Difference In Fiber Density Research Articles

Fixel-Based Analysis Reveals Tau-Related White Matter Changes in Early Stages of Alzheimer's Disease.

Several studies have shown white matter (WM) abnormalities in Alzheimer's disease (AD) using diffusion tensor imaging (DTI). Nonetheless, robust characterization of WM changes has been challenging due to the methodological limitations of DTI. We applied fixel-based analyses (FBA) to examine microscopic differences in fiber density (FD) and macroscopic changes in fiber cross-section (FC) in early stages of AD (N = 393, 212 females). FBA was also compared with DTI, free-water corrected (FW)-DTI and diffusion kurtosis imaging (DKI). We further investigated the correlation of FBA and tensor-derived metrics with AD pathology and cognition. FBA metrics were decreased in the entire cingulum bundle, uncinate fasciculus and anterior thalamic radiations in Aβ-positive patients with mild cognitive impairment compared to control groups. Metrics derived from DKI, and FW-DTI showed similar alterations whereas WM degeneration detected by DTI was more widespread. Tau-PET uptake in medial temporal regions was only correlated with reduced FC mainly in the parahippocampal cingulum in Aβ-positive individuals. This tau-related WM alteration was also associated with impaired memory. Despite the spatially extensive between-group differences in DTI-metrics, the link between WM and tau aggregation was only revealed using FBA metrics implying high sensitivity but low specificity of DTI-based measures in identifying subtle tau-related WM degeneration. No relationship was found between amyloid load and any diffusion-MRI measures. Our results indicate that early tau-related WM alterations in AD are due to macrostructural changes specifically captured by FBA metrics. Thus, future studies assessing the effects of AD pathology in WM tracts should consider using FBA metrics.

Improvement of the thalamocortical white matter network in people with stable treated relapsing-remitting multiple sclerosis over time.

Advanced imaging techniques (tractography) enable the mapping of white matter (WM) pathways and the understanding of brain connectivity patterns. We combined tractography with a network-based approach to examine WM microstructure on a network level in people with relapsing-remitting multiple sclerosis (pw-RRMS) and healthy controls (HCs) over 2 years. Seventy-six pw-RRMS matched with 43 HCs underwent clinical assessments and 3T MRI scans at baseline (BL) and 2-year follow-up (2-YFU). Probabilistic tractography was performed, accounting for the effect of lesions, producing connectomes of 25 million streamlines. Network differences in fibre density across pw-RRMS and HCs at BL and 2-YFU were quantified using network-based statistics (NBS). Longitudinal network differences in fibre density were quantified using NBS in pw-RRMS, and were tested for correlations with disability, cognition and fatigue scores. Widespread network reductions in fibre density were found in pw-RRMS compared with HCs at BL in cortical regions, with more reductions detected at 2-YFU. Pw-RRMS had reduced fibre density at BL in the thalamocortical network compared to 2-YFU. This effect appeared after correction for age, was robust across different thresholds, and did not correlate with lesion volume or disease duration. Pw-RRMS demonstrated a robust and long-distance improvement in the thalamocortical WM network, regardless of age, disease burden, duration or therapy, suggesting a potential locus of neuroplasticity in MS. This network's role over the disease's lifespan and its potential implications in prognosis and treatment warrants further investigation.

Disconnectome associated with progressive white matter hyperintensities in aging: a virtual lesion study.

White matter hyperintensities (WMH) are commonly seen on T2-weighted magnetic resonance imaging (MRI) in older adults and are associated with an increased risk of cognitive decline and dementia. This study aims to estimate changes in the structural connectome due to age-related WMH by using a virtual lesion approach. High-quality diffusion-weighted imaging data of 30 healthy subjects were obtained from the Human Connectome Project (HCP) database. Diffusion tractography using q-space diffeomorphic reconstruction (QSDR) and whole brain fiber tracking with 107 seed points was conducted using diffusion spectrum imaging studio and the brainnetome atlas was used to parcellate a total of 246 cortical and subcortical nodes. Previously published WMH frequency maps across age ranges (50's, 60's, 70's, and 80's) were used to generate virtual lesion masks for each decade at three lesion frequency thresholds, and these virtual lesion masks were applied as regions of avoidance (ROA) in fiber tracking to estimate connectivity changes. Connections showing significant differences in fiber density with and without ROA were identified using paired tests with False Discovery Rate (FDR) correction. Disconnections appeared first from the striatum to middle frontal gyrus (MFG) in the 50's, then from the thalamus to MFG in the 60's and extending to the superior frontal gyrus in the 70's, and ultimately including much more widespread cortical and hippocampal nodes in the 80's. Changes in the structural disconnectome due to age-related WMH can be estimated using the virtual lesion approach. The observed disconnections may contribute to the cognitive and sensorimotor deficits seen in aging.

