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.

Evaluation of data uncertainty for deep-learning-based CT noise reduction using ensemble patient data and a virtual imaging trial framework.

Deep learning-based image reconstruction and noise reduction (DLIR) methods have been increasingly deployed in clinical CT. Accurate assessment of their data uncertainty properties is essential to understand the stability of DLIR in response to noise. In this work, we aim to evaluate the data uncertainty of a DLIR method using real patient data and a virtual imaging trial framework and compare it with filtered-backprojection (FBP) and iterative reconstruction (IR). The ensemble of noise realizations was generated by using a realistic projection domain noise insertion technique. The impact of varying dose levels and denoising strengths were investigated for a ResNet-based deep convolutional neural network (DCNN) model trained using patient images. On the uncertainty maps, DCNN shows more detailed structures than IR although its bias map has less structural dependency, which implies that DCNN is more sensitive to small changes in the input. Both visual examples and histogram analysis demonstrated that hotspots of uncertainty in DCNN may be associated with a higher chance of distortion from the truth than IR, but it may also correspond to a better detection performance for some of the small structures.

Image quality evaluation in deep-learning-based CT noise reduction using virtual imaging trial methods: Contrast-dependent spatial resolution.

BACKGROUND: Deep-learning-based image reconstruction and noise reduction methods (DLIR) have been increasingly deployed in clinical CT. Accurate image quality assessment of these methods is challenging as the performance measured using physical phantoms may not represent the true performance of DLIR in patients since DLIR is trained mostly on patient images. PURPOSE: In this work, we aim to develop a patient-data-based virtual imaging trial framework and, as a first application, use it to measure the spatial resolution properties of a DLIR method. METHODS: The patient-data-based virtual imaging trial framework consists of five steps: (1) insertion of lesions into projection domain data using the acquisition geometry of the patient exam to simulate different lesion characteristics; (2) insertion of noise into projection domain data using a realistic photon statistical model of the CT system to simulate different dose levels; (3) creation of DLIR-processed images from projection or image data; (4) creation of ensembles of DLIR-processed patient images from a large number of noise and lesion realizations; and (5) evaluation of image quality using ensemble DLIR images. This framework was applied to measure the spatial resolution of a ResNet based deep convolutional neural network (DCNN) trained on patient images. Lesions in a cylindrical shape and different contrast levels (-500, -100, -50, -20, -10 HU) were inserted to the lower right lobe of the liver in a patient case. Multiple dose levels were simulated (50%, 25%, 12.5%). Each lesion and dose condition had 600 noise realizations. Multiple reconstruction and denoising methods were used on all the noise realizations, including the original filtered-backprojection (FBP), iterative reconstruction (IR), and the DCNN method with three different strength setting (DCNN-weak, DCNN-medium, and DCNN-strong). Mean lesion signal was calculated by performing ensemble averaging of all the noise realizations for each lesion and dose condition and then subtracting the lesion-present images from the lesion absent images. Modulation transfer functions (MTFs) both in-plane and along the z-axis were calculated based on the mean lesion signals. The standard deviations of MTFs at each condition were estimated with bootstrapping: randomly sampling (with replacement) all the DLIR/FBP/IR images from the ensemble data (600 samples) at each condition. The impact of varying lesion contrast, dose levels, and denoising strengths were evaluated. Statistical analysis with paired t-test was used to compare the z-axis and in-plane spatial resolution of five algorithms for five different contrasts and three dose levels. RESULTS: The in-plane and z-axis spatial resolution degradation of DCNN becomes more severe as the contrast or radiation dose decreased, or DCNN denoising strength increased. In comparison with FBP, a 59.5% and 4.1% reduction of in-plane and z-axis MTF (in terms of spatial frequencies at 50% MTF), respectively, was observed at low contrast (-10 HU) for DCNN with the highest denoising strength at 25% routine dose level. When the dose level reduces from 50% to 12.5% of routine dose, the in-plane and z-axis MTFs reduces from 92.1% to 76.3%, and from 98.9% to 95.5%, respectively, at contrast of -100 HU, using FBP as the reference. For most conditions of contrasts and dose levels, significant differences were found among the five algorithms, with the following relationship in both in-plane and cross-plane spatial resolution: FBP > DCNN-Weak > IR > DCNN-Medium > DCNN-Strong. The spatial resolution difference among algorithms decreases at higher contrast or dose levels. CONCLUSIONS: A patient-data-based virtual imaging trial framework was developed and applied to measuring the spatial resolution properties of a DCNN noise reduction method at different contrast and dose levels using real patient data. As with other non-linear image reconstruction and post-processing techniques, the evaluated DCNN method degraded the in-plane and z-axis spatial resolution at lower contrast levels, lower radiation dose, and higher denoising strength.

