White Matter Microstructural Properties Research Articles

Tracts in the limbic system show microstructural alterations post COVID-19 recovery.

Delirium, memory loss, attention deficit and fatigue are frequently reported by COVID survivors, yet the neurological pathways underlying these symptoms are not well understood. To study the possible mechanisms for these long-term sequelae after COVID-19 recovery, we investigated the microstructural properties of white matter in Indian cohorts of COVID-recovered patients and healthy controls. For the cross-sectional study presented here, we recruited 44 COVID-recovered patients and 29 healthy controls in New Delhi, India. Using deterministic whole-brain tractography on the acquired diffusion MRI scans, we traced 20 white matter tracts and compared fractional anisotropy, axial, mean and radial diffusivity between the cohorts. Our results revealed statistically significant differences (PFWE < 0.01) in the uncinate fasciculus, cingulum cingulate, cingulum hippocampus and arcuate fasciculus in COVID survivors, suggesting the presence of microstructural abnormalities. Additionally, in a subsequent subgroup analysis based on infection severity (healthy control, non-hospitalized patients and hospitalized patients), we observed a correlation between tract diffusion measures and COVID-19 infection severity. Although there were significant differences between healthy controls and infected groups, we found no significant differences between hospitalized and non-hospitalized COVID patients. Notably, the identified tracts are part of the limbic system and orbitofrontal cortex, indicating microstructural differences in neural circuits associated with memory and emotion. The observed white matter alterations in the limbic system resonate strongly with the functional deficits reported in Long COVID. Overall, our study provides additional evidence that damage to the limbic system could be a neuroimaging signature of Long COVID. The findings identify targets for follow-up studies investigating the long-term physiological and psychological impact of COVID-19.

Structural white matter properties and cognitive resilience to tau pathology.

We assessed whether macro- and/or micro-structural white matter properties are associated with cognitive resilience to Alzheimer's disease pathology years prior to clinical onset. We examined whether global efficiency, an indicator of communication efficiency in brain networks, and diffusion measurements within the limbic network and default mode network moderate the association between amyloid-β/tau pathology and cognitive decline. We also investigated whether demographic and health/risk factors are associated with white matter properties. Higher global efficiency of the limbic network, as well as free-water corrected diffusion measures within the tracts of both networks, attenuated the impact of tau pathology on memory decline. Education, age, sex, white matter hyperintensities, and vascular risk factors were associated with white matter properties of both networks. White matter can influence cognitive resilience against tau pathology, and promoting education and vascular health may enhance optimal white matter properties. Aβ and tau were associated with longitudinal memory change over ∼7.5 years. White matter properties attenuated the impact of tau pathology on memory change. Health/risk factors were associated with white matter properties.

White matter trajectories over the lifespan.

White matter (WM) changes occur throughout the lifespan at a different rate for each developmental period. We aggregated 10879 structural MRIs and 6186 diffusion-weighted MRIs from participants between 2 weeks to 100 years of age. Age-related changes in gray matter and WM partial volumes and microstructural WM properties, both brain-wide and on 29 reconstructed tracts, were investigated as a function of biological sex and hemisphere, when appropriate. We investigated the curve fit that would best explain age-related differences by fitting linear, cubic, quadratic, and exponential models to macro and microstructural WM properties. Following the first steep increase in WM volume during infancy and childhood, the rate of development slows down in adulthood and decreases with aging. Similarly, microstructural properties of WM, particularly fractional anisotropy (FA) and mean diffusivity (MD), follow independent rates of change across the lifespan. The overall increase in FA and decrease in MD are modulated by demographic factors, such as the participant's age, and show different hemispheric asymmetries in some association tracts reconstructed via probabilistic tractography. All changes in WM macro and microstructure seem to follow nonlinear trajectories, which also differ based on the considered metric. Exponential changes occurred for the WM volume and FA and MD values in the first five years of life. Collectively, these results provide novel insight into how changes in different metrics of WM occur when a lifespan approach is considered.

