Older age, male sex, and cerebral microbleeds predict white matter loss after traumatic brain injury.

Little is known on how mild traumatic brain injury affects white matter based on age at injury, sex, cerebral microbleeds, and time since injury. Here, we study the fractional anisotropy of white matter to study these effects in 109 participants aged 18-77 (46 females, age µ ± σ = 40 ± 17 years) imaged within [Formula: see text] 1 week and [Formula: see text] 6 months post-injury. Age is found to be linearly associated with white matter degradation, likely due not only to injury but also to cumulative effects of other pathologies and to their interactions with injury. Age is associated with mean anisotropy decreases in the corpus callosum, middle longitudinal fasciculi, inferior longitudinal and occipitofrontal fasciculi, and superficial frontal and temporal fasciculi. Over [Formula: see text] 6 months, the mean anisotropies of the corpus callosum, left superficial frontal fasciculi, and left corticospinal tract decrease significantly. Independently of other predictors, age and cerebral microbleeds contribute to anisotropy decrease in the callosal genu. Chronically, the white matter of commissural tracts, left superficial frontal fasciculi, and left corticospinal tract degrade appreciably, independently of other predictors. Our findings suggest that large commissural and intra-hemispheric structures are at high risk for post-traumatic degradation. This study identifies detailed neuroanatomic substrates consistent with brain injury patients' age-dependent deficits in information processing speed, interhemispheric communication, motor coordination, visual acuity, sensory integration, reading speed/comprehension, executive function, personality, and memory. We also identify neuroanatomic features underlying white matter degradation whose severity is associated with the male sex. Future studies should compare our findings to functional measures and other neurodegenerative processes.

The Indigenous South American Tsimane Exhibit Relatively Modest Decrease in Brain Volume With Age Despite High Systemic Inflammation.

Brain atrophy is correlated with risk of cognitive impairment, functional decline, and dementia. Despite a high infectious disease burden, Tsimane forager-horticulturists of Bolivia have the lowest prevalence of coronary atherosclerosis of any studied population and present few cardiovascular disease (CVD) risk factors despite a high burden of infections and therefore inflammation. This study (a) examines the statistical association between brain volume (BV) and age for Tsimane and (b) compares this association to that of 3 industrialized populations in the United States and Europe. This cohort-based panel study enrolled 746 participants aged 40-94 (396 males), from whom computed tomography (CT) head scans were acquired. BV and intracranial volume (ICV) were calculated from automatic head CT segmentations. The linear regression coefficient estimate ß^T of the Tsimane (T), describing the relationship between age (predictor) and BV (response, as a percentage of ICV), was calculated for the pooled sample (including both sexes) and for each sex. ß^T was compared to the corresponding regression coefficient estimate ß^R of samples from the industrialized reference (R) countries. For all comparisons, the null hypothesis ß T = ß R was rejected both for the combined samples of males and females, as well as separately for each sex. Our results indicate that the Tsimane exhibit a significantly slower decrease in BV with age than populations in the United States and Europe. Such reduced rates of BV decrease, together with a subsistence lifestyle and low CVD risk, may protect brain health despite considerable chronic inflammation related to infectious burden.

Acute cognitive impairment after traumatic brain injury predicts the occurrence of brain atrophy patterns similar to those observed in Alzheimer's disease.

Traumatic brain injuries (TBIs) are often followed by persistent structural brain alterations and by cognitive sequalae, including memory deficits, reduced neural processing speed, impaired social function, and decision-making difficulties. Although mild TBI (mTBI) is a risk factor for Alzheimer's disease (AD), the extent to which these conditions share patterns of macroscale neurodegeneration has not been quantified. Comparing such patterns can not only reveal how the neurodegenerative trajectories of TBI and AD are similar, but may also identify brain atrophy features which can be leveraged to prognosticate AD risk after TBI. The primary aim of this study is to systematically map how TBI affects white matter (WM) and gray matter (GM) properties in AD-analogous patterns. Our findings identify substantial similarities in the regional macroscale neurodegeneration patterns associated with mTBI and AD. In cerebral GM, such similarities are most extensive in brain areas involved in memory and executive function, such as the temporal poles and orbitofrontal cortices, respectively. Our results indicate that the spatial pattern of cerebral WM degradation observed in AD is broadly similar to the pattern of diffuse axonal injury observed in TBI, which frequently affects WM structures like the fornix, corpus callosum, and corona radiata. Using machine learning, we find that the severity of AD-like brain changes observed during the chronic stage of mTBI can be accurately prognosticated based on acute assessments of post-traumatic mild cognitive impairment. These findings suggest that acute post-traumatic cognitive impairment predicts the magnitude of AD-like brain atrophy, which is itself associated with AD risk.

Brain Segmentation From Computed Tomography of Healthy Aging and Geriatric Concussion at Variable Spatial Resolutions.

