Marthony Robins

Volumetric quantification of lung nodules in CT with iterative reconstruction (ASiR and MBIR)

PURPOSE Volume quantifications of lung nodules with multidetector computed tomography (CT) images provide useful information for monitoring nodule developments. The accuracy and precision of the volume quantification, however, can be impacted by imaging and reconstruction parameters. This study aimed to investigate the impact of iterative reconstruction algorithms on the accuracy and precision of volume quantification with dose and slice thickness as additional variables. METHODS Repeated CT images were acquired from an anthropomorphic chest phantom with synthetic nodules (9.5 and 4.8 mm) at six dose levels, and reconstructed with three reconstruction algorithms [filtered backprojection (FBP), adaptive statistical iterative reconstruction (ASiR), and model based iterative reconstruction (MBIR)] into three slice thicknesses. The nodule volumes were measured with two clinical software (A: Lung VCAR, B: iNtuition), and analyzed for accuracy and precision. RESULTS Precision was found to be generally comparable between FBP and iterative reconstruction with no statistically significant difference noted for different dose levels, slice thickness, and segmentation software. Accuracy was found to be more variable. For large nodules, the accuracy was significantly different between ASiR and FBP for all slice thicknesses with both software, and significantly different between MBIR and FBP for 0.625 mm slice thickness with Software A and for all slice thicknesses with Software B. For small nodules, the accuracy was more similar between FBP and iterative reconstruction, with the exception of ASIR vs FBP at 1.25 mm with Software A and MBIR vs FBP at 0.625 mm with Software A. CONCLUSIONS The systematic difference between the accuracy of FBP and iterative reconstructions highlights the importance of extending current segmentation software to accommodate the image characteristics of iterative reconstructions. In addition, a calibration process may help reduce the dependency of accuracy on reconstruction algorithms, such that volumes quantified from scans of different reconstruction algorithms can be compared. The little difference found between the precision of FBP and iterative reconstructions could be a result of both iterative reconstructions diminished noise reduction at the edge of the nodules as well as the loss of resolution at high noise levels with iterative reconstruction. The findings do not rule out potential advantage of IR that might be evident in a study that uses a larger number of nodules or repeated scans.

Techniques for virtual lung nodule insertion: volumetric and morphometric comparison of projection-based and image-based methods for quantitative CT

Virtual nodule insertion paves the way towards the development of standardized databases of hybrid CT images with known lesions. The purpose of this study was to assess three methods (an established and two newly developed techniques) for inserting virtual lung nodules into CT images. Assessment was done by comparing virtual nodule volume and shape to the CT-derived volume and shape of synthetic nodules. 24 synthetic nodules (three sizes, four morphologies, two repeats) were physically inserted into the lung cavity of an anthropomorphic chest phantom (KYOTO KAGAKU). The phantom was imaged with and without nodules on a commercial CT scanner (SOMATOM Definition Flash, Siemens) using a standard thoracic CT protocol at two dose levels (1.4 and 22 mGy CTDIvol). Raw projection data were saved and reconstructed with filtered back-projection and sinogram affirmed iterative reconstruction (SAFIRE, strength 5) at 0.6 mm slice thickness. Corresponding 3D idealized, virtual nodule models were co-registered with the CT images to determine each nodules location and orientation. Virtual nodules were voxelized, partial volume corrected, and inserted into nodule-free CT data (accounting for system imaging physics) using two methods: projection-based Technique A, and image-based Technique B. Also a third Technique C based on cropping a region of interest from the acquired image of the real nodule and blending it into the nodule-free image was tested. Nodule volumes were measured using a commercial segmentation tool (iNtuition, TeraRecon, Inc.) and deformation was assessed using the Hausdorff distance. Nodule volumes and deformations were compared between the idealized, CT-derived and virtual nodules using a linear mixed effects regression model which utilized the mean, standard deviation, and coefficient of variation ([Formula: see text], [Formula: see text] and [Formula: see text] of the regional Hausdorff distance. Overall, there was a close concordance between the volumes of the CT-derived and virtual nodules. Percent differences between them were less than 3% for all insertion techniques and were not statistically significant in most cases. Correlation coefficient values were greater than 0.97. The deformation according to the Hausdorff distance was also similar between the CT-derived and virtual nodules with minimal statistical significance in the ([Formula: see text]) for Techniques A, B, and C. This study shows that both projection-based and image-based nodule insertion techniques yield realistic nodule renderings with statistical similarity to the synthetic nodules with respect to nodule volume and deformation. These techniques could be used to create a database of hybrid CT images containing nodules of known size, location and morphology.

Inter-algorithm lesion volumetry comparison of real and 3D simulated lung lesions in CT

The purpose of this study was to establish volumetric exchangeability between real and computational lung lesions in CT. We compared the overall relative volume estimation performance of segmentation tools when used to measure real lesions in actual patient CT images and computational lesions virtually inserted into the same patient images (i.e., hybrid datasets). Pathologically confirmed malignancies from 30 thoracic patient cases from Reference Image Database to Evaluate Therapy Response (RIDER) were modeled and used as the basis for the comparison. Lesions included isolated nodules as well as those attached to the pleura or other lung structures. Patient images were acquired using a 16 detector row or 64 detector row CT scanner (Lightspeed 16 or VCT; GE Healthcare). Scans were acquired using standard chest protocols during a single breath-hold. Virtual 3D lesion models based on real lesions were developed in Duke Lesion Tool (Duke University), and inserted using a validated image-domain insertion program. Nodule volumes were estimated using multiple commercial segmentation tools (iNtuition, TeraRecon, Inc., Syngo.via, Siemens Healthcare, and IntelliSpace, Philips Healthcare). Consensus based volume comparison showed consistent trends in volume measurement between real and virtual lesions across all software. The average percent bias (± standard error) shows -9.2±3.2% for real lesions versus -6.7±1.2% for virtual lesions with tool A, 3.9±2.5% and 5.0±0.9% for tool B, and 5.3±2.3% and 1.8±0.8% for tool C, respectively. Virtual lesion volumes were statistically similar to those of real lesions (< 4% difference) with p >.05 in most cases. Results suggest that hybrid datasets had similar inter-algorithm variability compared to real datasets.

Development and comparison of projection and image space 3D nodule insertion techniques

This study aimed to develop and compare two methods of inserting computerized virtual lesions into CT datasets. 24 physical (synthetic) nodules of three sizes and four morphologies were inserted into an anthropomorphic chest phantom (LUNGMAN, KYOTO KAGAKU). The phantom was scanned (Somatom Definition Flash, Siemens Healthcare) with and without nodules present, and images were reconstructed with filtered back projection and iterative reconstruction (SAFIRE) at 0.6 mm slice thickness using a standard thoracic CT protocol at multiple dose settings. Virtual 3D CAD models based on the physical nodules were virtually inserted (accounting for the system MTF) into the nodule-free CT data using two techniques. These techniques include projection-based and image-based insertion. Nodule volumes were estimated using a commercial segmentation tool (iNtuition, TeraRecon, Inc.). Differences were tested using paired t-tests and R2 goodness of fit between the virtually and physically inserted nodules. Both insertion techniques resulted in nodule volumes very similar to the real nodules (<3% difference) and in most cases the differences were not statistically significant. Also, R2 values were all <0.97 for both insertion techniques. These data imply that these techniques can confidently be used as a means of inserting virtual nodules in CT datasets. These techniques can be instrumental in building hybrid CT datasets composed of patient images with virtually inserted nodules.

Can a 3D task transfer function accurately represent the signal transfer properties of low-contrast lesions in non-linear CT systems?

The purpose of this study was to investigate how accurately the task-transfer function (TTF) models the signal transfer properties of low-contrast features in a non-linear CT system. A cylindrical phantom containing 24 anthropomorphic liver lesions (modeled from patient lesions) was designed using computer-aided design software (Rhinoceros 3D). Lesions had irregular shapes, 2 sizes (523, 2145 mm3), and 2 contrast levels (80, 100 HU). The phantom was printed with a state-of-the-art multimaterial 3D printer (Stratasys J750). CT images were acquired on a clinical CT scanner (Siemens Flash) at 4 dose levels (CTDIVol, 32 cm phantom: 1.5, 3, 6, 22 mGy) and reconstructed using 2 FBP kernels (B31f, B45f) and 2 iterative kernels (SAFIRE, strength-2: I31f, and I44f). 3D-TTFs were estimated by combining TTFs measured using low-contrast rod inserts (in-plane) and a slanted edge (z-direction) printed in-phantom. CAD versions of lesions were blurred by 3D-TTFs and virtually superimposed into corresponding phantom images using a previously validated technique. We compared lesion morphometry (i.e., size and shape) measurements between 3D printed “physical” and TTF-blurred “simulated” lesions across multiple acquisitions. Lesion size was quantified using a commercial segmentation software (Syngo.via). Lesion shape was quantified by measuring the Jaccard index between the segmented masks of paired physical and simulated lesions. The relative volume difference D between physical and simulated lesions was mostly less than the natural variability COV of the physical lesions. For large and small lesions, the COV1,𝑘,𝑙 was greater or similar to D𝑘,𝑙 in 12 and 13 out of 16 imaging scenarios, respectively. Simulated and physical lesion shapes were similar, with an average simulated-physical Jaccard index of 0.70 (out of max value of unity). These results suggest 3D-TTFs closely models the signal transfer properties of linear and non-linear CT conditions for low-contrast objects.

