Age and sex effects on advanced white matter microstructure measures in 15,628 older adults: A UK biobank study

AbstractA comprehensive characterization of the brain’s white matter is critical for improving our understanding of healthy and diseased aging. Here we used diffusion-weighted magnetic resonance imaging (dMRI) to estimate age and sex effects on white matter microstructure in a cross-sectional sample of 15,628 adults aged 45–80 years old (47.6% male, 52.4% female). Microstructure was assessed using the following four models: a conventional single-shell model, diffusion tensor imaging (DTI); a more advanced single-shell model, the tensor distribution function (TDF); an advanced multi-shell model, neurite orientation dispersion and density imaging (NODDI); and another advanced multi-shell model, mean apparent propagator MRI (MAPMRI). Age was modeled using a data-driven statistical approach, and normative centile curves were created to provide sex-stratified white matter reference charts. Participant age and sex substantially impacted many aspects of white matter microstructure across the brain, with the advanced dMRI models TDF and NODDI detecting such effects the most sensitively. These findings and the normative reference curves provide an important foundation for the study of healthy and diseased brain aging.

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White matter microstructure shows sex differences in late childhood: Evidence from 6,797 children

10.1101/2021.08.19.456728 ◽

2021 ◽

Author(s):

Katherine E. Lawrence ◽

Zvart Abaryan ◽

Emily Laltoo ◽

Leanna M. Hernandez ◽

Michael Gandal ◽

...

Keyword(s):

Sex Differences ◽

White Matter ◽

Diffusion Tensor ◽

Adult Brain ◽

Neurite Density ◽

White Matter Microstructure ◽

White Matter Region ◽

Weighted Magnetic Resonance Imaging ◽

Health And Disease ◽

The Impact

AbstractSex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion-weighted magnetic resonance imaging (dMRI) approaches. However, the effect of sex on white matter microstructure prior to adulthood remains poorly understood, with previous developmental work focusing on conventional microstructure metrics and yielding mixed results. Here we thoroughly and rigorously characterized sex differences in white matter microstructure among over 6,000 children from the Adolescent Brain Cognitive Development (ABCD) Study who were between 9 and 10 years old. Microstructure was quantified using both the conventional model - diffusion tensor imaging (DTI) - and an advanced model, restriction spectrum imaging (RSI). DTI metrics included fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). RSI metrics included normalized isotropic, directional, and total intracellular diffusion (N0, ND, NT). We found significant and replicable sex differences in DTI or RSI microstructure metrics in every white matter region examined across the brain. The impact of sex on FA was regionally specific. Across white matter regions, boys exhibited greater MD, AD, and RD than girls, on average. Girls displayed increased N0, ND, and NT compared to boys, on average, suggesting greater cell and neurite density in girls. Together, these robust and replicable findings provide an important foundation for understanding sex differences in health and disease.

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Arterial Stiffness Is Associated with White Matter Disruption and Cognitive Impairment: A Community-Based Cohort Study

Journal of Alzheimer s Disease ◽

10.3233/jad-201424 ◽

2021 ◽

Vol 80 (2) ◽

pp. 567-576

Author(s):

Fei Han ◽

Fei-Fei Zhai ◽

Ming-Li Li ◽

Li-Xin Zhou ◽

Jun Ni ◽

...

Keyword(s):

Cognitive Function ◽

White Matter ◽

Arterial Stiffness ◽

Cognitive Decline ◽

Sex Education ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

White Matter Injury ◽

White Matter Integrity ◽

Cross Sectional

Background: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. Objective: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. Methods: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. Results: Increased baPWV was significantly associated with lower mean global fractional anisotropy (β= –0.118, p < 0.001), higher mean diffusivity (β= 0.161, p < 0.001), axial diffusivity (β= 0.160, p < 0.001), and radial diffusivity (β= 0.147, p < 0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (β= –0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. Conclusion: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.

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Evaluating the performance of 3-tissue constrained spherical deconvolution pipelines for within-tumor tractography

10.1101/629873 ◽

2019 ◽

Cited By ~ 5

Author(s):

Hannelore Aerts ◽

Thijs Dhollander ◽

Daniele Marinazzo

Keyword(s):

White Matter ◽

Tumor Tissue ◽

Diffusion Tensor ◽

Orientation Distribution ◽

Constrained Spherical Deconvolution ◽

Spherical Deconvolution ◽

Fiber Orientation Distribution ◽

Tissue Compartments ◽

Diffusion Tensor Imaging Dti ◽

Single Shell

AbstractThe use of diffusion MRI (dMRI) for assisting in the planning of neurosurgery has become increasingly common practice, allowing to non-invasively map white matter pathways via tractography techniques. Limitations of earlier pipelines based on the diffusion tensor imaging (DTI) model have since been revealed and improvements were made possible by constrained spherical deconvolution (CSD) pipelines. CSD allows to resolve a full white matter (WM) fiber orientation distribution (FOD), which can describe so-called “crossing fibers”: complex local geometries of WM tracts, which DTI fails to model. This was found to have a profound impact on tractography results, with substantial implications for presurgical decision making and planning. More recently, CSD itself has been extended to allow for modeling of other tissue compartments in addition to the WM FOD, typically resulting in a 3-tissue CSD model. It seems likely this may improve the capability to resolve WM FODs in the presence of infiltrating tumor tissue. In this work, we evaluated the performance of 3-tissue CSD pipelines, with a focus on within-tumor tractography. We found that a technique named single-shell 3-tissue CSD (SS3T-CSD) successfully allowed tractography within infiltrating gliomas, without increasing existing single-shell dMRI acquisition requirements.