Unique information from common diffusion MRI models about white-matter differences across the human adult lifespan

Abstract Diffusion Magnetic Resonance Imaging (dMRI) is sensitive to white matter microstructural changes across the human lifespan. Several models have been proposed to provide more sensitive and specific metrics than those provided by the conventional Diffusion Tensor Imaging (DTI) analysis. However, previous results using different metrics have led to contradictory conclusions regarding the effect of age on fibre demyelination and axonal loss in adults. Moreover, it remains unclear whether these metrics provide distinct information about the effects of age, for example, on different white-matter tracts. To address this, we analysed dMRI data from 651 adults approximately uniformly aged from 18 to 88 years in the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) cohort, using six dMRI metrics: Fractional Anisotropy (FA) from standard DTI; Mean Signal Diffusion (MSD) and Mean Signal Kurtosis (MSK) from Diffusional Kurtosis Imaging (DKI) applied to directional averaged diffusion-weighted signals; and Neurite Density Index (NDI), Orientation Dispersion Index (ODI), and isotropic Free water volume fraction (Fiso) estimated from Neurite Orientation Dispersion and Density Imaging (NODDI). Averaging across white-matter regions-of-interest (ROIs), second-order polynomial fits revealed that MSD, MSK, and Fiso showed the strongest effects of age, with significant quadratic components suggesting more rapid and sometimes inverted effects in old age. Analysing the data in different age subgroups revealed that some apparent discrepancies in previous studies may be explained by the use of cohorts with different age ranges. Factor analysis of the six metrics across all ROIs revealed three independent factors that can be associated to 1) tissue microscopic properties (e.g., differences in fibre density/myelin), 2) free-water contamination, and 3) tissue configuration complexity (e.g., crossing, dispersing, fanning fibres). While FA captures a combination of different factors, other dMRI metrics are strongly aligned to specific factors (NDI and MSK with Factor 1, Fiso with Factor 2, and ODI with Factor 3). To assess whether directional diffusion and kurtosis quantities provide additional information about the effects of age, further factor analyses were also performed, which showed that additional information about the effects of age may be present in radial and axial kurtosis estimates (but not standard axial and radial diffusivity). In summary, our study offers an explanation for previous discrepancies reported in dMRI ageing studies and provides further insights on the interpretation of different dMRI metrics in the context of white-matter microstructural properties.

What lies beneath: White matter microstructure in pediatric myalgic encephalomyelitis/chronic fatigue syndrome using diffusion MRI.

Recent studies in adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggest that changes in brain white matter microstructural organization may correlate with core ME/CFS symptoms, and represent a potential biomarker of disease. However, this has yet to be investigated in the pediatric ME/CFS population. We examined group differences in macrostructural and microstructural white matter properties, and their relationship with clinical measures, between adolescents recently diagnosed with ME/CFS and healthy controls. Forty-eight adolescents (25 ME/CFS, 23 controls, mean age 16 years) underwent brain diffusion MRI, and a robust multi-analytic approach was used to evaluate white and gray matter volume, regional brain volume, cortical thickness, fractional anisotropy, mean/axial/radial diffusivity, neurite dispersion and density, fiber density, and fiber cross section. From a clinical perspective, adolescents with ME/CFS showed greater fatigue and pain, poorer sleep quality, and poorer performance on cognitive measures of processing speed and sustained attention compared with controls. However, no significant group differences in white matter properties were observed, with the exception of greater white matter fiber cross section of the left inferior longitudinal fasciculus in the ME/CFS group compared with controls, which did not survive correction for intracranial volume. Overall, our findings suggest that white matter abnormalities may not be predominant in pediatric ME/CFS in the early stages following diagnosis. The discrepancy between our null findings and white matter abnormalities identified in the adult ME/CFS literature could suggest that older age and/or longer illness duration influence changes in brain structure and brain-behavior relationships that are not yet established in adolescence.

Face recognition ability can be predicted by microstructural properties of white matter: a study of diffusion tensor imaging (DTI).

