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Krzysztof J. Geras

Publications and source records attributed to Krzysztof J. Geras.

At least 19 recordsLinked to original sources

Transcriptome-informed multi-modal AI for predicting neoadjuvant therapy response from breast cancer biopsies

Scarcity of labeled data limits development of deep learning biomarkers in oncology. We develop a two-stage AI model predicting pathological complete response (pCR) to neoadjuvant therapy in breast cancer. The first stage learns the transcriptome from histopathology using 8,742 patients across 32 cancer types, corroborated by pathologist review and spatial agreement with measured expression. This simplifies the second stage to predicting pCR from inferred expression and clinical variables. Developed using 1,080 patients (five cohorts) and evaluated in 1,412 patients (nine cohorts), the model achieves a pooled AUROC of 0.79 (95% CI, 0.73-0.85), discriminating responders within molecular subtypes. It outperforms histopathological biomarkers, remaining stable across intratumoral sampling and with minimal biopsy tissue. Ablations show transcriptome-wide inference improves discrimination over clinical variables alone or one-stage pathology models, and robustness by avoiding genomic assays' gene selection constraints. These results indicate that biologically informed compression may generalize to data-sparse applications in precision oncology.

cs.AI↗

Causal multi-modal AI for personalized chemosensitivity prediction

Chemotherapy improves survival for some patients with breast cancer, but doctors cannot reliably predict who. Current guidelines rely on recurrence scores as a proxy for treatment benefit, which may contribute to the overprescription of chemotherapy. Here we present a causal multi-modal AI model that predicts personalized chemosensitivity using routinely collected pathology and clinical information. We developed our model on a multi-national dataset of 9,141 patients (twelve cohorts, nine countries) and evaluated it on another 1,994 patients (five cohorts, three countries). The model generated treatment-specific recurrence probabilities for each patient, with near-perfect calibration and strong prognostic discrimination across both 5- and 10-year follow-up horizons. Moreover, its chemotherapy benefit predictions demonstrated robust predictive performance, and out-performed existing recurrence-score-based tests. Compared to the standard of care, using the model to support personally tailored therapeutic decisions could reduce the number of patients receiving chemotherapy by 30% while achieving the same recurrence-free rate. Tumors predicted to be highly chemosensitive displayed concordant molecular and morphological programs of proliferation, cell cycle progression, and replication stress. The model's predictive capabilities transferred zero-shot to non-breast cancers, indicating our causal multi-modal AI approach may provide a universal strategy to predict treatment outcomes across cancer types.

cs.AI↗

Pitfalls of Administrative Censoring in Survival Models with Time-Indexed Inputs

Survival models can model time-to-event outcomes using partially observed data. They are widely used in clinical prediction, including cancer risk, disease progression, treatment response, and mortality. Recent models often rely on rich inputs collected at a specific clinical encounter, such as medical images, laboratory tests, electronic health record snapshots, or sensor measurements. In large retrospective datasets, these inputs are usually collected over many calendar years. As a result, they may contain clues about when they were acquired through changes in devices, protocols, documentation, patient mix, or clinical practice. This creates a potential failure mode when outcomes are observed only up to a fixed study end date. More recent records necessarily have less potential follow-up than older records. A model that can infer the record date from the input may therefore learn to predict how much follow-up was available rather than the patient's true risk of experiencing the event. We call this failure mode administrative-cutoff leakage. In this paper, we characterize when this leakage can occur, distinguish it from classical informative censoring and genuine temporal changes in risk, and propose practical ways to detect it. In simulations, we show that administrative-cutoff leakage can inflate fixed-horizon AUC and can also affect Harrell's C-index under realistic follow-up patterns. We then demonstrate the same behavior in a real mammography cohort. These results motivate a simple design principle for survival prediction: for an n-year prediction task, the dataset should provide at least n years of potential follow-up after the latest input date. Otherwise, the models may be subject to bias induced by administrative-cutoff leakage.

cs.LG↗

Understanding differences in applying DETR to natural and medical images

Transformer-based detectors have shown success in computer vision tasks with natural images. These models, exemplified by the Deformable DETR, are optimized through complex engineering strategies tailored to the typical characteristics of natural scenes. However, medical imaging data presents unique challenges such as extremely large image sizes, fewer and smaller regions of interest, and object classes which can be differentiated only through subtle differences. This study evaluates the applicability of these transformer-based design choices when applied to a screening mammography dataset that represents these distinct medical imaging data characteristics. Our analysis reveals that common design choices from the natural image domain, such as complex encoder architectures, multi-scale feature fusion, query initialization, and iterative bounding box refinement, do not improve and sometimes even impair object detection performance in medical imaging. In contrast, simpler and shallower architectures often achieve equal or superior results. This finding suggests that the adaptation of transformer models for medical imaging data requires a reevaluation of standard practices, potentially leading to more efficient and specialized frameworks for medical diagnosis.