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Characteristics of the corpus callosum in chronic schizophrenia treated with clozapine or risperidone and those never-treated

BMC Psychiatry ◽

10.1186/s12888-021-03552-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Bo Tao ◽

Yuan Xiao ◽

Hengyi Cao ◽

Wenjing Zhang ◽

Chengmin Yang ◽

...

Keyword(s):

White Matter ◽

Corpus Callosum ◽

Clinical Symptoms ◽

Diffusion Tensor ◽

Structural Characteristics ◽

Chronic Schizophrenia ◽

Cross Sectional Study ◽

Antipsychotic Treatment ◽

Cross Sectional

Abstract Background The corpus callosum (CC) deficits have been well documented in chronic schizophrenia. However, the long-term impacts of antipsychotic monotherapies on callosal anatomy remain unclear. This cross-sectional study sought to explore micro- and macro-structural characteristics of the CC in never-treated patients and those with long-term mono-antipsychotic treatment. Methods The study included 23 clozapine-treated schizophrenia patients (CT-SCZ), 19 risperidone-treated schizophrenia patients (RT-SCZ), 23 never-treated schizophrenia patients (NT-SCZ), and 35 healthy controls (HCs). High resolution structural images and diffusion tensor imaging (DTI) data for each participant were obtained via a 3.0 T MR scanner. FreeSurfer was used to examine the volumes and fractional anisotropy (FA) values of the CC for each participant. Results There were significant deficits in the total and sub-regional CC volume and white matter integrity in NT-SCZ in comparison with healthy subjects. Compared with NT-SCZ, both CT-SCZ and RT-SCZ showed significantly increased FA values in the anterior CC region, while only RT-SCZ showed significantly increased volume in the mid-anterior CC region. Moreover, the volume of the mid-anterior CC region was significantly smaller in CT-SCZ compared to HCs. No correlations of clinical symptoms with callosal metrics were observed in schizophrenia patients. Conclusions Our findings provide insight into micro- and macro-structural characteristics of the CC in chronic schizophrenia patients with or without antipsychotics. These results suggest that the pathology itself is responsible for cerebral abnormalities in schizophrenia and that chronic exposure to antipsychotics may have an impact on white matter structure of schizophrenia patients, especially in those with risperidone treatment.

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White Matter Changes on Diffusion Tensor Imaging in the FINGER Randomized Controlled Trial

Journal of Alzheimer s Disease ◽

10.3233/jad-200423 ◽

2020 ◽

Vol 78 (1) ◽

pp. 75-86

Author(s):

Ruth Stephen ◽

Alina Solomon ◽

Tiia Ngandu ◽

Esko Levälahti ◽

Juha O. Rinne ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Controlled Trial ◽

Intervention Group ◽

Control Group ◽

Pathological Changes ◽

Cognitive Changes ◽

Randomized Controlled ◽

White Matter Microstructure ◽

Multidomain Intervention

Background: Early pathological changes in white matter microstructure can be studied using the diffusion tensor imaging (DTI). It is not only important to study these subtle pathological changes leading to cognitive decline, but also to ascertain how an intervention would impact the white matter microstructure and cognition in persons at-risk of dementia. Objectives: To study the impact of a multidomain lifestyle intervention on white matter and cognitive changes during the 2-year Finnish Geriatric Intervention Study to prevent Cognitive Impairment and Disability (FINGER), a randomized controlled trial in at-risk older individuals (age 60–77 years) from the general population. Methods: This exploratory study consisted of a subsample of 60 FINGER participants. Participants were randomized to either a multidomain intervention (diet, exercise, cognitive training, and vascular risk management, n = 34) or control group (general health advice, n = 26). All underwent baseline and 2-year brain DTI. Changes in fractional anisotropy (FA), diffusivity along domain (F1) and non-domain (F2) diffusion orientations, mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and their correlations with cognitive changes during the 2-year multidomain intervention were analyzed. Results: FA decreased, and cognition improved more in the intervention group compared to the control group (p < 0.05), with no significant intergroup differences for changes in F1, F2, MD, AxD, or RD. The cognitive changes were significantly positively related to FA change, and negatively related to RD change in the control group, but not in the intervention group. Conclusion: The 2-year multidomain FINGER intervention may modulate white matter microstructural alterations.

