Phase-contrast virtual chest radiography.

Respiratory X-ray imaging enhanced by phase contrast has shown improved airway visualization in animal models. Limitations in current X-ray technology have nevertheless hindered clinical translation, leaving the potential clinical impact an open question. Here, we explore phase-contrast chest radiography in a realistic in silico framework. Specifically, we use preprocessed virtual patients to generate in silico chest radiographs by Fresnel-diffraction simulations of X-ray wave propagation. Following a reader study conducted with clinical radiologists, we predict that phase-contrast edge enhancement will have a negligible impact on improving solitary pulmonary nodule detection (6 to 20 mm). However, edge enhancement of bronchial walls visualizes small airways (< 2 mm), which are invisible in conventional radiography. Our results show that phase-contrast chest radiography could play a future role in observing small-airway obstruction (e.g., relevant for asthma or early-stage chronic obstructive pulmonary disease), which cannot be directly visualized using current clinical methods, thereby motivating the experimental development needed for clinical translation. Finally, we discuss quantitative requirements on distances and X-ray source/detector specifications for clinical implementation of phase-contrast chest radiography.

Technology Characterization Through Diverse Evaluation Methodologies: Application to Thoracic Imaging in Photon-Counting Computed Tomography.

OBJECTIVE: Different methods can be used to condition imaging systems for clinical use. The purpose of this study was to assess how these methods complement one another in evaluating a system for clinical integration of an emerging technology, photon-counting computed tomography (PCCT), for thoracic imaging. METHODS: Four methods were used to assess a clinical PCCT system (NAEOTOM Alpha; Siemens Healthineers, Forchheim, Germany) across 3 reconstruction kernels (Br40f, Br48f, and Br56f). First, a phantom evaluation was performed using a computed tomography quality control phantom to characterize noise magnitude, spatial resolution, and detectability. Second, clinical images acquired using conventional and PCCT systems were used for a multi-institutional reader study where readers from 2 institutions were asked to rank their preference of images. Third, the clinical images were assessed in terms of in vivo image quality characterization of global noise index and detectability. Fourth, a virtual imaging trial was conducted using a validated simulation platform (DukeSim) that models PCCT and a virtual patient model (XCAT) with embedded lung lesions imaged under differing conditions of respiratory phase and positional displacement. Using known ground truth of the patient model, images were evaluated for quantitative biomarkers of lung intensity histograms and lesion morphology metrics. RESULTS: For the physical phantom study, the Br56f kernel was shown to have the highest resolution despite having the highest noise and lowest detectability. Readers across both institutions preferred the Br56f kernel (71% first rank) with a high interclass correlation (0.990). In vivo assessments found superior detectability for PCCT compared with conventional computed tomography but higher noise and reduced detectability with increased kernel sharpness. For the virtual imaging trial, Br40f was shown to have the best performance for histogram measures, whereas Br56f was shown to have the most precise and accurate morphology metrics. CONCLUSION: The 4 evaluation methods each have their strengths and limitations and bring complementary insight to the evaluation of PCCT. Although no method offers a complete answer, concordant findings between methods offer affirmatory confidence in a decision, whereas discordant ones offer insight for added perspective. Aggregating our findings, we concluded the Br56f kernel best for high-resolution tasks and Br40f for contrast-dependent tasks.

Modeling and identification of affective parameters on cadmium's durability and evaluating cadmium pollution indicators caused by using chemical fertilizers in long term.

Soil contamination by anthropogenic heavy metals has become a global issue. This study aimed to investigate cadmium (Cd) concentration, mobility, and contamination indices of Cd in soils in the Hamadan province, west of Iran. To investigate the concentration of Cd in soil, one hundred soil samples from wheat farms and five samples from control lands were collected. Pollution indexes, including Cd mobility, enrichment factor, geoaccumulation index, contamination index, and availability ratio, were investigated. The structural equation model was also used to evaluate effective parameters on cadmium durability in soil. Results showed that mean values of available phosphorus (P) were 83.65, 129, and 65 (mg kg-1) in three land-use types rainfed, irrigated, and controlled, respectively. The mean values of Cd in different land-use types of rainfed, irrigated, and controlled were 0.15, 0.18, and 0.08 (mg kg-1), respectively. The results indicated that the amount of Cd in both forms (available and total) in ones that received fertilizer, especially P fertilizers, was higher than in the controlled one. Other pollution indexes revealed that the study area had been slightly contaminated due to anthropogenic activities. Lime, clay, lead, and OM were identified as affective parameters on cadmium durability. Finally, the results demonstrated that the mobility rate was high. Cd had a higher potential mobility in soil samples in the rain-fed and irrigated land than in the controlled land, and Cd had a low retention time.

