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Purpose: Gas exchange in systemic sclerosis (SSc) is known to be affected by fibrotic changes in the pulmonary parenchyma. However, SSc patients without detectable fibrosis can still have impaired gas transfer. We aim to investigate whether pulmonary vascular changes could partly explain a reduction in gas transfer of SSc patients without fibrosis., Materials and Methods: We selected 77 patients whose visual computed tomography (CT) scoring showed no fibrosis. Pulmonary vessels were detected automatically in CT images, and their local radii were calculated. The frequency of occurrence for each radius was calculated, and, from this radius histogram, 2 imaging biomarkers (α and β) were extracted, wherein α reflects the relative contribution of small vessels compared with large vessels, and β represents the vessel tree capacity. Correlations between imaging biomarkers and gas transfer [single-breath diffusion capacity for carbon monoxide corrected for hemoglobin concentration (DLCOc) %predicted] were evaluated with Spearman correlation. Multivariable stepwise linear regression was performed with DLCOc %predicted as the dependent variable and age, BMI, sPAP, FEV1 %predicted, TLC %predicted, FVC %predicted, α, β, voxel size, and CT-derived lung volume as independent variables., Results: Both α and β were significantly correlated with gas transfer (R=-0.29, P-value=0.011 and R=0.32, P-value=0.004, respectively). The multivariable stepwise linear regression analysis selected sPAP [coefficient=-0.78; 95% confidence interval (CI)=-1.07, -0.49; P-value<0.001], β (coefficient=8.6; 95% CI=4.07, 13.1; P-value<0.001), and FEV1% predicted (coefficient=0.3; 95% CI=0.12, 0.48; P-value=0.001) as significant independent predictors of DLCOc %predicted (R=0.71, P-value<0.001)., Conclusions: In SSc patients without detectable pulmonary fibrosis, impaired gas exchange is associated with alterations in pulmonary vascular morphology.

Objectives: Balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) can have variable outcomes. To gain more insight into this variation, we designed a method for visualizing and quantifying changes in pulmonary perfusion by automatically comparing computed tomography (CT) pulmonary angiography before and after BPA treatment. We validated these quantifications of perfusion changes against hemodynamic changes measured with right-sided heart catheterization., Materials and Methods: We studied 14 consecutive CTEPH patients (12 women; age, 70.5 ± 24), who underwent CT pulmonary angiography and right-sided heart catheterization, before and after BPA. Posttreatment images were registered to pretreatment CT scans (using the Elastix toolbox) to obtain corresponding locations. Pulmonary vascular trees and their centerlines were detected using a graph cuts method and a distance transform method, respectively. Areas distal from vessels were defined as pulmonary parenchyma. Subsequently, the density changes within the vascular centerlines and parenchymal areas were calculated and corrected for inspiration level differences. For visualization, the densitometric changes were displayed in color-coded overlays. For quantification, the median and interquartile range of the density changes in the vascular and parenchymal areas (ΔVD and ΔPD) were calculated. The recorded changes in hemodynamic parameters, including changes in systolic, diastolic, and mean pulmonary artery pressure (ΔsPAP, ΔdPAP, and ΔmPAP, respectively) and vascular resistance (ΔPVR), were used as reference assessments of the treatment effect. Spearman correlation coefficients were employed to investigate the correlations between changes in perfusion and hemodynamic changes., Results: Comparative imaging maps showed distinct patterns in perfusion changes among patients. Within pulmonary vessels, the interquartile range of ΔVD correlated significantly with ΔsPAP (R = -0.58, P = 0.03), ΔdPAP (R = -0.71, P = 0.005), ΔmPAP (R = -0.71, P = 0.005), and ΔPVR (R = -0.77, P = 0.001). In the parenchyma, the median of ΔPD had significant correlations with ΔdPAP (R = -0.58, P = 0.030) and ΔmPAP (R = -0.59, P = 0.025)., Conclusions: Comparative imaging analysis in CTEPH patients offers insight into differences in BPA treatment effect. Quantification of perfusion changes provides noninvasive measures that reflect hemodynamic changes.

