Synopsis

Overhauser Dynamic Nuclear Polarization (ODNP) is a method to achieve continuous hyperpolarization in MR measurements. Here, the polarization of free radicals is transferred to 1H using High Frequency (HF) pulses at the electron Larmor frequency. At UltraLow Fields (ULF) the frequency of the HF pulse lies in the range of several 100 MHz and is able to penetrate large sample volumes, making continuous in vivo ODNP measurements possible. Since conventional Faraday coils are not sensitive enough at ULF, a Superconducting QUantum Interference Device (SQUID) based detector is employed. First ex vivo images using ODNP enhanced MR have been acquired successfully.

Introduction

Conventional hyperpolarizers ¹ produce hyperpolarized contrast agents, which can be injected into a sample. The hyperpolarized state decays with time and lasts for minutes or even only seconds, ² limiting the usability of this technique. Here, we demonstrate a method which allows for continuous hyperpolarization of a sample using Overhauser Dynamic Nuclear Polarization (ODNP) at UltraLow magnetic Fields (ULF) below 10 mT, ³ Continuous-ODNP requires free electrons within the sample, which are provided by free radicals.² However, there are two major problems with continuous ODNP. First, the free radicals have to be biocompatible in order to perform in vivo measurements.^4,5 Secondly, the hyperpolarization is induced by a High Frequency (HF) pulse, with frequencies 660 times higher than the corresponding nuclear Larmor frequency. In conventional high field MRI-scanners, the penetration depth of such HF pulses is too short to hyperpolarize a sufficiently large sample volume.⁶ A simple approach to increase the penetration depth is to employ ULF MRI where the HF pulse can penetrate several centimeters into the sample. To counteract the inherent low sensitivity of conventional Faraday coils at ULF, a Superconducting QUantum Interference Device (SQUID)-based detector is used. Here, we present a SQUID-detector based ULF MRI scanner. This is an optimal tool for the investigation of different free radicals intended for ODNP, an important step towards the development of new biocompatible free radicals.

With continuous ODNP, signal enhancement factors of up to two orders of magnitude can be achieved.⁷ Using a hyperpolarization field strength of about 20 mT would enhance the MR signal to a level comparable to the thermal equilibrium magnetization of 1T. This fact alone would allow one to perform unique experiments at ULF, such as the detection of functional MRI signals.

Methods

The SQUID-based ULF MRI setup contains a tetracoil for B₀ field generation, a Helmholtz B₁ coil, three gradient coils for spatial encoding (G_phase and G_read), as well as a Helmholtz Bp coil for prepolarization of the sample.⁸ The SQUID-based magnetic field detector is immersed inside a low-noise liquid helium fiber glass dewar [Fig. 1 (a) and (b)].⁹ A second order gradiometric pickup coil with 40 mm diameter is used for signal detection. The sample is positioned 12 mm below the lowest loop of the pickup coil. The HF pulse B_HF, used for ODNP enhancement, is transmitted by a loop antenna (30mm diameter). Various loop configurations can be tuned to frequencies of 80 – 250 MHz.

Due to the high sensitivity of the SQUID to signals from the DC up to the GHz range, the whole system is placed inside a multilayer shielding chamber, which shields static magnetic fields as well as electric HF fields.¹⁰

For first proof-of-principle measurements inside a biological environment, carboxy-proxyl free radicals ¹¹ were injected into the lower belly of a rat carcass ex vivo. The HF excitation coil together with a marker tube was placed on the outside of the belly as shown in Fig. 1 (d).

The spin-echo pulse sequence used to acquire the ULF MR images is shown in Fig. 1 (c). For comparison, the rat was also scanned at a clinical 3 T scanner, using a standard gradient echo sequence.

Results

Discussion

Acknowledgements

References

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