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BACKGROUND AND OBJECTIVES: To study longitudinal associations between blood-based neural biomarkers (including total tau, neurofilament light [NfL], glial fibrillary acidic protein [GFAP], and ubiquitin C-terminal hydrolase-L1) and white matter neuroimaging biomarkers in collegiate athletes with sport-related concussion (SRC) from 24 hours postinjury to 1 week after return to play. METHODS: We analyzed clinical and imaging data of concussed collegiate athletes in the Concussion Assessment, Research, and Education (CARE) Consortium. The CARE participants completed same-day clinical assessments, blood draws, and diffusion tensor imaging (DTI) at 3 time points: 24-48 hours postinjury, point of becoming asymptomatic, and 7 days after return to play. DTI probabilistic tractography was performed for each participant at each time point to render 27 participant-specific major white matter tracts. The microstructural organization of these tracts was characterized by 4 DTI metrics. Mixed-effects models with random intercepts were applied to test whether white matter microstructural abnormalities are associated with the blood-based biomarkers at the same time point. An interaction model was used to test whether the association varies across time points. A lagged model was used to test whether early blood-based biomarkers predict later microstructural changes. RESULTS: Data from 77 collegiate athletes were included in the following analyses. Among the 4 blood-based biomarkers, total tau had significant associations with the DTI metrics across the 3 time points. In particular, high tau level was associated with high radial diffusivity (RD) in the right corticospinal tract (β = 0.25, SE = 0.07, p FDR-adjusted = 0.016) and superior thalamic radiation (β = 0.21, SE = 0.07, p FDR-adjusted = 0.042). NfL and GFAP had time-dependent associations with the DTI metrics. NfL showed significant associations only at the asymptomatic time point (|β|s > 0.12, SEs 0.14, SEs

Sport-related concussion (SRC) is an important public health issue. White-matter alterations after SRC are widely studied by neuroimaging approaches, such as diffusion magnetic resonance imaging (MRI). Although the exact anatomical location of the alterations may differ, significant white-matter alterations are commonly observed in long fiber tracts, but are never proven. In the present study, we performed streamline tractography to characterize the association between tract length and white-matter microstructural alterations after SRC. Sixty-eight collegiate athletes diagnosed with acute concussion (24-48 h post-injury) and 64 matched contact-sport controls were included in this study. The athletes underwent diffusion tensor imaging (DTI) in 3.0 T MRI scanners across three study sites. DTI metrics were used for tract-based spatial statistics to map white-matter regions-of-interest (ROIs) with significant group differences. Whole-brain white-mater streamline tractography was performed to extract affected white-matter streamlines (i.e., streamlines passing through the identified ROIs). In the concussed athletes, streamline counts and DTI metrics of the affected white-matter fiber tracts were summarized and compared with unaffected white-matter tracts across tract length in the same participant. The affected white-matter tracts had a high streamline count at length of 80-100 mm and high length-adjusted affected ratio for streamline length longer than 80 mm. DTI mean diffusivity was higher in the affected streamlines longer than 100 mm with significant associations with the Brief Symptom Inventory score. Our findings suggest that long fibers in the brains of collegiate athletes are more vulnerable to acute SRC with higher mean diffusivity and a higher affected ratio compared with the whole distribution.

IntroductionHead injuries (HI) are a risk factor for dementia, but the underlying etiology is not fully known. Understanding whether tau might mediate this relationship is important.MethodsCognition and tau deposition were compared between 752 individuals with (impaired, n = 302) or without cognitive impairment (CN, n = 450) with amyloid and [18F]flortaucipir positron emission tomography, HI history information, and cognitive testing from the Alzheimer's Disease Neuroimaging Initiative and the Indiana Memory and Aging Study.ResultsSixty-three (38 CN, 25 impaired) reported a history of HI. Higher neuropsychiatric scores and poorer memory were observed in those with a history of HI. Tau was higher in individuals with a history of HI, especially those who experienced a loss of consciousness (LOC). Results were driven by impaired individuals, especially amyloid beta-positive individuals with history of HI with LOC.DiscussionThese findings suggest biological changes, such as greater tau, are associated with HI in individuals with cognitive impairment. Small effect sizes were observed; thus, further studies should replicate and extend these results.

