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Availability of large and diverse medical datasets is often challenged by privacy and data sharing restrictions. For successful application of machine learning techniques for disease diagnosis, prognosis, and precision medicine, large amounts of data are necessary for model building and optimization. To help overcome such limitations in the context of brain MRI, we present GenMIND: a collection of generative models of normative regional volumetric features derived from structural brain imaging. GenMIND models are trained on real brain imaging regional volumetric measures from the iSTAGING consortium, which encompasses over 40,000 MRI scans across 13 studies, incorporating covariates such as age, sex, and race. Leveraging GenMIND, we produce and offer 18,000 synthetic samples spanning the adult lifespan (ages 22-90 years), alongside the model's capability to generate unlimited data. Experimental results indicate that samples generated from GenMIND agree with the distributions obtained from real data. Most importantly, the generated normative data significantly enhance the accuracy of downstream machine learning models on tasks such as disease classification. Data and models are available at: https://huggingface.co/spaces/rongguangw/GenMIND.

Pediatric central nervous system tumors are the leading cause of cancer-related deaths in children. The five-year survival rate for high-grade glioma in children is less than 20%. The development of new treatments is dependent upon multi-institutional collaborative clinical trials requiring reproducible and accurate centralized response assessment. We present the results of the BraTS-PEDs 2023 challenge, the first Brain Tumor Segmentation (BraTS) challenge focused on pediatric brain tumors. This challenge utilized data acquired from multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. BraTS-PEDs 2023 aimed to evaluate volumetric segmentation algorithms for pediatric brain gliomas from magnetic resonance imaging using standardized quantitative performance evaluation metrics employed across the BraTS 2023 challenges. The top-performing AI approaches for pediatric tumor analysis included ensembles of nnU-Net and Swin UNETR, Auto3DSeg, or nnU-Net with a self-supervised framework. The BraTSPEDs 2023 challenge fostered collaboration between clinicians (neuro-oncologists, neuroradiologists) and AI/imaging scientists, promoting faster data sharing and the development of automated volumetric analysis techniques. These advancements could significantly benefit clinical trials and improve the care of children with brain tumors.

We describe the design and results from the BraTS 2023 Intracranial Meningioma Segmentation Challenge. The BraTS Meningioma Challenge differed from prior BraTS Glioma challenges in that it focused on meningiomas, which are typically benign extra-axial tumors with diverse radiologic and anatomical presentation and a propensity for multiplicity. Nine participating teams each developed deep-learning automated segmentation models using image data from the largest multi-institutional systematically expert annotated multilabel multi-sequence meningioma MRI dataset to date, which included 1000 training set cases, 141 validation set cases, and 283 hidden test set cases. Each case included T2, T2/FLAIR, T1, and T1Gd brain MRI sequences with associated tumor compartment labels delineating enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Participant automated segmentation models were evaluated and ranked based on a scoring system evaluating lesion-wise metrics including dice similarity coefficient (DSC) and 95% Hausdorff Distance. The top ranked team had a lesion-wise median dice similarity coefficient (DSC) of 0.976, 0.976, and 0.964 for enhancing tumor, tumor core, and whole tumor, respectively and a corresponding average DSC of 0.899, 0.904, and 0.871, respectively. These results serve as state-of-the-art benchmarks for future pre-operative meningioma automated segmentation algorithms. Additionally, we found that 1286 of 1424 cases (90.3%) had at least 1 compartment voxel abutting the edge of the skull-stripped image edge, which requires further investigation into optimal pre-processing face anonymization steps., Comment: 16 pages, 11 tables, 10 figures, MICCAI

Prior to the deep learning era, shape was commonly used to describe the objects. Nowadays, state-of-the-art (SOTA) algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from numerous shape-related publications in premier vision conferences as well as the growing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models). For the medical domain, we present a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D models of surgical instrument, called MedShapeNet, created to facilitate the translation of data-driven vision algorithms to medical applications and to adapt SOTA vision algorithms to medical problems. As a unique feature, we directly model the majority of shapes on the imaging data of real patients. As of today, MedShapeNet includes 23 dataset with more than 100,000 shapes that are paired with annotations (ground truth). Our data is freely accessible via a web interface and a Python application programming interface (API) and can be used for discriminative, reconstructive, and variational benchmarks as well as various applications in virtual, augmented, or mixed reality, and 3D printing. Exemplary, we present use cases in the fields of classification of brain tumors, facial and skull reconstructions, multi-class anatomy completion, education, and 3D printing. In future, we will extend the data and improve the interfaces. The project pages are: https://medshapenet.ikim.nrw/ and https://github.com/Jianningli/medshapenet-feedback, Comment: 16 pages

