Line-based iterative geometric calibration method for a tomosynthesis system.

BACKGROUND: A next generation tomosynthesis (NGT) system, capable of two-dimensional source motion, detector motion in the perpendicular direction, and magnification tomosynthesis, was constructed to investigate different acquisition geometries. Existing position-based geometric calibration methods proved ineffective when applied to the NGT geometries. PURPOSE: A line-based iterative calibration method is developed to perform accurate geometric calibration for the NGT system. METHODS: The proposed method calculates the system geometry through virtual line segments created by pairs of fiducials within a calibration phantom, by minimizing the error between the line equations computed from the true and estimated fiducial projection pairs. It further attempts to correct the 3D fiducial locations based on the initial geometric calibration. The method's performance was assessed via simulation and experimental setups with four distinct NGT geometries: X, T, XZ, and TZ. The X geometry resembles a conventional DBT acquisition along the chest wall. The T geometry forms a "T"-shaped source path in mediolateral (ML) and posteroanterior (PA) directions. A descending detector motion is added to both X and T geometries to form the XZ and TZ geometries, respectively. Simulation studies were conducted to assess the robustness of the method to geometric perturbations and inaccuracies in fiducial locations. Experimental studies were performed to assess the impact of phantom magnification and the performance of the proposed method for various geometries, compared to the traditional position-based method. Star patterns were evaluated for both qualitative and quantitative analyses; the Fourier spectral distortions (FSDs) graphs and the contrast transfer function (CTF) were extracted. The limit of spatial resolution (LSR) was measured at 5% modulation of the CTF. RESULTS: The proposed method presented is highly robust to geometric perturbation and fiducial inaccuracies. After the line-based iterative method, the mean distance between the true and estimated fiducial projections was [X, T, XZ, TZ]: [0.01, 0.01, 0.02, 0.01] mm. The impact of phantom magnification was observed; a contact-mode acquisition of a calibration phantom successfully provided an accurate geometry for 1.85× magnification images of a star pattern, with the X geometry. The FSD graphs for the contact-mode T geometry acquisition presented evidence of super-resolution, with the LSR of [0°-quadrant: 8.57, 90°-quadrant: 8.47] lp/mm. Finally, a contact-mode XZ geometry acquisition and a 1.50× magnification TZ geometry acquisition were reconstructed with three calibration methods-position-based, line-based, and iterative line-based. As more advanced methods are applied, the CTF becomes more isotropic, the FSD graphs demonstrate less spectral leakage as super-resolution is achieved, and the degree of blurring artifacts reduces significantly. CONCLUSIONS: This study introduces a robust calibration method tailored to the unique requirements of advanced tomosynthesis systems. By employing virtual line segments and iterative techniques, we ensure accurate geometric calibration while mitigating the limitations posed by the complex acquisition geometries of the NGT system. Our method's ability to handle various NGT configurations and its tolerance to fiducial misalignment make it a superior choice compared to traditional calibration techniques.

Non-Isocentric Geometry for Next-Generation Tomosynthesis With Super-Resolution.

Our lab at the University of Pennsylvania (UPenn) is investigating novel designs for digital breast tomosynthesis. We built a next-generation tomosynthesis system with a non-isocentric geometry (superior-to-inferior detector motion). This paper examines four metrics of image quality affected by this design. First, aliasing was analyzed in reconstructions prepared with smaller pixelation than the detector. Aliasing was assessed with a theoretical model of r -factor, a metric calculating amplitudes of alias signal relative to input signal in the Fourier transform of the reconstruction of a sinusoidal object. Aliasing was also assessed experimentally with a bar pattern (illustrating spatial variations in aliasing) and 360°-star pattern (illustrating directional anisotropies in aliasing). Second, the point spread function (PSF) was modeled in the direction perpendicular to the detector to assess out-of-plane blurring. Third, power spectra were analyzed in an anthropomorphic phantom developed by UPenn and manufactured by Computerized Imaging Reference Systems (CIRS), Inc. (Norfolk, VA). Finally, calcifications were analyzed in the CIRS Model 020 BR3D Breast Imaging Phantom in terms of signal-to-noise ratio (SNR); i.e., mean calcification signal relative to background-tissue noise. Image quality was generally superior in the non-isocentric geometry: Aliasing artifacts were suppressed in both theoretical and experimental reconstructions prepared with smaller pixelation than the detector. PSF width was also reduced at most positions. Anatomic noise was reduced. Finally, SNR in calcification detection was improved. (A potential trade-off of smaller-pixel reconstructions was reduced SNR; however, SNR was still improved by the detector-motion acquisition.) In conclusion, the non-isocentric geometry improved image quality in several ways.

