Model Ensemble for Brain Tumor Segmentation in Magnetic Resonance Imaging

Segmenting brain tumors in multi-parametric magnetic resonance imaging enables performing quantitative analysis in support of clinical trials and personalized patient care. This analysis provides the potential to impact clinical decision-making processes, including diagnosis and prognosis. In 2023, the well-established Brain Tumor Segmentation (BraTS) challenge presented a substantial expansion with eight tasks and 4,500 brain tumor cases. In this paper, we present a deep learning-based ensemble strategy that is evaluated for newly included tumor cases in three tasks: pediatric brain tumors (PED), intracranial meningioma (MEN), and brain metastases (MET). In particular, we ensemble outputs from state-of-the-art nnU-Net and Swin UNETR models on a region-wise basis. Furthermore, we implemented a targeted post-processing strategy based on a cross-validated threshold search to improve the segmentation results for tumor sub-regions. The evaluation of our proposed method on unseen test cases for the three tasks resulted in lesion-wise Dice scores for PED: 0.653, 0.809, 0.826; MEN: 0.876, 0.867, 0.849; and MET: 0.555, 0.6, 0.58; for the enhancing tumor, tumor core, and whole tumor, respectively. Our method was ranked first for PED, third for MEN, and fourth for MET, respectively.

Unifying Invariant and Variant Features for Graph Out-of-Distribution via Probability of Necessity and Sufficiency

Graph Out-of-Distribution (OOD), requiring that models trained on biased data generalize to the unseen test data, has considerable real-world applications. One of the most mainstream methods is to extract the invariant subgraph by aligning the original and augmented data with the help of environment augmentation. However, these solutions might lead to the loss or redundancy of semantic subgraphs and result in suboptimal generalization. To address this challenge, we propose exploiting Probability of Necessity and Sufficiency (PNS) to extract sufficient and necessary invariant substructures. Beyond that, we further leverage the domain variant subgraphs related to the labels to boost the generalization performance in an ensemble manner. Specifically, we first consider the data generation process for graph data. Under mild conditions, we show that the sufficient and necessary invariant subgraph can be extracted by minimizing an upper bound, built on the theoretical advance of the probability of necessity and sufficiency. To further bridge the theory and algorithm, we devise the model called Sufficiency and Necessity Inspired Graph Learning (SNIGL), which ensembles an invariant subgraph classifier on top of latent sufficient and necessary invariant subgraphs, and a domain variant subgraph classifier specific to the test domain for generalization enhancement. Experimental results demonstrate that our SNIGL model outperforms the state-of-the-art techniques on six public benchmarks, highlighting its effectiveness in real-world scenarios.

Data Alchemy: Mitigating Cross-Site Model Variability Through Test Time Data Calibration

Deploying deep learning-based imaging tools across various clinical sites poses significant challenges due to inherent domain shifts and regulatory hurdles associated with site-specific fine-tuning. For histopathology, stain normalization techniques can mitigate discrepancies, but they often fall short of eliminating inter-site variations. Therefore, we present Data Alchemy, an explainable stain normalization method combined with test time data calibration via a template learning framework to overcome barriers in cross-site analysis. Data Alchemy handles shifts inherent to multi-site data and minimizes them without needing to change the weights of the normalization or classifier networks. Our approach extends to unseen sites in various clinical settings where data domain discrepancies are unknown. Extensive experiments highlight the efficacy of our framework in tumor classification in hematoxylin and eosin-stained patches. Our explainable normalization method boosts classification tasks' area under the precision-recall curve(AUPR) by 0.165, 0.545 to 0.710. Additionally, Data Alchemy further reduces the multisite classification domain gap, by improving the 0.710 AUPR an additional 0.142, elevating classification performance further to 0.852, from 0.545. Our Data Alchemy framework can popularize precision medicine with minimal operational overhead by allowing for the seamless integration of pre-trained deep learning-based clinical tools across multiple sites.

BraTS-PEDs: Results of the Multi-Consortium International Pediatric Brain Tumor Segmentation Challenge 2023

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.

