Microstructure
& Connectivity Lab

Publication collection

Microstructure

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2026
NMR in BiomedicineArticle

Standard Model Imaging in the Brain and Spinal Cord of MS Patients: Initial Assessment and Comparison to Diffusion Tensor Imaging

Atlee Witt et al. · Last author: Kurt Schilling

Same-session brain and spinal cord imaging compares standard diffusion tensor measurements with Standard Model Imaging in 34 people with relapsing-remitting multiple sclerosis and 36 controls. Neurite density estimates show sensitivity to pathology in both regions, while the usefulness of other measurements depends on the anatomical setting.

MicrostructureSpinal Cord
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Standard model imaging parameter maps in the brain and spinal cord of a person with relapsing-remitting MS.
2026
Human Brain MappingArticle

Lifespan Trajectories of Asymmetry in White Matter Tracts

Sam Bogdanov et al. · Last author: Kurt G. Schilling

White matter asymmetry changes with age and depends on which tissue or pathway feature is measured. Using 35,120 individuals from 50 studies, this work charts 30 paired pathways from birth to 100 years. It provides a reference for interpreting lateralization across development and aging.

LifespanTractographyMicrostructure
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Examples of age-dependent white matter asymmetry across microstructural and macrostructural features.
2026
NatureArticle

White matter micro- and macrostructure brain charts for the human lifespan

Michael E. Kim et al. · Last author: Kurt G. Schilling

White matter growth charts built from 35,120 brain scans provide reference trajectories from birth to 100 years. The study measures tissue properties and pathway shape across 72 tracts, enabling age- and sex-adjusted comparisons. Public models, processing tools, and shareable derived data support independent use of the charts.

LifespanMicrostructureTractography
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Lifespan trajectories of white matter microstructure across major brain pathways.
2026
Magnetic Resonance ImagingArticle

Advancing high-resolution 7 T diffusion MRI: Evaluating phase-encoding correction strategies for distortion correction from basic to four-way acquisitions

Kurt G. Schilling, Alexander J.S. Beckett, Matthew Amandola, Erica B. Walker, David A. Feinberg, Silvia A. Bunge, An T. Vu

At 0.9 mm resolution on a NexGen 7T scanner, this study compares 11 time-matched diffusion acquisition and correction strategies. Four-direction phase encoding provides the strongest geometric fidelity and repeatability in five adults scanned twice. The findings inform high-resolution protocols for both fine superficial connections and long-range pathways.

Image ProcessingTractographyMicrostructure
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High-resolution diffusion images and tractography from the four-direction phase-encoding acquisition.
2025
Frontiers in NeuroimagingArticle

Leveling up: along-level diffusion tensor imaging in the spinal cord of multiple sclerosis patients

Atlee A. Witt et al. · Last author: Kurt G. Schilling

Analyzing spinal cord measurements by cervical level reveals localized changes in relapsing-remitting multiple sclerosis that whole-cord averages can miss. The study combines diffusion and structural measurements within white and gray matter regions. Gray matter atrophy relates to disability, while the measured microstructural changes do not show significant disability associations.

Spinal CordMicrostructure
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Whole-cord morphometry, lesion load, and diffusion measurements in healthy controls and people with relapsing-remitting MS.
2025
Imaging NeuroscienceArticle

Characterization of neurite and soma organization in the brain and spinal cord with diffusion MRI

Kurt G. Schilling, Marco Palombo, Atlee A. Witt, Kristin P. O’Grady, Marco Pizzolato, Bennett A. Landman, Seth A. Smith

A shared 3T diffusion MRI protocol characterizes brain and spinal cord microstructure using DTI, Standard Model Imaging, and SANDI. The study evaluates image quality, tissue contrast, and repeatability across the neuroaxis. It establishes the feasibility of combined measurements while identifying greater reproducibility and partial volume challenges in the cord.

