Kim L. Sandler

Kaiwen Xu, Thomas Li, Mirza S. Khan et al.

Field-of-view (FOV) tissue truncation beyond the lungs is common in routine lung screening computed tomography (CT). This poses limitations for opportunistic CT- based body composition (BC) assessment as key anatomical structures are missing. Traditionally, extending the FOV of CT is considered as a CT reconstruction problem using limited data. However, this approach relies on the projection domain data which might not be available in application. In this work, we formulate the problem from the semantic image extension perspective which only requires image data as inputs. The proposed two-stage method identifies a new FOV border based on the estimated extent of the complete body and imputes missing tissues in the truncated region. The training samples are simulated using CT slices with complete body in FOV, making the model development self-supervised. We evaluate the validity of the proposed method in automatic BC assessment using lung screening CT with limited FOV. The proposed method effectively restores the missing tissues and reduces BC assessment error introduced by FOV tissue truncation. In the BC assessment for a large-scale lung screening CT dataset, this correction improves both the intra-subject consistency and the correlation with anthropometric approximations. The developed method is available at https://github.com/MASILab/S-EFOV.

Thomas Z. Li, John M. Still, Kaiwen Xu et al.

The accuracy of predictive models for solitary pulmonary nodule (SPN) diagnosis can be greatly increased by incorporating repeat imaging and medical context, such as electronic health records (EHRs). However, clinically routine modalities such as imaging and diagnostic codes can be asynchronous and irregularly sampled over different time scales which are obstacles to longitudinal multimodal learning. In this work, we propose a transformer-based multimodal strategy to integrate repeat imaging with longitudinal clinical signatures from routinely collected EHRs for SPN classification. We perform unsupervised disentanglement of latent clinical signatures and leverage time-distance scaled self-attention to jointly learn from clinical signatures expressions and chest computed tomography (CT) scans. Our classifier is pretrained on 2,668 scans from a public dataset and 1,149 subjects with longitudinal chest CTs, billing codes, medications, and laboratory tests from EHRs of our home institution. Evaluation on 227 subjects with challenging SPNs revealed a significant AUC improvement over a longitudinal multimodal baseline (0.824 vs 0.752 AUC), as well as improvements over a single cross-section multimodal scenario (0.809 AUC) and a longitudinal imaging-only scenario (0.741 AUC). This work demonstrates significant advantages with a novel approach for co-learning longitudinal imaging and non-imaging phenotypes with transformers. Code available at https://github.com/MASILab/lmsignatures.

Aravind R. Krishnan, Kaiwen Xu, Thomas Li et al.

The reconstruction kernel in computed tomography (CT) generation determines the texture of the image. Consistency in reconstruction kernels is important as the underlying CT texture can impact measurements during quantitative image analysis. Harmonization (i.e., kernel conversion) minimizes differences in measurements due to inconsistent reconstruction kernels. Existing methods investigate harmonization of CT scans in single or multiple manufacturers. However, these methods require paired scans of hard and soft reconstruction kernels that are spatially and anatomically aligned. Additionally, a large number of models need to be trained across different kernel pairs within manufacturers. In this study, we adopt an unpaired image translation approach to investigate harmonization between and across reconstruction kernels from different manufacturers by constructing a multipath cycle generative adversarial network (GAN). We use hard and soft reconstruction kernels from the Siemens and GE vendors from the National Lung Screening Trial dataset. We use 50 scans from each reconstruction kernel and train a multipath cycle GAN. To evaluate the effect of harmonization on the reconstruction kernels, we harmonize 50 scans each from Siemens hard kernel, GE soft kernel and GE hard kernel to a reference Siemens soft kernel (B30f) and evaluate percent emphysema. We fit a linear model by considering the age, smoking status, sex and vendor and perform an analysis of variance (ANOVA) on the emphysema scores. Our approach minimizes differences in emphysema measurement and highlights the impact of age, sex, smoking status and vendor on emphysema quantification.

Kaiwen Xu, Aravind R. Krishnan, Thomas Z. Li et al.

