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Purpose: Measuring the size of nodules on chest CT is important for lung cancer staging and measuring therapy response. 3D volumetry has been proposed as a more robust alternative to 1D and 2D sizing methods. There have also been substantial advances in methods to reduce radiation dose in CT. The purpose of this work was to investigate the effect of dose reduction and reconstruction methods on variability in 3D lung-nodule volumetry., Methods: Reduced-dose CT scans were simulated by applying a noise-addition tool to the raw (sinogram) data from clinically indicated patient scans acquired on a multidetector-row CT scanner (Definition Flash, Siemens Healthcare). Scans were simulated at 25%, 10%, and 3% of the dose of their clinical protocol (CTDIvol of 20.9 mGy), corresponding to CTDIvol values of 5.2, 2.1, and 0.6 mGy. Simulated reduced-dose data were reconstructed with both conventional filtered backprojection (B45 kernel) and iterative reconstruction methods (SAFIRE: I44 strength 3 and I50 strength 3). Three lab technologist readers contoured "measurable" nodules in 33 patients under each of the different acquisition/reconstruction conditions in a blinded study design. Of the 33 measurable nodules, 17 were used to estimate repeatability with their clinical reference protocol, as well as interdose and inter-reconstruction-method reproducibilities. The authors compared the resulting distributions of proportional differences across dose and reconstruction methods by analyzing their means, standard deviations (SDs), and t-test and F-test results., Results: The clinical-dose repeatability experiment yielded a mean proportional difference of 1.1% and SD of 5.5%. The interdose reproducibility experiments gave mean differences ranging from -5.6% to -1.7% and SDs ranging from 6.3% to 9.9%. The inter-reconstruction-method reproducibility experiments gave mean differences of 2.0% (I44 strength 3) and -0.3% (I50 strength 3), and SDs were identical at 7.3%. For the subset of repeatability cases, inter-reconstruction-method mean/SD pairs were (1.4%, 6.3%) and (-0.7%, 7.2%) for I44 strength 3 and I50 strength 3, respectively. Analysis of representative nodules confirmed that reader variability appeared unaffected by dose or reconstruction method., Conclusions: Lung-nodule volumetry was extremely robust to the radiation-dose level, down to the minimum scanner-supported dose settings. In addition, volumetry was robust to the reconstruction methods used in this study, which included both conventional filtered backprojection and iterative methods.

Objectives: To investigate volumetric and density changes in the ipsilateral and contralateral lobes following volume reduction of an emphysematous target lobe., Methods: The study included 289 subjects with heterogeneous emphysema, who underwent bronchoscopic volume reduction of the most diseased lobe with endobronchial valves and 132 untreated controls. Lobar volume and low-attenuation relative area (RA) changes post-procedure were measured from computed tomography images. Regression analysis (Spearman's rho) was performed to test the association between change in the target lobe volume and changes in volume and density variables in the other lobes., Results: The target lobe volume at full inspiration in the treatment group had a mean reduction of -0.45 L (SE = 0.034, P < 0.0001), and was associated with volume increases in the ipsilateral lobe (rho = -0.68, P < 0.0001) and contralateral lung (rho = -0.16, P = 0.006), and overall reductions in expiratory RA (rho = 0.31, P < 0.0001) and residual volume (RV)/total lung capacity (TLC) (rho = 0.13, P = 0.03)., Conclusions: When the volume of an emphysematous target lobe is reduced, the volume is redistributed primarily to the ipsilateral lobe, with an overall reduction. Image-based changes in lobar volumes and densities indicate that target lobe volume reduction is associated with statistically significant overall reductions in air trapping, consistent with expansion of the healthier lung., Key Points: Computed tomography allows assessment of the treatment of emphysema with endobronchial valves. • Endobronchial valves can reduce the volume of an emphysematous lung lobe. • Compensatory expansion is greater in ipsilateral lobes than in the contralateral lung. • Reduced air trapping is measurable by RV/TLC and smaller low attenuation area.

