Fractional Anisotropy Reduction Research Articles

Microstructures in striato-thalamo-orbitofrontal circuit in methamphetamine users.

Background Striato-thalamo-orbitofrontal (STO) circuit plays a key role in the development of drug addiction. Few studies have investigated its microstructural abnormalities in methamphetamine (MA) users. Purpose To evaluate the microstructural changes and relevant clinical relevance of the STO circuit in MA users using diffusion tensor imaging (DTI). Material and Methods Twenty-eight MA users and 28 age-matched normal volunteers were enrolled. 3T magnetic resonance imaging (MRI) was employed to obtain structural T1-weighted (T1W) imaging and diffusion-tensor imaging (DTI) data. Freesurfer software was used for automated segmentation of the bilateral nucleus accumbens (NAc), thalami, and orbitofrontal cortex (OFC). Four DTI measures maps, fractional anisotropy (FA), mean diffusivity (MD), axial diffusion (AD), and radial diffusion (RD) were generated and non-linearly co-registered to structural space. Comparisons of DTI measures of the STO circuit were carried out between MA and controls using repeated measures analysis of variance. Correlation analyses were performed between STO circuit DTI measures and clinical characteristics. Results The MA group had significant FA reduction in the bilateral NAc, OFC, and right thalamus ( P < 0.05). Lower left OFC FA and right NAc FA/AD were associated with longer duration of MA use. Lower right OFC FA was associated with younger age at first MA use. Higher FA and lower MD/RD in the thalamus, as well as higher left OFC RD, were associated with increased psychiatric symptoms. Conclusion The STO circuit has reduced microstructural integrity in MA users. Microstructural changes in the thalamus may compensate for dysfunction in functionally connected cortices, which needs further investigation.

Shared abnormality of white matter integrity in schizophrenia and bipolar disorder: A comparative voxel-based meta-analysis

Patients with schizophrenia and bipolar disorder (BD) shared a significant overlap in genetic susceptibility, pharmacological treatment responses, neuropsychological deficits, and epidemiological features. However, it remains unknown whether these clinical overlaps are mediated by shared or disorder-specific abnormalities of white matter integrity. In this voxel-based meta-analytic comparison of whole-brain white matter integrity, we aimed to identify the shared or disorder-specific structural abnormalities between schizophrenia and BD. A comprehensive literature search was conducted up to February 2016 to identify studies that compared between patients and healthy controls (HC) by using whole-brain diffusion approach (schizophrenia: 24 datasets with 754 patients vs. 775 HC; BD: 23 datasets with 705 patients vs. 679 HC). Voxel-wise meta-analyses were conducted and restricted to unified template using seed-based d-Mapping. Abnormal white matter integrity was calculated within each condition and a direct comparison of effect size was performed of alterations between two conditions. Two regions with significant reductions of fractional anisotropy (FA) characterized abnormal water diffusion in both disorders: the genu of the corpus callosum (CC) and posterior cingulum fibers. There was no significant difference found between the two disorders. Our results highlighted shared impairments of FA at genu of the CC and left posterior cingulum fibers, which suggests that, phenotypic overlap between schizophrenia and BD could be related to common brain circuit dysfunction.

Microstructural abnormalities in white and gray matter in obese adolescents with and without type 2 diabetes.

Aims/hypothesesIn adults, type 2 diabetes and obesity have been associated with structural brain changes, even in the absence of dementia. Some evidence suggested similar changes in adolescents with type 2 diabetes but comparisons with a non-obese control group have been lacking. The aim of the current study was to examine differences in microstructure of gray and white matter between adolescents with type 2 diabetes, obese adolescents and healthy weight adolescents.MethodsMagnetic resonance imaging data were collected from 15 adolescents with type 2 diabetes, 21 obese adolescents and 22 healthy weight controls. Volumetric differences in the gray matter between the three groups were examined using voxel based morphology, while tract based spatial statistics was used to examine differences in the microstructure of the white matter.ResultsAdolescents with type 2 diabetes and obese adolescents had reduced gray matter volume in the right hippocampus, left putamen and caudate, bilateral amygdala and left thalamus compared to healthy weight controls. Type 2 diabetes was also associated with significant regional changes in fractional anisotropy within the corpus callosum, fornix, left inferior fronto-occipital fasciculus, left uncinate, left internal and external capsule. Fractional anisotropy reductions within these tracts were explained by increased radial diffusivity, which may suggest demyelination of white matter tracts. Mean diffusivity and axial diffusivity did not differ between the groups.Conclusion/interpretationOur data shows that adolescent obesity alone results in reduced gray matter volume and that adolescent type 2 diabetes is associated with both white and gray matter abnormalities.

