Ehsan Abadi

Fakrul Islam Tushar, Ehsan Abadi, Saman Sotoudeh-Paima et al.

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.

Fakrul Islam Tushar, Husam Nujaim, Wanyi Fu et al.

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.

Fakrul Islam Tushar, Lavsen Dahal, Saman Sotoudeh-Paima et al.

Purpose: The credibility of Artificial Intelligence (AI) models for medical imaging continues to be a challenge, affected by the diversity of models, the data used to train the models, and applicability of their combination to produce reproducible results for new data. In this work, we aimed to explore whether emerging Virtual Imaging Trials (VIT) methodologies can provide an objective resource to approach this challenge. Approach: The study was conducted for the case example of COVID-19 diagnosis using clinical and virtual computed tomography (CT) and chest radiography (CXR) processed with convolutional neural networks. Multiple AI models were developed and tested using 3D ResNet-like and 2D EfficientNetv2 architectures across diverse datasets. Results: Model performance was evaluated using the area under the curve (AUC) and the DeLong method for AUC confidence intervals. The models trained on the most diverse datasets showed the highest external testing performance, with AUC values ranging from 0.73-0.76 for CT and 0.70-0.73 for CXR. Internal testing yielded higher AUC values (0.77-0.85 for CT and 0.77-1.0 for CXR), highlighting a substantial drop in performance during external validation, which underscores the importance of diverse and comprehensive training and testing data. Most notably, the VIT approach provided objective assessment of the utility of diverse models and datasets, while offering insight into the influence of dataset characteristics, patient factors, and imaging physics on AI efficacy. Conclusions: The VIT approach enhances model transparency and reliability, offering nuanced insights into the factors driving AI performance and bridging the gap between experimental and clinical settings.

Fakrul Islam Tushar, Lavsen Dahal, Cindy McCabe et al.

AI models for lung cancer screening are limited by data scarcity, impacting generalizability and clinical applicability. Generative models address this issue but are constrained by training data variability. We introduce SYN-LUNGS, a framework for generating high-quality 3D CT images with detailed annotations. SYN-LUNGS integrates XCAT3 phantoms for digital twin generation, X-Lesions for nodule simulation (varying size, location, and appearance), and DukeSim for CT image formation with vendor and parameter variability. The dataset includes 3,072 nodule images from 1,044 simulated CT scans, with 512 lesions and 174 digital twins. Models trained on clinical + simulated data outperform clinical only models, achieving 10% improvement in detection, 2-9% in segmentation and classification, and enhanced synthesis. By incorporating anatomy-informed simulations, SYN-LUNGS provides a scalable approach for AI model development, particularly in rare disease representation and improving model reliability.

David Fenwick, Navid NaderiAlizadeh, Vahid Tarokh et al.

Protocol optimization is critical in Computed Tomography (CT) to achieve high diagnostic image quality while minimizing radiation dose. However, due to the complex interdependencies among CT acquisition and reconstruction parameters, traditional optimization methods rely on exhaustive testing of combinations of these parameters, which is often impractical. This study introduces a novel methodology that combines virtual imaging tools with reinforcement learning to optimize CT protocols more efficiently. Human models with liver lesions were imaged using a validated CT simulator and reconstructed with a novel CT reconstruction toolkit. The optimization parameter space included tube voltage, tube current, reconstruction kernel, slice thickness, and pixel size. The optimization process was performed using a Proximal Policy Optimization (PPO) agent, which was trained to maximize an image quality objective, specifically the detectability index (d') of liver lesions in the reconstructed images. Optimization performance was compared against an exhaustive search performed on a supercomputer. The proposed reinforcement learning approach achieved the global maximum d' across test cases while requiring 79.7% fewer steps than the exhaustive search, demonstrating both accuracy and computational efficiency. The proposed framework is flexible and can accommodate various image quality objectives. The findings highlight the potential of integrating virtual imaging tools with reinforcement learning for CT protocol management.

Lavsen Dahal, Mobina Ghojoghnejad, Dhrubajyoti Ghosh et al.

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/.

Wanyi Fu, Shobhit Sharma, Ehsan Abadi et al.

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.