Brain Diffusion Tensor Imaging Research Articles

Brain diffusion tensor imaging in dogs with degenerative myelopathy.

BackgroundDegenerative myelopathy (DM) in dogs shares similarities with superoxide dismutase 1‐associated human amyotrophic lateral sclerosis (ALS). Brain microstructural lesions are quantified using diffusion tensor imaging (DTI) in ALS patients.ObjectiveCharacterize brain neurodegenerative changes in DM‐affected dogs using DTI.AnimalsSixteen DM‐affected and 8 control dogs.MethodsProspective observational study. Brain DTI was performed at baseline and every 3 months on DM‐affected dogs and compared to controls. Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated on specified regions of interest. Gait scores (0, normal to 14, tetraplegia) were assigned at each scan. Diffusion tensor imaging values in DM‐affected dogs were compared to controls, gait scores, and evaluated over time.ResultsMean age was 5.7 years (SD 3.2) in controls and 9.7 years (SD 1.4) in DM‐affected dogs. In DM‐affected dogs, mean baseline gait score was 4 (SD 1), and mean score change from baseline to last scan was 4.82 (SD 2.67). Nine dogs had ≤3 scans; 7 had >3 scans. Accounting for age, no differences in DTI indices were identified for any brain or proximal spinal cord regions between DM‐affected dogs and controls (P > .05). Diffusion tensor imaging values poorly correlated with gait scores (R 2 < .2). No significant changes were identified in diffusion indices over time (P > .05).Conclusions and Clinical ImportanceDiffusion tensor imaging indices did not differentiate DM‐affected from control dogs, detect longitudinal changes, or differentiate disease severity. Findings do not yet support brain DTI as an imaging biomarker.

Cross-sectional and longitudinal interaction effects of physical activity and APOE-ε4 on white matter integrity in older adults: The MAPT study

Physical activity (PA) has been shown to modulate the detrimental effect of carrying the apolipoprotein-E epsilon 4 (APOE-ɛ4) allele on brain structure. However, the current literature mainly provides cross-sectional data, and longitudinal studies investigating the interaction between genotype and PA on white matter (WM) integrity are lacking. We investigated both the cross-sectional and the longitudinal interactive effects of APOE-ɛ4 and PA on WM integrity in older adults. Fractional anisotropy, as well as axial, radial, and mean diffusivity, extracted from brain diffusion tensor imaging (DTI) were used to assess WM integrity in non-demented older adults. They were categorized according to their APOE-ɛ4 status (carriers vs. non-carriers), and their level of total (TPA), moderate to vigorous (MVPA) and light (LPA) PA were assessed using a questionnaire. Mixed model regressions were performed to test the interactive effects of APOE-ɛ4 status and PA on WM integrity at baseline and over a 3-year follow-up. 190 subjects with a mean age 74.5 years (SD=3.9) were examined. Despite a lack of cross-sectional associations, sensitivity analyses revealed that, in the carrier group only, higher levels of LPA, but not MVPA, were mainly associated with higher axial and mean diffusivity values over time. This study partially confirms the previously reported interactive associations between PA, APOE-ɛ4 genotype and WM integrity, supporting the hypothesis that PA may protect against fiber loss in WM tracts containing crossing fibers. Future studies assessing sedentary behaviors in addition to PA could bring relevant contributions to the field. CLINICAL TRIAL REGISTRATION NUMBER FROM CLINICALTRIALS.GOV: NCT00672685.

Localization and Identification of Brain Microstructural Abnormalities in Paediatric Concussion.

