Sarthak Pati

Sarthak Pati, Ujjwal Baid, Brandon Edwards et al.

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.

Matthias Eisenmann, Annika Reinke, Vivienn Weru et al. · utoronto

The number of international benchmarking competitions is steadily increasing in various fields of machine learning (ML) research and practice. So far, however, little is known about the common practice as well as bottlenecks faced by the community in tackling the research questions posed. To shed light on the status quo of algorithm development in the specific field of biomedical imaging analysis, we designed an international survey that was issued to all participants of challenges conducted in conjunction with the IEEE ISBI 2021 and MICCAI 2021 conferences (80 competitions in total). The survey covered participants' expertise and working environments, their chosen strategies, as well as algorithm characteristics. A median of 72% challenge participants took part in the survey. According to our results, knowledge exchange was the primary incentive (70%) for participation, while the reception of prize money played only a minor role (16%). While a median of 80 working hours was spent on method development, a large portion of participants stated that they did not have enough time for method development (32%). 25% perceived the infrastructure to be a bottleneck. Overall, 94% of all solutions were deep learning-based. Of these, 84% were based on standard architectures. 43% of the respondents reported that the data samples (e.g., images) were too large to be processed at once. This was most commonly addressed by patch-based training (69%), downsampling (37%), and solving 3D analysis tasks as a series of 2D tasks. K-fold cross-validation on the training set was performed by only 37% of the participants and only 50% of the participants performed ensembling based on multiple identical models (61%) or heterogeneous models (39%). 48% of the respondents applied postprocessing steps.

Matthias Eisenmann, Annika Reinke, Vivienn Weru et al.

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multi-center study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and postprocessing (66%). The "typical" lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work.

Anahita Fathi Kazerooni, Nastaran Khalili, Xinyang Liu et al.

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.

Ramya Muthukrishnan, Angelina Heyler, Keshava Katti et al.

In this study, we automate quantitative mammographic breast density estimation with neural networks and show that this tool is a strong use case for federated learning on multi-institutional datasets. Our dataset included bilateral CC-view and MLO-view mammographic images from two separate institutions. Two U-Nets were separately trained on algorithm-generated labels to perform segmentation of the breast and dense tissue from these images and subsequently calculate breast percent density (PD). The networks were trained with federated learning and compared to three non-federated baselines, one trained on each single-institution dataset and one trained on the aggregated multi-institution dataset. We demonstrate that training on multi-institution datasets is critical to algorithm generalizability. We further show that federated learning on multi-institutional datasets improves model generalization to unseen data at nearly the same level as centralized training on multi-institutional datasets, indicating that federated learning can be applied to our method to improve algorithm generalizability while maintaining patient privacy.

Sarthak Pati, Szymon Mazurek, Spyridon Bakas

Generative Artificial Intelligence (GenAI) is a field of AI that creates new data samples from existing ones. It utilizing deep learning to overcome the scarcity and regulatory constraints of healthcare data by generating new data points that integrate seamlessly with original datasets. This paper explores the background and motivation for GenAI, and introduces the Generally Nuanced Deep Learning Framework for Synthesis (GaNDLF-Synth) to address a significant gap in the literature and move towards democratizing the implementation and assessment of image synthesis tasks in healthcare. GaNDLF-Synth describes a unified abstraction for various synthesis algorithms, including autoencoders, generative adversarial networks, and diffusion models. Leveraging the GANDLF-core framework, it supports diverse data modalities and distributed computing, ensuring scalability and reproducibility through extensive unit testing. The aim of GaNDLF-Synth is to lower the entry barrier for GenAI, and make it more accessible and extensible by the wider scientific community.

Florian Kofler, Hendrik Möller, Josef A. Buchner et al.

This paper introduces panoptica, a versatile and performance-optimized package designed for computing instance-wise segmentation quality metrics from 2D and 3D segmentation maps. panoptica addresses the limitations of existing metrics and provides a modular framework that complements the original intersection over union-based panoptic quality with other metrics, such as the distance metric Average Symmetric Surface Distance. The package is open-source, implemented in Python, and accompanied by comprehensive documentation and tutorials. panoptica employs a three-step metrics computation process to cover diverse use cases. The efficacy of panoptica is demonstrated on various real-world biomedical datasets, where an instance-wise evaluation is instrumental for an accurate representation of the underlying clinical task. Overall, we envision panoptica as a valuable tool facilitating in-depth evaluation of segmentation methods.

Florian Kofler, Marcel Rosier, Mehdi Astaraki et al.

