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.

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.

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.

Optimized signal of calcifications in wide-angle digital breast tomosynthesis: a virtual imaging trial.

OBJECTIVES: Evaluate microcalcification detectability in digital breast tomosynthesis (DBT) and synthetic 2D mammography (SM) for different acquisition setups using a virtual imaging trial (VIT) approach. MATERIALS AND METHODS: Medio-lateral oblique (MLO) DBT acquisitions on eight patients were performed at twice the automatic exposure controlled (AEC) dose. The noise was added to the projections to simulate a given dose trajectory. Virtual microcalcification models were added to a given projection set using an in-house VIT framework. Three setups were evaluated: (1) standard acquisition with 25 projections at AEC dose, (2) 25 projections with a convex dose distribution, and (3) sparse setup with 13 projections, every second one over the angular range. The total scan dose and angular range remained constant. DBT volume reconstruction and synthetic mammography image generation were performed using a Siemens prototype algorithm. Lesion detectability was assessed through a Jackknife-alternative free-response receiver operating characteristic (JAFROC) study with six observers. RESULTS: For DBT, the area under the curve (AUC) was 0.97 ± 0.01 for the standard, 0.95 ± 0.02 for the convex, and 0.89 ± 0.03 for the sparse setup. There was no significant difference between standard and convex dose distributions (p = 0.309). Sparse projections significantly reduced detectability (p = 0.001). Synthetic images had a higher AUC with the convex setup, though not significantly (p = 0.435). DBT required four times more reading time than synthetic mammography. DISCUSSION: A convex setup did not significantly improve detectability in DBT compared to the standard setup. Synthetic images exhibited a non-significant increase in detectability with the convex setup. Sparse setup significantly reduced detectability in both DBT and synthetic mammography. CLINICAL RELEVANCE STATEMENT: This virtual imaging trial study allowed the design and efficient testing of different dose distribution trajectories with real mammography images, using a dose-neutral protocol. KEY POINTS: • In DBT, a convex dose distribution did not increase the detectability of microcalcifications compared to the current standard setup but increased detectability for the SM images. • A sparse setup decreased microcalcification detectability in both DBT and SM images compared to the convex and current clinical setups. • Optimal microcalcification cluster detection in the system studied was achieved using either the standard or convex dose setting, with the default number of projections.

Technical note: Realization and uncertainty analysis for an adjustable 3D structured breast phantom in digital breast tomosynthesis.

BACKGROUND: Projection imaging phantoms are often optimized for 2-dimensional image characteristics in homogeneous backgrounds. Therefore, evaluation of image quality in tomosynthesis (DBT) lacks accepted and established phantoms. PURPOSE: We describe a 3D breast phantom with a structured, variable background. The phantom is an adaptable and advanced version of the L1 phantom by Cockmartin et al. Phantom design and its use for quality assurance measurements for DBT devices are described. Four phantoms were compared to assess the objectivity. METHODS: The container size was increased to a diameter of 24 cm and a total height of 53.5 mm. Spiculated masses were replaced by five additional non-spiculated masses for higher granularity in threshold diameter resolution. These patterns are adjustable to the imaging device. The masses were printed in one session with a base layer using two-component 3D printing. New materials compared to the L1 phantom improved the attenuation difference between the lesion models and the background. Four phantoms were built and intra-human observer, inter-human observer and inter-phantom variations were determined. The latter assess the reproducibility of the phantom production. Coefficients of variance (V) were calculated for all three variations. RESULTS: The difference of the attenuation coefficients between the lesion models and the background was 0.20 cm-1 (with W/Al at 32 kV, equivalent to 19-20 keV effective energy) compared to 0.21 cm-1 for 50/50 glandular/adipose breast tissue and cancerous lesions. PMMA equivalent thickness of the phantom was 47.0 mm for the Siemens Mammomat Revelation. For the masses, the V i n t r a $V_{intra}$ for the intra-observer variation was 0.248, the averaged inter-observer variation, V ¯ i n t e r $\overline{V}_{inter}$ was 0.383. V p h a n t o m $V_{phantom}$ for phantom variance was 0.321. For the micro-calcifications, V i n t r a $V_{intra}$ was 0.0429, V ¯ i n t e r = $\overline{V}_{inter}=$ 0.0731 and V p h a n t o m = $V_{phantom}=$ 0.0759. CONCLUSIONS: Position, orientation and shape of the masses are reproducible and attenuation differences appropriate. The phantom presented proved to be a candidate test object for quality control.

The impact on lesion detection via a multi-vendor study: A phantom-based comparison of digital mammography, digital breast tomosynthesis, and synthetic mammography.

