Search

Purpose Quantitative computed tomography (QCT)-derived measures of lung density are valued methods for objectively characterizing lung parenchymal and peripheral airways disease and are being used in a growing number of lung disease focused trials. Detector and reconstruction improvements in CT technology have allowed for significant radiation dose reduction in image acquisition with comparable qualitative image quality. We report the impact of detector type and reconstruction type on QCT lung density measures in relation to decreasing dose indices. Methods Two sets of studies were completed in an in vivo pig model with a SOMATOM Definition Flash CT system: (a) prior to system upgrade with conventional detectors (UFC) and filtered back projection (FBP), and (b) post system upgrade with integrated electronic detectors (STELLAR) and iterative reconstruction (SAFIRE). CT data were acquired across estimated CT volume dose indices (CTDIvol ) ranging from 0.75 to 15 mGy at both inspiratory and expiratory breath holds. Semiautomated lung segmentations allowed calculation of histogram median, kurtosis, and 15th percentile. Percentage of voxels below -910 HU and -950 HU (inspiratory), and -856 HU (expiratory) were also examined. The changes in these QCT metrics from dose reduction (15 mGy down to 0.75 mGy) were calculated relative to paired reference values (15 mGy). Results were compared based on detector and reconstruction type. Results In this study, STELLAR detectors improved concordance with 15 mGy values down to 3 mGy for inspiratory scans and 6 mGy for expiratory scans. The addition of SAFIRE reconstruction in all acquired measurements resulted in minimal deviation from reference values at 0.75 mGy. Conclusion The use of STELLAR integrated electronic detectors and SAFIRE iterative reconstruction may allow for comparable lung density measures with CT dose indices down to 0.75 mGy.

Osteoporosis associated with reduced bone mineral density (BMD) and microarchitectural changes puts patients at an elevated risk of fracture. Modern multidetector row CT (MDCT) technology, producing high spatial resolution at increasingly lower dose radiation, is emerging as a viable modality for trabecular bone (Tb) imaging. Wide variation in CT scanners raises concerns of data uniformity in multisite and longitudinal studies. A comprehensive cadaveric study was performed to evaluate MDCT-derived Tb microarchitectural measures. A human pilot study was performed comparing continuity of Tb measures estimated from two MDCT scanners with significantly different image resolution features.Micro-CT imaging of cadaveric ankle specimens (n=25) was used to examine the validity of MDCT-derived Tb microarchitectural measures. Repeat scan reproducibility of MDCT-based Tb measures and their ability to predict mechanical properties were examined. To assess multiscanner data continuity of Tb measures, the distal tibias of 20 volunteers (age:26.2±4.5Y,10F) were scanned using the Siemens SOMATOM Definition Flash and the higher resolution Siemens SOMATOM Force scanners with an average 45-day time gap between scans. The correlation of Tb measures derived from the two scanners over 30% and 60% peel regions at the 4% to 8% of distal tibia was analyzed.MDCT-based Tb measures characterizing bone network area density, plate-rod microarchitecture, and transverse trabeculae showed good correlations (r∈0.85,0.92) with the gold standard micro-CT-derived values of matching Tb measures. However, other MDCT-derived Tb measures characterizing trabecular thickness and separation, erosion index, and structure model index produced weak correlation (r0.8) with their micro-CT-derived values. Most MDCT Tb measures were found repeatable (ICC∈0.94,0.98). The Tb plate-width measure showed a strong correlation (r = 0.89) with experimental yield stress, while the transverse trabecular measure produced the highest correlation (r = 0.81) with Young's modulus. The data continuity experiment showed that, despite significant differences in image resolution between two scanners (10% MTF along xy-plane and z-direction - Flash: 16.2 and 17.9 lp/cm; Force: 24.8 and 21.0 lp/cm), most Tb measures had high Pearson correlations (r0.95) between values estimated from the two scanners. Relatively lower correlation coefficients were observed for the bone network area density (r = 0.91) and Tb separation (r = 0.93) measures.Most MDCT-derived Tb microarchitectural measures are reproducible and their values derived from two scanners strongly correlate with each other as well as with bone strength. This study has highlighted those MDCT-derived measures which show the greatest promise for characterization of bone network area density, plate-rod and transverse trabecular distributions with a good correlation (r ≥ 0.85) compared with their micro-CT-derived values. At the same time, other measures representing trabecular thickness and separation, erosion index, and structure model index produced weak correlations (r0.8) with their micro-CT-derived values, failing to accurately portray the projected trabecular microarchitectural features. Strong correlations of Tb measures estimated from two scanners suggest that image data from different scanners can be used successfully in multisite and longitudinal studies with linear calibration required for some measures. In summary, modern MDCT scanners are suitable for effective quantitative imaging of peripheral Tb microarchitecture if care is taken to focus on appropriate quantitative metrics.