Changes in White Matter Microstructure Over 3 Years in People With and Without Stroke.

Cerebral white matter health can be estimated by MRI-derived indices of microstructure. White matter dysfunction is increasingly recognized as a contributor to neurodegenerative disorders affecting cognition and to functional outcomes after stroke. Reduced indices of white matter microstructure have been demonstrated cross-sectionally in stroke survivors compared with stroke-free participants, but longitudinal changes in the structure of white matter after stroke remain largely unexplored. We aimed to characterize white matter micro- and macrostructure over 3 years after stroke and study associations with white matter metrics and cognitive functions. Patients with first-ever or recurrent ischemic stroke of any etiology in any vascular territory were compared with stroke-free age- and sex-matched controls. Those diagnosed with hemorrhagic stroke, TIA, venous infarction, or significant medical comorbidities, psychiatric and neurodegenerative disorders, substance abuse, or history of dementia were excluded. Diffusion-weighted MRI data at 3, 12, and 36 months were analyzed using a longitudinal fixel-based analysis, sensitive to fiber tract-specific differences within a voxel. It was used to examine whole-brain white matter degeneration in stroke compared with control participants. We studied microstructural differences in fiber density and macrostructural changes in fiber-bundle cross-section, in relation to cognitive performance. Analyses were performed controlling for age, intracranial volume, and education (family-wise error-corrected p < 0.05, nonparametric testing over 5,000 permutations). We included 71 participants with stroke (age 66 ± 12 years, 22 women) and 36 controls (age 69 ± 5 years, 13 women). We observed extensive white matter structural degeneration across the whole brain, particularly affecting the thalamic, cerebellar, striatal, and superior longitudinal tracts and corpus callosum. Importantly, follow-up regression analyses in 72 predefined tracts showed that the decline in fiber density and cross-section from 3 months to 3 years was associated with worse cognitive performance at 3 years after stroke, especially affecting visuospatial processing, processing speed, language, and recognition memory. We conclude that white matter neurodegeneration in ipsi- and contralesional thalamic, striatal, and cerebellar tracts continues to be greater in stroke survivors compared with stroke-free controls. White matter degeneration persists even years after stroke and is associated with poststroke cognitive impairment. ClinicalTrails.gov NCT02205424.

White matter abnormalities characterize the acute stage of sports-related mild traumatic brain injury.

Sports-related concussion, a form of mild traumatic brain injury, is characterized by transient disturbances of brain function. There is increasing evidence that functional brain changes may be driven by subtle abnormalities in white matter microstructure, and diffusion MRI has been instrumental in demonstrating these white matter abnormalities in vivo. However, the reported location and direction of the observed white matter changes in mild traumatic brain injury are variable, likely attributable to the inherent limitations of the white matter models used. This cross-sectional study applies an advanced and robust technique known as fixel-based analysis to investigate fibre tract-specific abnormalities in professional Australian Football League players with a recent mild traumatic brain injury. We used the fixel-based analysis framework to identify common abnormalities found in specific fibre tracts in participants with an acute injury (≤12 days after injury; n = 14). We then assessed whether similar changes exist in subacute injury (>12 days and <3 months after injury; n = 15). The control group was 29 neurologically healthy control participants. We assessed microstructural differences in fibre density and fibre bundle morphology and performed whole-brain fixel-based analysis to compare groups. Subsequent tract-of-interest analyses were performed within five selected white matter tracts to investigate the relationship between the observed tract-specific abnormalities and days since injury and the relationship between these tract-specific changes with cognitive abnormalities. Our whole-brain analyses revealed significant increases in fibre density and bundle cross-section in the acute mild traumatic brain injury group when compared with controls. The acute mild traumatic brain injury group showed even more extensive differences when compared with the subacute injury group than with controls. The fibre structures affected in acute concussion included the corpus callosum, left prefrontal and left parahippocampal white matter. The fibre density and cross-sectional increases were independent of time since injury in the acute injury group, and were not associated with cognitive deficits. Overall, this study demonstrates that acute mild traumatic brain injury is characterized by specific white matter abnormalities, which are compatible with tract-specific cytotoxic oedema. These potential oedematous changes were absent in our subacute mild traumatic brain injury participants, suggesting that they may normalize within 12 days after injury, although subtle abnormalities may persist in the subacute stage. Future longitudinal studies are needed to elucidate individualized recovery after brain injury.

