Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and Alzheimer disease. Diffusion tensor imaging (DTI) can estimate the microstructural integrity of white matter tracts in MCI. We evaluated the microstructural changes in the white matter of MCI patients with DTI. We recruited 11 patients with MCI who met the working criteria of MCI and 11 elderly normal controls. The mean diffusivity (MD) and fractional anisotropy (FA) were measured in 26 regions of the brain with the regions of interest (ROIs) method. In the MCI patients, FA values were significantly decreased in the hippocampus, the posterior limb of the internal capsule, the splenium of corpus callosum, and in the superior and inferior longitudinal fasciculus compared to the control group. MD values were significantly increased in the hippocampus, the anterior and posterior limbs of the internal capsules, the splenium of the corpus callosum, the right frontal lobe, and in the superior and the inferior longitudinal fasciculus. Microstructural changes of several corticocortical tracts associated with cognition were identified in patients with MCI. FA and MD values of DTI may be used as novel biomarkers for the evaluation of neurodegenerative disorders.
Mild Cognitive Impairment; Alzheimer Disease; Diffusion Tensor Imaging; Mean Diffusivity; Fractional Anisotropy
Autism spectrum disorder (ASD) is increasingly viewed as a disorder of functional networks, highlighting the importance of investigating white matter and interregional connectivity. We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle cerebellar peduncle in children with ASD and typically developing (TD) children.
DTI data were obtained from 26 children with ASD and 24 matched TD children. Fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusion were calculated for the whole brain, genu, body and splenium of the corpus callosum, genu, anterior and posterior limbs of the internal capsule, and middle cerebellar peduncle.
Children with ASD had reduced FA and increased radial diffusion for whole brain white matter and all three segments of the corpus callosum and internal capsule, compared to TD children. Increased MD was found for the whole brain and anterior and posterior limbs of the internal capsule. Reduced axial diffusion was found for the body of corpus callosum. Reduced FA was also found for middle cerebellar peduncle.
Our findings suggest widespread white matter compromise in children with ASD. Abnormalities in the corpus callosum indicate impaired interhemispheric transfer. Results for internal capsule and middle cerebellar peduncle add to the currently limited DTI evidence on subcortico-cortical tracts in ASD. The robust impairment found in all three segments of the internal capsule is consistent with studies documenting impairment of elementary sensorimotor function in ASD.
Autism; diffusion tensor imaging; corpus callosum; internal Capsule; middle cerebellar peduncle
Medial temporal lobe and temporoparietal brain regions are among the earliest neocortical sites to undergo pathophysiologic alterations in Alzheimer’s disease (AD), although the underlying white matter changes in these regions is less well known. We employed diffusion tensor imaging to evaluate early alterations in regional white matter integrity in participants diagnosed with mild cognitive impairment (MCI). The following regions of interests (ROIs) were examined: 1) anterior cingulum (AC); 2) posterior cingulum (PC); 3) genu of the corpus callosum; 4) splenium of the corpus callosum; and 5) as a control site for comparison, posterior limb of the internal capsule. Forty nondemented participants were divided into demographically-similar groups based on cognitive status (MCI: n = 20; normal control: n = 20), and fractional anisotropy (FA) estimates of each ROI were obtained. MCI participants showed greater posterior white matter (i.e., PC, splenium) but not anterior white matter (i.e., AC, genu) changes, after adjusting for age, stroke risk, and whole brain volume. FA differences of the posterior white matter were best accounted for by changes in radial but not axial diffusivity. PC FA was also significantly positively correlated with hippocampal volume as well as with performance on tests of verbal memory, whereas stroke risk was significantly correlated with genu FA and was unrelated to PC FA. When investigating subtypes of our MCI population, amnestic MCI participants showed lower PC white matter integrity relative to those with non-amnestic MCI. Findings implicate involvement of posterior microstructural white matter degeneration in the development of MCI-related cognitive changes and suggest that reduced FA of the PC may be a candidate neuroimaging marker of AD risk.
