Fast field-cycling (FFC) nuclear magnetic resonance relaxometry is a well-established method to determine the relaxation rates as a function of magnetic field strength. This so-called nuclear magnetic relaxation dispersion gives insight into the underlying molecular dynamics of a wide range of complex systems and has gained interest especially in the characterisation of biological tissues and diseases. The combination of FFC techniques with magnetic resonance imaging (MRI) offers a high potential for new types of image contrast more specific to pathological molecular dynamics. This article reviews the progress in FFC-MRI over the last decade and gives an overview of the hardware systems currently in operation. We discuss limitations and error correction strategies specific to FFC-MRI such as field stability and homogeneity, signal-to-noise ratio, eddy currents and acquisition time. We also report potential applications with impact in biology and medicine. Finally, we discuss the challenges and future applications in transferring the underlying molecular dynamics into novel types of image contrast by exploiting the dispersive properties of biological tissue or MRI contrast agents. GRAPHICAL ABSTRACT

Dementia, the most severe expression of cognitive impairment, is among the main causes of disability in older adults and currently affects over 55 million individuals. Dementia prevention is a global public health priority, and recent studies have shown that dementia risk can be reduced through non-pharmacological interventions targeting different lifestyle areas. The FINnish GERiatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) has shown a positive effect on cognition in older adults at risk of dementia through a 2-year multidomain intervention targeting lifestyle and vascular risk factors. The LETHE project builds on these findings and will provide a digital-enabled FINGER intervention model for delaying or preventing the onset of cognitive decline. An individualised ICT-based multidomain, preventive lifestyle intervention program will be implemented utilising behaviour and intervention data through passive and active data collection. Artificial intelligence and machine learning methods will be used for data-driven risk factor prediction models. An initial model based on large multinational datasets will be validated and integrated into an 18-month trial integrating digital biomarkers to further improve the model. Furthermore, the LETHE project will investigate the concept of federated learning to, on the one hand, protect the privacy of the health and behaviour data and, on the other hand, to provide the opportunity to enhance the data model easily by integrating additional clinical centres.

Contrast agents with a strong R1 dispersion have been shown to be effective in generating target-specific contrast in MRI. The utilization of this R1 field dependence requires the adaptation of an MRI scanner for fast field-cycling (FFC). Here, we present the first implementation and validation of FFC-MRI at a clinical field strength of 3 T. A field-cycling range of ±100 mT around the nominal B0 field was realized by inserting an additional insert coil into an otherwise conventional MRI system. System validation was successfully performed with selected iron oxide magnetic nanoparticles and comparison to FFC-NMR relaxometry measurements. Furthermore, we show proof-of-principle R1 dispersion imaging and demonstrate the capability of generating R1 dispersion contrast at high field with suppressed background signal. With the presented ready-to-use hardware setup it is possible to investigate MRI contrast agents with a strong R1 dispersion at a field strength of 3 T.

Many smart magnetic resonance imaging (MRI) probes provide response to a biomarker based on modulation of their rotational correlation time. The magnitude of such MRI signal changes is highly dependent on the magnetic field and the response decreases dramatically at high fields (>2 T). To overcome the loss of efficiency of responsive probes at high field, with fast‐field cycling magnetic resonance imaging (FFC‐MRI) we exploit field‐dependent information rather than the absolute difference in the relaxation rate measured in the absence and in the presence of the biomarker at a given imaging field. We report here the application of fast field‐cycling techniques combined with the use of a molecular probe for the detection of Zn²⁺ to achieve 166 % MRI signal enhancement at 3 T, whereas the same agent provides no detectable response using conventional MRI. This approach can be generalized to any biomarker provided the detection is based on variation of the rotational motion of the probe.

In the search for a novel MRI contrast agent which relies on T1 shortening due to quadrupolar interaction between Bi nuclei and protons, a fast scanning wideband system for zero-field nuclear quadrupole resonance (NQR) spectroscopy is required. Established NQR probeheads with motor-driven tune/match stages are usually bulky and slow, which can be prohibitive if it comes to Bi compounds with low SNR (excessive averaging) and long quadrupolar T1 times. Moreover many experiments yield better results at low temperatures such as 77 K (liquid nitrogen, LN) thus requiring easy to use cryo-probeheads. In this paper we present electronically tuned wideband probeheads for bands in the frequency range 20-120 MHz which can be immersed in LN and which enable very fast explorative scans over the whole range. To this end we apply an interleaved subspectrum sampling strategy (ISS) which relies on the electronic tuning capability. The superiority of the new concept is demonstrated with an experimental scan of triphenylbismuth from 24 to 116 MHz, both at room temperature and in LN. Especially for the first transition which exhibits extremely long T1 times (64 ms) the and low signal the new approach allows an acceleration factor by more than 100 when compared to classical methods.