White matter maturation is a nonlinear and heterogeneous phenomenon characterized by axonal packing, increased axon caliber, and a prolonged period of myelination. While current in vivo diffusion MRI ...(dMRI) methods, like diffusion tensor imaging (DTI), have successfully characterized the gross structure of major white matter tracts, these measures lack the specificity required to unravel the distinct processes that contribute to microstructural development. Neurite orientation dispersion and density imaging (NODDI) is a dMRI approach that probes tissue compartments and provides biologically meaningful measures that quantify neurite density index (NDI) and orientation dispersion index (ODI). The purpose of this study was to characterize the magnitude and timing of major white matter tract maturation with NODDI from infancy through adolescence in a cross-sectional cohort of 104 subjects (0.6–18.8 years). To probe the regional nature of white matter development, we use an along-tract approach that partitions tracts to enable more fine-grained analysis. Major white matter tracts showed exponential age-related changes in NDI with distinct maturational patterns. Overall, analyses revealed callosal fibers developed before association fibers. Our along-tract analyses elucidate spatially varying patterns of maturation with NDI that are distinct from those obtained with DTI. ODI was not significantly associated with age in the majority of tracts. Our results support the conclusion that white matter tract maturation is heterochronous process and, furthermore, we demonstrate regional variability in the developmental timing within major white matter tracts. Together, these results help to disentangle the distinct processes that contribute to and more specifically define the time course of white matter maturation.
•Neurite density index increases nonlinearly with age in major white matter tracts.•Callosal fibers develop earlier than association fibers using neurite density index.•Neurite density index rate of change varies along the length of tracts.•Orientation dispersion index is not related to age in the majority of tracts.
Imaging the perivascular spaces (PVS), also known as Virchow-Robin space, has significant clinical value, but there remains a need for neuroimaging techniques to improve mapping and quantification of ...the PVS. Current technique for PVS evaluation is a scoring system based on visual reading of visible PVS in regions of interest, and often limited to large caliber PVS. Enhancing the visibility of the PVS could support medical diagnosis and enable novel neuroscientific investigations. Increasing the MRI resolution is one approach to enhance the visibility of PVS but is limited by acquisition time and physical constraints. Alternatively, image processing approaches can be utilized to improve the contrast ratio between PVS and surrounding tissue. Here we combine T1- and T2-weighted images to enhance PVS contrast, intensifying the visibility of PVS. The Enhanced PVS Contrast (EPC) was achieved by combining T1- and T2-weighted images that were adaptively filtered to remove non-structured high-frequency spatial noise. EPC was evaluated on healthy young adults by presenting them to two expert readers and also through automated quantification. We found that EPC improves the conspicuity of the PVS and aid resolving a larger number of PVS. We also present a highly reliable automated PVS quantification approach, which was optimized using expert readings.
Diffusion tensor imaging (DTI) has been extensively used to map changes in brain tissue related to neurological disorders. Among the most widespread DTI findings are increased mean diffusivity and ...decreased fractional anisotropy of white matter tissue in neurodegenerative diseases. Here we utilize multi-shell diffusion imaging to separate diffusion signal of the brain parenchyma from non-parenchymal fluid within the white matter. We show that unincorporated anisotropic water in perivascular space (PVS) significantly, and systematically, biases DTI measures, casting new light on the biological validity of many previously reported findings. Despite the challenge this poses for interpreting these past findings, our results suggest that multi-shell diffusion MRI provides a new opportunity for incorporating the PVS contribution, ultimately strengthening the clinical and scientific value of diffusion MRI.
•Perivascular space (PVS) fluid significantly contributes to diffusion tensor imaging metrics.•Increased PVS fluid results in increased mean diffusivity and decreased fractional anisotropy.•PVS contribution to diffusion signal is overlooked and demands further investigation.
