BrainForge: an online data analysis platform for integrative neuroimaging acquisition, analysis, and sharing.

BrainForge is a cloud-enabled, web-based analysis platform for neuroimaging research. This website allows users to archive data from a study and effortlessly process data on a high-performance computing cluster. After analyses are completed, results can be quickly shared with colleagues. BrainForge solves multiple problems for researchers who want to analyze neuroimaging data, including issues related to software, reproducibility, computational resources, and data sharing. BrainForge can currently process structural, functional, diffusion, and arterial spin labeling MRI modalities, including preprocessing and group level analyses. Additional pipelines are currently being added, and the pipelines can accept the BIDS format. Analyses are conducted completely inside of Singularity containers and utilize popular software packages including Nipype, Statistical Parametric Mapping, the Group ICA of fMRI Toolbox, and FreeSurfer. BrainForge also features several interfaces for group analysis, including a fully automated adaptive ICA approach.

Multi-study evaluation of neuroimaging-based prediction of medication class in mood disorders.

Clinicians often face a dilemma in diagnosing bipolar disorder patients with complex symptoms who spend more time in a depressive state than a manic state. The current gold standard for such diagnosis, the Diagnostic and Statistical Manual (DSM), is not objectively grounded in pathophysiology. In such complex cases, relying solely on the DSM may result in misdiagnosis as major depressive disorder (MDD). A biologically-based classification algorithm that can accurately predict treatment response may help patients suffering from mood disorders. Here we used an algorithm to do so using neuroimaging data. We used the neuromark framework to learn a kernel function for support vector machine (SVM) on multiple feature subspaces. The neuromark framework achieves up to 95.45% accuracy, 0.90 sensitivity, and 0.92 specificity in predicting antidepressant (AD) vs. mood stabilizer (MS) response in patients. We incorporated two additional datasets to evaluate the generalizability of our approach. The trained algorithm achieved up to 89% accuracy, 0.88 sensitivity, and 0.89 specificity in predicting the DSM-based diagnosis on these datasets. We also translated the model to distinguish responders to treatment from nonresponders with up to 70% accuracy. This approach reveals multiple salient biomarkers of medication-class of response within mood disorders.

Federated Analysis in COINSTAC Reveals Functional Network Connectivity and Spectral Links to Smoking and Alcohol Consumption in Nearly 2,000 Adolescent Brains.

With the growth of decentralized/federated analysis approaches in neuroimaging, the opportunities to study brain disorders using data from multiple sites has grown multi-fold. One such initiative is the Neuromark, a fully automated spatially constrained independent component analysis (ICA) that is used to link brain network abnormalities among different datasets, studies, and disorders while leveraging subject-specific networks. In this study, we implement the neuromark pipeline in COINSTAC, an open-source neuroimaging framework for collaborative/decentralized analysis. Decentralized exploratory analysis of nearly 2000 resting-state functional magnetic resonance imaging datasets collected at different sites across two cohorts and co-located in different countries was performed to study the resting brain functional network connectivity changes in adolescents who smoke and consume alcohol. Results showed hypoconnectivity across the majority of networks including sensory, default mode, and subcortical domains, more for alcohol than smoking, and decreased low frequency power. These findings suggest that global reduced synchronization is associated with both tobacco and alcohol use. This proof-of-concept work demonstrates the utility and incentives associated with large-scale decentralized collaborations spanning multiple sites.

Decentralized Brain Age Estimation Using MRI Data.

Recent studies have demonstrated that neuroimaging data can be used to estimate biological brain age, as it captures information about the neuroanatomical and functional changes the brain undergoes during development and the aging process. However, researchers often have limited access to neuroimaging data because of its challenging and expensive acquisition process, thereby limiting the effectiveness of the predictive model. Decentralized models provide a way to build more accurate and generalizable prediction models, bypassing the traditional data-sharing methodology. In this work, we propose a decentralized method for biological brain age estimation using support vector regression models and evaluate it on three different feature sets, including both volumetric and voxelwise structural MRI data as well as resting functional MRI data. The results demonstrate that our decentralized brain age regression models can achieve similar performance compared to the models trained with all the data in one location.

ENIGMA + COINSTAC: Improving Findability, Accessibility, Interoperability, and Re-usability.

The FAIR principles, as applied to clinical and neuroimaging data, reflect the goal of making research products Findable, Accessible, Interoperable, and Reusable. The use of the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymized Computation (COINSTAC) platform in the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium combines the technological approach of decentralized analyses with the sociological approach of sharing data. In addition, ENIGMA + COINSTAC provides a platform to facilitate the use of machine-actionable data objects. We first present how ENIGMA and COINSTAC support the FAIR principles, and then showcase their integration with a decentralized meta-analysis of sex differences in negative symptom severity in schizophrenia, and finally present ongoing activities and plans to advance FAIR principles in ENIGMA + COINSTAC. ENIGMA and COINSTAC currently represent efforts toward improved Access, Interoperability, and Reusability. We highlight additional improvements needed in these areas, as well as future connections to other resources for expanded Findability.

