Ken Chang

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.

Sourav Kumar, A. Lakshminarayanan, Ken Chang et al.

Federated Learning (FL) wherein multiple institutions collaboratively train a machine learning model without sharing data is becoming popular. Participating institutions might not contribute equally, some contribute more data, some better quality data or some more diverse data. To fairly rank the contribution of different institutions, Shapley value (SV) has emerged as the method of choice. Exact SV computation is impossibly expensive, especially when there are hundreds of contributors. Existing SV computation techniques use approximations. However, in healthcare where the number of contributing institutions are likely not of a colossal scale, computing exact SVs is still exorbitantly expensive, but not impossible. For such settings, we propose an efficient SV computation technique called SaFE (Shapley Value for Federated Learning using Ensembling). We empirically show that SaFE computes values that are close to exact SVs, and that it performs better than current SV approximations. This is particularly relevant in medical imaging setting where widespread heterogeneity across institutions is rampant and fast accurate data valuation is required to determine the contribution of each participant in multi-institutional collaborative learning.

Charles Lu, Ken Chang, Praveer Singh et al.

Breast cancer is the most common cancers and early detection from mammography screening is crucial in improving patient outcomes. Assessing mammographic breast density is clinically important as the denser breasts have higher risk and are more likely to occlude tumors. Manual assessment by experts is both time-consuming and subject to inter-rater variability. As such, there has been increased interest in the development of deep learning methods for mammographic breast density assessment. Despite deep learning having demonstrated impressive performance in several prediction tasks for applications in mammography, clinical deployment of deep learning systems in still relatively rare; historically, mammography Computer-Aided Diagnoses (CAD) have over-promised and failed to deliver. This is in part due to the inability to intuitively quantify uncertainty of the algorithm for the clinician, which would greatly enhance usability. Conformal prediction is well suited to increase reliably and trust in deep learning tools but they lack realistic evaluations on medical datasets. In this paper, we present a detailed analysis of three possible applications of conformal prediction applied to medical imaging tasks: distribution shift characterization, prediction quality improvement, and subgroup fairness analysis. Our results show the potential of distribution-free uncertainty quantification techniques to enhance trust on AI algorithms and expedite their translation to usage.

Yabin Zhang, Chong Wang, Yunhe Gao et al.

Chest X-rays (CXRs) are among the most frequently performed imaging examinations worldwide, yet rising imaging volumes increase radiologist workload and the risk of diagnostic errors. Although artificial intelligence (AI) systems have shown promise for CXR interpretation, most generate only final predictions, without making explicit how visual evidence is translated into radiographic findings and diagnostic predictions. We present CheXOne, a reasoning-enabled vision-language model for CXR interpretation. CheXOne jointly generates diagnostic predictions and explicit, clinically grounded reasoning traces that connect visual evidence, radiographic findings, and these predictions. The model is trained on 14.7 million instruction and reasoning samples curated from 30 public datasets spanning 36 CXR interpretation tasks, using a two-stage framework that combines instruction tuning with reinforcement learning to improve reasoning quality. We evaluate CheXOne in zero-shot settings across visual question answering, report generation, visual grounding and reasoning assessment, covering 17 evaluation settings. CheXOne outperforms existing medical and general-domain foundation models and achieves strong performance on independent public benchmarks. A clinical reader study demonstrates that CheXOne-drafted reports are comparable to or better than resident-written reports in 55% of cases, while effectively addressing clinical indications and enhancing both report writing and CXR interpretation efficiency. Further analyses involving radiologists reveal that the generated reasoning traces show high clinical factuality and provide causal support for the final predictions, offering a plausible explanation for the performance gains. These results suggest that explicit reasoning can improve model performance, interpretability and clinical utility in AI-assisted CXR interpretation.

Joy T Wu, Daniel Beckmann, Sarah Miller et al.

