Field-Cycling MRI for Identifying Minor Ischemic Stroke Below 0.2 T.

Background Field-cycling imaging (FCI) is a new technology developed at the University of Aberdeen that measures change in T1 relaxation time constant of tissues over a range of low magnetic field strengths (0.2-200 mT) by rapidly switching between different fields during the pulse sequence. This provides new sources of contrast, including some invisible to clinical MRI scanners, and may be a useful alternative imaging modality for stroke. Purpose To test whether a prototype whole-body FCI scanner can be used to identify infarct regions in patients with subacute ischemic stroke. Materials and Methods This prospective study screened consecutive adult patients admitted to a single center stroke unit from February 2018 to March 2020 and April to December 2021. Included participants with confirmed ischemic stroke underwent FCI 1-6 days after ictus. FCI scans were obtained at four to six evolution fields between 0.2 mT and 0.2 T, with five evolution times from 5 to 546 msec. T1 maps were generated. The Wilcoxon signed-rank test was used to compare infarct region and contralateral unaffected brain, and Spearman rank correlation was used to examine associations between infarct to contralateral tissue contrast ratio and field strengths. Two independent readers blinded to clinical images rated the FCI scans. Results Nine participants (mean age, 62 years ± 16 [SD]; all male) successfully completed FCI. FCI scans below 0.2 T exhibited hyperintense T1 regions corresponding to the infarct region identified at baseline imaging, visually confirmed with 86% interrater agreement (Cohen κ = 0.69). Infarct to contralateral tissue contrast ratio increased as magnetic field decreased between 0.2 mT and 0.2 T (r[24] = -0.68; P < .001). T1 dispersion slopes differed between infarct and unaffected tissues (median, 0.23 [IQR, 0.18-0.37] vs 0.35 [IQR, 0.27-0.43]; P = .03). Conclusion Whole-brain FCI can be used to identify subacute ischemic stroke by T1 relaxation mechanisms at field strengths as low as 0.2 mT. Research Registry no. 1813 Published under a CC BY 4.0 license. Supplemental material is available for this article.

Joint multi-field T1 quantification for fast field-cycling MRI.

PURPOSE: Recent developments in hardware design enable the use of fast field-cycling (FFC) techniques in MRI to exploit the different relaxation rates at very low field strength, achieving novel contrast. The method opens new avenues for in vivo characterizations of pathologies but at the expense of longer acquisition times. To mitigate this, we propose a model-based reconstruction method that fully exploits the high information redundancy offered by FFC methods. METHODS: The proposed model-based approach uses joint spatial information from all fields by means of a Frobenius - total generalized variation regularization. The algorithm was tested on brain stroke images, both simulated and acquired from FFC patients scans using an FFC spin echo sequences. The results are compared to three non-linear least squares fits with progressively increasing complexity. RESULTS: The proposed method shows excellent abilities to remove noise while maintaining sharp image features with large signal-to-noise ratio gains at low-field images, clearly outperforming the reference approach. Especially patient data show huge improvements in visual appearance over all fields. CONCLUSION: The proposed reconstruction technique largely improves FFC image quality, further pushing this new technology toward clinical standards.

A Novel Class of 1 H-MRI Contrast Agents Based on the Relaxation Enhancement Induced on Water Protons by 14 N-Containing Imidazole Moieties.

This study reports the development of a completely new class of MRI contrast agents, displaying remarkable relaxation effects in the absence of paramagnetic metal ions. Their detection requires the acquisition of images at variable magnetic field strength as provided by fast field cycling imaging scanners. They contain poly-histidine chains (poly-His), whose imidazole groups generate 14 N-quadrupolar-peaks that cause a relaxation enhancement of water protons at a frequency (1.38±0.3 MHz) that is readily detectable from the frequencies associated with endogenous proteins. The poly-His quadrupolar peaks are detectable only when the polymer is in a solid-like form, that is, at pH>6.6. Above this value, their intensity is pH dependent and can be used to report on the occurring pH changes. On this basis, the poly-His moieties were conjugated to biocompatible polymers, such as polylactic and glycolic acid, in order to form stable nanoparticles able to encapsulate structured water in their core. FFC images were acquired to assess their contrast-generating ability.