How reliable are texture measurements

The purpose of this study was to assess the bias (objectivity) and variability (robustness) of computed tomography (CT) texture features (internal heterogeneities) across a series of image acquisition settings and reconstruction algorithms. We simulated a series of CT images using a computational phantom with anatomically-informed texture. 288 clinically-relevant simulation conditions were generated representing three slice thicknesses (0.625, 1.25, 2.5 mm), four in-plane pixel sizes (0.4, 0.5, 0.7, 0.9 mm), three dose levels (CTDIvol = 1.90, 3.75, 7.50 mGy), and 8 reconstruction kernels. Each texture feature was sampled with 4 unique volumes of interest (VOIs) (244, 1953, 15625, 125000 mm3). Twenty-one statistical texture features were calculated and compared between the ground truth phantom (i.e., pre-imaging) and its corresponding post-imaging simulations. Metrics of comparison included (1) the percent relative difference (PRD) between the post-imaging simulation and the ground truth, and (2) the coefficient of variation (%COV) across simulated instances of texture features. The PRD and %COV ranged from -100% to 4500%, and 0.8% to 49%, respectively. PRD decreased with increased slice thickness, in-plane pixel size, and dose. The dynamic range of results indicate that image acquisition and reconstruction conditions (i.e., slice thicknesses, in-plane pixel sizes, dose levels, and reconstruction kernels) can lead to significant bias and variability in texture feature measurements.

Bias and variability in morphology features of lung lesions across CT imaging conditions

CT imaging method can influence radiomic features. The purpose of this study was to characterize the intra-protocol and inter-protocol variability and bias of quantitative morphology features of lung lesions across a range of CT imaging conditions. A total of 15 lung lesions were simulated (five in each of three spiculation classes: low, medium, and high). For each lesion, a series of simulated CT images representing different imaging conditions were synthesized by applying 3D blur and adding correlated noise based on the measured noise and resolution properties of five commercial multi-slice CT systems, representing three dose levels (CTDIvol of 1.90, 3.75, 7.50 mGy), three slice thicknesses (0.625, 1.25, 2.5 mm), and 33 clinical reconstruction kernels. Five repeated image volumes were synthesized for each lesion and imaging condition. A series of 21 shape-based morphology features were extracted from both “ground truth” (i.e., pre-blur without noise) and “image rendered” lesions (i.e., post-blur and with noise). For each morphology feature, the intra-protocol and inter-protocol variability was characterized by calculating the average coefficient of variation (COV) across repeats and imaging conditions, respectively (average was across all lesions). The bias was quantified by comparing the percent relative error in the morphology metric between the imaged lesions and ground truth lesions. The average intra-protocol COV metric ranged from 0.2% to 3%. The average inter-protocol COV ranged from 3% to 106% with most features being around 30%. Percent relative error was most biased at 73% for Ellipsoid Volume and least biased at -0.27% for Flatness. Results of the study indicate that different reconstructions can lead to significant bias and variability in the measurements of morphological features.