Machine learning (ML) has shown great promise for revolutionizing a number of areas, including healthcare. However, it is also facing a reproducibility crisis, especially in medicine. ML models that are carefully constructed from and evaluated on a training set might not generalize well on data from different patient populations or acquisition instrument settings and protocols. We tackle this problem in the context of neuroimaging of Alzheimer's disease (AD), schizophrenia (SZ) and brain aging. We develop a weighted empirical risk minimization approach that optimally combines data from a source group, e.g., subjects are stratified by attributes such as sex, age group, race and clinical cohort to make predictions on a target group, e.g., other sex, age group, etc. using a small fraction (10%) of data from the target group. We apply this method to multi-source data of 15,363 individuals from 20 neuroimaging studies to build ML models for diagnosis of AD and SZ, and estimation of brain age. We found that this approach achieves substantially better accuracy than existing domain adaptation techniques: it obtains area under curve greater than 0.95 for AD classification, area under curve greater than 0.7 for SZ classification and mean absolute error less than 5 years for brain age prediction on all target groups, achieving robustness to variations of scanners, protocols, and demographic or clinical characteristics. In some cases, it is even better than training on all data from the target group, because it leverages the diversity and size of a larger training set. We also demonstrate the utility of our models for prognostic tasks such as predicting disease progression in individuals with mild cognitive impairment. Critically, our brain age prediction models lead to new clinical insights regarding correlations with neurophysiological tests.

Automated brain tumor segmentation methods have become well-established and reached performance levels offering clear clinical utility. These methods typically rely on four input magnetic resonance imaging (MRI) modalities: T1-weighted images with and without contrast enhancement, T2-weighted images, and FLAIR images. However, some sequences are often missing in clinical practice due to time constraints or image artifacts, such as patient motion. Consequently, the ability to substitute missing modalities and gain segmentation performance is highly desirable and necessary for the broader adoption of these algorithms in the clinical routine. In this work, we present the establishment of the Brain MR Image Synthesis Benchmark (BraSyn) in conjunction with the Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2023. The primary objective of this challenge is to evaluate image synthesis methods that can realistically generate missing MRI modalities when multiple available images are provided. The ultimate aim is to facilitate automated brain tumor segmentation pipelines. The image dataset used in the benchmark is diverse and multi-modal, created through collaboration with various hospitals and research institutions., Comment: Technical report of BraSyn

A myriad of algorithms for the automatic analysis of brain MR images is available to support clinicians in their decision-making. For brain tumor patients, the image acquisition time series typically starts with an already pathological scan. This poses problems, as many algorithms are designed to analyze healthy brains and provide no guarantee for images featuring lesions. Examples include, but are not limited to, algorithms for brain anatomy parcellation, tissue segmentation, and brain extraction. To solve this dilemma, we introduce the BraTS inpainting challenge. Here, the participants explore inpainting techniques to synthesize healthy brain scans from lesioned ones. The following manuscript contains the task formulation, dataset, and submission procedure. Later, it will be updated to summarize the findings of the challenge. The challenge is organized as part of the ASNR-BraTS MICCAI challenge., Comment: 14 pages, 6 figures

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN - a multi-view, weakly-supervised deep clustering method - which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer's disease and brain endophenotypes associated with hypertension, from MRI and SNP data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-driven neuroimaging phenotypes.