Impact of super-resolution and image acquisition on the detection of calcifications in digital breast tomosynthesis.

OBJECTIVES: A virtual clinical trial (VCT) method is proposed to determine the limit of calcification detection in tomosynthesis. METHODS: Breast anatomy, focal findings, image acquisition, and interpretation (n = 14 readers) were simulated using screening data (n = 660 patients). Calcifications (0.2-0.4 mm3) were inserted into virtual breast phantoms. Digital breast tomosynthesis (DBT) acquisitions were simulated assuming various acquisition geometries: source motion (continuous and step-and-shoot), detector element size (140 and 70 µm), and reconstructed voxel size (35-140 µm). VCT results were estimated using multiple-reader multiple-case analyses and d' statistics. Signal-to-noise (SNR) analyses were also performed using BR3D phantoms. RESULTS: Source motion and reconstructed voxel size demonstrated significant changes in the performance of imaging systems. Acquisition geometries that use 70 µm reconstruction voxel size and step-and-shoot motion significantly improved calcification detection. Comparing 70 with 100 µm reconstructed voxel size for step-and-shoot, the ΔAUC was 0.0558 (0.0647) and d' ratio was 1.27 (1.29) for 140 µm (70 µm) detector element size. Comparing step-and-shoot with a continuous motion for a 70 µm reconstructed voxel size, the ΔAUC was 0.0863 (0.0434) and the d' ratio was 1.40 (1.19) for 140 µm (70 µm) detector element. Small detector element sizes (e.g., 70 µm) did not significantly improve detection. The SNR results with the BR3D phantom show that calcification detection is dependent upon reconstructed voxel size and detector element size, supporting VCT results with comparable agreement (ratios: d' = 1.16 ± 0.11, SNR = 1.34 ± 0.13). CONCLUSION: DBT acquisition geometries that use super-resolution (smaller reconstructed voxels than the detector element size) combined with step-and-shoot motion have the potential to improve the detection of calcifications. CLINICAL RELEVANCE: Calcifications may not always be discernable in tomosynthesis because of differences in acquisition and reconstruction methods. VCTs can identify strategies to optimize acquisition and reconstruction parameters for calcification detection in tomosynthesis, most notably through super-resolution in the reconstruction. KEY POINTS: • Super-resolution improves calcification detection and SNR in tomosynthesis; specifically, with the use of smaller reconstruction voxels. • Calcification detection using step-and-shoot motion is superior to that using continuous tube motion. • A detector element size of 70 µm does not provide better detection than 140 µm for small calcifications at the threshold of detectability.

Spatial dependency of multiplanar reconstruction in digital breast tomosynthesis.

Tomosynthesis acquires projections over a limited angular range, resulting in anisotropic sampling in the Fourier domain. The volume of the sampled space is therefore spatially dependent; different Fourier components are sampled for the same object, depending upon where the object is located relative to the system origin. A next-generation tomosynthesis (NGT) system was developed at the University of Pennsylvania to increase the spatial isotropy in DBT, by incorporating additional system motions. In this work, we investigate the spatial dependency of image quality in tomosynthesis and compare conventional and NGT tomosynthesis in terms of multiplanar reconstruction (MPR). Two test objects, a high-frequency star pattern and a low-frequency octagon phantom, were placed throughout the detector field of view at various obliquities to analyze the anisotropic nature of tomosynthesis. Reconstructions of the star pattern were analyzed both qualitatively and quantitatively using the Fourier distortion metric (FSD). Reconstructions of the octagon phantom were analyzed qualitatively. In a separate experiment, a container filled with water and acrylic beads of various diameters were imaged at various locations to simulate low-contrast objects mimicking breast tissue. We show that the spatial dependency of MPR is unique to the tilt angle, orientation, and frequency of the input. The NGT geometry benefitted the visualization of objects by reducing the out-of-plane artifacts in MPR.

