Search

Virtual Imaging Trials (VIT) offer a cost-effective and scalable approach for evaluating medical imaging technologies. Computational phantoms, which mimic real patient anatomy and physiology, play a central role in VITs. However, the current libraries of computational phantoms face limitations, particularly in terms of sample size and diversity. Insufficient representation of the population hampers accurate assessment of imaging technologies across different patient groups. Traditionally, the more realistic computational phantoms were created by manual segmentation, which is a laborious and time-consuming task, impeding the expansion of phantom libraries. This study presents a framework for creating realistic computational phantoms using a suite of automatic segmentation models and performing three forms of automated quality control on the segmented organ masks. The result is the release of over 2500 new computational phantoms, so-named XCAT3.0 after the ubiquitous XCAT computational construct. This new formation embodies 140 structures and represents a comprehensive approach to detailed anatomical modeling. The developed computational phantoms are formatted in both voxelized and surface mesh formats. The framework is combined with an in-house CT scanner simulator to produce realistic CT images. The framework has the potential to advance virtual imaging trials, facilitating comprehensive and reliable evaluations of medical imaging technologies. Phantoms may be requested at https://cvit.duke.edu/resources/. Code, model weights, and sample CT images are available at https://xcat-3.github.io/.

This submission comprises the proceedings of the 1st Virtual Imaging Trials in Medicine conference, organized by Duke University on April 22-24, 2024. The listed authors serve as the program directors for this conference. The VITM conference is a pioneering summit uniting experts from academia, industry and government in the fields of medical imaging and therapy to explore the transformative potential of in silico virtual trials and digital twins in revolutionizing healthcare. The proceedings are categorized by the respective days of the conference: Monday presentations, Tuesday presentations, Wednesday presentations, followed by the abstracts for the posters presented on Monday and Tuesday.

Importance: Clinical imaging trials are crucial for definitive evaluation of medical innovations, but the process is inefficient, expensive, and ethically-constrained. Virtual imaging trial (VIT) approach address these limitations by emulating the components of a clinical trial. An in silico rendition of the National Lung Screening Trial (NCLS) via Virtual Lung Screening Trial (VLST) demonstrates the promise of VITs to expedite clinical trials, reduce risks to subjects, and facilitate the optimal use of imaging technologies in clinical settings. Design, Setting, and Participants: A diverse virtual patient population of 294 subjects was created from human models (XCAT) emulating the characteristics of cases on NLST, with two types of simulated lung nodules. The cohort was assessed using simulated CT and CXR systems to generate images that reflect the NLST imaging technologies. Deep learning models trained for lesion detection in CXR and CT served as virtual readers. Results: The study analyzed 294 CT and CXR simulated images from 294 virtual patients, with a lesion-level AUC of 0.81 (95% CI: 0.79-0.84) for CT and 0.56 (95% CI: 0.54-0.58) for CXR. At the patient level, CT demonstrated an AUC of 0.84 (95% CI: 0.80-0.89), compared to 0.52 (95% CI: 0.45-0.58) for CXR. Subgroup analyses on CT results indicated superior detection of homogeneous lesions (lesion-level AUC 0.97) than heterogeneous lesions (lesion-level AUC 0.72). Performance was particularly high for identifying larger nodules (AUC of 0.98 for nodules > 8 mm). The VLST results closely mirrored the NLST, particularly in size-based detection trends, with CT achieving high AUCs for nodules > 8 mm and similar challenges in detecting smaller nodules. Conclusion and Relevance: The VIT results closely replicated those of the earlier NLST, underscoring its potential to replicate real clinical imaging trials.

Accurate 3D modeling of human organs plays a crucial role in building computational phantoms for virtual imaging trials. However, generating anatomically plausible reconstructions of organ surfaces from computed tomography scans remains challenging for many structures in the human body. This challenge is particularly evident when dealing with the large intestine. In this study, we leverage recent advancements in geometric deep learning and denoising diffusion probabilistic models to refine the segmentation results of the large intestine. We begin by representing the organ as point clouds sampled from the surface of the 3D segmentation mask. Subsequently, we employ a hierarchical variational autoencoder to obtain global and local latent representations of the organ's shape. We train two conditional denoising diffusion models in the hierarchical latent space to perform shape refinement. To further enhance our method, we incorporate a state-of-the-art surface reconstruction model, allowing us to generate smooth meshes from the obtained complete point clouds. Experimental results demonstrate the effectiveness of our approach in capturing both the global distribution of the organ's shape and its fine details. Our complete refinement pipeline demonstrates remarkable enhancements in surface representation compared to the initial segmentation, reducing the Chamfer distance by 70%, the Hausdorff distance by 32%, and the Earth Mover's distance by 6%. By combining geometric deep learning, denoising diffusion models, and advanced surface reconstruction techniques, our proposed method offers a promising solution for accurately modeling the large intestine's surface and can easily be extended to other anatomical structures.

