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Mindboggle (http://mindboggle.info) is an open source brain morphometry platform that takes in preprocessed T1-weighted MRI data and outputs volume, surface, and tabular data containing label, feature, and shape information for further analysis. In this article, we document the software and demonstrate its use in studies of shape variation in healthy and diseased humans. The number of different shape measures and the size of the populations make this the largest and most detailed shape analysis of human brains ever conducted. Brain image morphometry shows great potential for providing much-needed biological markers for diagnosing, tracking, and predicting progression of mental health disorders. Very few software algorithms provide more than measures of volume and cortical thickness, while more subtle shape measures may provide more sensitive and specific biomarkers. Mindboggle computes a variety of (primarily surface-based) shapes: area, volume, thickness, curvature, depth, Laplace-Beltrami spectra, Zernike moments, etc. We evaluate Mindboggle's algorithms using the largest set of manually labeled, publicly available brain images in the world and compare them against state-of-the-art algorithms where they exist. All data, code, and results of these evaluations are publicly available.

The United States National Institutes of Health (NIH) commit significant support to open-source data and software resources in order to foment reproducibility in the biomedical imaging sciences. Here, we report and evaluate a recent product of this commitment: Advanced Neuroimaging Tools (ANTs), which is approaching its 2.0 release. The ANTs open source software library consists of a suite of state-of-the-art image registration, segmentation and template building tools for quantitative morphometric analysis. In this work, we use ANTs to quantify, for the first time, the impact of similarity metrics on the affine and deformable components of a template-based normalization study. We detail the ANTs implementation of three similarity metrics: squared intensity difference, a new and faster cross-correlation, and voxel-wise mutual information. We then use two-fold cross-validation to compare their performance on openly available, manually labeled, T1-weighted MRI brain image data of 40 subjects (UCLA's LPBA40 dataset). We report evaluation results on cortical and whole brain labels for both the affine and deformable components of the registration. Results indicate that the best ANTs methods are competitive with existing brain extraction results (Jaccard=0.958) and cortical labeling approaches. Mutual information affine mapping combined with cross-correlation diffeomorphic mapping gave the best cortical labeling results (Jaccard=0.669±0.022). Furthermore, our two-fold cross-validation allows us to quantify the similarity of templates derived from different subgroups. Our open code, data and evaluation scripts set performance benchmark parameters for this state-of-the-art toolkit. This is the first study to use a consistent transformation framework to provide a reproducible evaluation of the isolated effect of the similarity metric on optimal template construction and brain labeling. ►A new, fast implementation of the cross-correlation that increases computational efficiency by a factor of 4 to 5 and allows larger correlation windows to be used for registration without excessive increase in computation time. ►Open-source implementation of the mutual information for symmetric diffeomorphic registration. ►A reproducible system for performance evaluation of the mean squares metric, cross-correlation metric and mutual information metric on optimal template-based brain extraction and regional brain labeling. The full evaluation system is documented in a bash script that is also released and available. The script is also being translated to python. ►Quantification of the similarity between optimal templates derived from different population subsets and with different similarity metrics.

Many studies of the human brain have explored the relationship between cortical thickness and cognition, phenotype, or disease. Due to the subjectivity and time requirements in manual measurement of cortical thickness, scientists have relied on robust software tools for automation which facilitate the testing and refinement of neuroscientific hypotheses. The most widely used tool for cortical thickness studies is the publicly available, surface-based FreeSurfer package. Critical to the adoption of such tools is a demonstration of their reproducibility, validity, and the documentation of specific implementations that are robust across large, diverse imaging datasets. To this end, we have developed the automated, volume-based Advanced Normalization Tools (ANTs) cortical thickness pipeline comprising well-vetted components such as SyGN (multivariate template construction), SyN (image registration), N4 (bias correction), Atropos (n-tissue segmentation), and DiReCT (cortical thickness estimation). In this work, we have conducted the largest evaluation of automated cortical thickness measures in publicly available data, comparing FreeSurfer and ANTs measures computed on 1205 images from four open data sets (IXI, MMRR, NKI, and OASIS), with parcellation based on the recently proposed Desikan–Killiany–Tourville (DKT) cortical labeling protocol. We found good scan–rescan repeatability with both FreeSurfer and ANTs measures. Given that such assessments of precision do not necessarily reflect accuracy or an ability to make statistical inferences, we further tested the neurobiological validity of these approaches by evaluating thickness-based prediction of age and gender. ANTs is shown to have a higher predictive performance than FreeSurfer for both of these measures. In promotion of open science, we make all of our scripts, data, and results publicly available which complements the use of open image data sets and the open source availability of the proposed ANTs cortical thickness pipeline. •A complete, volumetric-based cortical thickness pipeline is proposed.•The pipeline consists of well-vetted components fine-tuned by the original developers.•Approximately 1200 data were analyzed with no major failures.•All software is open source as part of the ANTs repository.•Analysis and visualization scripts using the R statistical package are also publicly available.