Impact of Tomosynthesis Acquisition on 3D Segmentations of Breast Outline and Adipose/Dense Tissue with AI: A Simulation-Based Study.

Digital breast tomosynthesis (DBT) reconstructions introduce out-of-plane artifacts and false-tissue boundaries impacting the dense/adipose and breast outline (convex hull) segmentations. A virtual clinical trial method was proposed to segment both the breast tissues and the breast outline in DBT reconstructions. The DBT images of a representative population were simulated using three acquisition geometries: a left-right scan (conventional, I), a two-directional scan in the shape of a "T" (II), and an extra-wide range (XWR, III) left-right scan at a six-times higher dose than I. The nnU-Net was modified including two losses for segmentation: (1) tissues and (2) breast outline. The impact of loss (1) and the combination of loss (1) and (2) was evaluated using models trained with data simulating geometry I. The impact of the geometry was evaluated using the combined loss (1&2). The loss (1&2) improved the convex hull estimates, resolving 22.2% of the false classification of air voxels. Geometry II was superior to I and III, resolving 99.1% and 96.8% of the false classification of air voxels. Geometry III (Dice = (0.98, 0.94)) was superior to I (0.92, 0.78) and II (0.93, 0.74) for the tissue segmentation (adipose, dense, respectively). Thus, the loss (1&2) provided better segmentation, and geometries T and XWR improved the dense/adipose and breast outline segmentations relative to the conventional scan.

Multiclass Segmentation of Breast Tissue and Suspicious Findings: A Simulation-Based Study for the Development of Self-Steering Tomosynthesis.

In breast tomosynthesis, multiple low-dose projections are acquired in a single scanning direction over a limited angular range to produce cross-sectional planes through the breast for three-dimensional imaging interpretation. We built a next-generation tomosynthesis system capable of multidirectional source motion with the intent to customize scanning motions around "suspicious findings". Customized acquisitions can improve the image quality in areas that require increased scrutiny, such as breast cancers, architectural distortions, and dense clusters. In this paper, virtual clinical trial techniques were used to analyze whether a finding or area at high risk of masking cancers can be detected in a single low-dose projection and thus be used for motion planning. This represents a step towards customizing the subsequent low-dose projection acquisitions autonomously, guided by the first low-dose projection; we call this technique "self-steering tomosynthesis." A U-Net was used to classify the low-dose projections into "risk classes" in simulated breasts with soft-tissue lesions; class probabilities were modified using post hoc Dirichlet calibration (DC). DC improved the multiclass segmentation (Dice = 0.43 vs. 0.28 before DC) and significantly reduced false positives (FPs) from the class of the highest risk of masking (sensitivity = 81.3% at 2 FPs per image vs. 76.0%). This simulation-based study demonstrated the feasibility of identifying suspicious areas using a single low-dose projection for self-steering tomosynthesis.

Renally Excretable Silver Telluride Nanoparticles as Contrast Agents for X-ray Imaging.

