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Greg Zaharchuk

Publications and source records attributed to Greg Zaharchuk.

At least 19 recordsLinked to original sources

CheXmix: Unified Generative Pretraining for Vision Language Models in Medical Imaging

Recent medical multimodal foundation models are built as multimodal LLMs (MLLMs) by connecting a CLIP-pretrained vision encoder to an LLM using LLaVA-style finetuning. This two-stage, decoupled approach introduces a projection layer that can distort visual features. This is especially concerning in medical imaging where subtle cues are essential for accurate diagnoses. In contrast, early-fusion generative approaches such as Chameleon eliminate the projection bottleneck by processing image and text tokens within a single unified sequence, enabling joint representation learning that leverages the inductive priors of language models. We present CheXmix, a unified early-fusion generative model trained on a large corpus of chest X-rays paired with radiology reports. We expand on Chameleon's autoregressive framework by introducing a two-stage multimodal generative pretraining strategy that combines the representational strengths of masked autoencoders with MLLMs. The resulting models are highly flexible, supporting both discriminative and generative tasks at both coarse and fine-grained scales. Our approach outperforms well-established generative models across all masking ratios by 6.0% and surpasses CheXagent by 8.6% on AUROC at high image masking ratios on the CheXpert classification task. We further inpaint images over 51.0% better than text-only generative models and outperform CheXagent by 45% on the GREEN metric for radiology report generation. These results demonstrate that CheXmix captures fine-grained information across a broad spectrum of chest X-ray tasks. Our code is at: https://github.com/StanfordMIMI/CheXmix.

cs.CV

COPE: Chain-Of-Thought Prediction Engine for Open-Source Large Language Model Based Stroke Outcome Prediction from Clinical Notes

Predicting outcomes in acute ischemic stroke (AIS) guides clinical decision-making, patient counseling, and resource allocation. Clinical notes contain rich contextual information, but their unstructured nature limits their use in traditional predictive models. We developed and evaluated the Chain-of-Thought (CoT) Outcome Prediction Engine (COPE), a reasoning-enhanced large language model framework, for predicting 90-day functional outcomes after AIS from unstructured clinical notes. This study included 464 AIS patients with discharge summaries and 90-day modified Rankin Scale (mRS) scores. COPE uses a two-step CoT framework based on sequential open-source LLaMA-3-8B models: the first generates clinical reasoning, and the second outputs an mRS prediction. We compared COPE with GPT-4.1, ClinicalBERT, a structured variable-based machine learning model (Clinical ML), and a single-step LLM without CoT. Performance was evaluated using mean absolute error (MAE), accuracy within +/-1 mRS point, and exact accuracy. COPE achieved an MAE of 1.01 (95% CI 0.92-1.11), +/-1 accuracy of 74.4% (69.9, 78.8%), and exact accuracy of 32.8% (28.0, 37.6%), comparable to GPT-4.1 and superior to ClinicalBERT [MAE 1.24 (1.13-1.36)], Clinical ML [1.28 (1.18-1.39)], and the single-step LLM [1.20 (1.09-1.33)]. Subgroup analyses showed consistent performance across sex and age, with slightly higher error among older patients, those undergoing thrombectomy, and those with longer summaries. These findings demonstrate that COPE, a lightweight, interpretable, and privacy-preserving open-source framework, provides an accurate and practical solution for outcome prediction from unstructured clinical text.

cs.AI

Score-based Generative Diffusion Models to Synthesize Full-dose FDG Brain PET from MRI in Epilepsy Patients