MicrostructureSpinal Cord
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SANDI neurite and soma parameter maps in the brain and cervical spinal cord.
2025
Human Brain MappingArticle

White Matter Geometry Confounds Diffusion Tensor Imaging Along Perivascular Space (DTI-ALPS) Measures

Kurt G. Schilling, Allen Newton, Chantal Tax, Markus Nilsson, Maxime Chamberland, Adam Anderson, Bennett Landman, Maxime Descoteaux

The study tests whether DTI-ALPS measurements specifically reflect diffusion along perivascular spaces. Analyses of high-resolution diffusion and vascular imaging show strong effects of fiber crossings, dispersion, and undulation. These anatomical influences complicate interpreting an ALPS index as a direct measurement of glymphatic function across individuals or groups.

MicrostructureImage Processing
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Crossing fibers contribute to radial diffusion asymmetry, a geometrical confound for DTI-ALPS.
2025
Human Brain MappingArticle

Microstructural Characterization of Short Association Fibers Related to Long-Range White Matter Tracts in Normative Development

Chloe Cho, Maxime Chamberland, Francois Rheault, Daniel Moyer, Bennett A. Landman, Kurt G. Schilling

This study compares the development of short association fibers and long-range pathways in 616 participants aged 5.6–21.9 years. Diffusion tensor and NODDI measurements reveal shared age-related patterns alongside distinct features of superficial white matter. The results provide a reference for future studies of atypical development.

MicrostructureLifespanTractography
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Short association fibers mapped relative to long-range white matter pathways.
2025
Scientific ReportsArticle

The relationship of white matter tract orientation to vascular geometry in the human brain

Kurt G. Schilling et al. · Last author: Bennett Landman

Diffusion and susceptibility-weighted imaging reveal how white matter pathways relate to the orientation of nearby blood vessels. Vessels often align with some local fiber populations but do not consistently follow the dominant tract direction or an entire pathway. The findings help interpret MRI contrasts influenced by both vascular and axonal geometry.

MicrostructureTractography
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Examples of alignment and misalignment between white matter tract orientations and vasculature.
2025
Magnetic Resonance in MedicineReview

Considerations and recommendations from the ISMRM diffusion study group for preclinical diffusion MRI : Part 2—Ex vivo imaging: Added value and acquisition

Kurt G. Schilling et al. · Last author: Ileana O. Jelescu

The second ISMRM preclinical diffusion MRI paper examines the value of ex vivo imaging and how to acquire reliable data. It covers specimen selection, fixation, preparation, and scanning. The recommendations explain both the opportunities for detailed tissue characterization and the experimental differences that complicate comparison with living tissue.

Reviews & ConsensusMicrostructure
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High-resolution ex vivo human imaging supports detailed tissue maps and tractography.
2025
Magnetic Resonance in MedicineReview

Considerations and recommendations from the ISMRM diffusion study group for preclinical diffusion MRI : Part 1: In vivo small-animal imaging

Ileana O. Jelescu et al. · Last author: Kurt G. Schilling

The first paper in the ISMRM preclinical diffusion MRI series presents community recommendations for imaging living small animals. It covers model selection, preparation, acquisition, processing, and interpretation, with an emphasis on reproducibility. The authors also identify open methodological questions and resources for sharing data and software.

Reviews & ConsensusMicrostructureTractography
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Diffusion MRI across small-animal models illustrates differences in brain size, geometry, and tissue organization.
2025
Human Brain MappingArticle

Head Motion in Diffusion Magnetic Resonance Imaging: Quantification, Mitigation, and Structural Associations in Large, Cross-Sectional Datasets Across the Lifespan

Kurt G. Schilling et al. · Last author: Bennett A. Landman

Across 13 cohorts spanning infancy to old age, this study characterizes head motion and its relationship to diffusion MRI measurements. Scan–rescan comparisons examine the effectiveness of modern preprocessing, while population analyses investigate structural associations with motion. The findings help distinguish acquisition artifacts from differences associated with the people who move.

Image ProcessingLifespanMicrostructure
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Head motion varies across age, tending to decrease toward young adulthood and increase with aging.
2023
NeuroImageArticle

Denoising of diffusion MRI in the cervical spinal cord – effects of denoising strategy and acquisition on intra-cord contrast, signal modeling, and feature conspicuity

Kurt G. Schilling et al. · Last author: Kristin P. O’Grady

Phantom and human experiments compare three denoising methods for spinal cord diffusion MRI. MPPCA and Patch2Self improved image quality, tissue contrast, and precision even with the small direction counts common in clinical scans, while all tested methods improved visibility of multiple sclerosis lesions in diffusion-weighted images.