The Brain Tumor Segmentation (BraTS) cluster of challenges has significantly advanced brain tumor image analysis by providing large, curated datasets and addressing clinically relevant tasks. However, despite its success and popularity, algorithms and models developed through BraTS have seen limited adoption in both scientific and clinical communities. To accelerate their dissemination, we introduce BraTS orchestrator, an open-source Python package that provides seamless access to state-of-the-art segmentation and synthesis algorithms for diverse brain tumors from the BraTS challenge ecosystem. Available on GitHub (https://github.com/BrainLesion/BraTS), the package features intuitive tutorials designed for users with minimal programming experience, enabling both researchers and clinicians to easily deploy winning BraTS algorithms for inference. By abstracting the complexities of modern deep learning, BraTS orchestrator democratizes access to the specialized knowledge developed within the BraTS community, making these advances readily available to broader neuro-radiology and neuro-oncology audiences.

Akis Linardos, Sarthak Pati, Ujjwal Baid et al.

We present the design and results of the MICCAI Federated Tumor Segmentation (FeTS) Challenge 2024, which focuses on federated learning (FL) for glioma sub-region segmentation in multi-parametric MRI and evaluates new weight aggregation methods aimed at improving robustness and efficiency. Six participating teams were evaluated using a standardized FL setup and a multi-institutional dataset derived from the BraTS glioma benchmark, consisting of 1,251 training cases, 219 validation cases, and 570 hidden test cases with segmentations for enhancing tumor (ET), tumor core (TC), and whole tumor (WT). Teams were ranked using a cumulative scoring system that considered both segmentation performance, measured by Dice Similarity Coefficient (DSC) and the 95th percentile Hausdorff Distance (HD95), and communication efficiency assessed through the convergence score. A PID-controller-based method achieved the top overall ranking, obtaining mean DSC values of 0.733, 0.761, and 0.751 for ET, TC, and WT, respectively, with corresponding HD95 values of 33.922 mm, 33.623 mm, and 32.309 mm, while also demonstrating the highest communication efficiency with a convergence score of 0.764. These findings advance the state of federated learning for medical imaging, surpassing top-performing methods from previous challenge iterations and highlighting PID controllers as effective mechanisms for stabilizing and optimizing weight aggregation in FL. The challenge code is available at https://github.com/FeTS-AI/Challenge.

Ibrahim Ethem Hamamci, Sezgin Er, Omer Faruk Durugol et al.

Panoramic X-rays are frequently used in dentistry for treatment planning, but their interpretation can be both time-consuming and prone to error. Artificial intelligence (AI) has the potential to aid in the analysis of these X-rays, thereby improving the accuracy of dental diagnoses and treatment plans. Nevertheless, designing automated algorithms for this purpose poses significant challenges, mainly due to the scarcity of annotated data and variations in anatomical structure. To address these issues, we organized the Dental Enumeration and Diagnosis on Panoramic X-rays Challenge (DENTEX) in association with the International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) in 2023. This challenge aims to promote the development of algorithms for multi-label detection of abnormal teeth, using three types of hierarchically annotated data: partially annotated quadrant data, partially annotated quadrant-enumeration data, and fully annotated quadrant-enumeration-diagnosis data, inclusive of four different diagnoses. In this paper, we present a comprehensive analysis of the methods and results from the challenge. Our findings reveal that top performers succeeded through diverse, specialized strategies, from segmentation-guided pipelines to highly-engineered single-stage detectors, using advanced Transformer and diffusion models. These strategies significantly outperformed traditional approaches, particularly for the challenging tasks of tooth enumeration and subtle disease classification. By dissecting the architectural choices that drove success, this paper provides key insights for future development of AI-powered tools that can offer more precise and efficient diagnosis and treatment planning in dentistry. The evaluation code and datasets can be accessed at https://github.com/ibrahimethemhamamci/DENTEX

Ibrahim Ethem Hamamci, Sezgin Er, Anjany Sekuboyina et al.

