In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates.
OBJECTIVE
As islet transplantation begins to show promise as a clinical method, there is a critical need for reliable, noninvasive techniques to monitor islet graft survival. Previous work in our laboratory has shown that human islets labeled with a superparamagnetic iron oxide contrast agent and transplanted into mice could be detected by magnetic resonance imaging (MRI). The potential translation of these findings to the clinical situation requires validation of our methodology in a non-human primate model, which we have now carried out in baboons (Papio hamadryas) and reported here.


METHODS
For islet labeling, we adapted the Food and Drug Administration-approved superparamagnetic iron oxide contrast agent, Feridex, which is used clinically for liver imaging. After partial pancreatectomy, Feridex-labeled islets were prepared and autotransplanted underneath the renal capsule and into the liver. Longitudinal in vivo MRI at days 1, 3, 8, 16, 23, and 30 after transplantation was performed to track the islet grafts.


RESULTS
The renal subcapsular islet graft was easily detectable on T2*-weighted MR images as a pocket of signal loss disrupting the contour of the kidney at the transplantation site. Islets transplanted in the liver appeared as distinct signal voids dispersed throughout the liver parenchyma. A semiautomated computational analysis of our MRI data established the feasibility of monitoring both the renal and intrahepatic grafts during the studied posttransplantation period.


CONCLUSIONS
This study establishes a method for the noninvasive, longitudinal detection of pancreatic islets transplanted into non-human primates using a low-field clinical MRI system.
Medarova
Zdravka
Z
Department of Radiology, Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
Vallabhajosyula
Prashanth
P
Tena
Aseda
A
Evgenov
Natalia
N
Pantazopoulos
Pamela
P
Tchipashvili
Vaja
V
Weir
Gordon
G
Sachs
David
D
Moore
Anna
A
D000818:Animals; D017209:Apoptosis; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007501:Iron / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000473:pathology*; D007668:Kidney; D016031:Liver Transplantation / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D010087:Oxides; D010180:Pancreatectomy; D010215:Papio; D013370:Subrenal Capsule Assay / Q000379:methods*; D014182:Transplantation, Autologous / Q000473:pathology*; D014183:Transplantation, Heterologous
D003287:Contrast Media; D003911:Dextrans; D007328:Insulin; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide