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Brain : a Journal of Neurology Feb 2021Poor outcomes after traumatic brain injury (TBI) are common yet remain difficult to predict. Diffuse axonal injury is important for outcomes, but its assessment remains...
Poor outcomes after traumatic brain injury (TBI) are common yet remain difficult to predict. Diffuse axonal injury is important for outcomes, but its assessment remains limited in the clinical setting. Currently, axonal injury is diagnosed based on clinical presentation, visible damage to the white matter or via surrogate markers of axonal injury such as microbleeds. These do not accurately quantify axonal injury leading to misdiagnosis in a proportion of patients. Diffusion tensor imaging provides a quantitative measure of axonal injury in vivo, with fractional anisotropy often used as a proxy for white matter damage. Diffusion imaging has been widely used in TBI but is not routinely applied clinically. This is in part because robust analysis methods to diagnose axonal injury at the individual level have not yet been developed. Here, we present a pipeline for diffusion imaging analysis designed to accurately assess the presence of axonal injury in large white matter tracts in individuals. Average fractional anisotropy is calculated from tracts selected on the basis of high test-retest reliability, good anatomical coverage and their association to cognitive and clinical impairments after TBI. We test our pipeline for common methodological issues such as the impact of varying control sample sizes, focal lesions and age-related changes to demonstrate high specificity, sensitivity and test-retest reliability. We assess 92 patients with moderate-severe TBI in the chronic phase (≥6 months post-injury), 25 patients in the subacute phase (10 days to 6 weeks post-injury) with 6-month follow-up and a large control cohort (n = 103). Evidence of axonal injury is identified in 52% of chronic and 28% of subacute patients. Those classified with axonal injury had significantly poorer cognitive and functional outcomes than those without, a difference not seen for focal lesions or microbleeds. Almost a third of patients with unremarkable standard MRIs had evidence of axonal injury, whilst 40% of patients with visible microbleeds had no diffusion evidence of axonal injury. More diffusion abnormality was seen with greater time since injury, across individuals at various chronic injury times and within individuals between subacute and 6-month scans. We provide evidence that this pipeline can be used to diagnose axonal injury in individual patients at subacute and chronic time points, and that diffusion MRI provides a sensitive and complementary measure when compared to susceptibility weighted imaging, which measures diffuse vascular injury. Guidelines for the implementation of this pipeline in a clinical setting are discussed.
Topics: Adult; Anisotropy; Axons; Brain Injuries, Traumatic; Diffusion Magnetic Resonance Imaging; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Reproducibility of Results; White Matter
PubMed: 33257929
DOI: 10.1093/brain/awaa372 -
Scientific Reports Feb 2021The ability to characterize heterogeneous and anisotropic water diffusion processes within macroscopic MRI voxels non-invasively and in vivo is a desideratum in biology,...
The ability to characterize heterogeneous and anisotropic water diffusion processes within macroscopic MRI voxels non-invasively and in vivo is a desideratum in biology, neuroscience, and medicine. While an MRI voxel may contain approximately a microliter of tissue, our goal is to examine intravoxel diffusion processes on the order of picoliters. Here we propose a new theoretical framework and efficient experimental design to describe and measure such intravoxel structural heterogeneity and anisotropy. We assume that a constrained normal tensor-variate distribution (CNTVD) describes the variability of positive definite diffusion tensors within a voxel which extends its applicability to a wide range of b-values while preserving the richness of diffusion tensor distribution (DTD) paradigm unlike existing models. We introduce a new Monte Carlo (MC) scheme to synthesize realistic 6D DTD numerical phantoms and invert the MR signal. We show that the signal inversion is well-posed and estimate the CNTVD parameters parsimoniously by exploiting the different symmetries of the mean and covariance tensors of CNTVD. The robustness of the estimation pipeline is assessed by adding noise to calculated MR signals and compared with the ground truth. A family of invariant parameters and glyphs which characterize microscopic shape, size and orientation heterogeneity within a voxel are also presented.
Topics: Algorithms; Anisotropy; Coloring Agents; Diffusion; Diffusion Tensor Imaging; Image Interpretation, Computer-Assisted
PubMed: 33531530
DOI: 10.1038/s41598-021-81264-x -
The Journal of Headache and Pain Jul 2023New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. The pathogenesis of NDPH remains...
BACKGROUND
New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. The pathogenesis of NDPH remains unclear, and there are few white matter imaging studies related to NDPH. The purpose of this study was to investigate the micro-structural abnormalities of white matter in NDPH and provided insights into the pathogenesis of this disease based on tract-based spatial statistics (TBSS).
