Decrease In Fractional Anisotropy Research Articles

Normal-Appearing White Matter Deteriorates over the Year After an Ischemic Stroke and Is Associated with Global Cognition.

Normal-appearing white matter (NAWM) is a hub of plasticity, but data relating to its influence on post-ischemic stroke (IS) outcome remain scarce. The aim of this study was to evaluate the relationship between NAWM integrity and cognitive outcome after an IS. A longitudinal study was conducted including supra-tentorial IS patients. A 3-Tesla brain MRI was performed at baseline and 1year, allowing the analyses of mean fractional anisotropy (FA) and mean diffusivity (MD) in NAWM masks, along with the volume of white matter hyperintensities (WMH) and IS. A Montreal Cognitive Assessment (MoCA), an Isaacs set test, and a Zazzo's cancellation task were performed at baseline, 3months and 1year. Mixed models were built, followed by Tract-based Spatial Statistics (TBSS) analyses. Ninety-five patients were included in the analyses (38% women, median age 69 ± 20). FA significantly decreased, and MD significantly increased between baseline and 1year, while cognitive scores improved. Patients who decreased their NAWM FA more over the year had a slower cognitive improvement on MoCA (β = - 0.11, p = 0.05). The TBSS analyses showed that patients who presented the highest decrease of FA in various tracts of white matter less improved their MoCA performances, regardless of WMH and IS volumes, demographic confounders, and clinical severity. NAWM integrity deteriorates over the year after an IS, and is associated with a cognitive recovery slowdown. The diffusion changes recorded here in patients starting with an early preserved white matter structure could have long term impact on cognition.

Cerebral perfusion and tractography in obese children

To study the relationship of the structure of the white matter of the brain, neurovascularization and cognitive functions in obese children and adolescents. The study included 64 obese patients, aged 12-17 years, and 54 children without excess body weight. A general clinical examination, neuropsychological testing (the Raven's test with the calculation of IQ, MoCA, the Rey 15-Item Memory Test (RMT), 1 and 2), magnetic resonance imaging (MR) tractography and contrast-free perfusion of the brain were conducted. Obese children and adolescents had both a decrease in scores on MoCA and the Raven's test, and in terms of IQ, while according to RMT-1, there were significant differences in the two groups, and in RMT-2 the results were comparable. Perfusion analysis showed a decrease in vascularization in the white matter area of the occipital lobe on the left and its increase in the temporal lobe area also on the left. When assessing the white matter according to MR tractography, a decrease in fractional anisotropy was noted in the area of the hook-shaped beam on the right and left, anterior and posterior commissural tracts. These changes were correlated with neuropsychological results. In obese children and adolescents, there was a destruction of the integrity of the white matter and neurovascularization of the brain associated with a deficit of cognitive functions.

Age, Sex, and Cerebral Microbleeds Affect White Matter Integrity Across Adulthood After Mild Traumatic Brain Injury

The contributions of age, sex, and cerebral microbleeds (CMBs) to WM changes after mild traumatic brain injury (mTBI) have not been studied. We used diffusion tensor imaging (DTI) to map WM fractional anisotropy (FA) changes across the first ~6 months post-mTBI in 109 subjects aged 18-77 (46 females; age µ: 40 y, σ: 17 y) imaged within ~1 week post-injury and ~6 months later. After partialing out age, sex, and CMB counts, significant mean FA decreases were found in the anterior body, posterior body, and splenium of the corpus callosum (CC; p = 0.003, 0.009 and 0.015, respectively), left superficial frontal fasciculus (p = 0.008), and left branch of the corticospinal tract (CST; p = 0.007). Age contributed to mean FAs measured acutely in the CC body (p = 0.04), and chronically in the CC genu (p < 0.001), CC body (p = 0.01), and middle longitudinal fasciculi (p = 0.04), older adults exhibiting larger decreases. CMB counts were positively associated with mean FA decreases in the CC body (p = 0.04) and middle longitudinal fasciculi (p = 0.04). Significant age-by-sex and CMB count-by-age interactions mediated FA decreases in the CC genu (p = 0.02 and p = 0.03, respectively), older males exhibiting larger decreases. Thus, the CC, longitudinal fasciculi, superficial frontal WM and CST are particularly vulnerable to post-traumatic neurodegeneration moderated by age, sex and CMB count, men and older adults being at highest risk for adverse effects. Future research should investigate our findings relative to cognitive function.