Aging; diffusion tensor imaging; memory; mild cognitive impairment; posterior cingulum; white matter
The purpose of this investigation was to examine the diffusion properties of cerebral white matter in children with recent onset epilepsy (n=19) compared to healthy controls (n=11). Subjects underwent DTI with quantification of mean diffusion (MD), fractional anisotropy (FA), axial diffusivity (Dax) and radial diffusivity (Drad) for regions of interest including anterior and posterior corpus callosum, fornix, cingulum, and internal and external capsules. Quantitative volumetrics were also performed for the corpus callosum and its subregions (anterior, midbody and posterior) and total lobar white and gray matter for the frontal, parietal, temporal and occipital lobes. The results demonstrated no group differences in total lobar gray or white matter volumes or volume of the corpus callosum and its subregions, but did show reduced FA and increased Drad in the posterior corpus callosum and cingulum. These results provide the earliest indication of microstructural abnormality in cerebral white matter among children with idiopathic epilepsies. This abnormality occurs in the context of normal volumetrics and suggests disruption in myelination processes.
DTI; volumetrics; MRI; epilepsy
We acquired diffusion tensor images on 33 normal adults aged 22–64 and 15 adolescents aged 14–21. We assessed relative anisotropy in stereotaxically located regions of interest in the internal capsule, corpus callosum, anterior thalamic radiations, frontal anterior fasciculus, fronto-occipital fasciculus, temporal lobe white matter, cingulum bundle, frontal inferior longitudinal fasciculus, frontal superior longitudinal fasciculus, and optic radiations. All of these structures except the optic radiations, corpus callosum, and frontal inferior longitudinal fasciculus exhibited differences in anisotropy between adolescents and adults. Areas with anisotropy increasing with age included the anterior limb of the internal capsule, superior levels of the frontal superior longitudinal fasciculus and the inferior portion of the temporal white matter. Areas with anisotropy decreasing with age included the posterior limb of the internal capsule, anterior thalamic radiations, fronto-occipital fasciculus, anterior portion of the frontal anterior fasciculus, inferior portion of the frontal superior longitudinal fasciculus, cingulum bundle and superior portion of the temporal axis. Sex differences were found in the majority of areas but were most marked in the cingulum bundle and internal capsule. These results suggest continuing white matter development between adolescence and adulthood.
Age; White matter; Magnetic resonance imaging
This study investigated the relationship of brain white matter (WM) lesions affecting specific neural networks with decreased mobility in ninety-nine healthy community-dwelling subjects ≥75-years old prospectively enrolled by age and mobility status. We assessed lesion burden in the genu, body and splenium of corpus callosum; anterior, superior and posterior corona radiata; anterior and posterior limbs of internal capsule; corticospinal tract; and superior longitudinal fasciculus. Burden in the splenium of corpus callosum (SCC) demonstrated the highest correlation particularly with walking speed (r=0.4, p<10−4), and in logistic regression it was the best regional predictor of low mobility performance. We also found that independent of mobility, corona radiata has the largest lesion burden with anterior (ACR) and posterior (PCR) aspects being the most frequently affected. The results suggest that compromised inter-hemispheric integration of visuospatial information through the SCC plays an important role in mobility impairment in the elderly. The relatively high lesion susceptibility of ACR and PCR in all subjects may obscure the importance of these lesions in mobility impairment.
aging; mobility; brain; white matter; white matter hyperintensity; splenium of corpus callosum; corona radiata; magnetic resonance imaging
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.
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.
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
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.
To investigate microstructure of white matter fiber tracts in pediatric bipolar disorder (PBD) and attention deficit hyperactivity disorder (ADHD).
A diffusion tensor imaging (DTI) study was conducted at 3 Tesla on age and IQ-matched children and adolescents with PBD (n=13), ADHD (n=13), and healthy controls (HC) (n=15). Three DTI parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), and regional fiber coherence index (r-FCI), were examined in eight fiber tracts: Anterior corona radiata (ACR); anterior limb of the internal capsule (ALIC); superior region of the internal capsule (SRI); posterior limb of the internal capsule (PLIC); superior longitudinal fasciculus (SLF); inferior longitudinal fasciculus (ILF); cingulum (CG); splenium (SP).
