension, perhaps in other neurodegenerative diseases as well. Copyright © 2009 John Wiley & Sons, Ltd.     

Combined analyses of gray matter voxel-based morphometry and white matter tract-based spatial statistics in pediatric bipolar mania

Background

Ample evidence has suggested the presence of gray matter (GM) and white matter (WM) abnormalities in bipolar disorder (BD) patients, including pediatric bipolar disorder (PBD). However, little research has been done in PBD patients that carefully classify the mood states. The aim of the present study is to investigate the brain structural changes in PBD-mania children and adolescents.

Methods

Eighteen children and adolescents with bipolar mania (male/female, 6/12) aged 10–18 years old and 18 age- and sex-matched healthy controls were included in the present study. The 3D T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data were obtained on a Siemens 3.0 T scanner. Voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) analysis were conducted to compare the gray matter volume and white matter fractional anisotropy (FA) value between patients and controls. Correlations of the MRI data of each survived area with clinical characteristics in PBD patients were further analyzed.

Results

As compared with the control group, PBD-mania children showed decreased gray matter volume in the left hippocampus. Meanwhile, significant lower FA value was detected in the right anterior cingulate (AC) in the patient group. No region of increased gray matter volume or FA value was observed in PBD-mania. The hippocampal volume was negatively associated with the Young Mania Rating Scale (YMRS) score when controlling for clinical characteristics in PBD-mania patients, however, there was no significant correlation of FA value of the survived area with illness duration, the onset age, number of episodes, or the YMRS score in PBD-mania patients.

Limitation

The present outcomes require replication in larger samples and verification in medication free subjects.

Conclusions

Our findings highlighted that extensive brain structural lesions (including GM and WM) were existed in PBD-mania. The widespread occurrence of structural abnormalities mainly located in the anterior limbic network (ALN) which suggested that this network might contribute to emotional and cognitive dysregulations in PBD.     

Diffusional kurtosis imaging and white matter microstructure modeling in a clinical study of major depressive disorder

Major depressive disorder (MDD) is a globally prevalent psychiatric disorder that results from disruption of multiple neural circuits involved in emotional regulation. Although previous studies using diffusion tensor imaging (DTI) found smaller values of fractional anisotropy (FA) in the white matter, predominantly in the frontal lobe, of patients with MDD, studies using diffusion kurtosis imaging (DKI) are scarce. Here, we used DKI whole‐brain analysis with tract‐based spatial statistics (TBSS) to investigate the brain microstructural abnormalities in MDD. Twenty‐six patients with MDD and 42 age‐ and sex‐matched control subjects were enrolled. To investigate the microstructural pathology underlying the observations in DKI, a compartment model analysis was conducted focusing on the corpus callosum. In TBSS, the patients with MDD showed significantly smaller values of FA in the genu and frontal portion of the body of the corpus callosum. The patients also had smaller values of mean kurtosis (MK) and radial kurtosis (RK), but MK and RK abnormalities were distributed more widely compared with FA, predominantly in the frontal lobe but also in the parietal, occipital, and temporal lobes. Within the callosum, the regions with smaller MK and RK were located more posteriorly than the region with smaller FA. Model analysis suggested significantly smaller values of intra‐neurite signal fraction in the body of the callosum and greater fiber dispersion in the genu, which were compatible with the existing literature of white matter pathology in MDD. Our results show that DKI is capable of demonstrating microstructural alterations in the brains of patients with MDD that cannot be fully depicted by conventional DTI. Though the issues of model validation and parameter estimation still remain, it is suggested that diffusion MRI combined with a biophysical model is a promising approach for investigation of the pathophysiology of MDD.     

FSL在DTI大脑图像分析中的应用现状

随着弥散张量成像(diffusion tensor imaging,DTI)技术在大脑结构方面应用研究的增多,与之相关的数据分析软件也在增多,其中FMRIB Software Library(FSL)在示踪时使用的是基于概率性示踪的算法,在进行交叉纤维示踪和灰质连接上有很大优势。本文主要根据数据分析方式的不同对FSL包含的两个子工具(tract-based spatial statistics,TBSS和FMRIB’s diffusion toolbox,FDT)在DTI大脑图像分析方面的应用现状进行分类介绍,主要涉及老年抑郁症、精神分裂症以及认知功能等领域。本文首先简要介绍DTI原理,然后根据数据分析方式的不同,在TBSS部分分为全脑分析和感兴趣区域(region of interest,ROI)分析两方面,在FDT部分分为全脑示踪、ROI互连分析、基于连通度的分类三方面进行介绍,最后对FSL的局限性以及发展状况进行总结。     

Neurocognitive and neuroimaging correlates of pediatric traumatic brain injury: a diffusion tensor imaging (DTI) study.