Fluorodeoxyglucose (FDG) PET to evaluate patients with epilepsy is one of the most common applications for simultaneous PET/MRI, given the need to image both brain structure and metabolism, but is suboptimal due to the radiation dose in this young population. Little work has been done synthesizing diagnostic quality PET images from MRI data or MRI data with ultralow-dose PET using advanced generative AI methods, such as diffusion models, with attention to clinical evaluations tailored for the epilepsy population. Here we compared the performance of diffusion- and non-diffusion-based deep learning models for the MRI-to-PET image translation task for epilepsy imaging using simultaneous PET/MRI in 52 subjects (40 train/2 validate/10 hold-out test). We tested three different models: 2 score-based generative diffusion models (SGM-Karras Diffusion [SGM-KD] and SGM-variance preserving [SGM-VP]) and a Transformer-Unet. We report results on standard image processing metrics as well as clinically relevant metrics, including congruency measures (Congruence Index and Congruency Mean Absolute Error) that assess hemispheric metabolic asymmetry, which is a key part of the clinical analysis of these images. The SGM-KD produced the best qualitative and quantitative results when synthesizing PET purely from T1w and T2 FLAIR images with the least mean absolute error in whole-brain specific uptake value ratio (SUVR) and highest intraclass correlation coefficient. When 1% low-dose PET images are included in the inputs, all models improve significantly and are interchangeable for quantitative performance and visual quality. In summary, SGMs hold great potential for pure MRI-to-PET translation, while all 3 model types can synthesize full-dose FDG-PET accurately using MRI and ultralow-dose PET.

eess.IV

Deep Learning-Based Prediction of PET Amyloid Status Using Multi-Contrast MRI

Identifying amyloid-beta positive patients is crucial for determining eligibility for Alzheimer's disease (AD) clinical trials and new disease-modifying treatments, but currently requires PET or CSF sampling. Previous MRI-based deep learning models for predicting amyloid positivity, using only T1w sequences, have shown moderate performance. We trained deep learning models to predict amyloid PET positivity and evaluated whether multi-contrast inputs improve performance. A total of 4,058 exams with multi-contrast MRI and PET-based quantitative amyloid deposition were obtained from three public datasets: the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Open Access Series of Imaging Studies 3 (OASIS3), and the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4). Two separate EfficientNet models were trained for amyloid positivity prediction: one with only T1w images and the other with both T1w and T2-FLAIR images as network inputs. The area under the curve (AUC), accuracy, sensitivity, and specificity were determined using an internal held-out test set. The trained models were further evaluated using an external test set. In the held-out test sets, the T1w and T1w+T2FLAIR models demonstrated AUCs of 0.62 (95% CI: 0.60, 0.64) and 0.67 (95% CI: 0.64, 0.70) (p = 0.006); accuracies were 61% (95% CI: 60%, 63%) and 64% (95% CI: 62%, 66%) (p = 0.008); sensitivities were 0.88 and 0.71; and specificities were 0.23 and 0.53, respectively. The trained models showed similar performance in the external test set. Performance of the current model on both test sets exceeded that of the publicly available model. In conclusion, the use of multi-contrast MRI, specifically incorporating T2-FLAIR in addition to T1w images, significantly improved the predictive accuracy of PET-determined amyloid status from MRI scans using a deep learning approach.

eess.IV

Merlin: A Computed Tomography Vision-Language Foundation Model and Dataset

The large volume of abdominal computed tomography (CT) scans coupled with the shortage of radiologists have intensified the need for automated medical image analysis tools. Previous state-of-the-art approaches for automated analysis leverage vision-language models (VLMs) that jointly model images and radiology reports. However, current medical VLMs are generally limited to 2D images and short reports. Here to overcome these shortcomings for abdominal CT interpretation, we introduce Merlin, a 3D VLM that learns from volumetric CT scans, electronic health record data and radiology reports. This approach is enabled by a multistage pretraining framework that does not require additional manual annotations. We trained Merlin using a high-quality clinical dataset of paired CT scans (>6 million images from 15,331 CT scans), diagnosis codes (>1.8 million codes) and radiology reports (>6 million tokens). We comprehensively evaluated Merlin on 6 task types and 752 individual tasks that covered diagnostic, prognostic and quality-related tasks. The non-adapted (off-the-shelf) tasks included zero-shot classification of findings (30 findings), phenotype classification (692 phenotypes) and zero-shot cross-modal retrieval (image-to-findings and image-to-impression). The model-adapted tasks included 5-year chronic disease prediction (6 diseases), radiology report generation and 3D semantic segmentation (20 organs). We validated Merlin at scale, with internal testing on 5,137 CT scans and external testing on 44,098 CT scans from 3 independent sites and 2 public datasets. The results demonstrated high generalization across institutions and anatomies. Merlin outperformed 2D VLMs, CT foundation models and off-the-shelf radiology models. We also release our trained models, code, and dataset, available at: https://github.com/StanfordMIMI/Merlin.

