Significant Increase In Fractional Anisotropy Research Articles

Mindfulness-Based Stress Reduction, Fear Conditioning, and The Uncinate Fasciculus: A Pilot Study.

Mindfulness has been suggested to impact emotional learning, but research on these processes is scarce. The classical fear conditioning/extinction/extinction retention paradigm is a well-known method for assessing emotional learning. The present study tested the impact of mindfulness training on fear conditioning and extinction memory and further investigated whether changes in white matter fiber tracts might support such changes. The uncinate fasciculus (UNC) was of particular interest in the context of emotional learning. In this pilot study, 46 healthy participants were quasi-randomized to a Mindfulness-Based Stress Reduction (MBSR, N = 23) or waitlist control (N = 23) group and underwent a two-day fear conditioning, extinction learning, and extinction memory protocol before and after the course or control period. Skin conductance response (SCR) data served to measure the physiological response during conditioning and extinction memory phases. Diffusion tensor imaging (DTI) data were analyzed with probabilistic tractography and analyzed for changes of fractional anisotropy in the UNC. During conditioning, participants were able to maintain a differential response to conditioned vs. not conditioned stimuli following the MBSR course (i.e., higher sensitivity to the conditioned stimuli), while controls dropped the response. Extinction memory results were not interpretable due to baseline differences. MBSR participants showed a significant increase in fractional anisotropy in the UNC, while controls did not (group by time interaction missed significance). Pre-post changes in UNC were correlated with changes in the response to the conditioned stimuli. The findings suggest effects of mindfulness practice on the maintenance of sensitivity of emotional responses and suggest underlying neural plasticity. (ClinicalTrials.gov, Identifier NCT01320969, https://clinicaltrials.gov/ct2/show/NCT01320969).

Bone Marrow Endothelial Progenitor Cell Transplantation After Ischemic Stroke: An Investigation Into Its Possible Mechanism.

We tested the hypothesis that endothelial progenitor cell (EPC)-mediated functional recovery after stroke may be associated with the endothelial nitric oxide synthase (eNOS)/brain-derived neurotrophic factor (BDNF) signaling pathway. Mice were infused with either EPCs or saline after being subjected to middle cerebral artery occlusion. The EPC-treated mice also received intravenous injections of either Nω-nitro-l-arginine methyl ester (L-NAME, the NOS inhibitor) or saline. The activation of eNOS and the expression of BDNF were significantly increased in ischemic brain of the EPC-treated mice, along with increased angiogenesis and neurogenesis. On diffusion tensor imaging (DTI), significant increases in fractional anisotropy and fiber count were observed in white matter, indicating axonal growth stimulated by EPCs. However, the EPC-treated mice that were received an L-NAME injection failed to exhibit the observed increases in angiogenesis, neurogenesis, and axonal growth. In addition, the neurons cocultured with EPCs in vitro exhibited the increased expression of BDNF and decreased apoptosis after oxygen-glucose deprivation compared with the control group. This EPC-induced protective effect was virtually absent in the L-NAME treatment group. The eNOS/BDNF pathway may be involved in the EPC-mediated functional recovery of stroke mice. DTI is feasible for dynamically tracking the orientation of axonal projections after EPC treatment.

Comparison of different stimulation parameters of repetitive transcranial magnetic stimulation for unilateral spatial neglect in stroke patients

