Aperture Neuro

Macaque MRI bridges non-invasive systems neuroscience with cellular and circuit-level mechanisms, but preprocessing remains fragmented across tools that are difficult to integrate, adapt to non-human primate acquisitions, and deploy reproducibly. We present Brainana, an automated, BIDS-compatible preprocessing framework for macaque neuroimaging. Brainana integrates structural and functional preprocessing, cortical surface reconstruction, quality control, transform tracking, and atlas projection within a containerized package, with cloud access for users without local compute. It incorporates macaque-trained deep learning models for brain extraction and tissue segmentation, conformation to standardize variable acquisitions, and surface reconstruction optimizations for macaque neuroanatomy. Across 23 imaging sites, Brainana processed data spanning heterogeneous scanners, protocols, species, and resolutions, yielding accurate anatomical correspondence across 130 monkeys, reliable native-space cortical surfaces, localized task-evoked activations, and reproducible brain-wide resting-state correlation structure. Brainana enables reproducible, scalable, and accessible macaque MRI preprocessing that supports cross-study comparison and multimodal integration across spatial scales, from neurons to networks.

Cerebral microbleeds (CMBs) are established imaging biomarkers of cerebral small vessel disease and are a defining feature of cerebral amyloid angiopathy (CAA), yet their automated detection in susceptibility-weighted imaging (SWI) remains challenging due to high false-positive rates from vessel cross-sections, iron and calcium deposits, and other hypointense mimics. We present a fully automated, three-stage cascade pipeline that combines subject-adaptive unsupervised candidate generation with two successive lightweight 3D ResNet classifiers, trained with only human-in-the-loop quality-assurance (QA) labels (yes/no per candidate) rather than dense voxel-wise segmentation masks. The candidate generation stage is performed by fitting a Gaussian Mixture Model (GMM) to each subjects SWI intensity histogram to define an adaptive low-intensity threshold, followed by anatomical masking to exclude physiologically irrelevant regions (image edges, ventricles/CSF/choroid plexus, and cerebellum), and filters candidates by size and sphericity. The model was trained and evaluated across a nested 3x5-fold cross-validation on N = 30 subjects from a publicly available labeled microbleed dataset and a CAA cohort (11,424 CMB candidate lesions) with data augmentation during training. Stage A classifies all geometric candidates as CMB or non-CMB and Stage B refines the predicted positives to suppress false positives (cascade AUC = 0.9587, sensitivity = 0.712, specificity = 0.975, PPV = 0.676, F1 = 0.693). The cascade reduces Stage A false positives by 76.8% (888/1,157 false positives eliminated) while retaining competitive sensitivity. Inference was performed on 141 SWI scans, detecting a mean 40.3 CMBs per scan and being preferred for use in 85% of high CMB cases, as evaluated by a blinded neurologist. The inference pipeline outputs binary CMB segmentation NIfTI images and radiologist-ready QA visualizations.

As multisite and multi-study data aggregation becomes increasingly common for improving statistical power and sample diversity, robust harmonization methods are needed to address biases introduced by batch variation, particularly in neuroimaging research. Although a variety of harmonization approaches are available, the lack of systematic guidance for diagnosing batch effects and selecting appropriate methods remains a major challenge. To address this gap, we introduce ComBatFamQC, a comprehensive R package designed to streamline batch-effect diagnosis, harmonization, and post-harmonization analysis. ComBatFamQC integrates a user-friendly Shiny app for interactive batch-effect diagnostics, state-of-the-art harmonization methods from the ComBat family, including ComBat, longitudinal ComBat, ComBat-GAM, and CovBat, and tools for downstream analysis after harmonization. The package provides qualitative visualizations, statistical tests for batch-effect assessment, and a consistent interface that supports both in-sample and out-of-sample harmonization through the Shiny app, the R console, or the command line. In addition, it includes functions for post-harmonization analyses to facilitate downstream modeling. Its modular design also supports the systematic incorporation of future harmonization methods and expanded downstream analysis capabilities.