White matter microstructural and morphometric alterations in autism: implications for intellectual capabilities

BackgroundNeuroimage literature of autism spectrum disorder (ASD) has a moderate-to-high risk of bias, partially because those combined with intellectual impairment (II) and/or minimally verbal (MV) status are generally ignored. We aimed to provide more comprehensive insights into white matter alterations of ASD, inclusive of individuals with II (ASD-II-Only) or MV expression (ASD-MV).MethodsSixty-five participants with ASD (ASD-Whole; 16.6 ± 5.9 years; comprising 34 intellectually able youth, ASD-IA, and 31 intellectually impaired youth, ASD-II, including 24 ASD-II-Only plus 7 ASD-MV) and 38 demographic-matched typically developing controls (TDC; 17.3 ± 5.6 years) were scanned in accelerated diffusion-weighted MRI. Fixel-based analysis was undertaken to investigate the categorical differences in fiber density (FD), fiber cross section (FC), and a combined index (FDC), and brain symptom/cognition associations.ResultsASD-Whole had reduced FD in the anterior and posterior corpus callosum and left cerebellum Crus I, and smaller FDC in right cerebellum Crus II, compared to TDC. ASD-IA, relative to TDC, had no significant discrepancies, while ASD-II showed almost identical alterations to those from ASD-Whole vs. TDC. ASD-II-Only had greater FD/FDC in the isthmus splenium of callosum than ASD-MV. Autistic severity negatively correlated with FC in right Crus I. Nonverbal full-scale IQ positively correlated with FC/FDC in cerebellum VI. FD/FDC of the right dorsolateral prefrontal cortex showed a diagnosis-by-executive function interaction.LimitationsWe could not preclude the potential effects of age and sex from the ASD cohort, although statistical tests suggested that these factors were not influential. Our results could be confounded by variable psychiatric comorbidities and psychotropic medication uses in our ASD participants recruited from outpatient clinics, which is nevertheless closer to a real-world presentation of ASD. The outcomes related to ASD-MV were considered preliminaries due to the small sample size within this subgroup. Finally, our study design did not include intellectual impairment-only participants without ASD to disentangle the mixture of autistic and intellectual symptoms.ConclusionsASD-associated white matter alterations appear driven by individuals with II and potentially further by MV. Results suggest that changes in the corpus callosum and cerebellum are key for psychopathology and cognition associated with ASD. Our work highlights an essential to include understudied subpopulations on the spectrum in research.

Timing of selective basal ganglia white matter loss in premanifest Huntington’s disease

ObjectivesTo investigate the timeframe prior to symptom onset when cortico-basal ganglia white matter (white matter) loss begins in premanifest Huntington’s disease (preHD), and which striatal and thalamic sub-region white matter tracts are most vulnerable. MethodsWe performed fixel-based analysis, which allows resolution of crossing white matter fibres at the voxel level, on diffusion tractography derived white matter tracts of striatal and thalamic sub-regions in two independent cohorts; TrackON-HD, which included 72 preHD (approx. 11 years before disease onset) and 85 controls imaged at three time points over two years; and the HD young adult study (HD-YAS), which included 54 preHD (approx. 25 years before disease onset) and 53 controls, imaged at one time point. Group differences in fibre density and cross section (FDC) were investigated. ResultsWe found no significant group differences in cortico-basal ganglia sub-region FDC in preHD gene carriers 25 years before onset. In gene carriers 11 years before onset, there were reductions in striatal (limbic and caudal motor) and thalamic (premotor, motor and sensory) FDC at baseline, with no significant change over 2 years. Caudal motor-striatal, pre-motor-thalamic, and primary motor-thalamic FDC at baseline, showed significant correlations with the Unified Huntington’s disease rating scale (UHDRS) total motor score (TMS). Limbic cortico-striatal FDC and apathy were also significantly correlated. ConclusionsOur findings suggest that limbic and motor white matter tracts to the striatum and thalamus are most susceptible to early degeneration in HD but that approximately 25 years from onset, these tracts appear preserved. These findings may have importance in determining the optimum time to initiate future disease modifying therapies in HD.

