Multi-Scale White Matter Tract Embedded Brain Finite Element Model Predicts the Location of Traumatic Diffuse Axonal Injury.
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ABSTRACT:
SUBMITTER: Hajiaghamemar M
PROVIDER: S-EPMC7757550 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Diffusion tensor imaging (DTI) has been useful in showing compromise after traumatic axonal injury (TAI) at the chronic stage; however, white matter (WM) compromise from acute stage of TAI to chronic stage is not yet well understood. This study aims to examine changes in WM integrity following TAI by obtaining DTI, on average, 1?d post injury and again approximately seven months post-injury. Sixteen patients with complicated mild to severe brain injuries consistent with TAI were recruited in the intensive care unit of a Level I trauma center. Thirteen of these patients were studied longitudinally over the course of the first seven months post-injury. The first scan occurred, on average, 1?d after injury and the second an average of seven months post-injury. Ten healthy individuals, similar to the cohort of patients, were recruited as controls. Whole brain WM and voxel-based analyses of DTI data were conducted. DTI metrics of interest included: fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD). tract-based spatial statistics were used to examine DTI metrics spatially. Acutely, AD and RD increased and RD positively correlated with injury severity. Longitudinal analysis showed reduction in FA and AD (p<0.01), but no change in RD. Possible explanations for the microstructural changes observed over time are discussed.
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Project description:Axonal structure underlies white matter functionality and plays a major role in brain connectivity. The current literature on the axonal structure is based on the analysis of two-dimensional (2D) cross-sections, which, as we demonstrate, is precarious. To be able to quantify three-dimensional (3D) axonal morphology, we developed a novel pipeline, called ACSON (AutomatiC 3D Segmentation and morphometry Of axoNs), for automated 3D segmentation and morphometric analysis of the white matter ultrastructure. The automated pipeline eliminates the need for time-consuming manual segmentation of 3D datasets. ACSON segments myelin, myelinated and unmyelinated axons, mitochondria, cells and vacuoles, and analyzes the morphology of myelinated axons. We applied the pipeline to serial block-face scanning electron microscopy images of the corpus callosum of sham-operated (n = 2) and brain injured (n = 3) rats 5 months after the injury. The 3D morphometry showed that cross-sections of myelinated axons were elliptic rather than circular, and their diameter varied substantially along their longitudinal axis. It also showed a significant reduction in the myelinated axon diameter of the ipsilateral corpus callosum of rats 5 months after brain injury, indicating ongoing axonal alterations even at this chronic time-point.
| S-EPMC6465365 | biostudies-literature
Project description:The brains of large mammals have lower rates of metabolism than those of small mammals, but the functional consequences of this scaling are not well understood. An attractive target for analysis is axons, whose size, speed and energy consumption are straightforwardly related. Here we show that from shrews to whales, the composition of white matter shifts from compact, slow-conducting, and energetically expensive unmyelinated axons to large, fast-conducting, and energetically inexpensive myelinated axons. The fastest axons have conduction times of 1-5 ms across the neocortex and <1 ms from the eye to the brain, suggesting that in select sets of communicating fibers, large brains reduce transmission delays and metabolic firing costs at the expense of increased volume. Delays and potential imprecision in cross-brain conduction times are especially great in unmyelinated axons, which may transmit information via firing rate rather than precise spike timing. In neocortex, axon size distributions can account for the scaling of per-volume metabolic rate and suggest a maximum supportable firing rate, averaged across all axons, of 7 +/- 2 Hz. Axon size distributions also account for the scaling of white matter volume with respect to brain size. The heterogeneous white matter composition found in large brains thus reflects a metabolically constrained trade-off that reduces both volume and conduction time.
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Project description:Sports-related concussions have been shown to lead to persistent subclinical anomalies of the motor and cognitive systems in young asymptomatic athletes. In advancing age, these latent alterations correlate with detectable motor and cognitive function decline. Until now, the interacting effects of concussions and the normal ageing process on white matter tract integrity remain unknown. Here we used a tract-based spatial statistical method to uncover potential white matter tissue damage in 15 retired athletes with a history of concussions, free of comorbid medical conditions. We also investigated potential associations between white matter integrity and declines in cognitive and motor functions. Compared to an age- and education-matched control group of 15 retired athletes without concussions, former athletes with concussions exhibited widespread white matter anomalies along many major association, interhemispheric, and projection tracts. Group contrasts revealed decreases in fractional anisotropy, as well as increases in mean and radial diffusivity measures in the concussed group. These differences were primarily apparent in fronto-parietal networks as well as in the frontal aspect of the corpus callosum. The white matter anomalies uncovered in concussed athletes were significantly associated with a decline in episodic memory and lateral ventricle expansion. Finally, the expected association between frontal white matter integrity and motor learning found in former non-concussed athletes was absent in concussed participants. Together, these results show that advancing age in retired athletes presenting with a history of sports-related concussions is linked to diffuse white matter abnormalities that are consistent with the effects of traumatic axonal injury and exacerbated demyelination. These changes in white matter integrity might explain the cognitive and motor function declines documented in this population.