Purpose: A test object (phantom) is an important tool to evaluate comparability and stability of CTscanners used in multicenter and longitudinal studies. However, there are many sources of error that can interfere with the test object-derived quantitative measurements. Here the authors investigated three major possible sources of operator error in the use of a test object employed to assess pulmonary density-related as well as airway-related metrics. Methods: Two kinds of experiments were carried out to assess measurement variability caused by imperfect scanning status. The first one consisted of three experiments. A COPDGene test object was scanned using a dual source multidetector computed tomographic scanner (Siemens Somatom Flash) with the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) inspiration protocol (120 kV, 110 mAs, pitch = 1, slice thickness = 0.75 mm, slice spacing = 0.5 mm) to evaluate the effects of tilt angle, water bottle offset, and air bubble size. After analysis of these results, a guideline was reached in order to achieve more reliable results for this test object. Next the authors applied the above findings to 2272 test object scans collected over 4 years as part of the SPIROMICS study. The authors compared changes of the data consistency before and after excluding the scans that failed to pass the guideline. Results: This study established the following limits for the test object: tilt index ≤0.3, water bottle offset limits of [−6.6 mm, 7.4 mm], and no air bubble within the water bottle, where tilt index is a measure incorporating two tilt angles around x- and y-axis. With 95% confidence, the density measurement variation for all five interested materials in the test object (acrylic, water,lung, inside air, and outside air) resulting from all three error sources can be limited to ±0.9 HU (summed in quadrature), when all the requirements are satisfied. The authors applied these criteria to 2272 SPIROMICS scans and demonstrated a significant reduction in measurement variation associated with the test object. Conclusions: Three operator errors were identified which significantly affected the usability of the acquired scan images of the test object used for monitoring scanner stability in a multicenter study. The authors’ results demonstrated that at the time of test object scan receipt at a radiology core laboratory, quality control procedures should include an assessment of tilt index, water bottle offset, and air bubble size within the water bottle. Application of this methodology to 2272 SPIROMICS scans indicated that their findings were not limited to the scanner make and model used for the initial test but was generalizable to both Siemens and GE scanners which comprise the scanner types used within the SPIROMICS study.

Purpose Computed Tomography (CT) imaging of the lung, reported in Hounsfield Units (HU), can be parameterized as a quantitative image biomarker for the diagnosis and monitoring of lung density changes due to emphysema, a type of chronic obstructive pulmonary disease (COPD). CT lung density metrics are global measurements based on lung CT number histograms, and are typically a quantity specifying either the percentage of voxels with CT numbers below a threshold, or a single CT number below which a fixed relative lung volume, nth percentile, falls. To reduce variability in the density metrics specified by CT attenuation, the Quantitative Imaging Biomarkers Alliance (QIBA) Lung Density Committee has organized efforts to conduct phantom studies in a variety of scanner models to establish a baseline for assessing the variations in patient studies that can be attributed to scanner calibration and measurement uncertainty. Methods Data were obtained from a phantom study on CT scanners from four manufacturers with several protocols at various tube potential voltage (kVp) and exposure settings. Free from biological variation, these phantom studies provide an assessment of the accuracy and precision of the density metrics across platforms solely due to machine calibration and uncertainty of the reference materials. The phantom used in this study has three foam density references in the lung density region, which, after calibration against a suite of Standard Reference Materials (SRM) foams with certified physical density, establishes a HU-electron density relationship for each machine-protocol. We devised a 5-step calibration procedure combined with a simplified physical model that enabled the standardization of the CT numbers reported across a total of 22 scanner-protocol settings to a single energy (chosen at 80 keV). A standard deviation was calculated for overall CT numbers for each density, as well as by scanner and other variables, as a measure of the variability, before and after the standardization. In addition, a linear mixed-effects model was used to assess the heterogeneity across scanners, and the 95% confidence interval of the mean CT number was evaluated before and after the standardization. Results We show that after applying the standardization procedures to the phantom data, the instrumental reproducibility of the CT density measurement of the reference foams improved by more than 65%, as measured by the standard deviation of the overall mean CT number. Using the lung foam that did not participate in the calibration as a test case, a mixed effects model analysis shows that the 95% confidence intervals are [-862.0 HU, -851.3 HU] before standardization, and [-859.0 HU, -853.7 HU] after standardization to 80 keV. This is in general agreement with the expected CT number value at 80 keV of -855.9 HU with 95% CI of [-857.4 HU, -854.5 HU] based on the calibration and the uncertainty in the SRM certified density. Conclusions This study provides a quantitative assessment of the variations expected in CT lung density measures attributed to non-biological sources such as scanner calibration and scanner x-ray spectrum and filtration. By removing scanner-protocol dependence from the measured CT numbers, higher accuracy and reproducibility of quantitative CT measures were attainable. The standardization procedures developed in study may be explored for possible application in CT lung density clinical data.