Continued white matter fibre degeneration over 3 years after ischemic stroke

AbstractBackgroundWe aimed to chart white matter integrity over 3 years after stroke, to examine if post‐stroke loss of white matter continues to be accelerated compared to control participants.MethodWe applied a longitudinal “fixel”‐based analysis, sensitive to fibre tract‐specific differences within a voxel, to assess axonal loss in stroke (N=71, 22 women) compared to control participants (N=36, 13 women) across the whole brain. We studied microstructural differences in fibre density and macrostructural (morphological) changes in fibre cross‐section.ResultIn stroke participants, we observed significantly lower fibre density and cross‐section from 3 months to 3 years. The changes were widespread and affected the corpus callosum, bilateral inferior fronto‐occipital fasciculus, right superior longitudinal fasciculus.ConclusionWe conclude that ischemic stroke is associated with extensive and continued neurodegeneration that significantly affects white matter micro and macrostructure across the whole brain. These findings confirm that the deleterious effects of stroke on white matter continue several years following the event.

Ex Vivo and In Vivo Evaluation of Fibrinogen Concentrate to Mitigate Post-Surgical Bleeding in Neonates

Introduction: Bleeding is a serious complication among neonates undergoing cardiopulmonary bypass (CPB) and it is linked to significant morbidity and mortality. Current standard of care treatment for bleeding after CPB focuses on the transfusion of adult blood products, including platelets and cryoprecipitate. However, prior work by Nellenbach et al. has demonstrated structural differences between neonatal and adult clotting components. Importantly, neonatal and adult fibrin do not fully integrate during clot formation which may contribute to ineffective clot formation and/or increased thrombotic risk following transfusion of adult cryoprecipitate to neonates. There has been increased interest in using human fibrinogen concentrate (HFC) in treating bleeding in the post-CPB neonate; however, HFC has not been validated in this population through evidence-based means. This study analyzed structural and degradation properties of post-CPB clots +/- the ex vivo addition of HFC and compared structural and degradation properties of post-CPB clots after the in vivo transfusion of HFC versus cryoprecipitate.Methods: Human neonatal plasma samples were collected from patients undergoing CPB at the Children's Hospital of Atlanta. For ex vivo studies, samples were taken at baseline, post-bypass, and post-transfusion of cryoprecipitate (n = 18 patients). Clots were formed for analysis from samples alone as well as post-bypass samples with the addition of 0.5 or 0.9 mg/mL HFC (RiaSTAP, CSL Behring) and structure was examined through confocal microscopy. Clot degradation was assessed through a microfluidic fibrinolysis assay. For in vivo studies, samples were taken at baseline, post-transfusion of cryoprecipitate or HFC, upon ICU arrival, and at 24 hours post-surgery (n = 36 patients). Clots were formed from samples and structure was examined through confocal microscopy. Clot degradation was assessed through a plate-based fibrinolysis assay.Results: In ex vivo studies, clot structural analysis demonstrated no significant differences in fiber density between samples collected at different time points (baseline = 0.541 ± 0.105, post-bypass = 0.431 ± 0.111, post-transfusion = 0.594 ± 0.170). The addition of 0.5 mg/mL or 0.9 mg/mL HFC to post-bypass samples led to a significant increase in fiber density (0.5 mg/mL HFC=0.654 ± 0.158, p=0.02; 0.9 mg/mL HFC= 0.797 ± 0.193, p<0.0001). Functional microfluidic analysis of clot degradation demonstrated significantly faster degradation times among post-bypass samples when compared to baseline samples (baseline degradation rate = 11.061 ± 6.087, post-bypass degradation rate = 25.906 ± 9.990 microns/hour, p=0.04). The addition of 0.5 mg/mL HFC resulted in a slower degradation rate from the original post-CPB degradation rate, but did not reach statistical significance (0.5 mg/mL HFC=14.091 ± 2.241, p=0.14). However, the addition of 0.9 mg/mL HFC resulted in a significantly slower degradation rate (0.9 mg/mL HFC=8.594 ± 6.087, p=0.01). Studies comparing in vivo transfusion of cryoprecipitate and HFC demonstrated no significant difference between treatment groups in clot density or degradation rate for any sample time point.Conclusion: We identify patterns in structural properties of clots formed after the transfusion of HFC that are consistent with successful hemostasis. However, caution is warranted regarding potentially thrombotic risks and should be carefully analyzed in future studies.Figure: Effect of Ex Vivo HFC Addition on Clot Structure and Degradation. (A) Representative confocal imaging of clots formed from different samples and HFC dosages (scale = 50 um). (B) Effect of HFC Addition on Clot Fiber Density. Addition of both 0.5 and 0.9 mg/mL HFC dosages to post-bypass sample result in statistically significant increases in fiber density compared to post-bypass samples. (C) Effect of HFC Addition on Clot Degradation Profiles. Addition of 0.9 mg/mL HFC to post-bypass sample leads to statistically significant slower fibrinolysis. [Display omitted] DisclosuresBrown: Selsym Biotech, Inc.: Other: Co-Founder and CEO. OffLabel Disclosure:RiaSTAP (human fibrinogen concentrate) is FDA approved for the treatment of congenital hypofibrinogenemia.