Effects of diet and social status on white matter integrity in female cynomolgus monkeys

AbstractBackgroundMounting evidence suggests that diet may influence risk for cognitive impairment and neurodegenerative disease, including Alzheimer’s disease. Nonhuman primates are important models of cognitive aging and Alzheimer’s disease‐like neuropathology given their complex central nervous systems and susceptibility to diet‐induced diseases. Diffusion magnetic resonance imaging (MRI) studies in humans report age‐related increases in mean diffusivity (MD) and decreases in fractional anisotropy (FA). Whether nonhuman primate models of Alzheimer’s disease‐like neuropathology show similar changes in diffusivity, and whether diet affects these changers is unknown. As such, the purpose of this study was to determine the longitudinal effects of diet (Mediterranean vs Western) and social subordination stress on diffusion MRI measures of white matter structural integrity in a nonhuman primate model of aging.MethodIn this IACUC approved study, thirty‐seven middle‐aged cynomolgus monkeys (Macaca fascicularis) were evaluated longitudinally with diffusion MRI measures (FA, MD, axial diffusivity [AxD], and radial diffusivity [RD]). Monkeys were scanned at baseline and after 31 months of diet consumption (∼ equivalent to a 9‐year follow up in humans). Diffusion MRIs were preprocessed (corrected for eddy current and geometric distortion) and co‐registered to high resolution T1w MRI to derive diffusion measures. For statistical analyses, cerebral white matter and 9 bilateral regions of interest (ROIs) were selected from NeuroMaps nonhuman primate atlas. Statistical analyses were performed with repeated measures analysis of variance.ResultWe observed social status differences in frontal (p=0.021) and occipital (p=0.029) white mater ROIs, with greater longitudinal increase or smaller longitudinal decrease in FA among subordinates compared to dominants. Diet and social status interacted to impact AxD in the genu of the corpus callosum (p=0.028). Finally, subordinates in the Mediterranean group demonstrated greater longitudinal diffusivity increases compared to 1) dominants in the Mediterranean group, 2) dominants in the Western group, and 3) subordinates in the Western group (Figure below).ConclusionWhile the biological mechanisms underlying these findings require future investigation, our observations suggest that diet and social subordination stress illicit changes in structural white matter integrity that could modify vulnerability to Alzheimer’s disease‐like neuropathology in middle‐aged nonhuman primates.

Optimal indicator for histogram analysis of fractional anisotropy for normal-appearing white matter in multiple sclerosis

Background: Normal-appearing white matter (NAWM) lesions are known to be present in multiple sclerosis (MS); however, it is not easy to distinguish these lesions from others in MRI. This study aimed to investigate the most useful value for estimating NAWM damage using fractional anisotropy (FA) histograms analysis. Methods: Data from patients with relapsing-remitting MS and healthy controls were analyzed using a 1.5T MRI system with SENSE-Head-8 coil. FA maps with diffusion- weighted images were acquired using a single-shot echo-planar imaging sequence. The median, standard deviation (SD), kurtosis, and skewness of white matter (WM) of each subject were compared between MS and healthy controls using an in-house application. Results: FA decrease in 8 patients with MS was observed upon comparison with 12 controls and leaned toward the left side. While the SDs of the healthy controls were not significantly different from those of patients with MS, patients with MS expressed significantly lower median values, and higher kurtosis and skewness compared to healthy controls. A trend for inverse associations existed between median and expanded disability status scale scores. Conclusion: Our data suggests that median FA values can allow for distinguishing between patients with MS and healthy controls with high accuracy.

Spermidine supplementation and diffusion weighted imaging in subjective cognitive decline