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Project description:High-resolution finite element models derived from micro-computed tomography images are often used to study the effects of trabecular microarchitecture and loading mode on tissue stress, but the degree to which existing finite element methods correctly predict the location of tissue failure is not well characterized. In the current study, we determined the relationship between the location of highly strained tissue, as determined from high-resolution finite element models, and the location of tissue microdamage, as determined from three-dimensional fluoroscopy imaging, which was performed after the microdamage was generated in-vitro by mechanical testing. Fourteen specimens of human vertebral cancellous bone were assessed (8 male donors, 2 female donors, 47-78 years of age). Regions of stained microdamage, were 50-75% more likely to form in highly strained tissue (principal strains exceeding 0.4%) than elsewhere, and generally the locations of the regions of microdamage were significantly correlated (p<0.05) with the locations of highly strained tissue. This spatial correlation was stronger for the largest regions of microdamage (?1,000,000?m(3) in volume); 87% of large regions of microdamage were located near highly strained tissue. Together, these findings demonstrate that there is a strong correlation between regions of microdamage and regions of high strain in human cancellous bone, particularly for the biomechanically more important large instances of microdamage.
| S-EPMC4663152 | biostudies-literature
Project description:The primary progressive aphasias (PPA) are a heterogeneous group of language-led neurodegenerative diseases resulting from large-scale brain network degeneration. White matter (WM) pathways bind networks together, and might therefore hold information about PPA pathogenesis. Here we used diffusion tensor imaging and tract-based spatial statistics to compare WM tract changes between PPA syndromes and with respect to Alzheimer's disease and healthy controls in 33 patients with PPA (13 nonfluent/agrammatic PPA); 10 logopenic variant PPA; and 10 semantic variant PPA. Nonfluent/agrammatic PPA was associated with predominantly left-sided and anterior tract alterations including uncinate fasciculus (UF) and subcortical projections; semantic variant PPA with bilateral alterations in inferior longitudinal fasciculus and UF; and logopenic variant PPA with bilateral but predominantly left-sided alterations in inferior longitudinal fasciculus, UF, superior longitudinal fasciculus, and subcortical projections. Tract alterations were more extensive than gray matter alterations, and the extent of alteration across tracts and PPA syndromes varied between diffusivity metrics. These WM signatures of PPA syndromes illustrate the selective vulnerability of brain language networks in these diseases and might have some pathologic specificity.
| S-EPMC3601331 | biostudies-literature
Project description:IntroductionWhite matter damage in the visual pathway is common in multiple sclerosis (MS) and is associated with retinal thinning, although the underlying mechanism of association remains unclear. The goal of this work was to evaluate the presence and extent of white matter tract integrity (WMTI) alterations in the optic radiation (OR) in people with MS and to investigate the association between WMTI metrics and retinal thinning in the eyes of MS patients without a history of optic neuritis (ON) as measured by optical coherence tomography (OCT). We hypothesized that WMTI metrics would reflect axonal damage that occurs in the OR in MS, and that axonal alterations revealed by WMTI would be associated with retinal thinning.MethodsTwenty-nine MS patients without previous ON in at least one eye and twenty-nine age-matched healthy controls (HC) were scanned on a dedicated high-gradient 3-Tesla MRI scanner with 300 mT/m maximum gradient strength using a multi-shell diffusion MRI protocol (b = 800, 1500, 2400 s/mm2). The patients were divided into two subgroups according to history without ON (N = 18) or with ON in one eye (N = 11). Diffusion tensor imaging (DTI) metrics and WMTI metrics derived from diffusion kurtosis imaging were assessed in normal-appearing white matter (NAWM) of the OR and in focal lesions. Retinal thickness in the eyes of MS patients was measured by OCT. Student's t-test was used to assess group differences between MRI metrics. Linear regression was used to study the relationship between OCT metrics, including retinal nerve fiber layer (RNFL) and combined ganglion cell and inner plexiform layer thickness (GCL/IPL), visual acuity measures and DTI and WMTI metrics.ResultsOR NAWM in MS showed significantly decreased axonal water fraction (AWF) compared to HC (0.36 vs 0.39, p < 0.001), with similar trends observed in AWF of lesions compared to NAWM (0.27 vs 0.36, p < 0.001). Fractional anisotropy (FA) was lower in OR NAWM of MS patients compared to HC (0.49 vs 0.52, p < 0.001). In patients without ON, AWF was the only diffusion MRI metric that was significantly associated with average RNFL (r = 0.68, p = 0.005), adjusting for age, sex and disease duration and correcting for multiple comparisons. Of all the DTI and WMTI metrics, AWF was the strongest and most significant predictor of average RNFL thickness in MS patients without ON. There was no significant correlation between visual acuity scores and DTI or WMTI metrics after correction for multiple comparisons.ConclusionAxonal damage may be the substrate of previously observed DTI alterations in the OR, as supported by the significant reduction in AWF within both NAWM and lesions of the OR in MS. Our results support the concept that axonal damage is widespread throughout the visual pathway in MS and may be mediated through trans-synaptic degeneration.