cs.CV

LSOR: Longitudinally-Consistent Self-Organized Representation Learning

Interpretability is a key issue when applying deep learning models to longitudinal brain MRIs. One way to address this issue is by visualizing the high-dimensional latent spaces generated by deep learning via self-organizing maps (SOM). SOM separates the latent space into clusters and then maps the cluster centers to a discrete (typically 2D) grid preserving the high-dimensional relationship between clusters. However, learning SOM in a high-dimensional latent space tends to be unstable, especially in a self-supervision setting. Furthermore, the learned SOM grid does not necessarily capture clinically interesting information, such as brain age. To resolve these issues, we propose the first self-supervised SOM approach that derives a high-dimensional, interpretable representation stratified by brain age solely based on longitudinal brain MRIs (i.e., without demographic or cognitive information). Called Longitudinally-consistent Self-Organized Representation learning (LSOR), the method is stable during training as it relies on soft clustering (vs. the hard cluster assignments used by existing SOM). Furthermore, our approach generates a latent space stratified according to brain age by aligning trajectories inferred from longitudinal MRIs to the reference vector associated with the corresponding SOM cluster. When applied to longitudinal MRIs of the Alzheimer's Disease Neuroimaging Initiative (ADNI, N=632), LSOR generates an interpretable latent space and achieves comparable or higher accuracy than the state-of-the-art representations with respect to the downstream tasks of classification (static vs. progressive mild cognitive impairment) and regression (determining ADAS-Cog score of all subjects). The code is available at https://github.com/ouyangjiahong/longitudinal-som-single-modality.

cs.CV

Non-inferiority of Deep Learning Acute Ischemic Stroke Segmentation on Non-Contrast CT Compared to Expert Neuroradiologists

To determine if a convolutional neural network (CNN) deep learning model can accurately segment acute ischemic changes on non-contrast CT compared to neuroradiologists. Non-contrast CT (NCCT) examinations from 232 acute ischemic stroke patients who were enrolled in the DEFUSE 3 trial were included in this study. Three experienced neuroradiologists independently segmented hypodensity that reflected the ischemic core on each scan. The neuroradiologist with the most experience (expert A) served as the ground truth for deep learning model training. Two additional neuroradiologists (experts B and C) segmentations were used for data testing. The 232 studies were randomly split into training and test sets. The training set was further randomly divided into 5 folds with training and validation sets. A 3-dimensional CNN architecture was trained and optimized to predict the segmentations of expert A from NCCT. The performance of the model was assessed using a set of volume, overlap, and distance metrics using non-inferiority thresholds of 20%, 3ml, and 3mm. The optimized model trained on expert A was compared to test experts B and C. We used a one-sided Wilcoxon signed-rank test to test for the non-inferiority of the model-expert compared to the inter-expert agreement. The final model performance for the ischemic core segmentation task reached a performance of 0.46+-0.09 Surface Dice at Tolerance 5mm and 0.47+-0.13 Dice when trained on expert A. Compared to the two test neuroradiologists the model-expert agreement was non-inferior to the inter-expert agreement, p < 0.05. The CNN accurately delineates the hypodense ischemic core on NCCT in acute ischemic stroke patients with an accuracy comparable to neuroradiologists.

eess.IV

Random Expert Sampling for Deep Learning Segmentation of Acute Ischemic Stroke on Non-contrast CT

Purpose: Multi-expert deep learning training methods to automatically quantify ischemic brain tissue on Non-Contrast CT Materials and Methods: The data set consisted of 260 Non-Contrast CTs from 233 patients of acute ischemic stroke patients recruited in the DEFUSE 3 trial. A benchmark U-Net was trained on the reference annotations of three experienced neuroradiologists to segment ischemic brain tissue using majority vote and random expert sampling training schemes. We used a one-sided Wilcoxon signed-rank test on a set of segmentation metrics to compare bootstrapped point estimates of the training schemes with the inter-expert agreement and ratio of variance for consistency analysis. We further compare volumes with the 24h-follow-up DWI (final infarct core) in the patient subgroup with full reperfusion and we test volumes for correlation to the clinical outcome (mRS after 30 and 90 days) with the Spearman method. Results: Random expert sampling leads to a model that shows better agreement with experts than experts agree among themselves and better agreement than the agreement between experts and a majority-vote model performance (Surface Dice at Tolerance 5mm improvement of 61% to 0.70 +- 0.03 and Dice improvement of 25% to 0.50 +- 0.04). The model-based predicted volume similarly estimated the final infarct volume and correlated better to the clinical outcome than CT perfusion. Conclusion: A model trained on random expert sampling can identify the presence and location of acute ischemic brain tissue on Non-Contrast CT similar to CT perfusion and with better consistency than experts. This may further secure the selection of patients eligible for endovascular treatment in less specialized hospitals.

