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Background: This Special Report summarizes the 2022, AAPM grand challenge on Truth-based CT image reconstruction., Purpose: To provide an objective framework for evaluating CT reconstruction methods using virtual imaging resources consisting of a library of simulated CT projection images of a population of human models with various diseases., Methods: Two hundred unique anthropomorphic, computational models were created with varied diseases consisting of 67 emphysema, 67 lung lesions, and 66 liver lesions. The organs were modeled based on clinical CT images of real patients. The emphysematous regions were modeled using segmentations from patient CT cases in the COPDGene Phase I dataset. For the lung and liver lesion cases, 1-6 malignant lesions were created and inserted into the human models, with lesion diameters ranging from 5.6 to 21.9 mm for lung lesions and 3.9 to 14.9 mm for liver lesions. The contrast defined between the liver lesions and liver parenchyma was 82 ± 12 HU, ranging from 50 to 110 HU. Similarly, the contrast between the lung lesions and the lung parenchyma was defined as 781 ± 11 HU, ranging from 725 to 805 HU. For the emphysematous regions, the defined HU values were -950 ± 17 HU ranging from -918 to -979 HU. The developed human models were imaged with a validated CT simulator. The resulting CT sinograms were shared with the participants. The participants reconstructed CT images from the sinograms and sent back their reconstructed images. The reconstructed images were then scored by comparing the results against the corresponding ground truth values. The scores included both task-generic (root mean square error [RMSE] and structural similarity matrix [SSIM]), and task-specific (detectability index [d'] and lesion volume accuracy) metrics. For the cases with multiple lesions, the measured metric was averaged across all the lesions. To combine the metrics with each other, each metric was normalized to a range of 0 to 1 per disease type, with "0" and "1" being the worst and best measured values across all cases of the disease type for all received reconstructions., Results: The True-CT challenge attracted 52 participants, out of which 5 successfully completed the challenge and submitted the requested 200 reconstructions. Across all participants and disease types, SSIM absolute values ranged from 0.22 to 0.90, RMSE from 77.6 to 490.5 HU, d' from 0.1 to 64.6, and volume accuracy ranged from 1.2 to 753.1 mm 3 . The overall scores demonstrated that participant "A" had the best performance in all categories, except for the metrics of d' for lung lesions and RMSE for liver lesions. Participant "A" had an average normalized score of 0.41 ± 0.22, 0.48 ± 0.32, and 0.42 ± 0.33 for the emphysema, lung lesion, and liver lesion cases, respectively., Conclusions: The True-CT challenge successfully enabled objective assessment of CT reconstructions with the unique advantage of access to a diverse population of diseased human models with known ground truth. This study highlights the significant potential of virtual imaging trials in objective assessment of medical imaging technologies., (© 2025 American Association of Physicists in Medicine.)

Importance: Clinical imaging trials are crucial for evaluation of medical innovations, but the process is inefficient, expensive, and ethically-constrained. Virtual imaging trial (VIT) approach addresses 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., Objectives: To demonstrate that a virtual imaging trial platform can accurately emulate a major clinical trial, specifically the National Lung Screening Trial (NLST) that compared computed tomography (CT) and chest radiography (CXR) imaging for lung cancer screening., Design Setting and Participants: A virtual patient population of 294 subjects was created from human models (XCAT) emulating the NLST, with two types of simulated cancerous lung nodules. Each virtual patient in the cohort was assessed using simulated CT and CXR systems to generate images reflecting the NLST imaging technologies. Deep learning models trained for lesion detection, AI CT-Reader, and AI CXR-Reader served as virtual readers., Main Outcomes and Measures: The primary outcome was the difference in the Receiver Operating Characteristic Area Under the Curve (AUC) for CT and CXR modalities., Results: The study analyzed paired CT and CXR simulated images from 294 virtual patients. The AI CT-Reader outperformed the AI CXR-Reader across all levels of analysis. At the patient level, CT demonstrated superior diagnostic performance with an AUC of 0.92 (95% CI: 0.90-0.95), compared to CXR's AUC of 0.72 (0.67-0.77). Subgroup analyses of lesion types revealed CT had significantly better detection of homogeneous lesions (AUC 0.97, 95% CI: 0.95-0.98) compared to heterogeneous lesions (0.89; 0.86-0.93). Furthermore, when the specificity of the AI CT-Reader was adjusted to match the NLST sensitivity of 94% for CT, the VLST results closely mirrored the NLST findings, further highlighting the alignment between the two studies., Conclusion and Relevance: The VIT results closely replicated those of the earlier NLST, underscoring its potential to replicate real clinical imaging trials. Integration of virtual trials may aid in the evaluation and improvement of imaging-based diagnosis.

