Non-Invasive Evaluation of the Location, the Functional Integrity and the Oxygen Supply of Implants:¹⁹F Nuclear Magnetic Resonance Imaging of Perfluorocarbon-Loaded BA²⁺-Alginate Beads

Abstract

19F nuclear magnetic resonance imaging (MRI) can be used as a non-invasive tool to simultaneously determine the location, the integrity and the oxygen supply of Ba2+-alginate implants. This requires that the beads (implants) are pre-loaded with the perfluorocarbon compound F-44E. Implantation of solid 19F-labelled beads into the peritoneum, below the kidney capsule or into the muscle of Wistar WU rats demonstrated that these beads could be detected by 19F-MRI for up to 18 months after implantation. This indicated that F-44E is not considerably released from the beads during implantation. The signal to noise ratio of liquid-core beads was higher by a factor of 4 than the signal to noise ratio of solid beads, but liquid-core beads were more fragile and also too large for implantation under the kidney capsule and into the intramuscular tissue. Quantitative 2-dimensional 19F-T1 maps (resolution 0.5 x 0.5 mm) could be deduced from 19F-MRI measurements. These T1-maps correlated to the local pO2-values. The partial oxygen pressure estimated in F-44E-loaded Ba2+-alginate beads showed that the oxygen supply inside the beads was very poor when they were implanted below the kidney capsule or into the peritoneal cavity. These low pO2-values obtained for the renal subcapsular site and the peritoneum may explain the failure of previous immunoisolated islet transplantation studies using these locations.

Long-Term Graft Function of Adult Rat and Human Islets Encapsulated in Novel Alginate-Based Microcapsules After Transplantation in Immunocompetent Diabetic Mice

“…The most likely explanation for these findings is that the microcapsules float freely in the peritoneal cavity without any vascularization. The supply of the encapsulated islets with nutrients and oxygen is, therefore, rather limited as evidenced by 19 F nuclear magnetic resonance imaging (29). Therefore, compromised nutrient and oxygen supply to the islets might lead to mass loss (8) and, in turn, a reduction in insulin secretion.…”

In Vivo Noninvasive Monitoring of Dissolved Oxygen Concentration Within an Implanted Tissue-Engineered Pancreatic Construct

“…While noninvasive evaluation of oxygen supply at different implantation sites has been performed using cell-free PFC constructs, 35,36 our work involves the investigation of oxygen levels within functional, cell-containing pancreatic implants. In this study, we demonstrated that in vivo realtime oxygen measurements within a tissue-engineered pancreatic construct, implanted in a diabetic mouse model, can…”

Development and Validation of Noninvasive Magnetic Resonance Relaxometry for the In Vivo Assessment of Tissue-Engineered Graft Oxygenation

“…PFC-loaded alginate beads implanted into the rodent kidney capsule, peritoneal cavity, and quadriceps femoris muscle reveal a hypoxic environment unconducive to islet survival. 38,[42][43][44] Macroencapsulated cell systems, however, are often implanted into the subcutaneous space 2 and these studies, limited to microencapsulation, did not examine the oxygen availability of this site.…”