[18F]FDG-PET/CT is a cornerstone imaging modality for tumor staging and treatment response assessment across many cancer types, yet expert reader shortages necessitate more efficient diagnostic aids. While standalone AI models for automatic lesion segmentation exist, clinical translation remains hindered by concerns about interpretability, explainability, reliability, and workflow integration. We present GazeXPErT, a 4D eye-tracking dataset capturing expert search patterns during tumor detection and measurement on 346 FDG-PET/CT scans. Each study was read by a trainee and a board-certified nuclear medicine or radiology specialist using an eye-tracking-enabled annotation platform that simulates routine clinical reads. From 3,948 minutes of raw 60Hz eye-tracking data, 9,030 unique gaze-to-lesion trajectories were extracted, synchronized with PET/CT image slices, and rendered in COCO-style format for multiple machine learning applications. Baseline validation experiments demonstrate that a 3D nnUNet tumor segmentation model achieved superior performance when incorporating expert gaze patterns versus without (DICE score 0.6819 versus 0.6008), and that vision transformers trained on sequential gaze and PET/CT images can improve dynamic lesion localization (74.95% predicted gaze point closer to tumor) and expert intention prediction (Accuracy 67.53% and AUROC 0.747). GazeXPErT is a valuable resource designed to explore multiple machine learning problems beyond these baseline experiments, which include and are not limited to, visual grounding or causal reasoning, clinically explainable feature augmentation, human-computer interaction, human intention prediction or understanding, and expert gaze-rewarded modeling approaches to AI in oncologic FDG-PET/CT imaging.

Mohammad H. Abbasi, Favour Nerrise, Shaurnav Ghosh et al.

We present NeuroQA, a large-scale benchmark for visual question answering in 3D brain magnetic resonance imaging (MRI), with 56,953 QA pairs from 12,977 subjects across 12 datasets. It spans ages 5-104 and five clinical domains: Alzheimer's, Parkinson's, tumors, white matter disease, and neurodevelopment. Unlike prior medical Visual Question Answering (VQA) efforts that operate on 2D slices or rely on narrow diagnostic labels, NeuroQA pairs every item with a full 3D volume. It evaluates 11 clinically grounded reasoning skills across Yes/No, multiple-choice, and open-ended formats. Of the 203 templates, 131 are image-grounded (answerable from a 3-plane viewer) and 72 are image-informed (ground truth from quantitative volumetry or clinical instruments). To remove text-only shortcuts, we apply answer-distribution refinement, reducing closed-format text-only accuracy from $>$80% to 44.6%; image necessity is assessed separately through an image-grounding protocol released with the benchmark. A 38-rule deterministic pipeline and two rounds of expert review verify every QA pair against FreeSurfer measurements, metadata, or radiology report fields, with zero same-subject contradictions across templates. We conduct a clinician evaluation in which two clinicians independently assess 100 frozen test items on a three-plane viewer. On closed-format (Yes/No + multiple-choice) test-public items, the best zero-shot vision-language model and a supervised 3D CNN baseline reach 47.5% and 43.7% accuracy respectively, both below the 49.4% text-only majority-template floor. NeuroQA adopts a two-tier release with public QA pairs for open-access datasets and reproducible generation scripts for datasets restricted by data use agreements (DUAs), plus subject-level splits, a held-out private test set, and an online leaderboard.

Raghav Mehta, Angelos Filos, Ujjwal Baid et al.

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.

Nishanth Arun, Nathan Gaw, Praveer Singh et al.

Saliency maps have become a widely used method to make deep learning models more interpretable by providing post-hoc explanations of classifiers through identification of the most pertinent areas of the input medical image. They are increasingly being used in medical imaging to provide clinically plausible explanations for the decisions the neural network makes. However, the utility and robustness of these visualization maps has not yet been rigorously examined in the context of medical imaging. We posit that trustworthiness in this context requires 1) localization utility, 2) sensitivity to model weight randomization, 3) repeatability, and 4) reproducibility. Using the localization information available in two large public radiology datasets, we quantify the performance of eight commonly used saliency map approaches for the above criteria using area under the precision-recall curves (AUPRC) and structural similarity index (SSIM), comparing their performance to various baseline measures. Using our framework to quantify the trustworthiness of saliency maps, we show that all eight saliency map techniques fail at least one of the criteria and are, in most cases, less trustworthy when compared to the baselines. We suggest that their usage in the high-risk domain of medical imaging warrants additional scrutiny and recommend that detection or segmentation models be used if localization is the desired output of the network. Additionally, to promote reproducibility of our findings, we provide the code we used for all tests performed in this work at this link: https://github.com/QTIM-Lab/Assessing-Saliency-Maps.

Melanie Rieff, Maya Varma, Ossian Rabow et al.