Vascular contributions to early cognitive decline are increasingly recognized, prompting further investigation into the nature of related changes in perivascular spaces (PVS). Using magnetic ...resonance imaging, we show that, compared to a cognitively normal sample, individuals with early cognitive dysfunction have altered PVS presence and distribution, irrespective of Amyloid-β. Surprisingly, we noted lower PVS presence in the anterosuperior medial temporal lobe (asMTL) (1.29 times lower PVS volume fraction in cognitively impaired individuals, p < 0.0001), which was associated with entorhinal neurofibrillary tau tangle deposition (beta (standard error) = -0.98 (0.4); p = 0.014), one of the hallmarks of early Alzheimer’s disease pathology. We also observed higher PVS volume fraction in centrum semi-ovale of the white matter, but only in female participants (1.47 times higher PVS volume fraction in cognitively impaired individuals, p = 0.0011). We also observed PVS changes in participants with history of hypertension (higher in the white matter and lower in the asMTL). Our results suggest that anatomically specific alteration of the PVS is an early neuroimaging feature of cognitive impairment in aging adults, which is differentially manifested in female.
•We report perivascular space (PVS) differences in mild cognitive impairment.•PVS changes in anterosuperior medial temporal lobe associated with Tau uptake.•PVS differences were independent of Amyloid uptake.•Cognitively impaired females had higher PVS volume fraction in white matter.•PVS volume fraction changes in participants with history of hypertension.
The functional significance and mechanisms determining the development and individual variability of structural brain asymmetry remain unclear. Here, we systematically analyzed all relevant ...components of the most prominent structural asymmetry, brain torque (BT), and their relationships with potential genetic and nongenetic modifiers in a sample comprising 24,112 individuals from six cohorts.
BT features, including petalia, bending, dorsoventral shift, brain tissue distribution asymmetries, and cortical surface positional asymmetries, were directly modeled using a set of automatic three-dimensional brain shape analysis approaches. Age-, sex-, and handedness-related effects on BT were assessed. The genetic architecture and phenomic associations of BT were investigated using genome- and phenome-wide association scans.
Our results confirmed the population-level predominance of the typical counterclockwise torque and suggested a first attenuating, then enlarging dynamic across the life span (3–81 years) primarily for frontal, occipital, and perisylvian BT features. Sex/handedness, BT, and cognitive function of verbal-numerical reasoning were found to be interrelated statistically. We observed differential heritability of up to 56% for BT, especially in temporal language areas. Individual variations of BT were also associated with various phenotypic variables of neuroanatomy, cognition, lifestyle, sociodemographics, anthropometry, physical health, and adult and child mental health. Our genomic analyses identified a number of genetic associations at lenient significance levels, which need to be further validated using larger samples in the future.
This study provides a comprehensive description of BT and insights into biological and other factors that may contribute to the development and individual variations of BT.
Neocortical maturation is a dynamic process that proceeds in a hierarchical manner; however, the spatiotemporal organization of cortical microstructure with diffusion MRI has yet to be fully defined. ...This study characterized cortical microstructural maturation using diffusion MRI (fwe‐diffusion tensor imaging DTI and neurite orientation dispersion and density imaging NODDI multicompartment modeling) in a cohort of 637 children and adolescents between 8 and 21 years of age. We found spatially heterogeneous developmental patterns broadly demarcated into functional domains where NODDI metrics increased, and fwe‐DTI metrics decreased with age. By applying nonlinear growth models in a vertex‐wise analysis, we observed a general posterior‐to‐anterior pattern of maturation, where the fwe‐DTI measures mean diffusivity and radial diffusivity reached peak maturation earlier than the NODDI metrics neurite density index. Using non‐negative matrix factorization, we found occipito‐parietal cortical regions that correspond to lower order sensory domains mature earlier than fronto‐temporal higher order association domains. Our findings corroborate previous histological and neuroimaging studies that show spatially varying patterns of cortical maturation that may reflect unique developmental processes of cytoarchitectonically determined regional patterns of change.
We quantified regional patterns of cortical maturation across childhood and adolescence using multiple advanced diffusion MRI models that probe different aspects of the microstructural organization of the developing cortex. We found heterogeneous patterns of cortical maturation that proceed in a hierarchical manner, which we interpret as varying degrees of myelination, dendritic arborization, and axonal pruning.