Scanner-specific validation of a CT simulator using a COPD-emulated anthropomorphic phantom.

Traditional methods of quantitative analysis of CT images typically involve working with patient data, which is often expensive and limited in terms of ground truth. To counter these restrictions, quantitative assessments can instead be made through Virtual Imaging Trials (VITs) which simulate the CT imaging process. This study sought to validate DukeSim (a scanner-specific CT simulator) utilizing clinically relevant biomarkers for a customized anthropomorphic chest phantom. The physical phantom was imaged utilizing two commercial CT scanners (Siemens Somatom Force and Definition Flash) with varying imaging parameters. A computational version of the phantom was simulated utilizing DukeSim for each corresponding real acquisition. Biomarkers were computed and compared between the real and virtually acquired CT images to assess the validity of DukeSim. The simulated images closely matched the real images both qualitatively and quantitatively, with the average biomarker percent difference of 3.84% (range 0.19% to 18.27%). Results showed that DukeSim is reasonably well validated across various patient imaging conditions and scanners, which indicates the utility of DukeSim for further VIT studies where real patient data may not be feasible.

Task-based validation and application of a scanner-specific CT simulator using an anthropomorphic phantom.

BACKGROUND: Quantitative analysis of computed tomography (CT) images traditionally utilizes real patient data that can pose challenges with replicability, efficiency, and radiation exposure. Instead, virtual imaging trials (VITs) can overcome these hurdles through computer simulations of models of patients and imaging systems. DukeSim is a scanner-specific CT imaging simulator that has previously been validated with simple cylindrical phantoms, but not with anthropomorphic conditions and clinically relevant measurements. PURPOSE: To validate a scanner-specific CT simulator (DukeSim) for the assessment of lung imaging biomarkers under clinically relevant conditions across multiple scanners using an anthropomorphic chest phantom, and to demonstrate the utility of virtual trials by studying the effects or radiation dose and reconstruction kernels on the lung imaging quantifications. METHODS: An anthropomorphic chest phantom with customized tube inserts was imaged with two commercial scanners (Siemens Force and Siemens Flash) at 28 dose and reconstruction conditions. A computational version of the chest phantom was used with a scanner-specific CT simulator (DukeSim) to simulate virtual images corresponding to the settings of the real acquisitions. Lung imaging biomarkers were computed from both real and simulated CT images and quantitatively compared across all imaging conditions. The VIT framework was further utilized to investigate the effects of radiation dose (20-300 mAs) and reconstruction settings (Qr32f, Qr40f, and Qr69f reconstruction kernels using ADMIRE strength 3) on the accuracy of lung imaging biomarkers, compared against the ground-truth values modeled in the computational chest phantom. RESULTS: The simulated CT images matched closely the real images for both scanners and all imaging conditions qualitatively and quantitatively, with the average biomarker percent error of 3.51% (range 0.002%-18.91%). The VIT study showed that sharper reconstruction kernels had lower accuracy with errors in mean lung HU of 84-94 HU, lung volume of 797-3785 cm3 , and lung mass of -800 to 1751 g. Lower tube currents had the lower accuracy with errors in mean lung HU of 6-84 HU, lung volume of 66-3785 cm3 , and lung mass of 170-1751 g. Other imaging biomarkers were consistent under the studied reconstruction settings and tube currents. CONCLUSION: We comprehensively evaluated the realism of DukeSim in an anthropomorphic setup across a diverse range of imaging conditions. This study paves the way toward utilizing VITs more reliably for conducting medical imaging experiments that are not practical using actual patient images.

