Daily Papers

The visual examination of tissue biopsy sections is fundamental for cancer diagnosis, with pathologists analyzing sections at multiple magnifications to discern tumor cells and their subtypes. However, existing attention-based multiple instance learning (MIL) models, used for analyzing Whole Slide Images (WSIs) in cancer diagnostics, often overlook the contextual information of tumor and neighboring tiles, leading to misclassifications. To address this, we propose the Context-Aware Multiple Instance Learning (CAMIL) architecture. CAMIL incorporates neighbor-constrained attention to consider dependencies among tiles within a WSI and integrates contextual constraints as prior knowledge into the MIL model. We evaluated CAMIL on subtyping non-small cell lung cancer (TCGA-NSCLC) and detecting lymph node (CAMELYON16) metastasis, achieving test AUCs of 0.959\% and 0.975\%, respectively, outperforming other state-of-the-art methods. Additionally, CAMIL enhances model interpretability by identifying regions of high diagnostic value.

Recent advances in multi-modal algorithms have driven and been driven by the increasing availability of large image-text datasets, leading to significant strides in various fields, including computational pathology. However, in most existing medical image-text datasets, the text typically provides high-level summaries that may not sufficiently describe sub-tile regions within a large pathology image. For example, an image might cover an extensive tissue area containing cancerous and healthy regions, but the accompanying text might only specify that this image is a cancer slide, lacking the nuanced details needed for in-depth analysis. In this study, we introduce STimage-1K4M, a novel dataset designed to bridge this gap by providing genomic features for sub-tile images. STimage-1K4M contains 1,149 images derived from spatial transcriptomics data, which captures gene expression information at the level of individual spatial spots within a pathology image. Specifically, each image in the dataset is broken down into smaller sub-image tiles, with each tile paired with 15,000-30,000 dimensional gene expressions. With 4,293,195 pairs of sub-tile images and gene expressions, STimage-1K4M offers unprecedented granularity, paving the way for a wide range of advanced research in multi-modal data analysis an innovative applications in computational pathology, and beyond.

With over 85 million CT scans performed annually in the United States, creating tumor-related reports is a challenging and time-consuming task for radiologists. To address this need, we present RadGPT, an Anatomy-Aware Vision-Language AI Agent for generating detailed reports from CT scans. RadGPT first segments tumors, including benign cysts and malignant tumors, and their surrounding anatomical structures, then transforms this information into both structured reports and narrative reports. These reports provide tumor size, shape, location, attenuation, volume, and interactions with surrounding blood vessels and organs. Extensive evaluation on unseen hospitals shows that RadGPT can produce accurate reports, with high sensitivity/specificity for small tumor (<2 cm) detection: 80/73% for liver tumors, 92/78% for kidney tumors, and 77/77% for pancreatic tumors. For large tumors, sensitivity ranges from 89% to 97%. The results significantly surpass the state-of-the-art in abdominal CT report generation. RadGPT generated reports for 17 public datasets. Through radiologist review and refinement, we have ensured the reports' accuracy, and created the first publicly available image-text 3D medical dataset, comprising over 1.8 million text tokens and 2.7 million images from 9,262 CT scans, including 2,947 tumor scans/reports of 8,562 tumor instances. Our reports can: (1) localize tumors in eight liver sub-segments and three pancreatic sub-segments annotated per-voxel; (2) determine pancreatic tumor stage (T1-T4) in 260 reports; and (3) present individual analyses of multiple tumors--rare in human-made reports. Importantly, 948 of the reports are for early-stage tumors.