Multimodal in-context learning (ICL) remains underexplored despite significant potential for domains such as medicine. Clinicians routinely encounter diverse, specialized tasks requiring adaptation from limited examples, such as drawing insights from a few relevant prior cases or considering a constrained set of differential diagnoses. While multimodal large language models (MLLMs) have shown advances in medical visual question answering (VQA), their ability to learn multimodal tasks from context is largely unknown. We introduce SMMILE, the first expert-driven multimodal ICL benchmark for medical tasks. Eleven medical experts curated problems, each including a multimodal query and multimodal in-context examples as task demonstrations. SMMILE encompasses 111 problems (517 question-image-answer triplets) covering 6 medical specialties and 13 imaging modalities. We further introduce SMMILE++, an augmented variant with 1038 permuted problems. A comprehensive evaluation of 15 MLLMs demonstrates that most models exhibit moderate to poor multimodal ICL ability in medical tasks. In open-ended evaluations, ICL contributes only an 8% average improvement over zero-shot on SMMILE and 9.4% on SMMILE++. We observe a susceptibility for irrelevant in-context examples: even a single noisy or irrelevant example can degrade performance by up to 9.5%. Moreover, we observe that MLLMs are affected by a recency bias, where placing the most relevant example last can lead to substantial performance improvements of up to 71%. Our findings highlight critical limitations and biases in current MLLMs when learning multimodal medical tasks from context. SMMILE is available at https://smmile-benchmark.github.io.

Kendall Schmidt, Benjamin Bearce, Ken Chang et al.

The correct interpretation of breast density is important in the assessment of breast cancer risk. AI has been shown capable of accurately predicting breast density, however, due to the differences in imaging characteristics across mammography systems, models built using data from one system do not generalize well to other systems. Though federated learning (FL) has emerged as a way to improve the generalizability of AI without the need to share data, the best way to preserve features from all training data during FL is an active area of research. To explore FL methodology, the breast density classification FL challenge was hosted in partnership with the American College of Radiology, Harvard Medical School's Mass General Brigham, University of Colorado, NVIDIA, and the National Institutes of Health National Cancer Institute. Challenge participants were able to submit docker containers capable of implementing FL on three simulated medical facilities, each containing a unique large mammography dataset. The breast density FL challenge ran from June 15 to September 5, 2022, attracting seven finalists from around the world. The winning FL submission reached a linear kappa score of 0.653 on the challenge test data and 0.413 on an external testing dataset, scoring comparably to a model trained on the same data in a central location.

Ikbeom Jang, Garrison Danley, Ken Chang et al.

Ranking by pairwise comparisons has shown improved reliability over ordinal classification. However, as the annotations of pairwise comparisons scale quadratically, this becomes less practical when the dataset is large. We propose a method for reducing the number of pairwise comparisons required to rank by a quantitative metric, demonstrating the effectiveness of the approach in ranking medical images by image quality in this proof of concept study. Using the medical image annotation software that we developed, we actively subsample pairwise comparisons using a sorting algorithm with a human rater in the loop. We find that this method substantially reduces the number of comparisons required for a full ordinal ranking without compromising inter-rater reliability when compared to pairwise comparisons without sorting.

Charles Lu, Ken Chang, Praveer Singh et al.

Despite the intense attention and considerable investment into clinical machine learning research, relatively few applications have been deployed at a large-scale in a real-world clinical environment. While research is important in advancing the state-of-the-art, translation is equally important in bringing these techniques and technologies into a position to ultimately impact healthcare. We believe a lack of appreciation for several considerations are a major cause for this discrepancy between expectation and reality. To better characterize a holistic perspective among researchers and practitioners, we survey several practitioners with commercial experience in developing CML for clinical deployment. Using these insights, we identify several main categories of challenges in order to better design and develop clinical machine learning applications.

Charles Lu, Andreanne Lemay, Ken Chang et al.

Deep learning has the potential to automate many clinically useful tasks in medical imaging. However translation of deep learning into clinical practice has been hindered by issues such as lack of the transparency and interpretability in these "black box" algorithms compared to traditional statistical methods. Specifically, many clinical deep learning models lack rigorous and robust techniques for conveying certainty (or lack thereof) in their predictions -- ultimately limiting their appeal for extensive use in medical decision-making. Furthermore, numerous demonstrations of algorithmic bias have increased hesitancy towards deployment of deep learning for clinical applications. To this end, we explore how conformal predictions can complement existing deep learning approaches by providing an intuitive way of expressing uncertainty while facilitating greater transparency to clinical users. In this paper, we conduct field interviews with radiologists to assess possible use-cases for conformal predictors. Using insights gathered from these interviews, we devise two clinical use-cases and empirically evaluate several methods of conformal predictions on a dermatology photography dataset for skin lesion classification. We show how to modify conformal predictions to be more adaptive to subgroup differences in patient skin tones through equalized coverage. Finally, we compare conformal prediction against measures of epistemic uncertainty.