cs.CV

Simulation of Arbitrary Level Contrast Dose in MRI Using an Iterative Global Transformer Model

Deep learning (DL) based contrast dose reduction and elimination in MRI imaging is gaining traction, given the detrimental effects of Gadolinium-based Contrast Agents (GBCAs). These DL algorithms are however limited by the availability of high quality low dose datasets. Additionally, different types of GBCAs and pathologies require different dose levels for the DL algorithms to work reliably. In this work, we formulate a novel transformer (Gformer) based iterative modelling approach for the synthesis of images with arbitrary contrast enhancement that corresponds to different dose levels. The proposed Gformer incorporates a sub-sampling based attention mechanism and a rotational shift module that captures the various contrast related features. Quantitative evaluation indicates that the proposed model performs better than other state-of-the-art methods. We further perform quantitative evaluation on downstream tasks such as dose reduction and tumor segmentation to demonstrate the clinical utility.

eess.IV

One Model to Synthesize Them All: Multi-contrast Multi-scale Transformer for Missing Data Imputation

Multi-contrast magnetic resonance imaging (MRI) is widely used in clinical practice as each contrast provides complementary information. However, the availability of each imaging contrast may vary amongst patients, which poses challenges to radiologists and automated image analysis algorithms. A general approach for tackling this problem is missing data imputation, which aims to synthesize the missing contrasts from existing ones. While several convolutional neural networks (CNN) based algorithms have been proposed, they suffer from the fundamental limitations of CNN models, such as the requirement for fixed numbers of input and output channels, the inability to capture long-range dependencies, and the lack of interpretability. In this work, we formulate missing data imputation as a sequence-to-sequence learning problem and propose a multi-contrast multi-scale Transformer (MMT), which can take any subset of input contrasts and synthesize those that are missing. MMT consists of a multi-scale Transformer encoder that builds hierarchical representations of inputs combined with a multi-scale Transformer decoder that generates the outputs in a coarse-to-fine fashion. The proposed multi-contrast Swin Transformer blocks can efficiently capture intra- and inter-contrast dependencies for accurate image synthesis. Moreover, MMT is inherently interpretable as it allows us to understand the importance of each input contrast in different regions by analyzing the in-built attention maps of Transformer blocks in the decoder. Extensive experiments on two large-scale multi-contrast MRI datasets demonstrate that MMT outperforms the state-of-the-art methods quantitatively and qualitatively.

eess.IV

Brain MRI-to-PET Synthesis using 3D Convolutional Attention Networks

Accurate quantification of cerebral blood flow (CBF) is essential for the diagnosis and assessment of a wide range of neurological diseases. Positron emission tomography (PET) with radiolabeled water (15O-water) is considered the gold-standard for the measurement of CBF in humans. PET imaging, however, is not widely available because of its prohibitive costs and use of short-lived radiopharmaceutical tracers that typically require onsite cyclotron production. Magnetic resonance imaging (MRI), in contrast, is more readily accessible and does not involve ionizing radiation. This study presents a convolutional encoder-decoder network with attention mechanisms to predict gold-standard 15O-water PET CBF from multi-sequence MRI scans, thereby eliminating the need for radioactive tracers. Inputs to the prediction model include several commonly used MRI sequences (T1-weighted, T2-FLAIR, and arterial spin labeling). The model was trained and validated using 5-fold cross-validation in a group of 126 subjects consisting of healthy controls and cerebrovascular disease patients, all of whom underwent simultaneous $15O-water PET/MRI. The results show that such a model can successfully synthesize high-quality PET CBF measurements (with an average SSIM of 0.924 and PSNR of 38.8 dB) and is more accurate compared to concurrent and previous PET synthesis methods. We also demonstrate the clinical significance of the proposed algorithm by evaluating the agreement for identifying the vascular territories with abnormally low CBF. Such methods may enable more widespread and accurate CBF evaluation in larger cohorts who cannot undergo PET imaging due to radiation concerns, lack of access, or logistic challenges.

