Multiparametric functional MRI for non-invasive assessment of acute and chronic renal transplant pathology in mice

• Applicants: Privatdozentin Dr. Katja Derlin; Professorin Dr. Faikah Güler (†)
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology ; Nephrology
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 250941805

Long term renal allograft survival remains limited despite recent improvements in immunosuppressive therapy. During the early phase after transplantation, differentiation between acute allograft rejection and delayed graft function due to ischemia reperfusion (IR) injury is crucial. At later stages, chronic renal allograft rejection is an important cause for allograft failure. However, the mechanisms are largely unexplained and non-invasive diagnostic methods to early detect chronic graft pathology have not been established so far. In previous experiments, we showed that functional MRI allows non-invasive assessment of renal pathology in a mouse model of acute kidney injury following IR injury. The purpose of our project is therefore, to use functional multiparametric MRI to investigate renal pathology in mouse models of acute and chronic renal graft pathology. Furthermore, the functional MRI techniques will be validated by direct comparison with renal histology, immunohistochemistry and molecular examinations.In the first part, functional MRI techniques for evaluation of renal perfusion (arterial spin labeling), tissue edema (T1-/T2-mapping), renal hypoxia (BOLD) and cellular infiltration, renal fibrosis and renal microstructure (diffusion/ diffusion tensor imaging) will be optimized for examination of kidney transplants in mouse models. The second part will address acute renal graft pathology. The functional MRI techniques will be used to investigate renal graft pathology after acute rejection (allogenic transplantation) and IR injury (isogenic transplantation). MRI parameters will be compared directly with renal histology and immunohistochemistry (renal morphology, cellular infiltration, tubular necrosis, vessel density, ROS formation), FACS analysis and proinflammatory cytokines. The third part will focus on examination of chronic renal allograft pathology following chronic rejection (allogenic transplantation) and IR injury induced graft fibrosis. Similar to the second part, MRI parameters will be correlated with molecular and histological changes of graft tissue.Non-invasive assessment of renal transplant pathology using functional MRI would be important for preclinical research and drug development, as early detection of graft pathology and longitudinal follow-up within the same animal is possible. In addition, functional MRI of renal transplants may improve diagnostic possibilities in patients after kidney transplantation.

• DFG Programme: Research Grants