Virtual Imaging Trials for Coronavirus Disease (COVID-19).

OBJECTIVE. The virtual imaging trial is a unique framework that can greatly facilitate the assessment and optimization of imaging methods by emulating the imaging experiment using representative computational models of patients and validated imaging simulators. The purpose of this study was to show how virtual imaging trials can be adapted for imaging studies of coronavirus disease (COVID-19), enabling effective assessment and optimization of CT and radiography acquisitions and analysis tools for reliable imaging and management of COVID-19. MATERIALS AND METHODS. We developed the first computational models of patients with COVID-19 and as a proof of principle showed how they can be combined with imaging simulators for COVID-19 imaging studies. For the body habitus of the models, we used the 4D extended cardiac-torso (XCAT) model that was developed at Duke University. The morphologic features of COVID-19 abnormalities were segmented from 20 CT images of patients who had been confirmed to have COVID-19 and incorporated into XCAT models. Within a given disease area, the texture and material of the lung parenchyma in the XCAT were modified to match the properties observed in the clinical images. To show the utility, three developed COVID-19 computational phantoms were virtually imaged using a scanner-specific CT and radiography simulator. RESULTS. Subjectively, the simulated abnormalities were realistic in terms of shape and texture. Results showed that the contrast-to-noise ratios in the abnormal regions were 1.6, 3.0, and 3.6 for 5-, 25-, and 50-mAs images, respectively. CONCLUSION. The developed toolsets in this study provide the foundation for use of virtual imaging trials in effective assessment and optimization of CT and radiography acquisitions and analysis tools to help manage the COVID-19 pandemic.

Modeling Patient-Informed Liver Contrast Perfusion in Contrast-enhanced Computed Tomography.

OBJECTIVE: To determine the correlation between patient attributes and contrast enhancement in liver parenchyma and demonstrate the potential for patient-informed prediction and optimization of contrast enhancement in liver imaging. METHODS: The study included 418 chest/abdomen/pelvis computed tomography scans, with 75% to 25% training-testing split. Two regression models were built to predict liver parenchyma contrast enhancement over time: first model (model A) utilized patient attributes (height, weight, sex, age, bolus volume, injection rate, scan times, body mass index, lean body mass) and bolus-tracking data. A second model (model B) only used the patient attributes. Pearson coefficient was used to assess predictive accuracy. RESULTS: Weight- and height-related features were found to be statistically significant predictors (P < 0.05), weight being the strongest. Of the 2 models, model A (r = 0.75) showed greater accuracy than model B (r = 0.42). CONCLUSIONS: Patient attributes can be used to build prediction model for liver parenchyma contrast enhancement. The model can have utility in optimization and improved consistency in contrast-enhanced liver imaging.

A comparison of COVID-19 and imaging radiation risk in clinical patient populations.

The outbreak of coronavirus SARS-COV2 affected more than 180 countries necessitating fast and accurate diagnostic tools. Reverse transcriptase polymerase chain reaction (RT-PCR) has been identified as a gold standard test with Chest CT and Chest Radiography showing promising results as well. However, radiological solutions have not been used extensively for the diagnosis of COVID-19 disease, partly due to radiation risk. This study aimed to provide quantitative comparison of imaging radiation risk versus COVID risk. The analysis was performed in terms of mortality rate per age group. COVID-19 mortality was extracted from epidemiological data across 299, 004 patients published by ISS-Integrated surveillance of COVID-19 in Italy. For radiological risk, the study considered 659 Chest CT performed in adult patients. Organ doses were estimated using a Monte Carlo method and then used to calculate Risk Index that was converted into an upper bound for related mortality rate following NCI-SEER data. COVID-19 mortality showed a rapid rise for ages >30 years old (min: 0.30%; max: 30.20%), whereas only four deaths were reported in the analysed patient cohort for ages <20 years old. The rates decreased for radiation risk across age groups. The median mortality rate across all ages for Chest-CT and Chest-Radiography were 0.007% (min: 0.005%; max: 0.011%) and 0.0003% (min: 0.0002%; max: 0.0004%), respectively. COVID-19, Chest Radiography, and Chest CT mortality rates showed different magnitudes and trends across age groups. In higher ages, the risk of COVID-19 far outweighs that of radiological exams. Based on risk comparison alone, Chest Radiography and CT for COVID-19 care is justified for patients older than 20 and 30 years old, respectively. Notwithstanding other aspects of diagnosis, the present results capture a component of risk consideration associated with the use of imaging for COVID. Once integrated with other diagnostic factors, they may help inform better management of the pandemic.

