In recent years (ultra) low field Magnetic Resonance Imaging (MRI) developed to a tool, which can be combined with other imaging techniques such as magnetic particle imaging1 or magneto encephalography2. Yet the full potential of low field MRI is not nearly exploited. In this project the combination of a state of the art (ultra) low field system, based on a Superconducting QUantum Interference Device (SQUID) detector, and just recently developed hyperpolarization techniques with parahydrogen is realized3. With this combination new hyperpolarized contrast agents can be developed and tested. Due to the increased sensitivity of the SQUID based detection system it will become realistic to accomplish in vivo measurements with these hyperpolarized contrast agents. The successful performance of in vivo experiments might open a completely new playground for radiologists and might provide a powerful tool for diagnostic.

SQUID sensor

The heart of the planed system is the SQUID sensor consisting of a SQUID inductively coupled to a superconducting gradiometer. A magnetic field applied to the lowest loop of the gradiometer induces a supercurrent and hence a flux in the SQUID loop. This flux transformer increases the sensitivity to nearby magnetic sources while providing a high level of rejection to distant magnetic noise sources, such as elevators, cars, and nearby laboratory equipment. A magnetic field noise of approximately 0.5 fT/Hz-1/2 can easily be reached by using commercially available SQUIDs, but can be decreased even further to 0.2 fT/Hz-1/2. The gradiometer and SQUID are immersed in liquid helium contained in a low-noise fiberglass dewar with negligible magnetic noise.

Figure 1 shows a schematic of the low field MRI system configuration. To suppress the Earth’s field a mu metal shield is used.

A tetra coil is used to produce the imaging field B0, ranging from 50 µT to 2 mT. A Maxwell pair produces the diagonal gradient field, two sets of planar gradient coils produce off-diagonal fields and an excitation coil provides oscillating B1 pulses to manipulate the polarization of the sample. The loops of the B1 coil should be perpendicular to the other coils to reduce the mutual inductance between the coils.

An aluminum shield surrounding the entire system reduces environmental magnetic field noise.

Setup Optimization

Unlike as in conventional MRI, the fields and gradients needed for low field MRI are quite small and all coils can be wound out of standard copper wire. The spins of the sample precess about the static magnetic field B0, which determines the precession frequency. Due to the hyperpolarization of the sample and the use of a SQUID instead of a Faraday coil, the size of the detected NMR signal does not depend on the frequency, thus we are free to choose B0 to best suit our measurement. To get the optimal polarization transfer from parahydrogen to the catalyst to be hyperpolarized, B0 should be around 2 mT. The B0 coil is powered by a DC current source with an exceptionally long time constant as indicated by the low pass filter in the block diagram (fig. 2). Unlike traditional MRI, the homogeneity requirements of our B0 field are quite modest: a homogeneity of 0.01% across the sample volume results in a line-width of 5 Hz, which is smaller than the typical T2 broadening (broadening due to spin-spin dephasing). The spins are excited by an oscillating field B 1, which we call the excitation field.  The coil is wound around two frames in a Helmholtz arrangement. An open geometry of the coils allows flexibility for setting up the experiment. As the amplifiers does not need to be active during measurement, physical relays can be included to decouple them during signal acquisition (see fig. 2).

Three pairs of gradient producing coils can be implemented for spatial decoding of the signal. All three gradients are bi-planar designs and can produce similarly sized gradients, thus allowing an interchangeably use during an MRI sequence. The gradient coils are pulsed and can be relayed out (like the B1 coil) during signal acquisition. First a system is constructed for comparison with already existing setups, which uses Faraday coils for the signal detection4. Theory predicts, that the signal to noise ratio should increase by a factor of 5 to 10 using a SQUID based sensor for detection5. After optimizing the system the goal of the project will be to develop biocompatible hyperpolarized contrast agents with parahydrogen3, which can be used for first in vivo studies.

Development of hyperpolarized contrast agents

Recently it was found that a hyperpolarized equilibrium can be reached using an exchange reaction between parahydrogen and a catalyst at mT fields3. The catalyst used in ref. [3] is not soluble in water and therefore needs substances, like ethanol, in concentrations toxic for mammals. So, the catalyst needs to be modified in a way that it becomes water soluble while exchange reactions with parahydrogen still work at (ultra) low fields.

 

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