There is a great individual difference in people's face recognition ability (FRA). This study aimed to reveal the neural mechanism underlying such individual differences. Elastic-net regression models were constructed to predict FRA based on the white matter (WM) microstructural properties. We found that FRA can be accurately predicted by the WM microstructural properties. For the right inferior longitudinal fasciculus (ILF) and bilateral arcuate fasciculus (AF), FRA was correlated negatively to fractional anisotropy (FA), but positively to radial diffusivity (RD). In contrast, for the corpus callosum forceps minor (CFM), FRA was correlated positively to FA, but negatively to RD. Such various patterns of the WM microstructural properties suggested a positive correlation between FRA and fiber diameter for the right ILF and bilateral AF, but a negative correlation between FRA and diameter of the CFM. These findings reflected that FRA was correlated positively to connectivities of the right ILF and bilateral AF, but negatively to those of the CFM. These findings not only confirmed the significant role of the right ILF in face recognition, but also revealed the involvement of the bilateral AF and CFM in face recognition, particularly implying the important role of hemisphere lateralization modulated by transcallosal connectivity in face recognition.

The effects of puberty and sex on adolescent white matter development: A systematic review

Adolescence, the transition between childhood and adulthood, is characterized by rapid brain development in white matter (WM) that is attributed in part to rising levels in adrenal and gonadal hormones. The extent to which pubertal hormones and related neuroendocrine processes explain sex differences in WM during this period is unclear. In this systematic review, we sought to examine whether there are consistent associations between hormonal changes and morphological and microstructural properties of WM across species and whether these effects are sex-specific. We identified 90 (75 human, 15 non-human) studies that met inclusion criteria for our analyses. While studies in human adolescents show notable heterogeneity, results broadly demonstrate that increases in gonadal hormones across pubertal development are associated with macro- and microstructural changes in WM tracts that are consistent with the sex differences found in non-human animals, particularly in the corpus callosum. We discuss limitations of the current state of the science and recommend important future directions for investigators in the field to consider in order to advance our understanding of the neuroscience of puberty and to promote forward and backward translation across model organisms.

Brainstem white matter microstructure is associated with hyporesponsiveness and overall sensory features in autistic children

BackgroundElevated or reduced responses to sensory stimuli, known as sensory features, are common in autistic individuals and often impact quality of life. Little is known about the neurobiological basis of sensory features in autistic children. However, the brainstem may offer critical insights as it has been associated with both basic sensory processing and core features of autism.MethodsDiffusion-weighted imaging (DWI) and parent-report of sensory features were acquired from 133 children (61 autistic children with and 72 non-autistic children, 6–11 years-old). Leveraging novel DWI processing techniques, we investigated the relationship between sensory features and white matter microstructure properties (free-water-elimination-corrected fractional anisotropy [FA] and mean diffusivity [MD]) in precisely delineated brainstem white matter tracts. Follow-up analyses assessed relationships between microstructure and sensory response patterns/modalities and analyzed whole brain white matter using voxel-based analysis.ResultsResults revealed distinct relationships between brainstem microstructure and sensory features in autistic children compared to non-autistic children. In autistic children, more prominent sensory features were generally associated with lower MD. Further, in autistic children, sensory hyporesponsiveness and tactile responsivity were strongly associated with white matter microstructure in nearly all brainstem tracts. Follow-up voxel-based analyses confirmed that these relationships were more prominent in the brainstem/cerebellum, with additional sensory-brain findings in the autistic group in the white matter of the primary motor and somatosensory cortices, the occipital lobe, the inferior parietal lobe, and the thalamic projections.LimitationsAll participants communicated via spoken language and acclimated to the sensory environment of an MRI session, which should be considered when assessing the generalizability of this work to the whole of the autism spectrum.ConclusionsThese findings suggest unique brainstem white matter contributions to sensory features in autistic children compared to non-autistic children. The brainstem correlates of sensory features underscore the potential reflex-like nature of behavioral responses to sensory stimuli in autism and have implications for how we conceptualize and address sensory features in autistic populations.