Spinal CordImage ProcessingMicrostructure
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Spinal cord diffusion images before and after denoising across vendors and acquisition settings.
2023
Aging BrainArticle

Short superficial white matter and aging: A longitudinal multi-site study of 1293 subjects and 2711 sessions

Kurt G. Schilling et al. · Last author: Bennett A. Landman

Short superficial white matter pathways show widespread age-related diffusion changes and regionally varying reductions in length and volume. Data from 1,293 participants distinguish changes in fibers connecting neighboring gyri from those running within a gyrus, extending aging research beyond long-range bundles.

LifespanTractographyMicrostructure
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The short superficial white matter pathways used to characterize aging across longitudinal cohorts.
2023
Imaging NeuroscienceArticle

White matter tract microstructure, macrostructure, and associated cortical gray matter morphology across the lifespan

Kurt G. Schilling et al. · Last author: Bennett A. Landman

Across 2,789 imaging sessions spanning ages 0–100, this study links tract microstructure, tract geometry, and the morphology of connected cortex. Different features and pathways mature and decline on different schedules, and developmental age associations are related to patterns observed during aging.

LifespanTractographyMicrostructure
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Tract-specific lifespan trajectories of fractional anisotropy and intracellular volume fraction.
2022
Brain Structure and FunctionArticle

Aging and white matter microstructure and macrostructure: a longitudinal multi-site diffusion MRI study of 1218 participants

Kurt G. Schilling et al. · Last author: Bennett A. Landman

Across 1,218 older adults, diffusion measurements and tract shape both changed with age. Microstructural trends were relatively widespread, while volume, length, and surface-area changes differed more across pathways, suggesting that bundle geometry adds complementary information about aging.

LifespanTractographyMicrostructure
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White matter pathways colored by age associations with microstructural and shape measurements.
2022
Cerebral Cortex CommunicationsArticle

Anomalous and heterogeneous characteristics of the BOLD hemodynamic response function in white matter

Kurt G Schilling, Muwei Li, Francois Rheault, Zhaohua Ding, Adam W Anderson, Hakmook Kang, Bennett A Landman, John C Gore

White matter has a different BOLD hemodynamic response from gray matter, and the response varies within and between pathways. These differences also relate to diffusion MRI measures of tissue microstructure.

Functional ConnectivityMicrostructure
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Hemodynamic response functions vary across and along white matter pathways.
2022
Magnetic Resonance ImagingArticle

Minimal number of sampling directions for robust measures of the spherical mean diffusion weighted signal: Effects of sampling directions, b-value, signal-to-noise ratio, hardware, and fitting strategy

Kurt G. Schilling, Marco Palombo, Kristin P. O'Grady, Anna J.E. Combes, Adam W. Anderson, Bennett A. Landman, Seth A. Smith

Simulations and brain and spinal cord measurements establish how many diffusion directions are needed to estimate the spherical mean signal reliably. A lookup table links sampling requirements to diffusion weighting, signal-to-noise ratio, and fitting choices.

MicrostructureImage ProcessingSpinal Cord
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Brain spherical-mean diffusion signals estimated from full and reduced acquisition schemes.
2022
Human Brain MappingArticle

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

Kurt G. Schilling, Chantal M. W. Tax, Francois Rheault, Bennett A. Landman, Adam W. Anderson, Maxime Descoteaux, Laurent Petit

Distinct white matter bundles frequently share the same local orientation before diverging, creating ambiguities that better crossing-fiber detection cannot resolve. This study maps such bottlenecks across the brain and finds them throughout major pathway classes, including regions often described as containing a single fiber orientation.