Objective: In this study three different stimulation parameters of repetitive transcranial magnetic stimulation (rTMS) were tested to compare the efficacy of continuous theta burst stimulation (continuous TBS) for rehabilitation of unilateral spatial neglect (USN) in stroke patients. Methods: Carefully selected cohort of thirty-eight stroke patients were randomly assigned to three treatment groups (1Hz group, 10Hz group and continuous TBS group) and sham group. Intervention in patients in the treatment group consisted of rTMS, while patients in the sham group received pseudo-stimulation for two weeks. All patients were administered star cancellation and line bisection tests at 4 different time points of the study. Further, all study subjects in the three treatment groups and sham group underwent diffusion-tensor imaging (DTI) at the beginning and at the end of treatment to calculate fractional anisotropy (FA) and mean diffusivity (MD). Results: Among the three stimulation parameters, star cancellation and line bisection tests revealed significant differences in outcomes at the end of treatments and one month after the end of treatments, compared to beginning of the treatments. Importantly, continuous TBS group patients displayed the best curative effect, based on behavioral scoring, at one month after end of the treatments, followed by the 1Hz group and 10Hz group. DTI results showed a significant increase in FA and MD in superior longitudinal fasciculus, superior occipitofrontal fascicle and inferior fronto-occipital fasciculus on the left side, as well as the capsula external and inferior fronto-occipital fasciculus on the right side, in patients after continuous TBS. In addition, compared to the sham group, patients stimulated with continuous TBS exhibited a dramatic increase in FA in the left external capsule. Conclusion: Our study presents strong evidence that rTMS significantly improves neurocognitive functions in USN, with continuous TBS showing the best curative effect. Enhanced connections in the white matter tract network related to visual attention, as assessed by DTI, might be the potential mechanism for the observed recovery in USN using continuous TBS.

Diffusion tensor magnetic resonance imaging in very early onset pediatric multiple sclerosis

Objectives: Active myelination during childhood may influence the impact of multiple sclerosis (MS) on brain structural integrity. We studied normal-appearing white matter (NAWM) in children with MS onset before age 12 years using diffusion tensor (DT) magnetic resonance imaging (MRI). Methods: DT MRI scans were obtained from 22 MS children with their first attack before age 12 years, and 31 healthy controls from two referral centers. Using probabilistic tractography, brain tissue integrity within interhemispheric, intrahemispheric, and projection tracts was compared between patients and site-matched controls. The impact of disease and age at MRI on tract NAWM fractional anisotropy (FA) and mean diffusivity (MD) values was evaluated using linear models. Results: Compared to controls, pediatric MS patients had reduced FA and increased MD of the bilateral superior longitudinal fasciculus and corpus callosum (CC), without center-by-group interaction. CC NAWM average FA was correlated with brain T2 lesion volume. In controls, the majority of the tracts analyzed showed a significant increase of FA and decrease of MD with age. Such a linear correlation was lost in patients. Conclusions: In very young pediatric MS patients, DT MRI abnormalities affect brain WM tracts differentially, and are only partially correlated with focal WM lesions. Impaired maturation of WM tracts with age may be an additional factor contributing to these findings.

Structural white matter changes in descending motor tracts correlate with improvements in motor impairment after undergoing a treatment course of tDCS and physical therapy.

Motor impairment after stroke has been related to the structural and functional integrity of corticospinal tracts including multisynaptic motor fibers and tracts such as the cortico-rubral-spinal and the cortico-tegmental-spinal tract. Furthermore, studies have shown that the concurrent use of transcranial direct current stimulation (tDCS) with peripheral sensorimotor activities can improve motor impairment. We examined microstructural effects of concurrent non-invasive bihemispheric stimulation and physical/occupational therapy for 10 days on the structural components of the CST as well as other descending motor tracts which will be referred to here as alternate motor fibers (aMF). In this pilot study, ten chronic patients with a uni-hemispheric stroke underwent Upper-Extremity Fugl-Meyer assessments (UE-FM) and diffusion tensor imaging (DTI) for determining diffusivity measures such as fractional anisotropy (FA) before and after treatment in a section of the CST and aMF that spanned between the lower end of the internal capsule (below each patient’s lesion) and the upper pons region on the affected and unaffected hemisphere. The treated group (tDCS + PT/OT) showed significant increases in the proportional UE-FM scores (+21%; SD 10%), while no significant changes were observed in an untreated comparison group. Significant increases in FA (+0.007; SD 0.0065) were found in the ipsilesional aMF in the treated group while no significant changes were found in the contralesional aMF, in either CST, or in any tracts in the untreated group. The FA changes in the ipsilesional aMF significantly correlated with the proportional change in the UE-FM (r = 0.65; p < 0.05). The increase in FA might indicate an increase in motor fiber alignment, myelination, and overall fiber integrity. Crossed and uncrossed fibers from multiple cortical regions might be one reason why the aMF fiber system showed more plastic structural changes that correlate with motor improvements than the CST.