Blood pressure changes impact corticospinal integrity and downstream gait and balance control

Blood pressure (BP) plays an important role in white matter integrity. We sought to determine the role of intra-individual BP changes on white matter and evaluate the impact on gait speed and imbalance by sex. We identified 990 eligible participants in the population-based Mayo Clinic Study of Aging and analyzed fractional anisotropy (FA) in white matter regions. Using structural equation models (SEM), we assessed the effect of BP slope on corticospinal tract (CST) FA and downstream effects on gait speed and imbalance after age and sex effects. Of 990 participants, 438 (44%) were female with mean age of 76 years. In linear models predicting CST FA, a greater change in BP slope (0.0004; p = 0.026) and female sex (0.017; p < 0.001) were significant predictors of lower CST FA. SEMs showed that older age, female sex, and higher BP slope predicted lower CST FA, and lower CST FA predicted worse downstream motor control. Therefore, intra-individual BP slope and variability impact corticospinal tract microstructural properties of white matter with females having increased susceptibility to damage.

Altered MRI Diffusion Properties of the White Matter Tracts Connecting Frontal and Thalamic Brain Regions in First-Episode, Drug-Naïve Patients With Postpartum Depression.

Although progress has been made in exploring postpartum depression (PPD), the involvement of cerebral structure connectivity in PPD patients keeps unclear. To explore structural connectivity alternations in mothers with PPD, diffusion tensor imaging (DTI) and automated fiber quantification (AFQ) were used to calculate brain white matter microstructure properties. Cross-sectional. A total of 51 women with first-episode, treatment-näive PPD, and 49 matched healthy postpartum women (HPW) controls. A 3.0 T; single-shot echo-planar imaging sequence. DTI measurements of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were obtained for 18 specific white matter tracts. The relationship between PDD symptoms, hormone levels, and postpartum days was also investigated. Two sample t test and Pearson's correlation analysis. The analysis was performed by using a permutation-based multiple-comparison correction approach, with the threshold of P < 0.05 (family wise error corrected [FWE-corrected]) separately across the four different outcome measures. Women with PPD showed significantly increased FA and AD in right anterior thalamic radiation (ATR) tract and significantly increased FA and significantly reduced RD in the cingulum tract, compared to women without PPD. The RD values of right cingulum were significantly positively correlated with postpartum days in HPW (r=0.39). There were no significant relationships between brain measures and hormone levels in either patients or controls. DTI measures have revealed altered integrity in the white matter of the cortical-thalamic circuits in women with PPD compared to HPW. Damage to these circuits may be a structural basis for the impaired emotional regulation and blunted mother-infant bonding in mothers with PPD and a potential target for the development of new treatments. 2 TECHNICAL EFFICACY: Stage 3.

Alterations in white matter microstructural properties after lingual strength exercise in patients with dysphagia.

Central nervous system effects of lingual strengthening exercise to treat dysphagia remain largely unknown. This pilot study measured changes in microstructural white matter to capture alterations in neural signal processing following lingual strengthening exercise. Diffusion-weighted images were acquired from seven participants with dysphagia of varying etiologies, before and after lingual strengthening exercise (20 reps, 3×/day, 3 days/week, 8 weeks), using a 10-min diffusion sequence (9 b0, 56 directions with b1000) on GE750 3T scanner. Tract-Based Spatial Statistics evaluated voxel-based group differences for fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity and local diffusion homogeneity (LDH). Paired t-tests evaluated treatment differences on each metric (P < 0.05). After lingual strengthening exercise, lingual pressure generation increased (avg increase = 46.1 hPa; nonsignificant P = 0.52) with these changes in imaging metrics: (1) decrease in fractional anisotropy, forceps minor; (2) increase in mean diffusivity, right inferior fronto-occipital fasciculus (IFOF); (3) decrease in mean diffusivity, left uncinate fasciculus; (4) decrease in axial diffusivity, both left IFOF and left uncinate fasciculus; (5) increase in LDH, right anterior thalamic radiation and (6) decrease in LDH, temporal portion of right superior longitudinal fasciculus. There was a positive correlation between diffusion tensor imaging metrics and change in lingual pressure generation in left IFOF and the temporal portion of right superior longitudinal fasciculus. These findings suggest that lingual strengthening exercise can induce changes in white matter structural and functional properties in a small group of patients with dysphagia of heterogeneous etiologies. These procedures should be repeated with a larger group of patients to improve interpretation of overall lingual strengthening exercise effects on cortical structure and function.