METHODS
Twenty-one patients with NDPH and 25 healthy controls (HCs) were included in this study. T1 structural and diffusion magnetic resonance imaging (MRI) were acquired from all participants. Differences in the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) between patients with NDPH and HCs were investigated using TBSS analysis.
RESULTS
Significantly decreased FA, increased MD and RD were found in patients with NDPH compared to HCs. White matter regions overlaid with decreased FA, increased MD and RD were found in 16 white matter tracts from the Johns Hopkins University ICBM-DTI-81 White-Matter Atlas and Johns Hopkins University White-Matter Tractography Atlas. Specifically, these white matter regions included the right anterior thalamic radiation (ATR), body of the corpus callosum (BCC), bilateral cingulum, left hippocampal cingulum (CGH), left corticospinal tract (CST), forceps major, fornix, left inferior fronto-occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), left posterior limb of the internal capsule (PLIC), right retrolenticular part of the internal capsule (RPIC), splenium of the corpus callosum (SCC), right superior longitudinal fasciculus (SLF) and left uncinate fasciculus (UF). After Bonferroni correction, there were no correlations between the FA, MD, AD and RD values and the clinical characteristics of patients with NDPH (p > 0.05/96).
CONCLUSION
The results of our research indicated that patients with NDPH might have widespread abnormalities in the white matter of the brain.
Topics: Humans; White Matter; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; Nerve Fibers; Anisotropy; Headache; Brain
PubMed: 37394419
DOI: 10.1186/s10194-023-01620-2 -
Magnetic Resonance in Medicine Jan 2021To demonstrate an optimized rectification strategy for fiber orientation density functions (fODFs).
PURPOSE
To demonstrate an optimized rectification strategy for fiber orientation density functions (fODFs).
THEORY AND METHODS
In white matter, fODFs can be estimated with diffusion MRI. However, because of signal noise, imaging artifacts and other factors, experimentally determined fODFs may take on unphysical negative values in some directions. Here, we show how to rectify such fODFs to eliminate all negative values while minimizing the mean square difference between the original and rectified fODFs. The method is demonstrated for a mathematical model and for fODFs estimated from experimental human data using both constrained spherical deconvolution and fiber ball imaging. Comparison with an alternative nonoptimized rectification approach is also provided.
RESULTS
For the mathematical model, it is found that the optimized rectification procedure removes negative fODF values while at the same time reducing the mean square error. Relative to the alternative rectification approach, the optimized fODFs are substantially more accurate. For the experimental data, the optimized fODFs have a lower average fractional anisotropy axonal and often fewer small peaks than the original, unrectified fODFs. The calculation of optimized fODFs is straightforward where the main step is the finding of the root to an equation in one variable, as may be efficiently accomplished with the bisection method.
CONCLUSION
Unphysical negative fODF values can be easily eliminated in a manner that minimizes the mean square difference between the original and rectified fODFs. Optimized fODF rectification may be useful in applications for which negative values are problematic.
Topics: Anisotropy; Axons; Brain; Diffusion Magnetic Resonance Imaging; Humans; Image Processing, Computer-Assisted; White Matter
PubMed: 32710476
DOI: 10.1002/mrm.28406 -
Magnetic Resonance in Medicine Aug 2021Reperfusion therapy enables effective treatment of ischemic stroke presenting within 4-6 hours. However, tissue progression from ischemia to infarction is variable, and...
PURPOSE
Reperfusion therapy enables effective treatment of ischemic stroke presenting within 4-6 hours. However, tissue progression from ischemia to infarction is variable, and some patients benefit from treatment up until 24 hours. Improved imaging techniques are needed to identify these patients. Here, it was hypothesized that time dependence in diffusion MRI may predict tissue outcome in ischemic stroke.
METHODS
Diffusion MRI data were acquired with multiple diffusion times in five non-reperfused patients at 2, 9, and 100 days after stroke onset. Maps of "rate of kurtosis change" (k), mean kurtosis, ADC, and fractional anisotropy were derived. The ADC maps defined lesions, normal-appearing tissue, and the lesion tissue that would either be infarcted or remain viable by day 100. Diffusion parameters were compared (1) between lesions and normal-appearing tissue, and (2) between lesion tissue that would be infarcted or remain viable.
RESULTS
Positive values of k were observed within stroke lesions on day 2 (P = .001) and on day 9 (P = .023), indicating diffusional exchange. On day 100, high ADC values indicated infarction of 50 ± 20% of the lesion volumes. Tissue infarction was predicted by high k values both on day 2 (P = .026) and on day 9 (P = .046), by low mean kurtosis values on day 2 (P = .043), and by low fractional anisotropy values on day 9 (P = .029), but not by low ADC values.