TractographyMicrostructure
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Distinct pathways converge within a small occipital white matter region, illustrating the tractography bottleneck problem.
2021
NeuroImageArticle

On the generalizability of diffusion MRI signal representations across acquisition parameters, sequences and tissue types: Chronicles of the MEMENTO challenge

Alberto De Luca et al. · Last author: Kurt G. Schilling

The MEMENTO challenge tests how diffusion MRI signal models generalize to unseen measurements and different encoding schemes. Results show that fitting choices and hyperparameters matter alongside model selection, with double and oscillating encoding proving especially challenging.

MicrostructureImage Processing
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Measured and predicted diffusion signals compared across models and tissue configurations.
2020
Journal of Neuroscience MethodsReview

Challenges for biophysical modeling of microstructure

Ileana O. Jelescu, Marco Palombo, Francesca Bagnato, Kurt G. Schilling

This review follows diffusion MRI biophysical models from design to clinical application. It explains how model assumptions, acquisition choices, parameter estimation, and validation determine what can be inferred about tissue, and why interpreting model parameters becomes especially difficult in disease.

MicrostructureReviews & Consensus
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A roadmap for developing, estimating, and validating diffusion MRI models of tissue microstructure.
2019
NeuroinformaticsArticle

A Web-Based Atlas Combining MRI and Histology of the Squirrel Monkey Brain

Kurt G. Schilling, Yurui Gao, Matthew Christian, Vaibhav Janve, Iwona Stepniewska, Bennett A. Landman, Adam W. Anderson

CHIASM combines structural MRI, diffusion MRI, histological stains, and motor-cortex tracing in a common squirrel monkey reference space. The integrated atlas lets researchers compare tissue appearance across modalities and use labeled cortical regions and white matter pathways for anatomical localization.

Image ProcessingTractographyMicrostructure
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MRI contrasts and matched histological modalities included in the squirrel monkey atlas.
2019
NeuroImageArticle

Diffusion MRI microstructural models in the cervical spinal cord – Application, normative values, and correlations with histological analysis

Kurt G. Schilling, Samantha By, Haley R. Feiler, Bailey A. Box, Kristin P. O’Grady, Atlee Witt, Bennett A. Landman, Seth A. Smith

DTI, NODDI, and spherical mean techniques were evaluated in the cervical spinal cords of 21 healthy participants. Comparisons with a histological template showed sensitivity to tissue differences but limited specificity for the biological properties that model parameters are often assumed to measure.

Spinal CordMicrostructure
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Population-average DTI, NODDI, and spherical mean technique parameter maps in the cervical spinal cord.
2019
NMR in BiomedicineArticle

Histologically derived fiber response functions for diffusion MRI vary across white matter fibers—An ex vivo validation study in the squirrel monkey brain

Kurt G. Schilling, Yurui Gao, Iwona Stepniewska, Vaibhav Janve, Bennett A. Landman, Adam W. Anderson

Histology from three squirrel monkey brains shows that diffusion MRI fiber response functions vary across white matter regions. Choosing a different response function changes reconstructed fiber orientations and can alter tractography accuracy.

MicrostructureTractography
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Histologically derived fiber response functions vary across regions of the same brain.
2018
Human Brain MappingArticle

Confirmation of a gyral bias in diffusion MRI fiber tractography

Kurt Schilling, Yurui Gao, Vaibhav Janve, Iwona Stepniewska, Bennett A. Landman, Adam W. Anderson

Comparing tractography with myelin-stained histology confirms that streamlines preferentially terminate on gyral crowns. The bias persists across tracking algorithms, diffusion models, weightings, and high-resolution acquisitions, complicating interpretation of cortical connectivity from streamline density.

TractographyMicrostructure
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Histology and diffusion MRI workflow for testing tractography bias across gyral blades.
2018
NeuroImageArticle

Histological validation of diffusion MRI fiber orientation distributions and dispersion

Kurt G. Schilling, Vaibhav Janve, Yurui Gao, Iwona Stepniewska, Bennett A. Landman, Adam W. Anderson

Histological validation compares several diffusion reconstruction methods against three-dimensional fiber geometry. Models captured overall angular structure better than discrete peak counts or low-angle crossings, and no method led across all accuracy criteria; dispersion estimates also showed limited agreement with histology.

