Optic radiations representing different eccentricities age differently.

The neural pathways that carry information from the foveal, macular, and peripheral visual fields have distinct biological properties. The optic radiations (OR) carry foveal and peripheral information from the thalamus to the primary visual cortex (V1) through adjacent but separate pathways in the white matter. Here, we perform white matter tractometry using pyAFQ on a large sample of diffusion MRI (dMRI) data from subjects with healthy vision in the U.K. Biobank dataset (UKBB; N = 5382; age 45-81). We use pyAFQ to characterize white matter tissue properties in parts of the OR that transmit information about the foveal, macular, and peripheral visual fields, and to characterize the changes in these tissue properties with age. We find that (1) independent of age there is higher fractional anisotropy, lower mean diffusivity, and higher mean kurtosis in the foveal and macular OR than in peripheral OR, consistent with denser, more organized nerve fiber populations in foveal/parafoveal pathways, and (2) age is associated with increased diffusivity and decreased anisotropy and kurtosis, consistent with decreased density and tissue organization with aging. However, anisotropy in foveal OR decreases faster with age than in peripheral OR, while diffusivity increases faster in peripheral OR, suggesting foveal/peri-foveal OR and peripheral OR differ in how they age.

Probing Evidence of Cerebral White Matter Microstructural Disruptions in Ischemic Heart Disease Before and Following Cardiac Rehabilitation: A Diffusion Tensor MR Imaging Study.

BACKGROUND: Ischemic heart disease (IHD) is linked to brain white matter (WM) breakdown but how age or disease effects WM integrity, and whether it is reversible using cardiac rehabilitation (CR), remains unclear. PURPOSE: To assess the effects of brain aging, cardiovascular disease, and CR on WM microstructure in brains of IHD patients following a cardiac event. STUDY TYPE: Retrospective. POPULATION: Thirty-five IHD patients (9 females; mean age = 59 ± 8 years), 21 age-matched healthy controls (10 females; mean age = 59 ± 8 years), and 25 younger controls (14 females; mean age = 26 ± 4 years). FIELD STRENGTH/SEQUENCE: 3 T diffusion-weighted imaging with single-shot echo planar imaging acquired at 3 months and 9 months post-cardiac event. ASSESSMENT: Tract-based spatial statistics (TBSS) and tractometry were used to compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in cerebral WM between: 1) older and younger controls to distinguish age-related from disease-related WM changes; 2) IHD patients at baseline (pre-CR) and age-matched controls to investigate if cardiovascular disease exacerbates age-related WM changes; and 3) IHD patients pre-CR and post-CR to investigate the neuroplastic effect of CR on WM microstructure. STATISTICAL TESTS: Two-sample unpaired t-test (age: older vs. younger controls; IHD: IHD pre-CR vs. age-matched controls). One-sample paired t-test (CR: IHD pre- vs. post-CR). Statistical threshold: P < 0.05 (FWE-corrected). RESULTS: TBSS and tractometry revealed widespread WM changes in older controls compared to younger controls while WM clusters of decreased FA in the fornix and increased MD in body of corpus callosum were observed in IHD patients pre-CR compared to age-matched controls. Robust WM improvements (increased FA, increased AD) were observed in IHD patients post-CR. DATA CONCLUSION: In IHD, both brain aging and cardiovascular disease may contribute to WM disruptions. IHD-related WM disruptions may be favorably modified by CR. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Mahalanobis distance tractometry (MaD-Tract) - a framework for personalized white matter anomaly detection applied to TBI.

Imaging-based quantitative measures from diffusion-weighted MRI (dMRI) offer the ability to non-invasively extract microscopic information from human brain tissues. Group-level comparisons of such measures represent an important approach to investigate abnormal brain conditions. These types of analyses are especially useful when the regions of abnormality spatially coincide across subjects. When this is not true, approaches for individualized analyses are necessary. Here we present a framework for single-subject multidimensional analysis based on the Mahalanobis distance. This is conducted along specific white matter pathways represented by tractography-derived streamline bundles. A definition for abnormality was constructed from Wilk's criterion, which accounts for normative sample size, number of features used in the Mahalanobis distance, and multiple comparisons. One example of a condition exhibiting high heterogeneity across subjects is traumatic brain injury (TBI). Using the Mahalanobis distance computed from the three eigenvalues of the diffusion tensor along the cingulum, uncinate, and parcellated corpus callosum tractograms, 8 severe TBI patients were individually compared to a normative sample of 49 healthy controls. For all TBI patients, the analyses showed statistically significant deviations from the normative data at one or multiple locations along the analyzed bundles. The detected anomalies were widespread across the analyzed tracts, consistent with the expected heterogeneity that is hallmark of TBI. Each of the controls subjects was also compared to the remaining 48 subjects in the control group in a leave-one-out fashion. Only two segments were identified as abnormal out of the entire analysis in the control group, thus the method also demonstrated good specificity.