GenerateCT, the first approach to generating 3D medical imaging conditioned on free-form medical text prompts, incorporates a text encoder and three key components: a novel causal vision transformer for encoding 3D CT volumes, a text-image transformer for aligning CT and text tokens, and a text-conditional super-resolution diffusion model. Without directly comparable methods in 3D medical imaging, we benchmarked GenerateCT against cutting-edge methods, demonstrating its superiority across all key metrics. Importantly, we evaluated GenerateCT's clinical applications in a multi-abnormality classification task. First, we established a baseline by training a multi-abnormality classifier on our real dataset. To further assess the model's generalization to external data and performance with unseen prompts in a zero-shot scenario, we employed an external set to train the classifier, setting an additional benchmark. We conducted two experiments in which we doubled the training datasets by synthesizing an equal number of volumes for each set using GenerateCT. The first experiment demonstrated an 11% improvement in the AP score when training the classifier jointly on real and generated volumes. The second experiment showed a 7% improvement when training on both real and generated volumes based on unseen prompts. Moreover, GenerateCT enables the scaling of synthetic training datasets to arbitrary sizes. As an example, we generated 100,000 3D CTs, fivefold the number in our real set, and trained the classifier exclusively on these synthetic CTs. Impressively, this classifier surpassed the performance of the one trained on all available real data by a margin of 8%. Last, domain experts evaluated the generated volumes, confirming a high degree of alignment with the text prompt. Access our code, model weights, training data, and generated data at https://github.com/ibrahimethemhamamci/GenerateCT

G Anthony Reina, Alexey Gruzdev, Patrick Foley et al.

Federated learning (FL) is a computational paradigm that enables organizations to collaborate on machine learning (ML) projects without sharing sensitive data, such as, patient records, financial data, or classified secrets. Open Federated Learning (OpenFL https://github.com/intel/openfl) is an open-source framework for training ML algorithms using the data-private collaborative learning paradigm of FL. OpenFL works with training pipelines built with both TensorFlow and PyTorch, and can be easily extended to other ML and deep learning frameworks. Here, we summarize the motivation and development characteristics of OpenFL, with the intention of facilitating its application to existing ML model training in a production environment. Finally, we describe the first use of the OpenFL framework to train consensus ML models in a consortium of international healthcare organizations, as well as how it facilitates the first computational competition on FL.

Dominic LaBella, Ujjwal Baid, Omaditya Khanna et al.

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, FLAIR, T1, and T1Gd brain MRI sequences with associated tumor compartment labels delineating enhancing tumor, non-enhancing tumor, and surrounding non-enhancing 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.

Spyridon Bakas, Siddhesh P. Thakur, Shahriar Faghani et al.

Glioblastoma is the most common primary adult brain tumor, with a grim prognosis - median survival of 12-18 months following treatment, and 4 months otherwise. Glioblastoma is widely infiltrative in the cerebral hemispheres and well-defined by heterogeneous molecular and micro-environmental histopathologic profiles, which pose a major obstacle in treatment. Correctly diagnosing these tumors and assessing their heterogeneity is crucial for choosing the precise treatment and potentially enhancing patient survival rates. In the gold-standard histopathology-based approach to tumor diagnosis, detecting various morpho-pathological features of distinct histology throughout digitized tissue sections is crucial. Such "features" include the presence of cellular tumor, geographic necrosis, pseudopalisading necrosis, areas abundant in microvascular proliferation, infiltration into the cortex, wide extension in subcortical white matter, leptomeningeal infiltration, regions dense with macrophages, and the presence of perivascular or scattered lymphocytes. With these features in mind and building upon the main aim of the BraTS Cluster of Challenges https://www.synapse.org/brats2024, the goal of the BraTS-Path challenge is to provide a systematically prepared comprehensive dataset and a benchmarking environment to develop and fairly compare deep-learning models capable of identifying tumor sub-regions of distinct histologic profile. These models aim to further our understanding of the disease and assist in the diagnosis and grading of conditions in a consistent manner.

Florian Kofler, Marcel Rosier, Mehdi Astaraki et al.

BrainLesion Suite is a versatile toolkit for building modular brain lesion image analysis pipelines in Python. Following Pythonic principles, BrainLesion Suite is designed to provide a 'brainless' development experience, minimizing cognitive effort and streamlining the creation of complex workflows for clinical and scientific practice. At its core is an adaptable preprocessing module that performs co-registration, atlas registration, and optional skull-stripping and defacing on arbitrary multi-modal input images. BrainLesion Suite leverages algorithms from the BraTS challenge to synthesize missing modalities, inpaint lesions, and generate pathology-specific tumor segmentations. BrainLesion Suite also enables quantifying segmentation model performance, with tools such as panoptica to compute lesion-wise metrics. Although BrainLesion Suite was originally developed for image analysis pipelines of brain lesions such as glioma, metastasis, and multiple sclerosis, it can be adapted for other biomedical image analysis applications. The individual BrainLesion Suite packages and tutorials are accessible on GitHub.

Santhosh Parampottupadam, Melih Coşğun, Sarthak Pati et al.