The use of nanoparticles in the biomedical field has gained much attention due to their applications in biomedical imaging, drug delivery, and therapeutics. Silver telluride nanoparticles (Ag2Te NPs) have been recently shown to be highly effective computed tomography (CT) and dual-energy mammography contrast agents with good stability and biocompatibility, as well as to have potential for many other biomedical purposes. Despite their numerous advantageous properties for diagnosis and treatment of disease, the clinical translation of Ag2Te NPs is dependent on achieving high levels of excretion, a limitation for many nanoparticle types. In this work, we have synthesized and characterized a library of Ag2Te NPs and identified conditions that led to 3 nm core size and were renally excretable. We found that these nanoparticles have good biocompatibility, strong X-ray contrast generation, and rapid renal clearance. Our CT data suggest that renal elimination of nanoparticles occurred within 2 h of administration. Moreover, biodistribution data indicate that 93% of the injected dose (%ID) has been excreted from the main organs in 24 h, 95% ID in 7 days, and 97% ID in 28 days with no signs of acute toxicity in the tissues studied under histological analysis. To our knowledge, this renal clearance is the best reported for Ag2Te NP, while being comparable to the highest renal clearance reported for any type of nanoparticle. Together, the results herein presented suggest the use of GSH-Ag2Te NPs as an X-ray contrast agent with the potential to be clinically translated in the future.

MaasPenn Radiomics Reproducibility Score: A Novel Quantitative Measure for Evaluating the Reproducibility of CT-Based Handcrafted Radiomic Features.

The reproducibility of handcrafted radiomic features (HRFs) has been reported to be affected by variations in imaging parameters, which significantly affect the generalizability of developed signatures and translation to clinical practice. However, the collective effect of the variations in imaging parameters on the reproducibility of HRFs remains unclear, with no objective measure to assess it in the absence of reproducibility analysis. We assessed these effects of variations in a large number of scenarios and developed the first quantitative score to assess the reproducibility of CT-based HRFs without the need for phantom or reproducibility studies. We further assessed the potential of image resampling and ComBat harmonization for removing these effects. Our findings suggest a need for radiomics-specific harmonization methods. Our developed score should be considered as a first attempt to introduce comprehensive metrics to quantify the reproducibility of CT-based handcrafted radiomic features. More research is warranted to demonstrate its validity in clinical contexts and to further improve it, possibly by the incorporation of more realistic situations, which better reflect real patients' situations.

Achieving Isotropic Super-Resolution with a Non-Isocentric Acquisition Geometry in a Next-Generation Tomosynthesis System.

We have constructed a prototype next-generation tomosynthesis (NGT) system that supports a non-isocentric acquisition geometry for digital breast tomosynthesis (DBT). In this geometry, the detector gradually descends in the superior-to-inferior direction. The aim of this work is to demonstrate that this geometry offers isotropic super-resolution (SR), unlike clinical DBT systems which are characterized by anisotropies in SR. To this end, a theoretical model of a sinusoidal test object was developed with frequency exceeding the alias frequency of the detector. We simulated two geometries: (1) a conventional geometry with a stationary detector, and (2) a non-isocentric geometry. The input frequency was varied over the full 360° range of angles in the plane of the object. To investigate whether SR was achieved, we calculated the Fourier transform of the reconstruction. The amplitude of the tallest peak below the alias frequency was measured relative to the peak at the input frequency. This ratio (termed the r-factor) should approach zero to achieve high-quality SR. In the conventional geometry, the r-factor was minimized (approaching zero) if the orientation of the frequency was parallel with the source motion, yet exceeded unity (prohibiting SR) in the orientation perpendicular to the source motion. However, in the non-isocentric geometry, the r-factor was minimized (approaching zero) for all orientations of the frequency, meaning SR was achieved isotropically. In summary, isotropic SR in DBT can be achieved using the non-isocentric acquisition geometry supported by the NGT system.

Silver chalcogenide nanoparticles: a review of their biomedical applications.

Silver chalcogenide (Ag2X, where X = S, Se, or Te) nanoparticles have been extensively investigated for their applications in electronics but have only recently been explored for biomedical applications. In the past 10 years, Ag2X, primarily silver sulfides at first, have become of great importance as quantum dots, since they not only possess excellent deep tissue imaging properties in the near-infrared regions I and II, but also have low toxicities. Their appealing properties have led to numerous recent developments of Ag2X for biomedical applications. Furthermore, Ag2X have been discovered in the past 2-3 years to be potent X-ray contrast agents, adding to the numerous biomedical uses of these nanoparticles. In this review, we discuss the most recent advances in silver chalcogenide nanoparticle use in areas such as bio-imaging, theranostics, and biosensors. Moreover, we examine the advances in synthetic approaches for these nanoparticles, which include aqueous and organic syntheses routes. Finally, we discuss the advantages and current limitations in the use of silver chalcogenides for different biomedical applications and their potential for advancement and expansions in use.