White matter degeneration revealed by fiber-specific analysis relates to recovery of hand function after stroke.

Recent developments of higher‐order diffusion‐weighted imaging models have enabled the estimation of specific white matter fiber populations within a voxel, addressing limitations of traditional imaging markers of white matter integrity. We applied fixel based analysis (FBA) to investigate the evolution of fiber‐specific white matter changes in a prospective study of stroke patients and upper limb motor deficit over 1 year after stroke. We studied differences in fiber density and macrostructural changes in fiber cross‐section. Motor function was assessed by grip strength. We conducted a whole‐brain analysis of fixel metrics and predefined corticospinal tract (CST) region of interest in relation to changes in motor functions. In 30 stroke patients (mean age 62.3 years, SD ±16.9; median NIHSS 4, IQR 2–5), whole‐brain FBA revealed progressing loss of fiber density and cross‐section in the ipsilesional corticospinal tract and long‐range fiber tracts such as the superior longitudinal fascicle and trans‐callosal tracts extending towards contralesional white matter tracts. Lower FBA metrics measured at the brainstem section of the CST 1 month after stroke were significantly associated with lower grip strength 3 months (p = .009, adjusted R 2 = 0.259) and 1 year (T4: p < .001, adj. R 2 = 0.515) after stroke. Compared to FA, FBA metrics showed a comparably strong association with grip strength at later time points. Using FBA, we demonstrate progressive fiber‐specific white matter loss after stroke and association with functional motor outcome. Our results promote the application of fiber‐specific analysis to detect secondary neurodegeneration after stroke in relation to clinical recovery.

Age-Related Differences in White Matter: Understanding Tensor-Based Results Using Fixel-Based Analysis.

Aging is associated with widespread alterations in cerebral white matter (WM). Most prior studies of age differences in WM have used diffusion tensor imaging (DTI), but typical DTI metrics (e.g., fractional anisotropy; FA) can reflect multiple neurobiological features, making interpretation challenging. Here, we used fixel-based analysis (FBA) to investigate age-related WM differences observed using DTI in a sample of 45 older and 25 younger healthy adults. Age-related FA differences were widespread but were strongly associated with differences in multi-fiber complexity (CX), suggesting that they reflected differences in crossing fibers in addition to structural differences in individual fiber segments. FBA also revealed a frontolimbic locus of age-related effects and provided insights into distinct microstructural changes underlying them. Specifically, age differences in fiber density were prominent in fornix, bilateral anterior internal capsule, forceps minor, body of the corpus callosum, and corticospinal tract, while age differences in fiber cross section were largest in cingulum bundle and forceps minor. These results provide novel insights into specific structural differences underlying major WM differences associated with aging.

Longitudinal fixel-based analysis reveals restoration of white matter alterations following balance training in young brain-injured patients

Background and objectivesTraumatic brain injury (TBI) is one of the leading causes of death and disability in children and adolescents. Young TBI patients suffer from gross motor deficits, such as postural control deficits, which can severely compromise their daily life activities. However, little attention has been devoted to uncovering the underlying white matter changes in response to training in TBI. In this study, we used longitudinal fixel-based analysis (FBA), an advanced diffusion imaging analysis technique, to investigate the effect of a balance training program on white matter fibre density and morphology in a group of young TBI patients. MethodsYoung patients with moderate-to-severe TBI (N = 17, 10 females, mean age = 13 ± 3 years) and age-matched controls (N = 17) underwent a home-based balance training program. Diffusion MRI scans together with gross motor assessments, including the gross motor items of the Bruininks-Oseretsky Test of Motor Proficiency, the Activities-Specific Balance Confidence (ABC) Scale, and the Sensory Organization Test (SOT) were administered before and at completion of 8-weeks of training. We used FBA to compare microstructural differences in fibre density (FD), macrostructural (morphological) changes in fibre cross-section (FC), and the combined FD and FC (FDC) metric across the whole brain. We then performed a longitudinal analysis to test whether training restores the white matter in the regions found to be damaged before treatment. ResultsWhole-brain fixel-based analysis revealed lower FD and FC in TBI patients compared to the control group across several commissural tracts, association fibres and projection fibres, with FD reductions of up to 50%. Following training, TBI patients showed a significant interaction effect between Group and Time for the SOT test, as well as significant increases in macrostructural white matter (i.e., FC & FDC) in left sensorimotor tracts. The amount of change in FC and FDC over time was, however, not associated with behavioural changes. DiscussionOur fixel-based findings identified both microstructural and macrostructural abnormalities in young TBI patients. The longitudinal results provide a deeper understanding of the neurobiological mechanisms underlying balance training, which will allow clinicians to make more effective treatment decisions in everyday clinical practice with brain-injured patients.