Federated Analysis of Neuroimaging Data: A Review of the Field.

The field of neuroimaging has embraced sharing data to collaboratively advance our understanding of the brain. However, data sharing, especially across sites with large amounts of protected health information (PHI), can be cumbersome and time intensive. Recently, there has been a greater push towards collaborative frameworks that enable large-scale federated analysis of neuroimaging data without the data having to leave its original location. However, there still remains a need for a standardized federated approach that not only allows for data sharing adhering to the FAIR (Findability, Accessibility, Interoperability, Reusability) data principles, but also streamlines analyses and communication while maintaining subject privacy. In this paper, we review a non-exhaustive list of neuroimaging analytic tools and frameworks currently in use. We then provide an update on our federated neuroimaging analysis software system, the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC). In the end, we share insights on future research directions for federated analysis of neuroimaging data.

Federation of Brain Age Estimation in Structural Neuroimaging Data.

Brain age estimation is a widely used approach to evaluate the impact of various neurological or psychiatric brain disorders on the brain developmental or aging process. Current studies show that neuroimaging data can be used to predict brain age, as it captures structural and functional changes that the brain undergoes during development and the aging process. A robust brain age prediction model not only has the potential in assisting early diagnosis of brain disorders but also helps in monitoring and evaluating effects of a treatment. Although access to large amounts of data helps build better models and validate their effectiveness, researchers often have limited access to brain data because of its challenging and expensive acquisition process. This data is not always sharable due to privacy restrictions. Decentralized models provide a way which does not require data exchange between the multiple involved groups. In this work, we propose a decentralized approach for brain age prediction and evaluate our models using features extracted from structural MRI data. Results demonstrate that our decentralized brain age model achieves similar performance compared to the models trained with all the data in one location.

Three-Day Remote Monitoring of Gait Among Young and Older Adults Using Participants' Personal Smartphones.

Conventional one-time gait analyses do not evaluate walking across more than a few steps, cannot monitor changes longitudinally, and do not reflect performance in real-life environments. To successfully quantify age-related gait decrement, technology that can continuously monitor gait is vital. This study examined the feasibility and validity for participant smartphones to remotely assess gait. In addition, the authors investigated whether smartphone-derived measures could differentiate between young and older adults (fallers and nonfallers). A total of 63 adults completed clinical and gait assessment in the laboratory and donned their smartphones for 3 days in the real-life environment. A custom-built Android application collected triaxial accelerations with spatiotemporal gait measures computed and compared between groups. Across 11 brands and 10 Android versions, smartphone-derived gait parameters were valid. Furthermore, results indicated age-related differences in walking during the 3-day assessment. However, no disparities were found between older adult groups. Smartphone-based evaluations may improve real-life screening of adults with gait deficits.

Decentralized Multisite VBM Analysis During Adolescence Shows Structural Changes Linked to Age, Body Mass Index, and Smoking: a COINSTAC Analysis.

There has been an upward trend in developing frameworks that enable neuroimaging researchers to address challenging questions by leveraging data across multiple sites all over the world. One such open-source framework is the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC) that works on Windows, macOS, and Linux operating systems and leverages containerized analysis pipelines to analyze neuroimaging data stored locally across multiple physical locations without the need for pooling the data at any point during the analysis. In this paper, the COINSTAC team partnered with a data collection consortium to implement the first-ever decentralized voxelwise analysis of brain imaging data performed outside the COINSTAC development group. Decentralized voxel-based morphometry analysis of over 2000 structural magnetic resonance imaging data sets collected at 14 different sites across two cohorts and co-located in different countries was performed to study the structural changes in brain gray matter which linked to age, body mass index (BMI), and smoking. Results produced by the decentralized analysis were consistent with and extended previous findings in the literature. In particular, a widespread cortical gray matter reduction (resembling a 'default mode network' pattern) and hippocampal increase with age, bilateral increases in the hypothalamus and basal ganglia with BMI, and cingulate and thalamic decreases with smoking. This work provides a critical real-world test of the COINSTAC framework in a "Large-N" study. It showcases the potential benefits of performing multivoxel and multivariate analyses of large-scale neuroimaging data located at multiple sites.

COINSTAC: Decentralizing the future of brain imaging analysis.

In the era of Big Data, sharing neuroimaging data across multiple sites has become increasingly important. However, researchers who want to engage in centralized, large-scale data sharing and analysis must often contend with problems such as high database cost, long data transfer time, extensive manual effort, and privacy issues for sensitive data. To remove these barriers to enable easier data sharing and analysis, we introduced a new, decentralized, privacy-enabled infrastructure model for brain imaging data called COINSTAC in 2016. We have continued development of COINSTAC since this model was first introduced. One of the challenges with such a model is adapting the required algorithms to function within a decentralized framework. In this paper, we report on how we are solving this problem, along with our progress on several fronts, including additional decentralized algorithms implementation, user interface enhancement, decentralized regression statistic calculation, and complete pipeline specifications.