Abstract
We developed a novel method for mapping the location, surface area, thickness, and volume of frontoinsular cortex (FI) using structural and diffusion magnetic resonance imaging. FI lies in ...the ventral part of anterior insular cortex and is characterized by its distinctive population von Economo neurons (VENs). Functional neuroimaging studies have revealed its involvement in affective processing, and histopathology has implicated VEN loss in behavioral-variant frontotemporal dementia and chronic alcoholism; however, structural neuroimaging of FI has been relatively limited. We delineated FI by jointly modeling cortical surface geometry and its coincident diffusion microstructure parameters. We found that neurite orientation dispersion in cortical gray matter can be used to map FI in specific individuals, and the derived measures reflect a range of behavioral factors in young adults from the Human Connectome Project (N=1052). FI volume was larger in the left hemisphere than the right (31%), and the percentage volume of FI was larger in women than men (15.3%). FI volume was associated with measures of decision-making (delay discounting, substance abuse), emotion (negative intrusive thinking and perception of hostility), and social behavior (theory of mind and working memory for faces). The common denominator is that larger FI size is related to greater self-control and social awareness.
Gray matter morphology in the prefrontal cortex and subcortical regions, including the hippocampus and amygdala, are affected in youth with classical congenital adrenal hyperplasia (CAH). It remains ...unclear if white matter connecting these aforementioned brain regions is compromised in youth with CAH.
To examine brain white matter microstructure in youth with CAH compared to controls.
A cross-sectional sample of 23 youths with CAH due to 21-hydroxylase deficiency (12.9 ± 3.5 year; 61% female) and 33 healthy controls (13.1 ± 2.8 year; 61% female) with 3T multishell diffusion-weighted magnetic resonance brain scans.
Complementary modeling approaches, including diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to examine in vivo white matter microstructure in six white matter tracts that innervate the prefrontal and subcortical regions.
DTI showed CAH youth had lower fractional anisotropy in both the fornix and stria terminalis and higher mean diffusivity in the fornix compared to controls. NODDI modeling revealed that CAH youth have a significantly higher orientation dispersion index in the stria terminalis compared to controls. White matter microstructural integrity was associated with smaller hippocampal and amygdala volumes in CAH youth.
These patterns of microstructure reflect less restricted water diffusion likely due to less coherency in oriented microstructure. These results suggest that white matter microstructural integrity in the fornix and stria terminalis is compromised and may be an additional related brain phenotype alongside affected hippocampus and amygdala neurocircuitry in individuals with CAH.
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.
Obstructive sleep apnea (OSA) may lead to white mater (WM) disruptions and cognitive deficits. However, no studies have investigated the full extent of the brain WM, and its associations with ...cognitive deficits in OSA remain unclear. We thus applied diffusion tensor imaging (DTI) tractography with multi‐fiber models and used atlas‐based bundle‐specific approach to investigate the WM abnormalities for various tracts of the cerebral cortex, thalamus, brainstem, and cerebellum in patients with untreated OSA. We enrolled 100 OSA patients and 63 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values mapped on 33 regions of interest including WM tracts of cortex, thalamus, brainstem, and cerebellum were obtained from tractography‐based reconstructions. We compared FA/MD values between groups and correlated FA/MD with clinical data in the OSA group after controlling for age and body mass index. OSA patients showed significantly lower FA values in multiple WM fibers including corpus callosum, inferior fronto‐occipital fasciculus, middle/superior longitudinal fasciculi, thalamic radiations, and uncinate (FDR <0.05). Higher FA values were found in medial lemniscus of patients compared to controls (FDR <0.05). Lower FA values of rostrum of corpus callosum correlated with lower visual memory performance in OSA group (p < .005). Our quantitative DTI analysis demonstrated that untreated OSA could negatively impact the integrity of pathways more broadly, including brainstem structures such as medial lemniscus, in comparison to previous findings. Fiber tract abnormalities of the rostral corpus callosum were associated with impaired visual memory in untreated OSA may provide insights into the related pathomechanism.
The authors enrolled 100 obstructive sleep apnea (OSA) patients and 63 healthy controls. Our quantitative DTI analysis demonstrated that untreated OSA could negatively impact the integrity of pathways more broadly, including brainstem structures such as medial lemniscus, in comparison to previous findings. Fiber tract abnormalities of the rostral corpus callosum were associated with impaired visual memory in untreated OSA may provide insights into the related pathomechanism.
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