Anatomically consistent field-of-view (FOV) completion to recover truncated body sections has important applications in quantitative analyses of computed tomography (CT) with limited FOV. Existing solution based on conditional generative models relies on the fidelity of synthetic truncation patterns at training phase, which poses limitations for the generalizability of the method to potential unknown types of truncation. In this study, we evaluate a zero-shot method based on a pretrained unconditional generative diffusion prior, where truncation pattern with arbitrary forms can be specified at inference phase. In evaluation on simulated chest CT slices with synthetic FOV truncation, the method is capable of recovering anatomically consistent body sections and subcutaneous adipose tissue measurement error caused by FOV truncation. However, the correction accuracy is inferior to the conditionally trained counterpart.

Chongyu Qu, Zhengyi Lu, Yuxiang Lai et al.

Multimodal fusion has emerged as a promising paradigm for disease diagnosis and prognosis, integrating complementary information from heterogeneous data sources such as medical images, clinical records, and radiology reports. However, existing fusion methods process all available modalities through the network, either treating them equally or learning to assign different contribution weights, leaving a fundamental question unaddressed: for a given patient, should certain modalities be used at all? We present AdaFuse, an adaptive multimodal fusion framework that leverages reinforcement learning (RL) to learn patient-specific modality selection and fusion strategies for lung cancer risk prediction. AdaFuse formulates multimodal fusion as a sequential decision process, where the policy network iteratively decides whether to incorporate an additional modality or proceed to prediction based on the information already acquired. This sequential formulation enables the model to condition each selection on previously observed modalities and terminate early when sufficient information is available, rather than committing to a fixed subset upfront. We evaluate AdaFuse on the National Lung Screening Trial (NLST) dataset. Experimental results demonstrate that AdaFuse achieves the highest AUC (0.762) compared to the best single-modality baseline (0.732), the best fixed fusion strategy (0.759), and adaptive baselines including DynMM (0.754) and MoE (0.742), while using fewer FLOPs than all triple-modality methods. Our work demonstrates the potential of reinforcement learning for personalized multimodal fusion in medical imaging, representing a shift from uniform fusion strategies toward adaptive diagnostic pipelines that learn when to consult additional modalities and when existing information suffices for accurate prediction.

Riqiang Gao, Mirza S. Khan, Yucheng Tang et al.

Image Quality Assessment (IQA) is important for scientific inquiry, especially in medical imaging and machine learning. Potential data quality issues can be exacerbated when human-based workflows use limited views of the data that may obscure digital artifacts. In practice, multiple factors such as network issues, accelerated acquisitions, motion artifacts, and imaging protocol design can impede the interpretation of image collections. The medical image processing community has developed a wide variety of tools for the inspection and validation of imaging data. Yet, IQA of computed tomography (CT) remains an under-recognized challenge, and no user-friendly tool is commonly available to address these potential issues. Here, we create and illustrate a pipeline specifically designed to identify and resolve issues encountered with large-scale data mining of clinically acquired CT data. Using the widely studied National Lung Screening Trial (NLST), we have identified approximately 4% of image volumes with quality concerns out of 17,392 scans. To assess robustness, we applied the proposed pipeline to our internal datasets where we find our tool is generalizable to clinically acquired medical images. In conclusion, the tool has been useful and time-saving for research study of clinical data, and the code and tutorials are publicly available at https://github.com/MASILab/QA_tool.

Thomas Z. Li, Aravind R. Krishnan, Lianrui Zuo et al.

The development of multimodal models for pulmonary nodule diagnosis is limited by the scarcity of labeled data and the tendency for these models to overfit on the training distribution. In this work, we leverage self-supervised learning from longitudinal and multimodal archives to address these challenges. We curate an unlabeled set of patients with CT scans and linked electronic health records from our home institution to power joint embedding predictive architecture (JEPA) pretraining. After supervised finetuning, we show that our approach outperforms an unregularized multimodal model and imaging-only model in an internal cohort (ours: 0.91, multimodal: 0.88, imaging-only: 0.73 AUC), but underperforms in an external cohort (ours: 0.72, imaging-only: 0.75 AUC). We develop a synthetic environment that characterizes the context in which JEPA may underperform. This work innovates an approach that leverages unlabeled multimodal medical archives to improve predictive models and demonstrates its advantages and limitations in pulmonary nodule diagnosis.

Chongyu Qu, Allen J. Luna, Thomas Z. Li et al.