Objectives: To propose and evaluate a technique for automatic quantification of fissural completeness from chest computed tomography (CT) in a database of subjects with severe emphysema., Methods: Ninety-six CT studies of patients with severe emphysema were included. The lungs, fissures and lobes were automatically segmented. The completeness of the fissures was calculated as the percentage of the lobar border defined by a fissure. The completeness score of the automatic method was compared with a visual consensus read by three radiologists using boxplots, rank sum tests and ROC analysis., Results: The consensus read found 49% (47/96), 15% (14/96) and 67% (64/96) of the right major, right minor and left major fissures to be complete. For all fissures visually assessed as being complete the automatic method resulted in significantly higher completeness scores (mean 92.78%) than for those assessed as being partial or absent (mean 77.16%; all p values <0.001). The areas under the curves for the automatic fissural completeness were 0.88, 0.91 and 0.83 for the right major, right minor and left major fissures respectively., Conclusions: An automatic method is able to quantify fissural completeness in a cohort of subjects with severe emphysema consistent with a visual consensus read of three radiologists., Key Points: • Lobar fissures are important for assessing the extent and distribution of lung disease • Modern CT allows automatic lobar segmentation and assessment of the fissures • This segmentation can also assess the completeness of the fissures. • Such assessment is important for decisions about novel therapies (eg for emphysema).

Rationale and Objectives: Lung and lobar volume measurements from computed tomographic (CT) imaging are being used in clinical trials to assess new minimally invasive emphysema treatments aiming to reduce lung volumes. Establishing the reproducibility of lung volume measurements is important if they are to be accepted as treatment planning and outcome variables. The aims of this study were to (1) investigate the correlation between lung volumes assessed on CT imaging and on pulmonary function testing (PFT), (2) compare the two methods' reproducibility, and (3) assess the reproducibility of CT lobar volumes., Materials and Methods: CT imaging and body plethysmography were performed at baseline and after a 9-month interval in multicenter emphysema treatment trials. Lung volumes were measured at total lung capacity (TLC) and at residual volume (RV). Lobar volumes were measured on CT imaging using a semiautomated technique. The correlations between CT and PFT volumes were computed for 486 subjects at baseline. Reproducibility was assessed in terms of the intraclass correlation coefficient (ICC) for 126 subjects from the control group at TLC and 120 subjects at RV., Results: Correlations between CT and PFT lung volumes were 0.86 at TLC and 0.67 at RV. At TLC, the ICCs were 0.943 for CT imaging and 0.814 for PFT. At RV, the ICCs were 0.886 for CT imaging and 0.683 for PFT. CT lobar volumes showed good reproducibility (all P values < .05)., Conclusion: CT lung and lobar volume measurements could be captured in a multicenter trial setting with high reproducibility and were highly correlated with those obtained on PFT. CT imaging showed significantly better reproducibility than PFT between interval lung volume measurements, offering the potential for designing emphysema treatment trials involving fewer subjects.

Rationale and Objectives: Segmentation of lungs using high-resolution computer tomographic images in the setting of diffuse lung diseases is a major challenge in medical image analysis. Threshold-based techniques tend to leave out lung regions that have increased attenuation, such as in the presence of interstitial lung disease. In contrast, streak artifacts can cause the lung segmentation to "leak" into the chest wall. The purpose of this work was to perform segmentation of the lungs using a technique that selects an optimal threshold for a given patient by comparing the curvature of the lung boundary to that of the ribs., Methods: Our automated technique goes beyond fixed threshold-based approaches to include lung boundary curvature features. One would expect the curvature of the ribs and the curvature of the lung boundary around the ribs to be very close. Initially, the ribs are segmented by applying a threshold algorithm followed by morphologic operations. The lung segmentation scheme uses a multithreshold iterative approach. The threshold value is verified until the curvature of the ribs and the curvature of the lung boundary are closely matched. The curve of the ribs is represented using polynomial interpolation, and the lung boundary is matched in such a way that there is minimal deviation from this representation. Performance of this technique was compared with conventional (fixed threshold) lung segmentation techniques on 25 subjects using a volumetric overlap fraction measure., Results: The performance of the rib segmentation technique was significantly different from conventional techniques with an average higher mean volumetric overlap fraction of about 5%., Conclusions: The technique described here allows for accurate quantification of volumetric computed tomography and more advanced segmentation of abnormal areas.

Lung CAD systems require the ability to classify a variety of pulmonary structures as part of the diagnostic process. The purpose of this work was to develop a methodology for fully automated voxel-by-voxel classification of airways, fissures, nodules, and vessels from chest CT images using a single feature set and classification method. Twenty-nine thin section CT scans were obtained from the Lung Image Database Consortium (LIDC). Multiple radiologists labeled voxels corresponding to the following structures: airways (trachea to 6th generation), major and minor lobar fissures, nodules, and vessels (hilum to peripheral), and normal lung parenchyma. The labeled data was used in conjunction with a supervised machine learning approach (AdaBoost) to train a set of ensemble classifiers. Each ensemble classifier was trained to detect voxels part of a specific structure (either airway, fissure, nodule, vessel, or parenchyma). The feature set consisted of voxel attenuation and a small number of features based on the eigenvalues of the Hessian matrix (used to differentiate structures by shape). When each ensemble classifier was composed of 20 weak classifiers, the AUC values for the airway, fissure, nodule, vessel, and parenchyma classifiers were 0.984+/-0.011, 0.949+/-0.009, 0.945+/-0.018, 0.953+/-0.016, and 0.931+/-0.015, respectively. The strong results suggest that this could be an effective input to higher-level anatomical based segmentation models with the potential to improve CAD performance.