AbstractBackgroundSubjective Cognitive Decline (SCD) may represent an early, pre‐clinical manifestation of Alzheimer’s disease (Jessen et al., 2014), possibly accompanied by detrimental changes in white matter (WM) microstructure (Brueggen et al., 2019). Neuroprotective effects of increased external supply of spermidine were demonstrated in aged animal models (Madeo et al., 2018). This study investigated the effects of a 12‐month spermidine‐rich dietary supplementation on diffusion weighted imaging (DWI) parameters of central WM tracts in older persons with SCD.MethodThe monocentre, randomised, double‐blind, placebo‐controlled phase IIb SmartAge trial (clinicaltrial.gov: NCT03094546, Wirth et al., 2019) investigates the effects of a 12‐month dietary spermidine supplementation in SCD. Baseline and follow‐up DWI data were available for 72 SCDs (mean age 69±5 years; 38 placebo, 34 spermidine). Fractional anisotropy (FA) and mean diffusivity (MD) of central WM tracts were obtained through Tract Based Spatial Statistics. The interaction effect of intervention group and time was examined through analysis of variance. Exploratory analyses of within‐group changes from baseline to follow‐up were conducted using paired t‐tests. Correction for voxelwise multiple testing was applied.ResultNo statistically significant interaction effect of time and intervention group (spermidine vs. placebo) was present for FA and MD in central WM tracts. Exploratory within‐group analyses in the placebo group revealed a decrease of FA in areas comprising tracts within the limbic system and the MTL (right more than left), and an increase of FA in a small region of the right occipital lobe. Widespread increases of MD in the placebo group were observed in the right hemisphere and to a lesser extent in central regions of the left hemisphere. Within the spermidine group, no significant changes in FA or MD were present.ConclusionWhile our analyses did not show an interaction effect, we found detrimental within‐group changes in FA and MD from baseline to follow‐up in the placebo group but not in the spermidine group. Our findings thus suggest a potential beneficial influence of dietary spermidine supplementation on WM microstructure in SCD, to be followed up in future larger and longer‐lasting intervention studies.

Grey and white matter correlates of behavioural disinhibition assessed under semi-ecological conditions in behavioural variant frontotemporal dementia.

Behavioural variant frontotemporal dementia (bvFTD) is partly characterised by inhibition disorders. Neural correlates of disinhibition being poorly known, we aim to identify grey and white matter impairments associated to behavioural disinhibition. We assess behavioural disinhibition in a semi-ecological setting, noting occurrences of 16 behaviours - derived from clinical criteria of bvFTD - related to compulsivity, impulsivity or social disinhibition, in a population of 20 bvFTD and 20 healthy controls (HC). Subjects also undergo an MRI. In this study, voxel-based morphometry and diffusion tensor tractography (DTI) are used to investigate grey and white matter changes in bvFTD patients compared to HC. Grey matter atrophy and DTI metrics - fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) - are then correlated to behavioural disinhibition scores. Grey matter analysis was conducted on 15 bvFTD and 18 HC. Results mainly show an alteration of frontal and anterior temporal regions as well as subcortical regions (e.g., thalamus) in bvFTD patients compared to HC. Social disinhibition is correlated with a huge atrophy of the frontotemporal regions and of the cingulate cortex, while compulsivity and impulsivity are associated to smaller areas of the orbitofrontal and temporal regions. Based on these results, white matter analysis was conducted on 10 bvFTD patients and 11 HC. Results show a significant decrease of FA and increase of RD in the cingulum, the forceps minor (FM) and the uncinate fasciculus (UF) in bvFTD patients. In addition, patients show a significant increase of MD in the FM and the UF, as well as a significant increase of AD in the FM and right UF. Among bvFTD patients, compulsivity is associated to a weaker integrity of the cingulum while social disinhibition is correlated to alterations of the left UF. On the contrary, impulsivity is correlated with greater integrity of the bilateral uncinate. The cingulum is already known to be impaired in obsessive-compulsive disorder and UF impairments are related to behavioural and social disinhibition. Furthermore, positive correlation between impulsive behaviours and UF integrity are already reported, which is consistent with our findings based on a semi-ecological assessment of behavioural disinhibition.

T1/T2 ratio: A quantitative sensitive marker of brain tissue integrity in multiple sclerosis.

The aim of this study is to determine whether cerebral white matter (WM) microstructural damage, defined by decreased fractional anisotropy (FA) and increased axial (AD) and radial (RD) diffusivities, could be detected as accurately by measuring the T1/T2 ratio, in relapsing-remitting multiple sclerosis (RRMS) patients compared to healthy control (HC) subjects. Twenty-eight RRMS patients and 24 HC subjects were included in this study. Region-based analysis based on the ICBM-81 diffusion tensor imaging (DTI) atlas WM labels was performed to compare T1/T2 ratio to DTI values in normal-appearing WM (NAWM) regions of interest. Lesions segmentation was also performed and compared to the HC global WM. A significant 19.65% decrease of T1/T2 ratio values was observed in NAWM regions of RRMS patients compared to HC. A significant 6.30% decrease of FA, as well as significant 4.76% and 10.27% increases of AD and RD, respectively, were observed in RRMS compared to the HC group in various NAWM regions. Compared to the global WM HC mask, lesions have significantly decreased T1/T2 ratio and FA and increased AD and RD (p < . 001). Results showed significant differences between RRMS and HC in both DTI and T1/T2 ratio measurements. T1/T2 ratio even demonstrated extensive WM abnormalities when compared to DTI, thereby highlighting the ratio's sensitivity to subtle differences in cerebral WM structural integrity using only conventional MRI sequences.