Pulmonary emphysema is a progressive lung disease that requires accurate evaluation for optimal management. This task, possible using quantitative CT, is particularly challenging as scanner and patient attributes change over time, negatively impacting the CT-derived quantitative measures. Efforts to minimize such variations have been limited by the absence of ground truth in clinical data, thus necessitating reliance on clinical surrogates, which may not have one-to-one correspondence to CT-based findings. This study aimed to develop the first suite of human models with emphysema at multiple time points, enabling longitudinal assessment of disease progression with access to ground truth. A total of 14 virtual subjects were modeled across three time points. Each human model was virtually imaged using a validated imaging simulator (DukeSim), modeling an energy-integrating CT scanner. The models were scanned at two dose levels and reconstructed with two reconstruction kernels, slice thicknesses, and pixel sizes. The developed longitudinal models were further utilized to demonstrate utility in algorithm testing and development. Two previously developed image processing algorithms (CT-HARMONICA, EmphysemaSeg) were evaluated. The results demonstrated the efficacy of both algorithms in improving the accuracy and precision of longitudinal quantifications, from 6.1±6.3% to 1.1±1.1% and 1.6±2.2% across years 0-5. Further investigation in EmphysemaSeg identified that baseline emphysema severity, defined as >5% emphysema at year 0, contributed to its reduced performance. This finding highlights the value of virtual imaging trials in enhancing the explainability of algorithms. Overall, the developed longitudinal human models enabled ground-truth based assessment of image processing algorithms for lung quantifications.

Parametric response mapping (PRM) is a voxel-based quantitative CT imaging biomarker that measures the severity of chronic obstructive pulmonary disease (COPD) by analyzing both inspiratory and expiratory CT scans. Although PRM-derived measurements have been shown to predict disease severity and phenotyping, their quantitative accuracy is impacted by the variability of scanner settings and patient conditions. The aim of this study was to evaluate the variability of PRM-based measurements due to the changes in the scanner types and configurations. We developed 10 human chest models with emphysema and air-trapping at end-inspiration and end-expiration states. These models were virtually imaged using a scanner-specific CT simulator (DukeSim) to create CT images at different acquisition settings for energy-integrating and photon-counting CT systems. The CT images were used to estimate PRM maps. The quantified measurements were compared with ground truth values to evaluate the deviations in the measurements. Results showed that PRM measurements varied with scanner type and configurations. The emphysema volume was overestimated by 3 ± 9.5 % (mean ± standard deviation) of the lung volume, and the functional small airway disease (fSAD) volume was underestimated by 7.5±19 % of the lung volume. PRM measurements were more accurate and precise when the acquired settings were photon-counting CT, higher dose, smoother kernel, and larger pixel size. This study demonstrates the development and utility of virtual imaging tools for systematic assessment of a quantitative biomarker accuracy.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease and a major cause of death and disability worldwide. Quantitative CT is a powerful tool to better understand the heterogeneity and severity of this disease. Quantitative CT is being increasingly used in COPD research, and the recent advancements in CT technology have made it even more encouraging. One recent advancement has been the development of photon-counting detectors, offering higher spatial resolution, higher image contrast, and lower noise levels in the images. However, the quantification performance of this new technology compared to conventional scanners remains unknown. Additionally, different protocol settings (e.g., different dose levels, slice thicknesses, reconstruction kernels and algorithms) affect quantifications in an unsimilar fashion. This study investigates the potential advantages of photon-counting CT (PCCT) against conventional energy-integrating detector (EID) CT and explores the effects of protocol settings on lung density quantifications in COPD patients. This study was made possible using a virtual imaging platform, taking advantage of anthropomorphic phantoms with COPD (COPD-XCAT) and a scanner-specific CT simulator (DukeSim). Having the physical and geometrical properties of three Siemens commercial scanners (Flash, Force for EID and NAEOTOM Alpha for PCCT) modeled, we simulated CT images of ten COPD-XCAT phantoms at 0.63 and 3.17 mGy dose levels and reconstructed at three levels of kernel sharpness. The simulated CT images were quantified in terms of "Lung mean absolute error (MAE)," "LAA -950," "Perc 15," "Lung mass" imaging biomarkers and compared against the ground truth values of the phantoms. The intra-scanner assessment demonstrated the superior qualitative and quantitative performance of the PCCT scanner over the conventional scanners (21.01% and 22.74% mean lung MAE improvement, and 53.97% and 68.13% mean LAA -950 error improvement compared to Flash and Force). The results also showed that higher mAs, thinner slices, smoother kernels, and iterative reconstruction could lead to more accurate and precise quantification scores. This study underscored the qualitative and quantitative benefits of PCCT against conventional EID scanners as well as the importance of optimal protocol choice within scanners for more accurate quantifications.