Remote health assessments that gather real-world data (RWD) outside clinic settings require a clear understanding of appropriate methods for data collection, quality assessment, analysis and interpretation. Here we examine the performance and limitations of smartphones in collecting RWD in the remote mPower observational study of Parkinson’s disease (PD). Within the first 6 months of study commencement, 960 participants had enrolled and performed at least five self-administered active PD symptom assessments (speeded tapping, gait/balance, phonation or memory). Task performance, especially speeded tapping, was predictive of self-reported PD status (area under the receiver operating characteristic curve (AUC) = 0.8) and correlated with in-clinic evaluation of disease severity ( r  = 0.71; P  < 1.8 × 10 −6 ) when compared with motor Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Although remote assessment requires careful consideration for accurate interpretation of RWD, our results support the use of smartphones and wearables in objective and personalized disease assessments. Smartphone sensors that monitor disease symptoms enable remote assessment of Parkinson’s patients.

Current measures of health and disease are often insensitive, episodic, and subjective. Further, these measures generally are not designed to provide meaningful feedback to individuals. The impact of high-resolution activity data collected from mobile phones is only beginning to be explored. Here we present data from mPower, a clinical observational study about Parkinson disease conducted purely through an iPhone app interface. The study interrogated aspects of this movement disorder through surveys and frequent sensor-based recordings from participants with and without Parkinson disease. Benefitting from large enrollment and repeated measurements on many individuals, these data may help establish baseline variability of real-world activity measurement collected via mobile phones, and ultimately may lead to quantification of the ebbs-and-flows of Parkinson symptoms. App source code for these data collection modules are available through an open source license for use in studies of other conditions. We hope that releasing data contributed by engaged research participants will seed a new community of analysts working collaboratively on understanding mobile health data to advance human health. Design Type(s) observation design • time series design • repeated measure design Measurement Type(s) disease severity measurement Technology Type(s) Patient Self-Report Factor Type(s) Sample Characteristic(s) Homo sapiens Machine-accessible metadata file describing the reported data (ISA-Tab format)

Data sharing is increasingly recommended as a means of accelerating science by facilitating collaboration, transparency, and reproducibility. While few oppose data sharing philosophically, a range of barriers deter most researchers from implementing it in practice. To justify the significant effort required for sharing data, funding agencies, institutions, and investigators need clear evidence of benefit. Here, using the International Neuroimaging Data-sharing Initiative, we present a case study that provides direct evidence of the impact of open sharing on brain imaging data use and resulting peer-reviewed publications. We demonstrate that openly shared data can increase the scale of scientific studies conducted by data contributors, and can recruit scientists from a broader range of disciplines. These findings dispel the myth that scientific findings using shared data cannot be published in high-impact journals, suggest the transformative power of data sharing for accelerating science, and underscore the need for implementing data sharing universally. Data sharing is recognized as a way to promote scientific collaboration and reproducibility, but some are concerned over whether research based on shared data can achieve high impact. Here, the authors show that neuroimaging papers using shared data are no less likely to appear in top-ranked journals.

All fields of neuroscience that employ brain imaging need to communicate their results with reference to anatomical regions. In particular, comparative morphometry and group analysis of functional and physiological data require coregistration of brains to establish correspondences across brain structures. It is well established that linear registration of one brain to another is inadequate for aligning brain structures, so numerous algorithms have emerged to nonlinearly register brains to one another. This study is the largest evaluation of nonlinear deformation algorithms applied to brain image registration ever conducted. Fourteen algorithms from laboratories around the world are evaluated using 8 different error measures. More than 45,000 registrations between 80 manually labeled brains were performed by algorithms including: AIR, ANIMAL, ART, Diffeomorphic Demons, FNIRT, IRTK, JRD-fluid, ROMEO, SICLE, SyN, and four different SPM5 algorithms (“SPM2-type” and regular Normalization, Unified Segmentation, and the DARTEL Toolbox). All of these registrations were preceded by linear registration between the same image pairs using FLIRT. One of the most significant findings of this study is that the relative performances of the registration methods under comparison appear to be little affected by the choice of subject population, labeling protocol, and type of overlap measure. This is important because it suggests that the findings are generalizable to new subject populations that are labeled or evaluated using different labeling protocols. Furthermore, we ranked the 14 methods according to three completely independent analyses (permutation tests, one-way ANOVA tests, and indifference-zone ranking) and derived three almost identical top rankings of the methods. ART, SyN, IRTK, and SPM's DARTEL Toolbox gave the best results according to overlap and distance measures, with ART and SyN delivering the most consistently high accuracy across subjects and label sets. Updates will be published on the http://www.mindboggle.info/papers/ website.

