In the

In the selleck Enzastaurin present study, we pooled CT data with slice thickness between 5 and 10 mm in the same analysis because the accuracy of extrapolation did not differ with slice thickness (Table (Table3).3). This lack of an effect of slice thickness on the accuracy of extrapolation is in line with our recent study [18]. We intentionally omitted the evaluation of the appropriateness of thinner slices for extrapolation because thin slices can introduce artifacts into quantitative CT analysis [22].Mostly in animal experiments but also in some clinical situations [2,3,26], whole-lung quantitative CT is performed repeatedly during different lung conditions. Consequently, changes of lung volume, mass or differently aerated lung compartments are common endpoints of such CT studies.

We demonstrated that extrapolation enabled accurate quantification of intraindividual changes between consecutive CTs. Therefore, the extrapolation method will also ease analysis of repeated CT scans of the lung.Limitations of our studyThe principal limitations related to the retrospective study design are acknowledged but appear to be of limited importance to our analyses: The difference between the slice locations of prospectively or retrospectively chosen reference CT slices would differ by only a few millimeters [18]. Given this marginal difference between prospective and retrospective validation of the extrapolation method, we considered it unjustified to perform additional dedicated animal experiments. We could not include animals with a patchy distribution of lung opacifications in our analysis.

In a recent study evaluating the extrapolation method in humans, however, we have shown that neither the lung condition nor the distribution of opacifications affected the accuracy of extrapolation [18]. Moreover, common animal models of acute lung injury only rarely lead to real patchy lesions [5,8-10,13,20]. Blinding of investigators involved in the extrapolation procedure to the results of the respective whole-lung analyses was not considered Cilengitide necessary. The potential for investigator bias was significantly limited by the use of dedicated software which, after manual identification of the most cranial and most caudal CT slices, performed all steps of the extrapolation procedure and all calculations automatically.ConclusionsThe extrapolation method validated in this paper is highly accurate and has the potential to reduce significantly both radiation exposure and the time until the quantitative CT results are available.

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