Purpose: The aim was to evaluate computed tomography (CT)-measured pulmonary artery diameter (PAD) and lung density as predictors of pulmonary hypertension (PH) in subjects with systemic sclerosis (SSc). We compared these PAD values with normal values and between SSc subgroups with PH and/or interstitial lung disease (ILD). We investigated whether PAD predicts PH and whether lung densitometry, by using the 85th percentile density value (Perc85) as a measure for ILD, can predict PH., Materials and Methods: PAD and Perc85 were measured in axial CT scans and compared between 54 SSc and 76 control subjects. Four SSc subgroups were defined on the basis of PH (systolic PA pressure ≥35 mm Hg) and/or ILD (fibrosis score ≥7): PH-/ILD-, PH-/ILD+, PH+/ILD-, and PH+/ILD+. The association of PAD with age, body mass index, Perc85, lung function, and hemodynamic measures was investigated using univariate correlation along with the predictive value of these measures with respect to PH., Results: PAD in SSc was larger than that in controls (30.1±4.9 vs. 26.9±2.7 mm, P<0.001). PH+ patients showed increased PAD compared with PH- patients (34.2±4.2 vs. 28.6±4.3 mm, P<0.001), where PH+/ILD+ subjects showed the widest diameter (34.6±4.1 mm). In SSc patients, hemodynamic measures, age, body mass index, Perc85, and lung function correlated with PAD. PAD was best explained by Perc85, together with age (R=0.358). PAD best predicted PH (AUC, 0.877; P<0.001), and PAD≥30.7 mm showed 80% sensitivity and 87% specificity. Perc85 also predicted PH (AUC, 0.733; P=0.024)., Conclusions: In subjects with SSc, lung density and PAD are CT markers, each with predictive value for PH.

Objectives: The objectives of this study were to investigate whether computed tomography (CT) densitometry can be applied consistently in different centers; and to evaluate the reproducibility of densitometric quantification of emphysema by assessment of different sources of variation, ie, intersite, interscan and inter- and intraobserver variability, in comparison with intersubject variability., Materials and Methods: In 5 different hospitals, 119 patients with emphysema were scanned using standardized protocols. In each site, an observer performed a quantitative densitometric analysis (including blood recalibration) on the corresponding patient group (n=23-25) and one observer analyzed the entire group of 119 patients. After several months, the latter observer analyzed all data for a second time. Subsequently, different sources of variation were assessed by variance component analysis with and without volume correction of the data., Results: Inter- and intraobserver variability marginally contributes to the total variability (<0.001%). The interscan variability was 0.02% of the total variation after application of volume correction. The intersite variability was 48% as a result of one deviating CT scanner. Air recalibration normalized deviating air densities in CT scanners. Within sites, the intersubject variability ranged between 93% and 99% based on the analysis of 2 subsequent CT scans of the patients., Conclusions: Almost all variability in the density measurement of emphysema originates from differences between scanners and from differences in severity of emphysema between patients. Lung densitometry with multislice CT scanners is a highly reproducible measurement, especially if corrected for lung volume, because this reduces interscan variability.

Currently, lung densitometry for the assessment of pulmonary emphysema has been fully validated against pathology, pulmonary function, and health status, and it is therefore being applied in pharmacotherapeutic trials. Nevertheless, its application for the early detection of emphysema has not yet been introduced in daily clinical practice. The main reason for this is the fact that it is not yet regarded a fully optimized and standardized technique. In this work, an overview is given on the current status of different standardization aspects that play an important role in this, ie, image acquisition, choice of densitometric parameter and image processing. To address these issues, solutions have been sought from the literature and from original data from previous studies. Standardization and optimization of lung densitometry has reached a more advanced stage than has been reported so far. If normal values will become available, this technique will be feasible for clinical practice. As a result, standardization for the detection and assessment of other density-related lung diseases can be achieved in a shorter period of time.

Rationale and Objectives: To compare the sensitivities of 5 different computed tomography scanners (4 multislice CT [MSCT] and 1 single-slice CT) in the assessment of the progression of pulmonary emphysema., Methods: A Perspex cylinder phantom was constructed containing small pieces of polythene foam with densities representative of lung. Changing the cylinder's volume simulated subtle lung density changes. The sensitivity to density changes was defined by the variation in the residual errors from the linear regression line between time and density., Results: The single-slice CT scanner was significantly less sensitive to density changes than MSCT scanners. Also, among MSCT scanners, small but significant differences were found when the standardized acquisition protocol was used., Conclusions: Considering the large sensitivity differences between single- and multislice CT scanners, we would recommended using MSCT scanners in clinical multicenter trials in emphysema. The protocol standardization of MSCT scanners can still be further improved.