D-Rax: Domain-specific Radiologic assistant leveraging multi-modal data and eXpert model predictions

Large vision language models (VLMs) have progressed incredibly from research to applicability for general-purpose use cases. LLaVA-Med, a pioneering large language and vision assistant for biomedicine, can perform multi-modal biomedical image and data analysis to provide a natural language interface for radiologists. While it is highly generalizable and works with multi-modal data, it is currently limited by well-known challenges that exist in the large language model space. Hallucinations and imprecision in responses can lead to misdiagnosis which currently hinder the clinical adaptability of VLMs. To create precise, user-friendly models in healthcare, we propose D-Rax -- a domain-specific, conversational, radiologic assistance tool that can be used to gain insights about a particular radiologic image. In this study, we enhance the conversational analysis of chest X-ray (CXR) images to support radiological reporting, offering comprehensive insights from medical imaging and aiding in the formulation of accurate diagnosis. D-Rax is achieved by fine-tuning the LLaVA-Med architecture on our curated enhanced instruction-following data, comprising of images, instructions, as well as disease diagnosis and demographic predictions derived from MIMIC-CXR imaging data, CXR-related visual question answer (VQA) pairs, and predictive outcomes from multiple expert AI models. We observe statistically significant improvement in responses when evaluated for both open and close-ended conversations. Leveraging the power of state-of-the-art diagnostic models combined with VLMs, D-Rax empowers clinicians to interact with medical images using natural language, which could potentially streamline their decision-making process, enhance diagnostic accuracy, and conserve their time.

Analysis of the BraTS 2023 Intracranial Meningioma Segmentation Challenge

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.

The Brain Tumor Segmentation in Pediatrics (BraTS-PEDs) Challenge: Focus on Pediatrics (CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs)

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs challenge, focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors.

Unifying Invariance and Spuriousity for Graph Out-of-Distribution via Probability of Necessity and Sufficiency

Graph Out-of-Distribution (OOD), requiring that models trained on biased data generalize to the unseen test data, has a massive of real-world applications. One of the most mainstream methods is to extract the invariant subgraph by aligning the original and augmented data with the help of environment augmentation. However, these solutions might lead to the loss or redundancy of semantic subgraph and further result in suboptimal generalization. To address this challenge, we propose a unified framework to exploit the Probability of Necessity and Sufficiency to extract the Invariant Substructure (PNSIS). Beyond that, this framework further leverages the spurious subgraph to boost the generalization performance in an ensemble manner to enhance the robustness on the noise data. Specificially, we first consider the data generation process for graph data. Under mild conditions, we show that the invariant subgraph can be extracted by minimizing an upper bound, which is built on the theoretical advance of probability of necessity and sufficiency. To further bridge the theory and algorithm, we devise the PNSIS model, which involves an invariant subgraph extractor for invariant graph learning as well invariant and spurious subgraph classifiers for generalization enhancement. Experimental results demonstrate that our \textbf{PNSIS} model outperforms the state-of-the-art techniques on graph OOD on several benchmarks, highlighting the effectiveness in real-world scenarios.

Quantitative Metrics for Benchmarking Medical Image Harmonization

Image harmonization is an important preprocessing strategy to address domain shifts arising from data acquired using different machines and scanning protocols in medical imaging. However, benchmarking the effectiveness of harmonization techniques has been a challenge due to the lack of widely available standardized datasets with ground truths. In this context, we propose three metrics: two intensity harmonization metrics and one anatomy preservation metric for medical images during harmonization, where no ground truths are required. Through extensive studies on a dataset with available harmonization ground truth, we demonstrate that our metrics are correlated with established image quality assessment metrics. We show how these novel metrics may be applied to real-world scenarios where no harmonization ground truth exists. Additionally, we provide insights into different interpretations of the metric values, shedding light on their significance in the context of the harmonization process. As a result of our findings, we advocate for the adoption of these quantitative harmonization metrics as a standard for benchmarking the performance of image harmonization techniques.

Harmonization Across Imaging Locations(HAIL): One-Shot Learning for Brain MRI

For machine learning-based prognosis and diagnosis of rare diseases, such as pediatric brain tumors, it is necessary to gather medical imaging data from multiple clinical sites that may use different devices and protocols. Deep learning-driven harmonization of radiologic images relies on generative adversarial networks (GANs). However, GANs notoriously generate pseudo structures that do not exist in the original training data, a phenomenon known as "hallucination". To prevent hallucination in medical imaging, such as magnetic resonance images (MRI) of the brain, we propose a one-shot learning method where we utilize neural style transfer for harmonization. At test time, the method uses one image from a clinical site to generate an image that matches the intensity scale of the collaborating sites. Our approach combines learning a feature extractor, neural style transfer, and adaptive instance normalization. We further propose a novel strategy to evaluate the effectiveness of image harmonization approaches with evaluation metrics that both measure image style harmonization and assess the preservation of anatomical structures. Experimental results demonstrate the effectiveness of our method in preserving patient anatomy while adjusting the image intensities to a new clinical site. Our general harmonization model can be used on unseen data from new sites, making it a valuable tool for real-world medical applications and clinical trials.