The Effect of Contrast Material on Radiation Dose at CT: Part II. A Systematic Evaluation across 58 Patient Models.

Purpose To estimate the radiation dose as a result of contrast medium administration in a typical abdominal computed tomographic (CT) examination across a library of contrast material-enhanced computational patient models. Materials and Methods In part II of this study, first, the technique described in part I of this study was applied to enhance the extended cardiac-torso models with patient-specific iodine-time profiles reflecting the administration of contrast material. Second, the patient models were deployed to assess the patient-specific organ dose as a function of time in a typical abdominal CT examination using Monte Carlo simulation. In this hypothesis-generating study, organ dose refers to the total energy deposited in the unit mass of the tissue inclusive of iodine. Third, a study was performed as a strategy to anticipate the biologically relevant dose (absorbed dose to tissue) in highly perfused organs such as the liver and kidney. The time-varying organ-dose increment values relative to those for unenhanced CT examinations were reported. Results The results from the patient models subjected to the injection protocol indicated up to a total 53%, 30%, 35%, 54%, 27%, 18%, 17%, and 24% increase in radiation dose delivered to the heart, spleen, liver, kidneys, stomach, colon, small intestine, and pancreas, respectively. The biologically relevant dose increase with respect to the dose at an unenhanced CT examination was in the range of 0%-18% increase for the liver and 27% for the kidney across 58 patient models. Conclusion The administration of contrast medium increases the total radiation dose. However, radiation dose, while relevant to be included in estimating the risk associated with contrast-enhanced CT, may still not fully characterize the total biologic effects. Therefore, given the fact that many CT diagnostic decisions would be impossible without the use of iodine, this study suggests the need to consider the effect of iodinated contrast material on the organ doses to patients undergoing CT studies when designing CT protocols. © RSNA, 2017 Online supplemental material is available for this article.

A systematic task-based image quality assessment of photon-counting and energy integrating CT as a function of reconstruction kernel and phantom size.

BACKGROUND: Image quality of photon-counting and energy integrating CT scanners changes with object size, dose to the object, and kernel selection. PURPOSE: To comprehensively compare task-generic image quality of photon-counting CT (PCCT) and energy integrating CT (EICT) systems as a function of phantom size, dose, and reconstruction kernel. METHODS: A size-variant phantom (Mercury Phantom 3.0) was used to characterize the image quality of PCCT and EICT systems as a function of object size. The phantom contained five cylinders attached by slanted tapered sections. Each cylinder contained two sections: one uniform for noise, and the other with inserts for spatial resolution and contrast measurements. The phantom was scanned on Siemens' SOMATOM Force and NAEOTOM Alpha at 1.18 and 7.51 mGy without tube current modulation. CTDIvol was matched across two systems by setting the required tube currents, else, all other acquisition settings were fixed. CT sinograms were reconstructed using FBP and iterative (ADMIRE2 - Force; QIR2 - Alpha) algorithms with Body regular (Br) kernels. Noise Power Spectrum (NPS), Task Transfer Function (TTF), contrast-to-noise ratio (CNR), and detectability index (d') for a task of identifying 2-mm disk were evaluated based on AAPM TG-233 metrology using imQuest, an open-source software package. Averaged noise frequency (fav ) and 50% cut-off frequency for TTF (f50 ) were used as scalar metrics to quantify noise texture and spatial resolution, respectively. The difference between image quality metrics' measurements was calculated as IQPCCT - IQEICT . RESULTS: From Br40 (soft) to Br64 (sharp), f50 for air insert increased from 0.35 mm-1  ± 0.04 (standard deviation) to 0.76 mm-1  ± 0.17, 0.34 mm-1  ± 0.04 to 0.77 mm-1  ± 0.17, 0.37 mm-1  ± 0.02 to 0.95 mm-1  ± 0.17 for PCCT-T3D-QIR2, PCCT-70keV-QIR2, and EICT-ADMIRE2, respectively, when averaged over all sizes and dose levels. Similarly, from Br40 to Br64, noise magnitude increased from 10.86 HU ± 7.12 to 38.61 HU ± 18.84, 10.94 HU ± 7.08 to 38.82 HU ± 18.70, 13.74 HU ± 11.02 to 52.11 HU ± 26.22 for PCCT-T3D-QIR2, PCCT-70keV-QIR2, and EICT-ADMIRE2, respectively. The difference in fav was consistent across all sizes and dose levels. PCCT-70keV-VMI showed better consistency in contrast measurements for iodine and bone inserts than PCCT-T3D and EICT; however, PCCT-T3D had higher contrast for both inserts. From Br40 to Br64, considering all sizes and dose levels, CNR for iodine insert decreased from 52.30 ± 46.44 to 12.18 ± 10.07, 40.42 ± 33.42 to 9.48 ± 7.16, 39.94 ± 37.60 to 7.84 ± 6.67 for PCCT-T3D-QIR2, PCCT-70keV-QIR2, and EICT-ADMIRE2, respectively. CONCLUSIONS: Both PCCT image types, T3D and 70-keV-VMI exhibited similar or better noise, contrast, CNR than EICT when comparing kernels with similar names. For 512 × 512 matrix, PCCT's sharp kernels had lower resolution than EICT's sharp kernels. For all image quality metrics, except extreme low, every dose condition had a similar set of IQ-matching kernels. It suggests that considering patient size and dose level to determine IQ-matching kernel pairs across PCCT and EICT systems may not be imperative while translating protocols, except when the signal to the detector is extremely low.