Prevalence of white matter pathways coming into a single white matter voxel orientation: The bottleneck issue in tractography.

Characterizing and understanding the limitations of diffusion MRI fiber tractography is a prerequisite for methodological advances and innovations which will allow these techniques to accurately map the connections of the human brain. The so-called "crossing fiber problem" has received tremendous attention and has continuously triggered the community to develop novel approaches for disentangling distinctly oriented fiber populations. Perhaps an even greater challenge occurs when multiple white matter bundles converge within a single voxel, or throughout a single brain region, and share the same parallel orientation, before diverging and continuing towards their final cortical or sub-cortical terminations. These so-called "bottleneck" regions contribute to the ill-posed nature of the tractography process, and lead to both false positive and false negative estimated connections. Yet, as opposed to the extent of crossing fibers, a thorough characterization of bottleneck regions has not been performed. The aim of this study is to quantify the prevalence of bottleneck regions. To do this, we use diffusion tractography to segment known white matter bundles of the brain, and assign each bundle to voxels they pass through and to specific orientations within those voxels (i.e. fixels). We demonstrate that bottlenecks occur in greater than 50-70% of fixels in the white matter of the human brain. We find that all projection, association, and commissural fibers contribute to, and are affected by, this phenomenon, and show that even regions traditionally considered "single fiber voxels" often contain multiple fiber populations. Together, this study shows that a majority of white matter presents bottlenecks for tractography which may lead to incorrect or erroneous estimates of brain connectivity or quantitative tractography (i.e., tractometry), and underscores the need for a paradigm shift in the process of tractography and bundle segmentation for studying the fiber pathways of the human brain.

Microstructural damage of the cortico-striatal and thalamo-cortical fibers in Fabry disease: a diffusion MRI tractometry study.

PURPOSE: Recent evidences have suggested the possible presence of an involvement of the extrapyramidal system in Fabry disease (FD), a rare X-linked lysosomal storage disorder. We aimed to investigate the microstructural integrity of the main tracts of the cortico-striatal-thalamo-cortical loop in FD patients. METHODS: Forty-seven FD patients (mean age = 42.3 ± 16.3 years, M/F = 28/21) and 49 healthy controls (mean age = 42.3 ± 13.1 years, M/F = 19/28) were enrolled in this study. Fractional anisotropy (FA), axial (AD), radial (RD), and mean diffusivity (MD) maps were computed for each subject, and connectomes were built using a standard atlas. Diffusion metrics and connectomes were then combined to carry on a diffusion MRI tractometry analysis. The main afferent and efferent pathways of the cortico-striatal-thalamo-cortical loop (namely, bundles connecting the precentral gyrus (PreCG) with the striatum and the thalamus) were evaluated. RESULTS: We found the presence of a microstructural involvement of cortico-striatal-thalamo-cortical loop in FD patients, predominantly affecting the left side. In particular, we found significant lower mean FA values of the left cortico-striatal fibers (p = 0.001), coupled to higher MD (p = 0.001) and RD (p < 0.001) values, as well as higher MD (p = 0.01) and RD (p = 0.01) values at the level of the thalamo-cortical fibers. CONCLUSION: We confirmed the presence of an alteration of the extrapyramidal system in FD patients, in line with recent evidences suggesting the presence of brain changes as a possible reflection of the subtle motor symptoms present in this condition. Our results suggest that, along with functional changes, microstructural damage of this pathway is also present in FD patients.

Bundle-specific tractography with incorporated anatomical and orientational priors.