Diffusion Tensor Imaging in Mild Traumatic Brain Injuries – Acute State and Short-Term Recovery

Mild traumatic brain injuries (MTBI), in most cases, cannot be detected using imaging modalities like CT or MRI. However, diffusion tensor imaging (DTI) reveals subtle changes in white matter integrity as a result of head trauma and plays an important role in refining diagnosis and management of MTBI. We use DTI to detect the microstructural changes in collegial football players induced by axonal injuries and to monitor their evolution during the recovery process. Three players suffered a MTBI during play or practice and underwent scanning within 24h with follow-ups after one and two weeks. Scalar diffusion indices were derived from diffusion tensors and analyzed using tract-based spatial statistics (TBSS) and voxel-wise t-tests to detect brain regions showing significant group differences between the injured subjects and controls. Both analyses revealed overlapping regions in the corticospinal tract with significant increase in fractional anisotropy and decreases in transverse and mean diffusivity within 24 hours. In voxel-wise t-tests strong indications for recovery were found spatially and temporally. For mean and transverse diffusivity, regions showing significant differences shrunk between the first and the follow-up scans. Although the sample size is small, these findings are remarkably consistent across all subjects and scans.

Microstructural abnormality in white matter, regulatory T lymphocytes, and depressive symptoms after stroke.

The purpose of the present study was to investigate the existence of microstructure abnormalities in the white matter circuit in stroke patients and its relationship to depressive episodes. To target the prevention of depression, we also investigated the relationship between lymphocyte subsets and cerebral abnormalities in patients. Participants included 18 patients with acute ischemic stroke and 22 healthy control subjects. Diffusion tensor imaging was performed. Whole-brain voxel-based analysis was used to compare fractional anisotropy (FA) between groups. Blood samples were obtained, and the lymphocyte subsets were evaluated using flow cytometry. Follow-up examinations were conducted on 12 patients at 6 months. FA was decreased in the bilateral anterior limb of the internal capsule in stroke patients. At the 6-month follow-up examination, there was a significant increase in FA, which was associated with a lower depression scale score. Patients showed a decreased percentage of circulated regulatory T lymphocytes, and the degree of reduction was related to the decrease in the FA value in the internal capsule. FA reductions in the anterior limb of the internal capsule cause abnormality in the frontal-subcortical circuits and confer a biological vulnerability, which in combination with environmental stressors results in the onset of depression. Our findings also demonstrated the possibility of preventing post-stroke depression by targeting the role of regulatory T lymphocytes in brain tissue repair and regeneration after stroke.

The value of diffusion tensor imaging in differentiating high-grade gliomas from brain metastases: a systematic review and meta-analysis.

PurposeDifferentiation of high-grade gliomas and solitary brain metastases is an important clinical issue because the treatment strategies differ greatly. Our study aimed to investigate the potential value of diffusion tensor imaging (DTI) in differentiating high-grade gliomas from brain metastases using a meta-analytic approach.Materials and MethodsWe searched Pubmed, Embase and the Cochrane Library for relevant articles published in English. Studies that both investigated high-grade gliomas and brain metastases using DTI were included. Random effect model was used to compare fractional anisotropy (FA) and mean diffusivity (MD) values in the two tumor entities.ResultsNine studies were included into the meta-analysis. In the peritumoral region, compared with brain metastases, high-grade gliomas had a significant increase of FA (SMD = 0.47; 95% CI, 0.22–0.71; P<0.01) and a significant decrease of MD (SMD = −1.49; 95% CI, −1.91 to −1.06; P<0.01). However, in the intratumoral area, no significant change in FA (SMD = 0.16; 95% CI, −0.49 to 0.82; P = 0.73) or MD (SMD = 0.34; 95% CI, −0.91 to 1.60; P = 0.59) was detected between gliomas and metastases.ConclusionsHigh-grade gliomas may be distinguished from brain metastases by comparing the peritumoral FA and MD values. DTI appears to be a promising tool in diagnosing solitary intracranial lesions.