Significantly lower FA was observed in ACR in both PBD and ADHD relative to HC. In addition, FA and r-FCI values were significantly lower in ADHD relative to PBD and HC in both the ALIC and the SRI. Further, ADC was significantly greater in ADHD relative to both the PBD and HC in ACR, ALIC, PLIC, SRI, CG, ILF, and SLF.
Decreased FA in ACR implies an impaired fiber density or reduced myelination in both PBD and ADHD in this prefrontal tract. These abnormalities, together with the reduced fiber coherence, extended to cortico-bulbar tracts in ADHD. Increased ADC across multiple white matter tracts in ADHD indicates extensive cellular abnormalities with less diffusion restriction in ADHD relative to PBD.
Bipolar disorder; ADHD; diffusion tensor imaging; white-matter fiber tracts; fraction anisotropy; apparent diffusion coefficients
There is evidence to suggest that obsessive–compulsive disorder (OCD) is associated with structural abnormalities in cortico–striato–thalamic circuits, yet the extent of white matter abnormalities is not well established. In this study, we used diffusion tensor imaging (DTI) to examine white matter integrity in specific regions of interest (ROIs) in patients with OCD.
Patients with OCD and sex-, age- and IQ-matched healthy controls underwent DTI. The primary objective was to explore whether patients with OCD had white matter abnormalities in the anterior limb of the internal capsule (ALIC), the uncinate fasciculus, the genu of the corpus callosum and the cingulum. The secondary objective was to evaluate the relation between fractional anisotropy and mean diffusivity in these ROIs and other clinical variables (including age at onset of OCD, OCD severity and levels of depressive and anxiety symptomatology) in patients with OCD.
There were 15 patients and 17 controls enrolled in our study. Compared with healthy controls, patients with OCD showed increased fractional anisotropy in bilateral regions of the ALIC adjacent to the body of the caudate, as well as decreased fractional anisotropy in the right anterior limb near the head of the caudate. Patients also had decreased mean diffusivity in the body of the right cingulum and the left anterior cingulum compared with controls. Correlational analyses revealed significant associations of fractional anisotropy and mean diffusivity in select circuits with OCD, depression and anxiety severity scores.
Inclusion of patients with OCD receiving pharmacotherapy may have been a limitation. In addition, the patients were heterogeneous in terms of their obsessive–compulsive symptom profiles; we did not distinguish between different obsessive–compulsive symptom dimensions.
The study results provide further evidence for OCD-related white matter abnormalities in the ALIC and cingulum, consistent with a corticostriatal model of OCD.
The integrity of white matter, as measured in vivo with diffusion tensor imaging (DTI), is disrupted in normal aging. A current consensus is that in adults advancing age affects anterior brain regions disproportionately more than posterior regions; however, the mainstay of studies supporting this anterior-posterior gradient is based primarily on measures of the corpus callosum. Using our quantitative fiber tracking approach, we assessed fiber tract integrity of samples of major white matter cortical, subcortical, interhemispheric, and cerebellar systems (11 bilateral and 2 callosal) on DTI data collected at 1.5 T magnet strength. Participants were 55 men (age 20-78 years) and 65 women (age 28-81 years), deemed healthy and cognitively intact following interview and behavioral testing. Fiber integrity was measured as orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, which was quantified separately for longitudinal diffusivity (λL), an index of axonal length or number, and transverse diffusivity (λT), an index of myelin integrity. Aging effects were more evident in diffusivity than FA measures. Men and women, examined separately, showed similar age-related increases in longitudinal and transverse diffusivity in fibers of the internal and external capsules bilaterally and the fornix. FA was lower and diffusivity higher in anterior than posterior fibers of regional paired comparisons (genu versus splenium and frontal versus occipital forceps). Diffusivity with older age was generally greater or FA lower in the superior than inferior fiber systems (longitudinal fasciculi, cingulate bundles), with little to no evidence for age-related degradation in pontine or cerebellar systems. The most striking sex difference emerged for the corpus callosum, for which men showed significant decline in FA and increase in longitudinal and transverse diffusivity in the genu but not splenium. By contrast, in women the age effect was present in both callosal regions, albeit modestly more so in the genu than splenium. Functional meaningfulness of these age-related differences was supported by significant correlations between DTI signs of white matter degradation and poorer performance on cognitive or motor tests. This survey of multiple fiber systems throughout the brain revealed a differential pattern of age’s effect on regional FA and diffusivity and suggests mechanisms of functional degradation, attributed at least in part to compromised fiber microstructure affecting myelin and axonal morphology.