Sex interaction of white matter microstructure and verbal IQ in corpus callosum in typically developing children and adolescents

BackgroundChildhood is an extremely important time for neural development that has a critical role in human intelligence. Efficient information processing is crucial for higher intelligence, so the intra- or inter-hemispheric interaction is vital. However, the relationship between neuroanatomical connections and intelligence in typically developing children, as well as sex differences in this relationship, remains unknown. MethodsParticipants were 253 typically developing children (121 boys and 132 girls) aged 5–18. We acquired diffusion tensor imaging data and intelligence using an age-appropriate version of the IQ test; Wechsler Intelligence Scale for Children (WISC) or Wechsler Adult Intelligence Scale (WAIS). We conducted whole-brain multiple regression analysis to investigate the association between fractional anisotropy (FA), which reflects white matter microstructural properties, and each composite score of IQ test (full-scale IQ, performance IQ, and verbal IQ). ResultsFA was positively correlated with full-scale IQ in bilateral inferior occipitofrontal fasciculus, genu, and splenium of corpus callosum (CC). FA in the right superior longitudinal fasciculus, bilateral inferior longitudinal fasciculus, and splenium of CC were also positively correlated with performance IQ. Furthermore, we found significant sex interaction between FA in the CC and verbal IQ. FA was positively correlated in boys, and negatively correlated in girls. ConclusionResults suggest that efficient anatomical connectivity between parietal and frontal regions is crucial for children’s intelligence. Moreover, inter-hemispheric connections play a critical role in verbal abilities in boys.

Brain tissue microstructural and free-water composition 13 years after very preterm birth

There have been many studies demonstrating children born very preterm exhibit brain white matter microstructural alterations, which have been related to neurodevelopmental difficulties. These prior studies have often been based on diffusion MRI modelling and analysis techniques, which commonly focussed on white matter microstructural properties in children born very preterm. However, there have been relatively fewer studies investigating the free-water content of the white matter, and also the microstructure and free-water content of the cortical grey matter, in children born very preterm. These biophysical properties of the brain change rapidly during fetal and neonatal brain development, and therefore such properties are likely also adversely affected by very preterm birth. In this study, we investigated the relationship of very preterm birth (<30 weeks’ gestation) to both white matter and cortical grey matter microstructure and free-water content in childhood using advanced diffusion MRI analyses. A total of 130 very preterm participants and 45 full-term control participants underwent diffusion MRI at age 13 years. Diffusion tissue signal fractions derived by Single-Shell 3-Tissue Constrained Spherical Deconvolution were used to investigate brain tissue microstructural and free-water composition. The tissue microstructural and free-water composition metrics were analysed using a voxel-based analysis and cortical region-of-interest analysis approach. Very preterm 13-year-olds exhibited reduced white matter microstructural density and increased free-water content across widespread regions of the white matter compared with controls. Additionally, very preterm 13-year-olds exhibited reduced microstructural density and increased free-water content in specific temporal, frontal, occipital and cingulate cortical regions. These brain tissue composition alterations were strongly associated with cerebral white matter abnormalities identified in the neonatal period, and concurrent adverse cognitive and motor outcomes in very preterm children. The findings demonstrate brain microstructural and free-water alterations up to thirteen years from neonatal brain abnormalities in very preterm children that relate to adverse neurodevelopmental outcomes.

Diffusion Tensor Based White Matter Tract Atlases for Pediatric Populations.

