Ultralow Field Magnetic Resonance Imaging
Why ULF MRI?
In recent years UltraLow Field Magnetic Resonance Imaging (ULF MRI) developed to a tool, which can be combined with other imaging techniques such as magnetic particle imaging or magnetoencephalography. Yet the full potential of low field MRI is not nearly exploited. In this project a state of the art ultralow field system using a detection coil based on a Superconducting QUantum Interference Device (SQUID) is combined with hyperpolarization techniques based on Overhauser Dynamic Nuclear Polarization (ODNP) and parahydrogen.
The ULF MRI system provides an optimal platform for the development and testing of these two hyperpolarizing techniques. Due to the increased sensitivity of the SQUID based detection system and ODNP hyperpolarization it will become realistic to accomplish in vivo imaging with a quality of high field scanners. The successful performance of in vivo experiments might provide enough signal to realize functional MRI at ultralow fields. This is an important step for a combined ultralow field MRI and MEG system. A system which would provide the high spatial resolution of fMRI and the high temporal resolution of MEG.
Possibilities of ULF MRI
The major goal of our project group is the development of in vivo hyperpolarization techniques. The ULF MRI system, which will be further advanced with novel SQUID technology and imaging capabilities, will not only serve as a platform to test these novel techniques in phantoms and small animals, it will also be used to push the limits of ULF MRI into regions of conventional high field MRI. The most promising candidate for in vivo hyperpolarization so far is ODNP using free radicals to transport the much higher polarization of electrons to, for example, protons. The major advantage to test and optimize biocompatible free radicals at low fields is the low electron Larmor frequency in the range of 100 MHz at these fields. This allows to use conventional RF technology and full RF penetration into larger objects or small animals. Assuming a (continuous) ODNP amplification of about 50 at a Bp field of 20 mT will roughly provide a signal amplification that is comparable to thermal polarization at 1T. This already allows to perform unique experiments with an SNR at 1T combined with significant longer transversal relaxation times T2 at only 0.1 to 20 mT. Another target of this project is to transfer this technique to high fields such as 7T to 14T. Assuming a similar ODNP amplification of 50 at these high fields (which should be theoretical feasible) will give a proton MR signal comparable to thermal polarization at about 500T. Focusing on neuroscientific applications this might even offer the possibility to directly detect fingerprints of neuronal currents within the MR signal. At magnetic fields of 7T to 14T the corresponding electron Larmor frequency is in the millimeter range which limits tissue penetration to probably only the cerebral cortex at the surface (in small animals). The required microwave RF technology is developed in collaboration with our long-standing collaboration partner Prof. Jens Anders at the Electrical Engineering Department at the University of Ulm.
The ULF MRI system
The heart of the ultralow field 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 picture and a schematic of the low field MRI system configuration. To suppress the Earth’s field and external noise a three layered shielding chamber, consisting of two mu metal layers and one aluminum layer is used
Unlike as in conventional MRI, the fields and gradients needed for low field MRI are 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. A tetra coil configuration is used to produce the B0 field, ranging from 10 µT to 2 mT. 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 or to reach a higher level of polarization with ODNP, a prepolarizing coil Bp can be used to bump up B0 to 12 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 1 Hz, which is smaller than the typical T2 broadening (broadening due to spin-spin dephasing). The spins are excited by an oscillating field B1, 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 are implemented for spatial decoding of the signal. Two 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. An additional gradient in a Maxwell configuration is driven by a homemade low noise current source, which effectively adds no additional noise during the SQUID read out and hence can be used as read gradient.
ODNP and SABRE results
One outstanding advantage of our ULF MRI system is the possibility for continuous ODNP hyperpolarization in vivo. In ODNP the much higher polarization of electrons is transferred to the protons via an rf pulse in the range of the electron Larmor frequency. Since the electron Larmor frequency is about 660 times higher than for protons, in the mT range this frequency corresponds to about 100 MHz. This frequency is still able to penetrate tissue, making ODNP continuously possible for in vivo hyperpolarization.
However, ODNP works only in the presence of free radicals, which are usually provided by toxic substances like (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl known as TEMPO. To circumvent that problem the chemistry department of the University of Tuebingen is developing on the one hand biocompatible substances providing free radicals and on the other hand immobilizing the TEMPO molecules in silica nano particles, making them biocompatible.First tests on phantoms and plants with this technique were already performed and first MR images were acquired (see fig. 3).
Towards in vivo experiments on small animals
The main goal of this project is to test the in vivo compatibility and functionality of ODNP. The next steps will be to use the optimized ULF MRI system to accomplish first in vivo measurements on a small number of rats. Since all components needed for this experiment are already tested, we are optimistic to demonstrate the feasibility of the combination of SQUID based MRI, ODNP and in vivo experiments on small animals. We hope to have even enough signal do demonstrate first functional MRI measurements in the ULF regime. A further, future goal is to transfer ODNP to high fields such as 7T to 14T, which will give a proton MR signal comparable to thermal polarization at about 500T. The required microwave RF technology will be developed in collaboration with our long-standing collaboration partner Prof. Jens Anders at the Electrical Engineering Department at the University of Ulm.