Anatomical white matter bundles vary in shape, size, length, and complexity, making diffusion MRI tractography reconstruction of some bundles more difficult than others. As a result, bundles reconstruction often suffers from a poor spatial extent recovery. To fill-up the white matter volume as much and as best as possible, millions of streamlines can be generated and filtering techniques applied to address this issue. However, well-known problems and biases are introduced such as the creation of a large number of false positives and over-representation of easy-to-track parts of bundles and under-representation of hard-to-track. To address these challenges, we developed a Bundle-Specific Tractography (BST) algorithm. It incorporates anatomical and orientational prior knowledge during the process of streamline tracing to increase reproducibility, sensitivity, specificity and efficiency when reconstructing certain bundles of interest. BST outperforms classical deterministic, probabilistic, and global tractography methods. The increase in anatomically plausible streamlines, with larger spatial coverage, helps to accurately represent the full shape of bundles, which could greatly enhance and robustify tract-based and connectivity-based neuroimaging studies.

Dimensionality reduction of diffusion MRI measures for improved tractometry of the human brain.

Various diffusion MRI (dMRI) measures have been proposed for characterising tissue microstructure over the last 15 years. Despite the growing number of experiments using different dMRI measures in assessments of white matter, there has been limited work on: 1) examining their covariance along specific pathways; and on 2) combining these different measures to study tissue microstructure. Indeed, it quickly becomes intractable for existing analysis pipelines to process multiple measurements at each voxel and at each vertex forming a streamline, highlighting the need for new ways to visualise or analyse such high-dimensional data. In a sample of 36 typically developing children aged 8-18 years, we profiled various commonly used dMRI measures across 22 brain pathways. Using a data-reduction approach, we identified two biologically-interpretable components that capture 80% of the variance in these dMRI measures. The first derived component captures properties related to hindrance and restriction in tissue microstructure, while the second component reflects characteristics related to tissue complexity and orientational dispersion. We then demonstrate that the components generated by this approach preserve the biological relevance of the original measurements by showing age-related effects across developmentally sensitive pathways. In summary, our findings demonstrate that dMRI analyses can benefit from dimensionality reduction techniques, to help disentangling the neurobiological underpinnings of white matter organisation.

Reducing variability in along-tract analysis with diffusion profile realignment.

Diffusion weighted magnetic resonance imaging (dMRI) provides a non invasive virtual reconstruction of the brain's white matter structures through tractography. Analyzing dMRI measures along the trajectory of white matter bundles can provide a more specific investigation than considering a region of interest or tract-averaged measurements. However, performing group analyses with this along-tract strategy requires correspondence between points of tract pathways across subjects. This is usually achieved by creating a new common space where the representative streamlines from every subject are resampled to the same number of points. If the underlying anatomy of some subjects was altered due to, e.g., disease or developmental changes, such information might be lost by resampling to a fixed number of points. In this work, we propose to address the issue of possible misalignment, which might be present even after resampling, by realigning the representative streamline of each subject in this 1D space with a new method, coined diffusion profile realignment (DPR). Experiments on synthetic datasets show that DPR reduces the coefficient of variation for the mean diffusivity, fractional anisotropy and apparent fiber density when compared to the unaligned case. Using 100 in vivo datasets from the human connectome project, we simulated changes in mean diffusivity, fractional anisotropy and apparent fiber density. Independent Student's t-tests between these altered subjects and the original subjects indicate that regional changes are identified after realignment with the DPR algorithm, while preserving differences previously detected in the unaligned case. This new correction strategy contributes to revealing effects of interest which might be hidden by misalignment and has the potential to improve the specificity in longitudinal population studies beyond the traditional region of interest based analysis and along-tract analysis workflows.

Deep Normative Tractometry for Identifying Joint White Matter Macro- and Micro-structural Abnormalities in Alzheimer's Disease.

This study introduces the Deep Normative Tractometry (DNT) framework, that encodes the joint distribution of both macrostructural and microstructural profiles of the brain white matter tracts through a variational autoencoder (VAE). By training on data from healthy controls, DNT learns the normative distribution of tract data, and can delineate along-tract micro-and macro-structural abnormalities. Leveraging a large sample size via generative pre-training, we assess DNT's generalizability using transfer learning on data from an independent cohort acquired in India. Our findings demonstrate DNT's capacity to detect widespread diffusivity abnormalities along tracts in mild cognitive impairment and Alzheimer's disease, aligning closely with results from the Bundle Analytics (BUAN) tractometry pipeline. By incorporating tract geometry information, DNT may be able to distinguish disease-related abnormalities in anisotropy from tract macrostructure, and shows promise in enhancing fine-scale mapping and detection of white matter alterations in neurodegenerative conditions.