Hockey Concussion Education Project, Part 3. White matter microstructure in ice hockey players with a history of concussion: a diffusion tensor imaging study

The aim of this study was to examine the brain's white matter microstructure by using MR diffusion tensor imaging (DTI) in ice hockey players with a history of clinically symptomatic concussion compared with players without a history of concussion. Sixteen players with a history of concussion (concussed group; mean age 21.7 ± 1.5 years; 6 female) and 18 players without a history of concussion (nonconcussed group; mean age 21.3 ± 1.8 years, 10 female) underwent 3-T DTI at the end of the 2011-2012 Canadian Interuniversity Sports ice hockey season. Tract-based spatial statistics (TBSS) was used to test for group differences in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and the measure "trace," or mean diffusivity. Cognitive evaluation was performed using the Immediate Postconcussion Assessment and Cognitive Test (ImPACT) and the Sport Concussion Assessment Tool-2 (SCAT2). TBSS revealed a significant increase in FA and AD, and a significant decrease in RD and trace in several brain regions in the concussed group, compared with the nonconcussed group (p < 0.05). The regions with increased FA and decreased RD and trace included the right posterior limb of the internal capsule, the right corona radiata, and the right temporal lobe. Increased AD was observed in a small area in the left corona radiata. The DTI measures correlated with neither the ImPACT nor the SCAT2 scores. The results of the current study indicate that a history of concussion may result in alterations of the brain's white matter microstructure in ice hockey players. Increased FA based on decreased RD may reflect neuroinflammatory or neuroplastic processes of the brain responding to brain trauma. Future studies are needed that include a longitudinal analysis of the brain's structure and function following a concussion to elucidate further the complex time course of DTI changes and their clinical meaning.

The Effect of Respiratory and Cardiac Motion in Liver Diffusion Tensor Imaging (DTI)

To evaluate the effect of respiratory and cardiac motion on diffusion tensor imaging (DTI) metrics in healthy human liver. Fifteen healthy subjects, participating in either part of this study, were scanned using a 1.5-T magnetic resonance imaging (MRI) device. Coronal liver DTI (6 diffusion-encoding directions; b, 300 mm/s) during breath holding was compared to free breathing. Cardiac motion effects were evaluated by comparing breath-held DTI scans acquired during both diastole and systole. Free breathing resulted in a significantly increased mean diffusivity (P < 0.05), λ1 (P < 0.01), λ2 (P < 0.05), and λ3 (P < 0.01) compared to breath holding. During systole significant increases in fractional anisotropy (P < 0.05), mean diffusivity (P < 0.05), and λ1 (P < 0.05), compared to systole, were found in the left lobe. The right lobe, which is less affected by cardiac motion, showed no significant change in DTI metrics over the cardiac cycle. Respiratory and cardiac motion tends to increase liver DTI metrics.

Change in fractional anisotropy during treatment of diabetic ketoacidosis in children

The pathophysiology resulting in cerebral edema in pediatric diabetic ketoacidosis (DKA) is unknown. To investigate the changes in white matter microstructure in this disease, we measured diffusion tensor imaging (DTI) parameters, including apparent diffusion coefficient (ADC), fractional anisotropy (FA), and radial and axial diffusivity in children with DKA at two time points during treatment. A prospective observational study was conducted at Seattle Children's Hospital, Seattle, WA. Thirty-two children admitted with DKA (pH < 7.3, bicarbonate < 15 mEq/l, glucose > 300 mg/dl, and ketosis; 11.9 ± 3.2 y; and 47% male) were enrolled and underwent two serial paired diffusion magnetic resonance imaging (MRI) scans following hospital admission. Seventeen of the 32 participants had diffusion tensor images of adequate quality for tract-based spatial statistics (TBSS) analysis. TBSS mapping demonstrated main white matter tract areas with a significant increase in FA and areas with a significant decrease in ADC, from the first to the second MRI. Both radial and axial diffusivity terms showed change, with a diffuse pattern of involvement. Consistent DTI changes occurred during DKA treatment over a short time frame. These findings describe widespread water diffusion abnormalities in DKA, supporting an association between clinical illness and DTI markers of microstructural change in white matter.