cs.CV

Multi-task Deep Learning for Cerebrovascular Disease Classification and MRI-to-PET Translation

Accurate quantification of cerebral blood flow (CBF) is essential for the diagnosis and assessment of cerebrovascular diseases such as Moyamoya, carotid stenosis, aneurysms, and stroke. Positron emission tomography (PET) is currently regarded as the gold standard for the measurement of CBF in the human brain. PET imaging, however, is not widely available because of its prohibitive costs, use of ionizing radiation, and logistical challenges, which require a co-localized cyclotron to deliver the 2 min half-life Oxygen-15 radioisotope. Magnetic resonance imaging (MRI), in contrast, is more readily available and does not involve ionizing radiation. In this study, we propose a multi-task learning framework for brain MRI-to-PET translation and disease diagnosis. The proposed framework comprises two prime networks: (1) an attention-based 3D encoder-decoder convolutional neural network (CNN) that synthesizes high-quality PET CBF maps from multi-contrast MRI images, and (2) a multi-scale 3D CNN that identifies the brain disease corresponding to the input MRI images. Our multi-task framework yields promising results on the task of MRI-to-PET translation, achieving an average structural similarity index (SSIM) of 0.94 and peak signal-to-noise ratio (PSNR) of 38dB on a cohort of 120 subjects. In addition, we show that integrating multiple MRI modalities can improve the clinical diagnosis of brain diseases.

eess.IV

The RSNA-ASNR-MICCAI BraTS 2021 Benchmark on Brain Tumor Segmentation and Radiogenomic Classification

The BraTS 2021 challenge celebrates its 10th anniversary and is jointly organized by the Radiological Society of North America (RSNA), the American Society of Neuroradiology (ASNR), and the Medical Image Computing and Computer Assisted Interventions (MICCAI) society. Since its inception, BraTS has been focusing on being a common benchmarking venue for brain glioma segmentation algorithms, with well-curated multi-institutional multi-parametric magnetic resonance imaging (mpMRI) data. Gliomas are the most common primary malignancies of the central nervous system, with varying degrees of aggressiveness and prognosis. The RSNA-ASNR-MICCAI BraTS 2021 challenge targets the evaluation of computational algorithms assessing the same tumor compartmentalization, as well as the underlying tumor's molecular characterization, in pre-operative baseline mpMRI data from 2,040 patients. Specifically, the two tasks that BraTS 2021 focuses on are: a) the segmentation of the histologically distinct brain tumor sub-regions, and b) the classification of the tumor's O[6]-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. The performance evaluation of all participating algorithms in BraTS 2021 will be conducted through the Sage Bionetworks Synapse platform (Task 1) and Kaggle (Task 2), concluding in distributing to the top ranked participants monetary awards of $60,000 collectively.

cs.CV

Self-Supervised Longitudinal Neighbourhood Embedding

Longitudinal MRIs are often used to capture the gradual deterioration of brain structure and function caused by aging or neurological diseases. Analyzing this data via machine learning generally requires a large number of ground-truth labels, which are often missing or expensive to obtain. Reducing the need for labels, we propose a self-supervised strategy for representation learning named Longitudinal Neighborhood Embedding (LNE). Motivated by concepts in contrastive learning, LNE explicitly models the similarity between trajectory vectors across different subjects. We do so by building a graph in each training iteration defining neighborhoods in the latent space so that the progression direction of a subject follows the direction of its neighbors. This results in a smooth trajectory field that captures the global morphological change of the brain while maintaining the local continuity. We apply LNE to longitudinal T1w MRIs of two neuroimaging studies: a dataset composed of 274 healthy subjects, and Alzheimer's Disease Neuroimaging Initiative (ADNI, N=632). The visualization of the smooth trajectory vector field and superior performance on downstream tasks demonstrate the strength of the proposed method over existing self-supervised methods in extracting information associated with normal aging and in revealing the impact of neurodegenerative disorders. The code is available at \url{https://github.com/ouyangjiahong/longitudinal-neighbourhood-embedding.git}.