Tractometry of Human Visual White Matter Pathways in Health and Disease.

Diffusion-weighted MRI (dMRI) provides a unique non-invasive view of human brain tissue properties. The present review article focuses on tractometry analysis methods that use dMRI to assess the properties of brain tissue within the long-range connections comprising brain networks. We focus specifically on the major white matter tracts that convey visual information. These connections are particularly important because vision provides rich information from the environment that supports a large range of daily life activities. Many of the diseases of the visual system are associated with advanced aging, and tractometry of the visual system is particularly important in the modern aging society. We provide an overview of the tractometry analysis pipeline, which includes a primer on dMRI data acquisition, voxelwise model fitting, tractography, recognition of white matter tracts, and calculation of tract tissue property profiles. We then review dMRI-based methods for analyzing visual white matter tracts: the optic nerve, optic tract, optic radiation, forceps major, and vertical occipital fasciculus. For each tract, we review background anatomical knowledge together with recent findings in tractometry studies on these tracts and their properties in relation to visual function and disease. Overall, we find that measurements of the brain's visual white matter are sensitive to a range of disorders and correlate with perceptual abilities. We highlight new and promising analysis methods, as well as some of the current barriers to progress toward integration of these methods into clinical practice. These barriers, such as variability in measurements between protocols and instruments, are targets for future development.

Microstructural brain assessment in late-life depression and apathy using diffusion MRI multi-compartments models and tractometry.

Late-life depression (LLD) is both common and disabling and doubles the risk of dementia onset. Apathy might constitute an additional risk of cognitive decline but clear understanding of its pathophysiology is lacking. While white matter (WM) alterations have been assessed using diffusion tensor imaging (DTI), this model cannot accurately represent WM microstructure. We hypothesized that a more complex multi-compartment model would provide new biomarkers of LLD and apathy. Fifty-six individuals (LLD n = 35, 26 females, 75.2 ± 6.4 years, apathy evaluation scale scores (41.8 ± 8.7) and Healthy controls, n = 21, 16 females, 74.7 ± 5.2 years) were included. In this article, a tract-based approach was conducted to investigate novel diffusion model biomarkers of LLD and apathy by interpolating microstructural metrics directly along the fiber bundle. We performed multivariate statistical analysis, combined with principal component analysis for dimensional data reduction. We then tested the utility of our framework by demonstrating classically reported from the literature modifications in LDD while reporting new results of biological-basis of apathy in LLD. Finally, we aimed to investigate the relationship between apathy and microstructure in different fiber bundles. Our study suggests that new fiber bundles, such as the striato-premotor tracts, may be involved in LLD and apathy, which bring new light of apathy mechanisms in major depression. We also identified statistical changes in diffusion MRI metrics in 5 different tracts, previously reported in major cognitive disorders dementia, suggesting that these alterations among these tracts are both involved in motivation and cognition and might explain how apathy is a prodromal phase of degenerative disorders.

Amyloid, Tau, and APOE in Alzheimer's Disease: Impact on White Matter Tracts.