Artificial intelligence-assisted imaging analysis has made substantial strides in tumor diagnosis and management. Here we present PASTA, a pan-tumor CT foundation model that achieves state-of-the-art performance on 45 of 46 representative oncology tasks -- including lesion segmentation, tumor detection in plain CT, tumor staging, survival prediction, structured report generation, and cross-modality transfer learning, significantly outperforming the second-best models on 35 tasks. This remarkable advancement is driven by our development of PASTA-Gen, an innovative synthetic tumor generation framework that produces a comprehensive dataset of 30,000 CT scans with pixel-level annotated lesions and paired structured reports, encompassing malignancies across ten organs and five benign lesion types. By leveraging this rich, high-quality synthetic data, we overcome a longstanding bottleneck in the development of CT foundation models -- specifically, the scarcity of publicly available, high-quality annotated datasets due to privacy constraints and the substantial labor required for scaling precise data annotation. Encouragingly, PASTA demonstrates exceptional data efficiency with promising practical value, markedly improving performance on various tasks with only a small amount of real-world data. The open release of both the synthetic dataset and PASTA foundation model effectively addresses the challenge of data scarcity, thereby advancing oncological research and clinical translation.

In the radiation therapy of nasopharyngeal carcinoma (NPC), clinicians typically delineate the gross tumor volume (GTV) using non-contrast planning computed tomography to ensure accurate radiation dose delivery. However, the low contrast between tumors and adjacent normal tissues necessitates that radiation oncologists manually delineate the tumors, often relying on diagnostic MRI for guidance. % In this study, we propose a novel approach to directly segment NPC gross tumors on non-contrast planning CT images, circumventing potential registration errors when aligning MRI or MRI-derived tumor masks to planning CT. To address the low contrast issues between tumors and adjacent normal structures in planning CT, we introduce a 3D Semantic Asymmetry Tumor segmentation (SATs) method. Specifically, we posit that a healthy nasopharyngeal region is characteristically bilaterally symmetric, whereas the emergence of nasopharyngeal carcinoma disrupts this symmetry. Then, we propose a Siamese contrastive learning segmentation framework that minimizes the voxel-wise distance between original and flipped areas without tumor and encourages a larger distance between original and flipped areas with tumor. Thus, our approach enhances the sensitivity of features to semantic asymmetries. % Extensive experiments demonstrate that the proposed SATs achieves the leading NPC GTV segmentation performance in both internal and external testing, e.g., with at least 2\% absolute Dice score improvement and 12\% average distance error reduction when compared to other state-of-the-art methods in the external testing.

Brain tumor growth is unique to each glioma patient and extends beyond what is visible in imaging scans, infiltrating surrounding brain tissue. Understanding these hidden patient-specific progressions is essential for effective therapies. Current treatment plans for brain tumors, such as radiotherapy, typically involve delineating a uniform margin around the visible tumor on pre-treatment scans to target this invisible tumor growth. This "one size fits all" approach is derived from population studies and often fails to account for the nuances of individual patient conditions. We present the GliODIL framework, which infers the full spatial distribution of tumor cell concentration from available multi-modal imaging, leveraging a Fisher-Kolmogorov type physics model to describe tumor growth. This is achieved through the newly introduced method of Optimizing the Discrete Loss (ODIL), where both data and physics-based constraints are softly assimilated into the solution. Our test dataset comprises 152 glioblastoma patients with pre-treatment imaging and post-treatment follow-ups for tumor recurrence monitoring. By blending data-driven techniques with physics-based constraints, GliODIL enhances recurrence prediction in radiotherapy planning, challenging traditional uniform margins and strict adherence to the Fisher-Kolmogorov partial differential equation (PDE) model, which is adapted for complex cases.

This paper reports Deep LOGISMOS approach to 3D tumor segmentation by incorporating boundary information derived from deep contextual learning to LOGISMOS - layered optimal graph image segmentation of multiple objects and surfaces. Accurate and reliable tumor segmentation is essential to tumor growth analysis and treatment selection. A fully convolutional network (FCN), UNet, is first trained using three adjacent 2D patches centered at the tumor, providing contextual UNet segmentation and probability map for each 2D patch. The UNet segmentation is then refined by Gaussian Mixture Model (GMM) and morphological operations. The refined UNet segmentation is used to provide the initial shape boundary to build a segmentation graph. The cost for each node of the graph is determined by the UNet probability maps. Finally, a max-flow algorithm is employed to find the globally optimal solution thus obtaining the final segmentation. For evaluation, we applied the method to pancreatic tumor segmentation on a dataset of 51 CT scans, among which 30 scans were used for training and 21 for testing. With Deep LOGISMOS, DICE Similarity Coefficient (DSC) and Relative Volume Difference (RVD) reached 83.2+-7.8% and 18.6+-17.4% respectively, both are significantly improved (p<0.05) compared with contextual UNet and/or LOGISMOS alone.

