Toward Next-Generation Molecular Imaging with a Clinical Low-Field (0.064 T) Point-of-Care MRI Scanner.

Low-field (LF) MRI promises soft-tissue imaging without the expensive, immobile magnets of clinical scanners but generally suffers from limited detection sensitivity and contrast. The sensitivity boost provided by hyperpolarization can thus be highly synergistic with LF MRI. Initial efforts to integrate a continuous-bubbling SABRE (signal amplification by reversible exchange) hyperpolarization setup with a portable, point-of-care 64 mT clinical MRI scanner are reported. Results from 1H SABRE MRI of pyrazine and nicotinamide are compared with those of benchtop NMR spectroscopy. Comparison with MRI signals from samples with known H2O/D2O ratios allowed quantification of the SABRE enhancements of imaged samples with various substrate concentrations (down to 3 mM). Respective limits of detection and quantification of 3.3 and 10.1 mM were determined with pyrazine 1H polarization (PH) enhancements of ∼1900 (PH ∼0.04%), supporting ongoing and envisioned efforts to realize SABRE-enabled MRI-based molecular imaging.

Low-field MRI for use in neurological diseases.

PURPOSE OF REVIEW: To review recent clinical uses of low-field magnetic resonance imaging (MRI) to guide incorporation into neurological practice. RECENT FINDINGS: Use of low-field MRI has been demonstrated in applications including tumours, vascular pathologies, multiple sclerosis, brain injury, and paediatrics. Safety, workflow, and image quality have also been evaluated. SUMMARY: Low-field MRI has the potential to increase access to critical brain imaging for patients who otherwise may not obtain imaging in a timely manner. This includes areas such as the intensive care unit and emergency room, where patients could be imaged at the point of care rather than be transported to the MRI scanner. Such systems are often more affordable than conventional systems, allowing them to be more easily deployed in resource constrained settings. A variety of systems are available on the market or in a research setting and are currently being used to determine clinical uses for these devices. The utility of such devices must be fully evaluated in clinical scenarios before adoption into standard practice can be achieved. This review summarizes recent clinical uses of low-field MR as well as safety, workflows, and image quality to aid practitioners in assessing this new technology.

Towards a barrier-free anthropomorphic brain phantom for quantitative magnetic resonance imaging: Design, first construction attempt, and challenges.

Existing magnetic resonance imaging (MRI) reference objects, or phantoms, are typically constructed from simple liquid or gel solutions in containers with specific geometric configurations to enable multi-year stability. However, there is a need for phantoms that better mimic the human anatomy without barriers between the tissues. Barriers result in regions without MRI signal between the different tissue mimics, which is an artificial image artifact. We created an anatomically representative 3D structure of the brain that mimicked the T1 and T2 relaxation properties of white and gray matter at 3 T. While the goal was to avoid barriers between tissues, the 3D printed barrier between white and gray matter and other flaws in the construction were visible at 3 T. Stability measurements were made using a portable MRI system operating at 64 mT, and T2 relaxation time was stable from 0 to 22 weeks. The phantom T1 relaxation properties did change from 0 to 10 weeks; however, they did not substantially change between 10 weeks and 22 weeks. The anthropomorphic phantom used a dissolvable mold construction method to better mimic anatomy, which worked in small test objects. The construction process, though, had many challenges. We share this work with the hope that the community can build on our experience.

Iron oxide nanoparticles as positive T1 contrast agents for low-field magnetic resonance imaging at 64 mT.

We have investigated the efficacy of superparamagnetic iron oxide nanoparticles (SPIONs) as positive T1 contrast agents for low-field magnetic resonance imaging (MRI) at 64 millitesla (mT). Iron oxide-based agents, such as the FDA-approved ferumoxytol, were measured using a variety of techniques to evaluate T1 contrast at 64 mT. Additionally, we characterized monodispersed carboxylic acid-coated SPIONs with a range of diameters (4.9-15.7 nm) in order to understand size-dependent properties of T1 contrast at low-field. MRI contrast properties were measured using 64 mT MRI, magnetometry, and nuclear magnetic resonance dispersion (NMRD). We also measured MRI contrast at 3 T to provide comparison to a standard clinical field strength. SPIONs have the capacity to perform well as T1 contrast agents at 64 mT, with measured longitudinal relaxivity (r1) values of up to 67 L mmol-1 s-1, more than an order of magnitude higher than corresponding r1 values at 3 T. The particles exhibit size-dependent longitudinal relaxivities and outperform a commercial Gd-based agent (gadobenate dimeglumine) by more than eight-fold at physiological temperatures. Additionally, we characterize the ratio of transverse to longitudinal relaxivity, r2/r1 and find that it is ~ 1 for the SPION based agents at 64 mT, indicating a favorable balance of relaxivities for T1-weighted contrast imaging. We also correlate the magnetic and structural properties of the particles with models of nanoparticle relaxivity to understand generation of T1 contrast. These experiments show that SPIONs, at low fields being targeted for point-of-care low-field MRI systems, have a unique combination of magnetic and structural properties that produce large T1 relaxivities.

In vivo quantitative MRI: T1 and T2 measurements of the human brain at 0.064 T.

OBJECTIVE: To measure healthy brain [Formula: see text] and [Formula: see text] relaxation times at 0.064 T. MATERIALS AND METHODS: [Formula: see text] and [Formula: see text] relaxation times were measured in vivo for 10 healthy volunteers using a 0.064 T magnetic resonance imaging (MRI) system and for 10 test samples on both the MRI and a separate 0.064 T nuclear magnetic resonance (NMR) system. In vivo [Formula: see text] and [Formula: see text] values are reported for white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) for automatic segmentation regions and manual regions of interest (ROIs). RESULTS: [Formula: see text] sample measurements on the MRI system were within 10% of the NMR measurement for 9 samples, and one sample was within 11%. Eight [Formula: see text] sample MRI measurements were within 25% of the NMR measurement, and the two longest [Formula: see text] samples had more than 25% variation. Automatic segmentations generally resulted in larger [Formula: see text] and [Formula: see text] estimates than manual ROIs. DISCUSSION: [Formula: see text] and [Formula: see text] times for brain tissue were measured at 0.064 T. Test samples demonstrated accuracy in WM and GM ranges of values but underestimated long [Formula: see text] in the CSF range. This work contributes to measuring quantitative MRI properties of the human body at a range of field strengths.

Challenges in ensuring the generalizability of image quantitation methods for MRI.

Image quantitation methods including quantitative MRI, multiparametric MRI, and radiomics offer great promise for clinical use. However, many of these methods have limited clinical adoption, in part due to issues of generalizability, that is, the ability to translate methods and models across institutions. Researchers can assess generalizability through measurement of repeatability and reproducibility, thus quantifying different aspects of measurement variance. In this article, we review the challenges to ensuring repeatability and reproducibility of image quantitation methods as well as present strategies to minimize their variance to enable wider clinical implementation. We present possible solutions for achieving clinically acceptable performance of image quantitation methods and briefly discuss the impact of minimizing variance and achieving generalizability towards clinical implementation and adoption.

Observation of iron oxide nanoparticle synthesis in magnetogels using magnetic resonance imaging.

We show that magnetic resonance imaging (MRI) can be used to visualize the spatiotemporal dynamics of iron oxide nanoparticle growth within a hydrogel network during in situ coprecipitation. The synthesis creates a magnetic nanoparticle loaded polymer gel, or magnetogel. During in situ coprecipitation, iron oxide nanoparticles nucleate and grow due to diffusion of a precipitating agent throughout an iron precursor loaded polymer network. The creation of iron oxide particles changes the magnetic properties of the gel, allowing the synthesis to be monitored via magnetic measurements. Formation of iron oxide nanoparticles generates dark, or hypointense, contrast in gradient echo (GRE) images acquired by MRI, allowing nanoparticle nucleation to be tracked in both space and time. We show that the growth of iron oxide nanoparticles in the hydrogel scaffold is consistent with a simple reaction-diffusion model.

Magnetic resonance fingerprinting Part 1: Potential uses, current challenges, and recommendations.

Magnetic resonance fingerprinting (MRF) is a powerful quantitative MRI technique capable of acquiring multiple property maps simultaneously in a short timeframe. The MRF framework has been adapted to a wide variety of clinical applications, but faces challenges in technical development, and to date has only demonstrated repeatability and reproducibility in small studies. In this review, we discuss the current implementations of MRF and their use in a clinical setting. Based on this analysis, we highlight areas of need that must be addressed before MRF can be fully adopted into the clinic and make recommendations to the MRF community on standardization and validation strategies of MRF techniques. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:675-692.

Identifying the Role of Block Length in Neural Heat Block to Reduce Temperatures During Infrared Neural Inhibition.

