Demographic bias in misdiagnosis by computational pathology models.

Despite increasing numbers of regulatory approvals, deep learning-based computational pathology systems often overlook the impact of demographic factors on performance, potentially leading to biases. This concern is all the more important as computational pathology has leveraged large public datasets that underrepresent certain demographic groups. Using publicly available data from The Cancer Genome Atlas and the EBRAINS brain tumor atlas, as well as internal patient data, we show that whole-slide image classification models display marked performance disparities across different demographic groups when used to subtype breast and lung carcinomas and to predict IDH1 mutations in gliomas. For example, when using common modeling approaches, we observed performance gaps (in area under the receiver operating characteristic curve) between white and Black patients of 3.0% for breast cancer subtyping, 10.9% for lung cancer subtyping and 16.0% for IDH1 mutation prediction in gliomas. We found that richer feature representations obtained from self-supervised vision foundation models reduce performance variations between groups. These representations provide improvements upon weaker models even when those weaker models are combined with state-of-the-art bias mitigation strategies and modeling choices. Nevertheless, self-supervised vision foundation models do not fully eliminate these discrepancies, highlighting the continuing need for bias mitigation efforts in computational pathology. Finally, we demonstrate that our results extend to other demographic factors beyond patient race. Given these findings, we encourage regulatory and policy agencies to integrate demographic-stratified evaluation into their assessment guidelines.

A Learnable Prior Improves Inverse Tumor Growth Modeling.

Biophysical modeling, particularly involving partial differential equations (PDEs), offers significant potential for tailoring disease treatment protocols to individual patients. However, the inverse problem-solving aspect of these models presents a substantial challenge, either due to the high computational requirements of model-based approaches or the limited robustness of deep learning (DL) methods. We propose a novel framework that leverages the unique strengths of both approaches in a synergistic manner. Our method incorporates a DL ensemble for initial parameter estimation, facilitating efficient downstream evolutionary sampling initialized with this DL-based prior. We showcase the effectiveness of integrating a rapid deep-learning algorithm with a high-precision evolution strategy in estimating brain tumor cell concentrations from magnetic resonance images. The DL-Prior plays a pivotal role, significantly constraining the effective sampling-parameter space. This reduction results in a fivefold convergence acceleration and a Dice-score of 95.

Toward image-based personalization of glioblastoma therapy: A clinical and biological validation study of a novel, deep learning-driven tumor growth model.

Background: The diffuse growth pattern of glioblastoma is one of the main challenges for accurate treatment. Computational tumor growth modeling has emerged as a promising tool to guide personalized therapy. Here, we performed clinical and biological validation of a novel growth model, aiming to close the gap between the experimental state and clinical implementation. Methods: One hundred and twenty-four patients from The Cancer Genome Archive (TCGA) and 397 patients from the UCSF Glioma Dataset were assessed for significant correlations between clinical data, genetic pathway activation maps (generated with PARADIGM; TCGA only), and infiltration (Dw) as well as proliferation (ρ) parameters stemming from a Fisher-Kolmogorov growth model. To further evaluate clinical potential, we performed the same growth modeling on preoperative magnetic resonance imaging data from 30 patients of our institution and compared model-derived tumor volume and recurrence coverage with standard radiotherapy plans. Results: The parameter ratio Dw/ρ (P < .05 in TCGA) as well as the simulated tumor volume (P < .05 in TCGA/UCSF) were significantly inversely correlated with overall survival. Interestingly, we found a significant correlation between 11 proliferation pathways and the estimated proliferation parameter. Depending on the cutoff value for tumor cell density, we observed a significant improvement in recurrence coverage without significantly increased radiation volume utilizing model-derived target volumes instead of standard radiation plans. Conclusions: Identifying a significant correlation between computed growth parameters and clinical and biological data, we highlight the potential of tumor growth modeling for individualized therapy of glioblastoma. This might improve the accuracy of radiation planning in the near future.

Algorithmic fairness in artificial intelligence for medicine and healthcare.

In healthcare, the development and deployment of insufficiently fair systems of artificial intelligence (AI) can undermine the delivery of equitable care. Assessments of AI models stratified across subpopulations have revealed inequalities in how patients are diagnosed, treated and billed. In this Perspective, we outline fairness in machine learning through the lens of healthcare, and discuss how algorithmic biases (in data acquisition, genetic variation and intra-observer labelling variability, in particular) arise in clinical workflows and the resulting healthcare disparities. We also review emerging technology for mitigating biases via disentanglement, federated learning and model explainability, and their role in the development of AI-based software as a medical device.

