scholarly journals Abnormal Neurite Density and Orientation Dispersion in Frontal Lobe Link to Elevated Hyperactive/Impulsive Behaviors in Young Adults with Traumatic Brain Injury

2021 ◽  
Author(s):  
Meng Cao ◽  
Yuyang Luo ◽  
Ziyan Wu ◽  
Kai Wu ◽  
Xiaobo Li
Keyword(s):  
Traumatic Brain Injury ◽  
Young Adults ◽  
Brain Injury ◽  
White Matter ◽  
Diffusion Weighted Mri ◽  
Dispersion Index ◽  
Superior Longitudinal Fasciculus ◽  
Neurite Density ◽  
Density Index ◽  
Post Traumatic

Traumatic brain injury is a major public health concern. A significant proportion of individuals experience post-traumatic brain injury behavioral impairments, especially in attention and inhibitory control domains. Traditional diffusion-weighted MRI techniques, such as diffusion tensor imaging, have provided tools to assess white matter structural disruptions reflecting the long-term brain tissue alterations associated with traumatic brain injury. The recently developed neurite orientation dispersion and density imaging is a more advanced diffusion-weighted MRI modality, which provides more refined characterization of brain tissue microstructures by assessing the neurite orientation dispersion and neurite density properties. In this study, we investigated the morphometrical and microstructural alterations at chronic brain injury stage and their relationships with the functional outcomes. Neurite orientation dispersion and density imaging data from 44 young adults with chronic traumatic brain injury (ranging from 18 - 27 years of age; 23 males/21 females) who had no prior-traumatic brain injury history of attention deficits and/or hyperactivity and 45 group-matched normal controls (23 males /22 females) were collected. Maps of fractional anisotropy, neurite orientation dispersion index, and neurite density index were calculated. Vertex-wise and voxel-wise analyses were conducted for gray matter and white matter, respectively. Post-hoc region of interest-based analyses were also performed. Compared to the controls, the group of traumatic brain injury showed significantly increased orientation dispersion index in various gray matter regions and significantly decreased orientation dispersion index in several white matter regions. Brain-behavioral association analyses indicated that the reduced neurite density index of left precentral gyrus and the reduced orientation dispersion index of left superior longitudinal fasciculus were significantly associated with elevated hyperactive/impulsive symptoms in the patients with traumatic brain injury. These findings suggest that traumatic brain injury-induced chronic neurite orientation dispersion alterations of left superior longitudinal fasciculus and left precentral may significantly contribute to post-traumatic brain injury hyperactive/impulsive behaviors in young adults with traumatic brain injury.

scholarly journals Traumatic brain injury: a comparison of diffusion and volumetric magnetic resonance imaging measures

2021 ◽  
Author(s):  
N J Bourke ◽  
M Yanez Lopez ◽  
P O Jenkins ◽  
S De Simoni ◽  
J H Cole ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
White Matter ◽  
Processing Speed ◽  
Axonal Injury ◽  
Mean Diffusivity ◽  
Dispersion Index ◽  
Neurite Density ◽  
Density Index

Abstract Cognitive impairment following traumatic brain injury remains hard to predict. This is partly because axonal injury, which is of fundamental importance, is difficult to measure clinically. Advances in MRI allow axonal injury to be detected after traumatic brain injury, but the most sensitive approach is unclear. Here we compare the performance of diffusion tensor imaging, neurite orientation dispersion and density-imaging and volumetric measures of brain atrophy in the identification of white matter abnormalities after traumatic brain injury. Thirty patients with moderate-severe traumatic brain injury in the chronic phase and 20 age-matched controls had T1-weighted and diffusion MRI. Neuropsychological tests of processing speed, executive functioning and memory were used to detect cognitive impairment. Extensive abnormalities in neurite density index and orientation dispersion index were observed, with distinct spatial patterns. Fractional anisotropy and mean diffusivity also indicated widespread abnormalities of white matter structure. Neurite density index was significantly correlated with processing speed. Slower processing speed was also related to higher mean diffusivity in the cortico-spinal tracts. Lower white matter volumes were seen following brain injury with greater effect sizes compared to diffusion metrics however volume was not sensitive to changes in cognitive performance. Volume was the most sensitive at detecting change between groups but was not specific for determining relationships with cognition. Abnormalities in fractional anisotropy and mean diffusivity were the most sensitive diffusion measures, however neurite density index and orientation dispersion index may be more spatially specific. Lower neurite density index may be a useful metric for examining slower processing speed.

scholarly journals The Evolution of White Matter Changes After Mild Traumatic Brain Injury: A DTI and NODDI Study

2018 ◽  
Author(s):  
Eva M. Palacios ◽  
Julia P Owen ◽  
Esther L. Yuh ◽  
Maxwell B. Wang ◽  
Mary J. Vassar ◽  
...  
Keyword(s):  
Machine Learning ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
Vasogenic Edema ◽  
Free Water ◽  
Cross Sectional ◽  
Neurite Density ◽  
Learning Analysis