BACKGROUND AND OBJECTIVES: The objective of this study is to assess the hypothesis that the length of axon heated, defined here as block length (BL), affects the temperature required for thermal inhibition of action potential propagation applied using laser heating. The presence of such a phenomenon has implications for how this technique, called infrared neural inhibition (INI), may be applied in a clinically safe manner since it suggests that temperatures required for therapy may be reduced through the proper spatial application of light. Here, we validate the presence of this phenomenon by assessing how the peak temperatures during INI are reduced when two different BLs are applied using irradiation from either one or two adjacent optical fibers. STUDY DESIGN/MATERIALS AND METHODS: Assessment of the role of BL was carried out over two phases. First, a computational proof of concept was performed in the neural conduction simulation environment, NEURON, simulating the response of action potentials to increased temperatures applied at different full-width at half-maxima (FWHM) along axons. Second, ex vivo validation of these predictions was performed by measuring the radiant exposure, peak temperature rise, and FWHM of heat distributions associated with INI from one or two adjacent optical fibers. Electrophysiological assessment of radiant exposures at inhibition threshold were carried out in ex vivo Aplysia californica (sea slug) pleural abdominal nerves ( n = 6), an invertebrate with unmyelinated axons. Measurement of the maximum temperature rise required for induced heat block was performed in a water bath using a fine wire thermocouple. Finally, magnetic resonance thermometry (MRT) was performed on a nerve immersed in saline to assess the elevated temperature distribution at these radiant exposures. RESULTS: Computational modeling in NEURON provided a theoretical proof of concept that the BL is an important factor contributing to the peak temperature required during neural heat block, predicting a 11.7% reduction in temperature rise when the FWHM along an axon is increased by 42.9%. Experimental validation showed that, when using two adjacent fibers instead of one, a 38.5 ± 2.2% (mean ± standard error of the mean) reduction in radiant exposure per pulse per fiber threshold at the fiber output (P = 7.3E-6) is measured, resulting in a reduction in peak temperature rise under each fiber of 23.5 ± 2.1% ( P = 9.3E-5) and 15.0 ± 2.4% ( P = 1.4E-3) and an increase in the FWHM of heating by 37.7 ± 6.4% ( P = 1E-3), 68.4 ± 5.2% ( P = 2.4E-5), and 51.9 ± 9.9% ( P = 1.7E-3) in three MRT slices. CONCLUSIONS: This study provides the first experimental evidence for a phenomenon during the heat block in which the temperature for inhibition is dependent on the BL. While more work is needed to further reduce the temperature during INI, the results highlight that spatial application of the temperature rise during INI must be considered. Optimized implementation of INI may leverage this cellular response to provide optical modulation of neural signals with lower temperatures over greater time periods, which may increase the utility of the technique for laboratory and clinical use. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Magnetic resonance fingerprinting review part 2: Technique and directions.

Magnetic resonance fingerprinting (MRF) is a general framework to quantify multiple MR-sensitive tissue properties with a single acquisition. There have been numerous advances in MRF in the years since its inception. In this work we highlight some of the recent technical developments in MRF, focusing on sequence optimization, modifications for reconstruction and pattern matching, new methods for partial volume analysis, and applications of machine and deep learning. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:993-1007.

Simultaneous multislice MRI thermometry with a single coil using incoherent blipped-controlled aliasing.

PURPOSE: To increase volume coverage in real-time MR thermometry for transcranial MR-guided focused ultrasound (tcMRgFUS) ablation, without multiple receive coils. THEORY AND METHODS: Multiband excitation and incoherent blipped-controlled aliasing were implemented in a 2DFT pulse sequence used clinically for tcMRgFUS, and an extended k-space hybrid reconstruction was developed that recovers slice-separated temperature maps assuming that heating is focal, given slice-separated pretreatment images. Simulations were performed to characterize slice leakage, the number of slices that can be simultaneously imaged with low-temperature error, and robustness across random slice-phase k-space permutations. In vivo experiments were performed using a single receive coil without heating to measure temperature precision, and gel phantom FUS experiments were performed to test the method with heating and with a water bath. RESULTS: Simulations showed that with large hot spots and identical magnitude images on each slice, up to three slices can be simultaneously imaged with less than 1∘ C temperature root-mean-square error. They also showed that hot spots do not alias coherently between slices, and that an average 86% of random slice-phase k-space permutations yielded less than 1∘ C temperature error. Temperature precision was not degraded compared to single-slice imaging in the in vivo SMS scans, and the gel phantom SMS temperature maps closely tracked single-slice temperature in the hot spot, with no coherent aliasing to other slices. CONCLUSIONS: Incoherent controlled aliasing SMS enables accurate reconstruction of focal heating maps from two or three slices simultaneously, using a single receive coil and a sparsity-promoting temperature reconstruction.

Multi-echo MR thermometry using iterative separation of baseline water and fat images.

