Development of a compact NMR system to measure pO2 in a tissue-engineered graft

Abstract

Cellular macroencapsulation devices, known as tissue engineered grafts (TEGs), enable the transplantation of allogeneic cells without the need for life-long systemic immunosuppression. Islet containing TEGs offer promise as a potential functional cure for type 1 diabetes. Previous research has indicated sustained functionality of implanted islets at high density in a TEG requires external supplementary oxygen delivery and an effective tool to monitor TEG oxygen levels. A proven oxygen-measurement approach employs a ¹⁹F oxygen probe molecule (a perfluorocarbon) implanted alongside therapeutic cells to enable oxygen- and temperature- dependent NMR relaxometry. Although the approach has proved effective, the clinical translation of ¹⁹F oxygen relaxometry for TEG monitoring will be limited by the current inaccessibility and high cost of MRI. Here, we report the development of an affordable, compact, and tabletop ¹⁹F NMR relaxometry system for monitoring TEG oxygenation. The system uses a 0.5 T Halbach magnet with a bore diameter (19 cm) capable of accommodating the human arm, a potential site of future TEG implantation. ¹⁹F NMR relaxometry was performed while controlling the temperature and oxygenation levels of a TEG using a custom-built perfusion setup. Despite the magnet's nonuniform field, a pulse sequence of broadband adiabatic full-passage pulses enabled accurate ¹⁹F longitudinal relaxation rate (R₁) measurements in times as short as ∼2 min (R₁ vs oxygen partial pressure and temperature (R² > 0.98)). The estimated sensitivity of R₁ to oxygen changes at 0.5 T was 1.62-fold larger than the sensitivity previously reported for 16.4 T. We conclude that TEG oxygenation monitoring with a compact, tabletop ¹⁹F NMR relaxometry system appears feasible.

Keywords: 19F NMR; adiabatic pulses; compact NMR; relaxometry; tissue engineered graft.