Pediatric frontal lobe epilepsy: white matter abnormalities and cognitive impairment

Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE). Its etiology remains unknown. With diffusion tensor imaging, we have studied cerebral white matter properties and associations with cognitive functioning in children with FLE and healthy controls. Thirty children aged 8-13 years with FLE of unknown cause and 39 healthy age-matched controls underwent neuropsychological assessment, structural and diffusion-weighted brain MRI. Patients were grouped as cognitively impaired or unimpaired, and their white matter diffusion properties were compared with the controls. Children with FLE had reduced apparent diffusion coefficients in various posteriorly located tract bundles, a reduced fractional anisotropy (FA) of the white matter tract between the right frontal and right occipital lobe, and smaller volumes of several collections of interlobar bundle tracts, compared with controls. The cognitively impaired patient group demonstrated significant increases in FA of the white matter of both occipital lobes, a reduced FA of white matter tract bundles between the right frontal and both left occipital lobe and subcortical white matter area, and smaller volumes of two collections of tract bundles connecting the frontal lobe with the temporal and parietal lobes, compared with controls. Children with FLE had white matter abnormalities mainly in posterior brain regions, not confined to the area of the seizure focus. Cognitively impaired children with FLE showed the most pronounced white matter abnormalities. These possibly reflect disturbed maturation and might be part of the etiology of the cognitive impairment.

Diffusion tensor imaging of the median nerve before and after carpal tunnel release in patients with carpal tunnel syndrome: feasibility study

To evaluate diffusion tensor imaging (DTI) indices of the median nerve pre and postoperatively in patients with carpal tunnel syndrome (CTS) to determine whether indices acquired prior to surgery differ from those acquired postoperatively. Following IRB approval, ten patients with a diagnosis of CTS were prospectively recruited. Eight patients completed the study (seven women, one man). All had bilateral asymmetric symptoms, with subsequent carpal tunnel release on the more symptomatic side. DTI of both wrists were performed using single-shot spin-echo echo-planar imaging (TR/TE, 7,000/103ms; b value 1,025s/mm(2)) preoperatively, 6weeks and 6months after carpal tunnel release. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the median nerve at the level of the distal radioulnar joint and pisiform were determined by one investigator blinded to clinical data, side, and time relative to surgery. All patients had resolution of symptoms on the surgical side at 6months. A significant increase in FA (p = 0.018) and decrease in ADC (p = 0.017) were found proximally at 6months compared to baseline on the operative side. A significant increase in FA was observed on the operative side distally at 6weeks (p = 0.012) and 6months (p = 0.017). There was a significant difference in the percentage change in FA values from baseline to 6months on the operative side in comparison with the non-operative side (p = 0.017). A significant increase in FA and decrease in ADC of the median nerve are seen following decompression surgery in patients with CTS.

Diffusion tensor parameters and principal eigenvector coherence: Relation to b-value intervals and field strength

Diffusion-weighted MRI images acquired at b-value greater than 1000smm−2 measure the diffusion of a restricted pool of water molecules. High b-value images are accompanied by a reduction in signal-to-noise ratio (SNR) due to the application of large diffusion gradients. By fitting the diffusion tensor model to data acquired at incremental b-value intervals, we determined the effect of SNR on tensor parameters in normal human brains, in vivo. In addition, we also investigated the impact of field strength on the diffusion tensor model. Data were acquired at 1.5 and 3T, at b-values 0, 1000, 2000 and 3000smm−2 in twenty diffusion-sensitised directions. Fractional anisotropy (FA), mean diffusivity (MD) and principal eigenvector coherence (κ) were calculated from diffusion tensors fitted between datasets with b-values 0–1000, 0–2000, 0–3000, 1000–2000 and 2000–3000smm−2. Field strength and b-value effects on diffusion parameters were analysed in white and grey matter regions of interest. Decreases in FA, κ and MD were found with increasing b-value in white matter. Univariate analysis showed a significant increase in FA with increasing field strength in highly organised white matter. These results suggest there are significant differences in diffusion parameters at 1.5 and 3T and that the optimal results, in terms of the highest values of FA in white matter, are obtained at 3T with a maximum b=1000smm−2.

Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model

Loss of basal forebrain cholinergic neurons is an early and key feature of Alzheimer's disease, and magnetic resonance imaging (MRI) volumetric measurement of the basal forebrain has recently gained attention as a potential diagnostic tool for this condition. The aim of this study was to determine whether loss of basal forebrain cholinergic neurons underpins changes which can be detected through diffusion MRI using diffusion tensor imaging (DTI) and probabilistic tractography in a mouse model. To cause selective basal forebrain cholinergic degeneration, the toxin saporin conjugated to a p75 neurotrophin receptor antibody (mu-p75-SAP) was used. This resulted in ~25% loss of the basal forebrain cholinergic neurons and significant loss of terminal cholinergic projections in the hippocampus, as determined by histology. To test whether lesion of cholinergic neurons caused basal forebrain, hippocampal, or whole brain atrophy, we performed manual segmentation analysis, which revealed no significant atrophy in lesioned animals compared to controls (Rb-IgG-SAP). However, analysis by DTI of the basal forebrain area revealed a significant increase in fractional anisotropy (FA; +7.7%), mean diffusivity (MD; +6.1%), axial diffusivity (AD; +8.5%) and radial diffusivity (RD; +4.0%) in lesioned mice compared to control animals. These parameters strongly inversely correlated with the number of choline acetyl transferase-positive neurons, with FA showing the greatest association (r(2)=0.72), followed by MD (r(2)=0.64), AD (r(2)=0.64) and RD (r(2)=0.61). Moreover, probabilistic tractography analysis of the septo-hippocampal tracts originating from the basal forebrain revealed an increase in streamline MD (+5.1%) and RD (+4.3%) in lesioned mice. This study illustrates that moderate loss of basal forebrain cholinergic neurons (representing only a minor proportion of all septo-hippocampal axons) can be detected by measuring either DTI parameters of the basal forebrain nuclei or tractography parameters of the basal forebrain tracts. These findings provide increased support for using DTI and probabilistic tractography as non-invasive tools for diagnosing and/or monitoring the progression of conditions affecting the integrity of the basal forebrain cholinergic system in humans, including Alzheimer's disease.

Association between white matter fiber integrity and subclinical psychotic symptoms in schizophrenia patients and unaffected relatives

In this study, we investigate whether aberrant integrity of white matter (WM) fiber tracts represents a genetically determined biological marker of schizophrenia (SZ), and its relation with clinical symptoms. We collected brain DTI data from 28 SZ patients, 18 first-degree relatives and 22 matched controls and used voxel-based analysis with tract-based spatial statistics (TBSS) in order to compare fractional anisotropy (FA) between groups. Mean voxel-based FA values from the entire skeleton of each group were compared. We did a multiple regression analysis, followed by single post-hoc contrasts between groups. FA values were extracted from the statistically significant areas. The results showed significantly smaller FA values for SZ patients in comparison with controls in cortico-spinal tracts, in commissural fibers, in thalamic projections, in association fibers and in cingulum bundles. A significant increase of FA in SZ patients in comparison with healthy controls was only found in the arcuate fasciculus. Relatives had intermediate values between patients and controls which were deemed significant in the comparison to patients and controls in association fibers, arcuate fasciculus and cingulum bundles. Lower FA values in association fibers were significantly associated with predisposition toward hallucinations (in SZ patients and relatives), with higher PANSS scores of positive symptoms and with duration of illness (SZ patients). Our results suggest that clinical and subclinical presentations of psychotic symptoms are associated with aberrant integrity of multiple WM tracts. This association may represent an endophenotype of schizophrenia, since it is present in unaffected relatives as well. Such endophenotypes may serve as quantitative traits for future genetic studies and as candidate markers for early and preclinical identification of subjects at risk.

P-796 - Assessment of alteration in white matter integrity in schizophrenia following administration of clozapine: tract-based spatial statistics of diffusion tensor imaging

Several diffusion tensor imaging (DTI) studies have shown disturbed white matter integrity in various brain areas in schizophrenia patients compared to controls, while studies investigating the effects of antipsychotics on white matter integrity is scarce, and the effect of clozapine on DTI measures have not yet been studied. The purpose of this study was to investigate the influence of clozapine on white matter integrity in patients with chronic schizophrenia by using Tract-Based-Spatial-Statistics (TBSS). DTI of sixteen patients with schizophrenia (M/F: 10/6) were performed before the initiation, and at 3rd month of clozapine treatment using a 1.5 T MR scanner (Magnetom TIM, Siemens, Germany). A voxelwise statistical analysis of fractional anisotropy (FA) maps was carried out using TBSS, part of the FSL software package. Voxelwise statistics on the skeletonised FA data was computed at a threshold level of p < 0.05. White matter structures with significant group differences in FA were extracted as ROIs, registered to and overlaid onto an anatomical template and labelled using the MRI Atlas of Human White Matter. TBSS-DTI revealed significant increases in FA after 3 months of clozapine administration in bilateral, but predominantly right hippocampus, genu and splenium of the corpus callosum, fornices, frontal, parietal and temporal white matter. To our knowledge this is the first study to show that clozapine treatment resulted in a widespread increase in FA, indicative of improved white matter integrity. Clozapine may exert its effects by improving intra- and interhemispheric connectivity among cortical and subcortical regions.