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Project description:BackgroundNeuroaxonal degeneration is one of the hallmarks of clinical deterioration in progressive multiple sclerosis (PMS).ObjectiveTo elucidate the association between neuroaxonal degeneration and both local cortical and connected white matter (WM) tract pathology in PMS.MethodsPost-mortem in situ 3T magnetic resonance imaging (MRI) and cortical tissue blocks were collected from 16 PMS donors and 10 controls. Cortical neuroaxonal, myelin, and microglia densities were quantified histopathologically. From diffusion tensor MRI, fractional anisotropy, axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were quantified in normal-appearing white matter (NAWM) and white matter lesions (WML) of WM tracts connected to dissected cortical regions. Between-group differences and within-group associations were investigated through linear mixed models.ResultsThe PMS donors displayed significant axonal loss in both demyelinated and normal-appearing (NA) cortices (p < 0.001 and p = 0.02) compared with controls. In PMS, cortical axonal density was associated with WML MD and AD (p = 0.003; p = 0.02, respectively), and NAWM MD and AD (p = 0.04; p = 0.049, respectively). NAWM AD and WML AD explained 12.6% and 22.6%, respectively, of axonal density variance in NA cortex. Additional axonal loss in demyelinated cortex was associated with cortical demyelination severity (p = 0.002), explaining 34.4% of axonal loss variance.ConclusionReduced integrity of connected WM tracts and cortical demyelination both contribute to cortical axonal loss in PMS.
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Project description:Post-traumatic stress disorder (PTSD) is a debilitating condition which can develop after exposure to traumatic stressors. Seventy-five adults were recruited from the community, 25 diagnosed with PTSD along with 25 healthy and 25 trauma-exposed age- and gender-matched controls. Participants underwent clinical assessment and magnetic resonance imaging. A previous voxel based morphometry (VBM) study using the same subject cohort identified decreased grey matter (GM) volumes within frontal/subcortical brain regions including the hippocampus, amygdala, and anterior cingulate cortex (ACC). This study examines the microstructural integrity of white matter (WM) tracts connecting the aforementioned regions/structures. Using diffusion tensor imaging, we investigated the integrity of frontal/subcortical WM tracts between all three subject groups. Trauma exposed subjects with and without PTSD diagnosis were identified to have significant disruption in WM integrity as indexed by decreased fractional anisotropy (FA) in the uncinate fasciculus (UF), cingulum cingulate gyrus (CCG), and corpus callosum (CC), when compared with healthy non-trauma-exposed controls. Significant negative correlations were found between total Clinician Administered PTSD scale (CAPS) lifetime clinical subscores and FA values of PTSD subjects in the right UF, CCG, CC body, and right superior longitudinal fasciculus (SLF). An analysis between UF and SLF FA values and VBM determined rostral ACC GM values found a negative correlation in PTSD subjects. Findings suggest that compromised WM integrity in important tracts connecting limbic structures such as the amygdala to frontal regions including the ACC (i.e., the UF and CCG) may contribute to impairments in threat/fear processing associated with PTSD.
| S-EPMC6866495 | biostudies-literature
Project description:Studies of posttraumatic stress disorder (PTSD) are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI) studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake). Using diffusion tensor imaging (DTI), we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA), as well as its component elements axial diffusivity (AD) and radial diffusivity (RD), and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the region's established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved.
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