Microstructure of Human Corpus Callosum across the Lifespan: Regional Variations in Axon Caliber, Density, and Myelin Content.

The myeloarchitecture of the corpus callosum (CC) is characterized as a mosaic of distinct differences in fiber density of small- and large-diameter axons along the anterior-posterior axis; however, regional and age differences across the lifespan are not fully understood. Using multiecho T2 magnetic resonance imaging combined with multi-T2 fitting, the myelin water fraction (MWF) and geometric-mean of the intra-/extracellular water T2 (geomT2IEW) in 395 individuals (7-85years; 41% males) were examined. The approach was validated where regional patterns along the CC closely resembled the histology; MWF matched mean axon diameter and geomT2IEW mirrored the density of large-caliber axons. Across the lifespan, MWF exhibited a quadratic association with age in all 10 CC regions with evidence of a positive linear MWF-age relationship among younger participants and minimal age differences in the remainder of the lifespan. Regarding geomT2IEW, a significant linear age × region interaction reflected positive linear age dependence mostly prominent in the regions with the highest density of small-caliber fibers-genu and splenium. In all, these two indicators characterize distinct attributes that are consistent with histology, which is a first. In addition, these results conform to rapid developmental progression of CC myelination leveling in middle age as well as age-related degradation of axon sheaths in older adults.

Compensatory brainstem functional and structural connectivity in patients with degenerative cervical myelopathy by probabilistic tractography and functional MRI

Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord impairment in adults. Previous supraspinal investigations have primarily focused on cortical changes in this patient population. As the nexus between the brain and the spinal cord, the brainstem has been understudied in patients with DCM. The current study examined the structural and functional connectivity between the brainstem and cortex in DCM patients using probabilistic tractography and resting-state functional MRI. A total of 26 study patients and 32 neurologically intact, healthy volunteers (HCs) participated in this prospective analysis. The study cohort included DCM patients (n = 18), as well as neurologically asymptomatic patients with evidence of cervical spine degenerative changes and spinal cord compression (n = 8). Results of the study demonstrated significant differences in fiber density (FD), fiber cross-section (FDC), and the functional connectivity (FC) between the study cohort and HCs. Through seeding the brainstem, the study cohort showed reductions in FD and FDC along the corticospinal tract, including regions extending through the corona radiata and internal capsule. By correlating FD and FDC with the Neck Disability Index (NDI), and the modified Japanese Orthopaedic Association (mJOA), we identified increasing total volume of projections to the thalamus, basal ganglia, and internal capsule, and increased functional connectivity to visual network and the posterior parietal cortices. These results support our hypothesis that DCM patients tend to have long-term FC reorganization not only localized to sensorimotor regions, but also to regulatory and visual processing regions, designed to ultimately preserve neurological function.

Structural connectome and connectivity lateralization of the multimodal vestibular cortical network