Diffusion Tensor Imaging (DTI) is a non-invasive neuroimaging method that has become the most widely employed MRI modality for investigations of white matter fiber pathways. DTI has proven especially valuable for improving our understanding of normative white matter maturation across the life span and has also been used to index clinical pathology and cognitive function. Despite its increasing popularity, especially in pediatric research, the majority of existing studies examining infant white matter maturation depend on regional or white matter skeleton-based approaches. These methods generally lack the sensitivity and spatial specificity of more advanced functional analysis options that provide information about microstructural properties of white matter along fiber bundles. DTI studies of early postnatal brain development show that profound microstructural and maturational changes take place during the first two years of life. The pattern and rate of these changes vary greatly throughout the brain during this time compared to the rest of the life span. For this reason, appropriate image processing of infant MR imaging requires the use of age-specific reference atlases. This article provides an overview of the pre-processing, atlas building, and the fiber tractography procedures used to generate two atlas resources, one for neonates and one for 1- to 2-year-old populations. Via the UNC-NAMIC DTI Fiber Analysis Framework, our pediatric atlases provide the computational templates necessary for the fully automatic analysis of infant DTI data. To the best of our knowledge, these atlases are the first comprehensive population diffusion fiber atlases in early pediatric ages that are publicly available.

Microstructural Properties of Human Brain Revealed by Fractional Anisotropy Can Predict the After-Effect of Intermittent Theta Burst Stimulation.

Intermittent theta burst stimulation (iTBS) delivered by transcranial magnetic stimulation (TMS) produces a long-term potentiation-like after-effect useful for investigations of cortical function and of potential therapeutic value. However, the iTBS after-effect over the primary motor cortex (M1) as measured by changes in motor evoked potential (MEP) amplitude exhibits a largely unexplained variability across individuals. Here, we present evidence that individual differences in white matter (WM) and gray matter (GM) microstructural properties revealed by fractional anisotropy (FA) predict the magnitude of the iTBS-induced after-effect over M1. The MEP amplitude change in the early phase (5–10 min post-iTBS) was associated with FA values in WM tracts such as right superior longitudinal fasciculus and corpus callosum. By contrast, the MEP amplitude change in the late phase (15–30 min post-iTBS) was associated with FA in GM, primarily in right frontal cortex. These results suggest that the microstructural properties of regions connected directly or indirectly to the target region (M1) are crucial determinants of the iTBS after-effect. FA values indicative of these microstructural differences can predict the potential effectiveness of repetitive TMS for both investigational use and clinical application.

Association of Outdoor Ambient Fine Particulate Matter With Intracellular White Matter Microstructural Properties Among Children

Outdoor particulate matter 2.5 μm or less in diameter (PM2.5) is a ubiquitous environmental neurotoxicant that may affect the developing brain. Little is known about associations between PM2.5 and white matter connectivity. To assess associations between annual residential PM2.5 exposure and white matter microstructure health in a US sample of children 9 to 10 years of age and to examine whether associations are specific to certain white matter pathways or vary across neuroimaging diffusion markers reflective of intracellular and extracellular microstructural processes. This cross-sectional study, the Adolescent Brain and Cognitive Development (ABCD) Study, was composed of 21 study sites across the US and used baseline data collected from children 9 to 10 years of age from September 1, 2016, to October 15, 2018. Data analysis was performed from September 15, 2020, to June 30, 2021. Annual mean PM2.5 exposure estimated by ensemble-based models and assigned to the primary residential addresses at baseline. Diffusion-weighted imaging (DWI) and tractography were used to delineate white matter tracts. The biophysical modeling technique of restriction spectrum imaging (RSI) was implemented to examine total hindered diffusion and restricted isotropic and anisotropic intracellular diffusion in each tract. Hierarchical mixed-effects models with natural splines were used to analyze the associations between PM2.5 exposure and DWI. In a study population of 7602 children (mean [SD] age, 119.1 [7.42] months; 3955 [52.0%] female; 160 [ 21.%] Asian, 1025 [13.5%] Black, 1616 [21.3%] Hispanic, 4025 [52.9%] White, and 774 [10.2%] other [identified by parents as American Indian/Native American or Alaska Native; Native Hawaiian, Guamanian, Samoan, other Pacific Islander; Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, or other Asian; or other race]), associations were seen between annual ambient PM2.5 and hemispheric differences in white matter microstructure. Hemisphere-stratified models revealed significant associations between PM2.5 exposure and restricted isotropic intracellular diffusion in the left cingulum, in the left superior longitudinal fasciculus, and bilaterally in the fornix and uncinate fasciculus. In tracts with strong positive associations, a PM2.5 increase from 8 to 12 μg/m3 was associated with increases of 2.16% (95% CI, 0.49%-3.84%) in the left cingulum, 1.95% (95% CI, 0.43%-3.47%) in the left uncinate, and 1.68% (95% CI, 0.01%-3.34%) in the right uncinate. Widespread negative associations were observed between PM2.5 and mean diffusivity. The findings of this cross-sectional study suggest that annual mean PM2.5 exposure during childhood is associated with increased restricted isotropic diffusion and decreased mean diffusivity of specific white matter tracts, potentially reflecting differences in the composition of white matter microarchitecture.