BACKGROUND AND PURPOSE: Deep learning has been demonstrated effective in many neuroimaging applications. However, in many scenarios, the number of imaging sequences capturing information related to small vessel disease lesions is insufficient to support data-driven techniques. Additionally, cohort-based studies may not always have the optimal or essential imaging sequences for accurate lesion detection. Therefore, it is necessary to determine which imaging sequences are crucial for precise detection. This study introduces a novel deep learning framework to detect enlarged perivascular spaces (ePVS) and aims to find the optimal combination of MRI sequences for deep learning-based quantification. MATERIALS AND METHODS: We implemented an effective lightweight U-Net adapted for ePVS detection and comprehensively investigated different combinations of information from SWI, FLAIR, T1-weighted (T1w), and T2-weighted (T2w) MRI sequences. The training data included 21 participants, which were randomly selected from the MESA cohort. Participants had ePVS 683 lesions on average. For T1w, T2w, and FLAIR images, the MESA study collected 3D isotropic MRI scans at six different sites with Siemens scanners. Our training data included participants from all these sites and all the scanner models, and the proposed model was applied to the whole brain instead of selective regions. RESULTS: The experimental results showed that T2w MRI is the most important for accurate ePVS detection, and the incorporation of SWI, FLAIR and T1w MRI in the deep neural network had minor improvements in accuracy and resulted in the highest sensitivity and precision (sensitivity =0.82, precision =0.83). The proposed method achieved comparable accuracy at a minimal time cost compared to manual reading.

Generative adversarial networks (GANs) are one powerful type of deep learning models that have been successfully utilized in numerous fields. They belong to a broader family called generative methods, which generate new data with a probabilistic model by learning sample distribution from real examples. In the clinical context, GANs have shown enhanced capabilities in capturing spatially complex, nonlinear, and potentially subtle disease effects compared to traditional generative methods. This review appraises the existing literature on the applications of GANs in imaging studies of various neurological conditions, including Alzheimer's disease, brain tumors, brain aging, and multiple sclerosis. We provide an intuitive explanation of various GAN methods for each application and further discuss the main challenges, open questions, and promising future directions of leveraging GANs in neuroimaging. We aim to bridge the gap between advanced deep learning methods and neurology research by highlighting how GANs can be leveraged to support clinical decision making and contribute to a better understanding of the structural and functional patterns of brain diseases.

Despite the great promise that machine learning has offered in many fields of medicine, it has also raised concerns about potential biases and poor generalization across genders, age distributions, races and ethnicities, hospitals, and data acquisition equipment and protocols. In the current study, and in the context of three brain diseases, we provide evidence which suggests that when properly trained, machine learning models can generalize well across diverse conditions and do not necessarily suffer from bias. Specifically, by using multi-study magnetic resonance imaging consortia for diagnosing Alzheimer's disease, schizophrenia, and autism spectrum disorder, we find that well-trained models have a high area-under-the-curve (AUC) on subjects across different subgroups pertaining to attributes such as gender, age, racial groups, and different clinical studies and are unbiased under multiple fairness metrics such as demographic parity difference, equalized odds difference, equal opportunity difference etc. We find that models that incorporate multi-source data from demographic, clinical, genetic factors and cognitive scores are also unbiased. These models have better predictive AUC across subgroups than those trained only with imaging features but there are also situations when these additional features do not help.

A plethora of machine learning methods have been applied to imaging data, enabling the construction of clinically relevant imaging signatures of neurological and neuropsychiatric diseases. Oftentimes, such methods don't explicitly model the heterogeneity of disease effects, or approach it via nonlinear models that are not interpretable. Moreover, unsupervised methods may parse heterogeneity that is driven by nuisance confounding factors that affect brain structure or function, rather than heterogeneity relevant to a pathology of interest. On the other hand, semi-supervised clustering methods seek to derive a dichotomous subtype membership, ignoring the truth that disease heterogeneity spatially and temporally extends along a continuum. To address the aforementioned limitations, herein, we propose a novel method, termed Surreal-GAN (Semi-SUpeRvised ReprEsentAtion Learning via GAN). Using cross-sectional imaging data, Surreal-GAN dissects underlying disease-related heterogeneity under the principle of semi-supervised clustering (cluster mappings from normal control to patient), proposes a continuously dimensional representation, and infers the disease severity of patients at individual level along each dimension. The model first learns a transformation function from normal control (CN) domain to the patient (PT) domain with latent variables controlling transformation directions. An inverse mapping function together with regularization on function continuity, pattern orthogonality and monotonicity was also imposed to make sure that the transformation function captures necessarily meaningful imaging patterns with clinical significance. We first validated the model through extensive semi-synthetic experiments, and then demonstrate its potential in capturing biologically plausible imaging patterns in Alzheimer's disease (AD).