Diffusion tensor imaging findings in young children with benign external hydrocephalus differ from the normal population

To compare a pediatric population diagnosed with benign external hydrocephalus (BEH) to normal age-matched controls using diffusion tensor imaging (DTI) techniques. We retrospectively identified 17 BEH patients by specific clinical and neuroimaging criteria. Fractional anisotropy (FA) and mean diffusivity (MD) values obtained from DTI scans were compared to a population of age-matched controls and group differences were examined by mixed model analysis. A longitudinal comparison was completed on a subset that underwent multiple scans (n = 8). In the genu of the corpus callosum (gCC), six of 15 BEH children had an FA value above the upper limit of 95% prediction interval, nine of 15 BEH children had MD values below the lower limit of 95% prediction interval. A similar trend applied to the other regions of interest (ROIs): splenium of the corpus callosum (sCC), ALIC, and PLIC. Statistical analysis demonstrated significant differences in FA within the gCC, sCC, and PLIC and in MD within the sCC between BEH patients and controls given (P = 0.05). No statistical differences were identified at any ROIs at the later scans. We found a significant increase in FA and decrease in MD in children with BEH compared with normal children in specific white matter (WM) ROIs, notably in the gCC and sCC; furthermore, in longitudinal comparison, DTI parameters normalized over time. The current study further demonstrates the ability of DTI to distinguish between subtle diffusion changes in periventricular white matter and establishes preliminary objective radiographic parameters for watchful observation of patients with BEH.

Potential Long-term Effects of MDMA on the Basal Ganglia–Thalamocortical Circuit: A Proton MR Spectroscopy and Diffusion-Tensor Imaging Study

To investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA, commonly known as "ecstasy") on the alterations of brain metabolites and anatomic tissue integrity related to the function of the basal ganglia-thalamocortical circuit by using proton magnetic resonance (MR) spectroscopy and diffusion-tensor MR imaging. This study was approved by a local institutional review board, and written informed consent was obtained from all subjects. Thirty-one long-term (>1 year) MDMA users and 33 healthy subjects were enrolled. Proton MR spectroscopy from the middle frontal cortex and bilateral basal ganglia and whole-brain diffusion-tensor MR imaging were performed with a 3.0-T system. Absolute concentrations of metabolites were computed, and diffusion-tensor data were registered to the International Consortium for Brain Mapping template to facilitate voxel-based group comparison. The mean myo-inositol level in the basal ganglia of MDMA users (left: 4.55 mmol/L ± 2.01 [standard deviation], right: 4.48 mmol/L ± 1.33) was significantly higher than that in control subjects (left: 3.25 mmol/L ± 1.30, right: 3.31 mmol/L ± 1.19) (P < .001). Cumulative lifetime MDMA dose showed a positive correlation with the levels of choline-containing compounds (Cho) in the right basal ganglia (r = 0.47, P = .02). MDMA users also showed a significant increase in fractional anisotropy (FA) in the bilateral thalami and significant changes in water diffusion in several regions related to the basal ganglia-thalamocortical circuit as compared with control subjects (P < .05; cluster size, >50 voxels). Increased myo-inositol and Cho concentrations in the basal ganglia of MDMA users are suggestive of glial response to degenerating serotonergic functions. The abnormal metabolic changes in the basal ganglia may consequently affect the inhibitory effect of the basal ganglia to the thalamus, as suggested by the increased FA in the thalamus and abnormal changes in water diffusion in the corresponding basal ganglia-thalamocortical circuit.

Abnormal white matter integrity in young children with autism

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