Reduced fractional anisotropy in patients with major depressive disorder and associations with vascular stiffness.

Previous studies revealed several alterations of the cerebral white matter in patients with major depressive disorder. However, it is unknown if these alterations are associated with vascular changes in the brain and other body parts. We compared diffusion tensor imaging derived fractional anisotropy in a well characterized sample of middle-aged patients with major depressive disorder (n = 290) and never-depressed controls (n = 346) by the method of tract-based spatial statistics. Subsequently, the potential role of pulse wave velocity as a mediator of depression- and age-related changes in extracted estimates of fractional anisotropy were analyzed.The results of the tract-based analysis revealed significantly reduced fractional anisotropy in the left posterior thalamic radiation associated with depression. Analyses of extracted data indicated additional reductions of fractional anisotropy bilaterally in the posterior thalamic radiation and in the left sagittal stratum. The analyses of indirect effects did not show any significant mediation of depression-related effects on fractional anisotropy via pulse wave velocity. However, age-related effects on fractional anisotropy were partially mediated by pulse wave velocity.In conclusion, major depressive disorder is associated with detrimental effects on cerebral white matter microstructure properties which are independent of vascular changes, as measured by pulse wave velocity. However, a portion of age-related detrimental effects on white matter is explained by vascular changes. Longitudinal studies are required for investigating changes in white matter and vascular parameters over time and their association with incident depression.

Accelerated Gray and White Matter Deterioration With Age in Schizophrenia.

Although brain changes in schizophrenia have been proposed to mirror those found with advancing age, the trajectory of gray matter and white matter changes during the disease course remains unclear. The authors sought to measure whether these changes in individuals with schizophrenia remain stable, are accelerated, or are diminished with age. Gray matter volume and fractional anisotropy were mapped in 326 individuals diagnosed with schizophrenia or schizoaffective disorder and in 197 healthy comparison subjects aged 20-65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Between-group differences in gray matter volume and fractional anisotropy were regionally localized across the lifespan using permutation testing and cluster-based inference. Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35, and the rate of fractional anisotropy deterioration with age was constant and best modeled with a straight line. The slope of this line was 60% steeper in schizophrenia relative to comparison subjects, indicating a significantly faster rate of white matter deterioration with age. The rates of reduction of gray matter volume and fractional anisotropy were significantly faster in males than in females, but an interaction between sex and diagnosis was not evident. The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate.

Neonatal diffusion tensor brain imaging predicts later motor outcome in preterm neonates with white matter abnormalities.

BackgroundWhite matter (WM) abnormalities associated with prematurity are one of the most important causes of neurological disability that involves spastic motor deficits in preterm newborns. This study aimed to evaluate regional microstructural changes in diffusion tensor imaging (DTI) associated with WM abnormalities.MethodsWe prospectively studied extremely low birth weight (ELBW; <1000 g) preterm infants who were admitted to the Neonatal Intensive Care Unit of Hanyang University Hospital between February 2011 and February 2014. WM abnormalities were assessed with conventional magnetic resonance (MR) imaging and DTI near term-equivalent age before discharge. Region-of-interests (ROIs) measurements were performed to examine the regional distribution of fractional anisotropy (FA) values.ResultsThirty-two out of 72 ELBW infants underwent conventional MR imaging and DTI at term-equivalent age. Ten of these infants developed WM abnormalities associated with prematurity. Five of ten of those with WM abnormalities developed cerebral palsy (CP). DTI in the WM abnormalities with CP showed a significant reduction of mean FA in the genu of the corpus callosum (p = 0.022), the ipsilateral posterior limb of the internal capsule (p = 0.019), and the ipsilateral centrum semiovale (p = 0.012) compared to normal WM and WM abnormalities without CP. In infants having WM abnormalities with CP, early FA values in neonatal DTI revealed abnormalities of the WM regions prior to the manifestation of hemiparesis.ConclusionsDTI performed at term equivalent age shows different FA values in WM regions among infants with or without WM abnormalities associated with prematurity and/or CP. Low FA values of ROIs in DTI are related with later development of spastic CP in preterm infants with WM abnormalities.Electronic supplementary materialThe online version of this article (doi:10.1186/s13052-016-0309-9) contains supplementary material, which is available to authorized users.

