Contrast enhanced longitudinal changes observed in an experimental bleomycin-induced lung fibrosis rat model by radial DCE-MRI at 9.4T

• René In 't Zandt - Lunds universitet

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• Lunds universitet - Lund Bildcenter LBIC

• Lunds universitet

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• Engelska

Elva hanråttor av Sprague-Dawley-stammen fick en enda intratrakeal dos av bleomycin (1000 iU), och fyra kontrollråttor fick saltlösning.

• Tidsserie
• Longitudinell

• Preklinisk studie

Eleven male Sprague-Dawley rats received a single intratracheal dose of bleomycin (1000iU) and four control rats received saline. Imaging was performed on days 7 and 28 post-induction. Ultra-short echo time imaging was used to image the lung for 7 minutes after which Clariscan was injected intravenously. Lung signal changes were measured for an additional 21 minutes. Images were reconstructed with a sliding-window approach, providing a temporal resolution of 10 seconds per image. After imaging on day 28, animals were euthanized, and lungs were collected for histology.

A total of 15 animals were included in this study. 4 animals were used as controls (receiving only Saline instillation) and 11 animals received bleomycin. Based on prior experiences with the bleomycin model, 5 out of 11 animals were designated as backup subjects from the imaging group of bleomycin exposed animals, to maintain the study's reliability and continuity in case of unexpected issues with the primary subjects, such as extensive weight loss or imaging or anesthesia related events. Day 7 and day 28 were chosen for DCE-MRI scan days as two representative days of dominant inflammatory and fibrotic time points respectively. The planned group size for DCE-MRI in bleomycin exposed animals was n=6. DCE-MRI was successful in 3 out of 4 control animals on day 7, for 1 animal the Venflon catheter punctured the venous artery and substantial amount of fluid was injected extra-vascular in the tail. This animal was removed from the DCE-MRI on day 28 due to vascular damage in the tail. Subsequently, only 3 controls were available for DCE-MRI on day 28 as well. In the bleomycin-exposed group, all DCE-MRI injections (n=6) were completed successfully on day 7. On day 28, one contrast agent injection partly failed as the images showed that only a fraction of the contrast agent reached the lung. This reduced the group size for DCE-MRI in bleomycin-exposed group animals to n=5. The tissue to air fraction was estimated based on microscopy sections in 4 control animals of which 3 were scanned using DCE-MRI and for 11 bleomycin-exposed animals of which 5 were scanned on day 28 using DCE-MRI (Fig 4A). During inspection of the samples, it was noted that the inflation procedure during fixation of the lung tissue clearly failed for one of the control animals (nr 03) and for one of the bleomycin-exposed animals (nr 07). This reduced the size of the bleomycin group to 10 individuals and the control group to 3 animals for the tissue fraction quantification. The data for animals 03 and 07 is included in the repository to demonstrate the effect of incomplete inflation of the lungs.

• Stillbild

Lunds universitet, Lund Bildcenter, LBIC

• Irma Mahmutovic Persson - Lunds universitet - Lunds Bildcenter LBIC

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Lund - 4003/2017

• Andra medicinska och farmaceutiska grundvetenskaper

• Allmän hälsa och välbefinnande

• Lungsjukdomar
• Bleomycin
• Magnetisk resonanstomografi
• Lungskada