Protocol selection formalism for minimizing detectable differences in morphological radiomics features of lung lesions in repeated CT acquisitions.

Background: The accuracy of morphological radiomic features (MRFs) can be affected by various acquisition settings and imaging conditions. To ensure that clinically irrelevant changes do not reduce sensitivity to capture the radiomics changes between successive acquisitions, it is essential to determine the optimal imaging systems and protocols to use. Purpose: The main goal of our study was to optimize CT protocols and minimize the minimum detectable difference (MDD) in successive acquisitions of MRFs. Method: MDDs were derived based on the previous research involving 15 realizations of nodule models at two different sizes. Our study involved simulations of two consecutive acquisitions using 297 different imaging conditions, representing variations in scanners' reconstruction kernels, dose levels, and slice thicknesses. Parametric polynomial models were developed to establish correlations between imaging system characteristics, lesion size, and MDDs. Additionally, polynomial models were used to model the correlation of the imaging system parameters. Optimization problems were formulated for each MRF to minimize the approximated function. Feature importance was determined for each MRF through permutation feature analysis. The proposed method was compared to the recommended guidelines by the quantitative imaging biomarkers alliance (QIBA). Results: The feature importance analysis showed that lesion size is the most influential parameter to estimate the MDDs in most of the MRFs. Our study revealed that thinner slices and higher doses had a measurable impact on reducing the MDDs. Higher spatial resolution and lower noise magnitude were identified as the most suitable or noninferior acquisition settings. Compared to QIBA, the proposed protocol selection guideline demonstrated a reduced coefficient of variation, with values decreasing from 1.49 to 1.11 for large lesions and from 1.68 to 1.12 for small lesions. Conclusion: The protocol optimization framework provides means to assess and optimize protocols to minimize the MDD to increase the sensitivity of the measurements in lung cancer screening.

Deep silicon photon-counting CT: A first simulation-based study for assessing perceptual benefits across diverse anatomies.