BackgroundMagnetoencephalography (MEG) is a unique technique in human neuroimaging combining high temporal resolution (millisecond or faster) with moderate spatial resolution (several millimeter). While many software packages for MEG data analysis exist, there is no pipeline developed for the specific purpose of enabling the automated analysis of very large, multi-site datasets. ResultsThe ENIGMA consortium was developed to enable large scale collaborations in the fields of neuroimaging and genetics. To facilitate ENIGMA MEG working group data analysis, we developed the ENIGMA MEG pipeline. The first ENIGMA MEG working group project involves spectral analysis of resting state MEG data, thus our current pipeline is designed to carry out that task. The goals of the ENIGMA MEG pipeline include ease of use, automated processing wherever possible, detailed logging and quality assurance (QA) features, the use of the brain imaging data structure (BIDS) format, anonymized output, and consistent processing across vendors. The pipeline is built using the MNE-Python framework and incorporates a re-trained version of the MEGnet deep neural network algorithm for automated artifact detection. QA tools are designed to enable high throughput evaluation of a large number of subject datasets. All software is open source and available on GitHub (https://github.com/nih-megcore/enigma_MEG). We used our pipeline to process data from three publicly available MEG cohorts, demonstrating its functionality and compatibility with large-scale processing. ConclusionsWhile the current ENIGMA pipeline is limited to resting state data and spectral analysis for the current working group project, the software is highly modularized, allowing straightforward extension to other analysis questions. Further development of the tool to enable connectivity and task-based MEG analysis are planned. The ENIGMA MEG pipeline represents an important first step to augment the existing arsenal of analysis tools, enabling multi-site, high throughput data analysis.

Traditional fMRI studies rely on predefined task paradigms, where fixed stimulus designs limit the flexibility with which brain-stimulus relationships can be explored. Here, we introduce Reinforcement Learning via Brain Feedback (RLBF), a framework and open-source software package for adaptive stimulus optimization using real-time fMRI. RLBF reverses the conventional direction of inference by using neural responses to guide the exploration of stimulus spaces through reinforcement learning, enabling optimization of predefined brain targets such as regional activity or multivariate neural signatures. The accompanying Python-based software provides a modular framework integrating real-time fMRI data processing, reinforcement learning agents, adaptive stimulus generation, simulation-based testing, and experiment monitoring. Its flexible architecture allows researchers to customize preprocessing pipelines, reward functions, stimulus spaces, and RL strategies for diverse closed-loop neuroimaging applications. We validate the framework in a proof-of-concept study (N=10), demonstrating real-time optimization of a simple visual stimulus space by adapting checkerboard contrast and frequency to maximize primary visual cortex (V1) responses within a single 10-minute fMRI session. RLBF provides an extensible foundation for brain-guided stimulus optimization and enables new approaches for investigating neural specificity, individualized brain-stimulus relationships, and adaptive experimental design.

PurposeTo develop and evaluate a multi-model consensus deep learning approach for automated gold fiducial marker (FM) segmentation in T1-weighted prostate MRI. Materials and MethodsIn this retrospective study, T1-weighted MRI and CT-derived reference standard segmentations were collected from 127 prostate cancer patients (all male; mean age, 70 years {+/-} 7 [standard deviation]; age range, 50-88 years; collected between October 2020 and January 2026) who each had three implanted gold FMs. A 3D U-Net was trained on 93 subjects using four random seeds to produce an ensemble. At inference, marker-class probability maps were averaged across models and the top three connected components selected. Performance was evaluated on 34 temporally held-out subjects (9 tuning, 25 test) using marker-level sensitivity and precision with exact (Clopper-Pearson) 95% confidence intervals (CIs). A model count ablation study was performed. The pipeline was deployed for on-scanner processing on Siemens MRI systems via the OpenRecon framework and as a browser-based application using WebAssembly, executing entirely client-side. ResultsThe four-model consensus achieved 96% (70 of 73) sensitivity and 95% (70 of 74) precision on 25 test subjects, with 29 of 34 (85%) subjects achieving perfect marker detection. Single models had a mean sensitivity of 84% (SD, 9%), improving to 96% with four-model consensus (SD, <1%). ConclusionMulti-model consensus deep learning substantially improved FM segmentation reliability over individual models, achieving high sensitivity and precision using only routinely acquired T1-weighted MRI.

Understanding vascular contributions to disease is a major unmet need. White matter lesions (WML) are an accepted imaging marker of cerebral small vessel disease, giving insights into its related pathologies. A unified approach for WML analyses in large multi-site data is lacking despite the need for pooling of data to overcome the limitations of often small heterogenous MRI studies which make subtyping and identifying patterns within disease groups difficult. Our ENIGMA-PD-WML pipeline is an open-source containerized pipeline containing all the code and packages required for pre-processing, processing and post-processing of T1-weighted and FLAIR data, outputting accurate and reproducible binary WML maps using a UNet approach. The pipeline provides a standardized image analysis approach for WML and outputs data in both native and MNI space to allow for sharing and pooling of data from multiple sites for large-data analysis. In addition to a reliable standardized approach for WML segmentation, key priorities when developing the pipeline included: usability, i.e., requiring minimal manual input and technical expertise to use, and suitability to run on various MRI scanners and acquisition parameters as is common in multi-site data. This paper describes the pipeline in detail, with rationale for each step, providing transparency and facilitating its usage to overcome reproducibility issues in large-scale WML analyses.

