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Abstract:
Introduction: Ultralow-field magnetic resonance imaging (ULF MRI) is a growing field with enormous potential for clinical translation. Although ULF MRI shows limited time and spatial resolution compared to high-field MRI, ULF MRI is cheaper, more widely accessible and the intrinsic contrast of tissues is different.[1]. ULF MRI can be dynamically improved using tailored biophysical/biochemical analysis.[2] Here we show how to use Overhauser dynamic nuclear polarization (ODNP) and signal amplification by reversible exchange (SABRE) to hyperpolarize ULF MRI in vitro and in vivo.[3]
Methods: We used continuous hyperpolarization via Overhauser dynamic nuclear polarization (ODNP) in combination with a SQUID (superconducting quantum interference device) based ULF MRI system operating at B0 ~ 150 µT for the in vivo hyperpolarized experiment. This technique’s bottleneck is finding suitable biocompatible free radicals, which are required to transfer spin order from electrons to protons via an RF field. The development of radicals followed previously reported methods.[4] SABRE was optimized for the spin order transfer from parahydrogen to the substrate via field cycling methods or different RF pulse sequences for hyperpolarization.
Results/Discussion: We show here first in vivo experiments using continuous hyperpolarization through ODNP in combination with a SQUID based system (fig. 1). Data showed that the stability of free radicals is a crucial parameter to take into account for in vivo experiments. For instance, 3-carboxy PROXYL demonstrated high kinetic stability in vivo when injected subcutaneously but higher oxidation when applied intravenously. Therefore, we investigated different radical carrier systems for in vivo imaging applications.[4] We have observed two hits with developed macromolecular functionalized hydroxide-based radicals. We also show novel 13C and 15N hyperpolarization by SABRE and compare them with SABRE-SHEATH [fig. 2(a)]. With the alt-SABRE scheme [fig. 2(b)] we gained 30% additional polarization[5] while with the LIGHT-SABRE scheme [fig. 2(c)], we obtained a similar polarization to standard SABRE. We achieved significant contrast to perform the first hyperpolarized 13C ULF MRI experiments.
Conclusions: We show here the first in vivo experiments using hyperpolarized Overhauser MRI. For future applications we found novel and biocompatible carrier systems for nitroxide-based radicals which show good ODNP performance.
The novel sequences for SABRE enhanced 13C and 15N polarization, enabling X-nucleus imaging at ULF. Provided the high demand for precise, portable, and accessible medical imaging, this work shows a significant advance in ULF imaging.
the DFG for grant Nr. BU 2694/6-1.