Purpose: The purpose of this study was to detect and analyze anomalies between a large number of computed tomography (CT) scanners, tracked over time, utilized to collect human pulmonary CT data for a national multicenter study: chronic obstructive pulmonary disease genetic epidemiology study (COPDGene). Methods: A custom designed CT reference standard “Test Object” has been developed to evaluate the relevant differences in CT attenuation between CT scanners in COPDGene. The materials used in the Test Object to assess CT scanner accuracy and precision included lung equivalent foam (−856 HU), internal air (−1000 HU), water (0 HU), and acrylic (120 HU). Nineteen examples of the Test Object were manufactured. Initially, all Test Objects were scanned on the same CT scanner before the Test Objects were sent to the 20 specific sites and 42 individual CT scanners that were used in the study. The Test Objects were scanned over 17 months while the COPDGene study continued to recruit subjects. A mixed linear effect statistical analysis of the CT scans on the 19 Test Objects was performed. The statistical model reflected influence of reconstruction kernels, tube current, individual Test Objects, CT scanner models, and temporal consistency on CT attenuation. Results: Depending on the Test Object material, there were significant differences between reconstruction kernels, tube current, individual Test Objects, CT scanner models, and temporal consistency. The two Test Object materials of most interest were lung equivalent foam and internal air. With lung equivalent foam, there were significant (p < 0.05) differences between the Siemens B31 (−856.6, ±0.82; mean ± SE) and the GE Standard (−856.6 ± 0.83) reconstruction kernel relative to the Siemens B35 reference standard (−852.5 ± 1.4). Comparing lung equivalent foam attenuation there were also significant differences between CT scanner models (p < 0.01), tube current (p < 0.005), and in temporal consistency (p < 0.005) at individual sites. However, there were no significant effects measurable using different examples of the Test Objects at the various sites compared to the reference scans of the 19 Test Objects. For internal air, significant (p < 0.005) differences were found between all reconstruction kernels (Siemens B31, GE Standard, and Phillips B) compared to the reference standard. There were significant differences between CT models (p < 0.005), and tube current (p < 0.005). There were no significant effects measurable using different examples of the Test Objects at the various sites compared to the reference scans of the 19 Test Objects. Differences, across scanners, between external air and internal air measures in this simple (relative to the in vivo lung) test object varied by as much as 15 HU. Conclusions: The authors conclude that the Test Object designed for this study was able to detect significant effects regarding individual CT scanners that altered the CT attenuation measurements relevant to the study that are used to determine lung density. Through an understanding of individual scanners, the Test Object analysis can be used to detect anomalies in an individual CT scanner and to statistically model out scanner differences and individual scanner changes over time in a large multicenter trial.

Purpose: Assessing pulmonary emphysema using Quantitative CT of the lung depends on accurate measures of CT density. Sinogram-Affirmed-Iterative-Reconstruction (SAFIRE) is a new approach for reconstructing CT data acquired at significantly lower doses. However, quantitative effects of this method remain unexplored. The authors investigated the effects on the median values of materials in the COPDGene2 test-object as a function of the reconstruction method [weighted filtered back projection (WFBP) versus SAFIRE], test-object size, dose, and material composition using a Siemens SOMATOM Definition FLASH CT scanner. Methods: The COPDGene2 test-object contains eight materials; acrylic, water, four foams (20 lb, 12 lb, lung-equivalent, and 4 lb emphysema-equivalent), internal and external-air. The test-object was scanned with three different outer ring sizes, simulating three different body habitus. There is an average size (36 cm) Ring A, large size (40 cm) Ring B, and small size Ring C (30 cm). The CT protocol used 120 kVp, 0.5 s rotation, 1.0 pitch, and a 0.6 slice collimation with progressively decreasing x-ray exposure values, 11.94–0.74 mGy. With a thorax length of 30 cm, the corresponding effective doses would be 5.01–0.31 mSv. The effects of using SAFIRE versus WFBP were assessed using a two tailed t-test for each ring size, material, and dose. Multivariable linear regression was used to evaluate the relative effects of ring size, material composition, dose, and reconstruction method on the measured median value in HU. Results: SAFIRE versus WFBP, at the largest ring size and two lowest doses there was a significant difference in median values of 4 lb-foam, p < 0.01. Using the smallest ring size at the lowest dose level there was a significant difference in the median value of 4 lb-foam, but the effect size was small, 1 HU. There is a significant difference in median values of both internal and external air using both the small and medium size rings at the three lowest dose levels, p < 0.05. There are significant differences noted at both high and low dose levels when using the large ring size in the median values of internal and external air when, p < 0.05. These effects on 4 lb-foam, inside and outside air are shown to be in part due to truncation effects on the median value since the lowest HU value in the CT scale used is −1024 HU. Multivariable linear regression results demonstrated significant effects on the measured material median value and standard deviation due to ring size, material composition, dose level, and reconstruction method, p < 0.05. Conclusions: The authors have shown that there is no significant effect on the median values obtained when using WFBP versus SAFIRE in materials with CT density between 120 and −856 HU using three different test-object sizes and CT doses that vary from 11.94 to 0.74 mGy. The authors have demonstrated there are significant effects on median values obtained when using WFBP versus SAFIRE in materials with CT density values between −937 and −1000 HU depending on the ring size and dose used. As expected, there is considerable reduction in image noise (lower standard deviation) using SAFIRE versus WFBP with all ring sizes, doses, and materials in the COPDGene2 test-object.