In the United States, approximately 2.53 million people sustain a concussion each year. Relative to adults, youth show greater cognitive deficits following concussion and a longer recovery. An accurate and reliable imaging method is needed to determine injury severity and symptom resolution. The primary objective of this study was to characterize concussions with diffusion tensor imaging (DTI). This was performed through a normative Z-scoring analysis of DTI metrics, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), to quantify patient-specific injuries and identify commonly damaged brain regions in paediatric concussion patients relative to healthy controls. It was hypothesized that personalizing the detection analysis through normative Z-scoring would provide an understanding of trauma-induced microstructural damage. Concussion patients were volunteers recruited from the Emergency Department of the McMaster Children’s Hospital with a recent concussion (n = 26), 9 males and 17 females, mean age 14.22 ± 2.64, while healthy paediatric brain DTI datasets (25 males and 24 females, mean age 13.52 ± 1.03) were obtained from an MRI data repository. Significant abnormalities were commonly found in the longitudinal fasciculus, fronto-occipital fasciculus, and corticospinal tract, while unique abnormalities were localized in a number of other areas reflecting the individuality of each child’s injury. Total injury burden, determined by the number of regions containing outliers per DTI metric per patient, was used as the metric to quantify the overall injury severity of each patient. The primary outcome of this analysis found that younger patients experienced a significantly greater injury burden when measured using fractional anisotropy (p < 0.001). These results show that DTI was able to detect microstructural changes caused by concussion, on a per-person basis, and has the potential to be a useful tool for improving diagnostic accuracy and prognosis of a concussion.

Combining advanced MRI and EEG techniques better explains long-term motor outcome after very preterm birth.

Preterm born children are at high risk for adverse motor neurodevelopment. The aim of this study was to establish the relationship between motor outcome and advanced magnetic resonance imaging (MRI) and electroencephalography (EEG) measures. In a prospective cohort study of 64 very preterm born children, the motor outcome was assessed at 9.83 (SD 0.70) years. Volumetric MRI, diffusion tensor imaging (DTI), and EEG were acquired at 10.85 (SD 0.49) years. We investigated associations between motor outcome and brain volumes (white matter, deep gray matter, cerebellum, and ventricles), white matter integrity (fractional anisotropy and mean, axial and radial diffusivity), and brain activity (upper alpha (A2) functional connectivity and relative A2 power). The independence of associations with motor outcome was investigated with a final model. For each technique, the measure with the strongest association was selected to avoid multicollinearity. Ventricular volume, radial diffusivity, mean diffusivity, relative A2 power, and A2 functional connectivity were significantly correlated to motor outcome. The final model showed that ventricular volume and relative A2 power were independently associated with motor outcome (B = -9.42 × 10-5, p = 0.027 and B = 28.9, p = 0.007, respectively). This study suggests that a lasting interplay exists between brain structure and function that might underlie motor outcome at school age. This is the first study that investigates the relationships between motor outcome and brain volumes, DTI, and brain function in preterm born children at school age. Ventricular volume and relative upper alpha power on EEG have an independent relation with motor outcome in preterm born children at school age. This suggests that there is a lasting interplay between structure and function that underlies adverse motor outcome.

Advanced Analysis of Diffusion Tensor Imaging Along With Machine Learning Provides New Sensitive Measures of Tissue Pathology and Intra-Lesion Activity in Multiple Sclerosis.

Tissue pathology in multiple sclerosis (MS) is highly complex, requiring multi-dimensional analysis. In this study, our goal was to test the feasibility of obtaining high angular resolution diffusion imaging (HARDI) metrics through single-shell modeling of diffusion tensor imaging (DTI) data, and investigate how advanced measures from single-shell HARDI and DTI tractography perform relative to classical DTI metrics in assessing MS pathology. We examined 52 relapsing-remitting MS patients who had 3T anatomical brain MRI and DTI. Single-shell HARDI modeling yielded 5 sub-voxel-based metrics, totalling 11 diffusion measures including 4 DTI and 2 tractography metrics. Based on machine learning of 3-dimensional regions of interest, we evaluated the importance of the measures through several tissue classification tasks. These included two within-subject comparisons: lesion versus normal appearing white matter (NAWM); and lesion core versus shell. Further, by stratifying patients as having high (above 75%ile) and low (below 25%ile) number of MS lesions, we also performed 2 classifications between subjects for lesions and NAWM respectively. Results showed that in lesion-NAWM analysis, HARDI orientation distribution function (ODF) energy, DTI fractional anisotropy (FA), and HARDI orientation dispersion index were the top three metrics, which together achieved 65.2% accuracy and 0.71 area under the receiver operating characteristic curve (AUROC). In core-shell analysis, DTI mean diffusivity (MD), radial diffusivity, and FA were the top three metrics, and MD dominated the classification, which achieved 59.3% accuracy and 0.59 AUROC alone. Between patients, FA was the leading feature in lesion comparisons, while ODF energy was the best in NAWM separation. Collectively, single-shell modeling of common diffusion data can provide robust orientation measures of lesion and NAWM pathology, and DTI metrics are most sensitive to intra-lesion abnormality. Combined analysis of both advanced and classical diffusion measures may be critical for improved understanding of MS pathology.

