Comparative Analysis of 2D and 3D ResNet Architectures for IDH and MGMT Mutation Detection in Glioma Patients

Gliomas are the most common cause of mortality among primary brain tumors. Molecular markers, including Isocitrate Dehydrogenase (IDH) and O[6]-methylguanine-DNA methyltransferase (MGMT) influence treatment responses and prognosis. Deep learning (DL) models may provide a non-invasive method for predicting the status of these molecular markers. To achieve non-invasive determination of gene mutations in glioma patients, we compare 2D and 3D ResNet models to predict IDH and MGMT status, using T1, post-contrast T1, and FLAIR MRI sequences. USCF glioma dataset was used, which contains 495 patients with known IDH and 410 patients with known MGMT status. The dataset was divided into training (60%), tuning (20%), and test (20%) subsets at the patient level. The 2D models take axial, coronal, and sagittal tumor slices as three separate models. To ensemble the 2D predictions the three different views were combined using logistic regression. Various ResNet architectures (ResNet10, 18, 34, 50, 101, 152) were trained. For the 3D approach, we incorporated the entire brain tumor volume in the ResNet10, 18, and 34 models. After optimizing each model, the models with the lowest tuning loss were selected for further evaluation on the separate test sets. The best-performing models in IDH prediction were the 2D ResNet50, achieving a test area under the receiver operating characteristic curve (AUROC) of 0.9096, and the 3D ResNet34, which reached a test AUROC of 0.8999. For MGMT status prediction, the 2D ResNet152 achieved a test AUROC of 0.6168; however, all 3D models yielded AUROCs less than 0.5. Overall, the study indicated that both 2D and 3D models showed high predictive value for IDH prediction, with slightly better performance in 2D models.

The 2024 Brain Tumor Segmentation (BraTS) Challenge: Glioma Segmentation on Post-treatment MRI

Gliomas are the most common malignant primary brain tumors in adults and one of the deadliest types of cancer. There are many challenges in treatment and monitoring due to the genetic diversity and high intrinsic heterogeneity in appearance, shape, histology, and treatment response. Treatments include surgery, radiation, and systemic therapies, with magnetic resonance imaging (MRI) playing a key role in treatment planning and post-treatment longitudinal assessment. The 2024 Brain Tumor Segmentation (BraTS) challenge on post-treatment glioma MRI will provide a community standard and benchmark for state-of-the-art automated segmentation models based on the largest expert-annotated post-treatment glioma MRI dataset. Challenge competitors will develop automated segmentation models to predict four distinct tumor sub-regions consisting of enhancing tissue (ET), surrounding non-enhancing T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity (SNFH), non-enhancing tumor core (NETC), and resection cavity (RC). Models will be evaluated on separate validation and test datasets using standardized performance metrics utilized across the BraTS 2024 cluster of challenges, including lesion-wise Dice Similarity Coefficient and Hausdorff Distance. Models developed during this challenge will advance the field of automated MRI segmentation and contribute to their integration into clinical practice, ultimately enhancing patient care.

Brain Tumor Segmentation (BraTS) Challenge 2024: Meningioma Radiotherapy Planning Automated Segmentation

The 2024 Brain Tumor Segmentation Meningioma Radiotherapy (BraTS-MEN-RT) challenge aims to advance automated segmentation algorithms using the largest known multi-institutional dataset of radiotherapy planning brain MRIs with expert-annotated target labels for patients with intact or post-operative meningioma that underwent either conventional external beam radiotherapy or stereotactic radiosurgery. Each case includes a defaced 3D post-contrast T1-weighted radiotherapy planning MRI in its native acquisition space, accompanied by a single-label "target volume" representing the gross tumor volume (GTV) and any at-risk post-operative site. Target volume annotations adhere to established radiotherapy planning protocols, ensuring consistency across cases and institutions. For pre-operative meningiomas, the target volume encompasses the entire GTV and associated nodular dural tail, while for post-operative cases, it includes at-risk resection cavity margins as determined by the treating institution. Case annotations were reviewed and approved by expert neuroradiologists and radiation oncologists. Participating teams will develop, containerize, and evaluate automated segmentation models using this comprehensive dataset. Model performance will be assessed using the lesion-wise Dice Similarity Coefficient and the 95% Hausdorff distance. The top-performing teams will be recognized at the Medical Image Computing and Computer Assisted Intervention Conference in October 2024. BraTS-MEN-RT is expected to significantly advance automated radiotherapy planning by enabling precise tumor segmentation and facilitating tailored treatment, ultimately improving patient outcomes.