We demonstrate that features extracted from structural MRI using un-CNN, an untrained convolutional neural network, achieve predictive performance comparable to or exceeding that of state-of-the-art pretrained foundation models across three structural MRI datasets and three downstream tasks. Un-CNN extends a classical 3D CNN architecture with multi-channel inputs, a hierarchical encoder with multi-scale feature aggregation, and covariance pooling. Untrained CNNs circumvent several key limitations of trained models, including high computational cost and memory requirements, the need to distribute large model weights, risks of data leakage, and challenges in reproducibility.

1.IntroductionUnderstanding mid-term test-retest reliability and within-subject variability is important for interpreting changes observed in longitudinal and intervention studies. The reliability of resting-state functional magnetic resonance imaging (rs-fMRI) is known to vary across measures and brain regions. However, how reliability differs across functional networks and connectivity-and amplitude-based measures, and whether multi-echo acquisition and processing modify these patterns, remain incompletely characterized. MethodsTwenty-two healthy volunteers underwent two rs-fMRI sessions 15.7 {+/-} 4.0 days apart on a Compact 3T scanner. Multi-echo, middle-echo, and independently acquired single-echo datasets were compared, with multi-echo independent component analysis additionally evaluated as a denoising approach. Functional connectivity (FC) and three amplitude-based measures were evaluated using the Schaefer 400 parcellation. Reliability was systematically assessed using intraclass correlation coefficient (ICC), within-subject standard deviation (wSD), and systematic bias at edge or regional, and network levels. ResultsAcquisition-dependent differences in reliability were generally modest. Multi-echo acquisition and processing increased functional connectivity strength and the magnitude of amplitude-based measures and improved inferior cortical coverage, but these enhancements did not consistently translate into substantially higher ICC or lower wSD. In contrast, reliability showed clear network-dependent differences. FC reliability varied markedly across network pairs and was not explained by connectivity strength alone; pairs involving the default mode and control networks generally showed more favorable profiles than several somatomotor and visual network pairs. Fractional amplitude of low-frequency fluctuations (fALFF) also showed network-dependent reliability, with the most favorable regional reproducibility observed in the default mode and control networks and lower reproducibility in the somatomotor and visual networks. ConclusionThese findings provide practical mid-term reliability benchmarks for rs-fMRI on a Compact 3T scanner and show that measurement stability varies more clearly across measures and functional networks than across acquisition approaches. Key pointsO_LIMid-term test-retest reliability varied more clearly across resting-state measures and functional networks than across acquisition and processing approaches. C_LIO_LIMulti-echo acquisition and processing enhanced functional connectivity strength, amplitude-based signal magnitude, and inferior cortical coverage but did not consistently improve reliability. C_LIO_LIFunctional connectivity strength and fractional amplitude of low-frequency fluctuations showed distinct network-specific reliability profiles, with more favorable reproducibility in default mode and control networks than in several somatomotor and visual networks. C_LI

PurposeRecent improvements in MRI gradient design and amplifiers, advanced MRI scanners are now routinely utilizing slew rates of several hundred T/m/s. However, full gradient performance cannot be exploited in high-resolution EPI due to peripheral nerve stimulation (PNS) limits. We aim to characterize and mitigate these PNS constraints using a simple sequence modification: PNS-optimized EPI gradient pulse shapes. MethodsPNS-Optimized Pulses for EPI (POPE): we selectively reduce the slew rate of gradient pulses at periods of high predicted PNS spikes, while leaving the rest of the waveform unchanged. PNS sensation was evaluated. ResultsPOPE allows 7%-35% faster imaging of EPI protocols resolutions of 1mm-0.3mm resolutions without exceeding predicted PNS. With such improvements, POPE allows robust 0.3 mm isotropic fMRI protocols that would have exceeded safety limits without it. ConclusionPOPE facilitates locally precise fMRI activation mapping on clinical 7T scanners at spatial resolution that were previously unattainable due to PNS limitations.