This study examined the sensitivity of diffusion tensor imaging (DTI) to microstructural white matter (WM) damage in mild and moderate pediatric traumatic brain injury (TBI). Fourteen children with TBI and 14 controls ages 10-18 had DTI scans and neurocognitive evaluations at 6-12 months post-injury. Groups did not differ in intelligence, but children with TBI showed slower processing speed, working memory and executive deficits, and greater behavioral dysregulation. The TBI group had lower fractional anisotropy (FA) in three WM regions: inferior frontal, superior frontal, and supracallosal. There were no group differences in corpus callosum. FA in the frontal and supracallosal regions was correlated with executive functioning. Supracallosal FA was also correlated with motor speed. Behavior ratings showed correlations with supracallosal FA. Parent-reported executive deficits were inversely correlated with FA. Results suggest that DTI measures are sensitive to long-term WM changes and associated with cognitive functioning following pediatric TBI.     

White matter organization in relation to upper limb motor control in healthy subjects: exploring the added value of diffusion kurtosis imaging

Diffusion tensor imaging (DTI) characterizes white matter (WM) microstructure. In many brain regions, however, the assumption that the diffusion probability distribution is Gaussian may be invalid, even at low b values. Recently, diffusion kurtosis imaging (DKI) was suggested to more accurately estimate this distribution. We explored the added value of DKI in studying the relation between WM microstructure and upper limb coordination in healthy controls (N = 24). Performance on a complex bimanual tracking task was studied with respect to the conventional DTI measures (DKI or DTI derived) and kurtosis metrics of WM tracts/regions carrying efferent (motor) output from the brain, corpus callosum (CC) substructures and whole brain WM. For both estimation models, motor performance was associated with fractional anisotropy (FA) of the CC-genu, CC-body, the anterior limb of the internal capsule, and whole brain WM (r _s range 0.42–0.63). Although DKI revealed higher mean, radial and axial diffusivity and lower FA than DTI (p < 0.001), the correlation coefficients were comparable. Finally, better motor performance was associated with increased mean and radial kurtosis and kurtosis anisotropy (r _s range 0.43–0.55). In conclusion, DKI provided additional information, but did not show increased sensitivity to detect relations between WM microstructure and bimanual performance in healthy controls.     

White matter microstructure of the cingulum and cerebellar peduncle is related to sustained attention and working memory: A diffusion tensor imaging study

The non-invasive imaging technique of diffusion tensor imaging (DTI) has been used to investigate the microstructural properties of white matter (WM). The present study investigated whether individual differences in the WM structure of normal subjects as measured by fractional anisotropy (FA) values correlate with cognitive performance in terms of sustained attention and working memory. Subjects underwent DTI and performed the Continuous Performance Test (CPT) and N-back task. FA values throughout the brain were correlated with behavioral performance on a voxel-by-voxel basis to investigate relationships between WM microstructure and cognitive function. The discriminability index of CPT correlated positively with FA of the right cingulum. Accuracy of the 2-back task correlated positively with FA in bilateral cerebellar peduncles. WM microstructure of the right cingulum and bilateral cerebellar peduncles appears related to cognitive function such as sustained attention and working memory in the human brain.     

Systematic review and voxel-based meta-analysis of diffusion tensor imaging studies in bipolar disorder

Background

Diffusion tensor imaging (DTI) studies have shown changes in the microstructure of white matter in bipolar disorder. Studies suggest both localised, predominantly fronto-limbic, as well as more widespread changes in white matter, but with some apparent inconsistency. A meta-analysis of white matter alterations in adults with bipolar disorder was undertaken.

Method

Whole-brain DTI studies comparing adults with bipolar disorder to healthy controls on fractional anisotropy (FA) were retrieved using searches of MEDLINE and EMBASE from between 2003 and December 2012. White-matter tract involvement was collated and quantified. Clusters of significantly altered FA were meta-analysed using effect-size signed differential mapping (ES-SDM).

Results

Ten VBA studies (252 patients and 256 controls) and five TBSS studies (138 patients and 98 controls) met inclusion criteria. Sixty-one clusters of significantly different FA between bipolar disorder and healthy controls were identified. Analysis of white-matter tracts indicated that all major classes of tracts are implicated. ES-SDM meta-analysis of VBA studies revealed three significant clusters of decreased FA in bipolar disorder (a right posterior temporoparietal cluster and two left cingulate clusters). Findings limited to the Bipolar Type I papers were more robust.