Effect of Nanoparticle Synthetic Conditions on Ligand Coating Integrity and Subsequent Nano-Biointeractions.

Most current nanoparticle formulations have relatively low clearance efficiency, which may hamper their likelihood for clinical translation. Herein, we sought to compare the clearance and cellular distribution profiles between sub-5 nm, renally-excretable silver sulfide nanoparticles (Ag2S-NPs) synthesized via either a bulk, high temperature, or a microfluidic, room temperature approach. We found that the thermolysis approach led to significant ligand degradation, but the surface coating shell was unaffected by the microfluidic synthesis. We demonstrated that the clearance was improved for Ag2S-NPs with intact ligands, with less uptake in the liver. Moreover, differential distribution in hepatic cells was observed, where Ag2S-NPs with degraded coatings tend to accumulate in Kupffer cells and those with intact coatings are more frequently found in hepatocytes. Therefore, understanding the impact of synthetic processes on ligand integrity and subsequent nano-biointeractions will aid in designing nanoparticle platforms with enhanced clearance and desired distribution profiles.

Incorporating Robustness to Imaging Physics into Radiomic Feature Selection for Breast Cancer Risk Estimation.

Digital mammography has seen an explosion in the number of radiomic features used for risk-assessment modeling. However, having more features is not necessarily beneficial, as some features may be overly sensitive to imaging physics (contrast, noise, and image sharpness). To measure the effects of imaging physics, we analyzed the feature variation across imaging acquisition settings (kV, mAs) using an anthropomorphic phantom. We also analyzed the intra-woman variation (IWV), a measure of how much a feature varies between breasts with similar parenchymal patterns-a woman's left and right breasts. From 341 features, we identified "robust" features that minimized the effects of imaging physics and IWV. We also investigated whether robust features offered better case-control classification in an independent data set of 575 images, all with an overall BI-RADS® assessment of 1 (negative) or 2 (benign); 115 images (cases) were of women who developed cancer at least one year after that screening image, matched to 460 controls. We modeled cancer occurrence via logistic regression, using cross-validated area under the receiver-operating-characteristic curve (AUC) to measure model performance. Models using features from the most-robust quartile of features yielded an AUC = 0.59, versus 0.54 for the least-robust, with p < 0.005 for the difference among the quartiles.

Fully Automated Volumetric Breast Density Estimation from Digital Breast Tomosynthesis.

Background While digital breast tomosynthesis (DBT) is rapidly replacing digital mammography (DM) in breast cancer screening, the potential of DBT density measures for breast cancer risk assessment remains largely unexplored. Purpose To compare associations of breast density estimates from DBT and DM with breast cancer. Materials and Methods This retrospective case-control study used contralateral DM/DBT studies from women with unilateral breast cancer and age- and ethnicity-matched controls (September 19, 2011-January 6, 2015). Volumetric percent density (VPD%) was estimated from DBT using previously validated software. For comparison, the publicly available Laboratory for Individualized Breast Radiodensity Assessment software package, or LIBRA, was used to estimate area-based percent density (APD%) from raw and processed DM images. The commercial Quantra and Volpara software packages were applied to raw DM images to estimate VPD% with use of physics-based models. Density measures were compared by using Spearman correlation coefficients (r), and conditional logistic regression was performed to examine density associations (odds ratios [OR]) with breast cancer, adjusting for age and body mass index. Results A total of 132 women diagnosed with breast cancer (mean age ± standard deviation [SD], 60 years ± 11) and 528 controls (mean age, 60 years ± 11) were included. Moderate correlations between DBT and DM density measures (r = 0.32-0.75; all P < .001) were observed. Volumetric density estimates calculated from DBT (OR, 2.3 [95% CI: 1.6, 3.4] per SD for VPD%DBT) were more strongly associated with breast cancer than DM-derived density for both APD% (OR, 1.3 [95% CI: 0.9, 1.9] [P < .001] and 1.7 [95% CI: 1.2, 2.3] [P = .004] per SD for LIBRA raw and processed data, respectively) and VPD% (OR, 1.6 [95% CI: 1.1, 2.4] [P = .01] and 1.7 [95% CI: 1.2, 2.6] [P = .04] per SD for Volpara and Quantra, respectively). Conclusion The associations between quantitative breast density estimates and breast cancer risk are stronger for digital breast tomosynthesis compared with digital mammography. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Yaffe in this issue.