Neurovisualization features of brain anatomy in children with spastic cerebral palsy revealed by magnetic resonance tractography

Aim. To perform quantitative evaluation of the degree of white matter tract abnormalities in children with spastic cerebral palsy by magnetic resonance tractography to determine severity of the disease, as well as to carry out a dynamic assessment of treatment effectiveness.Materials and methods. The study included 46 children (32 males, 14 females; average age 5.4 ± 1.1 years). The participants were divided into two groups. The experimental group consisted of 23 children with spastic cerebral palsy. The control group included 23 children without any neurological disorder. Examination of the brain was performed on the Siemens Essenza 1,5 Т system (Siemens, Germany) and included magnetic resonance tractography to reconstruct the major white matter tracts. The number of fibers, average fractional anisotropy value, apparent diffusion coefficient, and coefficient of myelination of major white matter tracts in the brain were calculated and analyzed.Results. We found a significant difference in the above-stated parameters between the groups. The experimental group showed a decrease in the absolute number of fibers at the central and posterior segments of the corpus callosum, corticospinal tracts, and left inferior longitudinal fasciculus. Besides, we detected a decrease in fractional anisotropy at 2–5 segments of the corpus callosum and right lateral corticospinal tract, an increase in the apparent diffusion coefficient at 2, 4, and 5 segments of the corpus callosum and left lateral corticospinal tract, and a decrease in the myelination coefficient in all the examined tracts, except for superior longitudinal fasciculus. We revealed a positive correlation between the intensity of the motor disturbance and the coefficient of myelination at the anterior corpus callosum and inferior longitudinal fasciculus.Conclusion. Magnetic resonance tractography is an informative technique for unbiased evaluation of white matter tract anatomy, as well the level and degree of motor tract damage. The most useful characteristics of white matter tract anatomy are the absolute number of fibers in the tract, fractional anisotropy, and coefficient of myelination. Some of them correlated with the intensity of motor disturbance, so they can be regarded as potential predictors of rehabilitation potential.

Magnetic resonance imaging investigations reveal that PM2.5 exposure triggers visual dysfunction in mice

ObjectivesTo investigate how PM2.5 exposure affects the microstructure, metabolites or functions of the visual system. MethodsC57BL/6J mice were randomly assigned to groups exposed to the filtered air (the control group) or the concentrated ambient PM2.5 (the PM2.5 group). Visual evoked potentials (VEP), electroretinograms (ERG), diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS) and resting-state functional MRI (rsfMRI) were performed. Parameters were obtained and compared between the two groups, including latencies and amplitudes of the P1 wave, N1 wave and P2 wave from VEP, latencies and amplitudes of the a wave and b wave from ERG, fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (AD) and radial diffusivity (RD) from DTI, visual cortex (VC) metabolites from 1H-MRS, and regional homogeneity (ReHo) from rsfMRI. ResultsCompared with the values of the control group, the PM2.5 group showed a prolonged N1 latency (43.11 ± 7.94 ms vs. 38.75 ± 4.60 ms) and lowered P1 amplitude (5.62 ± 4.38 μV vs. 8.56 ± 5.92 μV) on VEP (all p < 0.05). On ERG, the amplitude of the a wave was lowered (− 91.39 ± 56.29 μV vs. − 138.68 ± 89.05 μV), the amplitude of the b wave was lowered (194.38 ± 126.27 μV vs. 284.72 ± 170.99 μV), and the latency of the b wave was prolonged (37.78 ± 10.72 ms vs. 33.01 ± 4.34 ms) than the values of the control group (all p < 0.05). DTI indicated FA increase in the bilateral piriform cortex (Pir), FA decrease in the bilateral somatosensory cortex (S) and the bilateral striatum (Stri), AD decrease in the bilateral VC, the right S and the bilateral Pir, MD decrease in the bilateral Pir, and RD decrease in the bilateral Pir in the PM2.5 mice (all p < 0.05, Alphasim corrected). 1H-MRS showed Glutamate (Glu) increase and Phosphocholine (PCh) increase in the VC of the PM2.5 group than those of the control group (PCh 1.63 ± 0.25 vs. 1.50 ± 0.25; PCh/total creatine(tCr) 0.19 ± 0.03 vs. 0.18 ± 0.03; Glu 10.46 ± 1.50 vs. 9.60 ± 1.19; Glu/tcr 1.23 ± 0.11 vs. 1.12 ± 0.11) (all p < 0.05). rsfMRI showed higher ReHo in the PM2.5 mice in the left superior colliculus, the left motor cortex, the hippocampus, the periaqueductal gray and the right mesencephalic reticular formation (all p < 0.01, AlphaSim corrected). ConclusionsThis study revealed that PM2.5 exposure triggered visual dysfunction, and altered microstructure, metabolite and function in the retina and visual brain areas along the visual system.

