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 endinspiration 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 photoncounting 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 7.519 % 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.
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 to 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.
KEYWORDS: Lung, Data modeling, Computed tomography, Scanners, 3D modeling, Computer simulations, Modulation transfer functions, Chest imaging, Medicine, Medical research
Virtual Imaging Trials, known as VITs, provide a computational substitute for clinical trials. These traditional trials tend to be sluggish, costly, and frequently deficient in definitive evidence, all the while subjecting participants to ionizing radiation. Our VIT platform meticulously mimics essential components of the imaging process, encompassing everything from virtual patients and scanners to simulated readers. Within the scope of this intended research, we aim to authenticate our virtual imaging trial platform by duplicating the results of the National Lung Screening Trial (NLST) for lung cancer screening through the emulation of low-dose computed tomography (CT) and chest radiography (CXR) procedures. The methodology involves creating 66 unique computational phantoms, each with inserted simulated lung nodules. Replicating NLST CT imaging via Duke Legacy W20 scanner matched essential properties. Virtual imaging was done through DukeSim. A LUNA16-trained virtual reader, combining a 3D RetinaNet model (front-end) with a ResNet-10 false positive reduction model (back-end), evaluated the virtually imaged data, ensuring rigorous assessment. The back-end model achieved a sensitivity of over 95% at fewer than 3 false positives per scan for both the clinical and virtual imaged CTs. Notably, nodule diameter-based analysis showcases even higher sensitivity for nodules measuring 10 mm or more. In conclusion, the integration of diverse computational and imaging techniques, culminating in a virtual reader, demonstrates promising sensitivity. To capture both arms of the trial, future research will compare virtual reader performance on CT with CXR. This affirms the transformative potential of virtual imaging trials in advancing evidence-based medicine, offering an efficient and ethically conscious approach to medical research and development.
Chronic obstructive pulmonary disease (COPD) is one of the top three causes of death worldwide, characterized by emphysema and bronchitis. Airway measurements reflect the severity of bronchitis and other airway-related diseases. Airway structures can be objectively evaluated with quantitative computed tomography (CT). The accuracy of such quantifications is limited by the spatial resolution and image noise characteristics of the imaging system and can be potentially improved with the emerging photon-counting CT (PCCT) technology. This study evaluated the quantitative performance of PCCT against energy-integrating CT (EICT) systems for airway measurements, and further identified optimum CT imaging parameters for such quantifications. The study was performed using a novel virtual imaging framework by developing the first library of virtual patients with bronchitis. These virtual patients were developed based on CT images of confirmed COPD patients with varied bronchitis severity. The human models were virtually imaged at 6.3 and 12.6 mGy dose levels using a scanner-specific simulator (DukeSim), synthesizing clinical PCCT and EICT scanners (NAEOTOM Alpha, FLASH, Siemens). The projections were reconstructed with two algorithms and kernels at different matrix sizes and slice thicknesses. The CT images were used to quantify clinically relevant airway measurements (“Pi10” and “WA%”) and compared against their ground truth values. Compared to EICT, PCCT provided more accurate Pi10 and WA% measurements by 63.1% and 68.2%, respectively. For both technologies, sharper kernels and larger matrix sizes led to more reliable bronchitis quantifications. This study highlights the potential advantages of PCCT against EICT in characterizing bronchitis utilizing a virtual imaging platform.
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