Rapid field-cycling MRI using fast spin-echo.

PURPOSE: Fast field-cycling MRI (FFC-MRI) is a technique that promises to expand upon the diagnostic capabilities of conventional MRI by allowing the main field, B0 , to be varied during a pulse sequence, thus allowing access to new types of endogenous contrast. However, this necessitates longer scan times, which can limit the technique's application to clinical research. In this paper, an adaptation of the fast spin-echo (FSE) pulse sequence for use with FFC-MRI is presented, known as field-cycling fast spin-echo (FC-FSE). This technique allows much faster image acquisition, thus shortening scan times significantly. METHODS: Image quality and relaxometric accuracy were assessed by comparison of phantom images with data obtained using conventional techniques. As proof of principle, relaxometric images were obtained from the thighs of a human volunteer. RESULTS: Image quality remains good for speedup factors of up to 4-fold. The accuracy of relaxometry data is in good agreement with conventional techniques. Results from a volunteer study were encouraging, demonstrating that the technique is sensitive enough to detect quadrupole peaks in vivo. CONCLUSION: The technique has been demonstrated in phantom experiments with little loss of image quality or relaxometric accuracy. Initial in-vivo results pave the way for future clinical studies.

A flexible 8.5 MHz litz wire receive array for field-cycling imaging.

Objectives. Low frequency coils present unique challenges as loop losses, component losses, and the supporting electronics can significantly degrade the signal-to-noise ratio (SNR). SNR may already be a limiting factor with MRI at low field (and frequency), therefore the minimization of additional loss is particularly important. If interactions between loops are managed, array coils can provide increased SNR, coverage, and potentially imaging speed. In this work, we investigate methods to characterise and preserve SNR from a low frequency coil array, allowing a more geometrically conforming array for quick, no-tune application with various anatomies.Approach. Single and multi-turn, 16.2 cm diameter litz wire loops were constructed and characterised for losses under various loading conditions. Low noise preamplifiers were acquired and characterized, as well as interfacing electronics were developed and evaluated. A bench level SNR test was implemented to observe the effects of tuning and loading on individual coils. The results were used to select a design for construction of a 6-channel, flex array coil.Main results. Ultra fine strand litz wire exhibited lower losses than equivalent diameter solid wire which should translate to improved SNR and provides the mechanical flexibility needed in a conforming array. Single turn loop losses were dominant under all loading conditions; however, 2 and 3 turn loops were body loss dominated under modest loading conditions. Preamplifier blocking achieved was well short of our design goal and critical overlaps became necessary for coil-to-coil interaction control. Our finished array, a 3-channel posterior array coil and a 3-channel anterior array coil, conforms nicely to various anatomies and is providing consistent results in various volunteer study trials.Significance. Receive coils are challenging at low fields as loop losses often limit the final SNR. This is exacerbated in an array coil as loops may be smaller and not coupled well to the body. In this work we have demonstrated that body loss dominance is possible with 16.2 cm loops at 8.5 MHz. We have optimized, built, and tested low noise interfacing electronics and characterized the SNR penalties as the tuning and loading is varied, a key parameter in a geometrically flexible array designed for rapid setup. The resultant 6-channel, general-purpose array is supporting various Field-Cycling Imaging studies where body habitus and anatomies require a flexible, adaptable array coil which can be quickly positioned and utilized.

Monitoring tissue implants by field-cycling 1H-MRI via the detection of changes in the 14N-quadrupolar-peak from imidazole moieties incorporated in a "smart" scaffold material.

This study is focused on the development of innovative sensors to non-invasively monitor the tissue implant status by Fast-Field-Cycling Magnetic Resonance Imaging (FFC-MRI). These sensors are based on oligo-histidine moieties that are conjugated to PLGA polymers representing the structural matrix for cells hosting scaffolds. The presence of 14N atoms of histidine causes a quadrupolar relaxation enhancement (also called Quadrupolar Peak, QP) at 1.39 MHz. This QP falls at a frequency well distinct from the QPs generated by endogenous semisolid proteins. The relaxation enhancement is pH dependent in the range 6.5-7.5, thus it acts as a reporter of the scaffold integrity as it progressively degrades upon lowering the microenvironmental pH. The ability of this new sensors to generate contrast in an image obtained at 1.39 MHz on a FFC-MRI scanner is assessed. A good biocompatibility of the histidine-containing scaffolds is observed after its surgical implantation in healthy mice. Over time the scaffold is colonized by endogenous fibroblasts and this process is accompanied by a progressive decrease of the intensity of the relaxation peak. In respect to the clinically used contrast agents this material has the advantage of generating contrast without the use of potentially toxic paramagnetic metal ions.