Rationale and Objectives: Multislice computed tomography (MSCT) of the lungs provides a new opportunity for longitudinal assessment of lung densities because of shorter scan duration. The aim of the present study was to assess the intraindividual variation of lung densities measured by MSCT of patients with emphysema., Methods: Ten patients with emphysema participated in a study in which MSCT was obtained on two occasions, approximately 2 weeks apart. Scanning parameters were 140 kV, 20 mAs, 4 x 2.5-mm collimation, and effective slice thickness of 2.5 mm. Lung density was measured as the 15th percentile point and the relative area below -910 Hounsfield units (HU) by using Pulmo-LKEB software., Results: The mean difference of the 15th percentile point was -1.29 +/- 3.2 HU, and that for the relative area below the -910-HU parameter was -1.02% +/- 3.09%. Intraclass coefficients of variation were 0.96 (0.86-0.99) and 0.94 (0.8-0.98), respectively (95% confidence interval)., Conclusions: Lung density parameters of emphysema derived by MSCT provide an opportunity for analysis of the treatment effects of new drugs on the progression of emphysema.

Rationale and Objectives: To determine and analyze the most important error sources in lung CT densitometry in vivo., Methods: The authors examined the influences of CT acquisition errors, physiologic changes, and image segmentation errors on lung densitometry. Among others, spatial dependency and long-term reproducibility of the density measurements of blood and air were examined over a period of 4 years in a group of 28 patients with pulmonary emphysema. These results were related to the measured lung densities in this group., Results: The density measurement of blood and air is strongly dependent on the position in the thorax. Despite full-scanner calibrations, x-ray tube replacement can induce a significant increase in measured blood density., Conclusions: A change in a lung density parameter over time can actually be the result of tube replacement or changing blood density. A simple postprocessing technique can correct for these changes.

There is a lack of instruments that measure the quality of life of people with mental retardation. These types of instruments could be used in order to give an indication of the quality of care they receive. At the moment we are developing an instrument that measures quality of life. Our first task is to find an adequate definition of 'quality of life'. In this article an attempt is made to define this term as it relates to people with mental retardation. Starting from literature in the field of disabilities, reflections in the social sciences and philosophical analysis, a combined approach is adopted, according to which quality of life consists of specific objective and subjective factors.

Rationale and Objectives: The authors assessed the progression of pulmonary emphysema by means of quantitative analysis of computed tomography images., Methods: Twenty-three patients suffering from emphysema due to an alpha 1-antitrypsin deficiency, aged 45 +/- 7 years and exsmokers, were scanned twice with a 1-year time interval. At 90% of the vital lung capacity, slices with a thickness of 1.5 mm were acquired at the level of the carina and 5 cm above the carina; slices with a thickness of 1 cm were acquired 5 cm below the carina. The entire lung was scanned spirally at a respiratory status, corresponding with 75% of the total lung capacity at baseline. The mean lung densities (MLD) were calculated in an objective manner with new analytic software featuring automated detection of the lung contours., Results: Mean lung densities decreased by 14.2 +/- 12.0 Hounsfield units (HU; P < 0.001) above the carina, by 18.1 +/- 14.4 HU (P < 0.001) at the carina level, by 23.6 +/- 15.0 HU (P < 0.001) below the carina, and by 12.8 +/- 22.2 HU (P < 0.01) for the entire lung. The decrease in MLD was most obvious in the lower lung lobes. For the same patient group, the annual decrease in the forced expiratory volume (FEV1) and the carbon monoxide-diffusion were 120 +/- 190 mL (P < 0.01) and 10 +/- 70 mmol/kg/minute ( P < 0.2), respectively. No significant correlation was found between the decrease in MLD and the decrease in FEV1., Conclusions: Progression of emphysema can be assessed in an objective manner based on the mean lung density (MLD), measured from computed tomography volume scans as well as from single-slice scans. Mean lung density has proved to be more sensitive than FEV1 and carbon monoxide-diffusion.

Rationale and Objectives: To develop an analytic software package based on automated contour detection for the objective and reproducible assessment of emphysema from computed tomography (CT) scans., Methods: A semiautomated technique was developed for the definition of lung contours in CT cross-sections followed by the assessment of pulmonary CT parameters describing the disease state. For 78 images, the semiautomated contour detection was performed and compared with contours drawn by an experienced radiologist by calculating the systematic area difference (bias) and differences in pulmonary CT parameters such as the mean lung density (MLD). In addition, intraobserver and interobserver variabilities were determined in a subset of 15 images., Results: The areas enclosed by the semiautomatically detected contours were slightly larger than the manual ones (bias < 2.1%). The biases in the observer studies were smaller in the semiautomated versus the manual case (0.3% vs. 1.3%). The standard deviation of the MLD differences with a manual analysis was larger by a factor of five than in the semiautomated case. On average, manual analysis required 2 minutes, 18 seconds per lung; this time was reduced to 11.5 to 29 seconds with the semiautomated approach, depending on the respiration state., Conclusions: The semiautomated approach is preferred over the manual approach because of its higher consistency and its shorter analysis time.