The impact of CACNA1C gene, and its epistasis with ZNF804A, on white matter microstructure in health, schizophrenia and bipolar disorder1.

Genome-wide studies have identified allele A (adenine) of single nucleotide polymorphism (SNP) rs1006737 of the calcium-channel CACNA1C gene as a risk factor for both schizophrenia (SZ) and bipolar disorder (BD) as well as allele A for rs1344706 in the ZNF804A gene. These illnesses have also been associated with white matter abnormalities, reflected by reductions in fractional anisotropy (FA), measured using diffusion tensor imaging (DTI). We assessed the impact of the CACNA1C psychosis risk variant on FA in SZ, BD and health. 230 individuals (with existing ZNF804A rs1344706 genotype data) were genotyped for CACNA1C rs1006737 and underwent DTI. FA data was analysed with tract-based spatial statistics and threshold-free cluster enhancement significance correction (P < 0.05) to detect effects of CACNA1C genotype on FA, and its potential interaction with ZNF804A genotype and with diagnosis, on FA. There was no significant main effect of the CACNA1C genotype on FA, nor diagnosis by genotype(s) interactions. Nevertheless, when inspecting SZ in particular, risk allele carriers had significantly lower FA than the protective genotype individuals, in portions of the left middle occipital and parahippocampal gyri, right cerebellum, left optic radiation and left inferior and superior temporal gyri. Our data suggests a minor involvement of CACNA1C rs1006737 in psychosis via conferring susceptibility to white matter microstructural abnormalities in SZ. Put in perspective, ZNF804A rs1344706, not only had a significant main effect, but its SZ-specific effects were two orders of magnitude more widespread than that of CACNA1C rs1006737.

Using CForest to Analyze Diffusion Tensor Imaging Data: A Study of White Matter Integrity in Healthy Aging.

Healthy aging has been associated with a global reduction in white matter integrity, which is thought to reflect cognitive decline. The present study aimed to investigate this reduction over a broad range of the life span, using diffusion tensor imaging analyzed with conditional inference random forest modeling (CForest). This approach is sensitive to subtle and potentially nonlinear effects over the age continuum and was used to characterize the progression of decline in greater detail than has been possible in the past. Data were collected from 45 healthy individuals ranging in age from 19 to 67 years. Fractional anisotropy (FA) was estimated using probabilistic tractography for a number of major tracts across the brain. Age coincided with a nonlinear decrease in FA, with onset beginning at ∼30 years of age and the steepest declines occurring later in life. However, several tracts showed a transient increase before this decline. The progression of decline varied by tract, with steeper but later decline occurring in more anterior tracts. Finally, strongly right-handed individuals demonstrated relatively preserved FA until more than a decade following the onset of decline of others. These results demonstrate that using a novel, nonparametric analysis approach, previously reported reductions in FA with healthy aging were confirmed, while at the same time, new insight was provided into the onset and progression of decline, with evidence suggesting increases in integrity continuing into adulthood.

Progression of Regional Microstructural Degeneration in Parkinson's Disease: A Multicenter Diffusion Tensor Imaging Study.