Learn-Morph-Infer: A new way of solving the inverse problem for brain tumor modeling.

Current treatment planning of patients diagnosed with a brain tumor, such as glioma, could significantly benefit by accessing the spatial distribution of tumor cell concentration. Existing diagnostic modalities, e.g. magnetic resonance imaging (MRI), contrast sufficiently well areas of high cell density. In gliomas, however, they do not portray areas of low cell concentration, which can often serve as a source for the secondary appearance of the tumor after treatment. To estimate tumor cell densities beyond the visible boundaries of the lesion, numerical simulations of tumor growth could complement imaging information by providing estimates of full spatial distributions of tumor cells. Over recent years a corpus of literature on medical image-based tumor modeling was published. It includes different mathematical formalisms describing the forward tumor growth model. Alongside, various parametric inference schemes were developed to perform an efficient tumor model personalization, i.e. solving the inverse problem. However, the unifying drawback of all existing approaches is the time complexity of the model personalization which prohibits a potential integration of the modeling into clinical settings. In this work, we introduce a deep learning based methodology for inferring the patient-specific spatial distribution of brain tumors from T1Gd and FLAIR MRI medical scans. Coined as Learn-Morph-Infer, the method achieves real-time performance in the order of minutes on widely available hardware and the compute time is stable across tumor models of different complexity, such as reaction-diffusion and reaction-advection-diffusion models. We believe the proposed inverse solution approach not only bridges the way for clinical translation of brain tumor personalization but can also be adopted to other scientific and engineering domains.

The Liver Tumor Segmentation Benchmark (LiTS).

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in http://medicaldecathlon.com/. In addition, both data and online evaluation are accessible via https://competitions.codalab.org/competitions/17094.

Artificial intelligence for multimodal data integration in oncology.

In oncology, the patient state is characterized by a whole spectrum of modalities, ranging from radiology, histology, and genomics to electronic health records. Current artificial intelligence (AI) models operate mainly in the realm of a single modality, neglecting the broader clinical context, which inevitably diminishes their potential. Integration of different data modalities provides opportunities to increase robustness and accuracy of diagnostic and prognostic models, bringing AI closer to clinical practice. AI models are also capable of discovering novel patterns within and across modalities suitable for explaining differences in patient outcomes or treatment resistance. The insights gleaned from such models can guide exploration studies and contribute to the discovery of novel biomarkers and therapeutic targets. To support these advances, here we present a synopsis of AI methods and strategies for multimodal data fusion and association discovery. We outline approaches for AI interpretability and directions for AI-driven exploration through multimodal data interconnections. We examine challenges in clinical adoption and discuss emerging solutions.

Pan-cancer integrative histology-genomic analysis via multimodal deep learning.

The rapidly emerging field of computational pathology has demonstrated promise in developing objective prognostic models from histology images. However, most prognostic models are either based on histology or genomics alone and do not address how these data sources can be integrated to develop joint image-omic prognostic models. Additionally, identifying explainable morphological and molecular descriptors from these models that govern such prognosis is of interest. We use multimodal deep learning to jointly examine pathology whole-slide images and molecular profile data from 14 cancer types. Our weakly supervised, multimodal deep-learning algorithm is able to fuse these heterogeneous modalities to predict outcomes and discover prognostic features that correlate with poor and favorable outcomes. We present all analyses for morphological and molecular correlates of patient prognosis across the 14 cancer types at both a disease and a patient level in an interactive open-access database to allow for further exploration, biomarker discovery, and feature assessment.

Modelling glioma progression, mass effect and intracranial pressure in patient anatomy.

Increased intracranial pressure is the source of most critical symptoms in patients with glioma, and often the main cause of death. Clinical interventions could benefit from non-invasive estimates of the pressure distribution in the patient's parenchyma provided by computational models. However, existing glioma models do not simulate the pressure distribution and they rely on a large number of model parameters, which complicates their calibration from available patient data. Here we present a novel model for glioma growth, pressure distribution and corresponding brain deformation. The distinct feature of our approach is that the pressure is directly derived from tumour dynamics and patient-specific anatomy, providing non-invasive insights into the patient's state. The model predictions allow estimation of critical conditions such as intracranial hypertension, brain midline shift or neurological and cognitive impairments. A diffuse-domain formalism is employed to allow for efficient numerical implementation of the model in the patient-specific brain anatomy. The model is tested on synthetic and clinical cases. To facilitate clinical deployment, a high-performance computing implementation of the model has been publicly released.