Unlike other sensory systems, the structural connectivity patterns of the human vestibular cortex remain a matter of debate. Based on their functional properties and hypothesized centrality within the vestibular network, the ‘core’ cortical regions of this network are thought to be areas in the posterior peri-sylvian cortex, in particular the retro-insula (previously named the posterior insular cortex-PIC), and the subregion OP2 of the parietal operculum.To study the vestibular network, structural connectivity matrices from n=974 healthy individuals drawn from the public Human Connectome Project (HCP) repository were estimated using multi-shell diffusion-weighted data followed by probabilistic tractography and spherical-deconvolution informed filtering of tractograms in combination with subject-specific grey-matter parcellations. Weighted graph-theoretical measures, modularity, and ‘hubness’ of the multimodal vestibular network were then estimated, and a structural lateralization index was defined in order to assess the difference in fiber density of homonym regions in the right and left hemisphere. Differences in connectivity patterns between OP2 and PIC were also estimated.We found that the bilateral intraparietal sulcus, PIC, and to a lesser degree OP2, are key ‘hub’ regions within the multimodal vestibular network. PIC and OP2 structural connectivity patterns were lateralized to the left hemisphere, while structural connectivity patterns of the posterior peri-sylvian supramarginal and superior temporal gyri were lateralized to the right hemisphere. These lateralization patterns were independent of handedness.We also found that the structural connectivity pattern of PIC is consistent with a key role of PIC in visuo-vestibular processing and that the structural connectivity pattern of OP2 is consistent with integration of mainly vestibular somato-sensory and motor information. These results suggest an analogy between PIC and the simian visual posterior sylvian (VPS) area and OP2 and the simian parieto-insular vestibular cortex (PIVC).Overall, these findings may provide novel insights to the current models of vestibular function, as well as to the understanding of the complexity and lateralized signs of vestibular syndromes.

Pervasive White Matter Fiber Degeneration in Ischemic Stroke.

Background and Purpose- We examined if ischemic stroke is associated with white matter degeneration predominantly confined to the ipsi-lesional tracts or with widespread bilateral axonal loss independent of lesion laterality. Methods- We applied a novel fixel-based analysis, sensitive to fiber tract-specific differences within a voxel, to assess axonal loss in stroke (N=104, 32 women) compared to control participants (N=40, 15 women) across the whole brain. We studied microstructural differences in fiber density and macrostructural (morphological) changes in fiber cross-section. Results- In participants with stroke, we observed significantly lower fiber density and cross-section in areas adjacent, or connected, to the lesions (eg, ipsi-lesional corticospinal tract). In addition, the changes extended beyond directly connected tracts, independent of the lesion laterality (eg, corpus callosum, bilateral inferior fronto-occipital fasciculus, right superior longitudinal fasciculus). Conclusions- We conclude that ischemic stroke is associated with extensive neurodegeneration that significantly affects white matter integrity across the whole brain. These findings expand our understanding of the mechanisms of brain volume loss and delayed cognitive decline in stroke.

Fiber-specific white matter reductions in Parkinson hallucinations and visual dysfunction.

ObjectiveTo investigate the microstructural and macrostructural white matter changes that accompany visual hallucinations and low visual performance in Parkinson disease, a risk factor for Parkinson dementia.MethodsWe performed fixel-based analysis, a novel technique that provides metrics of specific fiber-bundle populations within a voxel (or fixel). Diffusion MRI data were acquired from patients with Parkinson disease (n = 105, of whom 34 were low visual performers and 19 were hallucinators) and age-matched controls (n = 35). We used whole-brain fixel-based analysis to compare microstructural differences in fiber density (FD), macrostructural differences in fiber bundle cross section (FC), and the combined FD and FC (FDC) metric across all white matter fixels. We then performed a tract-of-interest analysis comparing the most sensitive FDC metric across 11 tracts within the visual system.ResultsPatients with Parkinson disease hallucinations exhibited macrostructural changes (reduced FC) within the splenium of the corpus callosum and the left posterior thalamic radiation compared to patients without hallucinations. While there were no significant changes in FD, we found large reductions in the combined FDC metric in Parkinson hallucinators within the splenium (>50% reduction compared to nonhallucinators). Patients with Parkinson disease and low visual performance showed widespread microstructural and macrostructural changes within the genu and splenium of the corpus callosum, bilateral posterior thalamic radiations, and left inferior fronto-occipital fasciculus.ConclusionsWe demonstrate specific white matter tract degeneration affecting posterior thalamic tracts in patients with Parkinson disease with hallucinations and low visual performance, providing direct mechanistic support for attentional models of visual hallucinations.

Evaluation of nanocellulose carriers produced by four different bacterial strains for laccase immobilization

Properties of bacterial nanocellulose (BNC) produced by four different strains were studied and compared for laccase immobilization. Scanning electron microscope inspection indicated the four types of BNC had obvious differences in fiber density, diameter and distribution. BNC hydrogel demonstrated the highest fracture stress of 2.44 Mpa and the highest Young's modulus of 12.76 Mpa. Brunauer-Emmett-Teller analysis suggested the four BNC had significant difference in specific surface area, total pore volume and average pore size. Laccase was immobilized on BNC carriers via adsorption. Kinetic studies showed that the four types of BNC-immobilized laccase had different affinity with substrate, and all types of immobilized laccase showed high operational stability after ten consecutive biocatalytic cycles of reaction. The results suggest that the structure diversity of BNC from various strains may directly result in different efficiency in laccase immobilization, and a looser fiber network in BNC with larger porosity is helpful for enzyme immobilization.