The objective is the design of a Cellular Automata rule that can form patterns with 'touching' loops. A loop is defined as a closed path of 1-cells in a 2D grid on a zero background and with a zero border. A path cell is connected with two of its adjacent neighbors. In touching loops a path cell is also allowed to touch another on a diagonal. A CA rule was designed that can evolve stable touching loop patterns. The rule tries to cover the 2D space by overlapping tiles. The rule uses so-called templates, 5 x 5 matching patterns which are systematically derived from the given set of 3 x 3 tiles. The rule checks the pattern being evolved against a list of templates. If the outer neighbors of a template match, then the cell's state is set to the template's center value. Noise is injected if there is no matching template, or the tiles are not properly assembled. Thereby the evolution is driven to the desired loop patterns.

To investigate whether the pleurae, airways and vessels surrounding a nodule on non-contrast computed tomography (CT) can discriminate benign and malignant pulmonary nodules. The LIDC-IDRI dataset, one of the largest publicly available CT database, was exploited for study. A total of 1556 nodules from 694 patients were involved in statistical analysis, where nodules with average scorings <3 and >3 were respectively denoted as benign and malignant. Besides, 339 nodules from 113 patients with diagnosis ground-truth were independently evaluated. Computer algorithms were developed to segment pulmonary structures and quantify the distances to pleural surface, airways and vessels, as well as the counting number and normalized volume of airways and vessels near a nodule. Odds ratio (OR) and Chi-square (\chi^2) testing were performed to demonstrate the correlation between features of surrounding structures and nodule malignancy. A non-parametric receiver operating characteristic (ROC) analysis was conducted in logistic regression to evaluate discrimination ability of each structure. For benign and malignant groups, the average distances from nodules to pleural surface, airways and vessels are respectively (6.56, 5.19), (37.08, 26.43) and (1.42, 1.07) mm. The correlation between nodules and the counting number of airways and vessels that contact or project towards nodules are respectively (OR=22.96, \chi^2=105.04) and (OR=7.06, \chi^2=290.11). The correlation between nodules and the volume of airways and vessels are (OR=9.19, \chi^2=159.02) and (OR=2.29, \chi^2=55.89). The areas-under-curves (AUCs) for pleurae, airways and vessels are respectively 0.5202, 0.6943 and 0.6529. Our results show that malignant nodules are often surrounded by more pulmonary structures compared with benign ones, suggesting that features of these structures could be viewed as lung cancer biomarkers.

Medical image registration is a critical task that estimates the spatial correspondence between pairs of images. However, current traditional and deep-learning-based methods rely on similarity measures to generate a deforming field, which often results in disproportionate volume changes in dissimilar regions, especially in tumor regions. These changes can significantly alter the tumor size and underlying anatomy, which limits the practical use of image registration in clinical diagnosis. To address this issue, we have formulated image registration with tumors as a constraint problem that preserves tumor volumes while maximizing image similarity in other normal regions. Our proposed strategy involves a two-stage process. In the first stage, we use similarity-based registration to identify potential tumor regions by their volume change, generating a soft tumor mask accordingly. In the second stage, we propose a volume-preserving registration with a novel adaptive volume-preserving loss that penalizes the change in size adaptively based on the masks calculated from the previous stage. Our approach balances image similarity and volume preservation in different regions, i.e., normal and tumor regions, by using soft tumor masks to adjust the imposition of volume-preserving loss on each one. This ensures that the tumor volume is preserved during the registration process. We have evaluated our strategy on various datasets and network architectures, demonstrating that our method successfully preserves the tumor volume while achieving comparable registration results with state-of-the-art methods. Our codes is available at: https://dddraxxx.github.io/Volume-Preserving-Registration/.