Sharut Gupta, Praveer Singh, Ken Chang et al.

Model brittleness is a key concern when deploying deep learning models in real-world medical settings. A model that has high performance at one institution may suffer a significant decline in performance when tested at other institutions. While pooling datasets from multiple institutions and retraining may provide a straightforward solution, it is often infeasible and may compromise patient privacy. An alternative approach is to fine-tune the model on subsequent institutions after training on the original institution. Notably, this approach degrades model performance at the original institution, a phenomenon known as catastrophic forgetting. In this paper, we develop an approach to address catastrophic forget-ting based on elastic weight consolidation combined with modulation of batch normalization statistics under two scenarios: first, for expanding the domain from one imaging system's data to another imaging system's, and second, for expanding the domain from a large multi-institutional dataset to another single institution dataset. We show that our approach outperforms several other state-of-the-art approaches and provide theoretical justification for the efficacy of batch normalization modulation. The results of this study are generally applicable to the deployment of any clinical deep learning model which requires domain expansion.

Sharut Gupta, Praveer Singh, Ken Chang et al.

Model brittleness is a primary concern when deploying deep learning models in medical settings owing to inter-institution variations, like patient demographics and intra-institution variation, such as multiple scanner types. While simply training on the combined datasets is fraught with data privacy limitations, fine-tuning the model on subsequent institutions after training it on the original institution results in a decrease in performance on the original dataset, a phenomenon called catastrophic forgetting. In this paper, we investigate trade-off between model refinement and retention of previously learned knowledge and subsequently address catastrophic forgetting for the assessment of mammographic breast density. More specifically, we propose a simple yet effective approach, adapting Elastic weight consolidation (EWC) using the global batch normalization (BN) statistics of the original dataset. The results of this study provide guidance for the deployment of clinical deep learning models where continuous learning is needed for domain expansion.

Mehak Aggarwal, Nishanth Arun, Sharut Gupta et al.

While success of Deep Learning (DL) in automated diagnosis can be transformative to the medicinal practice especially for people with little or no access to doctors, its widespread acceptability is severely limited by inherent black-box decision making and unsafe failure modes. While saliency methods attempt to tackle this problem in non-medical contexts, their apriori explanations do not transfer well to medical usecases. With this study we validate a model design element agnostic to both architecture complexity and model task, and show how introducing this element gives an inherently self-explanatory model. We compare our results with state of the art non-trainable saliency maps on RSNA Pneumonia Dataset and demonstrate a much higher localization efficacy using our adopted technique. We also compare, with a fully supervised baseline and provide a reasonable alternative to it's high data labelling overhead. We further investigate the validity of our claims through qualitative evaluation from an expert reader.

Holger R. Roth, Ken Chang, Praveer Singh et al.

Building robust deep learning-based models requires large quantities of diverse training data. In this study, we investigate the use of federated learning (FL) to build medical imaging classification models in a real-world collaborative setting. Seven clinical institutions from across the world joined this FL effort to train a model for breast density classification based on Breast Imaging, Reporting & Data System (BI-RADS). We show that despite substantial differences among the datasets from all sites (mammography system, class distribution, and data set size) and without centralizing data, we can successfully train AI models in federation. The results show that models trained using FL perform 6.3% on average better than their counterparts trained on an institute's local data alone. Furthermore, we show a 45.8% relative improvement in the models' generalizability when evaluated on the other participating sites' testing data.

Nishanth Thumbavanam Arun, Nathan Gaw, Praveer Singh et al.

Saliency maps have become a widely used method to assess which areas of the input image are most pertinent to the prediction of a trained neural network. However, in the context of medical imaging, there is no study to our knowledge that has examined the efficacy of these techniques and quantified them using overlap with ground truth bounding boxes. In this work, we explored the credibility of the various existing saliency map methods on the RSNA Pneumonia dataset. We found that GradCAM was the most sensitive to model parameter and label randomization, and was highly agnostic to model architecture.

Maarten G. Poirot, Praneeth Vepakomma, Ken Chang et al.