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25,256 MRI scans from 6,314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing., Comment: federated learning, deep learning, convolutional neural network, segmentation, brain tumor, glioma, glioblastoma, FeTS, BraTS

Many supervised machine learning frameworks have been proposed for disease classification using functional magnetic resonance imaging (fMRI) data, producing important biomarkers. More recently, data pooling has flourished, making the result generalizable across a large population. But, this success depends on the population diversity and variability introduced due to the pooling of the data that is not a primary research interest. Here, we look at hierarchical Sparse Connectivity Patterns (hSCPs) as biomarkers for major depressive disorder (MDD). We propose a novel model based on hSCPs to predict MDD patients from functional connectivity matrices extracted from resting-state fMRI data. Our model consists of three coupled terms. The first term decomposes connectivity matrices into hierarchical low-rank sparse components corresponding to synchronous patterns across the human brain. These components are then combined via patient-specific weights capturing heterogeneity in the data. The second term is a classification loss that uses the patient-specific weights to classify MDD patients from healthy ones. Both of these terms are combined with the third term, a robustness loss function to improve the reproducibility of hSCPs. This reduces the variability introduced due to site and population diversity (age and sex) on the predictive accuracy and pattern stability in a large dataset pooled from five different sites. Our results show the impact of diversity on prediction performance. Our model can reduce diversity and improve the predictive and generalizing capability of the components. Finally, our results show that our proposed model can robustly identify clinically relevant patterns characteristic of MDD with high reproducibility.

The imaging community has increasingly adopted machine learning (ML) methods to provide individualized imaging signatures related to disease diagnosis, prognosis, and response to treatment. Clinical neuroscience and cancer imaging have been two areas in which ML has offered particular promise. However, many neurologic and neuropsychiatric diseases, as well as cancer, are often heterogeneous in terms of their clinical manifestations, neuroanatomical patterns or genetic underpinnings. Therefore, in such cases, seeking a single disease signature might be ineffectual in delivering individualized precision diagnostics. The current chapter focuses on ML methods, especially semi-supervised clustering, that seek disease subtypes using imaging data. Work from Alzheimer Disease and its prodromal stages, psychosis, depression, autism, and brain cancer are discussed. Our goal is to provide the readers with a broad overview in terms of methodology and clinical applications.

Deep learning (DL) models have provided state-of-the-art performance in various medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder translating DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties could enable clinical review of the most uncertain regions, thereby building trust and paving the way toward clinical translation. Several uncertainty estimation methods have recently been introduced for DL medical image segmentation tasks. Developing scores to evaluate and compare the performance of uncertainty measures will assist the end-user in making more informed decisions. In this study, we explore and evaluate a score developed during the BraTS 2019 and BraTS 2020 task on uncertainty quantification (QU-BraTS) and designed to assess and rank uncertainty estimates for brain tumor multi-compartment segmentation. This score (1) rewards uncertainty estimates that produce high confidence in correct assertions and those that assign low confidence levels at incorrect assertions, and (2) penalizes uncertainty measures that lead to a higher percentage of under-confident correct assertions. We further benchmark the segmentation uncertainties generated by 14 independent participating teams of QU-BraTS 2020, all of which also participated in the main BraTS segmentation task. Overall, our findings confirm the importance and complementary value that uncertainty estimates provide to segmentation algorithms, highlighting the need for uncertainty quantification in medical image analyses. Finally, in favor of transparency and reproducibility, our evaluation code is made publicly available at: https://github.com/RagMeh11/QU-BraTS., Comment: Accepted for publication at the Journal of Machine Learning for Biomedical Imaging (MELBA): https://www.melba-journal.org/papers/2022:026.html