The credibility of AI models in medical imaging is often challenged by reproducibility issues and obscured clinical insights, a reality highlighted during the COVID-19 pandemic by many reports of near-perfect artificial intelligence (AI) models that all failed to generalize. To address these concerns, we propose a virtual imaging trial framework, employing a diverse collection of medical images that are both clinical and simulated. In this study, COVID-19 serves as a case example to unveil the intrinsic and extrinsic factors influencing AI performance. Our findings underscore a significant impact of dataset characteristics on AI efficacy. Even when trained on large, diverse clinical datasets with thousands of patients, AI performance plummeted by up to 20% in generalization. However, virtual imaging trials offer a robust platform for objective assessment, unveiling nuanced insights into the relationships between patient- and physics-based factors and AI performance. For instance, disease extent markedly influenced AI efficacy, computed tomography (CT) out-performed chest radiography (CXR), while imaging dose exhibited minimal impact. Using COVID-19 as a case study, this virtual imaging trial study verified that radiology AI models often suffer from a reproducibility crisis. Virtual imaging trials not only offered a solution for objective performance assessment but also extracted several clinical insights. This study illuminates the path for leveraging virtual imaging to augment the reliability, transparency, and clinical relevance of AI in medical imaging., Comment: 3 tables, 4 figures, 1 Supplement

Research studies of artificial intelligence models in medical imaging have been hampered by poor generalization. This problem has been especially concerning over the last year with numerous applications of deep learning for COVID-19 diagnosis. Virtual imaging trials (VITs) could provide a solution for objective evaluation of these models. In this work utilizing the VITs, we created the CVIT-COVID dataset including 180 virtually imaged computed tomography (CT) images from simulated COVID-19 and normal phantom models under different COVID-19 morphology and imaging properties. We evaluated the performance of an open-source, deep-learning model from the University of Waterloo trained with multi-institutional data and an in-house model trained with the open clinical dataset called MosMed. We further validated the model's performance against open clinical data of 305 CT images to understand virtual vs. real clinical data performance. The open-source model was published with nearly perfect performance on the original Waterloo dataset but showed a consistent performance drop in external testing on another clinical dataset (AUC=0.77) and our simulated CVIT-COVID dataset (AUC=0.55). The in-house model achieved an AUC of 0.87 while testing on the internal test set (MosMed test set). However, performance dropped to an AUC of 0.65 and 0.69 when evaluated on clinical and our simulated CVIT-COVID dataset. The VIT framework offered control over imaging conditions, allowing us to show there was no change in performance as CT exposure was changed from 28.5 to 57 mAs. The VIT framework also provided voxel-level ground truth, revealing that performance of in-house model was much higher at AUC=0.87 for diffuse COVID-19 infection size >2.65% lung volume versus AUC=0.52 for focal disease with <2.65% volume. The virtual imaging framework enabled these uniquely rigorous analyses of model performance., Comment: 7 pages, 5 figures, 2 tables, presented at the Medical Imaging 2022: Computer-Aided Diagnosis, 2022

Organ segmentation of medical images is a key step in virtual imaging trials. However, organ segmentation datasets are limited in terms of quality (because labels cover only a few organs) and quantity (since case numbers are limited). In this study, we explored the tradeoffs between quality and quantity. Our goal is to create a unified approach for multi-organ segmentation of body CT, which will facilitate the creation of large numbers of accurate virtual phantoms. Initially, we compared two segmentation architectures, 3D-Unet and DenseVNet, which were trained using XCAT data that is fully labeled with 22 organs, and chose the 3D-Unet as the better performing model. We used the XCAT-trained model to generate pseudo-labels for the CT-ORG dataset that has only 7 organs segmented. We performed two experiments: First, we trained 3D-UNet model on the XCAT dataset, representing quality data, and tested it on both XCAT and CT-ORG datasets. Second, we trained 3D-UNet after including the CT-ORG dataset into the training set to have more quantity. Performance improved for segmentation in the organs where we have true labels in both datasets and degraded when relying on pseudo-labels. When organs were labeled in both datasets, Exp-2 improved Average DSC in XCAT and CT-ORG by 1. This demonstrates that quality data is the key to improving the model's performance., Comment: 6 pages, 3 figures, 2 tables, Accepted and Presented at SPIE Medical Imaging 2022

Despite the potential of weakly supervised learning to automatically annotate massive amounts of data, little is known about its limitations for use in computer-aided diagnosis (CAD). For CT specifically, interpreting the performance of CAD algorithms can be challenging given the large number of co-occurring diseases. This paper examines the effect of co-occurring diseases when training classification models by weakly supervised learning, specifically by comparing multi-label and multiple binary classifiers using the same training data. Our results demonstrated that the binary model outperformed the multi-label classification in every disease category in terms of AUC. However, this performance was heavily influenced by co-occurring diseases in the binary model, suggesting it did not always learn the correct appearance of the specific disease. For example, binary classification of lung nodules resulted in an AUC of < 0.65 when there were no other co-occurring diseases, but when lung nodules co-occurred with emphysema, the performance reached AUC > 0.80. We hope this paper revealed the complexity of interpreting disease classification performance in weakly supervised models and will encourage researchers to examine the effect of co-occurring diseases on classification performance in the future., Comment: 5 pages, 4 figures, Accepted at SPIE Medical Imaging Conference 2022