PURPOSE: To perform multi-echo water/fat separated proton resonance frequency (PRF)-shift temperature mapping. METHODS: State-of-the-art, iterative multi-echo water/fat separation algorithms produce high-quality water and fat images in the absence of heating but are not suitable for real-time imaging due to their long compute times and potential errors in heated regions. Existing fat-referenced PRF-shift temperature reconstruction methods partially address these limitations but do not address motion or large time-varying and spatially inhomogeneous B0 shifts. We describe a model-based temperature reconstruction method that overcomes these limitations by fitting a library of separated water and fat images measured before heating directly to multi-echo data measured during heating, while accounting for the PRF shift with temperature. RESULTS: Simulations in a mixed water/fat phantom with focal heating showed that the proposed algorithm reconstructed more accurate temperature maps in mixed tissues compared to a fat-referenced thermometry method. In a porcine phantom experiment with focused ultrasound heating at 1.5 Tesla, temperature maps were accurate to within 1∘ C of fiber optic probe temperature measurements and were calculated in 0.47 s per time point. Free-breathing breast and liver imaging experiments demonstrated motion and off-resonance compensation. The algorithm can also accurately reconstruct water/fat separated temperature maps from a single echo during heating. CONCLUSIONS: The proposed model-based water/fat separated algorithm produces accurate PRF-shift temperature maps in mixed water and fat tissues in the presence of spatiotemporally varying off-resonance and motion.

Dual-echo Z-shimmed proton resonance frequency-shift magnetic resonance thermometry near metallic ablation probes: Technique and temperature precision.

PURPOSE: To improve the precision of proton resonance frequency-shift magnetic resonance thermometry near ablation probes by recovering near-probe image signals that are typically lost due to magnetic susceptibility-induced field distortions. METHODS: A dual-echo gradient-recalled echo sequence was implemented, in which the first echo was under- or over-refocused in the slice dimension to recover image signal and temperature precision near a probe, and the second echo was fully refocused to obtain image signal everywhere else in the slice. A penalized maximum likelihood algorithm was implemented to estimate a single temperature map from both echoes. Agar phantom and ex vivo experiments with and without microwave heating at 3 T evaluated how much temperature precision was improved near a microwave ablator compared to a conventional single-echo scan as a function of slice and needle orientation in the magnet. RESULTS: The number of near-probe voxels with temperature standard deviation σ>1°C was decreased by 51% in the phantom experiment, averaged across orientations, and by 31% in the pork. Temperature maps near the probe were more smoother and more complete in all orientations. CONCLUSION: Dual-echo z-shimmed temperature imaging can recover image signal for more precise temperature mapping near metallic ablation probes. Magn Reson Med 78:2299-2306, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Erratum to: Open-source, small-animal magnetic resonance-guided focused ultrasound system.

[This corrects the article DOI: 10.1186/s40349-016-0066-7.].

Open-source, small-animal magnetic resonance-guided focused ultrasound system.

BACKGROUND: MR-guided focused ultrasound or high-intensity focused ultrasound (MRgFUS/MRgHIFU) is a non-invasive therapeutic modality with many potential applications in areas such as cancer therapy, drug delivery, and blood-brain barrier opening. However, the large financial costs involved in developing preclinical MRgFUS systems represent a barrier to research groups interested in developing new techniques and applications. We aim to mitigate these challenges by detailing a validated, open-source preclinical MRgFUS system capable of delivering thermal and mechanical FUS in a quantifiable and repeatable manner under real-time MRI guidance. METHODS: A hardware and software package was developed that includes closed-loop feedback controlled thermometry code and CAD drawings for a therapy table designed for a preclinical MRI scanner. For thermal treatments, the modular software uses a proportional integral derivative controller to maintain a precise focal temperature rise in the target given input from MR phase images obtained concurrently. The software computes the required voltage output and transmits it to a FUS transducer that is embedded in the delivery table within the magnet bore. The delivery table holds the FUS transducer, a small animal and its monitoring equipment, and a transmit/receive RF coil. The transducer is coupled to the animal via a water bath and is translatable in two dimensions from outside the magnet. The transducer is driven by a waveform generator and amplifier controlled by real-time software in Matlab. MR acoustic radiation force imaging is also implemented to confirm the position of the focus for mechanical and thermal treatments. RESULTS: The system was validated in tissue-mimicking phantoms and in vivo during murine tumor hyperthermia treatments. Sonications were successfully controlled over a range of temperatures and thermal doses for up to 20 min with minimal temperature overshoot. MR thermometry was validated with an optical temperature probe, and focus visualization was achieved with acoustic radiation force imaging. CONCLUSIONS: We developed an MRgFUS platform for small-animal treatments that robustly delivers accurate, precise, and controllable sonications over extended time periods. This system is an open source and could increase the availability of low-cost small-animal systems to interdisciplinary researchers seeking to develop new MRgFUS applications and technology.