cs.CV↗

A Multi-Modal AI System for Screening Mammography: Integrating 2D and 3D Imaging to Improve Breast Cancer Detection in a Prospective Clinical Study

Although digital breast tomosynthesis (DBT) improves diagnostic performance over full-field digital mammography (FFDM), false-positive recalls remain a concern in breast cancer screening. We developed a multi-modal artificial intelligence system integrating FFDM, synthetic mammography, and DBT to provide breast-level predictions and bounding-box localizations of suspicious findings. Our AI system, trained on approximately 500,000 mammography exams, achieved 0.945 AUROC on an internal test set. It demonstrated capacity to reduce recalls by 31.7% and radiologist workload by 43.8% while maintaining 100% sensitivity, underscoring its potential to improve clinical workflows. External validation confirmed strong generalizability, reducing the gap to a perfect AUROC by 35.31%-69.14% relative to strong baselines. In prospective deployment across 18 sites, the system reduced recall rates for low-risk cases. An improved version, trained on over 750,000 exams with additional labels, further reduced the gap by 18.86%-56.62% across large external datasets. Overall, these results underscore the importance of utilizing all available imaging modalities, demonstrate the potential for clinical impact, and indicate feasibility of further reduction of the test error with increased training set when using large-capacity neural networks.

eess.IV↗

Multi-modal AI for comprehensive breast cancer prognostication

Treatment selection in breast cancer is guided by molecular subtypes and clinical characteristics. However, current tools including genomic assays lack the accuracy required for optimal clinical decision-making. We developed a novel artificial intelligence (AI)-based approach that integrates digital pathology images with clinical data, providing a more robust and effective method for predicting the risk of cancer recurrence in breast cancer patients. Specifically, we utilized a vision transformer pan-cancer foundation model trained with self-supervised learning to extract features from digitized H&E-stained slides. These features were integrated with clinical data to form a multi-modal AI test predicting cancer recurrence and death. The test was developed and evaluated using data from a total of 8,161 female breast cancer patients across 15 cohorts originating from seven countries. Of these, 3,502 patients from five cohorts were used exclusively for evaluation, while the remaining patients were used for training. Our test accurately predicted our primary endpoint, disease-free interval, in the five evaluation cohorts (C-index: 0.71 [0.68-0.75], HR: 3.63 [3.02-4.37, p<0.001]). In a direct comparison (n=858), the AI test was more accurate than Oncotype DX, the standard-of-care 21-gene assay, achieving a C-index of 0.67 [0.61-0.74] versus 0.61 [0.49-0.73], respectively. Additionally, the AI test added independent prognostic information to Oncotype DX in a multivariate analysis (HR: 3.11 [1.91-5.09, p<0.001)]). The test demonstrated robust accuracy across major molecular breast cancer subtypes, including TNBC (C-index: 0.71 [0.62-0.81], HR: 3.81 [2.35-6.17, p=0.02]), where no diagnostic tools are currently recommended by clinical guidelines. These results suggest that our AI test improves upon the accuracy of existing prognostic tests, while being applicable to a wider range of patients.

cs.AI↗

Leveraging Neural Networks to Profile Health Care Providers with Application to Medicare Claims

Encompassing numerous nationwide, statewide, and institutional initiatives in the United States, provider profiling has evolved into a major health care undertaking with ubiquitous applications, profound implications, and high-stakes consequences. In line with such a significant profile, the literature has accumulated a number of developments dedicated to enhancing the statistical paradigm of provider profiling. Tackling wide-ranging profiling issues, these methods typically adjust for risk factors using linear predictors. While this approach is simple, it can be too restrictive to characterize complex and dynamic factor-outcome associations in certain contexts. One such example arises from evaluating dialysis facilities treating Medicare beneficiaries with end-stage renal disease. It is of primary interest to consider how the coronavirus disease (COVID-19) affected 30-day unplanned readmissions in 2020. The impact of COVID-19 on the risk of readmission varied dramatically across pandemic phases. To efficiently capture the variation while profiling facilities, we develop a generalized partially linear model (GPLM) that incorporates a neural network. Considering provider-level clustering, we implement the GPLM as a stratified sampling-based stochastic optimization algorithm that features accelerated convergence. Furthermore, an exact test is designed to identify under- and over-performing facilities, with an accompanying funnel plot to visualize profiles. The advantages of the proposed methods are demonstrated through simulation experiments and profiling dialysis facilities using 2020 Medicare claims from the United States Renal Data System.