Limitations

Voxel-based studies do not accurately identify tracts, and our ES-SDM analysis used only published peak voxels rather than raw DTI data.

Conclusions

There is consistent data indicating widespread white matter involvement with decreased white matter FA demonstrated in three disparate areas in bipolar disorder. White matter alterations are not limited to anterior fronto-limbic pathways in bipolar disorder.     

Age-related alterations in white matter microstructure measured by diffusion tensor imaging

Cerebral white matter (WM) undergoes various degenerative changes with normal aging, including decreases in myelin density and alterations in myelin structure. We acquired whole-head, high-resolution diffusion tensor images (DTI) in 38 participants across the adult age span. Maps of fractional anisotropy (FA), a measure of WM microstructure, were calculated for each participant to determine whether particular fiber systems of the brain are preferentially vulnerable to WM degeneration. Regional FA measures were estimated from nine regions of interest in each hemisphere and from the genu and splenium of the corpus callosum (CC). The results showed significant age-related decline in FA in frontal WM, the posterior limb of the internal capsule (PLIC), and the genu of the CC. In contrast, temporal and posterior WM was relatively preserved. These findings suggest that WM alterations are variable throughout the brain and that particular fiber populations within prefrontal region and PLIC are most vulnerable to age-related degeneration.     

The role of diffusion tensor imaging in the evaluation of ischemic brain injury - a review

Water diffusion in brain tissue is affected by the presence of barriers to translational motion such as cell membranes and myelin fibers. The measured water apparent diffusion coefficient (ADC) value is therefore frequently anisotropic and varies depending upon the orientation of restricting barriers (such as white matter tracts) relative to the diffusion-sensitive-gradient direction. Anisotropic water diffusion can be specified using indices of diffusion anisotropy [e.g. standard deviation of the individual ADC values, fractional anisotropy (FA), lattice index (LI)], which are derived from measurements of the full diffusion tensor. The rotationally invariant nature of particular diffusion anisotropy indices (e.g. FA, LI) allows orientation-independent comparisons of these parameters between different subjects. Pathophysiological processes (such as cerebral ischemia) that modify the integrity of the tissue microstructure result in significant alterations in tissue anisotropy and make this metric a useful endpoint for characterizing the temporal evolution of the disease. Diffusion-tensor imaging (DTI) studies of both experimental and human stroke suggest that DTI may provide additional information about the evolution of the disease that is not available from diffusion-weighted MRI (DWI) alone. Acute reductions in the average diffusivity [ = (lambda(1) + lambda(2) + lambda(3))/3 where lambda(1), lambda(2), and lambda(3) are the eigenvalues of the diffusion tensor] following the onset of cerebral ischemia are often accompanied by increases in diffusion anisotropy. In the transition from acute to sub-acute and chronic stroke, renormalizes and subsequently increases whereas diffusion anisotropy measures (e.g. FA) decline and remained reduced in chronic infarcts. Overall isotropic ADC changes during infarct evolution have been observed to be greater in white matter (WM) than in gray matter (GM) lesions (although there have been conflicting reports on this issue) and GM lesions tend to renormalize prior to WM lesions as the infarct evolves. Ischemic WM exhibits a significant decrease in diffusion anisotropy (relative to normal WM) during ischemic evolution whereas that of ischemic GM remains statistically unchanged. Furthermore, the percentage decrease in ischemic WM is largely determined by reductions in lambda(1), the eigenvalue that coincides with the long axis of the WM fiber tract. Variations in unidirectional ADC or over the ischemic time course limit the usefulness of this parameter alone as a predictor of ischemic injury. Consequently, ADC information has been combined with that of other MR parameters (including DTI) to unambiguously stage and predict ischemic brain injury over its entire temporal evolution. Combined and diffusion anisotropy measurements have identified three phases of diffusion abnormality: (1) reduced and elevated anisotropy; (2) reduced and reduced anisotropy; and (3) elevated and reduced anisotropy. However, variations in the differential patterns of and diffusion anisotropy evolution have been observed by a number of investigators and more work is needed to clarify the role of these measurements in characterizing the severity of the ischemic insult as well as the potential outcome in response to the initial ischemic injury. The use of DTI, in combination with more sophisticated analysis methods for performing multiparametric segmentation, such as multispectral analysis, may enhance the use of MRI for accurate diagnosis and prognosis of stroke. Furthermore, these techniques may also play an important role in the clinical evaluation of new stroke treatments.