Higher, better, faster!? Ultra-high field magnetic resonance imaging and spatially resolved spectroscopy

Magnetic Resonance Imaging (MRI) and spatially resolved spectroscopy are valuable Magnetic Resonance (MR) techniques ranging from clinical diagnostics and research to applications in environmental and plant sciences. The key advantage is the ability to non-invasively and non-destructively yield information which other techniques cannot provide. A disadvantage of MR techniques, however, is their relatively low sensitivity, which poses limitations to the minimal spatial resolution and target concentration or comes at the expense of long experiment times. The Signal-to-Noise Ratio (SNR) can generally be increased by increasing the main magnetic field strength B0, increasing the sensitivity of the detector, reducing the noise of the coil or enhancing the signal by hyperpolarisation techniques. In this thesis, we mainly focussed on SNR increase by increasing the B0 (cf. chapters 2-6) and to a certain extent by increasing the detector sensitivity (cf. chapters 2,3 and 5), as well as the enhancement by chemical shift saturation transfer (cf. chapter 6).

Ultra-high magnetic field strength for MRI and spatially resolved spectroscopy are anticipated by the research community both with excitement as well as with precaution. Opportunities in terms of increase of both SNR and spectral resolution meet the challenges concerning susceptibility artefacts which cause image distortions and line broadening. During the research project leading to this thesis, we have identified both opportunities as well as challenges on phantoms and biological specimen.

In chapter 1, the main milestones in the discovery of the fundamental physical phenomenon of nuclear magnetic resonance (NMR) and MRI techniques, as well as the road towards the different applications, are explained. The basics of MRI and spatially resolved spectroscopy are discussed, including MR image formation and the most commonly used sequences. The research field of Magnetic Resonance Microscopy (MRM) is set into context, and main hardware differences between the different research areas of MRI, i.e. clinical, preclinical and microimaging, are highlighted. The limitations to MR techniques, being the low SNR, and opportunities to increase the SNR are discussed. In terms of additional benefits and challenges at ultra-high field, susceptibility mismatches which represent a significant challenge in high field MRI are highlighted. A short introduction to spatially resolved spectroscopy methods is given.

In chapter 2, the SNR-increase was quantified systematically across different high-field microimaging systems. In chapter 3, we describe a method protocol for using the uNMR-nl ultra-high field spectrometer (22.3 T) and calibrate new or home-built microcoils. Sample preparation for using solenoid coils is described, and adjustments for MRI experiments are described. A case study for samples posing challenges to ultra-high field MRI due to susceptibility problems is shown in chapter 4. In chapter 5, magnetic resonance imaging and spatially resolved spectroscopy were combined to evaluate the potential of ultra-high field MRI for plant sciences. While the ultra-high magnetic field is suitable for spatially resolved spectroscopy due to the increased SNR improving the detection limit, chemical exchange saturation transfer (CEST) imaging can further improve the detection limit significantly for a number of metabolites which contain exchangeable protons. In chapter 6, we investigated the additional advantage of CEST at ultra-high field, namely the increase of the selectivity towards the desired metabolite on 7.0 T, 17.2 T and 22.3 T systems.

In the general discussion (Chapter 7), we summarise the main findings and conclusions of this thesis. The lessons from ultra-high field MRI and spatially resolved spectroscopy are discussed from a hardware and experimental point of view. We highlight that both the main magnetic field strength and other hardware components, such as gradient strength and detector sensitivity, are important. Experimental considerations, which in particular have to be taken into account when working at ultra-high-field strengths are the chemical shift displacement when performing localised spectroscopy, strategies to reduce susceptibility effects and sequence optimisation. Other strategies for SNR increase, such as cryoprobes and hyperpolarisation, are briefly discussed for a future outlook. As ultra-high field MRM is a research field which usually comes together with small sample sizes, perspectives for different applications such as clinical research, environmental sciences, wastewater treatment, and plant sciences are discussed. Finally, this chapter concludes with an outlook for ultra-high field MRI and spatially resolved spectroscopy for magnetic field strengths beyond 22.3 T.

Overall, we conclude that ultra-high field MRI and spatially resolved spectroscopy are highly beneficial as it leads to higher spatial resolutions, faster acquisition times and improved detection limits for metabolites. These advantages can be in the future further extended to a variety of applications. Novel acquisition approaches, hardware and sample preparation, can be additionally optimised for each application to benefit maximally from the state-of-the-art 22.3 T system.