Objective: Impaired understanding of noisy or degraded speech is a central feature of listening difficulties (LiD), but the possible causes of these symptoms are wide-ranging. Accordingly, recent research underscores the need to study these deficits using a test battery approach. Event-related potentials are useful objective metrics for studying LiD, but probing function across the speech processing hierarchy using traditional protocols is sequential and unrealistic in clinical settings. The novel chirped speech (Cheech) method combines natural speech with acoustic chirps to overcome these limitations. This study examines its utility for profiling childhood LiD. Methods: Twenty-eight children (15 typically developing, 13 with LiD), aged 8-17 years old, listened to a 17-minute Cheech story and detected a target word within the story via button press while EEG data were collected from 53 scalp sites. Results: Cheech successfully evoked responses from the auditory brainstem response through to the brain's language centers, as reflected by the N400 effect. Unlike TD children, those with LiD demonstrated N400 effects with atypical distributions that favored frontal rather than the typical parietal sites. A trend towards a delayed and reduced amplitude Wave V was also observed. Conclusions: Hierarchical examination of speech processing using Cheech primarily implicates altered language processing as a contributing factor to LiD, with the frontal topography of the N400 effect for those with LiD potentially suggesting a greater reliance on deliberate memory retrieval during the speech perception task. Significance: LiD could arise due to auditory and/or cognitive factors. The present results demonstrate the feasibility of objective, parallel measurement across this hierarchy and point to impaired language processing as a possible mechanism.

Purpose: To develop and evaluate an anatomy-aware deep learning framework for enhancement of neonatal 64mT T2-weighted MRI that improves anatomical visibility while preserving native ultra-low-field contrast and enabling quantitative structural analysis. Methods: A multitask network, jointly performing image enhancement and tissue segmentation, was trained on 75 and evaluated on 20 paired neonatal 64mT/3T MRI datasets spanning a broad range of gestational ages and pathologies. To preserve native 64mT contrast, 3T images were locally harmonized before training. The framework also generated quality-control maps and regional volumetric measurements. Volumetric agreement was further assessed in 40 paired term-born control datasets. Results: Enhanced 64mT images showed improved image quality metrics and better delineation of cortical, deep gray matter, ventricular, white matter, and posterior fossa structures while maintaining native contrast characteristics. Tissue segmentations demonstrated good agreement with reference 3T labels. Volumetric measurements showed excellent correspondence with 3T across major tissue compartments, with only small systematic regional biases. Conclusions: Anatomy-aware enhancement enables automated tissue segmentation and volumetric analysis directly from neonatal 64mT MRI while preserving native image contrast. These findings support the feasibility of quantitative neonatal neuroimaging at ultra-low field.

As neuroimaging analysis shifts toward large-scale, multi-site studies, managing the unwanted variability introduced by combining heterogeneous datasets has become a critical challenge. Although tools such as ComBat and its neuroimaging extensions are widely used to address this variability, they only permit the modeling of categorical site effects and cannot account for continuous sources of confounding, such as image quality, head motion, and acquisition parameters. We introduce ComCat, an extension of the ComBat framework that preserves biologically relevant covariates while removing the effects of categorical site indicators and continuous nuisance variables. The latter are modeled as smooth nonlinear functions via B-spline basis expansion. ComCat is applicable to a broad range of brain analysis tasks, including voxel- and surface-based morphometry, normative modeling, and machine learning-based prediction. To demonstrate its capabilities, we evaluated ComCat on brain age prediction across five datasets covering complementary multi-site harmonization scenarios: ON-Harmony (10 subjects x 6 scanners; n = 80); the Buchert traveling-phantom dataset (1 subject x 116 scanners; n = 531); the Tohoku single-scanner, varying-acquisition dataset (n = 121); MR-ART (148 subjects with varying motion levels); and an ABIDE subset comprising 229 control subjects and 208 individuals with autism spectrum disorder across 14 scanners. Using image quality measures derived from CAT12 as continuous nuisance variables, ComCat reduced the mean absolute error (MAE) in brain age prediction relative to ComBat-GAM in all five datasets, including the two scenarios where site information was unavailable or uninformative. In the ABIDE dataset, ComCat improved harmonization while preserving the difference between the control and ASD groups, demonstrating that scanner-related variance can be removed without affecting biologically meaningful signals. ComCat can operate with or without site labels and is agnostic to the source of image quality metrics.