Registration of longitudinal brain MRI scans containing pathologies is challenging due to dramatic changes in tissue appearance. Although there has been progress in developing general-purpose medical image registration techniques, they have not yet attained the requisite precision and reliability for this task, highlighting its inherent complexity. Here we describe the Brain Tumor Sequence Registration (BraTS-Reg) challenge, as the first public benchmark environment for deformable registration algorithms focusing on estimating correspondences between pre-operative and follow-up scans of the same patient diagnosed with a diffuse brain glioma. The BraTS-Reg data comprise de-identified multi-institutional multi-parametric MRI (mpMRI) scans, curated for size and resolution according to a canonical anatomical template, and divided into training, validation, and testing sets. Clinical experts annotated ground truth (GT) landmark points of anatomical locations distinct across the temporal domain. Quantitative evaluation and ranking were based on the Median Euclidean Error (MEE), Robustness, and the determinant of the Jacobian of the displacement field. The top-ranked methodologies yielded similar performance across all evaluation metrics and shared several methodological commonalities, including pre-alignment, deep neural networks, inverse consistency analysis, and test-time instance optimization per-case basis as a post-processing step. The top-ranked method attained the MEE at or below that of the inter-rater variability for approximately 60% of the evaluated landmarks, underscoring the scope for further accuracy and robustness improvements, especially relative to human experts. The aim of BraTS-Reg is to continue to serve as an active resource for research, with the data and online evaluation tools accessible at https://bratsreg.github.io/.

Late-life depression (LLD) is characterized by considerable heterogeneity in clinical manifestation. Unraveling such heterogeneity would aid in elucidating etiological mechanisms and pave the road to precision and individualized medicine. We sought to delineate, cross-sectionally and longitudinally, disease-related heterogeneity in LLD linked to neuroanatomy, cognitive functioning, clinical symptomatology, and genetic profiles. Multimodal data from a multicentre sample (N=996) were analyzed. A semi-supervised clustering method (HYDRA) was applied to regional grey matter (GM) brain volumes to derive dimensional representations. Two dimensions were identified, which accounted for the LLD-related heterogeneity in voxel-wise GM maps, white matter (WM) fractional anisotropy (FA), neurocognitive functioning, clinical phenotype, and genetics. Dimension one (Dim1) demonstrated relatively preserved brain anatomy without WM disruptions relative to healthy controls. In contrast, dimension two (Dim2) showed widespread brain atrophy and WM integrity disruptions, along with cognitive impairment and higher depression severity. Moreover, one de novo independent genetic variant (rs13120336) was significantly associated with Dim 1 but not with Dim 2. Notably, the two dimensions demonstrated significant SNP-based heritability of 18-27% within the general population (N=12,518 in UKBB). Lastly, in a subset of individuals having longitudinal measurements, Dim2 demonstrated a more rapid longitudinal decrease in GM and brain age, and was more likely to progress to Alzheimers disease, compared to Dim1 (N=1,413 participants and 7,225 scans from ADNI, BLSA, and BIOCARD datasets).

Neuroimaging biomarkers that distinguish between typical brain aging and Alzheimer's disease (AD) are valuable for determining how much each contributes to cognitive decline. Machine learning models can derive multi-variate brain change patterns related to the two processes, including the SPARE-AD (Spatial Patterns of Atrophy for Recognition of Alzheimer's Disease) and SPARE-BA (of Brain Aging) investigated herein. However, substantial overlap between brain regions affected in the two processes confounds measuring them independently. We present a methodology toward disentangling the two. T1-weighted MRI images of 4,054 participants (48-95 years) with AD, mild cognitive impairment (MCI), or cognitively normal (CN) diagnoses from the iSTAGING (Imaging-based coordinate SysTem for AGIng and NeurodeGenerative diseases) consortium were analyzed. First, a subset of AD patients and CN adults were selected based purely on clinical diagnoses to train SPARE-BA1 (regression of age using CN individuals) and SPARE-AD1 (classification of CN versus AD). Second, analogous groups were selected based on clinical and molecular markers to train SPARE-BA2 and SPARE-AD2: amyloid-positive (A+) AD continuum group (consisting of A+AD, A+MCI, and A+ and tau-positive CN individuals) and amyloid-negative (A-) CN group. Finally, the combined group of the AD continuum and A-/CN individuals was used to train SPARE-BA3, with the intention to estimate brain age regardless of AD-related brain changes. Disentangled SPARE models derived brain patterns that were more specific to the two types of the brain changes. Correlation between the SPARE-BA and SPARE-AD was significantly reduced. Correlation of disentangled SPARE-AD was non-inferior to the molecular measurements and to the number of APOE4 alleles, but was less to AD-related psychometric test scores, suggesting contribution of advanced brain aging to these scores., Comment: 4 figures, 3 tables

