Development of a compact NMR system to measure pO(2) in a tissue-engineered graft

开发一种紧凑型核磁共振系统,用于测量组织工程移植物中的氧分压 (pO₂)

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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 (19)F 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 (19)F 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 (19)F 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. (19)F 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 (19)F longitudinal relaxation rate (R(1)) measurements in times as short as ∼2 min (R(1) vs oxygen partial pressure and temperature (R(2) > 0.98)). The estimated sensitivity of R(1) 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 (19)F NMR relaxometry system appears feasible.

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