Evaluation of Radiographic Contrast-Induced Nephropathy by Functional Diffusion Weighted Imaging.

Contrast-induced nephropathy (CIN) resembles an important complication of radiographic contrast medium (XCM) displayed by a rise in creatinine levels 48–72 h after XCM administration. The purpose of the current study was to evaluate microstructural renal changes due to CIN in high-risk patients by diffusion weighted (DWI) and diffusion tensor imaging (DTI). Fifteen patients (five CIN and ten non-CIN) scheduled for cardiological intervention were included in the study. All patients were investigated pre- and post-intervention on a clinical 3T scanner. After anatomical imaging, renal DWI was performed by a paracoronal echo-planar-imaging sequence. Renal clinical routine serum parameters and advanced urinary injury markers were determined to monitor renal function. We observed a drop in cortical and medullar apparent diffusion coefficient (ADC) and fractional anisotropy (FA) before and after XCM administration in the CIN group. In contrast, the non-CIN group differed only in medullary ADC. The decrease of ADC and FA was apparent even before serum parameters of the kidney changed. In conclusion, DWI/DTI may be a useful tool for monitoring high-risk CIN patients as part of multi-modality based clinical protocol. Further studies, including advanced analysis of the diffusion signal, may improve the identification of patients at risk for CIN.

Dissociation of structural and functional connectomic coherence in glioma patients

With diffuse infiltrative glioma being increasingly recognized as a systemic brain disorder, the macroscopically apparent tumor lesion is suggested to impact on cerebral functional and structural integrity beyond the apparent lesion site. We investigated resting-state functional connectivity (FC) and diffusion-MRI-based structural connectivity (SC) (comprising edge-weight (EW) and fractional anisotropy (FA)) in isodehydrogenase mutated (IDHmut) and wildtype (IDHwt) patients and healthy controls. SC and FC were determined for whole-brain and the Default-Mode Network (DMN), mean intra- and interhemispheric SC and FC were compared across groups, and partial correlations were analyzed intra- and intermodally. With interhemispheric EW being reduced in both patient groups, IDHwt patients showed FA decreases in the ipsi- and contralesional hemisphere, whereas IDHmut patients revealed FA increases in the contralesional hemisphere. Healthy controls showed strong intramodal connectivity, each within the structural and functional connectome. Patients however showed a loss in structural and reductions in functional connectomic coherence, which appeared to be more pronounced in IDHwt glioma patients. Findings suggest a relative dissociation of structural and functional connectomic coherence in glioma patients at the time of diagnosis, with more structural connectomic aberrations being encountered in IDHwt glioma patients. Connectomic profiling may aid in phenotyping and monitoring prognostically differing tumor types.

Constrained-Spherical Deconvolution Tractography in the Evaluation of the Corticospinal Tract in Glioma Surgery.

Introduction: Tractography has demonstrated utility for surgical resection in the setting of primary brain tumors involving eloquent white matter (WM) pathways.Methods: Twelve patients with glioma in or near eloquent motor areas were analyzed. The motor status was recorded before and after surgery. Two different tractography approaches were used to generate the motor corticospinal tract (CST): Constrained spherical deconvolution probabilistic tractography (CSD-Prob) and single tensor deterministic tractography (Tens-DET). To define the degree of disruption of the CST after surgical resection of the tumor, we calculated the percentage of the CST affected by surgical resection, which was then correlated with the postoperative motor status. Moreover, the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of the CST generated by the CSD-Prob and the Tens-DET was measured and compared between the ipsilesional and contralesional side.Results: The CST was identified in all patients and its trajectory was displaced by the tumor. Only the CSD-Prob approach showed the CST with the characteristic fan-like projections from the precentral gyrus to the brainstem. Disruption of the CST was identified in 6/6 with postoperative motor deficit by CSD-Prob approach and in 5/6 in the Tens-DET. The degree of disruption was significantly associated with the motor deficit with the CSD-Prob approach (rho = −0.88, p = 0.021). However, with the Tens-DET approach the CST disruption did not show significant association with the motor function (rho = −0.27, p = 0.6). There was a significant decrease in FA (p = 0.006) and a significant increase in MD (p = 0.0004) and RD (p = 0.005) on the ipsilesional CST compared with the contralesional CST only with the CSD-Prob approach.Conclusion: CSD-Prob accurately represented the known anatomy of the CST and provided a meaningful estimate of microstructural changes of the CST affected by the tumor and its macrostructural damage after surgery. Newer surgical planning stations should include advanced models and algorithms of tractography in order to obtain more meaningful reconstructions of the WM pathways during glioma surgery.