Quantitative analysis of speckle-based X-ray dark-field imaging using numerical wave-optics simulations.

The dark-field signal measures the small-angle scattering strength and provides complementary diagnostic information. This is of particular interest for lung imaging due to the pronounced small-angle scatter from the alveolar microstructure. However, most dark-field imaging techniques are relatively complex, dose-inefficient, and require sophisticated optics and highly coherent X-ray sources. Speckle-based imaging promises to overcome these limitations due to its simple and versatile setup, only requiring the addition of a random phase modulator to conventional X-ray equipment. We investigated quantitatively the influence of sample structure, setup geometry, and source energy on the dark-field signal in speckle-based X-ray imaging with wave-optics simulations for ensembles of micro-spheres. We show that the dark-field signal is accurately predicted via a model originally derived for grating interferometry when using the mean frequency of the speckle pattern power spectral density as the characteristic speckle size. The size directly reflects the correlation length of the diffuser surface and did not change with energy or propagation distance within the near-field. The dark-field signal had a distinct dependence on sample structure and setup geometry but was also affected by beam hardening-induced modifications of the visibility spectrum. This study quantitatively demonstrates the behavior of the dark-field signal in speckle-based X-ray imaging.

Reply to Orlhac, F.; Buvat, I. Comment on "Ibrahim et al. The Effects of In-Plane Spatial Resolution on CT-Based Radiomic Features' Stability with and without ComBat Harmonization. Cancers 2021, 13, 1848".

We would like to thank Orlhac and Buvat [...].

VIRTUAL CLINICAL TRIALS IN MEDICAL IMAGING SYSTEM EVALUATION AND OPTIMISATION.

Virtual clinical trials (VCTs) can be used to evaluate and optimise medical imaging systems. VCTs are based on computer simulations of human anatomy, imaging modalities and image interpretation. OpenVCT is an open-source framework for conducting VCTs of medical imaging, with a particular focus on breast imaging. The aim of this paper was to evaluate the OpenVCT framework in two tasks involving digital breast tomosynthesis (DBT). First, VCTs were used to perform a detailed comparison of virtual and clinical reading studies for the detection of lesions in digital mammography and DBT. Then, the framework was expanded to include mechanical imaging (MI) and was used to optimise the novel combination of simultaneous DBT and MI. The first experiments showed close agreement between the clinical and the virtual study, confirming that VCTs can predict changes in performance of DBT accurately. Work in simultaneous DBT and MI system has demonstrated that the system can be optimised in terms of the DBT image quality. We are currently working to expand the OpenVCT software to simulate MI acquisition more accurately and to include models of tumour growth. Based on our experience to date, we envision a future in which VCTs have an important role in medical imaging, including support for more imaging modalities, use with rare diseases and a role in training and testing artificial intelligence (AI) systems.

Computational Breast Anatomy Simulation Using Multi-Scale Perlin Noise.