Shortage of labeled data has been holding the surge of deep learning in healthcare back, as sample sizes are often small, patient information cannot be shared openly, and multi-center collaborative studies are a burden to set up. Distributed machine learning methods promise to mitigate these problems. We argue for a split learning based approach and apply this distributed learning method for the first time in the medical field to compare performance against (1) centrally hosted and (2) non collaborative configurations for a range of participants. Two medical deep learning tasks are used to compare split learning to conventional single and multi center approaches: a binary classification problem of a data set of 9000 fundus photos, and multi-label classification problem of a data set of 156,535 chest X-rays. The several distributed learning setups are compared for a range of 1-50 distributed participants. Performance of the split learning configuration remained constant for any number of clients compared to a single center study, showing a marked difference compared to the non collaborative configuration after 2 clients (p < 0.001) for both sets. Our results affirm the benefits of collaborative training of deep neural networks in health care. Our work proves the significant benefit of distributed learning in healthcare, and paves the way for future real-world implementations.

Katharina Hoebel, Ken Chang, Jay Patel et al.

Segmentation tasks in medical imaging are inherently ambiguous: the boundary of a target structure is oftentimes unclear due to image quality and biological factors. As such, predicted segmentations from deep learning algorithms are inherently ambiguous. Additionally, "ground truth" segmentations performed by human annotators are in fact weak labels that further increase the uncertainty of outputs of supervised models developed on these manual labels. To date, most deep learning segmentation studies utilize predicted segmentations without uncertainty quantification. In contrast, we explore the use of Monte Carlo dropout U-Nets for the segmentation with additional quantification of segmentation uncertainty. We assess the utility of three measures of uncertainty (Coefficient of Variation, Mean Pairwise Dice, and Mean Voxelwise Uncertainty) for the segmentation of a less ambiguous target structure (liver) and a more ambiguous one (liver tumors). Furthermore, we assess how the utility of these measures changes with different patch sizes and cost functions. Our results suggest that models trained using larger patches and the weighted categorical cross-entropy as cost function allow the extraction of more meaningful uncertainty measures compared to smaller patches and soft dice loss. Among the three uncertainty measures Mean Pairwise Dice shows the strongest correlation with segmentation quality. Our study serves as a proof-of-concept of how uncertainty measures can be used to assess the quality of a predicted segmentation, potentially serving to flag low quality segmentations from a given model for further human review.

Vivek Sharma, Praneeth Vepakomma, Tristan Swedish et al.

Recently, there has been the development of Split Learning, a framework for distributed computation where model components are split between the client and server (Vepakomma et al., 2018b). As Split Learning scales to include many different model components, there needs to be a method of matching client-side model components with the best server-side model components. A solution to this problem was introduced in the ExpertMatcher (Sharma et al., 2019) framework, which uses autoencoders to match raw data to models. In this work, we propose an extension of ExpertMatcher, where matching can be performed without the need to share the client's raw data representation. The technique is applicable to situations where there are local clients and centralized expert ML models, but the sharing of raw data is constrained.

Vivek Sharma, Praneeth Vepakomma, Tristan Swedish et al.

In this work we introduce ExpertMatcher, a method for automating deep learning model selection using autoencoders. Specifically, we are interested in performing inference on data sources that are distributed across many clients using pretrained expert ML networks on a centralized server. The ExpertMatcher assigns the most relevant model(s) in the central server given the client's data representation. This allows resource-constrained clients in developing countries to utilize the most relevant ML models for their given task without having to evaluate the performance of each ML model. The method is generic and can be beneficial in any setup where there are local clients and numerous centralized expert ML models.

Bruno Lecouat, Ken Chang, Chuan-Sheng Foo et al.

Supervised deep learning algorithms have enabled significant performance gains in medical image classification tasks. But these methods rely on large labeled datasets that require resource-intensive expert annotation. Semi-supervised generative adversarial network (GAN) approaches offer a means to learn from limited labeled data alongside larger unlabeled datasets, but have not been applied to discern fine-scale, sparse or localized features that define medical abnormalities. To overcome these limitations, we propose a patch-based semi-supervised learning approach and evaluate performance on classification of diabetic retinopathy from funduscopic images. Our semi-supervised approach achieves high AUC with just 10-20 labeled training images, and outperforms the supervised baselines by upto 15% when less than 30% of the training dataset is labeled. Further, our method implicitly enables interpretation of the SSL predictions. As this approach enables good accuracy, resolution and interpretability with lower annotation burden, it sets the pathway for scalable applications of deep learning in clinical imaging.

Szu-Yeu Hu, Andrew Beers, Ken Chang et al.