ABSTRACTNeuroimaging biomarkers show promise for improving precision diagnosis and prognosis after mild traumatic brain injury (mTBI), but none has yet been adopted in routine clinical practice. Biophysical modeling of multishell diffusion MRI, using the neurite orientation dispersion and density imaging (NODDI) framework, may improve upon conventional diffusion tensor imaging (DTI) in revealing subtle patterns of underlying white matter microstructural pathology, such as diffuse axonal injury (DAI) and neuroinflammation, that are important for detecting mTBI and determining patient outcome. With a cross-sectional and longitudinal design, we assessed structural MRI, DTI and NODDI in 40 mTBI patients at 2 weeks and 6 months after injury and 14 matched control participants with orthopedic trauma but not suffering from mTBI at 2 weeks. Self-reported and performance-based cognitive measures assessing postconcussive symptoms, memory, executive functions and processing speed were investigated in post-acute and chronic phase after injury for the mTBI subjects. Machine learning analysis was used to identify mTBI patients with the best neuropsychological improvement over time and relate this outcome to DTI and NODDI biomarkers. In the cross-sectional comparison with the trauma control group at 2 weeks post-injury, mTBI patients showed decreased fractional anisotropy (FA) and increased mean diffusivity (MD) on DTI mainly in anterior tracts that corresponded to white matter regions of elevated free water fraction (FISO) on NODDI, signifying vasogenic edema. Patients showed decreases from 2 weeks to 6 months in white matter neurite density on NODDI, predominantly in posterior tracts. No significant longitudinal changes in DTI metrics were observed. The machine learning analysis divided the mTBI patients into two groups based on their recovery. Voxel-wise group comparison revealed associations between white matter orientation dispersion index (ODI) and FISO with degree and trajectory of improvement within the mTBI group. In conclusion, white matter FA and MD alterations early after mTBI might reflect vasogenic edema, as shown by elevated free water on NODDI. Longer-term declines in neurite density on NODDI suggest progressive axonal degeneration due to DAI, especially in tracts known to be integral to the structural connectome. Overall, these results show that the NODDI parameters appear to be more sensitive to longitudinal changes than DTI metrics. Thus, NODDI merits further study in larger cohorts for mTBI diagnosis, prognosis and treatment monitoring.

scholarly journals Diffuse axonal injury predicts neurodegeneration after moderate–severe traumatic brain injury

Brain ◽  
2020 ◽  
Author(s):  
Neil S N Graham ◽  
Amy Jolly ◽  
Karl Zimmerman ◽  
Niall J Bourke ◽  
Gregory Scott ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Severe Traumatic Brain Injury ◽  
Brain Atrophy ◽  
Diffusion Mri ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Post Traumatic

Abstract Traumatic brain injury is associated with elevated rates of neurodegenerative diseases such as Alzheimer’s disease and chronic traumatic encephalopathy. In experimental models, diffuse axonal injury triggers post-traumatic neurodegeneration, with axonal damage leading to Wallerian degeneration and toxic proteinopathies of amyloid and hyperphosphorylated tau. However, in humans the link between diffuse axonal injury and subsequent neurodegeneration has yet to be established. Here we test the hypothesis that the severity and location of diffuse axonal injury predicts the degree of progressive post-traumatic neurodegeneration. We investigated longitudinal changes in 55 patients in the chronic phase after moderate–severe traumatic brain injury and 19 healthy control subjects. Fractional anisotropy was calculated from diffusion tensor imaging as a measure of diffuse axonal injury. Jacobian determinant atrophy rates were calculated from serial volumetric T1 scans as a measure of measure post-traumatic neurodegeneration. We explored a range of potential predictors of longitudinal post-traumatic neurodegeneration and compared the variance in brain atrophy that they explained. Patients showed widespread evidence of diffuse axonal injury, with reductions of fractional anisotropy at baseline and follow-up in large parts of the white matter. No significant changes in fractional anisotropy over time were observed. In contrast, abnormally high rates of brain atrophy were seen in both the grey and white matter. The location and extent of diffuse axonal injury predicted the degree of brain atrophy: fractional anisotropy predicted progressive atrophy in both whole-brain and voxelwise analyses. The strongest relationships were seen in central white matter tracts, including the body of the corpus callosum, which are most commonly affected by diffuse axonal injury. Diffuse axonal injury predicted substantially more variability in white matter atrophy than other putative clinical or imaging measures, including baseline brain volume, age, clinical measures of injury severity and microbleeds (>50% for fractional anisotropy versus <5% for other measures). Grey matter atrophy was not predicted by diffuse axonal injury at baseline. In summary, diffusion MRI measures of diffuse axonal injury are a strong predictor of post-traumatic neurodegeneration. This supports a causal link between axonal injury and the progressive neurodegeneration that is commonly seen after moderate/severe traumatic brain injury but has been of uncertain aetiology. The assessment of diffuse axonal injury with diffusion MRI is likely to improve prognostic accuracy and help identify those at greatest neurodegenerative risk for inclusion in clinical treatment trials.