Objective: This study aims to develop and validate a novel framework, iPhantom, for automated creation of patient-specific phantoms or digital-twins (DT) using patient medical images. The framework is applied to assess radiation dose to radiosensitive organs in CT imaging of individual patients. Method: From patient CT images, iPhantom segments selected anchor organs (e.g. liver, bones, pancreas) using a learning-based model developed for multi-organ CT segmentation. Organs challenging to segment (e.g. intestines) are incorporated from a matched phantom template, using a diffeomorphic registration model developed for multi-organ phantom-voxels. The resulting full-patient phantoms are used to assess organ doses during routine CT exams. Result: iPhantom was validated on both the XCAT (n=50) and an independent clinical (n=10) dataset with similar accuracy. iPhantom precisely predicted all organ locations with good accuracy of Dice Similarity Coefficients (DSC) >0.6 for anchor organs and DSC of 0.3-0.9 for all other organs. iPhantom showed less than 10% dose errors for the majority of organs, which was notably superior to the state-of-the-art baseline method (20-35% dose errors). Conclusion: iPhantom enables automated and accurate creation of patient-specific phantoms and, for the first time, provides sufficient and automated patient-specific dose estimates for CT dosimetry. Significance: The new framework brings the creation and application of CHPs to the level of individual CHPs through automation, achieving a wider and precise organ localization, paving the way for clinical monitoring, and personalized optimization, and large-scale research., Comment: Main text: 11 pages, 8 figures; Supplement material: 7 pages, 5 figures, 7 tables

Purpose: To design multi-disease classifiers for body CT scans for three different organ systems using automatically extracted labels from radiology text reports.Materials & Methods: This retrospective study included a total of 12,092 patients (mean age 57 +- 18; 6,172 women) for model development and testing (from 2012-2017). Rule-based algorithms were used to extract 19,225 disease labels from 13,667 body CT scans from 12,092 patients. Using a three-dimensional DenseVNet, three organ systems were segmented: lungs and pleura; liver and gallbladder; and kidneys and ureters. For each organ, a three-dimensional convolutional neural network classified no apparent disease versus four common diseases for a total of 15 different labels across all three models. Testing was performed on a subset of 2,158 CT volumes relative to 2,875 manually derived reference labels from 2133 patients (mean age 58 +- 18;1079 women). Performance was reported as receiver operating characteristic area under the curve (AUC) with 95% confidence intervals by the DeLong method. Results: Manual validation of the extracted labels confirmed 91% to 99% accuracy across the 15 different labels. AUCs for lungs and pleura labels were: atelectasis 0.77 (95% CI: 0.74, 0.81), nodule 0.65 (0.61, 0.69), emphysema 0.89 (0.86, 0.92), effusion 0.97 (0.96, 0.98), and no apparent disease 0.89 (0.87, 0.91). AUCs for liver and gallbladder were: hepatobiliary calcification 0.62 (95% CI: 0.56, 0.67), lesion 0.73 (0.69, 0.77), dilation 0.87 (0.84, 0.90), fatty 0.89 (0.86, 0.92), and no apparent disease 0.82 (0.78, 0.85). AUCs for kidneys and ureters were: stone 0.83 (95% CI: 0.79, 0.87), atrophy 0.92 (0.89, 0.94), lesion 0.68 (0.64, 0.72), cyst 0.70 (0.66, 0.73), and no apparent disease 0.79 (0.75, 0.83). Conclusion: Weakly-supervised deep learning models were able to classify diverse diseases in multiple organ systems., Comment: 22 pages, 6 figures, 2 tables; Accepted for publication at Radiology: Artificial Intelligence

Imaging phantoms are test patterns used to measure image quality in computer tomography (CT) systems. A new phantom platform (Mercury Phantom, Gammex) provides test patterns for estimating the task transfer function (TTF) or noise power spectrum (NPF) and simulates different patient sizes. Determining which image slices are suitable for analysis currently requires manual annotation of these patterns by an expert, as subtle defects may make an image unsuitable for measurement. We propose a method of automatically classifying these test patterns in a series of phantom images using deep learning techniques. By adapting a convolutional neural network based on the VGG19 architecture with weights trained on ImageNet, we use transfer learning to produce a classifier for this domain. The classifier is trained and evaluated with over 3,500 phantom images acquired at a university medical center. Input channels for color images are successfully adapted to convey contextual information for phantom images. A series of ablation studies are employed to verify design aspects of the classifier and evaluate its performance under varying training conditions. Our solution makes extensive use of image augmentation to produce a classifier that accurately classifies typical phantom images with 98% accuracy, while maintaining as much as 86% accuracy when the phantom is improperly imaged.