This study aimed to identify the utility of diffusion tensor imaging (DTI) in measuring the regional distribution of abnormal microstructural progression in patients with Parkinson’s disease who were enrolled in the Parkinson's progression marker initiative (PPMI). One hundred and twenty two de-novo PD patients (age = 60.5±9) and 50 healthy controls (age = 60.6±11) had DTI scans at baseline and 12.6±1 months later. Automated image processing included an intra-subject registration of all time points and an inter-subjects registration to a brain atlas. Annualized rates of DTI variations including fractional anisotropy (FA), radial (rD) and axial (aD) diffusivity were estimated in a total of 118 white matter and subcortical regions of interest. A mixed effects model framework was used to determine the degree to which DTI changes differed in PD relative to changes in healthy subjects. Significant DTI changes were also tested for correlations with changes in clinical measures, dopaminergic imaging and CSF biomarkers in PD patients. Compared to normal aging, PD was associated with higher rates of FA reduction, rD and aD increases predominantly in the substantia nigra, midbrain and thalamus. The highest rates of FA reduction involved the substantia nigra (3.6±1.4%/year from baseline, whereas the highest rates of increased diffusivity involved the thalamus (rD: 8.0±2.9%/year, aD: 4.0±1.5%/year). In PD patients, high DTI changes in the substantia nigra correlated with increasing dopaminergic deficits as well as with declining α-synuclein and total tau protein concentrations in cerebrospinal fluid. Increased DTI rates in the thalamus correlated with progressive decline in global cognition in PD. The results suggest that higher rates of regional microstructural degeneration are potential markers of PD progression.

White Matter Diffusion of Major Fiber Tracts Implicated in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder found to have widespread alterations in the function and synchrony of brain regions. These differences may underlie alterations in microstructural organization, such as in white matter pathways. To investigate the diffusion of major white matter tracts, the current study examined multiple indices of white matter diffusion in 42 children and adults with ASD and 44 typically developing (TD) age- and IQ-matched peers using diffusion tensor imaging. Diffusivity measures were compared between groups for the following tracts: bilateral cingulum bundle, corpus callosum, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus. Results indicate a significant reduction in fractional anisotropy (FA) for the left superior longitudinal fasciculus (LSLF) in ASD children and adults compared with TD peers. A significant increase in radial diffusivity for ASD participants was also found in the same cluster along the LSLF. In addition, a significant positive correlation emerged for all subjects between FA for the LSLF and age, with FA increasing with age. These findings point to a significant alteration in long-distance white matter connectivity in children and adults with ASD, potentially underscoring the relationship between alterations in white matter diffusion and the ASD phenotype. These results also suggest that the white matter alterations in autism may be subtle and related to the developmental trajectory.

Neuroimaging of full term newborn´s brain with hypoxic-ischemic encephalopathy

Introduction. Hypoxic-ischemic encephalopathy (HIE) in full term newborn is the most frequent courses of neonatal mortality and development of neurology handicap. Magnetic resonance imaging (MRI) is common noninvasive method for detect of post hypoxic brain lesions in newborn. Method of research. We assessed MR-pattern of hypoxic brain injury using Philips Ingenia 1.5 Tl for examination newborn on 14-16 days after delivery. Protocol of MRI scans included axial and coronal plan T1, T2, Flair weighted imaging (WI) and diffusion tensor imaging (DTI) with program Fiber tracking and detected fractional anisotropy (FA). FA was measuring within cortico-spinal tract besides. 3D reconstruction allowed to visualized white matter along the axon direction of cortico-spinal tract. Studies. Four full term newborn (after 37 weeks gestation) have been examined and separated in two groups. First group included newborns with HIE (evidence of fetal distress, low Apgar Scores, low umbilical cord pH ˂ 7.1, necessity for resuscitation and neurological signs, second group consisted term newborn without any medical and problems of health. Results of research. We detected MR-patterns of basal ganglia and thalamus lesions in newborn with HIE (abnormal high signal intensity on T1 and Flair WI). We didn’t detect any abnormal MR scans in healthy newborns (control group). FA within cortico-spinal tracts besides (total and ROI-1) were lower in newborns with HI then in healthy ones. Conclusion. This investigation showed common MR patterns of brain lesions in full term newborns with HIE which included changes of signal intensity T1 and Flair from basal ganglia and thalamus as well as reduction of FA within cortico-spinal tract.