PurposeThe purpose of this work was to estimate and compare breast and lung doses of chest CT scans using organ-based tube current modulation (OBTCM) to those from conventional, attenuation-based automatic tube current modulation (ATCM) across a range of patient sizes.MethodsThirty-four patients (17 females, 17 males) who underwent clinically indicated CT chest/abdomen/pelvis (CAP) examinations employing OBTCM were collected from two multi-detector row CT scanners. Patient size metric was assessed as water equivalent diameter (Dw ) taken at the center of the scan volume. Breast and lung tissues were segmented from patient image data to create voxelized models for use in a Monte Carlo transport code. The OBTCM schemes for the chest portion were extracted from the raw projection data. ATCM schemes were estimated using a recently developed method. Breast and lung doses for each TCM scenario were estimated for each patient model. CTDIvol -normalized breast (nDbreast ) and lung (nDlung ) doses were subsequently calculated. The differences between OBTCM and ATCM normalized organ dose estimates were tested using linear regression models that included CT scanner and Dw as covariates.ResultsMean dose reduction from OBTCM in nDbreast was significant after adjusting for the scanner models and patient size (P = 0.047). When pooled with females and male patient, mean dose reduction from OBTCM in nDlung was observed to be trending after adjusting for the scanner model and patient size (P = 0.085).ConclusionsOne specific manufacturer's OBTCM was analyzed. OBTCM was observed to significantly decrease normalized breast relative to a modeled version of that same manufacturer's ATCM scheme. However, significant dose savings were not observed in lung dose over all. Results from this study support the use of OBTCM chest protocols for females only.

Purpose To determine feasibility and safety of biopsy and repeat biopsy for assessment of programmed cell death ligand-1 (PD-L1) status. Materials and Methods This retrospective analysis reviewed 101 patients who underwent transthoracic core needle biopsy for the KEYNOTE-001 (MK-3475) clinical trial of pembrolizumab, an antiprogrammed cell death-1 therapy for non-small cell lung cancer, from May 2012 to September 2014. Sixty-one male patients (mean age, 66.1 years; range 36-83 years) and 40 female patients (mean age, 66.8 years; age range, 36-90 years) were included. Data collected included population characteristics, treatment history, target location, size, and depth from pleura. Adequacy of the tissue sample for diagnostic testing and rates of biopsy-related complications were assessed. Statistical analysis was performed by using univariate and multivariate generalized linear models to determine significant risk factors for biopsy complications. Results A total of 110 intrathoracic biopsies were performed, and 101 (91.8%) were performed as repeat biopsies subsequent to a previous percutaneous or bronchoscopic biopsy or previous surgical biopsy or resection. More than 84.5% (93 of 110) of biopsies were performed in patients who had undergone previous local or systemic therapy. Specimens were adequate for evaluation of PD-L1 expression in 96.4% of biopsies. Procedure-related complications occurred in 28 biopsies (25.4%); pneumothorax was most common (22.7%). Overall mean number of core needle biopsy samples obtained was 7.9 samples. Conclusion Image-guided transthoracic core needle biopsy is an effective method for obtaining tissue for PD-L1 expression analysis. © RSNA, 2017.

PurposeCardiovascular magnetic resonance imaging exams can be performed during free-breathing. This may be especially important for boys with Duchenne muscular dystrophy (DMD) given their frequently limited breath-hold abilities. The impact of the respiratory compensation method on quantitative measurements of left ventricular (LV) rotational mechanics is incompletely understood. The purpose of this study was to evaluate differences in LV rotational mechanics acquired during breath-holding (BH), free-breathing with averaging (AVG), and free-breathing with respiratory bellows gating (BEL).MethodsLV short-axis tagged images from healthy subjects (N = 16) and DMD patients (N = 5) were acquired with BH, AVG, and BEL. LV twist and circumferential-longitudinal shear (CL-shear) angle were measured using the Fourier Analysis of STimulated echoes (FAST) method.ResultsPeak LV twist estimates using BEL were significantly lower compared with BH in both healthy subjects (10.2 ± 3.6 ° versus 12.9 ± 2.3 °, P = 0.003) and patients with DMD (8.6 ± 3.6 ° versus 10.5 ± 3.6 °, P = 0.004). AVG results were in between BEL and BH. No significant differences in CL-shear were detected between BEL and BH.ConclusionBreath-holding directly affects estimates of peak LV twist, but not CL-shear. Using a free-breathing strategy for the evaluation of cardiac function is important for intrasubject longitudinal studies, intersubject comparisons, and multicenter trials for patients with DMD. Magn Reson Med 77:864-869, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

