Tobacco smoke shortens T1 in a mouse model of COPD
Daniel Alamidi1, Amir Smailagic2, Abdel Bidar2, Nicole Parker2, Marita Olsson2, Sonya Jacksson2, Linda Swedin2, Paul Hockings3,4, Kerstin Lagerstrand1, and Lars E Olsson5

1Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, 2AstraZeneca R&D, Mölndal, Sweden, 3Medtech West, Chalmers University of Technology, Gothenburg, Sweden, 4Antaros Medical, BioVenture Hub, Mölndal, Sweden, 5Department of Medical Physics, Lund University, Translational Sciences, Malmö, Sweden


Tobacco smoking is the main cause of COPD. MRI may improve the characterization of COPD where lung T1 mapping has been used to study lung disease. We investigated whether tobacco smoke exposure affects lung T1 in a mouse model with repeated T1 readouts and biological measurements. Free breathing 3D-UTE T1 maps of the lungs were weekly performed over one month in mice exposed to air or tobacco smoke. The lung T1 was shortened in the tobacco smoke exposed mice, most likely due to early signs of smoking-induced lung pathology. Consequently, T1 is a potential biomarker of lung disease.


Lung T1 mapping has been applied to study chronic obstructive pulmonary disease (COPD)1,2 which is commonly caused by tobacco smoking and with limited understanding of its relationship to pathology. We have implemented a robust and repeatable 3D ultra-short echo time (UTE) T1 mapping protocol for mouse lungs3 that allows follow up of treatment over time. The purpose of this study was to investigate T1 as a readout of tobacco smoke (TS) exposure in lungs in a mouse model with repeated T1 readouts and functional and biological measurements.


Radial 3D-UTE T1 maps (TE/TR=8us/10ms, FOV=40x40x50 mm3, matrix size=1403, FA=3° and 17° with total scan time=20min) of the lungs were performed in anesthetized Balb/c free breathing mice (approved by the local animal research ethics committee) at 4.7T. The animals were exposed to air, Ctrl (n=8), or TS (n=12) and were scanned weekly over one month. Mean lung T1 values were calculated by fitting the spoiled gradient echo signal equation4 pixel-by-pixel and large pulmonary vessels were excluded in the quantification. Lung mechanics, bronchoalveolar lavage (BAL) fluid and histology analysis were carried out in all mice after the last imaging procedure. Parallel animal groups were added for weekly functional and biological readouts. Repeated ANOVA was used to test T1 differences over time.


Significant T1 shortening was found in TS exposed mice between baseline and two (p<0.001) and three (p<0.001) weeks exposure and between first and third (p<0.05) week (Fig 1). Significant T1 increase was found between third and fourth week (p<0.001). No significant T1 changes were observed in the control mice at any time point. Inflammatory cells were significantly increased (p<0.001) in BAL fluid after four weeks TS exposure. Lung T1 correlated to total cell count in BAL (r=0.62, p<0.01) between baseline and after one month TS exposure (Fig 2). No significant lung mechanic changes were observed at any time point for both groups. Mice exposed to TS had large lymphocytic perivascular inflammation and an increased number of macrophages within the lung parenchyma at week 1-4. Cellular debris was noted in the lungs after four weeks TS exposure.


Significant changes of lung T1 in TS exposed mice compared to mice exposed to air were demonstrated. The T1 shortening in the TS exposed mice most likely reflect early signs of smoking-induced lung pathology with structural pulmonary changes. Emphysematous and fibrotic5 tissue may shorten lung T1. However, these biological changes were not found in the histology analysis after this relatively short TS exposure time6. Lung T1 could be affected due to the presence of paramagnetic substances trapped in the lung tissue7. However, the significant T1 increase between week three and four in the TS exposed mice contradict with this theory. Reduced oxygen concentrations8 and increased inflammation9 would increase T1 in the lung and might explain the T1 increase between week three and four in the TS exposed mice. Our findings indicate that the TS exposed lungs most likely experience several different ongoing processes in time that changes the intrinsic T1 in lung parenchyma. The results support that T1 is a potential biomarker of tobacco-induced lung disease in an animal model of COPD.


This work was supported by AstraZeneca and Allmänna Sjukhusets i Malmö stiftelse för bekämpande av Cancer.


[1] Alamidi et al. COPD:JCOPD 2015 Oct 21:1-7. [2] Jobst et al. Plos One 2015;10:3. [3] Alamidi et al. Proc Eur Soc Magn Reson Med Biol 2015:301. [4] Fram et al. MRI 1987;5:201-8. [5] Stadler et al. MRM 2007;59:96-101. [6] Wright et al. Am J Physiol Lung Cell Mol Physiol 2008;295:L1-L5. [7] Kilburn. Environ Health Perspect 1984;55:97. [8] Edelman et al. Nat Med 1996;2:1236-9. [9] Bottomley et al. Med Phys 1987;14:1-37.


Fig 1. Mean lung T1 change normalized to baseline for control and TS exposed mice. Data are means ± SEM.

Fig 2. Lung T1 as a function of the total number of inflammatory cells (A) and macrophages (B) in mice exposed to TS in four weeks and control animals. Significant correlations between lung T1 and total number of inflammatory cells (r=0.62, p<0.01) and macrophages (r=0.64, p<0.01) were found, i.e. longer T1 correlated to increased number of inflammatory cells.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)