Brain; Aging; DTI; White matter; Fiber tracking; Diffusion
Disruption of cerebral white matter has been proposed as an explanation for age-related cognitive declines. However, the role of specific regions in specific cognitive declines remains unclear. We used diffusion tensor imaging to examine the associations between regional microstructural integrity of the white matter and performance on age-sensitive cognitive tasks in a sample of healthy adults (N = 52, age 19–81 years). White matter integrity was assessed by fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in multiple regions of interest (genu and splenium of corpus callosum, internal capsule limbs, prefrontal, temporal, superior/posterior parietal, occipital white matter) and related to processing speed, working memory, inhibition, task switching, and episodic memory. We found that age and regional white matter integrity differentially influenced cognitive performance. Age-related degradation in anterior brain areas was associated with decreased processing speed and poorer working memory, whereas reduced inhibition and greater task switching costs were linked to decline in posterior areas. Poorer episodic memory was associated with age-related differences in central white matter regions. The observed multiple dissociations among specific age-sensitive cognitive skills and their putative neuroanatomical substrates support the view that age-related cognitive declines are unlikely to stem from a single cause.
aging; brain; MRI; diffusion tensor imaging; cognition; white matter; disconnection
Quantitative fiber tracking derived from diffusion tensor imaging (DTI) was used to determine whether white matter association, projection, or commissural tracts are affected in nondemented individuals with HIV infection and to identify the regional distribution of sparing and impairment of fiber systems.
DTI measured fractional anisotropy and diffusivity, quantified separately for longitudinal (λL) diffusivity (index of axonal injury) and transverse (λT) diffusivity (index of myelin injury), in 11 association and projection white matter tracts and six commissural tracts in 29 men and 13 women with HIV infection and 88 healthy, age-matched controls (42 men and 46 women).
The total group of HIV-infected individuals had higher diffusivity (principally longitudinal) than controls in the posterior sectors of the corpus callosum, internal and external capsules, and superior cingulate bundles. High longitudinal diffusivity, indicative of axonal compromise, was especially prominent in posterior callosal sectors, fornix, and superior cingulate bundle in HIV with AIDS. Unmedicated patients had notably high transverse diffusivity, indicative of myelin compromise, in the occipital forceps, inferior cingulate bundle, and superior longitudinal fasciculus. Pontocerebellar projection fibers were resistant to HIV effects as were commissural fibers coursing through premotor and sensorimotor callosal sectors.
This quantitative survey of brain fiber tract integrity indicates that even nondemented HIV patients can have neuroradiological evidence for damage to association and commissural tracts. These abnormalities were vulnerable to exacerbation with AIDS and possibly mitigated by HAART.
AIDS; brain; cognition; dementia; diffusion tensor imaging; HAART; HIV; MRI; white matter
Although hypertension is a major risk factor for cerebrovascular disease (CVD) and is highly prevalent in African Americans, little is known about how blood pressure (BP) affects brain behavior relationships in this population. In predominantly Caucasian populations, high BP is associated with alterations in frontal-subcortical white matter and in executive functioning aspects of cognition. We investigated associations among BP, brain structure, and neuropsychological functioning in 52 middle-older aged African Americans without diagnosed history of CVD. All participants underwent diffusion tensor imaging (DTI) for examination of white matter integrity, indexed by fractional anisotropy (FA). Three regions of interest (ROI's) were derived in the anterior corpus callosum (genu), posterior corpus callosum (splenium), and across the whole brain. A brief neuropsychological battery was administered from which composite scores of executive function and memory were derived. Blood pressure was characterized by mean arterial blood pressure (MABP), an indicator of end-organ perfusion pressure. When controlling for age, higher MABP was associated with lower FA in the genu, and there was a trend for this sample relationship with regard to whole brain FA. When the sample was broken into groups based on treatment for BP regulation (medicated / nonmedicated), MABP was related to genu and whole-brain FA only in the non-medicated group. There were no associations in those individuals who reported taking medication to control blood pressure. Neither MABP nor FA was significantly related to either neuropsychological composite score regardless of medication use. These data provide important evidence that variation in BP may contribute to significant alterations in specific neural regions of white matter in non-medicated individuals without symptoms of overt CVD.
Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) may be effective in treating depression. Parental verbal abuse has been linked to decreased fractional anisotropy (FA) of white matter and reduced FA correlated with depression and anxiety scores. Utilizing a nonhuman primate model of mood and anxiety disorders following disrupted mother-infant attachment, we examined whether adverse rearing conditions lead to white matter impairment of the ALIC.
We examined white matter integrity using Diffusion Tensor Imaging (DTI) on a 3T-MRI. Twenty-one adult male Bonnet macaques participated in this study: 12 were reared under adverse [variable foraging demand (VFD)] conditions whereas 9 were reared under normative conditions. We examined ALIC, posterior limb of the internal capsule (PLIC) and occipital white matter.
VFD rearing was associated with significant reductions in FA in the ALIC with no changes evident in the PLIC or occipital cortex white matter.
Adverse rearing in monkeys persistently impaired frontal white matter tract integrity, a novel substrate for understanding affective susceptibility.
Diffusion tensor imaging; fractional anisotropy; white matter integrity; variable foraging demand
In recent years, diffusion tensor imaging (DTI) has become the modality of choice to investigate white matter pathology in the developing brain. To study neonate Krabbe disease with DTI, we evaluate the performance of linear and non-linear DTI registration algorithms for atlas based fiber tract analysis. The DTI scans of 10 age-matched neonates with infantile Krabbe disease are mapped into an atlas for the analysis of major fiber tracts - the genu and splenium of the corpus callosum, the internal capsules tracts and the uncinate fasciculi. The neonate atlas is based on 377 healthy control subjects, generated using an unbiased diffeomorphic atlas building method. To evaluate the performance of one linear and seven nonlinear commonly used registration algorithms for DTI we propose the use of two novel evaluation metrics: a regional matching quality criterion incorporating the local tensor orientation similarity, and a fiber property profile based metric using normative correlation. Our experimental results indicate that the whole tensor based registration method within the DTI-ToolKit (DTI-TK) shows the best performance for our application.
Diffusion tensor imaging; Registration; Krabbe disease; fiber tracts; MRI; Evaluation metrics
Complete recovery of motor function after stroke is rare with deficits persisting into the chronic phase of recovery. Diffusion tensor imaging (DTI) can evaluate relationships between white matter microstructure and motor function after stroke. The objective of this investigation was to characterize microstructural fiber integrity of motor and sensory regions of the corpus callosum (CC) and descending motor outputs of the posterior limb of the internal capsule (PLIC) in individuals with chronic stroke and evaluate the relationships between white matter integrity and motor function.
Standardized measures of upper extremity motor function were measured in thirteen individuals with chronic stroke. Manual dexterity was assessed in thirteen healthy age-matched control participants. DTI scans were completed for each participant. Fractional anisotropy (FA) of a cross-section of sensory and motor regions of the CC and the PLIC bilaterally were quantified. Multivariate analysis of variance evaluated differences between stroke and healthy groups. Correlational analyses were conducted for measures of motor function and FA. The stroke group exhibited reduced FA in the sensory (p = 0.001) region of the CC, contra- (p = 0.032) and ipsilesional (p = 0.001) PLIC, but not the motor region of the CC (p = 0.236). In the stroke group, significant correlations between contralesional PLIC FA and level of physical impairment (p = 0.005), grip strength (p = 0.006) and hand dexterity (p = 0.036) were observed.
Microstructural status of the sensory region of the CC is reduced in chronic stroke. Future work is needed to explore relationships between callosal sensorimotor fiber integrity and interhemispheric interactions post-stroke. In addition, contralesional primary motor output tract integrity is uniquely and closely associated with multiple dimensions of motor recovery in the chronic phase of stroke suggesting it may be an important biomarker of overall motor recovery.