Accurate lung cancer risk prediction remains challenging due to substantial variability across patient populations and clinical settings -- no single model performs best for all cohorts. To address this, we propose a personalized lung cancer risk prediction agent that dynamically selects the most appropriate model for each patient by combining cohort-specific knowledge with modern retrieval and reasoning techniques. Given a patient's CT scan and structured metadata -- including demographic, clinical, and nodule-level features -- the agent first performs cohort retrieval using FAISS-based similarity search across nine diverse real-world cohorts to identify the most relevant patient population from a multi-institutional database. Second, a Large Language Model (LLM) is prompted with the retrieved cohort and its associated performance metrics to recommend the optimal prediction algorithm from a pool of eight representative models, including classical linear risk models (e.g., Mayo, Brock), temporally-aware models (e.g., TD-VIT, DLSTM), and multi-modal computer vision-based approaches (e.g., Liao, Sybil, DLS, DLI). This two-stage agent pipeline -- retrieval via FAISS and reasoning via LLM -- enables dynamic, cohort-aware risk prediction personalized to each patient's profile. Building on this architecture, the agent supports flexible and cohort-driven model selection across diverse clinical populations, offering a practical path toward individualized risk assessment in real-world lung cancer screening.

Aravind R. Krishnan, Thomas Z. Li, Lucas W. Remedios et al.

Reconstruction kernels in computed tomography (CT) affect spatial resolution and noise characteristics, introducing systematic variability in quantitative imaging measurements such as emphysema quantification. Choosing an appropriate kernel is therefore essential for consistent quantitative analysis. We propose a multipath cycleGAN model for CT kernel harmonization, trained on a mixture of paired and unpaired data from a low-dose lung cancer screening cohort. The model features domain-specific encoders and decoders with a shared latent space and uses discriminators tailored for each domain.We train the model on 42 kernel combinations using 100 scans each from seven representative kernels in the National Lung Screening Trial (NLST) dataset. To evaluate performance, 240 scans from each kernel are harmonized to a reference soft kernel, and emphysema is quantified before and after harmonization. A general linear model assesses the impact of age, sex, smoking status, and kernel on emphysema. We also evaluate harmonization from soft kernels to a reference hard kernel. To assess anatomical consistency, we compare segmentations of lung vessels, muscle, and subcutaneous adipose tissue generated by TotalSegmentator between harmonized and original images. Our model is benchmarked against traditional and switchable cycleGANs. For paired kernels, our approach reduces bias in emphysema scores, as seen in Bland-Altman plots (p<0.05). For unpaired kernels, harmonization eliminates confounding differences in emphysema (p>0.05). High Dice scores confirm preservation of muscle and fat anatomy, while lung vessel overlap remains reasonable. Overall, our shared latent space multipath cycleGAN enables robust harmonization across paired and unpaired CT kernels, improving emphysema quantification and preserving anatomical fidelity.

Aravind R. Krishnan, Yihao Liu, Kaiwen Xu et al.

Paired inspiratory-expiratory CT scans enable the quantification of gas trapping due to small airway disease and emphysema by analyzing lung tissue motion in COPD patients. Deformable image registration of these scans assesses regional lung volumetric changes. However, variations in reconstruction kernels between paired scans introduce errors in quantitative analysis. This work proposes a two-stage pipeline to harmonize reconstruction kernels and perform deformable image registration using data acquired from the COPDGene study. We use a cycle generative adversarial network (GAN) to harmonize inspiratory scans reconstructed with a hard kernel (BONE) to match expiratory scans reconstructed with a soft kernel (STANDARD). We then deformably register the expiratory scans to inspiratory scans. We validate harmonization by measuring emphysema using a publicly available segmentation algorithm before and after harmonization. Results show harmonization significantly reduces emphysema measurement inconsistencies, decreasing median emphysema scores from 10.479% to 3.039%, with a reference median score of 1.305% from the STANDARD kernel as the target. Registration accuracy is evaluated via Dice overlap between emphysema regions on inspiratory, expiratory, and deformed images. The Dice coefficient between inspiratory emphysema masks and deformably registered emphysema masks increases significantly across registration stages (p<0.001). Additionally, we demonstrate that deformable registration is robust to kernel variations.

Lianrui Zuo, Kaiwen Xu, Dingjie Su et al.