RationaleThe Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) trial demonstrated that sirolimus stabilized lung function and improved measures of functional performance and quality of life in patients with lymphangioleiomyomatosis. The physiologic mechanisms of these beneficial actions of sirolimus are incompletely understood.ObjectivesTo prospectively determine the longitudinal computed tomographic lung imaging correlates of lung function change in MILES patients treated with placebo or sirolimus.MethodsWe determined the baseline to 12-month change in computed tomographic image-derived lung volumes and the volume of the lung occupied by cysts in the 31 MILES participants (17 in sirolimus group, 14 in placebo group) with baseline and 12-month scans.Measurements and main resultsThere was a trend toward an increase in median expiratory cyst volume percentage in the placebo group and a reduction in the sirolimus group (+2.68% vs. +0.97%, respectively; P = 0.10). The computed tomographic image-derived residual volume and the ratio of residual volume to total lung capacity increased more in the placebo group than in the sirolimus group (+214.4 ml vs. +2.9 ml [P = 0.054] and +0.05 ml vs. -0.01 ml [P = 0.0498], respectively). A Markov transition chain analysis of respiratory cycle cyst volume changes revealed greater dynamic variation in the sirolimus group than in the placebo group at the 12-month time point.ConclusionsCollectively, these data suggest that sirolimus attenuates progressive gas trapping in lymphangioleiomyomatosis, consistent with a beneficial effect of the drug on airflow obstruction. We speculate that a reduction in lymphangioleiomyomatosis cell burden around small airways and cyst walls alleviates progressive airflow limitation and facilitates cyst emptying.

Lack of classifier robustness is a barrier to widespread adoption of computer-aided diagnosis systems for computed tomography (CT). We propose a novel Robustness-Driven Feature Selection (RDFS) algorithm that preferentially selects features robust to variations in CT technical factors. We evaluated RDFS in CT classification of fibrotic interstitial lung disease using 3D texture features. CTs were collected for 99 adult subjects separated into three datasets: training, multi-reconstruction, testing. Two thoracic radiologists provided cubic volumes of interest corresponding to six classes: pulmonary fibrosis, ground-glass opacity, honeycombing, normal lung parenchyma, airway, vessel. The multi-reconstruction dataset consisted of CT raw sinogram data reconstructed by systematically varying slice thickness, reconstruction kernel, and tube current (using a synthetic reduced-tube-current algorithm). Two support vector machine classifiers were created, one using RDFS ("with-RDFS") and one not ("without-RDFS"). Classifier robustness was compared on the multi-reconstruction dataset, using Cohen's kappa to assess classification agreement against a reference reconstruction. Classifier performance was compared on the testing dataset using the extended g-mean (EGM) measure. With-RDFS exhibited superior robustness (kappa 0.899-0.989) compared to without-RDFS (kappa 0.827-0.968). Both classifiers demonstrated similar performance on the testing dataset (EGM 0.778 for with-RDFS; 0.785 for without-RDFS), indicating that RDFS does not compromise classifier performance when discarding nonrobust features. RDFS is highly effective at improving classifier robustness against slice thickness, reconstruction kernel, and tube current without sacrificing performance, a result that has implications for multicenter clinical trials that rely on accurate and reproducible quantitative analysis of CT images collected under varied conditions across multiple sites, scanners, and timepoints.