stat.ME↗

Leveraging Transformers to Improve Breast Cancer Classification and Risk Assessment with Multi-modal and Longitudinal Data

Breast cancer screening, primarily conducted through mammography, is often supplemented with ultrasound for women with dense breast tissue. However, existing deep learning models analyze each modality independently, missing opportunities to integrate information across imaging modalities and time. In this study, we present Multi-modal Transformer (MMT), a neural network that utilizes mammography and ultrasound synergistically, to identify patients who currently have cancer and estimate the risk of future cancer for patients who are currently cancer-free. MMT aggregates multi-modal data through self-attention and tracks temporal tissue changes by comparing current exams to prior imaging. Trained on 1.3 million exams, MMT achieves an AUROC of 0.943 in detecting existing cancers, surpassing strong uni-modal baselines. For 5-year risk prediction, MMT attains an AUROC of 0.826, outperforming prior mammography-based risk models. Our research highlights the value of multi-modal and longitudinal imaging in cancer diagnosis and risk stratification.

eess.IV↗

Multiple Instance Learning via Iterative Self-Paced Supervised Contrastive Learning

Learning representations for individual instances when only bag-level labels are available is a fundamental challenge in multiple instance learning (MIL). Recent works have shown promising results using contrastive self-supervised learning (CSSL), which learns to push apart representations corresponding to two different randomly-selected instances. Unfortunately, in real-world applications such as medical image classification, there is often class imbalance, so randomly-selected instances mostly belong to the same majority class, which precludes CSSL from learning inter-class differences. To address this issue, we propose a novel framework, Iterative Self-paced Supervised Contrastive Learning for MIL Representations (ItS2CLR), which improves the learned representation by exploiting instance-level pseudo labels derived from the bag-level labels. The framework employs a novel self-paced sampling strategy to ensure the accuracy of pseudo labels. We evaluate ItS2CLR on three medical datasets, showing that it improves the quality of instance-level pseudo labels and representations, and outperforms existing MIL methods in terms of both bag and instance level accuracy. Code is available at https://github.com/Kangningthu/ItS2CLR

cs.CV↗

MedFuse: Multi-modal fusion with clinical time-series data and chest X-ray images

Multi-modal fusion approaches aim to integrate information from different data sources. Unlike natural datasets, such as in audio-visual applications, where samples consist of "paired" modalities, data in healthcare is often collected asynchronously. Hence, requiring the presence of all modalities for a given sample is not realistic for clinical tasks and significantly limits the size of the dataset during training. In this paper, we propose MedFuse, a conceptually simple yet promising LSTM-based fusion module that can accommodate uni-modal as well as multi-modal input. We evaluate the fusion method and introduce new benchmark results for in-hospital mortality prediction and phenotype classification, using clinical time-series data in the MIMIC-IV dataset and corresponding chest X-ray images in MIMIC-CXR. Compared to more complex multi-modal fusion strategies, MedFuse provides a performance improvement by a large margin on the fully paired test set. It also remains robust across the partially paired test set containing samples with missing chest X-ray images. We release our code for reproducibility and to enable the evaluation of competing models in the future.

eess.IV↗

An efficient deep neural network to find small objects in large 3D images

3D imaging enables accurate diagnosis by providing spatial information about organ anatomy. However, using 3D images to train AI models is computationally challenging because they consist of 10x or 100x more pixels than their 2D counterparts. To be trained with high-resolution 3D images, convolutional neural networks resort to downsampling them or projecting them to 2D. We propose an effective alternative, a neural network that enables efficient classification of full-resolution 3D medical images. Compared to off-the-shelf convolutional neural networks, our network, 3D Globally-Aware Multiple Instance Classifier (3D-GMIC), uses 77.98%-90.05% less GPU memory and 91.23%-96.02% less computation. While it is trained only with image-level labels, without segmentation labels, it explains its predictions by providing pixel-level saliency maps. On a dataset collected at NYU Langone Health, including 85,526 patients with full-field 2D mammography (FFDM), synthetic 2D mammography, and 3D mammography, 3D-GMIC achieves an AUC of 0.831 (95% CI: 0.769-0.887) in classifying breasts with malignant findings using 3D mammography. This is comparable to the performance of GMIC on FFDM (0.816, 95% CI: 0.737-0.878) and synthetic 2D (0.826, 95% CI: 0.754-0.884), which demonstrates that 3D-GMIC successfully classified large 3D images despite focusing computation on a smaller percentage of its input compared to GMIC. Therefore, 3D-GMIC identifies and utilizes extremely small regions of interest from 3D images consisting of hundreds of millions of pixels, dramatically reducing associated computational challenges. 3D-GMIC generalizes well to BCS-DBT, an external dataset from Duke University Hospital, achieving an AUC of 0.848 (95% CI: 0.798-0.896).