Alzheimer's disease (AD) is characterized by cognitive decline and memory loss due to the abnormal accumulation of amyloid-beta (Aß) plaques and tau tangles in the brain; its onset and progression also depend on genetic factors such as the apolipoprotein E (APOE) genotype. Understanding how these factors affect the brain's neural pathways is important for early diagnostics and interventions. Tractometry is an advanced technique for 3D quantitative assessment of white matter tracts, localizing microstructural abnormalities in diseased populations in vivo. In this work, we applied BUAN (Bundle Analytics) tractometry to 3D diffusion MRI data from 730 participants in ADNI3 (phase 3 of the Alzheimer's Disease Neuroimaging Initiative; age range: 55-95 years, 349M/381F, 214 with mild cognitive impairment, 69 with AD, and 447 cognitively healthy controls). Using along-tract statistical analysis, we assessed the localized impact of amyloid, tau, and APOE genetic variants on the brain's neural pathways. BUAN quantifies microstructural properties of white matter tracts, supporting along-tract statistical analyses that identify factors associated with brain microstructure. We visualize the 3D profile of white matter tract associations with tau and amyloid burden in Alzheimer's disease; strong associations near the cortex may support models of disease propagation along neural pathways. Relative to the neutral genotype, APOE ϵ3/ϵ3, carriers of the AD-risk conferring APOE ϵ4 genotype show microstructural abnormalities, while carriers of the protective ϵ2 genotype also show subtle differences. Of all the microstructural metrics, mean diffusivity (MD) generally shows the strongest associations with AD pathology, followed by axial diffusivity (AxD) and radial diffusivity (RD), while fractional anisotropy (FA) is typically the least sensitive metric. Along-tract microstructural metrics are sensitive to tau and amyloid accumulation, showing the potential of diffusion MRI to track AD pathology and map its impact on neural pathways.

Tractometry of the Human Connectome Project: resources and insights.

Introduction: The Human Connectome Project (HCP) has become a keystone dataset in human neuroscience, with a plethora of important applications in advancing brain imaging methods and an understanding of the human brain. We focused on tractometry of HCP diffusion-weighted MRI (dMRI) data. Methods: We used an open-source software library (pyAFQ; https://yeatmanlab.github.io/pyAFQ) to perform probabilistic tractography and delineate the major white matter pathways in the HCP subjects that have a complete dMRI acquisition (n = 1,041). We used diffusion kurtosis imaging (DKI) to model white matter microstructure in each voxel of the white matter, and extracted tract profiles of DKI-derived tissue properties along the length of the tracts. We explored the empirical properties of the data: first, we assessed the heritability of DKI tissue properties using the known genetic linkage of the large number of twin pairs sampled in HCP. Second, we tested the ability of tractometry to serve as the basis for predictive models of individual characteristics (e.g., age, crystallized/fluid intelligence, reading ability, etc.), compared to local connectome features. To facilitate the exploration of the dataset we created a new web-based visualization tool and use this tool to visualize the data in the HCP tractometry dataset. Finally, we used the HCP dataset as a test-bed for a new technological innovation: the TRX file-format for representation of dMRI-based streamlines. Results: We released the processing outputs and tract profiles as a publicly available data resource through the AWS Open Data program's Open Neurodata repository. We found heritability as high as 0.9 for DKI-based metrics in some brain pathways. We also found that tractometry extracts as much useful information about individual differences as the local connectome method. We released a new web-based visualization tool for tractometry-"Tractoscope" (https://nrdg.github.io/tractoscope). We found that the TRX files require considerably less disk space-a crucial attribute for large datasets like HCP. In addition, TRX incorporates a specification for grouping streamlines, further simplifying tractometry analysis.

White matter microstructure, traumatic brain injury, and disruptive behavior disorders in girls and boys.

Introduction: Girls and boys presenting disruptive behavior disorders (DBDs) display differences in white matter microstructure (WMM) relative to typically developing (TD) sex-matched peers. Boys with DBDs are at increased risk for traumatic brain injuries (TBIs), which are also known to impact WMM. This study aimed to disentangle associations of WMM with DBDs and TBIs. Methods: The sample included 673 children with DBDs and 836 TD children, aged 9-10, from the Adolescent Brain Cognitive Development Study. Thirteen white matter bundles previously associated with DBDs were the focus of study. Analyses were undertaken separately by sex, adjusting for callous-unemotional traits (CU), attention-deficit hyperactivity disorder (ADHD), age, pubertal stage, IQ, ethnicity, and family income. Results: Among children without TBIs, those with DBDs showed sex-specific differences in WMM of several tracts relative to TD. Most differences were associated with ADHD, CU, or both. Greater proportions of girls and boys with DBDs than sex-matched TD children had sustained TBIs. Among girls and boys with DBDs, those who had sustained TBIs compared to those not injured, displayed WMM alterations that were robust to adjustment for all covariates. Across most DBD/TD comparisons, axonal density scores were higher among children presenting DBDs. Discussion: In conclusion, in this community sample of children, those with DBDs were more likely to have sustained TBIs that were associated with additional, sex-specific, alterations of WMM. These additional alterations further compromise the future development of children with DBDs.