Diffusion tensor imaging; Stroke; Motor recovery; White matter; Integrity; Corpus callosum; Internal capsule
Schizophrenia and ADHD are associated with similar deficits in working memory, attention, and inhibition. Both disorders also involve abnormalities of white matter integrity, possibly reflecting neural communication disruptions. There are likely some regional white matter abnormalities that underlie the common cognitive impairment, though also some regional abnormalities unique to each disorder. We used diffusion tensor imaging (DTI) to compare white matter integrity, as indicated by fractional anisotropy (FA), in adolescents with schizophrenia (n=15) or ADHD (n=14) and healthy controls (n=26). Schizophrenia patients had uniquely low FA, relative to the other two groups, in bilateral cerebral peduncles, anterior and posterior corpus callosum, right anterior corona radiata, and right superior longitudinal fasciculus. ADHD patients had uniquely high FA in left inferior and right superior frontal regions. Both clinical groups had lower FA than controls in left posterior fornix. The two disorders generally demonstrated distinct patterns of abnormal connectivity suggesting that common cognitive and behavioral deficits derive from distinct sources, though the posterior fornix may be involved in both disorders. Schizophrenia was associated with abnormally low FA in widespread circuitry indicative of general connectivity disruptions, whereas ADHD was associated with abnormally high FA in frontal networks that may indicate impaired branching of fibers.
diffusion tensor imaging; white matter; cognition; connectivity
Studies show white matter hyperintensities, regardless of location, primarily affect frontal lobe metabolism and function. This report investigates how regional white matter integrity (measured as fractional anisotropy (FA)) relates to brain metabolism in order to unravel the complex relationship between white matter change and brain metabolism.
To elucidate the relationship between white matter integrity and gray matter metabolism using diffusion tensor imaging (DTI) and fluorodeoxyglucose-positron emission tomography (FDG-PET) in a cohort of 16 subjects ranging from normal to demented (age>55).
Cross-sectional regression analyses using mean FA values from white matter regions underlying the medial prefrontal, inferior-lateral prefrontal, parietal association, and posterior temporal areas and corpus callosum were regressed with glucose metabolism (PET) using SPM2 (p < 0.005, voxel cluster > 100). Regional cerebral glucose metabolism was the primary outcome measure, with our major hypotheses being those hypometabolic cortical regions affected by Alzheimer’s disease would correlate with lower FA of associated tracks.
Our data show inter-regional positive correlations between FA and gray matter metabolism for the prefrontal cortex, temporal and parietal regions. Our results suggest left prefrontal FA is associated with left temporal and parietal metabolism. Further, left posterior temporal FA correlated with left prefrontal metabolism. Finally, bilateral parietal FA correlated with bilateral temporal metabolism.
These regions are associated with the cognitive processes affected in AD and Cerebrovascular Disease, suggesting a link with white matter degeneration and gray matter hypometabolism. Therefore cortical function and white matter degeneration are related in aging and dementia.
PET; DTI; FA; metabolism; white matter; dementia; Alzheimers disease
White matter tracts are like the “highways” of the brain, allowing for fast and efficient communication among diverse brain regions. The purpose of this paper is to review the results of autism studies that have used Diffusion Tensor Imaging (DTI), which is a neuroimaging method that allows us to examine the structure and integrity of these white matter tracts. From the 48 studies we reviewed, persons with ASD tended to have decreased white matter integrity spanning across many regions of the brain but most consistently in regions such as the corpus callosum (connecting the left and right hemispheres and associated with motor skill and complex information processing), the cingulum bundles (connecting regions along the middle-line of the brain with important frontal projections and associated with executive function), and white matter tracts that pass through the temporal lobe (connecting temporal lobe regions with other brain regions and associated with social functioning). The pattern of results in these studies suggests that the white matter tracts may be atypical in persons with ASD. Additionally, the review suggests that people with ASD may not exhibit the typical left-greater-than-right-brain asymmetry in white matter integrity compared to people with typical development. White matter alterations in persons with ASD are a target of emerging interventions and may help identify the brain basis of individual differences in this population.