cs.CV↗

Generative multitask learning mitigates target-causing confounding

We propose generative multitask learning (GMTL), a simple and scalable approach to causal representation learning for multitask learning. Our approach makes a minor change to the conventional multitask inference objective, and improves robustness to target shift. Since GMTL only modifies the inference objective, it can be used with existing multitask learning methods without requiring additional training. The improvement in robustness comes from mitigating unobserved confounders that cause the targets, but not the input. We refer to them as \emph{target-causing confounders}. These confounders induce spurious dependencies between the input and targets. This poses a problem for conventional multitask learning, due to its assumption that the targets are conditionally independent given the input. GMTL mitigates target-causing confounding at inference time, by removing the influence of the joint target distribution, and predicting all targets jointly. This removes the spurious dependencies between the input and targets, where the degree of removal is adjustable via a single hyperparameter. This flexibility is useful for managing the trade-off between in- and out-of-distribution generalization. Our results on the Attributes of People and Taskonomy datasets reflect an improved robustness to target shift across four multitask learning methods.

cs.LG↗

Characterizing and overcoming the greedy nature of learning in multi-modal deep neural networks

We hypothesize that due to the greedy nature of learning in multi-modal deep neural networks, these models tend to rely on just one modality while under-fitting the other modalities. Such behavior is counter-intuitive and hurts the models' generalization, as we observe empirically. To estimate the model's dependence on each modality, we compute the gain on the accuracy when the model has access to it in addition to another modality. We refer to this gain as the conditional utilization rate. In the experiments, we consistently observe an imbalance in conditional utilization rates between modalities, across multiple tasks and architectures. Since conditional utilization rate cannot be computed efficiently during training, we introduce a proxy for it based on the pace at which the model learns from each modality, which we refer to as the conditional learning speed. We propose an algorithm to balance the conditional learning speeds between modalities during training and demonstrate that it indeed addresses the issue of greedy learning. The proposed algorithm improves the model's generalization on three datasets: Colored MNIST, ModelNet40, and NVIDIA Dynamic Hand Gesture.

cs.LG↗

Meta-repository of screening mammography classifiers

Artificial intelligence (AI) is showing promise in improving clinical diagnosis. In breast cancer screening, recent studies show that AI has the potential to improve early cancer diagnosis and reduce unnecessary workup. As the number of proposed models and their complexity grows, it is becoming increasingly difficult to re-implement them. To enable reproducibility of research and to enable comparison between different methods, we release a meta-repository containing models for classification of screening mammograms. This meta-repository creates a framework that enables the evaluation of AI models on any screening mammography data set. At its inception, our meta-repository contains five state-of-the-art models with open-source implementations and cross-platform compatibility. We compare their performance on seven international data sets. Our framework has a flexible design that can be generalized to other medical image analysis tasks. The meta-repository is available at https://www.github.com/nyukat/mammography_metarepository.

cs.LG↗

Towards dynamic multi-modal phenotyping using chest radiographs and physiological data

The healthcare domain is characterized by heterogeneous data modalities, such as imaging and physiological data. In practice, the variety of medical data assists clinicians in decision-making. However, most of the current state-of-the-art deep learning models solely rely upon carefully curated data of a single modality. In this paper, we propose a dynamic training approach to learn modality-specific data representations and to integrate auxiliary features, instead of solely relying on a single modality. Our preliminary experiments results for a patient phenotyping task using physiological data in MIMIC-IV & chest radiographs in the MIMIC- CXR dataset show that our proposed approach achieves the highest area under the receiver operating characteristic curve (AUROC) (0.764 AUROC) compared to the performance of the benchmark method in previous work, which only used physiological data (0.740 AUROC). For a set of five recurring or chronic diseases with periodic acute episodes, including cardiac dysrhythmia, conduction disorders, and congestive heart failure, the AUROC improves from 0.747 to 0.798. This illustrates the benefit of leveraging the chest imaging modality in the phenotyping task and highlights the potential of multi-modal learning in medical applications.

eess.IV↗

Weakly-supervised High-resolution Segmentation of Mammography Images for Breast Cancer Diagnosis