PurposeTask Group 204 introduced effective diameter (ED) as the patient size metric used to correlate size-specific-dose-estimates. However, this size metric fails to account for patient attenuation properties and has been suggested to be replaced by an attenuation-based size metric, water equivalent diameter (DW). The purpose of this study is to investigate different size metrics, effective diameter, and water equivalent diameter, in combination with regional descriptions of scanner output to establish the most appropriate size metric to be used as a predictor for organ dose in tube current modulated CT exams.Methods101 thoracic and 82 abdomen/pelvis scans from clinically indicated CT exams were collected retrospectively from a multidetector row CT (Sensation 64, Siemens Healthcare) with Institutional Review Board approval to generate voxelized patient models. Fully irradiated organs (lung and breasts in thoracic scans and liver, kidneys, and spleen in abdominal scans) were segmented and used as tally regions in Monte Carlo simulations for reporting organ dose. Along with image data, raw projection data were collected to obtain tube current information for simulating tube current modulation scans using Monte Carlo methods. Additionally, previously described patient size metrics [ED, DW, and approximated water equivalent diameter (DWa)] were calculated for each patient and reported in three different ways: a single value averaged over the entire scan, a single value averaged over the region of interest, and a single value from a location in the middle of the scan volume. Organ doses were normalized by an appropriate mAs weighted CTDIvol to reflect regional variation of tube current. Linear regression analysis was used to evaluate the correlations between normalized organ doses and each size metric.ResultsFor the abdominal organs, the correlations between normalized organ dose and size metric were overall slightly higher for all three differently (global, regional, and middle slice) reported DW and DWa than they were for ED, but the differences were not statistically significant. However, for lung dose, computed correlations using water equivalent diameter calculated in the middle of the image data (DW,middle) and averaged over the low attenuating region of lung (DW,regional) were statistically significantly higher than correlations of normalized lung dose with ED.ConclusionsTo conclude, effective diameter and water equivalent diameter are very similar in abdominal regions; however, their difference becomes noticeable in lungs. Water equivalent diameter, specifically reported as a regional average and middle of scan volume, was shown to be better predictors of lung dose. Therefore, an attenuation-based size metric (water equivalent diameter) is recommended because it is more robust across different anatomic regions. Additionally, it was observed that the regional size metric reported as a single value averaged over a region of interest and the size metric calculated from a single slice/image chosen from the middle of the scan volume are highly correlated for these specific patient models and scan types.

Purpose: In AAPM Task Group 204, the size-specific dose estimate (SSDE) was developed by providing size adjustment factors which are applied to the Computed Tomography (CT) standardized dose metric, CTDIvol. However, that work focused on fixed tube current scans and did not specifically address tube current modulation (TCM) scans, which are currently the majority of clinical scans performed. The purpose of this study was to extend the SSDE concept to account for TCM by investigating the feasibility of using anatomic and organ specific regions of scanner output to improve accuracy of dose estimates. Methods: Thirty-nine adult abdomen/pelvis and 32 chest scans from clinically indicated CT exams acquired on a multidetector CT using TCM were obtained with Institutional Review Board approval for generating voxelized models. Along with image data, raw projection data were obtained to extract TCM functions for use in Monte Carlo simulations. Patient size was calculated using the effective diameter described in TG 204. In addition, the scanner-reported CTDIvol (CTDIvol,global) was obtained for each patient, which is based on the average tube current across the entire scan. For the abdomen/pelvis scans, liver, spleen, and kidneys were manually segmented from the patient datasets; for the chest scans, lungs and for female models only, glandular breast tissue were segmented. For each patient organ doses were estimated using Monte Carlo Methods. To investigate the utility of regional measures of scanner output, regional and organ anatomic boundaries were identified from image data and used to calculate regional and organ-specific average tube current values. From these regional and organ-specific averages, CTDIvol values, referred to as regional and organ-specific CTDIvol, were calculated for each patient. Using an approach similar to TG 204, all CTDIvol values were used to normalize simulated organ doses; and the ability of each normalized dose to correlate with patient size was investigated. Results: For all five organs, the correlations with patient size increased when organ doses were normalized by regional and organ-specific CTDIvol values. For example, when estimating dose to the liver, CTDIvol,global yielded a R2 value of 0.26, which improved to 0.77 and 0.86, when using the regional and organ-specific CTDIvol for abdomen and liver, respectively. For breast dose, the global CTDIvol yielded a R2 value of 0.08, which improved to 0.58 and 0.83, when using the regional and organ-specific CTDIvol for chest and breasts, respectively. The R2 values also increased once the thoracic models were separated for the analysis into females and males, indicating differences between genders in this region not explained by a simple measure of effective diameter. Conclusions: This work demonstrated the utility of regional and organ-specific CTDIvol as normalization factors when using TCM. It was demonstrated that CTDIvol,global is not an effective normalization factor in TCM exams where attenuation (and therefore tube current) varies considerably throughout the scan, such as abdomen/pelvis and even thorax. These exams can be more accurately assessed for dose using regional CTDIvol descriptors that account for local variations in scanner output present when TCM is employed. [ABSTRACT FROM AUTHOR]