In this paper, we propose a new pre-training scheme for U-net based image segmentation. We first train the encoding arm as a localization network to predict the center of the target, before extending it into a U-net architecture for segmentation. We apply our proposed method to the problem of segmenting the optic disc from fundus photographs. Our work shows that the features learned by encoding arm can be transferred to the segmentation network to reduce the annotation burden. We propose that an approach could have broad utility for medical image segmentation, and alleviate the burden of delineating complex structures by pre-training on annotations that are much easier to acquire.

Spyridon Bakas, Mauricio Reyes, Andras Jakab et al.

Gliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumor is a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses the state-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e., 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST/RANO criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that underwent gross total resection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset.

Andrew Beers, James Brown, Ken Chang et al.

Translating neural networks from theory to clinical practice has unique challenges, specifically in the field of neuroimaging. In this paper, we present DeepNeuro, a deep learning framework that is best-suited to putting deep learning algorithms for neuroimaging in practical usage with a minimum of friction. We show how this framework can be used to both design and train neural network architectures, as well as modify state-of-the-art architectures in a flexible and intuitive way. We display the pre- and postprocessing functions common in the medical imaging community that DeepNeuro offers to ensure consistent performance of networks across variable users, institutions, and scanners. And we show how pipelines created in DeepNeuro can be concisely packaged into shareable Docker containers and command-line interfaces using DeepNeuro's pipeline resources.

Andrew Beers, James Brown, Ken Chang et al.

Generative adversarial networks (GANs) are a class of unsupervised machine learning algorithms that can produce realistic images from randomly-sampled vectors in a multi-dimensional space. Until recently, it was not possible to generate realistic high-resolution images using GANs, which has limited their applicability to medical images that contain biomarkers only detectable at native resolution. Progressive growing of GANs is an approach wherein an image generator is trained to initially synthesize low resolution synthetic images (8x8 pixels), which are then fed to a discriminator that distinguishes these synthetic images from real downsampled images. Additional convolutional layers are then iteratively introduced to produce images at twice the previous resolution until the desired resolution is reached. In this work, we demonstrate that this approach can produce realistic medical images in two different domains; fundus photographs exhibiting vascular pathology associated with retinopathy of prematurity (ROP), and multi-modal magnetic resonance images of glioma. We also show that fine-grained details associated with pathology, such as retinal vessels or tumor heterogeneity, can be preserved and enhanced by including segmentation maps as additional channels. We envisage several applications of the approach, including image augmentation and unsupervised classification of pathology.

Ken Chang, Niranjan Balachandar, Carson K Lam et al.

Deep learning has become a promising approach for automated medical diagnoses. When medical data samples are limited, collaboration among multiple institutions is necessary to achieve high algorithm performance. However, sharing patient data often has limitations due to technical, legal, or ethical concerns. In such cases, sharing a deep learning model is a more attractive alternative. The best method of performing such a task is unclear, however. In this study, we simulate the dissemination of learning deep learning network models across four institutions using various heuristics and compare the results with a deep learning model trained on centrally hosted patient data. The heuristics investigated include ensembling single institution models, single weight transfer, and cyclical weight transfer. We evaluated these approaches for image classification in three independent image collections (retinal fundus photos, mammography, and ImageNet). We find that cyclical weight transfer resulted in a performance (testing accuracy = 77.3%) that was closest to that of centrally hosted patient data (testing accuracy = 78.7%). We also found that there is an improvement in the performance of cyclical weight transfer heuristic with high frequency of weight transfer.

Andrew Beers, Ken Chang, James Brown et al.

Deep learning has quickly become the weapon of choice for brain lesion segmentation. However, few existing algorithms pre-configure any biological context of their chosen segmentation tissues, and instead rely on the neural network's optimizer to develop such associations de novo. We present a novel method for applying deep neural networks to the problem of glioma tissue segmentation that takes into account the structured nature of gliomas - edematous tissue surrounding mutually-exclusive regions of enhancing and non-enhancing tumor. We trained multiple deep neural networks with a 3D U-Net architecture in a tree structure to create segmentations for edema, non-enhancing tumor, and enhancing tumor regions. Specifically, training was configured such that the whole tumor region including edema was predicted first, and its output segmentation was fed as input into separate models to predict enhancing and non-enhancing tumor. Our method was trained and evaluated on the publicly available BraTS dataset, achieving Dice scores of 0.882, 0.732, and 0.730 for whole tumor, enhancing tumor and tumor core respectively.