Cortical degeneration detected by neurite orientation dispersion and density imaging in chronic lacunar infarcts.

Although lacunar infarcts are focal lesions, they may also have more widespread effects. A reduction in cortical thickness in the remote cortex after lacunar infarcts has been detected by structural imaging; however, its underlying microstructural changes are yet to be elucidated. This study aimed to investigate the effects of lacunar infarcts on the microstructural abnormalities associated with cortical thickness reduction in the remote cortex. Thirty-seven patients with chronic lacunar infarcts were included. Brain structural magnetic resonance images (MRIs) and diffusion tensor images were acquired. We constructed the white matter tracts connecting with the lacunar infarcts and identified the connected cortical area based on a standard brain atlas warped into the subject space. Cortical thickness and microstructural neurite orientation dispersion and density imaging (NODDI) metrics of the ipsilesional and contralesional cortices were compared, and correlations between cortical thickness and NODDI metrics were also investigated. We found decreased cortical thickness and reduced neurite orientation dispersion index (ODI) in the ipsilesional cortex (2.47 vs. 2.50 mm, P=0.008; 0.451 vs. 0.456, P=0.035, respectively). In patients with precentral gyrus involvement (n=23), we found that ODI in the ipsilesional cortex was correlated with cortical thickness (r=0.437, P=0.037), and ODI in the contralesional cortex was also correlated with contralesional cortical thickness (r=0.440, P=0.036). NODDI metrics could reflect cortical microstructural changes following lacunar infarcts. The correlation between decreased ODI and reduced cortical thickness suggests that dendrites' loss might contribute to lacunar infarct-related cortical atrophy.

Abstract P64: Longitudinal Brain Structural Changes After Stroke

Background: Stroke causes focal and diffuse structural brain changes that may contribute to subsequent cognitive decline and dementia. We hypothesize that MRI structural measures can detect continued cerebral degeneration over the first year after stroke. We identify predictors for progression of brain atrophy, leukoaraiosis and diffusion tensor imaging (DTI) metrics. Methods: Patients with ischemic stroke were enrolled prospectively in an observational study that included serial brain MRI. Patients underwent MRI FLAIR and DTI at the time of acute stroke and were followed for at least 9 months with multiple MRIs between 30 days and 15 months post-stroke. We used FLAIR to measure brain atrophy as the percent brain parenchymal fraction (BPF) of the total intracranial volume (TICV) and white matter hyperintensity volume (WMHV) as a percentage of TICV. DTI was used to calculate Peak Skeletonized Mean Diffusivity (PSMD), a global measure of white matter integrity previously validated in cerebral small vessel disease. Longitudinal changes in BPF, WMHV or PSMD were measured from 30 days post-stroke onward using linear regression models that included age, stroke volume, baseline BPF and WMHV as predictors. Results: Twenty-six patients had a median of 4 follow-ups over 9-15 months. Median age was 74 years (range 51-84) and 38% were women. Mean stroke volume was 4.5cc (0 - 30cc). Mean BPF was 78% (72 - 86%) and mean baseline WMHV was 1.1% (0.1 - 3.9%). BPF was associated with age and declined by 0.7% per year (t(111) = 2.7, p = 0.007). Progression was associated with baseline BPF (t(111) = -3.4, p &lt; 0.001). WMHV in the non-stroke hemisphere was associated with age and increased by 0.10% per year (t(87) = -5.8, p &lt; 0.001). Accumulation was associated with age (t(87) = 5.8, p &lt; 0.001). PSMD was associated with baseline WMHV and had a relative increase of 1.9% per year in the non-stroke hemisphere and 4.5% in the stroke hemisphere (t(174) = -2.1, p = 0.03). Progression was associated with age (t(174) = 2.3, p = 0.03) and stroke volume (t(174) = 2.4, p = 0.02). Conclusions: During the months after ischemic stroke, BPF, WMHV and PSMD can detect persistent structural changes that may reflect later phases of stroke injury or ongoing contributions of aging, silent ischemia, or neurodegeneration.