The BraTS 2021 challenge celebrates its 10th anniversary and is jointly organized by the Radiological Society of North America (RSNA), the American Society of Neuroradiology (ASNR), and the Medical Image Computing and Computer Assisted Interventions (MICCAI) society. Since its inception, BraTS has been focusing on being a common benchmarking venue for brain glioma segmentation algorithms, with well-curated multi-institutional multi-parametric magnetic resonance imaging (mpMRI) data. Gliomas are the most common primary malignancies of the central nervous system, with varying degrees of aggressiveness and prognosis. The RSNA-ASNR-MICCAI BraTS 2021 challenge targets the evaluation of computational algorithms assessing the same tumor compartmentalization, as well as the underlying tumor's molecular characterization, in pre-operative baseline mpMRI data from 2,040 patients. Specifically, the two tasks that BraTS 2021 focuses on are: a) the segmentation of the histologically distinct brain tumor sub-regions, and b) the classification of the tumor's O[6]-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. The performance evaluation of all participating algorithms in BraTS 2021 will be conducted through the Sage Bionetworks Synapse platform (Task 1) and Kaggle (Task 2), concluding in distributing to the top ranked participants monetary awards of $60,000 collectively., Comment: 19 pages, 2 figures, 1 table

Heterogeneity in medical data, e.g., from data collected at different sites and with different protocols in a clinical study, is a fundamental hurdle for accurate prediction using machine learning models, as such models often fail to generalize well. This paper leverages a recently proposed normalizing-flow-based method to perform counterfactual inference upon a structural causal model (SCM), in order to achieve harmonization of such data. A causal model is used to model observed effects (brain magnetic resonance imaging data) that result from known confounders (site, gender and age) and exogenous noise variables. Our formulation exploits the bijection induced by flow for the purpose of harmonization. We infer the posterior of exogenous variables, intervene on observations, and draw samples from the resultant SCM to obtain counterfactuals. This approach is evaluated extensively on multiple, large, real-world medical datasets and displayed better cross-domain generalization compared to state-of-the-art algorithms. Further experiments that evaluate the quality of confounder-independent data generated by our model using regression and classification tasks are provided.

We propose a method for extracting physics-based biomarkers from a single multiparametric Magnetic Resonance Imaging (mpMRI) scan bearing a glioma tumor. We account for mass effect, the deformation of brain parenchyma due to the growing tumor, which on its own is an important radiographic feature but its automatic quantification remains an open problem. In particular, we calibrate a partial differential equation (PDE) tumor growth model that captures mass effect, parameterized by a single scalar parameter, tumor proliferation, migration, while localizing the tumor initiation site. The single-scan calibration problem is severely ill-posed because the precancerous, healthy, brain anatomy is unknown. To address the ill-posedness, we introduce an ensemble inversion scheme that uses a number of normal subject brain templates as proxies for the healthy precancer subject anatomy. We verify our solver on a synthetic dataset and perform a retrospective analysis on a clinical dataset of 216 glioblastoma (GBM) patients. We analyze the reconstructions using our calibrated biophysical model and demonstrate that our solver provides both global and local quantitative measures of tumor biophysics and mass effect. We further highlight the improved performance in model calibration through the inclusion of mass effect in tumor growth models -- including mass effect in the model leads to 10% increase in average dice coefficients for patients with significant mass effect. We further evaluate our model by introducing novel biophysics-based features and using them for survival analysis. Our preliminary analysis suggests that including such features can improve patient stratification and survival prediction., Comment: 10 pages, 3 supplementary pages

Resting-state fMRI has been shown to provide surrogate biomarkers for the analysis of various diseases. In addition, fMRI data helps in understanding the brain's functional working during resting state and task-induced activity. To improve the statistical power of biomarkers and the understanding mechanism of the brain, pooling of multi-center studies has become increasingly popular. But pooling the data from multiple sites introduces variations due to hardware, software, and environment. In this paper, we look at the estimation problem of hierarchical Sparsity Connectivity Patterns (hSCPs) in fMRI data acquired on multiple sites. We introduce a simple yet effective matrix factorization based formulation to reduce site-related effects while preserving biologically relevant variations. We leverage adversarial learning in the unsupervised regime to improve the reproducibility of the components. Experiments on simulated datasets display that the proposed method can estimate components with improved accuracy and reproducibility. We also demonstrate the improved reproducibility of the components while preserving age-related variation on a real dataset compiled from multiple sites.