Federated Learning (FL) offers a promising approach for training clinical AI models without centralizing sensitive patient data. However, its real-world adoption is hindered by challenges related to privacy, resource constraints, and compliance. Existing Differential Privacy (DP) approaches often apply uniform noise, which disproportionately degrades model performance, even among well-compliant institutions. In this work, we propose a novel compliance-aware FL framework that enhances DP by adaptively adjusting noise based on quantifiable client compliance scores. Additionally, we introduce a compliance scoring tool based on key healthcare and security standards to promote secure, inclusive, and equitable participation across diverse clinical settings. Extensive experiments on public datasets demonstrate that integrating under-resourced, less compliant clinics with highly regulated institutions yields accuracy improvements of up to 15% over traditional FL. This work advances FL by balancing privacy, compliance, and performance, making it a viable solution for real-world clinical workflows in global healthcare.

Florian Kofler, Felix Meissen, Felix Steinbauer et al.

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.

Ujjwal Baid, Sarthak Pati, Tahsin M. Kurc et al.

We evaluate the performance of federated learning (FL) in developing deep learning models for analysis of digitized tissue sections. A classification application was considered as the example use case, on quantifiying the distribution of tumor infiltrating lymphocytes within whole slide images (WSIs). A deep learning classification model was trained using 50*50 square micron patches extracted from the WSIs. We simulated a FL environment in which a dataset, generated from WSIs of cancer from numerous anatomical sites available by The Cancer Genome Atlas repository, is partitioned in 8 different nodes. Our results show that the model trained with the federated training approach achieves similar performance, both quantitatively and qualitatively, to that of a model trained with all the training data pooled at a centralized location. Our study shows that FL has tremendous potential for enabling development of more robust and accurate models for histopathology image analysis without having to collect large and diverse training data at a single location.

Ujjwal Baid, Satyam Ghodasara, Suyash Mohan et al.

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.

Sarthak Pati, Ujjwal Baid, Maximilian Zenk et al.

This manuscript describes the first challenge on Federated Learning, namely the Federated Tumor Segmentation (FeTS) challenge 2021. International challenges have become the standard for validation of biomedical image analysis methods. However, the actual performance of participating (even the winning) algorithms on "real-world" clinical data often remains unclear, as the data included in challenges are usually acquired in very controlled settings at few institutions. The seemingly obvious solution of just collecting increasingly more data from more institutions in such challenges does not scale well due to privacy and ownership hurdles. Towards alleviating these concerns, we are proposing the FeTS challenge 2021 to cater towards both the development and the evaluation of models for the segmentation of intrinsically heterogeneous (in appearance, shape, and histology) brain tumors, namely gliomas. Specifically, the FeTS 2021 challenge uses clinically acquired, multi-institutional magnetic resonance imaging (MRI) scans from the BraTS 2020 challenge, as well as from various remote independent institutions included in the collaborative network of a real-world federation (https://www.fets.ai/). The goals of the FeTS challenge are directly represented by the two included tasks: 1) the identification of the optimal weight aggregation approach towards the training of a consensus model that has gained knowledge via federated learning from multiple geographically distinct institutions, while their data are always retained within each institution, and 2) the federated evaluation of the generalizability of brain tumor segmentation models "in the wild", i.e. on data from institutional distributions that were not part of the training datasets.

Sarthak Pati, Siddhesh P. Thakur, İbrahim Ethem Hamamcı et al.

Deep Learning (DL) has the potential to optimize machine learning in both the scientific and clinical communities. However, greater expertise is required to develop DL algorithms, and the variability of implementations hinders their reproducibility, translation, and deployment. Here we present the community-driven Generally Nuanced Deep Learning Framework (GaNDLF), with the goal of lowering these barriers. GaNDLF makes the mechanism of DL development, training, and inference more stable, reproducible, interpretable, and scalable, without requiring an extensive technical background. GaNDLF aims to provide an end-to-end solution for all DL-related tasks in computational precision medicine. We demonstrate the ability of GaNDLF to analyze both radiology and histology images, with built-in support for k-fold cross-validation, data augmentation, multiple modalities and output classes. Our quantitative performance evaluation on numerous use cases, anatomies, and computational tasks supports GaNDLF as a robust application framework for deployment in clinical workflows.

Ludovic Venet, Sarthak Pati, Paul Yushkevich et al.

Variously stained histology slices are routinely used by pathologists to assess extracted tissue samples from various anatomical sites and determine the presence or extent of a disease. Evaluation of sequential slides is expected to enable a better understanding of the spatial arrangement and growth patterns of cells and vessels. In this paper we present a practical two-step approach based on diffeomorphic registration to align digitized sequential histopathology stained slides to each other, starting with an initial affine step followed by the estimation of a detailed deformation field.