Extrapolation from ten sections can make CT-based quantification of lung aeration more practicable -- Electronic supplementary material -- A. W. Reske1*, A. P. Reske1*, H. A. Gast2, M. Seiwerts2, A. Beda1, U. Gottschaldt3, C. Josten4, D. Schreiter5, N. Heller6, H. Wrigge7, M. B. Amato8 1 Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden, Germany; Departments of 2Diagnostic and Interventional Radiology, 3 Anesthesiology and Intensive Care Medicine, and 4Trauma and Reconstructive Surgery, University Hospital Leipzig, Leipzig, Germany; 5Department of Surgery, Surgical Intensive Care Unit, University Hospital Carl Gustav Carus, Dresden, Germany; 6Institute of Informatics, University of Leipzig, Leipzig, Germany; 7Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Germany; 8Cardio-Pulmonary Department, Pulmonary Divison, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil. *These authors contributed equally to this work Correspondence should be addressed to: Dr. med. Andreas Reske Klinik und Poliklinik fuer Anaesthesiologie und Intensivtherapie Universitaetsklinikum Carl Gustav Carus Fetscherstrasse 74, D-01307 Dresden, Germany e-mail: andreas.reske@uniklinikum-dresden.de Phone: +49 176 14455000 Fax: +49 351 458 4336 Patients and Methods We retrospectively analyzed complete lung CTs performed in emergency trauma patients as part of the diagnostic work-up or in patients with respiratory problems treated in the intensive care unit (ICU). Each CT had been requested by the treating physicians. All already segmented CT data in our database were eligible for this study. The retrospective, observational analysis of CT data was approved by the institutional Ethics Committee, which waived the need for informed consent. We intentionally report only basic demographic data because this work focuses on the extrapolation method. CT scanning Depending on availability, two multislice CT-scanners were used, either a Somatom Volume Zoom (Siemens, Erlangen, Germany: 120 kV tube voltage, 165 mAs tube current, 4 x 2.5 mm collimation), or a Philips MX8000 IDT 16 (Philips Medical Systems, Hamburg, Germany: 120 kV voltage, 170 mAs current, 16 x 1.5 mm collimation). Two different reconstruction methods were used during routine clinical imaging. Contiguous images were reconstructed with either 10 mm slice thickness and the enhancing filter “B60f” on the Siemens, or with 5 mm thickness and the standard filter “B” on the Philips scanner. All patients received contrast material (120 ml Iopamidol, Schering, Berlin, Germany). In this retrospective study, the degree of inspiration during CT could not be controlled: Spontaneously breathing patients were asked to hold their breath after inspiration (without checking for compliance) during CT. Mechanically ventilated patients were scanned during uninterrupted ventilation as is current clinical practice. Calibration of the CT-scanners was performed using air and the manufacturer’s standard phantom. CT analysis Because CT-images with gross motion artifacts are a potential problem for CT densitometry, such data sets were not eligible. The distribution of pulmonary opacifications was classified using all CT-sections according to Puybasset by two independent observers [ESM1]. The Osiris software (University Hospital Geneva, Switzerland) was used for manual segmentation of the lung parenchyma. The total lung volume (Vtotal) and mass (Mtotal), the pulmonary gas volume (Vgas), and the volumes and masses of four differently aerated lung compartments were calculated voxel-by-voxel according to established methods [ESM1-9]. The following HU-ranges were used to define differently aerated lung compartments: nonaerated, -100 to +100 HU; poorly aerated, -101 to -500 HU; normally aerated, -501 to -900 HU; and hyperaerated, -901 to -1.000 HU. All subvolumes and –masses, as well as Vgas were calculated as percentage of Vtotal or Mtotal, respectively. Extrapolation The extrapolation method uses ten CT-sections instead of all sections covering the whole lung (all CT-sections). The assumption of linear lung boundaries is made and the lung volume between two CT-sections treated as approximately conic section. In line with the only previous study using this approach [ESM10], the most cranial and caudal CT-sections and a further eight evenly spaced CT-sections between them were analyzed. In case it was impossible to retrospectively select eight CT-sections at perfectly equal intervals between the most cranial and caudal CT-sections, intervals were adapted to obtain an almost even distribution. These ten CT-sections were analyzed using the standard segmentation and densitometry methods and the results were extrapolated to the entire lung as illustrated in Figure 1 of the main manuscript [ESM10, ESM11]. In order to study whether the number of CT-sections used for extrapolation could be reduced even further, the procedure was repeated with five and three, respectively, evenly spaced CTsections in 45 patients. To test whether the extrapolation method was equally accurate for assessing intra-individual changes of volume and mass parameters between repeat CTs, we analyzed a subgroup of patients for whom data from repeat CT were available. Statistics Data are given as median and range (minimum and maximum values) or, if distribution of data was normal as confirmed by D'Agostino & Pearson omnibus and Shapiro-Wilk normality tests, as mean and standard deviation (±SD). The agreement between extrapolated values and the corresponding values calculated from all CT-sections was assessed according to Bland and Altman [ESM12, ESM13]. Bias values were compared between subgroups with MannWhitney or Kruskal-Wallis tests. Bonferroni-corrected Mann-Whitney tests were used for post-hoc testing. Statistical analysis was performed using SPSS 12.0 (SPSS Inc., Chicago, IL, USA) and GraphPad Prism 5.0 (GraphPad Software, San Diego, California, USA). Statistical significance was assumed if P < 0.05. Results We identified 173 eligible CT data sets in our data base. Some data sets had to be excluded because of image reconstruction involving overlap (n=12) or non-standard image reconstruction (n=4). Finally, we analyzed single helical CT data sets of 157 patients. For 26 of these patients, additional data from repeat CT were available. The mean lung height (cranio-caudal distance) was 226 ± 33 millimeters. The mean distance between the positions of CT-sections selected for extrapolation was 26 ± 4 millimeters. The mean number of CT-sections covering the lung was 25±3 for 10 mm, and 47±7 for 5 mm slices thickness. In a subgroup of patients, the accuracy of the extrapolation method was compared using ten, five and three CT-sections, respectively. Fifteen of these 45 patients had normal lungs. The distribution of opacifications was lobar in eight, diffuse in 10, and patchy in 12 patients. For Vtotal and Mtotal, bias was significantly greater for extrapolation from three as compared with five or ten CT-sections, respectively. In contrast, bias for Vtotal and Mtotal did not differ significantly when five or ten CT-sections were used for extrapolation (both P values greater than 0.1). While bias values for relative subvolumes and –masses of differently aerated lung compartments did not change significantly with the number of CT-sections used (all P values greater than 0.05), the limits of agreement were considerably broader (Table 3 of the main manuscript). In 26 patients, additional data from repeat CTs were analyzed. The median time between successive CTs was 2 (1-14) days. Absolute changes between two CTs and the agreement between extrapolated changes and the corresponding values from the whole lung are shown in table 4 of the main manuscript. References for the Electronic Supplementary Material ESM1: Puybasset L, Cluzel P, Gusman P, Grenier P, Preteux F, Rouby JJ (2000) Regional distribution of gas and tissue in acute respiratory distress syndrome. I. Consequences for lung morphology. CT Scan ARDS Study Group. Intensive Care Med 26:857–869. 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