Increased serum glial fibrillary acidic protein associates with microstructural white matter damage in multiple sclerosis: GFAP and DTI

BackgroundAstrocytes and microglial cells are now recognized as active players in contributing to the diffuse neuroaxonal damage associated with disease progression of multiple sclerosis (MS). The serum level of glial fibrillary acidic protein (GFAP), a biomarker for astrocytic activation, is increased in MS and associates with disease progression and disability. Similarly, diffusion tensor imaging (DTI) parameters for microstructural changes in brain, including demyelination and axonal loss, associate with disability. The association between brain DTI parameters and serum GFAP has not been previously explored in MS. The objective of the study was to get insights into DTI-measurable pathological correlates of elevated serum GFAP in the normal appearing white matter (NAWM) of MS. MethodsA total of 62 MS patients with median age of 49.2 years were included in the study. Study patients underwent DTI-MRI and blood sampling for GFAP determination by single molecule array (Simoa). Mean fractional anisotropy (FA) and mean (MD), axial (AD) and radial (RD) diffusivities were calculated within the entire NAWM and six segmented NAWM regions. The associations between the DTI parameters and GFAP levels were analysed using Spearman correlation analysis and multiple regression model with sex and disease modifying treatment (no, 1st line or 2nd line) as adjustments. ResultsElevated serum GFAP levels correlated significantly with decreased FA values within the entire (ρ = -0.39, p = 0.03), frontal (ρ = -0.42, p = 0.02), temporal (ρ = -0.37; p = 0.04) and cingulate (ρ = -0.38, p = 0.034) NAWM, and increased MD and RD within the frontal NAWM (ρ = 0.36, p = 0.046 for both). Similarly, higher GFAP associated with lower FA in frontal and cingulate NAWM in the multiple regression model corrected for confounding variables (standardised regression coefficient β = -0.29, p = 0.045 and β = -0.33, p = 0.025). ConclusionsOur results give evidence that increased serum GFAP levels associate with DTI-measurable micro-damage in the NAWM in MS. Our work supports the use of serum GFAP as a biomarker for MS pathology-related astrocytopathy and related diffuse white matter damage.

Sensitivity analysis of effective transverse shear viscoelastic and diffusional properties of myelinated white matter

Motivated by the need to interpret the results from a combined use of in vivo brain Magnetic Resonance Elastography (MRE) and Diffusion Tensor Imaging (DTI), we developed a computational framework to study the sensitivity of single-frequency MRE and DTI metrics to white matter microstructure and cell-level mechanical and diffusional properties. White matter was modeled as a triphasic unidirectional composite, consisting of parallel cylindrical inclusions (axons) surrounded by sheaths (myelin), and embedded in a matrix (glial cells plus extracellular matrix). Only 2D mechanics and diffusion in the transverse plane (perpendicular to the axon direction) was considered, and homogenized (effective) properties were derived for a periodic domain containing a single axon. The numerical solutions of the MRE problem were performed with ABAQUS and by employing a sophisticated boundary-conforming grid generation scheme. Based on the linear viscoelastic response to harmonic shear excitation and steady-state diffusion in the transverse plane, a systematic sensitivity analysis of MRE metrics (effective transverse shear storage and loss moduli) and DTI metric (effective radial diffusivity) was performed for a wide range of microstructural and intrinsic (phase-based) physical properties. The microstructural properties considered were fiber volume fraction, and the myelin sheath/axon diameter ratio. The MRE and DTI metrics are very sensitive to the fiber volume fraction, and the intrinsic viscoelastic moduli of the glial phase. The MRE metrics are nonlinear functions of the fiber volume fraction, but the effective diffusion coefficient varies linearly with it. Finally, the transverse metrics of both MRE and DTI are insensitive to the axon diameter in steady state. Our results are consistent with the limited anisotropic MRE and co-registered DTI measurements, mainly in the corpus callosum, available in the literature. We conclude that isotropic MRE and DTI constitutive models are good approximations for myelinated white matter in the transverse plane. The unidirectional composite model presented here is used for the first time to model harmonic shear stress under MRE-relevant frequency on the cell level. This model can be extended to 3D in order to inform the solution of the inverse problem in MRE, establish the biological basis of MRE metrics, and integrate MRE/DTI with other modalities towards increasing the specificity of neuroimaging.