The interconnection between the human lungs and other organs, such as the liver and kidneys, is crucial for understanding the underlying risks and effects of lung diseases and improving patient care. However, most research chest CT imaging is focused solely on the lungs due to considerations of cost and radiation dose. This restricted field of view (FOV) in the acquired images poses challenges to comprehensive analysis and hinders the ability to gain insights into the impact of lung diseases on other organs. To address this, we propose SCOPE (Spatial Coverage Optimization with Prior Encoding), a novel approach to capture the inter-organ relationships from CT images and extend the FOV of chest CT images. Our approach first trains a variational autoencoder (VAE) to encode 2D axial CT slices individually, then stacks the latent representations of the VAE to form a 3D context for training a latent diffusion model. Once trained, our approach extends the FOV of CT images in the z-direction by generating new axial slices in a zero-shot manner. We evaluated our approach on the National Lung Screening Trial (NLST) dataset, and results suggest that it effectively extends the FOV to include the liver and kidneys, which are not completely covered in the original NLST data acquisition. Quantitative results on a held-out whole-body dataset demonstrate that the generated slices exhibit high fidelity with acquired data, achieving an SSIM of 0.81.

Kaiwen Xu, Riqiang Gao, Mirza S. Khan et al.

A major goal of lung cancer screening is to identify individuals with particular phenotypes that are associated with high risk of cancer. Identifying relevant phenotypes is complicated by the variation in body position and body composition. In the brain, standardized coordinate systems (e.g., atlases) have enabled separate consideration of local features from gross/global structure. To date, no analogous standard atlas has been presented to enable spatial mapping and harmonization in chest computational tomography (CT). In this paper, we propose a thoracic atlas built upon a large low dose CT (LDCT) database of lung cancer screening program. The study cohort includes 466 male and 387 female subjects with no screening detected malignancy (age 46-79 years, mean 64.9 years). To provide spatial mapping, we optimize a multi-stage inter-subject non-rigid registration pipeline for the entire thoracic space. We evaluate the optimized pipeline relative to two baselines with alternative non-rigid registration module: the same software with default parameters and an alternative software. We achieve a significant improvement in terms of registration success rate based on manual QA. For the entire study cohort, the optimized pipeline achieves a registration success rate of 91.7%. The application validity of the developed atlas is evaluated in terms of discriminative capability for different anatomic phenotypes, including body mass index (BMI), chronic obstructive pulmonary disease (COPD), and coronary artery calcification (CAC).

Riqiang Gao, Yucheng Tang, Kaiwen Xu et al.

Clinical data elements (CDEs) (e.g., age, smoking history), blood markers and chest computed tomography (CT) structural features have been regarded as effective means for assessing lung cancer risk. These independent variables can provide complementary information and we hypothesize that combining them will improve the prediction accuracy. In practice, not all patients have all these variables available. In this paper, we propose a new network design, termed as multi-path multi-modal missing network (M3Net), to integrate the multi-modal data (i.e., CDEs, biomarker and CT image) considering missing modality with multiple paths neural network. Each path learns discriminative features of one modality, and different modalities are fused in a second stage for an integrated prediction. The network can be trained end-to-end with both medical image features and CDEs/biomarkers, or make a prediction with single modality. We evaluate M3Net with datasets including three sites from the Consortium for Molecular and Cellular Characterization of Screen-Detected Lesions (MCL) project. Our method is cross validated within a cohort of 1291 subjects (383 subjects with complete CDEs/biomarkers and CT images), and externally validated with a cohort of 99 subjects (99 with complete CDEs/biomarkers and CT images). Both cross-validation and external-validation results show that combining multiple modality significantly improves the predicting performance of single modality. The results suggest that integrating subjects with missing either CDEs/biomarker or CT imaging features can contribute to the discriminatory power of our model (p < 0.05, bootstrap two-tailed test). In summary, the proposed M3Net framework provides an effective way to integrate image and non-image data in the context of missing information.

Yiyuan Yang, Riqiang Gao, Yucheng Tang et al.