TractoSCR: a novel supervised contrastive regression framework for prediction of neurocognitive measures using multi-site harmonized diffusion MRI tractography.

Neuroimaging-based prediction of neurocognitive measures is valuable for studying how the brain's structure relates to cognitive function. However, the accuracy of prediction using popular linear regression models is relatively low. We propose a novel deep regression method, namely TractoSCR, that allows full supervision for contrastive learning in regression tasks using diffusion MRI tractography. TractoSCR performs supervised contrastive learning by using the absolute difference between continuous regression labels (i.e., neurocognitive scores) to determine positive and negative pairs. We apply TractoSCR to analyze a large-scale dataset including multi-site harmonized diffusion MRI and neurocognitive data from 8,735 participants in the Adolescent Brain Cognitive Development (ABCD) Study. We extract white matter microstructural measures using a fine parcellation of white matter tractography into fiber clusters. Using these measures, we predict three scores related to domains of higher-order cognition (general cognitive ability, executive function, and learning/memory). To identify important fiber clusters for prediction of these neurocognitive scores, we propose a permutation feature importance method for high-dimensional data. We find that TractoSCR obtains significantly higher accuracy of neurocognitive score prediction compared to other state-of-the-art methods. We find that the most predictive fiber clusters are predominantly located within the superficial white matter and projection tracts, particularly the superficial frontal white matter and striato-frontal connections. Overall, our results demonstrate the utility of contrastive representation learning methods for regression, and in particular for improving neuroimaging-based prediction of higher-order cognitive abilities. Our code will be available at: https://github.com/SlicerDMRI/TractoSCR.

Microstructural Mapping of Neural Pathways in Alzheimer's Disease using Macrostructure-Informed Normative Tractometry.

Introduction: Diffusion MRI is sensitive to the microstructural properties of brain tissues, and shows great promise in detecting the effects of degenerative diseases. However, many approaches analyze single measures averaged over regions of interest, without considering the underlying fiber geometry. Methods: Here, we propose a novel Macrostructure-Informed Normative Tractometry (MINT) framework, to investigate how white matter microstructure and macrostructure are jointly altered in mild cognitive impairment (MCI) and dementia. We compare MINT-derived metrics with univariate metrics from diffusion tensor imaging (DTI), to examine how fiber geometry may impact interpretation of microstructure. Results: In two multi-site cohorts from North America and India, we find consistent patterns of microstructural and macrostructural anomalies implicated in MCI and dementia; we also rank diffusion metrics' sensitivity to dementia. Discussion: We show that MINT, by jointly modeling tract shape and microstructure, has potential to disentangle and better interpret the effects of degenerative disease on the brain's neural pathways.

BundleCleaner: Unsupervised Denoising and Subsampling of Diffusion MRI-Derived Tractography Data.

We present BundleCleaner, an unsupervised multi-step framework that can filter, denoise and subsample bundles derived from diffusion MRI-based whole-brain tractography. Our approach considers both the global bundle structure and local streamline-wise features. We apply BundleCleaner to bundles generated from single-shell diffusion MRI data in an independent clinical sample of older adults from India using probabilistic tractography and the resulting 'cleaned' bundles can better align with the atlas bundles with reduced overreach. In a downstream tractometry analysis, we show that the cleaned bundles, represented with less than 20% of the original set of points, can robustly localize along-tract microstructural differences between 32 healthy controls and 34 participants with Alzheimer's disease ranging in age from 55 to 84 years old. Our approach can help reduce memory burden and improving computational efficiency when working with tractography data, and shows promise for large-scale multi-site tractometry.

Multi-Site Statistical Mapping of Along-Tract Microstructural Abnormalities in Bipolar Disorder with Diffusion MRI Tractometry.