Apolipoprotein ɛ4 Status and Brain Structure 12 Months after Mild Traumatic Injury: Brain Age Prediction Using Brain Morphometry and Diffusion Tensor Imaging.

Background: Apolipoprotein E (APOE) ɛ4 is associated with poor outcome following moderate to severe traumatic brain injury (TBI). There is a lack of studies investigating the influence of APOE ɛ4 on intracranial pathology following mild traumatic brain injury (MTBI). This study explores the association between APOE ɛ4 and MRI measures of brain age prediction, brain morphometry, and diffusion tensor imaging (DTI). Methods: Patients aged 16 to 65 with acute MTBI admitted to the trauma center were included. Multimodal MRI was performed 12 months after injury and associated with APOE ɛ4 status. Corrections for multiple comparisons were done using false discovery rate (FDR). Results: Of included patients, 123 patients had available APOE, volumetric, and DTI data of sufficient quality. There were no differences between APOE ɛ4 carriers (39%) and non-carriers in demographic and clinical data. Age prediction revealed high accuracy both for the DTI-based and the brain morphometry based model. Group comparisons revealed no significant differences in brain-age gap between ɛ4 carriers and non-carriers, and no significant differences in conventional measures of brain morphometry and volumes. Compared to non-carriers, APOE ɛ4 carriers showed lower fractional anisotropy (FA) in the hippocampal part of the cingulum bundle, which did not remain significant after FDR adjustment. Conclusion: APOE ɛ4 carriers might be vulnerable to reduced neuronal integrity in the cingulum. Larger cohort studies are warranted to replicate this finding.

729: Whole Brain Diffusion Tensor Imaging Analysis and Outcomes Following Pediatric Cardiac Arrest

Devine, Danielle1; Munjal, Neil2; Schmithorst, Vincent1; Ceschin, Rafael1; Meyers, Benjamin1; Clark, Robert3; Kochanek, Patrick4; Panigrahy, Ashok5; Fink, Ericka3 Author Information

Integrity of arcuate fasciculus is a good predictor of language impairment after subcortical stroke

Subcortical aphasia results from damage to subcortical regions, but the exact underlying mechanism is unclear. We investigated the influence of arcuate fasciculus (AF) damage on the severity of subcortical aphasia after stroke using brain diffusion tensor imaging (DTI). We enrolled subjects from the “Stroke Outcome Prediction (STOP)” database: 41 patients with first-ever, left hemispheric subcortical stroke (33 with hemorrhagic, eight with ischemic stroke) who underwent the Western Aphasia Battery (WAB) evaluation and DTI. We performed a correlation analysis between lesion volume (LV) and the DTI parameters of the AF, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), and AF type, and the WAB scores, and a classification and regression tree (CART) analysis to identify significant neuroimaging predictors for subcortical aphasia. FA significantly correlated with the aphasia quotient (AQ) and the naming score, and LV with the AQ and several WAB subtests (fluency, repetition, naming). At the subgroup level, FA and AF type showed significant correlations with the AQ, comprehension, and naming in the ischemic stroke group, while LV was associated with naming in the hemorrhagic stroke group. LV and FA were significant predictors of the AQ in all subjects, while FA was the only predictor of the language score in the hemorrhagic stroke group. Damage to the AF may be an important underlying mechanism of subcortical aphasia, and the FA value representing the integrity of the AF is an important predictor of the severity of subcortical aphasia.

High-Resolution 3D in vivo Brain Diffusion Tensor Imaging at Ultrahigh Fields: Following Maturation on Juvenile and Adult Mice.