Objective: A recent systematic review determined that the physiological effects of concussion may persist beyond clinical recovery. Preclinical models suggest that ongoing physiological effects are accompanied by increased cerebral vulnerability that is associated with risk for subsequent, more severe injury. This study examined the association between signal alterations on diffusion tensor imaging following clinical recovery of sport-related concussion in athletes with and without a subsequent second concussion. Methods: Average mean diffusivity (MD) was calculated in a region of interest (ROI) in which concussed athletes (n = 82) showed significantly elevated MD acutely after injury (

There has been a recent call for longitudinal cohort studies to track the physiological recovery of sport-related concussion (SRC) and its relationship with clinical recovery. Resting-state functional magnetic resonance imaging (rs-fMRI) has shown potential for detecting subtle changes in brain function after SRC. We investigated the effects of SRC on rs-fMRI metrics assessing local connectivity (regional homogeneity; REHO), global connectivity (average nodal strength), and the relative amplitude of slow oscillations of rs-fMRI (fractional amplitude of low-frequency fluctuations; fALFF). Athletes diagnosed with SRC (n = 92) completed visits with neuroimaging at 24-48 h post-injury (24 h), after clearance to begin the return-to-play (RTP) progression (asymptomatic), and 7 days following unrestricted RTP (post-RTP). Non-injured athletes (n = 82) completed visits yoked to the schedule of matched injured athletes and served as controls. Concussed athletes had elevated symptoms, worse neurocognitive performance, greater balance deficits, and elevated psychological symptoms at the 24-h visit relative to controls. These deficits were largely recovered by the asymptomatic visit. Concussed athletes still reported elevated psychological symptoms at the asymptomatic visit relative to controls. Concussed athletes also had elevated REHO in the right middle and superior frontal gyri at the 24-h visit that returned to normal levels by the asymptomatic visit. Additionally, REHO in these regions at 24 h predicted psychological symptoms at the asymptomatic visit in concussed athletes. Current results suggest that SRC is associated with an acute alteration in local connectivity that follows a similar time course as clinical recovery. Our results do not indicate strong evidence that concussion-related alterations in rs-fMRI persist beyond clinical recovery.

Previous studies have shown that mild traumatic brain injury (mTBI) can cause abnormalities in clinically relevant magnetic resonance imaging (MRI) sequences. No large-scale study, however, has prospectively assessed this in athletes with sport-related concussion (SRC). The aim of the current study was to characterize and compare the prevalence of acute, trauma-related MRI findings and clinically significant, non-specific MRI findings in athletes with and without SRC. College and high-school athletes were prospectively enrolled and participated in scanning sessions between January 2015 through August 2017. Concussed contact sport athletes (n = 138; 14 female [F]; 19.5 ± 1.6 years) completed up to four scanning sessions after SRC. Non-concussed contact (n = 135; 15 F; 19.7 ± 1.6) and non-contact athletes (n = 96; 15 F; 20.0 ± 1.7) completed similar scanning sessions and served as controls. Board-certified neuroradiologists, blinded to SRC status, reviewed T1-weighted and T2-weighted fluid-attenuated inversion recovery and T2*-weighted and T2-weighted images for acute (i.e., injury-related) or non-acute findings that prompted recommendation for clinical follow-up. Concussed athletes were more likely to have MRI findings relative to contact (30.4% vs. 15.6%; odds ratio [OR] = 2.32; p = 0.01) and non-contact control athletes (19.8%; OR = 2.11; p = 0.04). Female athletes were more likely to have MRI findings than males (43.2% vs. 19.4%; OR = 2.62; p = 0.01). One athlete with SRC had an acute, injury-related finding; group differences were largely driven by increased rate of non-specific white matter hyperintensities in concussed athletes. This prospective, large-scale study demonstrates that

The distribution of water diffusion in biological tissues may be estimated by a 3-D Fourier transform (FT) of diffusion-weighted measurements in q-space. In this study, methods for estimating diffusion spectrum measures (the zero-displacement probability, the mean-squared displacement, and the orientation distribution function) directly from the q-space signals are described. These methods were evaluated using both computer simulations and hybrid diffusion imaging (HYDI) measurements on a human brain. The HYDI method obtains diffusion-weighted measurements on concentric spheres in q-space. Monte Carlo computer simulations were performed to investigate effects of noise, q-space truncation, and sampling interval on the measures. This new direct computation approach reduces HYDI data processing time and image artifacts arising from 3-D FT and regridding interpolation. In addition, it is less sensitive to the noise and q-space truncation effects than conventional approach. Although this study focused on data using the HYDI scheme, this computation approach may be applied to other diffusion sampling schemes including Cartesian diffusion spectrum imaging. Index Terms--Diffusion, diffusion spectrum imaging, diffusion tensor imaging, orientation distribution function, q-space.

