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Alexander Leemans

Publications and source records attributed to Alexander Leemans.

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Proceedings for the Inaugural Meeting of the International Society for Tractography -- IST 2025 Bordeaux

This collection comprises the abstracts presented during poster, power pitch and oral sessions at the Inaugural Conference of the International Society for Tractography (IST Conference 2025), held in Bordeaux, France, from October 13-16, 2025. The conference was designed to foster meaningful exchange and collaboration between disparate fields. The overall focus was on advancing research, innovation, and community in the common fields of interest: neuroanatomy, tractography methods and scientific/clinical applications of tractography. The included abstracts cover the latest advancements in tractography, Diffusion MRI, and related fields including new work on; neurological and psychiatric disorders, deep brain stimulation targeting, and brain development. This landmark event brought together world-leading experts to discuss critical challenges and chart the future direction of the field.

eess.IV

Millennium Pathways for Tractography: 40 grand challenges to shape the future of tractography

In the spirit of the historic Millennium Prize Problems that heralded a new era for mathematics, the newly formed International Society for Tractography (IST) has launched the Millennium Pathways for Tractography, a community-driven roadmap designed to shape the future of the field. Conceived during the inaugural Tract-Anat Retreat, this initiative reflects a collective vision for advancing tractography over the coming decade and beyond. The roadmap consists of 40 grand challenges, developed by international experts and organized into seven categories spanning three overarching themes: neuroanatomy, tractography methods, and clinical applications. By defining shared short-, medium-, and long-term goals, these pathways provide a structured framework to confront fundamental limitations, promote rigorous validation, and accelerate the translation of tractography into a robust tool for neuroscience and medicine. Ultimately, the Millennium Pathways aim to guide and inspire future research and collaboration, ensuring the continued scientific and clinical relevance of tractography well into the future.

physics.med-ph

Considerations and recommendations from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 3 -- Ex vivo imaging: data processing, comparisons with microscopy, and tractography

Preclinical diffusion MRI (dMRI) has proven value in methods development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages that facilitate high spatial resolution and high signal-to-noise ratio (SNR) images, cutting-edge diffusion contrasts, and direct comparison with histological data as a methodological validation. However, there are a number of considerations that must be made when performing ex vivo experiments. The steps from tissue preparation, image acquisition and processing, and interpretation of results are complex, with many decisions that not only differ dramatically from in vivo imaging of small animals, but ultimately affect what questions can be answered using the data. This work concludes a 3-part series of recommendations and considerations for preclinical dMRI. Herein, we describe best practices for dMRI of ex vivo tissue, with a focus on image pre-processing, data processing and model fitting, and tractography. In each section, we attempt to provide guidelines and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should lie. We end by providing guidelines on code sharing and data sharing, and point towards open-source software and databases specific to small animal and ex vivo imaging.

physics.med-ph

Tractography derived quantitative estimates of tissue microstructure depend on streamline length: A characterization and method of adjustment

Tractography algorithms are used extensively to delineate white matter structures, by operating on the voxel-wise information generated through the application of diffusion tensor imaging (DTI) or other models to diffusion weighted (DW) magnetic resonance imaging (MRI) data. We demonstrate that these methods commonly yield systematic streamline length dependent distortions of tractography derived tissue microstructure parameters, such as fractional anisotropy (FA). This dependency may be described as piecewise linear. For streamlines shorter than an inflection point (determined for a group of tracts delineated for each individual brain), estimates of tissue microstructure exhibit a positive linear relation with streamline length. For streamlines longer than the point of inflection, the association is weaker, with the slope of the relationship between streamline length and tissue microstructure differing only marginally from zero. As the dependency is most pronounced for a range of streamline lengths encountered typically in DW imaging of the human brain (less than ~100 mm), our results suggest that some previous estimates of tissue microstructure should be treated with considerable caution. A method is described, whereby an Akaike information weighted average of linear, Blackman and piecewise linear model predictions, may be used to compensate effectively for the dependence of FA (and other estimates of tissue microstructure) on streamline length, across the entire range of streamline lengths present in each specimen.

q-bio.QM

Considerations and recommendations from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 2 -- Ex vivo imaging: added value and acquisition