Diffusion tensor imaging (DTI) is a well-established technique for mapping brain microstructure and white matter tracts in vivo. High resolution DTI, however, is usually associated with low intrinsic sensitivity and therefore long acquisition times. By increasing sensitivity, high magnetic fields can alleviate these demands, yet high fields are also typically associated with significant susceptibility-induced image distortions. This study explores the potential arising from employing new pulse sequences and emerging hardware at ultrahigh fields, to overcome these limitations. To this end, a 15.2 T MRI instrument equipped with a cryocooled surface transceiver coil was employed, and DTI experiments were compared between SPatiotemporal ENcoding (SPEN), a technique that tolerates well susceptibility-induced image distortions, and double-sampled Spin-Echo Echo-Planar Imaging (SE-EPI) methods. Following optimization, SE-EPI afforded whole brain DTI maps at 135 μm isotropic resolution that possessed higher signal-to-noise ratios (SNRs) than SPEN counterparts. SPEN, however, was a better alternative to SE-EPI when focusing on challenging regions of the mouse brain –including the olfactory bulb and the cerebellum. In these instances, the higher robustness of fully refocused SPEN acquisitions coupled to its built-in zooming abilities, provided in vivo DTI maps with 75 μm nominal isotropic spatial resolution. These DTI maps, and in particular the mean diffusion direction (MDD) details, exhibited variations that matched very well the anatomical features known from histological brain Atlases. Using these capabilities, the development of the olfactory bulb (OB) in live mice was followed from week 1 post-partum, until adulthood. The diffusivity of this organ showed a systematic decrease in its overall isotropic value and increase in its fractional anisotropy with age; this maturation was observed for all regions used in the OB's segmentation but was most evident for the lobules' centers, in particular for the granular cell layer. The complexity of the OB neuronal connections also increased during maturation, as evidenced by the growth in directionalities arising in the mean diffusivity direction maps.

White Matter Changes on Diffusion Tensor Imaging in the FINGER Randomized Controlled Trial.

Background:Early pathological changes in white matter microstructure can be studied using the diffusion tensor imaging (DTI). It is not only important to study these subtle pathological changes leading to cognitive decline, but also to ascertain how an intervention would impact the white matter microstructure and cognition in persons at-risk of dementia.Objectives:To study the impact of a multidomain lifestyle intervention on white matter and cognitive changes during the 2-year Finnish Geriatric Intervention Study to prevent Cognitive Impairment and Disability (FINGER), a randomized controlled trial in at-risk older individuals (age 60–77 years) from the general population.Methods:This exploratory study consisted of a subsample of 60 FINGER participants. Participants were randomized to either a multidomain intervention (diet, exercise, cognitive training, and vascular risk management, n = 34) or control group (general health advice, n = 26). All underwent baseline and 2-year brain DTI. Changes in fractional anisotropy (FA), diffusivity along domain (F1) and non-domain (F2) diffusion orientations, mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and their correlations with cognitive changes during the 2-year multidomain intervention were analyzed.Results:FA decreased, and cognition improved more in the intervention group compared to the control group (p < 0.05), with no significant intergroup differences for changes in F1, F2, MD, AxD, or RD. The cognitive changes were significantly positively related to FA change, and negatively related to RD change in the control group, but not in the intervention group.Conclusion:The 2-year multidomain FINGER intervention may modulate white matter microstructural alterations.

Differences in Advanced Magnetic Resonance Imaging in MOG-IgG and AQP4-IgG Seropositive Neuromyelitis Optica Spectrum Disorders: A Comparative Study.

Aims: To explore differences in advanced brain magnetic resonance imaging (MRI) characteristics between myelin oligodendrocyte (MOG) immunoglobulin (IgG) and aquaporin-4 (AQP4) IgG seropositive (+) neuromyelitis optica spectrum disorders (NMOSD).Methods: 33 AQP4-IgG and 18 MOG-IgG seropositive NMOSD patients and 61 healthy control (HC) subjects were included. All 112 participants were scanned with the same standardized MRI-protocol on a 3-Tesla MRI-scanner. Brain volume and diffusion tensor imaging (DTI) parameters were assessed.Results: MOG-IgG+ patients showed reduced parallel diffusivity within white matter tracts compared to HC whereas AQP4-IgG+ showed no significant brain parenchymal damage in DTI analysis. AQP4-IgG+ patients showed reduced whole brain volumes and reduced volumes of several deep gray matter structures compared to HC whereas MOG-IgG+ patients did not show reduced brain or deep gray matter volumes compared to HC.Conclusions: Microstructural brain parenchymal damage in MOG-IgG+ patients was more pronounced than in AQP4-IgG+ patients, compared with HC, whereas normalized brain volume reduction was more severe in AQP4-IgG+ patients. Longitudinal imaging studies are warranted to further investigate this trend in NMOSD. Our results suggest that MOG-IgG+ and AQP4-IgG+ NMOSD patients differ in cerebral MRI characteristics. Advanced MRI analysis did not help to differentiate between MOG-IgG+ and AQP4-IgG+ patients in our study.

Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus.

The central nervous system (CNS) is a likely reservoir of human immunodeficiency virus (HIV), vulnerable to viral rebound, inflammation, and clinical changes upon stopping antiretroviral therapy (ART). It is critical to evaluate the CNS safety of studies using analytic treatment interruption (ATI) to assess HIV remission. Thirty participants who started ART during acute HIV infection underwent CNS assessments across 4 ATI remission trials. ART resumption occurred with plasma viral load >1000 copies/mL. CNS measures included paired pre- vs post-ATI measures of mood, cognitive performance, and neurologic examination, with elective cerebrospinal fluid (CSF) sampling, brain diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). Median participant age was 30 years old and 29/30 were male. Participants' median time on ART before ATI was 3 years, and ATI lasted a median of 35 days. Post-ATI, there were no differences in median mood scores or neurologic findings and cognitive performance improved modestly. During ATI, a low level of CSF HIV-1 RNA was detectable in 6 of 20 participants with plasma viremia, with no group changes in CSF immune activation markers or brain DTI measures. Mild worsening was identified in post-ATI basal ganglia total choline MRS, suggesting an alteration in neuronal membranes. No adverse CNS effects were observed with brief, closely monitored ATI in participants with acutely treated HIV, except an MRS alteration in basal ganglia choline. Further studies are needed to assess CNS ATI safety in HIV remission trials, particularly for studies using higher thresholds to restart ART and longer ATI durations.

Simultaneous Diffusion and T1 Weighted Contrast Imaging for Human Brain Mapping

Introduction: Diffusion tensor imaging (DTI) is conventionally performed using echo planar imaging (EPI) for human brain mapping. However, EPI suffers from susceptibility distortion, requiring elaborate image post processing. Besides, DTI alone is limited in assessing gray and white matter boundaries of the brain, which is important for accurately imaging brain atrophy. The goal of this study was to design and evaluate simultaneous diffusion and T1 weighting high resolution imaging for human brain mapping. Materials and Methods: Three dimensional Magnetization-prepared rapid gradient-echo (3D MPRAGE) with T1 weighting, which is generally the method of choice for mapping gray and white matter structures in the brain, was extended to incorporate diffusion encoding using simulation and experiment to develop high resolution DTI and T1-weighted human brain data. Results: It is shown that the incorporation of DTI contrast (i.e. fractional anisotropy (FA) and mean diffusivity (MD)) into T1 weighted 3D MPRAGE using simulations as well as experimental results from in-vivo human brain studies at 4 Tesla magnetic field strength improves the contrast between gray and white matter sub-structural boundaries. Moreover, incorporating diffusion encoding into 3D MPRAGE avoids the inherent image distortions typically seen in EPI based DTI.Conclusion: This study suggests DTI weighted 3D MPRAGE combined with T1w is feasible for human brain imaging and expected to benefit improved assessment of gray/white matter boundaries.

Clinical and neuroimaging factors associated with aphasia severity in stroke patients: diffusion tensor imaging study

This study investigated factors associated with aphasia severity at both 2 weeks and 3 months after stroke using demographic and clinical variables, brain diffusion tensor imaging (DTI) parameters, and lesion volume measurements. Patients with left hemisphere stroke were assessed at 2 weeks (n = 68) and at 3 months (n = 20) after stroke. Demographic, clinical, and neuroimaging data were collected; language functions were assessed using the Western Aphasia Battery. For neuroimaging, DTI parameters, including the laterality index (LI) of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, mean diffusivity and fibre density (FD) of the arcuate fasciculus (AF), and lesion volume, were measured. Lesion volume, cortical involvement, and the National Institutes of Health Stroke Scale score significantly predicted aphasia severity at 2 weeks after stroke, whereas the aphasia quotient and presence of depression during the early subacute stage were significant predictors at 3 months after stroke. According to Pearson correlation, LI-AD and LI-FD were significantly correlated with the aphasia quotient 2 weeks after ischaemic stroke, and the LI-FA was significantly correlated with the aphasia quotient 2 weeks after haemorrhagic stroke, suggesting that the extent and mechanism of AF injuries differ between ischaemic and haemorrhagic strokes. These differences may contribute to aphasia severity.

