A Closer Radiological Look at Chronic Rejection after Murine Orthotopic Lung Transplantation

• Published in: The Journal of heart and lung transplantation Vol. 40; no. 4; pp. S347 - S348
• Main Authors: Kaes, J., Heigl, T., Aelbrecht, C., Velde, G. Vande, Vanstapel, A., Verleden, S., Neyrinck, A., Van Raemdonck, D., Verleden, G., Ceulemans, L., Vos, R., Vanaudenaerde, B.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.04.2021
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2021.01.980

Chronic lung allograft dysfunction (CLAD) is the main culprit for low survival after human lung transplantation (LTx). Within the clinical identification of CLAD, the immunological enigma of chronic rejection was lost. This is difficult to study in the complex patient setting; but an appropriate experimental model may help. Our goal was to further elaborate our mouse model of chronic rejection by implementing in vivo microCT (µCT). Using the orthotopic single left LTx model with cuffing method, isografts (n=9; C57BL/6N to C57BL/6N) and allografts (n=8; Balb/c to C57BL/6N) were transplanted. Mice received daily immunosuppression with 10 mg/kg cyclosporine A and 1.6 mg/kg methylprednisolone for 10 weeks. In vivo respiratory-gated time resolved µCT (SkyScan 1278, Bruker) was performed at postoperative week 1, 5 and 10, lung density and volume (at in and expiration) were quantified. In 1 isografts technical failure was observed (on both CT and histology), the other 8 demonstrated normal lung structure at week 10. 5 isografts had normal lung density at week 1, 5 and 10 (1.03±0.02; 1.04±0.01; 1.01±0.02), compared to 3 isografts which had significant increased lung density at week 1 (1.22±0.01; p<0.0001) (Figure) that decreased to normal at week 5 and week 10 vs week 1 (0.99±0.04; p=0.001; 1.00±0.01; p<0.0001). Within allografts, 2 failures were observed. Lung density of 6 allografts at week 1 was comparable to isografts at week 1 (1.01±0.01; p=0.92) but increased at week 5 and week 10 vs week 1 (1.09±0.02; p=0.002; 1.08±0.03; p=0.005). In allografts, 4 had a mild pattern and 2 had a severe pattern with density difference at week 10 (1.05±0.04 versus 1.14±0.01; p=0.002) (Figure). Same patterns were observed for lung volume, tidal volume and airway volume. Longitudinal µCT is useful to investigate lung volume, lung density, lung ventilation/tidal volume of the transplanted lung and can identify and monitor the evolution/severity of both chronic rejection and primary graft dysfunction (PGD).