Few would argue that science is better done in silos, with no transparency or sharing of methods and resources. Yet scientists and scientific stakeholders (e.g., academic institutions, funding agencies, journals) alike continue to find themselves at a relative impasse in the implementation of open science practices, slowing advancement and inadvertently perpetuating ongoing crises surrounding reproducibility. The present commentary draws attention to critical gaps in the current scientific ecosystem that perpetuate closed science practices and divide the community on how to best move forward. It also challenges scientists as individuals to improve the quality of their science by incorporating open practices in their everyday work, and provides a starter list of steps that any researcher can take to be the change they seek.

Establishing correspondences across brains for the purposes of comparison and group analysis is almost universally done by registering images to one another either directly or via a template. However, there are many registration algorithms to choose from. A recent evaluation of fully automated nonlinear deformation methods applied to brain image registration was restricted to volume-based methods. The present study is the first that directly compares some of the most accurate of these volume registration methods with surface registration methods, as well as the first study to compare registrations of whole-head and brain-only (de-skulled) images. We used permutation tests to compare the overlap or Hausdorff distance performance for more than 16,000 registrations between 80 manually labeled brain images. We compared every combination of volume-based and surface-based labels, registration, and evaluation. Our primary findings are the following: 1. de-skulling aids volume registration methods; 2. custom-made optimal average templates improve registration over direct pairwise registration; and 3. resampling volume labels on surfaces or converting surface labels to volumes introduces distortions that preclude a fair comparison between the highest ranking volume and surface registration methods using present resampling methods. From the results of this study, we recommend constructing a custom template from a limited sample drawn from the same or a similar representative population, using the same algorithm used for registering brains to the template.

Inconsistencies in survey-based (eg, questionnaire) data collection across biomedical, clinical, behavioral, and social sciences pose challenges to research reproducibility. ReproSchema is an ecosystem that standardizes survey design and facilitates reproducible data collection through a schema-centric framework, a library of reusable assessments, and computational tools for validation and conversion. Unlike conventional survey platforms that primarily offer graphical user interface-based survey creation, ReproSchema provides a structured, modular approach for defining and managing survey components, enabling interoperability and adaptability across diverse research settings. This study examines ReproSchema's role in enhancing research reproducibility and reliability. We introduce its conceptual and practical foundations, compare it against 12 platforms to assess its effectiveness in addressing inconsistencies in data collection, and demonstrate its application through 3 use cases: standardizing required mental health survey common data elements, tracking changes in longitudinal data collection, and creating interactive checklists for neuroimaging research. We describe ReproSchema's core components, including its schema-based design; reusable assessment library with >90 assessments; and tools to validate data, convert survey formats (eg, REDCap [Research Electronic Data Capture] and Fast Healthcare Interoperability Resources), and build protocols. We compared 12 platforms-Center for Expanded Data Annotation and Retrieval, formr, KoboToolbox, Longitudinal Online Research and Imaging System, MindLogger, OpenClinica, Pavlovia, PsyToolkit, Qualtrics, REDCap, SurveyCTO, and SurveyMonkey-against 14 findability, accessibility, interoperability, and reusability (FAIR) principles and assessed their support of 8 survey functionalities (eg, multilingual support and automated scoring). Finally, we applied ReproSchema to 3 use cases-NIMH-Minimal, the Adolescent Brain Cognitive Development and HEALthy Brain and Child Development Studies, and the Committee on Best Practices in Data Analysis and Sharing Checklist-to illustrate ReproSchema's versatility. ReproSchema provides a structured framework for standardizing survey-based data collection while ensuring compatibility with existing survey tools. Our comparison results showed that ReproSchema met 14 of 14 FAIR criteria and supported 6 of 8 key survey functionalities: provision of standardized assessments, multilingual support, multimedia integration, data validation, advanced branching logic, and automated scoring. Three use cases illustrating ReproSchema's flexibility include standardizing essential mental health assessments (NIMH-Minimal), systematically tracking changes in longitudinal studies (Adolescent Brain Cognitive Development and HEALthy Brain and Child Development), and converting a 71-page neuroimaging best practices guide into an interactive checklist (Committee on Best Practices in Data Analysis and Sharing). ReproSchema enhances reproducibility by structuring survey-based data collection through a structured, schema-driven approach. It integrates version control, manages metadata, and ensures interoperability, maintaining consistency across studies and compatibility with common survey tools. Planned developments, including ontology mappings and semantic search, will broaden its use, supporting transparent, scalable, and reproducible research across disciplines.