The value of preclinical diffusion MRI (dMRI) is substantial. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages including higher signal-to-noise ratio and spatial resolution compared to in vivo studies, and enabling more advanced diffusion contrasts. Another major advantage of ex vivo dMRI is the direct comparison with histological data as a methodological validation. However, there are a number of considerations that must be made when performing ex vivo experiments. The steps from tissue preparation, image acquisition and processing, and interpretation of results are complex, with decisions that not only differ dramatically from in vivo imaging of small animals, but ultimately affect what questions can be answered using the data. This work represents "Part 2" of a 3-part series of recommendations and considerations for preclinical dMRI. We describe best practices for dMRI of ex vivo tissue, with a focus on the value that ex vivo imaging adds to the field of dMRI and considerations in ex vivo image acquisition. We give general considerations and foundational knowledge that must be considered when designing experiments. We describe differences in specimens and models and discuss why some may be more or less appropriate for different studies. We then give guidelines for ex vivo protocols, including tissue fixation, sample preparation, and MR scanning. In each section, we attempt to provide guidelines and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should lie. An overarching goal herein is to enhance the rigor and reproducibility of ex vivo dMRI acquisitions and analyses, and thereby advance biomedical knowledge.

physics.med-ph

Considerations and Recommendations from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 1 -- In vivo small-animal imaging

Small-animal diffusion MRI (dMRI) has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the resultant data. This work aims to present selected recommendations and guidelines from the diffusion community, on best practices for preclinical dMRI of in vivo animals. We describe the general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in animal species and disease models and discuss why some may be more or less appropriate for different studies. We then give guidelines for in vivo acquisition protocols, including decisions on hardware, animal preparation, and imaging sequences, followed by advice for data processing including pre-processing, model-fitting, and tractography. Finally, we provide an online resource which lists publicly available preclinical dMRI datasets and software packages, to promote responsible and reproducible research. In each section, we attempt to provide guides and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should focus. While we mainly cover the central nervous system (on which most preclinical dMRI studies are focused), we also provide, where possible and applicable, recommendations for other organs of interest. An overarching goal herein is to enhance the rigor and reproducibility of small animal dMRI acquisitions and analyses, and thereby advance biomedical knowledge.

physics.med-ph

Harmonization of diffusion MRI datasets with adaptive dictionary learning

Diffusion magnetic resonance imaging is a noninvasive imaging technique that can indirectly infer the microstructure of tissues and provide metrics which are subject to normal variability across subjects. Potentially abnormal values or features may yield essential information to support analysis of controls and patients cohorts, but subtle confounds affecting diffusion MRI, such as those due to difference in scanning protocols or hardware, can lead to systematic errors which could be mistaken for purely biologically driven variations amongst subjects. In this work, we propose a new harmonization algorithm based on adaptive dictionary learning to mitigate the unwanted variability caused by different scanner hardware while preserving the natural biological variability present in the data. Overcomplete dictionaries, which are learned automatically from the data and do not require paired samples, are then used to reconstruct the data from a different scanner, removing variability present in the source scanner in the process. We use the publicly available database from an international challenge to evaluate the method, which was acquired on three different scanners and with two different protocols, and propose a new mapping towards a scanner-agnostic space. Results show that the effect size of the four studied diffusion metrics is preserved while removing variability attributable to the scanner. Experiments with alterations using a free water compartment, which is not simulated in the training data, shows that the effect size induced by the alterations is also preserved after harmonization. The algorithm is freely available and could help multicenter studies in pooling their data, while removing scanner specific confounds, and increase statistical power in the process.

eess.IV

Generalized Richardson-Lucy (GRL) for analyzing multi-shell diffusion MRI data

Spherical deconvolution is a widely used approach to quantify fiber orientation distribution from diffusion MRI data. The damped Richardson-Lucy (dRL) is developed to perform robust spherical deconvolution on single shell diffusion MRI data. While the dRL algorithm could in theory be directly applied to multi-shell data, it is not optimised to model the signal from multiple tissue types. In this work, we introduce a new framework based on dRL - dubbed Generalized Richardson Lucy (GRL) - that uses multi-shell data in combination with user-chosen tissue models to disentangle partial volume effects and increase the accuracy in FOD estimation. The optimal weighting of multi-shell data in the fit and the robustness to noise and partial volume effects of GRL was studied with synthetic data. Subsequently, we investigated the performances of GRL in comparison to dRL on a high-resolution diffusion MRI dataset from the Human Connectome Project and on an MRI dataset acquired at 3T on a clinical scanner. The feasibility of including intra-voxel incoherent motion (IVIM) effects in the modelling was studied on a third dataset. Results of simulations show that GRL can robustly disentangle different tissue types at SNR above 20 and improves the angular accuracy of the FOD estimation. On real data, GRL provides signal fraction maps that are physiologically plausible and consistent between datasets. When considering IVIM effects, high blood pseudo-diffusion fraction is observed in the medial temporal lobe and in the sagittal sinus. In comparison to dRL, GRL provides sharper FODs and less spurious peaks in presence of partial volume effects and results in a better tract termination at the grey/white matter interface or at the outer cortical surface. In conclusion, GRL offers a new modular and flexible framework to perform spherical deconvolution of multi-shell data.