Virtual clinical trials (VCTs) of medical imaging require realistic models of human anatomy. For VCTs in breast imaging, a multi-scale Perlin noise method is proposed to simulate anatomical structures of breast tissue in the context of an ongoing breast phantom development effort. Four Perlin noise distributions were used to replace voxels representing the tissue compartments and Cooper's ligaments in the breast phantoms. Digital mammography and tomosynthesis projections were simulated using a clinical DBT system configuration. Power-spectrum analyses and higher-order statistics properties using Laplacian fractional entropy (LFE) of the parenchymal texture are presented. These objective measures were calculated in phantom and patient images using a sample of 140 clinical mammograms and 500 phantom images. Power-law exponents were calculated using the slope of the curve fitted in the low frequency [0.1, 1.0] mm-1 region of the power spectrum. The results show that the images simulated with our prior and proposed Perlin method have similar power-law spectra when compared with clinical mammograms. The power-law exponents calculated are -3.10, -3.55, and -3.46, for the log-power spectra of patient, prior phantom and proposed phantom images, respectively. The results also indicate an improved agreement between the mean LFE estimates of Perlin-noise based phantoms and patients than our prior phantoms and patients. Thus, the proposed method improved the simulation of anatomic noise substantially compared to our prior method, showing close agreement with breast parenchyma measures.

The application of a workflow integrating the variable reproducibility and harmonizability of radiomic features on a phantom dataset.

Radiomics-the high throughput extraction of quantitative features from medical images and their correlation with clinical and biological endpoints- is the subject of active and extensive research. Although the field shows promise, the generalizability of radiomic signatures is affected significantly by differences in scan acquisition and reconstruction settings. Previous studies reported on the sensitivity of radiomic features (RFs) to test-retest variability, inter-observer segmentation variability, and intra-scanner variability. A framework involving robust radiomics analysis and the application of a post-reconstruction feature harmonization method using ComBat was recently proposed to address these challenges. In this study, we investigated the reproducibility of RFs across different scanners and scanning parameters using this framework. We analysed thirteen scans of a ten-layer phantom that were acquired differently. Each layer was subdivided into sixteen regions of interest (ROIs), and the scans were compared in a pairwise manner, resulting in seventy-eight different scenarios. Ninety-one RFs were extracted from each ROI. As hypothesized, we demonstrate that the reproducibility of a given RF is not a constant but is dependent on the heterogeneity found in the data under analysis. The number (%) of reproducible RFs varied across the pairwise scenarios investigated, having a wide range between 8 (8.8%) and 78 (85.7%) RFs. Furthermore, in contrast to what has been previously reported, and as hypothesized in the robust radiomics analysis framework, our results demonstrate that ComBat cannot be applied to all RFs but rather on a percentage of those-the "ComBatable" RFs-which differed depending on the data being harmonized. The number (%) of reproducible RFs following ComBat harmonization varied across the pairwise scenarios investigated, ranging from 14 (15.4%) to 80 (87.9%) RFs, and was found to depend on the heterogeneity in the data. We conclude that the standardization of image acquisition protocols remains the cornerstone for improving the reproducibility of RFs, and the generalizability of the signatures developed. Our proposed approach helps identify the reproducible RFs across different datasets.

The Effects of In-Plane Spatial Resolution on CT-Based Radiomic Features' Stability with and without ComBat Harmonization.

While handcrafted radiomic features (HRFs) have shown promise in the field of personalized medicine, many hurdles hinder its incorporation into clinical practice, including but not limited to their sensitivity to differences in acquisition and reconstruction parameters. In this study, we evaluated the effects of differences in in-plane spatial resolution (IPR) on HRFs, using a phantom dataset (n = 14) acquired on two scanner models. Furthermore, we assessed the effects of interpolation methods (IMs), the choice of a new unified in-plane resolution (NUIR), and ComBat harmonization on the reproducibility of HRFs. The reproducibility of HRFs was significantly affected by variations in IPR, with pairwise concordant HRFs, as measured by the concordance correlation coefficient (CCC), ranging from 42% to 95%. The number of concordant HRFs (CCC > 0.9) after resampling varied depending on (i) the scanner model, (ii) the IM, and (iii) the NUIR. The number of concordant HRFs after ComBat harmonization depended on the variations between the batches harmonized. The majority of IMs resulted in a higher number of concordant HRFs compared to ComBat harmonization, and the combination of IMs and ComBat harmonization did not yield a significant benefit. Our developed framework can be used to assess the reproducibility and harmonizability of RFs.