In this paper, we present a novel approach for segmenting pediatric brain tumors using a deep learning architecture, inspired by expert radiologists' segmentation strategies. Our model delineates four distinct tumor labels and is benchmarked on a held-out PED BraTS 2024 test set (i.e., pediatric brain tumor datasets introduced by BraTS). Furthermore, we evaluate our model's performance against the state-of-the-art (SOTA) model using a new external dataset of 30 patients from CBTN (Children's Brain Tumor Network), labeled in accordance with the PED BraTS 2024 guidelines and 2023 BraTS Adult Glioma dataset. We compare segmentation outcomes with the winning algorithm from the PED BraTS 2023 challenge as the SOTA model. Our proposed algorithm achieved an average Dice score of 0.642 and an HD95 of 73.0 mm on the CBTN test data, outperforming the SOTA model, which achieved a Dice score of 0.626 and an HD95 of 84.0 mm. Moreover, our model exhibits strong generalizability, attaining a 0.877 Dice score in whole tumor segmentation on the BraTS 2023 Adult Glioma dataset, surpassing existing SOTA. Our results indicate that the proposed model is a step towards providing more accurate segmentation for pediatric brain tumors, which is essential for evaluating therapy response and monitoring patient progress. Our source code is available at https://github.com/NUBagciLab/Pediatric-Brain-Tumor-Segmentation-Model.

For patients suffering from central nervous system tumors, prognosis estimation, treatment decisions, and postoperative assessments are made from the analysis of a set of magnetic resonance (MR) scans. Currently, the lack of open tools for standardized and automatic tumor segmentation and generation of clinical reports, incorporating relevant tumor characteristics, leads to potential risks from inherent decisions' subjectivity. To tackle this problem, the proposed Raidionics open-source software has been developed, offering both a user-friendly graphical user interface and stable processing backend. The software includes preoperative segmentation models for each of the most common tumor types (i.e., glioblastomas, lower grade gliomas, meningiomas, and metastases), together with one early postoperative glioblastoma segmentation model. Preoperative segmentation performances were quite homogeneous across the four different brain tumor types, with an average Dice around 85% and patient-wise recall and precision around 95%. Postoperatively, performances were lower with an average Dice of 41%. Overall, the generation of a standardized clinical report, including the tumor segmentation and features computation, requires about ten minutes on a regular laptop. The proposed Raidionics software is the first open solution enabling an easy use of state-of-the-art segmentation models for all major tumor types, including preoperative and postsurgical standardized reports.

Foundation models in computational pathology promise to unlock the development of new clinical decision support systems and models for precision medicine. However, there is a mismatch between most clinical analysis, which is defined at the level of one or more whole slide images, and foundation models to date, which process the thousands of image tiles contained in a whole slide image separately. The requirement to train a network to aggregate information across a large number of tiles in multiple whole slide images limits these models' impact. In this work, we present a slide-level foundation model for H&E-stained histopathology, PRISM, that builds on Virchow tile embeddings and leverages clinical report text for pre-training. Using the tile embeddings, PRISM produces slide-level embeddings with the ability to generate clinical reports, resulting in several modes of use. Using text prompts, PRISM achieves zero-shot cancer detection and sub-typing performance approaching and surpassing that of a supervised aggregator model. Using the slide embeddings with linear classifiers, PRISM surpasses supervised aggregator models. Furthermore, we demonstrate that fine-tuning of the PRISM slide encoder yields label-efficient training for biomarker prediction, a task that typically suffers from low availability of training data; an aggregator initialized with PRISM and trained on as little as 10% of the training data can outperform a supervised baseline that uses all of the data.

One of the primary challenges in brain tumor segmentation arises from the uncertainty of voxels close to tumor boundaries. However, the conventional process of generating ground truth segmentation masks fails to treat such uncertainties properly. Those "hard labels" with 0s and 1s conceptually influenced the majority of prior studies on brain image segmentation. As a result, tumor segmentation is often solved through voxel classification. In this work, we instead view this problem as a voxel-level regression, where the ground truth represents a certainty mapping from any pixel to the border of the tumor. We propose a novel ground truth label transformation, which is based on a signed geodesic transform, to capture the uncertainty in brain tumors' vicinity. We combine this idea with a Focal-like regression L1-loss that enables effective regression learning in high-dimensional output space by appropriately weighting voxels according to their difficulty. We thoroughly conduct an experimental evaluation to validate the components of our proposed method, compare it to a diverse array of state-of-the-art segmentation models, and show that it is architecture-agnostic. The code of our method is made publicly available (https://github.com/Oulu-IMEDS/SiNGR/).