Three-dimensional micro-structurally informed in silico myocardium-Towards virtual imaging trials in cardiac diffusion weighted MRI.

In silico tissue models (viz. numerical phantoms) provide a mechanism for evaluating quantitative models of magnetic resonance imaging. This includes the validation and sensitivity analysis of imaging biomarkers and tissue microstructure parameters. This study proposes a novel method to generate a realistic numerical phantom of myocardial microstructure. The proposed method extends previous studies by accounting for the variability of the cardiomyocyte shape, water exchange between the cardiomyocytes (intercalated discs), disorder class of myocardial microstructure, and four sheetlet orientations. In the first stage of the method, cardiomyocytes and sheetlets are generated by considering the shape variability and intercalated discs in cardiomyocyte-cardiomyocyte connections. Sheetlets are then aggregated and oriented in the directions of interest. The morphometric study demonstrates no significant difference (p>0.01) between the distribution of volume, length, and primary and secondary axes of the numerical and real (literature) cardiomyocyte data. Moreover, structural correlation analysis validates that the in-silico tissue is in the same class of disorderliness as the real tissue. Additionally, the absolute angle differences between the simulated helical angle (HA) and input HA (reference value) of the cardiomyocytes (4.3°±3.1°) demonstrate a good agreement with the absolute angle difference between the measured HA using experimental cardiac diffusion tensor imaging (cDTI) and histology (reference value) reported by (Holmes et al., 2000) (3.7°±6.4°) and (Scollan et al. 1998) (4.9°±14.6°). Furthermore, the angular distance between eigenvectors and sheetlet angles of the input and simulated cDTI is much smaller than those between measured angles using structural tensor imaging (as a gold standard) and experimental cDTI. Combined with the qualitative results, these results confirm that the proposed method can generate richer numerical phantoms for the myocardium than previous studies.

A scanner-specific framework for simulating CT images with tube current modulation.

Although tube current modulation (TCM) is routinely implemented in modern computed tomography (CT) scans, no existing CT simulator is capable of generating realistic images with TCM. The goal of this study was to develop such a framework to (1) facilitate patient-specific optimization of TCM parameters and (2) enable future virtual imaging trials (VITs) with more clinically realistic image quality and x-ray flux distributions. The framework was created by developing a TCM module and integrating it with an existing CT simulator (DukeSim). The developed module utilizes scanner-calibrated TCM parameters and two localizer radiographs to compute the mAs for each simulated CT projection. This simulation pipeline was validated in two parts. First, DukeSim was validated in the context of a commercial scanner with TCM (SOMATOM Force, Siemens Healthineers) by imaging a physical CT phantom (Mercury, Sun Nuclear) and its computational analogue. Second, the TCM module was validated by imaging a computational anthropomorphic phantom (ATOM, CIRS) using DukeSim with real and module-generated TCM profiles. The validation demonstrated DukeSim's realism in terms of noise magnitude, noise texture, spatial resolution, and image contrast (with average differences of 0.38%, 6.31%, 0.43%, and -9 HU, respectively). It also demonstrated the TCM module's realism in terms of projection-level mAs and resulting noise magnitude (2.86% and -2.60%, respectively). Finally, the framework was applied to a pilot VIT simulating images of three computational anthropomorphic phantoms (XCAT, with body mass indices (BMIs) of 24.3, 28.2, and 33.0) under five different TCM settings. The optimal TCM for each phantom was characterized based on various criteria, such as minimizing mAs or maximizing image quality. 'Very Weak' TCM minimized noise for the 24.3 BMI phantom, while 'Very Strong' TCM minimized noise for the 33.0 BMI phantom. This illustrates the utility of the developed framework for future optimization studies of TCM parameters and, more broadly, large-scale VITs with scanner-specific TCM.