When properly implemented and processed, anatomic T 1-weighted magnetic resonance imaging (MRI) can be ideal for the noninvasive quantification of white matter (WM) and gray matter (GM) in the living human brain. Although MRI is more suitable for distinguishing GM from WM than computed tomography (CT), the growing clinical use of the latter technique has renewed interest in head CT segmentation. Such interest is particularly strong in settings where MRI is unavailable, logistically unfeasible or prohibitively expensive. Nevertheless, whereas MRI segmentation is a sophisticated and technically-mature research field, the task of automatically classifying soft brain tissues from CT remains largely unexplored. Furthermore, brain segmentation methods for MRI hold considerable potential for adaptation and application to CT image processing. Here we demonstrate this by combining probabilistic, atlas-based classification with topologically-constrained tissue boundary refinement to delineate WM, GM and cerebrospinal fluid (CSF) from head CT images. The feasibility and utility of this approach are revealed by comparison of MRI-only vs. CT-only segmentations in geriatric concussion victims with both MRI and CT scans. Comparison of the two segmentations yields mean Sørensen-Dice coefficients of 85.5 ± 4.6% (WM), 86.7 ± 5.6% (GM) and 91.3 ± 2.8% (CSF), as well as average Hausdorff distances of 3.76 ± 1.85 mm (WM), 3.43 ± 1.53 mm (GM) and 2.46 ± 1.27 mm (CSF). Bootstrapping results suggest that the segmentation approach is sensitive enough to yield WM, GM and CSF volume estimates within ~5%, ~4%, and ~3% of their MRI-based estimates, respectively. To our knowledge, this is the first 3D segmentation approach for CT to undergo rigorous within-subject comparison with high-resolution MRI. Results suggest that (1) standard-quality CT allows WM/GM/CSF segmentation with reasonable accuracy, and that (2) the task of soft brain tissue classification from CT merits further attention from neuroimaging researchers.

Post-Traumatic Cerebral Microhemorrhages and their Effects Upon White Matter Connectivity in the Aging Human Brain.

Cerebral microbleeds (CMBs), a common manifestation of mild traumatic brain injury (mTBI), have been sporadically implicated in the neurocognitive deficits of mTBI victims but their clinical significance has not been established adequately. Here we investigate the longitudinal effects of post-mTBI CMBs upon the fractional anisotropy (FA) of white matter (WM) in 21 older mTBI patients across the first ~6 months post-injury. CMBs were segmented automatically from susceptibility-weighted imaging (SWI) by leveraging the intensity gradient properties of SWI to identify CMB-related hypointensities using gradient-based edge detection. A detailed diffusion magnetic resonance imaging (dMRI) atlas of WM was used to segment and cluster tractography streamlines whose prototypes were then identified. The correlation coefficient was calculated between (A) FA values at vertices along streamline prototypes and (B) topological (along-streamline) distances between these vertices and the nearest CMB. Across subjects, the CMB identification approach achieved a sensitivity of 97.1% ± 4.7% and a precision of 72.4% ± 11.0% across subjects. The correlation coefficient was found to be negative and, additionally, statistically significant for 12.3% ± 3.5% of WM clusters (p <; 0.05, corrected), whose FA was found to decrease, on average, by 11.8% ± 5.3% across the first 6 months post-injury. These results suggest that CMBs can be associated with deleterious effects upon peri-lesional WM and highlight the vulnerability of older mTBI patients to neurovascular injury.

Macroscale White Matter Alterations Due to Traumatic Cerebral Microhemorrhages Are Revealed by Diffusion Tensor Imaging.

With the advent of susceptibility-weighted imaging (SWI), the ability to identify cerebral microbleeds (CMBs) associated with mild traumatic brain injury (mTBI) has become increasingly commonplace. Nevertheless, the clinical significance of post-traumatic CMBs remains controversial partly because it is unclear whether mTBI-related CMBs entail brain circuitry disruptions which, although structurally subtle, are functionally significant. This study combines magnetic resonance and diffusion tensor imaging (MRI and DTI) to map white matter (WM) circuitry differences across 6 months in 26 healthy control volunteers and in 26 older mTBI victims with acute CMBs of traumatic etiology. Six months post-mTBI, significant changes (p < 0.001) in the mean fractional anisotropy of perilesional WM bundles were identified in 21 volunteers, and an average of 47% (σ = 21%) of TBI-related CMBs were associated with such changes. These results suggest that CMBs can be associated with lasting changes in perilesional WM properties, even relatively far from CMB locations. Future strategies for mTBI care will likely rely on the ability to assess how subtle circuitry changes impact neural/cognitive function. Thus, assessing CMB effects upon the structural connectome can play a useful role when studying CMB sequelae and their potential impact upon the clinical outcome of individuals with concussion.

Neuroinformatics and Analysis of Connectomic Alterations Due to Cerebral Microhemorrhages in Geriatric Mild Neurotrauma.

Connectomics alterations associated with subtle forms of cerebrovascular neuropathology-such as cerebral microbleeds (CMBs)-can result in substantial neurological and/or cognitive deficits in victims of traumatic brain injury (TBI). Quantifying CMB-related connectome changes in mild TBI (mTBI) patients requires ingenious neuroinformatics to integrate structural magnetic resonance imaging (sMRI) with diffusion-weighted imaging (DWI) for patient-tailored profiling while preserving the data scientist's ability to implement population studies. Such solutions, however, can assist the refinement of rehabilitation protocols and streamline large-scale analysis while accommodating the heterogeneity of mTBI. This study describes a pipeline for the multimodal integration of sMRI/DWI/DTI to quantify white matter (WM) neural network circuitry alterations associated with mTBI-related CMBs. The approach incorporates WM streamline matching, topology-compliant streamline prototyping and along-tract analysis within a unified framework. When applied to the analysis of neuroimaging data acquired from both mTBI and healthy control volunteers, the approach facilitates the identification of patient-specific CMB-related connectomic changes while incorporating the ability to perform group analyses. This pipeline for the identification and profiling of connectopathies can assist the adaptation of clinical rehabilitation protocols to patients' individual needs.