Artificial intelligence has significantly advanced skin cancer diagnosis by enabling rapid and accurate detection of malignant lesions. In this domain, most publicly available image datasets consist of single, isolated skin lesions positioned at the center of the image. While these lesion-centric datasets have been fundamental for developing diagnostic algorithms, they lack the context of the surrounding skin, which is critical for improving lesion detection. The iToBoS dataset was created to address this challenge. It includes 16,954 images of skin regions from 100 participants, captured using 3D total body photography. Each image roughly corresponds to a 7 times 9 cm section of skin with all suspicious lesions annotated using bounding boxes. Additionally, the dataset provides metadata such as anatomical location, age group, and sun damage score for each image. This dataset aims to facilitate training and benchmarking of algorithms, with the goal of enabling early detection of skin cancer and deployment of this technology in non-clinical environments.

AI-driven tumor analysis has garnered increasing attention in healthcare. However, its progress is significantly hindered by the lack of annotated tumor cases, which requires radiologists to invest a lot of effort in collecting and annotation. In this paper, we introduce a highly practical solution for robust tumor synthesis and segmentation, termed FreeTumor, which refers to annotation-free synthetic tumors and our desire to free patients that suffering from tumors. Instead of pursuing sophisticated technical synthesis modules, we aim to design a simple yet effective tumor synthesis paradigm to unleash the power of large-scale data. Specifically, FreeTumor advances existing methods mainly from three aspects: (1) Existing methods only leverage small-scale labeled data for synthesis training, which limits their ability to generalize well on unseen data from different sources. To this end, we introduce the adversarial training strategy to leverage large-scale and diversified unlabeled data in synthesis training, significantly improving tumor synthesis. (2) Existing methods largely ignored the negative impact of low-quality synthetic tumors in segmentation training. Thus, we employ an adversarial-based discriminator to automatically filter out the low-quality synthetic tumors, which effectively alleviates their negative impact. (3) Existing methods only used hundreds of cases in tumor segmentation. In FreeTumor, we investigate the data scaling law in tumor segmentation by scaling up the dataset to 11k cases. Extensive experiments demonstrate the superiority of FreeTumor, e.g., on three tumor segmentation benchmarks, average +8.9% DSC over the baseline that only using real tumors and +6.6% DSC over the state-of-the-art tumor synthesis method. Code will be available.

Identifying key pathological features in brain MRIs is crucial for the long-term survival of glioma patients. However, manual segmentation is time-consuming, requiring expert intervention and is susceptible to human error. Therefore, significant research has been devoted to developing machine learning methods that can accurately segment tumors in 3D multimodal brain MRI scans. Despite their progress, state-of-the-art models are often limited by the data they are trained on, raising concerns about their reliability when applied to diverse populations that may introduce distribution shifts. Such shifts can stem from lower quality MRI technology (e.g., in sub-Saharan Africa) or variations in patient demographics (e.g., children). The BraTS-2024 challenge provides a platform to address these issues. This study presents our methodology for segmenting tumors in the BraTS-2024 SSA and Pediatric Tumors tasks using MedNeXt, comprehensive model ensembling, and thorough postprocessing. Our approach demonstrated strong performance on the unseen validation set, achieving an average Dice Similarity Coefficient (DSC) of 0.896 on the BraTS-2024 SSA dataset and an average DSC of 0.830 on the BraTS Pediatric Tumor dataset. Additionally, our method achieved an average Hausdorff Distance (HD95) of 14.682 on the BraTS-2024 SSA dataset and an average HD95 of 37.508 on the BraTS Pediatric dataset. Our GitHub repository can be accessed here: Project Repository : https://github.com/python-arch/BioMbz-Optimizing-Brain-Tumor-Segmentation-with-MedNeXt-BraTS-2024-SSA-and-Pediatrics