Corticoefferent pathways in pure lower motor neuron disease: a diffusion tensor imaging study

Criteria for assessing upper motor neuron pathology in lower motor neuron disease (LMND) still remain major issues in clinical diagnosis. This study was designed to investigate patients with the clinical diagnosis of adult pure LMND by use of whole brain based diffusion tensor imaging (DTI) to delineate alterations of corticoefferent pathways in vivo. Comparison of fractional anisotropy (FA) maps was performed by whole brain-based spatial statistics for 37 LMND patients vs. 53 matched controls to detect white matter structural alterations. LMND patients were clinically differentiated in fast and slow progressors. Furthermore, tract specific alterations were investigated by fiber tracking techniques according to the staging hypothesis for amyotrophic lateral sclerosis (ALS). The analysis of white matter structural connectivity demonstrated widespread and characteristic patterns of alterations in patients with LMND, predominantly along the corticospinal tract (CST), with multiple clusters of regional FA reductions in the motor system at p<0.05 (corrected for multiple comparisons). Fast progressing LMND showed substantial CST involvement, while slow progressors showed less CST alterations. In the tract-specific analysis according to the ALS-staging pattern as suggested by Braak, fast progressing LMND showed significant alterations of ALS-related tract systems beyond the CST compared to slow progressors and controls. In clinically pure LMND patients, the involvement of corticoefferent fibers was demonstrated, in particular along the CST, supporting the hypothesis that LMND is a phenotypical variant of ALS. This finding suggests to treat these patients like ALS, including the opportunity to participate in clinical trials.

Altered functional connectivity in the default mode network is associated with cognitive impairment and brain anatomical changes in Parkinson's disease

ObjectiveTo assess whether functional neural connectivity is disrupted between the regions of the default mode network (DMN) in Parkinson's disease (PD) and how this connectivity is related to cognition, brain gray matter structure and white matter integrity and diffusivity. MethodsThirty-seven PD patients and 16 healthy controls were evaluated, using resting-state functional magnetic resonance imaging (MRI), T1-weighted MRI, diffusion-weighted imaging and a battery of cognitive tests. Functional connectivity between the regions of the DMN, specifically in the precuneus, anterior and posterior cingulate, medial prefrontal and temporal and inferior parietal cortices was assessed with seed-to-voxel connectivity; gray matter volume and white matter values were determined using voxel-based morphometry and tract-based spatial statistics. ResultsReduced functional connectivity was observed between the posterior cingulate and medial temporal lobe in PD. Lower cognitive performance, gray matter loss in posterior, medial temporal and parietal areas, and fractional anisotropy reduction in the white matter adjacent to DMN regions were also observed in PD patients compared with healthy controls. Lower DMN functional connectivity correlated with lower verbal and visual memory and visual abilities performance in PD. In addition, lower DMN functional connectivity correlated with lower gray matter volume in the posterior cingulate and precuneus, and with lower white matter fractional anisotropy of the inferior longitudinal and posterior cingulate fasciculi in PD. ConclusionsBy combining different neuroimaging techniques and cognitive data, results showed that functional connectivity alteration between the regions of the DMN is associated with lower cognitive performance and gray and white matter abnormalities in PD.

Whole brain white matter integrity measures on patients with moderate to severe traumatic brain injury (TBI). FA and entropy analysis

Introduction Mean Fractional Anisotropy (FA) along with Longitudinal and Transverse Apparent Diffusion Coefficients (ADC) are the established measures in assessing white matter (WM) integrity in TBI patients. A question is raised whether mean FA performs better than Shannon Entropy (SE) as a measure of discrimination between controls and patients with moderate to severe TBI. Purpose To assess WM integrity in moderate to severe TBI patients utilizing the established diffusion tensor measures, and compare FA with Shannon Entropy as measures of assessment of WM integrity. Materials and methods A group of 13 patients with moderate to severe TBI, 2–8 years post-ictus, has been compared with a group of 14 matched healthy controls. Diffusion Tensor Imaging (DTI) data were obtained at 3T with a pulse sequence employing 32 diffusion-encoding gradient directions. After data preprocessing, Tract Based Spatial Statistics (FSL-FMRIB) for FA, whole-brain histogram analysis for SE and Receiver Operating Curve (ROC) analysis for both FA and SE have been performed. Results Higher axial and transverse diffusivity and lower FA have been observed in TBI patients ( p P = 0.007), Global mean FA (0.8, P = 0.0066) and SE (0.8, p = 0.008). Conclusion Axial and transverse diffusivity are increased in TBI patients compared to controls. Diffuse Axonal Injury (DAI) is evident as global reduction of FA in TBI patients, which is driven by increased transverse diffusion changes. No significant difference is observed between FA and SE in TBI patient discrimination. Disclosure The authors declare no conflicts of interest including financial, consultant, institutional, and other relationships that might lead to bias or a any other conflict of interest. This work was supported by the Cyprus Research Promotion Foundation through a grant co-funded by the Cyprus Government and the European Regional Development Fund (F.C., PI; NEW INFRASTRUCTURE/STRATEGIC/0309/37). The authors would like to thank the study volunteers who participated in the project.