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Regional brain volumes, microstructure and neurodevelopment in moderate–late preterm children

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2019-317941 ◽

2020 ◽

Vol 105 (6) ◽

pp. 593-599 ◽

Cited By ~ 1

Author(s):

Claire E Kelly ◽

Deanne K Thompson ◽

Alicia J Spittle ◽

Jian Chen ◽

Marc L Seal ◽

...

Keyword(s):

White Matter ◽

Grey Matter ◽

Diffusion Tensor ◽

Brain Mri ◽

Developmental Outcomes ◽

Late Preterm ◽

Brain Volumes ◽

Regional Brain ◽

White Matter Microstructure ◽

Cortical Grey Matter

ObjectiveTo explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate–late preterm (MLPT).Study designA cohort of MLPT infants had brain MRI at approximately TEA (38–44 weeks’ postmenstrual age) and had a developmental assessment (Bayley Scales of Infant and Toddler Development and Infant Toddler Social Emotional Assessment) at 2 years’ corrected age. Relationships between cortical grey matter and white matter volumes and 2-year developmental outcomes were explored using voxel-based morphometry. Relationships between diffusion tensor measures of white matter microstructure (fractional anisotropy (FA) and axial (AD), radial (RD) and mean (MD) diffusivities) and 2-year developmental outcomes were explored using tract-based spatial statistics.Results189 MLPT children had data from at least one MRI modality (volumetric or diffusion) and data for at least one developmental domain. Larger cortical grey and white matter volumes in many brain regions, and higher FA and lower AD, RD and MD in several major white matter regions, were associated with better cognitive and language scores. There was little evidence that cortical grey matter and white matter volumes and white matter microstructure were associated with motor and behavioural outcomes.ConclusionsRegional cortical grey matter and white matter volumes and white matter microstructure are associated with cognitive and language development at 2 years of age in MLPT children. Thus, early alterations to brain volumes and microstructure may contribute to some of the developmental deficits described in MLPT children.

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Dysmature superficial white matter microstructure in developmental focal epilepsy

Brain Communications ◽

10.1093/braincomms/fcz002 ◽

2019 ◽

Vol 1 (1) ◽

Cited By ~ 3

Author(s):

Lauren M Ostrowski ◽

Daniel Y Song ◽

Emily L Thorn ◽

Erin E Ross ◽

Sally M Stoyell ◽

...

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Fine Motor ◽

Epilepsy Syndrome ◽

Healthy Controls ◽

Deep White Matter ◽

White Matter Microstructure ◽

Benign Epilepsy

Abstract Benign epilepsy with centrotemporal spikes is a common childhood epilepsy syndrome that predominantly affects boys, characterized by self-limited focal seizures arising from the perirolandic cortex and fine motor abnormalities. Concurrent with the age-specific presentation of this syndrome, the brain undergoes a developmentally choreographed sequence of white matter microstructural changes, including maturation of association u-fibres abutting the cortex. These short fibres mediate local cortico-cortical communication and provide an age-sensitive structural substrate that could support a focal disease process. To test this hypothesis, we evaluated the microstructural properties of superficial white matter in regions corresponding to u-fibres underlying the perirolandic seizure onset zone in children with this epilepsy syndrome compared with healthy controls. To verify the spatial specificity of these features, we characterized global superficial and deep white matter properties. We further evaluated the characteristics of the perirolandic white matter in relation to performance on a fine motor task, gender and abnormalities observed on EEG. Children with benign epilepsy with centrotemporal spikes (n = 20) and healthy controls (n = 14) underwent multimodal testing with high-resolution MRI including diffusion tensor imaging sequences, sleep EEG recordings and fine motor assessment. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region. We found distinct abnormalities corresponding to the perirolandic u-fibre region, with increased axial, radial and mean diffusivity and fractional anisotropy values in children with epilepsy (P = 0.039, P = 0.035, P = 0.042 and P = 0.017, respectively). Increased fractional anisotropy in this region, consistent with decreased integrity of crossing sensorimotor u-fibres, correlated with inferior fine motor performance (P = 0.029). There were gender-specific differences in white matter microstructure in the perirolandic region; males and females with epilepsy and healthy males had higher diffusion and fractional anisotropy values than healthy females (P ≤ 0.035 for all measures), suggesting that typical patterns of white matter development disproportionately predispose boys to this developmental epilepsy syndrome. Perirolandic white matter microstructure showed no relationship to epilepsy duration, duration seizure free, or epileptiform burden. There were no group differences in diffusivity or fractional anisotropy in superficial white matter outside of the perirolandic region. Children with epilepsy had increased radial diffusivity (P = 0.022) and decreased fractional anisotropy (P = 0.027) in deep white matter, consistent with a global delay in white matter maturation. These data provide evidence that atypical maturation of white matter microstructure is a basic feature in benign epilepsy with centrotemporal spikes and may contribute to the epilepsy, male predisposition and clinical comorbidities observed in this disorder.

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