physics.med-ph

Automated characterization of noise distributions in diffusion MRI data

Knowledge of the noise distribution in diffusion MRI is the centerpiece to quantify uncertainties arising from the acquisition process. Accurate estimation beyond textbook distributions often requires information about the acquisition process, which is usually not available. We introduce two new automated methods using the moments and maximum likelihood equations of the Gamma distribution to estimate all unknown parameters using only the magnitude data. A rejection step is used to make the framework automatic and robust to artifacts. Simulations were created for two diffusion weightings with parallel imaging. Furthermore, MRI data of a water phantom with different combinations of parallel imaging were acquired. Finally, experiments on freely available datasets are used to assess reproducibility when limited information about the acquisition protocol is available. Additionally, we demonstrated the applicability of the proposed methods for a bias correction and denoising task on an in vivo dataset. A generalized version of the bias correction framework for non integer degrees of freedom is also introduced. The proposed framework is compared with three other algorithms with datasets from three vendors, employing different reconstruction methods. Simulations showed that assuming a Rician distribution can lead to misestimation of the noise distribution in parallel imaging. Results showed that signal leakage in multiband can also lead to a misestimation of the noise distribution. Repeated acquisitions of in vivo datasets show that the estimated parameters are stable and have lower variability than compared methods. Results show that the proposed methods reduce the appearance of noise at high b-value. The proposed algorithms herein can estimate both parameters of the noise distribution automatically, are robust to signal leakage artifacts and perform best when used on acquired noise maps.

eess.IV

On the sensitivity of the diffusion MRI signal to brain activity in response to a motor cortex paradigm

Diffusion functional MRI (dfMRI) is a promising technique to map functional activations by acquiring diffusion-weighed spin-echo images. In previous studies, dfMRI showed higher spatial accuracy at activation mapping compared to classic functional MRI approaches. However, it remains unclear whether dfMRI measures result from changes in the intra-/extracellular environment, perfusion and/or T2 values. We designed an acquisition/quantification scheme to disentangle such effects in the motor cortex during a finger tapping paradigm. dfMRI was acquired at specific diffusion weightings to selectively suppress perfusion and free-water diffusion, then times series of the apparent diffusion coefficient (ADC-fMRI) and of the perfusion signal fraction (IVIM-fMRI) were derived. ADC-fMRI provided ADC estimates sensitive to changes in perfusion and free-water volume, but not to T2/T2* values. With IVIM-fMRI we isolated the perfusion contribution to ADC, while suppressing T2 effects. Compared to conventional gradient-echo BOLD fMRI, activation maps obtained with dfMRI and ADC-fMRI had smaller clusters, and the spatial overlap between the three techniques was below 50%. Increases of perfusion fractions were observed during task in both dfMRI and ADC-fMRI activations. Perfusion effects were more prominent with ADC-fMRI than with dfMRI but were significant in less than 25% of activation ROIs. Taken together, our results suggest that the sensitivity to task of dfMRI derives from a decrease of hindered diffusion and an increase of the pseudo-diffusion signal fraction, leading to different, more confined spatial activation patterns compared to classic functional MRI.

physics.med-ph

Reducing variability in along-tract analysis with diffusion profile realignment

Diffusion weighted MRI (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 HCP, we simulated changes in mean diffusivity, fractional anisotropy and apparent fiber density. Pairwise 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.

q-bio.QM

Automatic, fast and robust characterization of noise distributions for diffusion MRI

Knowledge of the noise distribution in magnitude diffusion MRI images is the centerpiece to quantify uncertainties arising from the acquisition process. The use of parallel imaging methods, the number of receiver coils and imaging filters applied by the scanner, amongst other factors, dictate the resulting signal distribution. Accurate estimation beyond textbook Rician or noncentral chi distributions often requires information about the acquisition process (e.g. coils sensitivity maps or reconstruction coefficients), which is not usually available. We introduce a new method where a change of variable naturally gives rise to a particular form of the gamma distribution for background signals. The first moments and maximum likelihood estimators of this gamma distribution explicitly depend on the number of coils, making it possible to estimate all unknown parameters using only the magnitude data. A rejection step is used to make the method automatic and robust to artifacts. Experiments on synthetic datasets show that the proposed method can reliably estimate both the degrees of freedom and the standard deviation. The worst case errors range from below 2% (spatially uniform noise) to approximately 10% (spatially variable noise). Repeated acquisitions of in vivo datasets show that the estimated parameters are stable and have lower variances than compared methods.

cs.CV