Pathways Linked to Internuclear Ophthalmoplegia on Diffusion-Tensor Imaging in a Case with Midbrain Infarction

Midbrain infarction shows diverse patterns of ophthalmoplegia; however, the association of ophthalmoplegia with a precise microanatomy has not been fully studied. Here, we report a patient with characteristic ophthalmoplegia and explore the associated pathologic fiber tracts using diffusion-tensor imaging (DTI). A 21-year-old woman with an 11-year history of mixed connective tissue disease (MCTD) abruptly developed bilateral internuclear ophthalmoplegia (INO) with upward gaze and convergence palsies. Plasma levels of U1-ribonucleoprotein, double-stranded-DNA antibodies, and cerebrospinal fluid interleukin-6 were all increased. Diffusion-weighted imaging showed an acute ischemic lesion in the periaqueductal gray matter. DTI exhibited a reduction of fractional anisotropy and an increase of apparent diffusion coefficient values in the tract involving the left medial longitudinal fasciculus (MLF) in the midbrain to the posterior commissure (PC) when compared to the right-sided tract in the midbrain and to the bilateral MLF in the upper pontine levels. Antiplatelet and immunosuppressant therapies dramatically improved her symptoms. We believe this is the first case of a patient with juvenile MCTD presenting with bilateral INO with an upward gaze and convergence palsies caused by midbrain infarction associated with vasculitis. It is suggested that DTI might identify the pathologic fiber tract connecting the left MLF in the midbrain to the PC.

Diffusion Tensor MR Imaging Evaluation of Callosal Abnormalities in Schizophrenia: A Meta-Analysis.

Widespread white matter (WM) abnormalities have been found in patients with schizophrenia. Corpus callosum (CC) is the key area that connects the left and right brain hemispheres. However, the results of studies considering different subregions of the CC as regions of interest in patients with schizophrenia have been inconsistent. To obtain a more consistent evaluation of the diffusion characteristics change of the corpus callosum (CC) related to schizophrenia. A meta-analysis involving fractional anisotropy (FA) values in the CC of 729 schizophrenic subjects and 682 healthy controls from 22 studies was conducted. Overall FA values in the CC of the schizophrenic group were less than that of the healthy control group [weighted mean difference (WMD) = -0.021,P< 0.001]. So were the FA values in the genus region (WMD = -0.019, P< 0.001) and the splenium region (WMD = -0.020, P< 0.001) of the CC respectively. The FA reduction was also significant in subjects with chronic schizophrenia (WMD = -0.032, P< 0.001) and first-episode schizophrenia (WMD = -0.014, P = 0.001). In present study, we demonstrated an overall FA decrease in the CC of schizophrenic patients. In the two subgroup analyses of the genu vs splenium region and chronic vs first-episode schizophrenia, the decrease of all groups was significant. Further studies with more homogenous populations and standardized DTI protocols are needed to confirm and extend these findings.

White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs

White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain's fiber bundles.