Mapping brain connectivity in primates remains a major challenge due to difficulties in resolving microscopic white matter architecture, while maintaining whole-brain coverage. Increasing imaging spatial resolution is key for disambiguating fibre configurations within smaller anatomical volumes. Here, we present novel developments that allow high-resolution diffusion MRI of the macaque brain using one of the world's highest-field human MRI scanners operating at 10.5 Tesla, allowing both in vivo and ex vivo macaque brain imaging. Our approach achieves very high spatial resolution across both tissue states, (up to 580 m)3 in vivo and (300 m)3 ex vivo, with diffusion weighting up to b = 6000 s/mm2. We detail methodological advances in data acquisition, image reconstruction, processing and whole-brain tractography that overcome critical challenges associated with ultra-high-field imaging. This work establishes a new framework for high-resolution in vivo and ex vivo neuroimaging of the NHP brain at 10.5 T using a human bore scanner, paving the way for subsequent analyses of brain connectivity across species and tissue states at unprecedented detail. The dataset, along with all processing pipelines, containerised workflows, and reusable web services, is openly shared to support reproducibility and future integration with microscopy for studying white matter microstructure and connections at the mesoscale.

Portable low-field MRI systems are a promising complement to conventional high-field systems, enabling broader access to MRI. However, correspondence in cortical thickness estimates between low- and high-field MRI in young people remains limited despite its importance for neurodevelopment and psychopathology. To evaluate how multiple low-field image processing approaches improve cortical thickness correspondence with high-field MRI in a large sample of young individuals, we collected ultra-low-field (64mT) and high-field (3T) MRI data from a community sample of young people. We applied deep learning-based image processing approaches (SynthSR v1.0, SynthSR v2.0, recon-all-clinical, and recon-any) to low-field data acquired across multiple sequences (T1- and T2-weighted) and orientations (axial, coronal, sagittal, and multi-orientation), with and without resampling and/or co-registration. We assessed global, lobar, and regional cortical thickness correspondence with 3T MRI measures using Pearson and intraclass correlations. We compared pipelines using Steigers Z-tests and Fishers Z-tests. A total of 150 individuals (mean age, 18.63{+/-}5.07; 80 female) were included. We observed the highest global correspondence with recon-all-clinical applied to coronal T1-weighted images (r=0.40, pFDR=2.6e-05). At the lobar and regional levels, multi-orientation T2-weighted images processed with recon-all-clinical showed the highest correspondence across the greatest number of regions (4/12 lobes; 13/68 regions). The highest correspondence and largest improvements were in frontal, cingulate, and temporal regions, including the right pars triangularis (r=0.52, pFDR=4.78e-11; Z=4.78, pFDR=4.25e-06), right caudal anterior cingulate (r=0.47, pFDR=3.83e-09; Z=5.46, pFDR=1.32e-07), and left parahippocampal (r=0.58, pFDR=2.98e-14; Z=5.17, pFDR=6.01e-07). We observed significantly improved cortical thickness correspondence in low-field MRI in young people. The recon-all-clinical pipeline yielded moderate correspondence, particularly in frontal, cingulate, and temporal regions. Our results highlight the potential of low-field MRI as an affordable and scalable approach for assessing cortical thickness in young people.

Accurate localization of anatomical landmarks is a foundational skill in anatomy and imaging that is often taught informally through expert mentorship, requiring access to data and desktop software. There is no openly accessible, interactive resource that teaches neuroanatomy with quantitative feedback. We present the AFIDs-Validator (validator.afids.io), an open-access, browser-based platform that pairs guided instruction with quantitative assessment. The platform combines (1) a learning mode in which a language-model neuroanatomy tutor operates inside an MRI viewer, giving anatomy-first instruction that responds to the learner's current image slice, orientation, and cursor position; and (2) a validation engine that accepts a learner's landmark file and returns per-landmark Euclidean error against expert-annotated references spanning 21 brain templates. To make the feedback interpretable, we analyzed 15,000 landmark annotations across 132 human subjects and found that landmark difficulty varies fourfold (median error ranged from 0.37 mm at the anterior commissure to 1.50 mm at the temporal horns) with heavy-tailed distributions at every landmark. These distributions are compiled into per-landmark reliability priors, so learners are scored against the empirical spread of trained raters rather than an arbitrary threshold, and difficult landmarks are not mistaken for poor performance. The AFIDs-Validator requires no installation, licensed software, or local data, and all code, reference data, and tutor design are openly released.