White matter integrity of watershed areas is potentially influenced by hypoperfusion in the presence permanent atrial fibrillation

Aim. To test a hypothesis of hypoperfusion-induced white matter changes in patients with atrial fibrillation (AFib) and to present statistics to compute sample size for the upcoming studies.Material and methods. We included 30 inpatients with AFib and investigated them with magnetic resonance imaging (MRI) with standard sequencies and diffusion tensor imaging (DTI). DTI data were analyzed with conventional ROI analysis in the Olea Sphere software and with watershed areas (WSA) mask in the FSL toolbox after nonlinear transformation of images to the Montreal Neurological Institute (MNI) space. Wilcoxon test was used to compare diffusion characteristics across subgroups.Results. Median age of participants was 73 years (69-78), 18 (60%) patients had moderate signs of small vessel disease with Fazekas score of one. Twenty-one patients had paroxysmal AFib. Analysis of WSA revealed decreased white matter integrity in the parieto-occipital cortical WSA with a pattern of significantly increased mean diffusivity (p=0,039), and marginally significant decrease in fractional anisotropy (p=0,056). Rank-based effect size across areas under comparison was either small (0,2) or negligible, and with statistical power in the range of 0,05-1.Conclusion. Atrial fibrillation could have pathophysiologically feasible mechanism to affect white matter integrity in the watershed areas.

DTI-derived parameters differ between moderate and severe traumatic brain injury and its association with psychiatric scores.

Diffusion tensor imaging (DTI) parameters in the corpus callosum have been suggested to be a biomarker for prognostic outcomes in individuals with diffuse axonal injury (DAI). However, differences between the DTI parameters on moderate and severe trauma in DAI over time are still unclear. A secondary goal was to study the association between the changes in the DTI parameters, anxiety, and depressive scores in DAI over time. Twenty subjects were recruited from a neurological outpatient clinic and evaluated at 2, 6, and 12months after the brain injury and compared to matched age and sex healthy controls regarding the DTI parameters in the corpus callosum. State-Trace Anxiety Inventory and Beck Depression Inventory were used to assess psychiatric outcomes in the TBI group over time. Differences were observed in the fractional anisotropy and mean diffusivity of the genu, body, and splenium of the corpus callosum between DAI and controls (p < 0.02). Differences in both parameters in the genu of the corpus callosum were also detected between patients with moderate and severe DAI (p < 0.05). There was an increase in the mean diffusivity values and the fractional anisotropy decrease in the DAI group over time (p < 0.02). There was no significant correlation between changes in the fractional anisotropy and mean diffusivity across the study and psychiatric outcomes in DAI. DTI parameters, specifically the mean diffusivity in the corpus callosum, may provide reliable characterization and quantification of differences determined by the brain injury severity. No correlation was observed with DAI parameters and the psychiatric outcome scores.

Diffusion MRI detects basal forebrain cholinergic abnormalities in the 3xTg-AD mouse model of Alzheimer's disease