White matter tracts of the brain allow neurons and neuronal networks to communicate and function with high efficiency. The aim of this review is to briefly introduce Diffusion Tensor Imaging (DTI) methods that examine white matter tracts and then to give an overview of the studies that have investigated white matter integrity in the brains of individuals with Autism Spectrum Disorder (ASD). From the 48 studies we reviewed, persons with ASD tended to have decreased fractional anisotropy and increased mean diffusivity in white matter tracts spanning many regions of the brain but most consistently in regions such as the corpus callosum, cingulum, and aspects of the temporal lobe. This decrease in fractional anisotropy was often accompanied by increased radial diffusivity. Additionally, the review suggests possible atypical lateralization in some white matter tracts of the brain and a possible atypical developmental trajectory of white matter microstructure in persons with ASD. Clinical implications and future research directions are discussed.
Diffusion Tensor Imaging; Neuroimaging; Autism; White Matter
Diffusion tensor imaging has been widely used to study brain diseases, disorders, development and aging. However, few studies have explored the effects of aging on diffusion imaging measures with higher b-values. Further the water diffusion in biological tissues appears bi-exponential although this also has not been explored with aging. In this study, hybrid diffusion imaging (HYDI) was used to study fifty-two healthy subjects with an age range from 18 to 72 years. The HYDI diffusion-encoding scheme consisted of five concentric q-space shells with b-values raging from 0 to 9375 s/mm2. Quantitative diffusion measures were investigated as a function of age and gender using both region-of-interest (whole brain white matter, genu and splenium of corpus callosum, posterior limb of the internal capsule) and whole-brain voxel based analyses. Diffusion measures included measures of the diffusion probability density function (zero displacement probability, and mean squared displacement), bi-exponential diffusion (i.e. volume fractions of fast/slow diffusion compartments and fast/slow diffusivities), and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity). The bi-exponential volume fraction, the fast diffusivity, and the axial diffusivity measures (f1, D1 and Da) were found to be more sensitive to normal aging than the restricted, slow and radial diffusion measures (Po, D2 and Dr). The bi-exponential volume fraction, f1, showed the most widespread age-dependence in the voxel-based analyses although both FA and mean diffusivity did show changes in frontal white matter regions that may be associated with age-related decline.
diffusion weighted imaging; diffusion tensor imaging; diffusion spectrum imaging; bi-exponential diffusion; age; gender
Normal-appearing white matter has been shown via diffusion tensor imaging to be affected in tuberous sclerosis complex. Under the hypothesis that some systems might be differentially affected, including the visual pathways and systems of social cognition, diffusion properties of various regions of white matter were compared. For 10 patients and 6 age-matched control subjects, 3 T magnetic resonance imaging was assessed using diffusion tensor imaging obtained in 35 directions. Three-dimensional volumes corresponding to the geniculocalcarine tracts were extracted via tractography, and two-dimensional regions of interest were used to sample other regions. Regression analysis indicated lower fractional anisotropy in the splenium of corpus callosum and geniculocalcarine tracts in tuberous sclerosis complex group, as well as lower axial diffusivity in the internal capsule, superior temporal gyrus, and geniculocalcarine tracts. Mean and radial diffusivity of the splenium of corpus callosum were higher in the tuberous sclerosis complex group. The differences in diffusion properties of white matter between tuberous sclerosis complex patients and control subjects suggest disorganized and structurally compromised axons with poor myelination. The visual and social cognition systems appear to be differentially involved, which might in part explain the behavioral and cognitive characteristics of the tuberous sclerosis complex population.
Reproducible Objective Quantification Scheme (ROQS) is a novel method for regional white matter measurements of diffusion tensor imaging (DTI) parameters that overcomes the limitations of previous approaches for analyzing large cohorts of subjects reliably. ROQS is a semi-automated technique that exploits the fiber orientation information from the diffusion tensor in conjunction with a binary masking and chain-linking algorithm to segment anatomically distinct white matter tracts for subsequent quantitative analysis of DTI parameters such as fractional anisotropy and apparent diffusion coefficient. When applied to 3 Tesla whole-brain DTI of normal adult volunteers, ROQS is shown to segment the corpus callosum much faster than manual region of interest (ROI) delineation, and with better reproducibility and accuracy.