cs.CV

Representation Disentanglement for Multi-modal brain MR Analysis

Multi-modal MRIs are widely used in neuroimaging applications since different MR sequences provide complementary information about brain structures. Recent works have suggested that multi-modal deep learning analysis can benefit from explicitly disentangling anatomical (shape) and modality (appearance) information into separate image presentations. In this work, we challenge mainstream strategies by showing that they do not naturally lead to representation disentanglement both in theory and in practice. To address this issue, we propose a margin loss that regularizes the similarity in relationships of the representations across subjects and modalities. To enable robust training, we further use a conditional convolution to design a single model for encoding images of all modalities. Lastly, we propose a fusion function to combine the disentangled anatomical representations as a set of modality-invariant features for downstream tasks. We evaluate the proposed method on three multi-modal neuroimaging datasets. Experiments show that our proposed method can achieve superior disentangled representations compared to existing disentanglement strategies. Results also indicate that the fused anatomical representation has potential in the downstream task of zero-dose PET reconstruction and brain tumor segmentation. The code is available at \url{https://github.com/ouyangjiahong/representation-disentanglement}.

cs.CV

OUTCOMES: Rapid Under-sampling Optimization achieves up to 50% improvements in reconstruction accuracy for multi-contrast MRI sequences

Multi-contrast Magnetic Resonance Imaging (MRI) acquisitions from a single scan have tremendous potential to streamline exams and reduce imaging time. However, maintaining clinically feasible scan time necessitates significant undersampling, pushing the limits on compressed sensing and other low-dimensional techniques. During MRI scanning, one of the possible solutions is by using undersampling designs which can effectively improve the acquisition and achieve higher reconstruction accuracy. However, existing undersampling optimization methods are time-consuming and the limited performance prevents their clinical applications. In this paper, we proposed an improved undersampling trajectory optimization scheme to generate an optimized trajectory within seconds and apply it to subsequent multi-contrast MRI datasets on a per-subject basis, where we named it OUTCOMES. By using a data-driven method combined with improved algorithm design, GPU acceleration, and more efficient computation, the proposed method can optimize a trajectory within 5-10 seconds and achieve 30%-50% reconstruction improvement with the same acquisition cost, which makes real-time under-sampling optimization possible for clinical applications.

eess.IV

Random Bundle: Brain Metastases Segmentation Ensembling through Annotation Randomization

We introduce a novel ensembling method, Random Bundle (RB), that improves performance for brain metastases segmentation. We create our ensemble by training each network on our dataset with 50% of our annotated lesions censored out. We also apply a lopsided bootstrap loss to recover performance after inducing an in silico 50% false negative rate and make our networks more sensitive. We improve our network detection of lesions's mAP value by 39% and more than triple the sensitivity at 80% precision. We also show slight improvements in segmentation quality through DICE score. Further, RB ensembling improves performance over baseline by a larger margin than a variety of popular ensembling strategies. Finally, we show that RB ensembling is computationally efficient by comparing its performance to a single network when both systems are constrained to have the same compute.

cs.CV

Brain Metastasis Segmentation Network Trained with Robustness to Annotations with Multiple False Negatives

Deep learning has proven to be an essential tool for medical image analysis. However, the need for accurately labeled input data, often requiring time- and labor-intensive annotation by experts, is a major limitation to the use of deep learning. One solution to this challenge is to allow for use of coarse or noisy labels, which could permit more efficient and scalable labeling of images. In this work, we develop a lopsided loss function based on entropy regularization that assumes the existence of a nontrivial false negative rate in the target annotations. Starting with a carefully annotated brain metastasis lesion dataset, we simulate data with false negatives by (1) randomly censoring the annotated lesions and (2) systematically censoring the smallest lesions. The latter better models true physician error because smaller lesions are harder to notice than the larger ones. Even with a simulated false negative rate as high as 50%, applying our loss function to randomly censored data preserves maximum sensitivity at 97% of the baseline with uncensored training data, compared to just 10% for a standard loss function. For the size-based censorship, performance is restored from 17% with the current standard to 88% with our lopsided bootstrap loss. Our work will enable more efficient scaling of the image labeling process, in parallel with other approaches on creating more efficient user interfaces and tools for annotation.

cs.CV