Degeneration of the basal forebrain (BF) is detected early in the course of Alzheimer's disease (AD). Reduction in the number of BF cholinergic (ChAT) neurons associated with age-related hippocampal cholinergic neuritic dystrophy is described in the 3xTg-AD mouse model; however, no prior diffusion MRI (dMRI) study has explored the presence of BF alterations in this model. Here we investigated the ability of diffusion MRI (dMRI) to detect abnormalities in BF microstructure for the 3xTg-AD mouse model, along with related pathology in the hippocampus (HP) and white matter (WM) tracks comprising the septo-hippocampal pathway. 3xTg-AD and normal control (NC) mice were imaged in vivo using the specific dMRI technique known as diffusional kurtosis imaging (DKI) at 2, 8, and 15 months of age, and 8 dMRI parameters were measured at each time point. Our results revealed significant lower dMRI values in the BF of 2 months-old 3xTg-AD mice compared with NC mice, most likely related to the increased number of ChAT neurons seen in this AD mouse model at this age. They also showed significant age-related dMRI changes in the BF of both groups between 2 and 8 months of age, mainly a decrease in fractional anisotropy and axial diffusivity, and an increase in radial kurtosis. These dMRI changes in the BF may be reflecting the complex aging and pathological microstructural changes described in this region. Group differences and age-related changes were also observed in the HP, fimbria (Fi) and fornix (Fx). In the HP, diffusivity values were significantly higher in the 2 months-old 3xTg-AD mice, and the HP of NC mice showed a significant increase in axial kurtosis after 8 months, reflecting a normal pattern of increased fiber density complexity, which was not seen in the 3xTg-AD mice. In the Fi, mean and radial diffusivity values were significantly higher, and fractional anisotropy, radial kurtosis and kurtosis fractional anisotropy were significantly lower in the 2 months-old 3xTg-AD mice. The age trajectories for both NC and TG mice in the Fi and Fx were similar between 2 and 8 months, but after 8 months there was a significant decrease in diffusivity metrics associated with an increase in kurtosis metrics in the 3xTg-AD mice. These later HP, Fi and Fx dMRI changes probably reflect the growing number of dystrophic neurites and AD pathology progression in the HP, accompanied by WM disruption in the septo-hippocampal pathway. Our results demonstrate that dMRI can detect early cytoarchitectural abnormalities in the BF, as well as related aging and neurodegenerative changes in the HP, Fi and Fx of the 3xTg-AD mice. Since DKI is widely available on clinical scanners, these results also support the potential of the considered dMRI parameters as in vivo biomarkers for AD disease progression.

Relationship between illness duration, corpus callosum changes, and sustained attention dysfunction in major depressive disorder.

Illness duration is the main index of cumulative illness severity during depression progression. Corpus callosum (CC) damage is among the most replicated neurobiological findings in major depressive disorder (MDD). We aimed to investigate the nature and extent of the association between illness duration and CC changes. Ninety-six MDD patients and 50 controls underwent diffusion and resting-state functional magnetic resonance imaging (fMRI). White matter micro-structure and inter-hemispheric functional connectivity were quantified by fractional anisotropy (FA) and voxel-mirrored homotopic connectivity (VMHC). The CC was reconstructed by tractography and divided into five sub-regions. The associations of illness duration with FA of each CC sub-region and voxel-wise VMHC were examined using correlation analyses. Also, we investigated the potential relationship between illness duration, CC changes, and clinical variables using mediation analyses. In MDD patients, longer illness duration was selectively associated with lower FA of CC sub-regions 2 [partial correlation coefficient (pr) =-0.269, P=0.009] and 5 (pr=-0.296, P=0.004) as well as higher VMHC in the supplementary motor areas (pr=0.378, P<0.001), precuneus (pr=0.384, P<0.001), and lingual gyrus (pr=0.373, P<0.001) connected by the affected CC sub-regions. Further subgroup analyses demonstrated pronounced FA decrease and VMHC increase in patients with illness duration over 20 years relative to healthy controls (HC) and other patient subgroups with shorter illness durations. Moreover, lower FA of CC sub-regions 2 and 5 mediated the association between longer illness duration and more severe sustained attention dysfunction. These findings provide evidence for compromised structure yet compensatory function of the CC with increasing depression illness duration, which may inform effective antidepressant treatment strategies at different disease stages.

Structural impairments in hippocampal and occipitotemporal networks specifically contribute to decline in place and face category processing but not to other visual object categories in healthy aging

