T Rodt

Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-β1.

BackgroundMicro-computed tomography (micro-CT) is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time.MethodsPulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1). Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis.ResultsWe found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed.ConclusionsTogether, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.

Phantom and cadaver measurements of dose and dose distribution in micro-CT of the chest in mice

Background Micro-computed tomography (CT) allows high-resolution imaging of the chest in mice for small animal research with a significant radiation dose applied. Purpose To report on measurement of the applied radiation dose using different scan protocols in micro-CT of the chest in mice. Material and Methods Repetitive dose measurements were performed for four different micro-CT protocols (with/without respiratory gating) and for micro-CT fluoroscopy used for chest imaging. Measurements were carried out using thermoluminescence dosimeters (TLD) in mouse cadavers and in a PMMA phantom allowing measurement of the radiation dose in the direct path of rays and assessment of scattered radiation. Results The dose measured inside and outside the chests of the cadavers varied between 190 und 210 mGy, respectively. The expected mean doses in mice in the direct path of rays for the four examined micro-CT protocols varied between 170 and 280 mGy. The mean values for 1 and 5 minutes of fluoroscopy were 17 mGy and 105 mGy, respectively. Conclusion The measured dose values are similar to the dose values for micro-CT of the chest reported so far. A relevant dose can be delivered by micro-CT of the chest, which could possibly interact with small animal studies. Therefore, the applied dose for a specific protocol should be known and adverse radiation effects be considered.

Evaluation of the use of a tablet computer with a high-resolution display for interpreting emergency CT scans.

PURPOSE Evaluation of the potential usability of an iPad 3 with a high-resolution display in CT emergency diagnosis compared to a 3 D PACS workstation. MATERIALS AND METHODS 3 readers used a 5-point Likert scale to evaluate 40 CCT scans and 40 CTPA scans to determine the detectability of early signs of infarction in CCT or segmental and subsegmental pulmonary embolisms in CT angiography of the pulmonary arteries (CTPA) on the iPad 3 (Apple Inc., USA) using an application for image viewing (Visage Ease, Visage Imaging GmbH, Berlin) and on a 3 D PACS workstation (Visage 7.1, Visage Imaging, Berlin) using a certified monitor for image viewing. The results were compared using the Wilcoxon rank sum test, Spearmans correlation coefficient, and a kappa statistic. RESULTS There was no significant difference in the median evaluations for the readings of both the CCT scans and the CTPA scans on the iPad 3 and on the workstation (p > 0.05) for all three readers. The mean Spearmans correlation coefficient for CCT and CTPA was 0.46 (± 0.2) and 0.69 (± 0.16), respectively, for the comparison iPad/PACS, 0.41 (± 0.16) and 0.68 (± 0.06), respectively, for the interobserver agreement on the iPad, and 0.35 (± 0.05) and 0.68 (± 0.10), respectively, for the interobserver agreement on the PACS. Mean kappa values for CCT of 0.52 (± 0.17) for the comparison iPad/PACS and 0.33 (± 0.16) and 0.32 (± 0.16), respectively, for the interobserver agreement on the iPad and the PACS were achieved. For CTPA average kappa values of 0.67 (± 0.19) were calculated for the comparison iPad/PACS and 0.69 (± 0.08) and 0.60 (± 0.14), respectively, for the interobserver concordance on the iPad 3 and the PACS. All differences were not statistically significant (p > 0.05). CONCLUSION The variability of the interpretation of typical emergency scans on an iPad 3 with a high-resolution display and on a 3 D PACS workstation does not differ from the interobserver variability.

Die in-vivo microCT-Cholangiographie zur Evaluation des biliären Systems im murinen Tiermodell

Ziele: Das Ziel dieser Studie war es, die microCT-Cholangiographie als neue Methode zur nicht-invasiven Abbildung des biliaren Systems in einem murinen Tiermodell zu entwickeln und zu evaluieren. Methode: Es wurden jeweils 3 EGF2B-transgene und 3 Wildtyp Mause (Stamm: Blc-6) in die Studie eingeschlossen. Samtliche Untersuchungen wurden unter Inhalationsnarkose durchgefuhrt (Isoflurane). Nach der Injektion von ca. 400µl Megluminiotroxinat (Biliscopin) in die Schwanzvene erfolgten zwei microCT-Untersuchungen an einem dedizierten Kleintierscanner (eXplore Locus, GE Healthcare). Die Untersuchungen wurden unmittelbar nach der Injektion sowie 30 Minuten p.i. durchgefuhrt. Die resultierende isotropen Datensatze mit einer Voxelgrose von 45µm wurden mit morphologischen Filtern nachverarbeitet (MeVisLab, Bremen) und mit einem Open-Source DICOM-Viewer (OsiriX) ausgewertet. Folgende Parameter wurden systematisch untersucht: Akute Toxizitat, Zeitpunkt und Auspragung des Kontrastmittelenhancements sowie Darstellbarkeit der intra- und extrahepatischen Gallenwege. Ergebnis: Die Injektion von Megluminiotroxinat (Biliscopin) wurde von allen Tieren gut toleriert. Es wurde eine sehr rasche hepato-biliare Ausscheidung beobachtet: Der proximale Dunndarm war bei allen Tieren bereits im ersten microCT-Scan kontrastiert. Folgende Strukturen konnten identiiziert werden: intrahepatische Gallenwege (5/6), Ductus cysticus (5/6), Gallenblase (6/6), DHC (6/6), proximaler Dunndarm (6/6). Schlussfolgerung: Die i.v. microCT-Cholangiographie ist eine vielversprechende Methode zur in-vivo Evaluation der biliaren Anatomie im murinen Tiermodell. Sie erlaubt eine verlassliche Darstellung der intra- und extrahepatischen Gallenwege. Korrespondierender Autor: von Falck C Medizinische Hochschule Hannover, Diagnostische Radiologie, Carl-Neuberg-Strasse 1, 30625 Hannover E-Mail: c.v.falck@gmx.de