OBJECTIVES: To assess perceptual benefits provided by the improved spatial resolution and noise performance of deep silicon photon-counting CT (Si-PCCT) over conventional energy-integrating CT (ECT) using polychromatic images for various clinical tasks and anatomical regions. MATERIALS AND METHODS: Anthropomorphic, computational models were developed for lungs, liver, inner ear, and head-and-neck (H&N) anatomies. These regions included specific abnormalities such as lesions in the lungs and liver, and calcified plaques in the carotid arteries. The anatomical models were imaged using a scanner-specific CT simulation platform (DukeSim) modeling a Si-PCCT prototype and a conventional ECT system at matched dose levels. The simulated polychromatic projections were reconstructed with matched in-plane resolutions using manufacturer-specific software. The reconstructed pairs of images were scored by radiologists to gauge the task-specific perceptual benefits provided by Si-PCCT compared to ECT based on visualization of anatomical and image quality features. The scores were standardized as z-scores for minimizing inter-observer variability and compared between the systems for evidence of statistically significant improvement (one-sided Wilcoxon rank-sum test with a significance level of 0.05) in perceptual performance for Si-PCCT. RESULTS: Si-PCCT offered favorable image quality and improved visualization capabilities, leading to mean improvements in task-specific perceptual performance over ECT for most tasks. The improvements for Si-PCCT were statistically significant for the visualization of lung lesion (0.08 ± 0.89 vs. 0.90 ± 0.48), liver lesion (-0.64 ± 0.37 vs. 0.95 ± 0.55), and soft tissue structures (-0.47 ± 0.90 vs. 0.33 ± 1.24) and cochlea (-0.47 ± 0.80 vs. 0.38 ± 0.62) in inner ear. CONCLUSIONS: Si-PCCT exhibited mean improvements in task-specific perceptual performance over ECT for most clinical tasks considered in this study, with statistically significant improvement for 6/20 tasks. The perceptual performance of Si-PCCT is expected to improve further with availability of spectral information and reconstruction kernels optimized for high resolution provided by smaller pixel size of Si-PCCT. The outcomes of this study indicate the positive potential of Si-PCCT for benefiting routine clinical practice through improved image quality and visualization capabilities.

A systematic assessment and optimization of photon-counting CT for lung density quantifications.

BACKGROUND: Photon-counting computed tomography (PCCT) has recently emerged into clinical use; however, its optimum imaging protocols and added benefits remains unknown in terms of providing more accurate lung density quantification compared to energy-integrating computed tomography (EICT) scanners. PURPOSE: To systematically assess the performance of a clinical PCCT scanner for lung density quantifications and compare it against EICT. METHODS: This cross-sectional study involved a retrospective analysis of subjects scanned (August-December 2021) using a clinical PCCT system. The influence of altering reconstruction parameters was studied (reconstruction kernel, pixel size, slice thickness). A virtual CT dataset of anthropomorphic virtual subjects was acquired to demonstrate the correspondence of findings to clinical dataset, and to perform systematic imaging experiments, not possible using human subjects. The virtual subjects were imaged using a validated, scanner-specific CT simulator of a PCCT and two EICT (defined as EICT A and B) scanners. The images were evaluated using mean absolute error (MAE) of lung and emphysema density against their corresponding ground truth. RESULTS: Clinical and virtual PCCT datasets showed similar trends, with sharper kernels and smaller voxel sizes increasing percentage of low-attenuation areas below -950 HU (LAA-950) by up to 15.7 ± 6.9% and 11.8 ± 5.5%, respectively. Under the conditions studied, higher doses, thinner slices, smaller pixel sizes, iterative reconstructions, and quantitative kernels with medium sharpness resulted in lower lung MAE values. While using these settings for PCCT, changes in the dose level (13 to 1.3 mGy), slice thickness (0.4 to 1.5 mm), pixel size (0.49 to 0.98 mm), reconstruction technique (70 keV-VMI to wFBP), and kernel (Qr48 to Qr60) increased lung MAE by 15.3 ± 2.0, 1.4 ± 0.6, 2.2 ± 0.3, 4.2 ± 0.8, and 9.1 ± 1.6 HU, respectively. At the optimum settings identified per scanner, PCCT images exhibited lower lung and emphysema MAE than those of EICT scanners (by 2.6 ± 1.0 and 9.6 ± 3.4 HU, compared to EICT A, and by 4.8 ± 0.8 and 7.4 ± 2.3 HU, compared to EICT B). The accuracy of lung density measurements was correlated with subjects' mean lung density (p < 0.05), measured by PCCT at optimum setting under the conditions studied. CONCLUSION: Photon-counting CT demonstrated superior performance in density quantifications, with its influences of imaging parameters in line with energy-integrating CT scanners. The technology offers improvement in lung quantifications, thus demonstrating potential toward more objective assessment of respiratory conditions.

Estimation of threshold thickness of residual normal tissue in lung dysfunction detectable by dynamic chest radiography: A virtual imaging trial.