BackgroundFunctional neuroimaging studies have identified a set of nodes in the occipital–temporal cortex that preferentially respond to faces in comparison with other visual objects. By contrast, the processing of places seems to rely on parahippocampal cortex and structures heavily implicated in memory (e.g., the hippocampus). It has been suggested that human aging leads to decreased neural specialization of core face and place processing areas and impairments in face and place perception.MethodsUsing mediation analysis, we tested the potential contribution of micro‐ and macrostructure within the hippocampal and occipitotemporal systems to age‐associated effects in face and place category processing (as measured by 1‐back working memory tasks) in 55 healthy adults (age range 23–79 years). To test for specific contributions of the studied structures to face/place processing, we also studied a distinct tract (i.e., the anterior thalamic radiation [ATR]) and cognitive performance for other visual object categories (objects, bodies, and verbal material). Constrained spherical deconvolution‐based tractography was used to reconstruct the fornix, the inferior longitudinal fasciculus (ILF), and the ATR. Hippocampal volumetric measures were segmented from FSL‐FIRST toolbox.ResultsIt was found that age associates with (a) decreases in fractional anisotropy (FA) in the fornix, in right ILF (but not left ILF), and in the ATR (b) reduced volume in the right and left hippocampus and (c) decline in visual object category processing. Importantly, mediation analysis showed that micro‐ and macrostructural impairments in the fornix and right hippocampus, respectively, associated with age‐dependent decline in place processing. Alternatively, microstructural impairments in right hemispheric ILF associated with age‐dependent decline in face processing. There were no other mediator effects of micro‐ and macrostructural variables on age–cognition relationships.ConclusionTogether, the findings support specific contributions of the fornix and right hippocampus in visuospatial scene processing and of the long‐range right hemispheric occipitotemporal network in face category processing.

Brain network hubs and cognitive performance of survivors of childhood infratentorial tumors

BackgroundChildhood infratentorial tumor patients frequently suffer from long-term cognitive deficits. As each constituent of their treatment can lead to neurotoxicity, cascade effects can lead to profound reorganization of the underlying brain network, the so-called ‘connectome’. However, to date, few studies have assessed the relationship between brain network topology, the functional role of network hubs (i.e. highly connected regions), and neurocognitive outcomes in adult survivors of childhood infratentorial tumors. MethodsIn this cross-sectional study, childhood infratentorial tumor survivors (n = 21: pilocytic astrocytoma (n = 8), ependymoma (n = 1) and medulloblastoma (n = 12)) and healthy controls (n = 21) were recruited. Using multishell diffusion-weighted MRI, microstructural organization and topology of supratentorial white matter was investigated; using a voxel-based approach, a fixel-based analysis, and a graph theoretical approach. In addition, neurocognitive subscales of the WAIS-IV intelligence test, and their relationship with nodal strength and network efficiency metrics were assessed. ResultsSimilar to earlier studies, we observed widespread decreases in fractional anisotropy (FA) in patients compared to controls, based on voxel-based analyses. In addition, the fixel-based analyses dissociated macro- from microstructural changes, which were encountered in in infratentorial versus supratentorial brain areas, respectively. Finally, regional reorganization (i.e. differences in local efficiency) occurred mainly in hubs, which suggests a specific vulnerability of these areas. These hubs were not only mostly affected, but also most strongly correlated with the intelligence subscales. ConclusionThis study suggests that network hubs are functionally important for intellectual outcomes in infratentorial tumor survivors. Furthermore, these regions could be the primary targets of treatment toxicity. Validation of this specific hypothesis in larger samples is required.

Tacrolimus Protects against Age-Associated Microstructural Changes in the Beagle Brain.

The overexpression of calcineurin leads to astrocyte hyperactivation, neuronal death, and inflammation, which are characteristics often associated with pathologic aging and Alzheimer's disease. In this study, we tested the hypothesis that tacrolimus, a calcineurin inhibitor, prevents age-associated microstructural atrophy, which we measured using higher-order diffusion MRI, in the middle-aged beagle brain (n = 30, male and female). We find that tacrolimus reduces hippocampal (p = 0.001) and parahippocampal (p = 0.002) neurite density index, as well as protects against an age-associated increase in the parahippocampal (p = 0.007) orientation dispersion index. Tacrolimus also protects against an age-related decrease in fractional anisotropy in the prefrontal cortex (p < 0.0001). We also show that these microstructural alterations precede cognitive decline and gross atrophy. These results support the idea that calcineurin inhibitors may have the potential to prevent aging-related pathology if administered at middle age.SIGNIFICANCE STATEMENT Hyperactive calcineurin signaling causes neuroinflammation and other neurobiological changes often associated with pathologic aging and Alzheimer's disease (AD). Controlling the expression of calcineurin before gross cognitive deficits are observable might serve as a promising avenue for preventing AD pathology. In this study, we show that the administration of the calcineurin inhibitor, tacrolimus, over 1 year prevents age- and AD-associated microstructural changes in the hippocampus, parahippocampal cortex, and prefrontal cortex of the middle-aged beagle brain, with no noticeable adverse effects. Tacrolimus is already approved by the Food and Drug Administration for use in humans to prevent solid organ transplant rejection, and our results bolster the promise of this drug to prevent AD and aging-related pathology.