In the last few years, deep learning classifiers have shown promising results in image-based medical diagnosis. However, interpreting the outputs of these models remains a challenge. In cancer diagnosis, interpretability can be achieved by localizing the region of the input image responsible for the output, i.e. the location of a lesion. Alternatively, segmentation or detection models can be trained with pixel-wise annotations indicating the locations of malignant lesions. Unfortunately, acquiring such labels is labor-intensive and requires medical expertise. To overcome this difficulty, weakly-supervised localization can be utilized. These methods allow neural network classifiers to output saliency maps highlighting the regions of the input most relevant to the classification task (e.g. malignant lesions in mammograms) using only image-level labels (e.g. whether the patient has cancer or not) during training. When applied to high-resolution images, existing methods produce low-resolution saliency maps. This is problematic in applications in which suspicious lesions are small in relation to the image size. In this work, we introduce a novel neural network architecture to perform weakly-supervised segmentation of high-resolution images. The proposed model selects regions of interest via coarse-level localization, and then performs fine-grained segmentation of those regions. We apply this model to breast cancer diagnosis with screening mammography, and validate it on a large clinically-realistic dataset. Measured by Dice similarity score, our approach outperforms existing methods by a large margin in terms of localization performance of benign and malignant lesions, relatively improving the performance by 39.6% and 20.0%, respectively. Code and the weights of some of the models are available at https://github.com/nyukat/GLAM

cs.CV↗

COVID-19 Prognosis via Self-Supervised Representation Learning and Multi-Image Prediction

The rapid spread of COVID-19 cases in recent months has strained hospital resources, making rapid and accurate triage of patients presenting to emergency departments a necessity. Machine learning techniques using clinical data such as chest X-rays have been used to predict which patients are most at risk of deterioration. We consider the task of predicting two types of patient deterioration based on chest X-rays: adverse event deterioration (i.e., transfer to the intensive care unit, intubation, or mortality) and increased oxygen requirements beyond 6 L per day. Due to the relative scarcity of COVID-19 patient data, existing solutions leverage supervised pretraining on related non-COVID images, but this is limited by the differences between the pretraining data and the target COVID-19 patient data. In this paper, we use self-supervised learning based on the momentum contrast (MoCo) method in the pretraining phase to learn more general image representations to use for downstream tasks. We present three results. The first is deterioration prediction from a single image, where our model achieves an area under receiver operating characteristic curve (AUC) of 0.742 for predicting an adverse event within 96 hours (compared to 0.703 with supervised pretraining) and an AUC of 0.765 for predicting oxygen requirements greater than 6 L a day at 24 hours (compared to 0.749 with supervised pretraining). We then propose a new transformer-based architecture that can process sequences of multiple images for prediction and show that this model can achieve an improved AUC of 0.786 for predicting an adverse event at 96 hours and an AUC of 0.848 for predicting mortalities at 96 hours. A small pilot clinical study suggested that the prediction accuracy of our model is comparable to that of experienced radiologists analyzing the same information.

cs.CV↗

Differences between human and machine perception in medical diagnosis

Deep neural networks (DNNs) show promise in image-based medical diagnosis, but cannot be fully trusted since their performance can be severely degraded by dataset shifts to which human perception remains invariant. If we can better understand the differences between human and machine perception, we can potentially characterize and mitigate this effect. We therefore propose a framework for comparing human and machine perception in medical diagnosis. The two are compared with respect to their sensitivity to the removal of clinically meaningful information, and to the regions of an image deemed most suspicious. Drawing inspiration from the natural image domain, we frame both comparisons in terms of perturbation robustness. The novelty of our framework is that separate analyses are performed for subgroups with clinically meaningful differences. We argue that this is necessary in order to avert Simpson's paradox and draw correct conclusions. We demonstrate our framework with a case study in breast cancer screening, and reveal significant differences between radiologists and DNNs. We compare the two with respect to their robustness to Gaussian low-pass filtering, performing a subgroup analysis on microcalcifications and soft tissue lesions. For microcalcifications, DNNs use a separate set of high frequency components than radiologists, some of which lie outside the image regions considered most suspicious by radiologists. These features run the risk of being spurious, but if not, could represent potential new biomarkers. For soft tissue lesions, the divergence between radiologists and DNNs is even starker, with DNNs relying heavily on spurious high frequency components ignored by radiologists. Importantly, this deviation in soft tissue lesions was only observable through subgroup analysis, which highlights the importance of incorporating medical domain knowledge into our comparison framework.

eess.IV↗