BACKGROUND: Dynamic chest radiography (DCR) is a recently developed functional x-ray imaging technique that detects pulmonary ventilation impairment as a decrease in changes in lung density during respiration. However, the diagnostic performance of DCR is uncertain owing to an insufficient number of clinical cases. One solution is virtual imaging trials (VITs), which is an emerging alternative method for efficiently evaluating medical imaging technology via computer simulation techniques. PURPOSE: This study aimed to estimate the typical threshold thickness of residual normal tissue below which the presence of emphysema may be detected by DCR via VITs using virtual patients with different physiques and a user-defined ground truth. METHODS: Twenty extended cardiac-torso (XCAT) phantoms that exhibited changes in lung density during respiration were generated to simulate virtual patients. To simulate a locally collapsed lung, an air sphere was inserted into each lung regions in the phantom. The XCAT phantom was virtually projected using an x-ray simulator. The respiratory changes in pixel value (ΔPV) were measured on the projected air spheres (simulated lesions) to calculate the percentage of decrease (ΔPV%) relative to ΔPVexp-ins in the absence of an air sphere. The relationship between the amount of residual normal tissue and ΔPV% was fitted to a cubic approximation curve (hereafter, performance curve), and the threshold at which the ΔPV% began to decrease (normal-tissuethre) was determined. The goodness of fit for each performance curve was evaluated according to the coefficient of determination (R2) and the 95% confidence interval derived from the standard errors between the measured and theoretical values corresponding to each performance curve. The ΔPV% was also visualized as a color scaling to validate the results of the VITs in both virtual and clinical patients. RESULTS: For each lung region in all body sizes, the ΔPV% decreased as the amount of residual normal tissue decreased and could be defined as a function of the amount of residual normal tissue in front of and behind the simulated lesions with high R2 values. Meanwhile, the difference between the measured and theoretical values corresponding to each performance curve was only partially included in the 95% confidence interval. The normal-tissuethre values were 146.0, 179.5, and 170.9 mm for the upper, middle, and lower lungs, respectively, which were demonstrated in virtual patients and one real patient, where the value of the residual normal tissue was less than that of normal-tissuethre; any reduction in the residual normal tissue was reflected as a reduced ΔPV and depicted as a reduced color intensity. CONCLUSIONS: The performance of DCR-based pulmonary impairment assessment depends on the amount of residual normal tissue in front of and behind the lesion rather than on the lesion size. The performance curve can be defined as a function of the amount of residual normal tissue in each lung region with a specific threshold of normal tissue remaining where lesions become detectable, shown as a decrease in ΔPV. The results of VITs are expected to accelerate future clinical trials for DCR-based pulmonary function assessment.

Development and Application of a Virtual Imaging Trial Framework for Longitudinal Quantification of Emphysema in CT.

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.

Development of physiologically-informed computational coronary artery plaques for use in virtual imaging trials.

BACKGROUND: As a leading cause of death, worldwide, cardiovascular disease is of great clinical importance. Among cardiovascular diseases, coronary artery disease (CAD) is a key contributor, and it is the attributed cause of death for 10% of all deaths annually. The prevalence of CAD is commensurate with the rise in new medical imaging technologies intended to aid in its diagnosis and treatment. The necessary clinical trials required to validate and optimize these technologies require a large cohort of carefully controlled patients, considerable time to complete, and can be prohibitively expensive. A safer, faster, less expensive alternative is using virtual imaging trials (VITs), utilizing virtual patients or phantoms combined with accurate computer models of imaging devices. PURPOSE: In this work, we develop realistic, physiologically-informed models for coronary plaques for application in cardiac imaging VITs. METHODS: Histology images of plaques at micron-level resolution were used to train a deep convolutional generative adversarial network (DC-GAN) to create a library of anatomically variable plaque models with clinical anatomical realism. The stability of each plaque was evaluated by finite element analysis (FEA) in which plaque components and vessels were meshed as volumes, modeled as specialized tissues, and subjected to the range of normal coronary blood pressures. To demonstrate the utility of the plaque models, we combined them with the whole-body XCAT computational phantom to perform initial simulations comparing standard energy-integrating detector (EID) CT with photon-counting detector (PCD) CT. RESULTS: Our results show the network is capable of generating realistic, anatomically variable plaques. Our simulation results provide an initial demonstration of the utility of the generated plaque models as targets to compare different imaging devices. CONCLUSIONS: Vast, realistic, and variable CAD pathologies can be generated to incorporate into computational phantoms for VITs. There they can serve as a known truth from which to optimize and evaluate cardiac imaging technologies quantitatively.