Fibre-specific white matter reductions in Alzheimer's disease and mild cognitive impairment.

Alzheimer's disease is increasingly considered a large-scale network disconnection syndrome, associated with progressive aggregation of pathological proteins, cortical atrophy, and functional disconnections between brain regions. These pathological changes are posited to arise in a stereotypical spatiotemporal manner, targeting intrinsic networks in the brain, most notably the default mode network. While this network-specific disruption has been thoroughly studied with functional neuroimaging, changes to specific white matter fibre pathways within the brain's structural networks have not been closely investigated, largely due to the challenges of modelling complex white matter structure. Here, we applied a novel technique known as 'fixel-based analysis' to comprehensively investigate fibre tract-specific differences at a within-voxel level (called 'fixels') to assess potential axonal loss in subjects with Alzheimer's disease and mild cognitive impairment. We hypothesized that patients with Alzheimer's disease would exhibit extensive degeneration across key fibre pathways connecting default network nodes, while patients with mild cognitive impairment would exhibit selective degeneration within fibre pathways connecting regions previously identified as functionally implicated early in Alzheimer's disease. Diffusion MRI data from Alzheimer's disease (n = 49), mild cognitive impairment (n = 33), and healthy elderly control subjects (n = 95) were obtained from the Australian Imaging, Biomarkers and Lifestyle study of ageing. We assessed microstructural differences in fibre density, and macrostructural differences in fibre bundle morphology using fixel-based analysis. Whole-brain analysis was performed to compare groups across all white matter fixels. Subsequently, we performed a tract of interest analysis comparing fibre density and cross-section across 11 selected white matter tracts, to investigate potentially subtle degeneration within fibre pathways in mild cognitive impairment, initially by clinical diagnosis alone, and then by including amyloid status (i.e. a positive or negative amyloid PET scan). Our whole-brain analysis revealed significant white matter loss manifesting both microstructurally and macrostructurally in Alzheimer's disease patients, evident in specific fibre pathways associated with default mode network nodes. Reductions in fibre density and cross-section in mild cognitive impairment patients were only exhibited within the posterior cingulum when statistical analyses were limited to tracts of interest. Interestingly, these degenerative changes did not appear to be associated with high amyloid accumulation, given that amyloid-negative, but not positive, mild cognitive impairment subjects exhibited subtle focal left posterior cingulum deficits. The findings of this study demonstrated a stereotypical distribution of white matter degeneration in patients with Alzheimer's disease, which was in line with canonical findings from other imaging modalities, and with a network-based conceptualization of the disease.awx355media15726254535001.

Left-Ventricular Assist Device Impact on Aortic Valve Mechanics, Proteomics and Ultrastructure

Aortic regurgitation is a prevalent, detrimental complication of left ventricular assist devices (LVADs). The altered hemodynamics of LVADs results in aortic valves (AVs) having distinct mechanical stimulation. Our hypothesis was that the altered AV hemodynamics modulates the valve cells and matrix, resulting in changes in valvular mechanical properties that then can lead to regurgitation. AVs were collected from 16 LVAD and 6 non-LVAD patients at time of heart transplant. Standard demographic and preoperative data were collected and comparisons between the two groups were calculated using standard statistical methods. Samples were analyzed using biaxial mechanical tensile testing, mass spectrometry-based proteomics, and transmission electron microscopy to assess ultrastructure. The maximum circumferential leaflet strain in LVAD patients was less than in non-LVAD patients (0.35 ± 0.10MPa versus 0.52 ± 0.18 MPa, p= 0.03) with a trend of reduced radial strain (p= 0.06) and a tendency for the radial strain to decrease with increasing LVAD duration (p= 0.063). Numerous proteins associated with actin and myosin, immune signaling and oxidative stress, and transforming growth factor β were increased in LVAD patients. Ultrastructural analysis showed a trend of increased fiber diameter in LVAD patients (46.2 ± 7.2 nm versus 45.1 ± 6.9 nm, p= 0.10), but no difference in fiber density. AVs in LVAD patients showed decreased compliance and increased expression of numerous proteins related to valve activation and injury compared to non-LVAD patients. Further knowledge of AV changes leading to regurgitation in LVAD patients and the pathways by which they occur may provide an opportunity for interventions to prevent and/or reverse this detrimental complication.