BraTS-Path Challenge: Assessing Heterogeneous Histopathologic Brain Tumor Sub-regions

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.

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.

RadRotator: 3D Rotation of Radiographs with Diffusion Models

Transforming two-dimensional (2D) images into three-dimensional (3D) volumes is a well-known yet challenging problem for the computer vision community. In the medical domain, a few previous studies attempted to convert two or more input radiographs into computed tomography (CT) volumes. Following their effort, we introduce a diffusion model-based technology that can rotate the anatomical content of any input radiograph in 3D space, potentially enabling the visualization of the entire anatomical content of the radiograph from any viewpoint in 3D. Similar to previous studies, we used CT volumes to create Digitally Reconstructed Radiographs (DRRs) as the training data for our model. However, we addressed two significant limitations encountered in previous studies: 1. We utilized conditional diffusion models with classifier-free guidance instead of Generative Adversarial Networks (GANs) to achieve higher mode coverage and improved output image quality, with the only trade-off being slower inference time, which is often less critical in medical applications; and 2. We demonstrated that the unreliable output of style transfer deep learning (DL) models, such as Cycle-GAN, to transfer the style of actual radiographs to DRRs could be replaced with a simple yet effective training transformation that randomly changes the pixel intensity histograms of the input and ground-truth imaging data during training. This transformation makes the diffusion model agnostic to any distribution variations of the input data pixel intensity, enabling the reliable training of a DL model on input DRRs and applying the exact same model to conventional radiographs (or DRRs) during inference.

CONFLARE: CONFormal LArge language model REtrieval

Retrieval-augmented generation (RAG) frameworks enable large language models (LLMs) to retrieve relevant information from a knowledge base and incorporate it into the context for generating responses. This mitigates hallucinations and allows for the updating of knowledge without retraining the LLM. However, RAG does not guarantee valid responses if retrieval fails to identify the necessary information as the context for response generation. Also, if there is contradictory content, the RAG response will likely reflect only one of the two possible responses. Therefore, quantifying uncertainty in the retrieval process is crucial for ensuring RAG trustworthiness. In this report, we introduce a four-step framework for applying conformal prediction to quantify retrieval uncertainty in RAG frameworks. First, a calibration set of questions answerable from the knowledge base is constructed. Each question's embedding is compared against document embeddings to identify the most relevant document chunks containing the answer and record their similarity scores. Given a user-specified error rate ({\alpha}), these similarity scores are then analyzed to determine a similarity score cutoff threshold. During inference, all chunks with similarity exceeding this threshold are retrieved to provide context to the LLM, ensuring the true answer is captured in the context with a (1-{\alpha}) confidence level. We provide a Python package that enables users to implement the entire workflow proposed in our work, only using LLMs and without human intervention.

Toward Clinically Trustworthy Deep Learning: Applying Conformal Prediction to Intracranial Hemorrhage Detection

As deep learning (DL) continues to demonstrate its ability in radiological tasks, it is critical that we optimize clinical DL solutions to include safety. One of the principal concerns in the clinical adoption of DL tools is trust. This study aims to apply conformal prediction as a step toward trustworthiness for DL in radiology. This is a retrospective study of 491 non-contrast head CTs from the CQ500 dataset, in which three senior radiologists annotated slices containing intracranial hemorrhage (ICH). The dataset was split into definite and challenging subsets, where challenging images were defined to those in which there was disagreement among readers. A DL model was trained on 146 patients (10,815 slices) from the definite data (training dataset) to perform ICH localization and classification for five classes of ICH. To develop an uncertainty-aware DL model, 1,546 cases of the definite data (calibration dataset) was used for Mondrian conformal prediction (MCP). The uncertainty-aware DL model was tested on 8,401 definite and challenging cases to assess its ability to identify challenging cases. After the MCP procedure, the model achieved an F1 score of 0.920 for ICH classification on the test dataset. Additionally, it correctly identified 6,837 of the 6,856 total challenging cases as challenging (99.7% accuracy). It did not incorrectly label any definite cases as challenging. The uncertainty-aware ICH detector performs on par with state-of-the-art models. MCP's performance in detecting challenging cases demonstrates that it is useful in automated ICH detection and promising for trustworthiness in radiological DL.