Investigating alterations in brain circuitry associated with bipolar disorder (BD) may offer a valuable approach to discover brain biomarkers for genetic and interventional studies of the disorder and related mental illnesses. Some diffusion MRI studies report evidence of microstructural abnormalities in white matter regions of interest, but we lack a fine-scale spatial mapping of brain microstructural differences along tracts in BD. We also lack large-scale studies that integrate tractometry data from multiple sites, as larger datasets can greatly enhance power to detect subtle effects and assess whether effects replicate across larger international datasets. In this multisite diffusion MRI study, we used BUndle ANalytics (BUAN, Chandio 2020), a recently developed analytic approach for tractography, to extract, map, and visualize profiles of microstructural abnormalities on 3D models of fiber tracts in 148 participants with BD and 259 healthy controls from 6 independent scan sites. Modeling site differences as random effects, we investigated along-tract white matter (WM) microstructural differences between diagnostic groups. QQ plots showed that group differences were gradually enhanced as more sites were added. Using the BUAN pipeline, BD was associated with lower mean fractional anisotropy (FA) in fronto-limbic, interhemispheric, and posterior pathways; higher FA was also noted in posterior bundles, relative to controls. By integrating tractography and anatomical information, BUAN effectively captures unique effects along white matter (WM) tracts, providing valuable insights into anatomical variations that may assist in the classification of diseases.

Multiparametric mapping of white matter reorganizations in patients with frontal glioma-related epilepsy.

AIMS: Epilepsy is a common symptom in diffuse lower-grade glioma (DLGG). The specific role of white matter (WM) alteration in patients with glioma-related epilepsy (GRE) is largely unknown. This study aims to investigate the reorganization of WM tracts and changes in structural networks related to GRE. METHODS: Diffusion-weighted images were collected from 70 patients with left frontal DLGG (GRE = 33, non-GRE = 37) and 41 healthy controls (HC). Tractometry with TractSeg was applied to segment tracts and quantify fractional anisotropy (FA) along each tract. Structural network was constructed using constrained spherical deconvolution and probabilistic tractography. FA and network properties were compared among three groups. RESULTS: Compared with HC, both GRE and non-GRE showed decreased FA in contralateral inferior fronto-occipital fasciculus, superior longitudinal fasciculus II and arcuate fasciculus, increased nodal efficiency in contralateral nodes of frontal-parietal and limbic networks, whereas decreased degree centrality and betweenness centrality in nodes of dorsal temporal lobe and rostral middle frontal gyrus (rMFG). Additionally, when compared GRE with non-GRE, increased FA in contralateral corticospinal tract (CST) and lower betweenness centrality in paracentral lobule (PCL) in GRE (all p < 0.05 after Bonferroni correction). CONCLUSION: This study indicates that patients with left frontal DLGG exhibit complex WM reorganization, and the altered regions mainly concentrated in the language, frontal-parietal and limbic networks. Moreover, the preserved integrity in contralateral CST and server decreased nodal betweenness in PCL may be potential neuroimaging markers underlying the occurrence of presurgical seizures of GRE.

A tractometry principal component analysis of white matter tract network structure and relationships with cognitive function in relapsing-remitting multiple sclerosis.

Understanding the brain changes underlying cognitive dysfunction is a key priority in multiple sclerosis (MS) to improve monitoring and treatment of this debilitating symptom. Functional connectivity network changes are associated with cognitive dysfunction, but it is less well understood how changes in normal appearing white matter relate to cognitive symptoms. If white matter tracts have network structure it would be expected that tracts within a network share susceptibility to MS pathology. In the present study, we used a tractometry approach to explore patterns of variance in white matter metrics across white matter (WM) tracts, and assessed how such patterns relate to neuropsychological test performance across cognitive domains. A sample of 102 relapsing-remitting MS patients and 27 healthy controls underwent MRI and neuropsychological testing. Tractography was performed on diffusion MRI data to extract 40 WM tracts and microstructural measures were extracted from each tract. Principal component analysis (PCA) was used to decompose metrics from all tracts to assess the presence of any co-variance structure among the tracts. Similarly, PCA was applied to cognitive test scores to identify the main cognitive domains. Finally, we assessed the ability of tract co-variance patterns to predict test performance across cognitive domains. We found that a single co-variance pattern which captured microstructure across all tracts explained the most variance (65% variance explained) and that there was little evidence for separate, smaller network patterns of pathology. Variance in this pattern was explained by effects related to lesions, but one main co-variance pattern persisted after this effect was regressed out. This main WM tract co-variance pattern contributed to explaining a modest degree of variance in one of our four cognitive domains in MS. These findings highlight the need to investigate the relationship between the normal appearing white matter and cognitive impairment further and on a more granular level, to improve the understanding of the network structure of the brain in MS.