Evaluation of Simulated Lesions as Surrogates to Clinical Lesions for Thoracic CT Volumetry: The Results of an International Challenge

RATIONALE AND OBJECTIVES To evaluate a new approach to establish compliance of segmentation tools with the computed tomography volumetry profile of the Quantitative Imaging Biomarker Alliance (QIBA); and determine the statistical exchangeability between real and simulated lesions through an international challenge. MATERIALS AND METHODS The study used an anthropomorphic phantom with 16 embedded physical lesions and 30 patient cases from the Reference Image Database to Evaluate Therapy Response with pathologically confirmed malignancies. Hybrid datasets were generated by virtually inserting simulated lesions corresponding to physical lesions into the phantom datasets using one projection-domain-based method (Method 1), two image-domain insertion methods (Methods 2 and 3), and simulated lesions corresponding to real lesions into the Reference Image Database to Evaluate Therapy Response dataset (using Method 2). The volumes of the real and simulated lesions were compared based on bias (measured mean volume differences between physical and virtually inserted lesions in phantoms as quantified by segmentation algorithms), repeatability, reproducibility, equivalence (phantom phase), and overall QIBA compliance (phantom and clinical phase). RESULTS For phantom phase, three of eight groups were fully QIBA compliant, and one was marginally compliant. For compliant groups, the estimated biases were -1.8 ± 1.4%, -2.5 ± 1.1%, -3 ± 1%, -1.8 ± 1.5% (±95% confidence interval). No virtual insertion method showed statistical equivalence to physical insertion in bias equivalence testing using Schuirmanns two one-sided test (±5% equivalence margin). Differences in repeatability and reproducibility across physical and simulated lesions were largely comparable (0.1%-16% and 7%-18% differences, respectively). For clinical phase, 7 of 16 groups were QIBA compliant. CONCLUSION Hybrid datasets yielded conclusions similar to real computed tomography datasets where phantom QIBA compliant was also compliant for hybrid datasets. Some groups deemed compliant for simulated methods, not for physical lesion measurements. The magnitude of this difference was small (<5.4%). While technical performance is not equivalent, they correlate, such that, volumetrically simulated lesions could potentially serve as practical proxies.

Estimability index for volume quantification of homogeneous spherical lesions in computed tomography

Abstract. Volume of lung nodules is an important biomarker, quantifiable from computed tomography (CT) images. The usefulness of volume quantification, however, depends on the precision of quantification. Experimental assessment of precision is time consuming. A mathematical estimability model was used to assess the quantification precision of CT nodule volumetry in terms of an index (e′), incorporating image noise and resolution, nodule properties, and segmentation software. The noise and resolution were characterized in terms of noise power spectrum and task transfer function. The nodule properties and segmentation algorithm were modeled in terms of a task function and a template function, respectively. The e′ values were benchmarked against experimentally acquired precision values from an anthropomorphic chest phantom across 54 acquisition protocols, 2 nodule sizes, and 2 volume segmentation softwares. e′ exhibited correlation with experimental precision across nodule sizes and acquisition protocols but dependence on segmentation software. Compared to the assessment of empirical precision, which required ∼300  h to perform the segmentation, the e′ method required ∼3  h from data collection to mathematical computation. A mathematical modeling of volume quantification provides efficient prediction of quantitative performance. It establishes a method to verify quantitative compliance and to optimize clinical protocols for chest CT volumetry.

Development of a Hausdorff distance based 3D quantification technique to evaluate the CT imaging system impact on depiction of lesion morphology

The purpose of this study was to develop a 3D quantification technique to assess the impact of imaging system on depiction of lesion morphology. Regional Hausdorff Distance (RHD) was computed from two 3D volumes: virtual mesh models of synthetic nodules or “virtual nodules” and CT images of physical nodules or “physical nodules”. The method can be described in following steps. First, the synthetic nodule was inserted into anthropomorphic Kyoto thorax phantom and scanned in a Siemens scanner (Flash). Then, nodule was segmented from the image. Second, in order to match the orientation of the nodule, the digital models of the “virtual” and “physical” nodules were both geometrically translated to the origin. Then, the “physical” was gradually rotated at incremental 10 degrees. Third, the Hausdorff Distance was calculated from each pair of “virtual” and “physical” nodules. The minimum HD value represented the most matching pair. Finally, the 3D RHD map and the distribution of RHD were computed for the matched pair. The technique was scalarized using the FWHM of the RHD distribution. The analysis was conducted for various shapes (spherical, lobular, elliptical, and speculated) of nodules. The calculated FWHM values of RHD distribution for the 8-mm spherical, lobular, elliptical, and speculated “virtual” and “physical” nodules were 0.23, 0.42, 0.33, and 0.49, respectively.