A whole-body Fast Field-Cycling scanner for clinical molecular imaging studies.

Fast Field-Cycling (FFC) is a well-established Nuclear Magnetic Resonance (NMR) technique that exploits varying magnetic fields to quantify molecular motion over a wide range of time scales, providing rich structural information from nanometres to micrometres, non-invasively. Previous work demonstrated great potential for FFC-NMR biomarkers in medical applications; our research group has now ported this technology to medical imaging by designing a whole-body FFC Magnetic Resonance Imaging (FFC-MRI) scanner capable of performing accurate measurements non-invasively over the entire body, using signals from water and fat protons. This is a unique tool to explore new biomarkers related to disease-induced tissue remodelling. Our approach required making radical changes in the design, construction and control of MRI hardware so that the magnetic field is switched within 12.5 ms to reach any field strength from 50 µT to 0.2 T, providing clinically useful images within minutes. Pilot studies demonstrated endogenous field-dependant contrast in biological tissues in good agreement with reference data from other imaging modalities, confirming that our system can perform multiscale structural imaging of biological tissues, from nanometres to micrometres. It is now possible to confirm ex vivo results obtained from previous clinical studies, offering applications in diagnosis, staging and monitoring treatment for cancer, stroke, osteoarthritis and oedema.

Simple algorithm for the correction of MRI image artefacts due to random phase fluctuations.

PURPOSE: Fast Field-Cycling (FFC) MRI is a novel technology that allows varying the main magnetic field B0 during the pulse sequence, from the nominal field (usually hundreds of millitesla) down to Earth's field or below. This technique uses resistive magnets powered by fast amplifiers. One of the challenges with this method is to stabilise the magnetic field during the acquisition of the NMR signal. Indeed, a typical consequence of field instability is small, random phase variations between each line of k-space resulting in artefacts, similar to those which occur due to homogeneous motion but harder to correct as no assumption can be made about the phase error, which appears completely random. Here we propose an algorithm that can correct for the random phase variations induced by field instabilities without prior knowledge about the phase error. METHODS: The algorithm exploits the fact that ghosts caused by field instability manifest in image regions which should be signal free. The algorithm minimises the signal in the background by finding an optimum phase correction for each line of k-space and repeats the operation until the result converges, leaving the background free of signal. CONCLUSION: We showed the conditions for which the algorithm is robust and successfully applied it on images acquired on FFC-MRI scanners. The same algorithm can be used for various applications other than Fast Field-Cycling MRI.

Rapid multi-field T(1) estimation algorithm for Fast Field-Cycling MRI.

Fast Field-Cycling MRI (FFC-MRI) is an emerging MRI technique that allows the main magnetic field to vary, allowing probing T1 at various magnetic field strengths. This technique offers promising possibilities but requires long scan times to improve the signal-to-noise ratio. This paper presents an algorithm derived from the two-point method proposed by Edelstein that can estimate T1 using only one image per field, thereby shortening the scan time by a factor of nearly two, taking advantage of the fact that the equilibrium magnetisation is proportional to the magnetic field strength. Therefore the equilibrium magnetisation only needs measuring once, then T1 can be found from inversion recovery experiments using the Bloch equations. The precision and accuracy of the algorithm are estimated using both simulated and experimental data, by Monte-Carlo simulations and by comparison with standard techniques on a phantom. The results are acceptable but usage is limited to the case where variations of the main magnetic field are fast compared with T1 and where the dispersion curve is relatively linear. The speed-up of T1-dispersion measurements resulting from the new method is likely to make FFC-MRI more acceptable when it is applied in the clinic.