Concurrent decrease of brain white matter tracts' thicknesses and fractional anisotropy after antenatal hypoxia‐ischemia detected with tract‐based spatial statistics analysis

To examine the extent of gray and white matter (WM) injury following global antenatal hypoxia-ischemia (H-I) and resulting in muscle hypertonia in newborns in a rabbit cerebral palsy model. Rabbit dams (n = 15) underwent uterine ischemia procedure resulting in a global fetal H-I at embryonic day 22 (embryonic 22 days gestation). Newborn's brains underwent high resolution diffusion tensor imaging on a 14 Tesla magnet ex vivo. Fractional anisotropy (FA) in brains of hypertonic (n = 9), nonhypertonic (n = 6), and sham control (n = 5) kits were compared voxel-wise using Tract-Based Spatial Statistics (TBSS) approach. Herein, we used a novel method to assess local WM tracts' thicknesses in TBSS analysis and compare between the groups. Significant (corrected P < 0.05) reduction of WM FA was found in corpus callosum splenium (91.2%), periventricular WM (83.5%), fimbria hippocampi (78.8%), cingulum (81.4%), anterior commissure (95%), internal capsule (83.2%), and optic tract (82.9%) in the hypertonic group. Significant (corrected P < 0.05) reduction in WM tracts' thicknesses was found in corpus callosum (73.3%), periventricular WM (82.5%), cingulum (73.4%), bilaterally in the hypertonic group. WM injury in newborn hypertonic kits 10 days after global fetal H-I is widespread and involves not only motor but also limbic and commissural fibers in multiple regions. WM injury in newborn hypertonic kits is manifested by changes in microstructural properties and decreased FA, as well as reduction of WM volumes, relative to nonhypertonic kits. J. Magn. Reson. Imaging 2017;45:700-709. 1 J. Magn. Reson. Imaging 2017;45:829-838.

Children with Poor Reading Skills at the Word Level Show Reduced Fractional Anisotropy in White Matter Tracts of Both Hemispheres.

Diffusion tensor imaging (DTI) studies showed that microstructural alterations are correlated to reading skills. In this study, we aim to investigate white matter microstructure of a group of Portuguese speakers with poor reading level, using different parameters of DTI. To perform this analysis, we selected children ranging from 8 to 12 years of age, poor readers (n = 17) and good readers (n = 23), evaluated in the word-level ability based on a Latent Class Analysis (LCA) of Academic Performance Test (TDE). Poor readers exhibited significant fractional anisotropy (FA) reductions in many tracts of both hemispheres, but small and restricted clusters of increased radial diffusivity (RD) in the left hemisphere. Spatial coherence of fibers might be the main source of differences, as changes in FA were not similarly accompanied in terms of extension by changes in RD. Widespread structural alterations in the white matter could prevent good reading ability at word level, which is consistent with recent studies demonstrating the involvement of multiple cortical regions and white matter tracts in reading disabilities.

Assessment of cochlear nerve deficiency and its effect on normal maturation of auditory tract by diffusion kurtosis imaging and diffusion tensor imaging: A correlational approach

ObjectiveThe use of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) was evaluated in assessing cochlear nerve deficiency (CND) and its effect on normal maturation of auditory tract. Methods25 CND patients and 25 controls (age matched: 2months to 17years, gender matched) were evaluated by mean kurtosis (MK), axial kurtosis, and radial kurtosis and compared against fractional anisotropy (FA), axial and radial diffusivities in internal auditory canal (IAC), lateral lemniscus (LL) and inferior colliculus (IC). The age related changes of auditory tract were studied through Pearson correlation between estimated indices and age of both CND and control populations. ResultsSignificant loss of MK (IAC: 10.71%, IC: 10.87%, LL: 15.63%) was observed in CND cases as against moderate reduction in FA (IAC: 8.57%, IC: 10%, LL: 7.69%) in all three anatomical locations. Similarly, substantial decline is observed in radial kurtosis (IAC: 27.03%, IC: 33.33%, LL: 31.43%) in comparison to moderate increase in radial diffusivity (IAC: 13.46%, IC: 24.39%, LL: 24%) in CND cases. No statistically significant change was seen in both axial kurtosis and diffusivities. In control populations, MK (r=0.473, p=0.011) and radial kurtosis (r=0.418, p=0.016) correlate positively with age and had no correlation in case of CND cases. FA (r=0.356, p=0.019) minimally correlated with age in control population but showed no statistically significant correlation in CND cases (r=0.198, p=0.036). ConclusionDKI metrics performed better than DTI in assessing microstructural changes of CND. In particular, MK and radial kurtosis are found to be more sensitive enough to differentiate the normal maturation of cochlear nerve from CND cases.