TractographyMicrostructure
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Histological fiber orientations compared with eight diffusion MRI reconstruction methods.
2017
NMR in BiomedicineArticle

Can increased spatial resolution solve the crossing fiber problem for diffusion MRI?

Kurt Schilling, Yurui Gao, Vaibhav Janve, Iwona Stepniewska, Bennett A. Landman, Adam W. Anderson

Ex vivo diffusion MRI and matched histology challenge the assumption that smaller voxels eliminate crossing fibers. Across the tested scales, finer resolution revealed more complex orientations, indicating that tissue geometry remains a fundamental obstacle even when image resolution improves.

TractographyMicrostructure
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Histology and diffusion MRI reveal fiber geometry and crossing-fiber estimates across spatial scales.
2017
Proceedings of SPIE: Medical Imaging 2017, Image ProcessingConference paper

Effects of b-Value and Number of Gradient Directions on Diffusion MRI Measures Obtained with Q-ball Imaging

Kurt G. Schilling, Vishwesh Nath, Justin Blaber, Robert L. Harrigan, Zhaohua Ding, Adam W. Anderson, Bennett A. Landman

This full conference paper uses eleven repeated diffusion acquisitions to examine q-ball measurement precision. It shows that directional sampling and the spherical harmonic model can bias tissue and orientation metrics, helping explain why acquisition choices must be evaluated together with the reconstruction method.

Image ProcessingMicrostructure
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Q-ball diffusion orientation estimates across diffusion weightings and gradient-direction counts.
2017
Magnetic Resonance ImagingArticle

Empirical consideration of the effects of acquisition parameters and analysis model on clinically feasible q-ball imaging

Kurt G. Schilling, Vishwesh Nath, Justin A. Blaber, Prasanna Parvathaneni, Adam W. Anderson, Bennett A. Landman

Repeated scans test how short clinical q-ball acquisitions balance diffusion weighting, direction count, and model complexity. The analysis shows that spherical harmonic order strongly affects derived metrics and that adding directions can be more useful than repeating measurements within a fixed scan time.

Image ProcessingMicrostructureTractography
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Q-ball orientation estimates across diffusion weightings, gradient counts, and spherical harmonic orders.
2017
Magnetic Resonance ImagingArticle

Reproducibility and variation of diffusion measures in the squirrel monkey brain, in vivo and ex vivo

Kurt Schilling, Yurui Gao, Iwona Stepniewska, Ann S. Choe, Bennett A. Landman, Adam W. Anderson

Repeated in vivo and ex vivo imaging of three squirrel monkeys establishes reference diffusion measurements and their variability. Mean diffusivity was relatively reproducible, while fractional anisotropy varied more across regions and subjects; fixation substantially changed both measures.

MicrostructureImage Processing
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Repeated in vivo and ex vivo diffusion orientation and anisotropy maps of the same squirrel monkey brain.
2017
NeuroinformaticsArticle

The VALiDATe29 MRI Based Multi-Channel Atlas of the Squirrel Monkey Brain

Kurt G. Schilling et al. · Last author: Adam W. Anderson

VALiDATe29 provides a common anatomical reference built from MRI of 29 squirrel monkeys. Structural, diffusion, and ex vivo templates are paired with cortical and white matter labels to support registration, regional measurements, and comparisons across animals and experiments.

Image ProcessingTractographyMicrostructure
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Surface renderings of cortical and white matter labels in the VALiDATe29 squirrel monkey atlas.
2016
NeuroImageArticle

Comparison of 3D Orientation Distribution Functions Measured with Confocal Microscopy and Diffusion MRI

Kurt Schilling, Vaibhav Janve, Yurui Gao, Iwona Stepniewska, Bennett A. Landman, Adam W. Anderson

Three-dimensional confocal microscopy provides a direct reference for testing diffusion MRI estimates of fiber orientation. Comparisons with constrained spherical deconvolution found good agreement for nearly parallel fibers but larger errors in crossing regions, including failure to resolve crossings below 60 degrees in this dataset.

TractographyMicrostructure
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Comparison of histological and diffusion MRI fiber orientations in crossing and fanning regions.