CONCLUSIONS
Diffusion time dependence predicted tissue outcome in ischemic stroke more accurately than the ADC, and may be useful for predicting reperfusion benefit.
Topics: Anisotropy; Brain Ischemia; Diffusion; Diffusion Magnetic Resonance Imaging; Humans; Ischemic Stroke; Stroke
PubMed: 33755261
DOI: 10.1002/mrm.28743 -
Alzheimer's Research & Therapy Feb 2023Neuropsychology and imaging changes have been reported in the preclinical stage of familial Alzheimer's disease (FAD). This study investigated the effects of APOEε4 and...
BACKGROUND
Neuropsychology and imaging changes have been reported in the preclinical stage of familial Alzheimer's disease (FAD). This study investigated the effects of APOEε4 and known pathogenic gene mutation on different cognitive domains and circuit imaging markers in preclinical FAD.
METHODS
One hundred thirty-nine asymptomatic subjects in FAD families, including 26 APOEε4 carriers, 17 APP and 20 PS1 mutation carriers, and 76 control subjects, went through a series of neuropsychological tests and MRI scanning. Test scores and imaging measures including volumes, diffusion indices, and functional connectivity (FC) of frontostriatal and hippocampus to posterior cingulate cortex pathways were compared between groups and analyzed for correlation.
RESULTS
Compared with controls, the APOEε4 group showed increased hippocampal volume and decreased FC of fronto-caudate pathway. The APP group showed increased recall scores in auditory verbal learning test, decreased fiber number, and increased radial diffusivity and FC of frontostriatal pathway. All three genetic groups showed decreased fractional anisotropy of hippocampus to posterior cingulate cortex pathway. These neuropsychological and imaging measures were able to discriminate genetic groups from controls, with areas under the curve from 0.733 to 0.837. Circuit imaging measures are differentially associated with scores in various cognitive scales in control and genetic groups.
CONCLUSIONS
There are neuropsychological and imaging changes in the preclinical stage of FAD, some of which are shared by APOEε4 and known pathogenic gene mutation, while some are unique to different genetic groups. These findings are helpful for the early identification of Alzheimer's disease and for developing generalized and individualized prevention and intervention strategies.
Topics: Humans; Alzheimer Disease; Cognition; Anisotropy; Gyrus Cinguli; Mutation
PubMed: 36850008
DOI: 10.1186/s13195-023-01192-y -
PloS One 2023Diffusion MRI classically uses gradient fields that vary linearly in space to encode the diffusion of water molecules in the signal magnitude by tempering its intensity....
Diffusion MRI classically uses gradient fields that vary linearly in space to encode the diffusion of water molecules in the signal magnitude by tempering its intensity. In spin ensembles, a presumably equal number of particles move in positive and negative direction, resulting in approximately zero change in net phase. Hence, in classical diffusion weighted MRI with a linear gradient field, the phase does not carry any information as the incoherent motion of the spins only impacts the magnitude of the signal. Conversely, when the linear gradient field is replaced with one that varies quadratically over space, the diffusion of water molecules in anisotropic media does give rise to a change in net phase and preserves large portion of the signal around the saddle point of the gradient field. In this work, the phase evolution of anisotropic fibre phantoms in the presence of quadratic gradient fields was studied in Monte Carlo simulations and diffusion MRI experiments. The simulations confirm the dependence of the phase change on the degree of anisotropy of the media and the diffusion weighting, as predicted by the derived analytic model. First MR experiments show a phase change depending on the diffusion time in an anisotropic synthetic fibre phantom, and approximately zero phase change for the experiment repeated in an isotropic agar phantom. As predicted by the analytic model, an increase of the diffusion time by approximately a factor of two leads to an increase of approximately a factor of two in the signal phase.
Topics: Anisotropy; Diffusion Magnetic Resonance Imaging; Phantoms, Imaging; Diffusion; Water
PubMed: 36996066
DOI: 10.1371/journal.pone.0281332 -
Human Brain Mapping Oct 2022Accelerated maturation of brain parenchyma close to term-equivalent age leads to rapid changes in diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI)...