Volumetric and Diffusion Abnormalities in Subcortical Nuclei of Older Adults With Cognitive Frailty.

Background: Cognitive frailty (CF) is defined as the simultaneous presence of physical frailty and cognitive impairment among older adults without dementia. Previous studies have revealed that neuropathological changes may contribute to the degeneration of subcortical nuclei in the process of cognitive impairment. However, it is unclear in CF. The aim of this study is to investigate the changes in subcortical nuclei in older adults with CF and their relationship with cognitive decline and physical frailty.Methods: A total of 26 older adults with CF and 26 matched healthy subjects were enrolled. Cognitive function and physical frailty were assessed with the Montreal Cognitive Assessment (MoCA) scale (Fuzhou version) and the Chinese version of the Edmonton Frailty Scale (EFS). Volumetric and diffusion tensor imaging (DTI) parameters of subcortical nuclei were measured with structural and DTI brain magnetic resonance imaging (MRI) and compared between groups. Partial correlation analysis was conducted between subcortical nuclei volumes, MoCA scores, and physical frailty indexes.Results: Significant volume reductions were found in five subcortical nuclei, including the bilateral thalami, left caudate, right pallidum, and accumbens area, in older adults with CF (P < 0.05), and the bilateral thalami was most obvious. Decreased fractional anisotropy and relative anisotropy values were observed only in the left thalamus in the CF group (P < 0.05). No group differences were found in apparent diffusion coefficient (ADC) values. The MoCA scores were positively correlated with the volumes of the bilateral thalami, right pallidum, and accumbens area (P < 0.05). Negative correlations were found between the physical frailty index and the volumes of the bilateral thalami, caudate, pallidum, and right accumbens area (P < 0.05).Conclusion: Microstructural changes occur in the subcortical nuclei of older adults with CF, and these changes are correlated with cognitive decline and physical frailty. Therefore, microstructural atrophy of the subcortical nuclei may be involved in the pathological progression of CF.

Disrupted white matter connectivity and organization of brain structural connectomes in tuberous sclerosis complex patients with neuropsychiatric disorders using diffusion tensor imaging.

Tuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome with variable and unpredictable neurological comorbidity that includes epilepsy, intellectual disability (ID), autism spectrum disorder, and neurobehavioral abnormalities. The degree of white matter involvement is believed to be associated with the severity of neurological impairment. The goal of the present study was to evaluate diffusion characteristics of tubers, white matter lesions, and brain structural network alterations in TSC patients using diffusion tensor imaging (DTI), graph theoretical analysis (GTA), and network-based statistical (NBS) analysis. Forty-two patients with a definitive diagnosis of TSC were recruited for this study. All patients underwent brain DTI examination using a 3T magnetic resonance imaging system. Mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) values, and fractional anisotropy (FA) mapping in 52 tubers and white matter lesions were measured and compared with those of contralateral normal regions. GTA was performed on the inter-regional connectivity matrix, and NBS analysis was used to identify the significance of any connected subnetworks evident in the set of altered connections. For neurological severity subgrouping, a neurological severity score was assigned to TSC patients including those with ID, seizure, autism, and other neuropsychiatric disorders (NPDs). Significantly higher MD, AD, and RD, and lower FA values, were found in TSC lesions compared with those measured in contralateral normal regions for tubers (P < 0.05). GTA and NBS analysis provided better local segregation but worse global integration of the structural network (regular-like network) in TSC patients with ID, seizure, and higher Neurological Severity Score. Disrupted subnetworks in TSC patients with severe status included connections from the frontal lobe to the parietal lobe, temporal lobe to the caudate, and temporal lobe to the insula. DTI has the potential to provide valuable information about cytoarchitectural changes in TSC lesions beyond morphological MRI findings alone. Using GTA and NBS, current results provide the information of disrupted white matter connectivity and organization in TSC patients with different neuropsychological impairments.