Quantitative accuracy of lung function measurement using parametric response mapping: A virtual imaging study.

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.

Proceedings Virtual Imaging Trials in Medicine 2024.

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.

VLST: Virtual Lung Screening Trial for Lung Cancer Detection Using Virtual Imaging Trial.

Importance: The efficacy of lung cancer screening can be significantly impacted by the imaging modality used. This Virtual Lung Screening Trial (VLST) addresses the critical need for precision in lung cancer diagnostics and the potential for reducing unnecessary radiation exposure in clinical settings. Objectives: To establish a virtual imaging trial (VIT) platform that accurately simulates real-world lung screening trials (LSTs) to assess the diagnostic accuracy of CT and CXR modalities. Design Setting and Participants: Utilizing computational models and machine learning algorithms, we created a diverse virtual patient population. The cohort, designed to mirror real-world demographics, was assessed using virtual imaging techniques that reflect historical imaging technologies. Main Outcomes and Measures: The primary outcome was the difference in the Area Under the Curve (AUC) for CT and CXR modalities across lesion types and sizes. Results: The study analyzed 298 CT and 313 CXR simulated images from 313 virtual patients, with a lesion-level AUC of 0.81 (95% CI: 0.78-0.84) for CT and 0.55 (95% CI: 0.53-0.56) for CXR. At the patient level, CT demonstrated an AUC of 0.85 (95% CI: 0.80-0.89), compared to 0.53 (95% CI: 0.47-0.60) for CXR. Subgroup analyses indicated CT's superior performance in detecting homogeneous lesions (AUC of 0.97 for lesion-level) and heterogeneous lesions (AUC of 0.71 for lesion-level) as well as in identifying larger nodules (AUC of 0.98 for nodules > 8 mm). Conclusion and Relevance: The VIT platform validated the superior diagnostic accuracy of CT over CXR, especially for smaller nodules, underscoring its potential to replicate real clinical imaging trials. These findings advocate for the integration of virtual trials in the evaluation and improvement of imaging-based diagnostic tools.

Exploration of the pulse pileup effects in a clinical CdTe-based photon-counting computed tomography.

BACKGROUND: High tube current generates a high flux of x-rays to photon counting detectors (PCDs) that can potentially result in the piling up of pulses formed by concurrent photons, which can cause count loss and energy resolution degradation. PURPOSE: To evaluate the performance of clinical photon-counting CT (PCCT) systems in high flux, potentially influenced by pulse pileup effects, in terms of task-generic image quality metrics. METHODS: A clinical phantom was scanned on a commercial PCCT scanner (NAEOTOM Alpha, Siemens) at 120 kV under fourteen different tube current levels (40-1000 mA) with a rotation time of 0.25 s and a pitch of 1. The dose levels corresponded to CTDIvol (32 cm phantom) of 0.79-19.8 mGy. CT sinograms were reconstructed using QIR-off mode (noniterative reconstruction algorithm), Br44 kernel, and a voxel size of 0.4102 × 0.4102 × 3 mm 3 $0.4102 \times 0.4102 \times 3{\mathrm{\ mm}}^3$ . imQuest, an open-source MATLAB-based software package was used to calculate noise power spectrum (NPS), task transfer function (TTF), contrast-to-noise ratio (CNR), and CT number according to AAPM Task Group 233 metrology. RESULTS: The 50% cut-off frequency of TTF (f50 ) remained mostly constant across all higher tube currents for all inserts, namely polyethylene, bone, air, and acrylic. Using the lowest two data points (40 and 80 mA), the expected relationship between noise magnitude and tube current was determined to be noise ∝ $ \propto \ $ mA-0.47 . The measured noise magnitude were up to 11.1% higher than the expected value at the highest tube current. The average frequency of NPS (fav ) decreased from 0.32 to 0.29 mm-1 as tube current increased from 40 to 1000 mA. No considerable effects were observed in CT number measurement of any insert; however, CT numbers for air and bone changed almost monotonically as tube current increased. Absolute CNR increased monotonically for all inserts; however, the difference between measured and expected CNRs were approximately -6% to 12% across all tube currents. CONCLUSIONS: Increasing tube currents did not affect the spatial resolution, but slightly affected the CT number and noise measurements of the clinical PCCT system. However, the effects were only considerable at clinically irrelevant tube currents used on a small 20-cm phantom. In general clinical practices, automatic exposure control techniques are used to decrease the variation of flux on the detector, which alleviates the chances of detector saturation due to high count rates. The observed effects could be due to pulse pileup, signal-dependent filtration of the system, or nonlinearities in the reconstruction algorithm. In conclusion, either the deadtime of the detector used in the photon-counting CT system is shorter such that count losses due to pulse pileup are negligible, or pulse pileup has inconsiderable effects on the image quality of clinical photon-counting CT systems in routine clinical practice due to possible corrections applied on the system.