Recently, multi-task networks have shown to both offer additional estimation capabilities, and, perhaps more importantly, increased performance over single-task networks on a "main/primary" task. However, balancing the optimization criteria of multi-task networks across different tasks is an area of active exploration. Here, we extend a previously proposed 3D attention-based network with four additional multi-task subnetworks for the detection of lung cancer and four auxiliary tasks (diagnosis of asthma, chronic bronchitis, chronic obstructive pulmonary disease, and emphysema). We introduce and evaluate a learning policy, Periodic Focusing Learning Policy (PFLP), that alternates the dominance of tasks throughout the training. To improve performance on the primary task, we propose an Internal-Transfer Weighting (ITW) strategy to suppress the loss functions on auxiliary tasks for the final stages of training. To evaluate this approach, we examined 3386 patients (single scan per patient) from the National Lung Screening Trial (NLST) and de-identified data from the Vanderbilt Lung Screening Program, with a 2517/277/592 (scans) split for training, validation, and testing. Baseline networks include a single-task strategy and a multi-task strategy without adaptive weights (PFLP/ITW), while primary experiments are multi-task trials with either PFLP or ITW or both. On the test set for lung cancer prediction, the baseline single-task network achieved prediction AUC of 0.8080 and the multi-task baseline failed to converge (AUC 0.6720). However, applying PFLP helped multi-task network clarify and achieved test set lung cancer prediction AUC of 0.8402. Furthermore, our ITW technique boosted the PFLP enabled multi-task network and achieved an AUC of 0.8462 (McNemar test, p < 0.01).

Riqiang Gao, Lingfeng Li, Yucheng Tang et al.

Annual low dose computed tomography (CT) lung screening is currently advised for individuals at high risk of lung cancer (e.g., heavy smokers between 55 and 80 years old). The recommended screening practice significantly reduces all-cause mortality, but the vast majority of screening results are negative for cancer. If patients at very low risk could be identified based on individualized, image-based biomarkers, the health care resources could be more efficiently allocated to higher risk patients and reduce overall exposure to ionizing radiation. In this work, we propose a multi-task (diagnosis and prognosis) deep convolutional neural network to improve the diagnostic accuracy over a baseline model while simultaneously estimating a personalized cancer-free progression time (CFPT). A novel Censored Regression Loss (CRL) is proposed to perform weakly supervised regression so that even single negative screening scans can provide small incremental value. Herein, we study 2287 scans from 1433 de-identified patients from the Vanderbilt Lung Screening Program (VLSP) and Molecular Characterization Laboratories (MCL) cohorts. Using five-fold cross-validation, we train a 3D attention-based network under two scenarios: (1) single-task learning with only classification, and (2) multi-task learning with both classification and regression. The single-task learning leads to a higher AUC compared with the Kaggle challenge winner pre-trained model (0.878 v. 0.856), and multi-task learning significantly improves the single-task one (AUC 0.895, p<0.01, McNemar test). In summary, the image-based predicted CFPT can be used in follow-up year lung cancer prediction and data assessment.

Riqiang Gao, Yuankai Huo, Shunxing Bao et al.

The field of lung nodule detection and cancer prediction has been rapidly developing with the support of large public data archives. Previous studies have largely focused on cross-sectional (single) CT data. Herein, we consider longitudinal data. The Long Short-Term Memory (LSTM) model addresses learning with regularly spaced time points (i.e., equal temporal intervals). However, clinical imaging follows patient needs with often heterogeneous, irregular acquisitions. To model both regular and irregular longitudinal samples, we generalize the LSTM model with the Distanced LSTM (DLSTM) for temporally varied acquisitions. The DLSTM includes a Temporal Emphasis Model (TEM) that enables learning across regularly and irregularly sampled intervals. Briefly, (1) the time intervals between longitudinal scans are modeled explicitly, (2) temporally adjustable forget and input gates are introduced for irregular temporal sampling; and (3) the latest longitudinal scan has an additional emphasis term. We evaluate the DLSTM framework in three datasets including simulated data, 1794 National Lung Screening Trial (NLST) scans, and 1420 clinically acquired data with heterogeneous and irregular temporal accession. The experiments on the first two datasets demonstrate that our method achieves competitive performance on both simulated and regularly sampled datasets (e.g. improve LSTM from 0.6785 to 0.7085 on F1 score in NLST). In external validation of clinically and irregularly acquired data, the benchmarks achieved 0.8350 (CNN feature) and 0.8380 (LSTM) on the area under the ROC curve (AUC) score, while the proposed DLSTM achieves 0.8905.