Contrary to expectations derived from preclinical studies of the effects of stress, and imaging studies of adults with PTSD, there is no evidence of hippocampus atrophy in children with PTSD. Multiple pediatric studies have reported reductions in the corpus callosum – the primary white matter tract in the brain. Consequently, in the present study, Diffusion Tensor Imaging was used to assess corpus callosum white matter integrity in 17 maltreated children with PTSD and 15 demographically matched normal controls. Children with PTSD had reduced fractional anisotropy in the medial and posterior corpus, a region which contains interhemispheric projections from brain structures involved in circuits that mediate the processing of emotional stimuli and various memory functions --- core disturbances associated with a history of trauma. Further exploration of the effects of stress on corpus callosum and white matter development appears a promising strategy to better understanding the pathophysiology of PTSD in children.
Posttraumatic Stress Disorder; Imaging; DTI; children
To investigate in preterm infants associations between Diffusion Tensor Imaging (DTI) parameters of the posterior limb of the internal capsule (PLIC) and corpus callosum (CC) and age, white matter (WM) injury and clinical factors.
In 84 preterm infants DTI was performed between 40–62 weeks postmenstrual age on 3 T MR. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) values and fibre lengths through the PLIC and the genu and splenium were determined. WM injury was categorised as normal/mildly, moderately and severely abnormal. Associations between DTI parameters and age, WM injury and clinical factors were analysed.
A positive association existed between FA and age at imaging for fibres through the PLIC (r = 0.48 p < 0.001) and splenium (r = 0.24 p < 0.01). A negative association existed between ADC and age at imaging for fibres through the PLIC (r = −0.65 p < 0.001), splenium (r = −0.35 p < 0.001) and genu (r = −0.53 p < 0.001). No association was found between DTI parameters and gestational age, degree of WM injury or categorical clinical factors.
These results indicate that in our cohort of very preterm infants, at this young age, the development of the PLIC and CC is ongoing and independent of the degree of prematurity or WM injury.
Diffusion tensor imaging; Fibre tractography; Very preterm infants; Term equivalent age; White matter injury
To use diffusion tensor imaging (DTI) to assess gray matter and white matter tract diffusion in behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SMD), and progressive nonfluent aphasia (PNFA).
This was a case-control study where 16 subjects with bvFTD, 7 with PNFA, and 4 with SMD were identified and matched by age and gender to 19 controls. All subjects had 3-T head MRI with a DTI sequence with diffusion encoding in 21 directions. Gray matter mean diffusivity (MD) was assessed using a region-of-interest (ROI) and voxel-level approach, and voxel-based morphometry was used to assess patterns of gray matter loss. White matter tract diffusivity (fractional anisotropy and radial diffusivity) was assessed by placing ROIs on tracts of interest.
In bvFTD, increased gray matter MD and gray matter loss were identified bilaterally throughout frontal and temporal lobes, with abnormal diffusivity observed in white matter tracts that connect to these regions. In SMD, gray matter loss and increased MD were identified predominantly in the left temporal lobe, with tract abnormalities observed in the inferior longitudinal fasciculus and uncinate fasciculus. In PNFA, gray matter loss and increased MD were observed in left inferior frontal lobe, insula, and supplemental motor area, with tract abnormalities observed in the superior longitudinal fasciculus.
The diffusivity of gray matter is increased in regions that are atrophic in frontotemporal dementia, suggesting disruption of the cytoarchitecture of remaining tissue. Furthermore, damage was identified in white matter tracts that interconnect these regions, supporting the hypothesis that these diseases involve different and specific brain networks.
= automated anatomic labeling;
= anterior cingulate;
= Alzheimer's Disease Research Center;
= Alzheimer's Disease Patient Registry;
= apraxia of speech;
= behavioral variant frontotemporal dementia;
= coefficient of variation;
= axial diffusivity;
= radial diffusivity;
= diffusion tensor imaging;
= fractional anisotropy;
= false discovery rate;
= field of view;
= frontotemporal dementia;
= full-width at half-maximum;
= genu of the corpus callosum;
= high-dimensional warping;
= inferior longitudinal fasciculus;
= mean diffusivity;
= magnetization prepared rapid acquisition gradient echo;
= posterior cingulate;
= progressive nonfluent aphasia;
= partial volume correction;
= region of interest;
= superior longitudinal fasciculus;
= semantic dementia;
= uncinate fasciculus.