scholarly journals Genetic inactivation of SARM1 axon degeneration pathway improves outcome trajectory after experimental traumatic brain injury based on pathological, radiological, and functional measures

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Donald V. Bradshaw ◽  
Andrew K. Knutsen ◽  
Alexandru Korotcov ◽  
Genevieve M. Sullivan ◽  
Kryslaine L. Radomski ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Diffusion Tensor ◽  
Traumatic Injury ◽  
Axon Degeneration ◽  
White Matter Tracts ◽  
Sleep Behavior ◽  
Increased Risk ◽  
Post Traumatic

AbstractTraumatic brain injury (TBI) causes chronic symptoms and increased risk of neurodegeneration. Axons in white matter tracts, such as the corpus callosum (CC), are critical components of neural circuits and particularly vulnerable to TBI. Treatments are needed to protect axons from traumatic injury and mitigate post-traumatic neurodegeneration. SARM1 protein is a central driver of axon degeneration through a conserved molecular pathway. Sarm1−/− mice with knockout (KO) of the Sarm1 gene enable genetic proof-of-concept testing of the SARM1 pathway as a therapeutic target. We evaluated Sarm1 deletion effects after TBI using a concussive model that causes traumatic axonal injury and progresses to CC atrophy at 10 weeks, indicating post-traumatic neurodegeneration. Sarm1 wild-type (WT) mice developed significant CC atrophy that was reduced in Sarm1 KO mice. Ultrastructural classification of pathology of individual axons, using electron microscopy, demonstrated that Sarm1 KO preserved more intact axons and reduced damaged or demyelinated axons. Longitudinal MRI studies in live mice identified significantly reduced CC volume after TBI in Sarm1 WT mice that was attenuated in Sarm1 KO mice. MR diffusion tensor imaging detected reduced fractional anisotropy in both genotypes while axial diffusivity remained higher in Sarm1 KO mice. Immunohistochemistry revealed significant attenuation of CC atrophy, myelin loss, and neuroinflammation in Sarm1 KO mice after TBI. Functionally, Sarm1 KO mice exhibited beneficial effects in motor learning and sleep behavior. Based on these findings, Sarm1 inactivation can protect axons and white matter tracts to improve translational outcomes associated with CC atrophy and post-traumatic neurodegeneration.

scholarly journals Genetic inactivation of SARM1 axon degeneration pathway improves outcome trajectory after experimental traumatic brain injury based on pathological, radiological, and functional measures

2021 ◽  
Author(s):  
Donald V. Bradshaw ◽  
Andrew K. Knutsen ◽  
Alexandru Korotcov ◽  
Genevieve M. Sullivan ◽  
Kryslaine L. Radomski ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Diffusion Tensor ◽  
Traumatic Injury ◽  
Axon Degeneration ◽  
White Matter Tracts ◽  
Increased Risk ◽  
Post Traumatic ◽  
Critical Components

ABSTRACTTraumatic brain injury (TBI) causes chronic symptoms and increased risk of neurodegeneration. Axons in white matter tracts, such as the corpus callosum (CC), are critical components of neural circuits and particularly vulnerable to TBI. Treatments are needed to protect axons from traumatic injury and mitigate post-traumatic neurodegeneration. The Sarm1 gene is a central driver of axon degeneration through a conserved molecular pathway. Sarm1-/- mice with knockout (KO) of the Sarm1 gene enable genetic proof-of-concept testing of Sarm1 inactivation as a therapeutic target. We evaluated Sarm1 deletion effects after TBI using a concussive model that causes traumatic axonal injury and progresses to CC atrophy at 10 weeks, indicating post-traumatic neurodegeneration. Sarm1 wild-type (WT) mice developed significant CC atrophy that was reduced in Sarm1 KO mice. Using electron microscopy to quantify individual axons demonstrated that Sarm1 KO preserved more intact axons and reduced damaged or demyelinated axons. MRI in live mice identified significantly reduced CC volume after TBI in Sarm1 WT mice that was attenuated in Sarm1 KO mice. MR diffusion tensor imaging detected reduced fractional anisotropy in both genotypes while axial diffusivity remained higher in Sarm1 KO mice. Immunohistochemistry revealed significant attenuation of CC atrophy, myelin loss, and neuroinflammation in Sarm1 KO mice after TBI. Functionally, TBI resulted in late-stage motor learning and sleep deficits that were ameliorated in Sarm1 KO mice. Based on these findings, Sarm1 inactivation can protect axons and white matter tracts to improve translational outcomes associated with CC atrophy and post-traumatic neurodegeneration.

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