Diffusion MRI (dMRI) enables assessment of white matter microstructural abnormalities in Alzheimers disease (AD), and multisite datasets enable more robust modeling of non-biological variation that can confound analyses. The Alzheimers Disease Neuroimaging Initiative (ADNI) includes over 10 dMRI protocols, necessitating robust methods to model protocol-related variability when pooling data. Here, we compared three harmonization approaches: (1) mixed-effects models, (2) ComBat-GAM, and (3) eHarmonize, a reference-based lifespan method. We assessed their ability to reduce protocol-related variability in diffusion tensor imaging fractional anisotropy (FA) and mean diffusivity (MD) while preserving associations with cognitive impairment (CI), and amyloid-beta (A{beta}) and tau PET burden in 1,086 ADNI3/4 participants. All approaches yielded more closely aligned FA/MD distributions across protocols. Associations with clinical indicators of CI were highly consistent across approaches, whereas PET associations were less widespread and more variable. Overall, multiple strategies effectively modeled protocol-related variability while preserving AD-related associations.

The human brain undergoes rapid developmental changes through early life, underpinning the emergence of function but also marking a period of vulnerability to a range of neurodevelopmental disorders. With dynamic changes to brain size, morphology, and imaging contrast, consistent and accurate computational neuroanatomy remains a challenge. Deep learning tools for segmentation, like SynthSeg, offer robustness to heterogeneously acquired MRI contrast but remain unproven in early development. Here, we aggregated a large cohort (26k) of MRI scans spanning infant to adult development, and evaluated SynthSeg performance. Automated quality control scores, visual inspection, and spatial overlap with expert-segmented MRI scans revealed poor quality output segmentations during development. In the infant period only 36% of scans (1094/3069) passed automated QC. Rescaling infant scans to adult brain sizes significantly improved spatial overlap, and cropping scans to match adult fields of view retrieved automated quality control. Evaluation of the SynthSeg rescale + crop pipeline demonstrated visible and quantitative improvements in segmentation throughout infancy and childhood. There were marked increases in successful segmentations in infant scans, with 91% of scans now passing QC (2803/3069). These findings facilitate computational analysis of typical and disrupted neurodevelopment and should be considered when training the next generation of computational tools.

Intracranial electroencephalography (iEEG) provides an unprecedented opportunity to directly record neural activity and causally perturb the human brain through electrical stimulation. Yet, the increasingly collaborative nature and complexity of modern iEEG studies pose substantial challenges for experimental control, data quality, and standardization. Unlike most experimental modalities, human iEEG data are acquired within dynamic clinical environments, where patient condition, recording quality, hardware configuration, and experimental protocols may vary across recording sessions and collaborating sites. The resulting heterogeneity creates opportunities for technical and procedural failures that often remain undetected until downstream analyses, when corrective action is no longer possible. Here, we present a framework for standardized session-level quality assurance in human iEEG research and provide an open-source implementation compatible with Brain Imaging Data Structure (BIDS)-organized datasets. The framework defines four complementary domains of quality assessment crucial for human iEEG studies: protocol fidelity, behavioral integrity, stimulation validation, and signal quality. These domains integrate electrophysiological recordings, behavioral event logs, and stimulation metadata to verify data completeness, confirm participant engagement, validate stimulation delivery, and identify potentially compromised recording channels. Automated quality metrics and standardized diagnostic visualizations are generated following each testing session, enabling rapid identification of technical and procedural failures while corrective action is still possible. By providing a standardized approach to session-level quality assurance, the framework improves data integrity, enhances reproducibility, facilitates analyst training, and supports harmonized data collection across laboratories and clinical sites.

Transparent assessment of diffusion magnetic resonance imaging (dMRI) techniques with empirical verification of confounding factors requires adequately designed protocols and collected datasets. Publicly available diffusion-weighted MR datasets often provide limited sampling across b-values, making it difficult to study optimal acquisition protocols or the relationships between different processes occurring in brain tissue. In this work, we introduce a new densely sampled longitudinal test-retest diffusion-weighted MR dataset of the brain. Our dataset was collected from eleven healthy volunteers, each scanned four times: two sessions on consecutive days, which form the test data, followed by two additional sessions completed one week later (retest data). The data were acquired using twenty-two b-values ranging from 10 to 3000 s/mm2, along with structural T1-weighted scans. Potential applications of the dataset include, but are not limited to, assessing longitudinal reproducibility and reliability of quantitative metrics, evaluating robust and outlier-resistant estimation techniques, investigating experimental factors affecting estimation procedures, and verifying optimal acquisition protocols for different signal models. The dataset is publicly available in raw and fully preprocessed variants.