Inherent to Computed tomography (CT) is image reconstruction, constructing 3D voxel values from noisy projection data. Modeling this inverse operation is not straightforward. Given the ill-posed nature of inverse problem in CT reconstruction, data-driven methods need regularization to enhance the accuracy of the reconstructed images. Besides, generalization of the results hinges upon the availability of large training datasets with access to ground truth. This paper offers a new strategy to reconstruct CT images with the advantage of ground truth accessible through a virtual imaging trial (VIT) platform. A learned primal-dual deep neural network (LPD-DNN) employed the forward model and its adjoint as a surrogate of the imaging's geometry and physics. VIT offered simulated CT projections paired with ground truth labels from anthropomorphic human models without image noise and resolution degradation. The models included a library of anthropomorphic, computational patient models (XCAT). The DukeSim simulator was utilized to form realistic projection data emulating the impact of the physics and geometry of a commercial-equivalent CT scanner. The resultant noisy sinogram data associated with each slice was thus generated for training. Corresponding linear attenuation coefficients of phantoms' materials at the effective energy of the x-ray spectrum were used as the ground truth labels. The LPD-DNN was deployed to learn the complex operators and hyper-parameters in the proximal primal-dual optimization. The obtained validation results showed a 12% normalized root mean square error with respect to the ground truth labels, a peak signal-to-noise ratio of 32 dB, a signal-to-noise ratio of 1.5, and a structural similarity index of 96%. These results were highly favorable compared to standard filtered-back projection reconstruction (65%, 17 dB, 1.0, 26%).

The purpose of this study was to develop a virtual imaging framework that simulates a new photon-counting CT (PCCT) system (NAEOTOM Alpha, Siemens). The PCCT simulator was built upon the DukeSim platform, which generates projection images of computational phantoms given the geometry and physics of the scanner and imaging parameters. DukeSim was adapted to account for the geometry of the PCCT prototype. To model the photon-counting detection process, we utilized a Monte Carlo-based detector model with the known properties of the detectors. We validated the simulation platform against experimental measurements. The images were acquired at four dose levels (CTDI vol of 1.5, 3.0, 6.0, and 12.0 mGy) and reconstructed with three kernels (Br36, Br40, Br48). The experimental acquisitions were replicated using our developed simulation platform. The real and simulated images were quantitatively compared in terms of image quality metrics (HU values, noise magnitude, noise power spectrum, and modulation transfer function). The clinical utility of our framework was demonstrated by conducting two clinical applications (COPD quantifications and lung nodule radiomics). The phantoms with relevant pathologies were imaged with DukeSim modeling the PCCT systems. Different imaging parameters (e.g., dose, reconstruction techniques, pixel size, and slice thickness) were altered to investigate their effects on task-based quantifications. We successfully implemented the acquisition and physics attributes of the PCCT prototype into the DukeSim platform. The discrepancy between the real and simulated data was on average about 2 HU in terms of noise magnitude, 0.002 mm -1 in terms of noise power spectrum peak frequency and 0.005 mm -1 in terms of the frequency at 50% MTF. Analysis suggested that lung lesion radiomics to be more accurate with reduced pixel size and slice thickness. For COPD quantifications, higher doses, thinner slices, and softer kernels yielded more accurate quantification of density-based biomarkers. Our developed virtual imaging platform enables systematic comparison of new PCCT technologies as well as optimization of the imaging parameters for specific clinical tasks.