Accelerated maturation of brain parenchyma close to term-equivalent age leads to rapid changes in diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) metrics of neonatal brains, which can complicate the evaluation and interpretation of these scans. In this study, we characterized the topography of age-related evolution of diffusion metrics in neonatal brains. We included 565 neonates who had MRI between 0 and 3 months of age, with no structural or signal abnormality-including 162 who had DTI scans. We analyzed the age-related changes of apparent diffusion coefficient (ADC) values throughout brain and DTI metrics (fractional anisotropy [FA] and mean diffusivity [MD]) along white matter (WM) tracts. Rate of change in ADC, FA, and MD values across 5 mm cubic voxels was calculated. There was significant reduction of ADC and MD values and increase of FA with increasing gestational age (GA) throughout neonates' brain, with the highest temporal rates in subcortical WM, corticospinal tract, cerebellar WM, and vermis. GA at birth had significant effect on ADC values in convexity cortex and corpus callosum as well as FA/MD values in corpus callosum, after correcting for GA at scan. We developed online interactive atlases depicting age-specific normative values of ADC (ages 34-46 weeks), and FA/MD (35-41 weeks). Our results show a rapid decrease in diffusivity metrics of cerebral/cerebellar WM and vermis in the first few weeks of neonatal age, likely attributable to myelination. In addition, prematurity and low GA at birth may result in lasting delay in corpus callosum myelination and cerebral cortex cellularity.
Topics: Anisotropy; Brain; Child, Preschool; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; White Matter
PubMed: 35599634
DOI: 10.1002/hbm.25956 -
Human Brain Mapping Feb 2023Sex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion-weighted magnetic...
Sex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion-weighted magnetic resonance imaging approaches. However, sex differences in white matter microstructure prior to adulthood remain poorly understood; previous developmental work focused on conventional microstructure metrics and yielded mixed results. Here, we rigorously characterized sex differences in white matter microstructure among over 6000 children from the Adolescent Brain Cognitive Development study who were between 9 and 10 years old. Microstructure was quantified using both the conventional model-diffusion tensor imaging (DTI)-and an advanced model, restriction spectrum imaging (RSI). DTI metrics included fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). RSI metrics included normalized isotropic, directional, and total intracellular diffusion (N0, ND, NT). We found significant and replicable sex differences in DTI or RSI microstructure metrics in every white matter region examined across the brain. Sex differences in FA were regionally specific. Across white matter regions, boys exhibited greater MD, AD, and RD than girls, on average. Girls displayed increased N0, ND, and NT compared to boys, on average, suggesting greater cell and neurite density in girls. Together, these robust and replicable findings provide an important foundation for understanding sex differences in health and disease.
Topics: Adult; Adolescent; Humans; Child; Male; Female; White Matter; Diffusion Tensor Imaging; Sex Characteristics; Brain; Diffusion Magnetic Resonance Imaging; Anisotropy
PubMed: 36177528
DOI: 10.1002/hbm.26079 -
Molecular Psychiatry Apr 2024Previous diffusion MRI studies have reported mixed findings on white matter microstructure alterations in obsessive-compulsive disorder (OCD), likely due to variation in...
Previous diffusion MRI studies have reported mixed findings on white matter microstructure alterations in obsessive-compulsive disorder (OCD), likely due to variation in demographic and clinical characteristics, scanning methods, and underpowered samples. The OCD global study was created across five international sites to overcome these challenges by harmonizing data collection to identify consistent brain signatures of OCD that are reproducible and generalizable. Single-shell diffusion measures (e.g., fractional anisotropy), multi-shell Neurite Orientation Dispersion and Density Imaging (NODDI) and fixel-based measures, were extracted from skeletonized white matter tracts in 260 medication-free adults with OCD and 252 healthy controls. We additionally performed structural connectome analysis. We compared cases with controls and cases with early (<18) versus late (18+) OCD onset using mixed-model and Bayesian multilevel analysis. Compared with healthy controls, adult OCD individuals showed higher fiber density in the sagittal stratum (B[SE] = 0.10[0.05], P = 0.04) and credible evidence for higher fiber density in several other tracts. When comparing early (n = 145) and late-onset (n = 114) cases, converging evidence showed lower integrity of the posterior thalamic radiation -particularly radial diffusivity (B[SE] = 0.28[0.12], P = 0.03)-and lower global efficiency of the structural connectome (B[SE] = 15.3[6.6], P = 0.03) in late-onset cases. Post-hoc analyses indicated divergent direction of effects of the two OCD groups compared to healthy controls. Age of OCD onset differentially affects the integrity of thalamo-parietal/occipital tracts and the efficiency of the structural brain network. These results lend further support for the role of the thalamus and its afferent fibers and visual attentional processes in the pathophysiology of OCD.
Topics: Humans; Obsessive-Compulsive Disorder; White Matter; Adult; Male; Female; Age of Onset; Connectome; Diffusion Tensor Imaging; Brain; Middle Aged; Diffusion Magnetic Resonance Imaging; Young Adult; Anisotropy; Bayes Theorem; Case-Control Studies; Adolescent
PubMed: 38228890
DOI: 10.1038/s41380-023-02390-8