Abstract
Hypoxia is one of the key factors affecting the survival of islet cells transplanted via the portal vein. Blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) is the only imaging technique that can detect the level of blood oxygen level in vivo. However, so far no study has indicated that BOLD-fMRI can be applied to monitor the liver oxygen level after islet transplantation. To evaluate the value of Carbogen-challenge BOLD MRI in assessing the level of hypoxia in liver tissue after portal microcapsules implanted. Fifty-one New Zealand rabbits were randomly divided into three experimental groups (15 in each group) were transplanted microencapsulated 1000 microbeads/kg (PV1 group), 3000 microbeads/kg (PV2 group), 5000 microbeads/kg (PV3 group), and 6 rabbits were injected with the same amount of saline as the control group, BOLD-fMRI was performed following carbogen breathing in each group after transplantation on 1d, 2d, 3d and 7d, T2* weighted image, R2* value and ΔR2* value parameters for the liver tissue. Pathological examinations including liver gross pathology, H&E staining and pimonidazole immunohistochemistry were performed after BOLD-fMRI. The differences of pathological results among each group were compared. The ΔR2* values and transplanted doses were analyzed. ΔR2* values at the 1-3d and 7d after transplantation were significantly different in each groups (P<0.05). ΔR2* values decreased gradually with the increase of transplanted dose, and was negatively correlated with transplant dose at 3d after transplantation (r = -0.929, P <0.001). Liver histopathological examination showed that the degree of hypoxia of liver tissue increased with the increase of transplanted doses, Carbogen-challenge BOLD-fMRI can assess the degree of liver hypoxia after portal microcapsules implanted, which provided a monitoring method for early intervention.
Highlights
Islet cell transplantation is an ideal treatment of type I diabetes mellitus and can effectively prevent the progress of diabetes mellitus [1,2,3]
Blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) is the only imaging technique that can detect the level of blood oxygen level in vivo
Assessment of liver hypoxia after portal microcapsules implantation the portal vein were obviously enlarged, a large number of degeneration and necrosis of hepatocytes were observed, and neutrophil infiltration was detected in the interstitium (Fig 1)
Summary
Islet cell transplantation is an ideal treatment of type I diabetes mellitus and can effectively prevent the progress of diabetes mellitus [1,2,3]. It is believed that the survival of islet cells after transplantation depends mainly on the revascularization of blood supply, which originates from the host. Before the establishment of blood supply, islet cells mainly depended on oxygen permeation with surrounding liver parenchyma to maintain their function and survival. Large dose of microcapsules will stay in the small branches of portal vein after entering the liver, which may cause vascular embolism, leading to ischemic blood oxygen in the surrounding liver tissue, necrosis and apoptosis, seriously affecting the oxygen permeation of islet cells, thereby leading to islet cell damage, and impairing the liver function, affecting the therapeutic effect [12,13,14,15]. No study has indicated that BOLD-fMRI can be applied to monitor the liver oxygen level after islet transplantation
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