Defects, such as cracks, porous structure, small grains that easily occur in the fabrication of copper indium gallium selenide (CIGS) thin film absorbers using non‐vacuum process have been the major obstacle to practical application of this technology so far. A gas‐pressure assisted sintering process has been developed to achieve dense, crack‐free, large‐grained CIGS films. The gas‐pressure assisted sintering effects on the microstructure, crystalline, and electric properties were investigated by scanning electron microscopy, X‐ray diffraction, and Hall‐effect analyzer. A uniform microstructure with a large grain size and small amount of isolated residual pores and good electric properties can be obtained by pre‐sintering at 500°C under 6 bar N2 overpressure and then annealing at 500°C for 20 minutes under a selenium atmosphere. [ABSTRACT FROM AUTHOR]

Objective We describe a novel method to spatially map interictal epileptiform discharges ( IEDs) through voxel-wise functional connectivity analysis of the functional magnetic resonance imaging (f MRI) portion of simultaneous electroencephalography ( EEG)-f MRI data. This method measures the local synchronicity of f MRI signals associated with IED and, in contrast to conventional methods, does not require modeling of neural activities or hemodynamic response. Methods Simultaneous EEG-f MRI was performed on six patients with focal epilepsy. IED events were detected from the EEG data. The f MRI data was subdivided into time segments of 20 s in length, and then reorganized into one set of concatenated time series containing the IED events and many sets without IEDs. Local degree centrality ( LDC), a metric of functional connectivity, was computed for each brain voxel to summarize its signal correlations to brain voxels within 14 mm of physical distance. This computation was repeated for each set of concatenated time series, yielding one whole-brain LDC map for time with the IED events and many maps for time without IED. A statistical score was computed for each voxel to detect the voxels with significant LDC value differences associated with IEDs. The f MRI data were also processed separately by conventional methods for comparison. Results In all six patients, regions with significant LDC increase during IEDs were concordant in location to both simultaneous EEG and the epileptogenic focus determined from separate clinical studies. In contrast, results from the conventional methods were concordant in only three patients. Significance We show that for focal epilepsy, voxel-wise functional connectivity analysis of EEG-f MRI data may improve IED localization and EEG concordance compared to the conventional analysis. This new analytic method may improve the robustness of interictal EEG-f MRI as a technique for mapping the epileptogenic focus, and helps study the local synchronization aspect of the epileptic network. [ABSTRACT FROM AUTHOR]

Evidence of category specificity from neuroimaging in the human visual system is generally limited to a few relatively coarse categorical distinctions-- e.g., faces versus bodies, or animals versus artifacts--leaving unknown the neural underpinnings of fine-grained category structure within these large domains. Here we use fMRI to explore brain activity for a set of categories within the animate domain, including six animal species--two each from three very different biological classes: primates, birds, and insects. Patterns of activity throughout ventral object vision cortex reflected the biological classes of the stimuli. Specifically, the abstract representational space-- measured as dissimilarity matrices defined between species-specific multivariate patterns of brain activity-- correlated strongly with behavioral judgments of biological similarity of the same stimuli. This biological class structure was uncorrelated with structure measured in retinotopic visual cortex, which correlated instead with a dissimilarity matrix defined by a model of V1 cortex for the same stimuli. Additionally, analysis of the shape of the similarity space in ventral regions provides evidence for a continuum in the abstract representational space--with primates at one end and insects at the other. Further investigation into the cortical topography of activity that contributes to this category structure reveals the partial engagement of brain systems active normally for inanimate objects in addition to animate regions. [ABSTRACT FROM AUTHOR]

Biclustering is the task of simultaneously clustering the samples and features of a data set. In doing so, subsets of samples that exhibit similar behaviors across subsets of features can be identified. Motivated by a longitudinal diffusion tensor imaging study of sport-related concussion (SRC), we present the problem of biclustering multivariate longitudinal data in which subjects and features are grouped simultaneously based on longitudinal patterns rather than magnitude. We propose a penalized regression based method for solving this problem by exploiting the heterogeneity in the longitudinal patterns within subjects and features. We evaluate the performance of the proposed methods via a simulation study and apply them to the motivating dataset, revealing distinctive patterns of white-matter abnormalities within subgroups of SRC cases.

Introduction: Head injuries (HI) are a risk factor for dementia, but the underlying etiology is not fully known. Understanding whether tau might mediate this relationship is important., Methods: Cognition and tau deposition were compared between 752 individuals with (impaired, n = 302) or without cognitive impairment (CN, n = 450) with amyloid and [ 18 F]flortaucipir positron emission tomography, HI history information, and cognitive testing from the Alzheimer's Disease Neuroimaging Initiative and the Indiana Memory and Aging Study., Results: Sixty-three (38 CN, 25 impaired) reported a history of HI. Higher neuropsychiatric scores and poorer memory were observed in those with a history of HI. Tau was higher in individuals with a history of HI, especially those who experienced a loss of consciousness (LOC). Results were driven by impaired individuals, especially amyloid beta-positive individuals with history of HI with LOC., Discussion: These findings suggest biological changes, such as greater tau, are associated with HI in individuals with cognitive impairment. Small effect sizes were observed; thus, further studies should replicate and extend these results., Competing Interests: Dr. Risacher has previously consulted for Biogen. Dr. Apostolova has previously consulted for Eli Lilly, Biogen, and Two Labs and received honoraria for participating in independent data safety monitoring boards and providing educational CME lectures and programs. Dr. Jagust has previously consulted for Biogen, Bioclinica, and Genentech. Dr. Landau has served on the scientific advisory board for KeifeRx. Dr. Weiner has served on advisory boards for Eli Lilly, Cerecin/Accera, Roche, Alzheon, Inc., Merck Sharp & Dohme Corp., Nestle/Nestec, PCORI/PPRN, Dolby Family Ventures, National Institute on Aging (NIA), Brain Health Registry, and ADNI; Editorial Boards for Alzheimer's & Dementia, TMRI, and MRI; has provided consulting for and/or acted as a speaker/lecturer to Cerecin/Accera, Inc., BioClinica, Nestle/Nestec, Roche, Genentech, NIH, The Buck Institute for Research on Aging, FUJIFILM‐Toyama Chemical (Japan), Garfield Weston, Baird Equity Capital, University of Southern California (USC), Cytox, and Japanese Organization for Medical Device Development, Inc. (JOMDD) and T3D Therapeutics; and holds stock options with Alzheon, Inc., Alzeca, and Anven. Dr. Saykin has received support from Avid Radiopharmaceuticals, a subsidiary of Eli Lilly (in kind contribution of PET tracer precursor), Bayer Oncology (Scientific Advisory Board), and Springer‐Nature Publishing (Editorial Office Support as Editor‐in‐Chief, Brain Imaging and Behavior). Mr. West, Ms. Deardorff, and Drs. Brosch, Farlow, Gao, McAllister, and Wu have no relevant disclosures., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Multiple sclerosis is a neurodegenerative and inflammatory disease, a hallmark of which is demyelinating lesions in the white matter. We hypothesized that alterations in white matter microstructures can be non-invasively characterized by advanced diffusion magnetic resonance imaging. Seven diffusion metrics were extracted from hybrid diffusion imaging acquisitions via classic diffusion tensor imaging, neurite orientation dispersion and density imaging, and q-space imaging. We investigated the sensitivity of the diffusion metrics in 36 sets of regions of interest in the brain white matter of six female patients (age 52.8 ± 4.3 years) with multiple sclerosis. Each region of interest set included a conventional T2-defined lesion, a matched perilesion area, and normal-appearing white matter. Six patients with multiple sclerosis (n = 5) or clinically isolated syndrome (n = 1) at a mild to moderate disability level were recruited. The patients exhibited microstructural alterations from normal-appearing white matter transitioning to perilesion areas and lesions, consistent with decreased tissue restriction, decreased axonal density, and increased classic diffusion tensor imaging diffusivity. The findings suggest that diffusion compartment modeling and q-space analysis appeared to be sensitive for detecting subtle microstructural alterations between perilesion areas and normal-appearing white matter., Competing Interests: None

Neurite orientation dispersion and density imaging (NODDI), a MRI multi-shell diffusion technique, has offered new insights for the study of microstructural changes in neurodegenerative diseases. Mainly, the present study aimed to determine the connection between NODDI-derived parameters and changes in white matter (WM) abnormalities at early stages of amyotrophic lateral sclerosis (ALS). Spinal cords from ALS mice (G93A-SOD1 mice) were scanned in a Bruker Avance III HD 17.6T magnet. Fluorescent axonal-tagged mice (YFP, G93A-SOD1 mice) were used for quantitative histological analysis. NODDI showed a decrease in intra-cellular volume fraction (-24%) and increases in orientation dispersion index (+35%) and isotropic volume fraction (+33%). In addition, histoathological results demonstrated a reductions in axonal area (-11%) and myelin content (-29%). A histological decrease in WM intra-axonal space (-71%) and an increase in the extra-axonal compartment (+22%) were also detected. Our studies demonstrate that NODDI may be a suitable technique for detecting presymptomatic spinal cord WM microstructural degeneration in ALS.