Insights into human cerebral white matter maturation and degeneration across the adult lifespan

White matter (WM) microstructural properties change across the adult lifespan and with neuronal diseases. Understanding microstructural changes due to aging is paramount to distinguish them from neuropathological changes. Conducted on a large cohort of 147 cognitively unimpaired subjects, spanning a wide age range of 21 to 94 years, our study evaluated sex- and age-related differences in WM microstructure. Specifically, we used diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) indices, sensitive measures of myelin and axonal density in WM, and myelin water fraction (MWF), a measure of the fraction of the signal of water trapped within the myelin sheets, to probe these differences. Furthermore, we examined regional correlations between MWF and DTI indices to evaluate whether the DTI metrics provide information complementary to MWF. While sexual dimorphism was, overall, nonsignificant, we observed region-dependent differences in MWF, that is, myelin content, and axonal density with age and found that both exhibit nonlinear, but distinct, associations with age. Furthermore, DTI indices were moderately correlated with MWF, indicating their good sensitivity to myelin content as well as to other constituents of WM tissue such as axonal density. The microstructural differences captured by our MRI metrics, along with their weak to moderate associations with MWF, strongly indicate the potential value of combining these outcome measures in a multiparametric approach. Furthermore, our results support the last-in-first-out and the gain-predicts-loss hypotheses of WM maturation and degeneration. Indeed, our results indicate that the posterior WM regions are spared from neurodegeneration as compared to anterior regions, while WM myelination follows a temporally symmetric time course across the adult life span.

Post SRS Target Diffusion Metrics for Response Prognostication in Idiopathic Trigeminal Neuralgia

Diffusion tensor imaging (DTI) is used to measure the movement of water molecules in biological tissue, which permits a thorough characterization of white matter microstructure through quantitative diffusivity metrics. The most commonly used diffusivity metric, fractional anisotropy (FA), provides insight into the overall white matter microstructural properties, whereas radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) suggest changes in myelination, axonal integrity & underlying neuro-inflammation and edema respectively. Study purpose is to find whether trigeminal nerve diffusivity metrics at a single, early time point after frameless SRS is predictive of long-term pain relief in patients with TN.Study cohort comprised of 44 pts with inclusion criteria were: 1) diagnosis of classic, type 1 TN 2) SRS treatment with no prior surgical procedures for TN; 3) 3 tesla MRI scans at 6 months posttreatment (range 5-7 months); and 4) at least 12 months of clinical follow-up. Patients with TN secondary to multiple sclerosis, cranial tumors, or vertebrobasilar dolichoectasia compressing the brainstem were excluded from the study. For each patient, diffusivity metrics (FA, MD, RD, and AD) were extracted from both the affected and unaffected trigeminal nerves at 6 months posttreatment 6 months diffusivity metrics were compared with long-term clinical outcome. Patients were identified as long-term responders if they achieved at least 75% reduction in preoperative pain for 12 months or longer following SRS. Average microstructural diffusivity differences (within group - pre and post treatment; across group - responder & non-responders) were analyzed using paired / Independent T test.Trigeminal nerve diffusivity at 6 months post-SRS was predictive of long-term clinical effectiveness, where long-term responders (n = 36) showed significantly lower fractional anisotropy at the radiosurgical target of their affected nerve compared to their contralateral, unaffected nerve and to nonresponders. Radial diffusivity and mean diffusivity, correlates of myelin alterations and inflammation, were also significantly higher in the affected nerve of long-term responders compared to their unaffected nerve. Nonresponders (n = 8) did not exhibit any characteristic diffusivity changes after SRS.DTI, FA specifically, appears to be a strong, objective measure to assess the effects of radiation on a nerve. Incorporating early DTI assessment can provide prognostic information that supplements clinical measures.