Coronary stenosis quantification in cardiac computed tomography angiography: multi-factorial optimization of image quality and radiation dose.

Background: The accuracy and variability of quantification in computed tomography angiography (CTA) are affected by the interplay of imaging parameters and patient attributes. The assessment of these combined effects has been an open engineering challenge. Purpose: In this study, we developed a framework that optimizes imaging parameters for accurate and consistent coronary stenosis quantification in cardiac CTA while accounting for patient-specific variables. Methods: The framework utilizes a task-specific image quality index, the estimability index (e'), approximated by a surrogate estimability polynomial function (EPF) capable of finding the optimal protocol that (1) maximizes image quality with an upper bound for desired radiation dose or (2) minimizes the dose level with a lower bound of acceptable image quality. The optimization process was formulated with the decision variables being subject to a set of constraints. The methodology was verified using CTA data from a prior clinical trial (prospective multi-center imaging study for evaluation of chest pain) by assessing the concordance of its prediction with the trial results. Further, the framework was used to derive an optimum protocol for each case based on the patient attributes, gauging how much improvement would have been possible if the derived optimized protocol would have been deployed. Results: The framework produced results consistent with imaging physics principles with approximated EPFs of 97% accuracy. The feature importance evaluation demonstrated a close match with earlier studies. The verification study found e' scores closely predicting the cardiologist scores to within 95% in terms of the area under the receiver operating characteristic curve and predicting potential for either an average of fourfold increase in e' within a targeted dose or a reduction in radiation dose by an average of 57% without reducing the image quality. Conclusions: The protocol optimization framework provides means to assess and optimize CTA in terms of either image quality or radiation dose objectives with its results predicting prior clinical trial findings.

Emphysema Quantifications With CT Scan: Assessing the Effects of Acquisition Protocols and Imaging Parameters Using Virtual Imaging Trials.

BACKGROUND: CT scan has notable potential to quantify the severity and progression of emphysema in patients. Such quantification should ideally reflect the true attributes and pathologic conditions of subjects, not scanner parameters. To achieve such an objective, the effects of the scanner conditions need to be understood so the influence can be mitigated. RESEARCH QUESTION: How do CT scan imaging parameters affect the accuracy of emphysema-based quantifications and biomarkers? STUDY DESIGN AND METHODS: Twenty anthropomorphic digital phantoms were developed with diverse anatomic attributes and emphysema abnormalities informed by a real COPD cohort. The phantoms were input to a validated CT scan simulator (DukeSim), modeling a commercial scanner (Siemens Flash). Virtual images were acquired under various clinical conditions of dose levels, tube current modulations (TCM), and reconstruction techniques and kernels. The images were analyzed to evaluate the effects of imaging parameters on the accuracy of density-based quantifications (percent of lung voxels with HU < -950 [LAA-950] and 15th percentile of lung histogram HU [Perc15]) across varied subjects. Paired t tests were performed to explore statistical differences between any two imaging conditions. RESULTS: The most accurate imaging condition corresponded to the highest acquired dose (100 mAs) and iterative reconstruction (SAFIRE) with the smooth kernel of I31, where the measurement errors (difference between measurement and ground truth) were 35 ± 3 Hounsfield Units (HU), -4% ± 5%, and 26 ± 10 HU (average ± SD), for the mean lung HU, LAA-950, and Perc15, respectively. Without TCM and at the I31 kernel, increase of dose (20 to 100 mAs) improved the lung mean absolute error (MAE) by 4.2 ± 2.3 HU (average ± SD). TCM did not contribute to a systematic improvement of lung MAE. INTERPRETATION: The results highlight that although CT scan quantification is possible, its reliability is impacted by the choice of imaging parameters. The developed virtual imaging trial platform in this study enables comprehensive evaluation of CT scan methods in reliable quantifications, an effort that cannot be readily made with patient images or simplistic physical phantoms.