PURPOSE: The aim of this study is to perform a test object-based comparison of the imaging performance of digital mammography (DM), digital breast tomosynthesis (DBT), and synthetic mammography (SM). METHODS: Two test objects were used, the CDMAM and the L1-structured phantom. Small-detail detectability was assessed using CDMAM and the microcalcification simulating specks in the L1-structured background. Detection of spiculated and non-spiculated mass-like objects was assessed using the L1 phantom. Six different systems were included: Amulet Innovality (Fujifilm), Senographe Pristina (GEHC), 3Dimensions (Hologic), Giotto Class (IMS), Clarity 2D/3D (Planmed), and Mammomat Revelation (Siemens). Images were acquired under automatic exposure control (AEC) and at adjusted levels of AEC/2 and 2 × AEC level. Threshold gold thickness (Ttr ) was established for the 0.13-mm-diameter CDMAM discs. Threshold diameters for the calcifications (dtr_c ), the spiculated masses (dtr_sm ), and for the non-spiculated masses (dtr_nsm ) were established. The threshold condition was defined as the thickness or diameter for a 62.5% correct score. RESULTS: Ttr for DM was generally superior to DBT, which in turn was superior to SM, but for most systems, these differences between modes were not significant. For L1, no significant differences in dtr_c were found between DM and DBT. The increase in dtr_c from DM to SM at AEC dose was 1%, 19%, 11%, 14%, 46%, and 27% for the Fujifilm, GEHC, Hologic, IMS, Planmed, and Siemens, respectively, indicating significantly poorer performance for all vendors except for Fujifilm, Hologic, and IMS. For both mass types, DBT performed better than SM, while SM showed no significant difference with DM (except for Fujifilm spiculated masses). The dose had an impact on small-detail detectability for both phantoms but did not influence the detection of either mass type. CONCLUSIONS: Both phantoms indicated potentially reduced small-detail detectability for SM versus DM and DBT and should therefore not be used in stand-alone mode. The L1 phantom demonstrated no significant difference in microcalcification detection between DM and DBT and also demonstrated the superiority of DBT, compared to DM for mass detection, for all six systems.

On the relevance of modulation transfer function measurements in digital mammography quality control.

Purpose: The relevance of presampling modulation transfer function (MTF) measurements in digital mammography (DM) quality control (QC) is examined. Two studies are presented: a case study on the impact of a reduction in MTF on the technical image quality score and analysis of the robustness of routine QC MTF measurements. Approach: In the first study, two needle computed radiography (CR) plates with identical sensitivities were used with differences in the 50% point of the MTF ( f MTF 0.5 ) larger than the limiting value in the European guidelines ( > 10 % change between successive measurements). Technical image quality was assessed via threshold gold thickness of the CDMAM phantom and threshold microcalcification diameter of the L1 structured phantom. For the second study, presampling MTF results from 595 half-yearly QC tests of 55 DM systems (16 types, six manufacturers) were analyzed for changes from the baseline value and changes in f MTF 0.5 between successive tests. Results: A reduction of 20% in f MTF 0.5 of the two CR plates was observed. There was a tendency to a lower score for task-based metrics, but none were significant. Averaging over 55 systems, the absolute relative change in f MTF 0.5 between consecutive tests (with 95% confidence interval) was 3% (2.5% to 3.4%). Analysis of the maximum relative change from baseline revealed changes of up to - 10 % for one a-Se based system and - 15 % for a group of CsI-based systems. Conclusions: A limit of 10% is a relevant action level for investigation. If exceeded, then the impact on performance has to be verified with extra metrics.

Verification of the accuracy of a hybrid breast imaging simulation framework for virtual clinical trial applications.

Purpose: The impact of system parameters on signal detectability can be studied with simulation platforms. We describe the steps taken to verify and confirm the accuracy of a local platform developed for the use in virtual clinical trials. Approach: The platform simulates specific targets into existing two-dimensional full-field digital mammography and digital breast tomosynthesis images acquired on a Siemens Inspiration system. There are three steps: (1) creation of voxel models or analytical objects; (2) generation of a realistic object template with accurate resolution, scatter, and noise properties; and (3) insertion and reconstruction. Four objects were simulated: a 0.5-mm aluminium (Al) sphere and a 0.2-mm-thick Al sheet in a PMMA stack, a 0.8-mm steel edge and a three-dimensional mass model in a structured background phantom. Simulated results were compared to acquired data. Results: Peak contrast and signal difference-to-noise ratio (SDNR) were in close agreement ( < 5 % error) for both sphere and sheet. The similarity of pixel value profiles for sphere and sheet in the x y direction and the artifact spread function for real and simulated spheres confirmed accurate geometric modeling. Absolute and relative average deviation between modulation transfer function measured from a real and simulated edges showed accurate sharpness modelling for spatial frequencies up to the Nyquist frequency. Real and simulated objects could not be differentiated visually. Conclusions: The results indicate that this simulation framework is a strong candidate for use in virtual clinical studies.

Erratum: verification of the accuracy of a hybrid breast imaging simulation framework for virtual clinical trial applications.

[This corrects the article DOI: 10.1117/1.JMI.7.4.042804.].