Microstructural properties within the amygdala and affiliated white matter tracts across adolescence

The amygdala is a heterogenous set of nuclei with widespread cortical connections that continues to develop postnatally with vital implications for emotional regulation. Using high-resolution anatomical and multi-shell diffusion MRI in conjunction with novel amygdala segmentation, cutting-edge tractography, and Neurite Orientation Dispersion and Density (NODDI) methods, the goal of the current study was to characterize age associations with microstructural properties of amygdala subnuclei and amygdala-related white matter connections across adolescence (N = 61, 26 males; ages of 8–22 years). We found age-related increases in the Neurite Density Index (NDI) in the lateral nucleus (LA), dorsal and intermediate divisions of the basolateral nucleus (BLDI), and ventral division of the basolateral nucleus and paralaminar nucleus (BLVPL). Additionally, there were age-related increases in the NDI of the anterior commissure, ventral amygdalofugal pathway, cingulum, and uncinate fasciculus, with the strongest age associations in the frontal and temporal regions of these white matter tracts. This is the first study to utilize NODDI to show neurite density of basolateral amygdala subnuclei to relate to age across adolescence. Moreover, age-related differences were also notable in white matter microstructural properties along the anterior commissure and ventral amydalofugal tracts, suggesting increased bilateral amygdalae to diencephalon structural connectivity. As these basolateral regions and the ventral amygdalofugal pathways have been involved in associative emotional conditioning, future research is needed to determine if age-related and/or individual differences in the development of these microstructural properties link to socio-emotional functioning and/or risk for psychopathology.

Age-Related Variations in Regional White Matter Volumetry and Microstructure During the Post-adolescence Period: A Cross-Sectional Study of a Cohort of 1,713 University Students.

Human brain white matter undergoes a protracted maturation that continues well into adulthood. Recent advances in diffusion-weighted imaging (DWI) methods allow detailed characterizations of the microstructural architecture of white matter, and they are increasingly utilized to study white matter changes during development and aging. However, relatively little is known about the late maturational changes in the microstructural architecture of white matter during post-adolescence. Here we report on regional changes in white matter volume and microstructure in young adults undergoing university-level education. As part of the MRi-Share multi-modal brain MRI database, multi-shell, high angular resolution DWI data were acquired in a unique sample of 1,713 university students aged 18–26. We assessed the age and sex dependence of diffusion metrics derived from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) in the white matter regions as defined in the John Hopkins University (JHU) white matter labels atlas. We demonstrate that while regional white matter volume is relatively stable over the age range of our sample, the white matter microstructural properties show clear age-related variations. Globally, it is characterized by a robust increase in neurite density index (NDI), and to a lesser extent, orientation dispersion index (ODI). These changes are accompanied by a decrease in diffusivity. In contrast, there is minimal age-related variation in fractional anisotropy. There are regional variations in these microstructural changes: some tracts, most notably cingulum bundles, show a strong age-related increase in NDI coupled with decreases in radial and mean diffusivity, while others, mainly cortico-spinal projection tracts, primarily show an ODI increase and axial diffusivity decrease. These age-related variations are not different between males and females, but males show higher NDI and ODI and lower diffusivity than females across many tracts. These findings emphasize the complexity of changes in white matter structure occurring in this critical period of late maturation in early adulthood.