MRI Application and Challenges of Hyperpolarized Carbon-13 Pyruvate in Translational and Clinical Cardiovascular Studies: A Literature Review.

Cardiovascular disease shows, or may even be caused by, changes in metabolism. Hyperpolarized magnetic resonance spectroscopy and imaging is a technique that could assess the role of different aspects of metabolism in heart disease, allowing real-time metabolic flux assessment in vivo. In this review, we introduce the main hyperpolarization techniques. Then, we summarize the use of dedicated radiofrequency 13C coils, and report a state of the art of 13C data acquisition. Finally, this review provides an overview of the pre-clinical and clinical studies on cardiac metabolism in the healthy and diseased heart. We furthermore show what advances have been made to translate this technique into the clinic in the near future and what technical challenges still remain, such as exploring other metabolic substrates.

Hardware and Software Setup for Quantitative 23Na Magnetic Resonance Imaging at 3T: A Phantom Study.

Magnetic resonance (MR) with sodium (23Na) is a noninvasive tool providing quantitative biochemical information regarding physiology, cellular metabolism, and viability, with the potential to extend MR beyond anatomical proton imaging. However, when using clinical scanners, the low detectable 23Na signal and the low 23Na gyromagnetic ratio require the design of dedicated radiofrequency (RF) coils tuned to the 23Na Larmor frequency and sequences, as well as the development of dedicated phantoms for testing the image quality, and an MR scanner with multinuclear spectroscopy (MNS) capabilities. In this work, we propose a hardware and software setup for evaluating the potential of 23Na magnetic resonance imaging (MRI) with a clinical scanner. In particular, the reliability of the proposed setup and the reproducibility of the measurements were verified by multiple acquisitions from a 3T MR scanner using a homebuilt RF volume coil and a dedicated sequence for the imaging of a phantom specifically designed for evaluating the accuracy of the technique. The final goal of this study is to propose a setup for standardizing clinical and research 23Na MRI protocols.

Machine Learning for the Design and the Simulation of Radiofrequency Magnetic Resonance Coils: Literature Review, Challenges, and Perspectives.

Radiofrequency (RF) coils for magnetic resonance imaging (MRI) applications serve to generate RF fields to excite the nuclei in the sample (transmit coil) and to pick up the RF signals emitted by the nuclei (receive coil). For the purpose of optimizing the image quality, the performance of RF coils has to be maximized. In particular, the transmit coil has to provide a homogeneous RF magnetic field, while the receive coil has to provide the highest signal-to-noise ratio (SNR). Thus, particular attention must be paid to the coil simulation and design phases, which can be performed with different computer simulation techniques. Being largely used in many sectors of engineering and sciences, machine learning (ML) is a promising method among the different emerging strategies for coil simulation and design. Starting from the applications of ML algorithms in MRI and a short description of the RF coil's performance parameters, this narrative review describes the applications of such techniques for the simulation and design of RF coils for MRI, by including deep learning (DL) and ML-based algorithms for solving electromagnetic problems.

Conductor Losses in Radiofrequency Coils for Magnetic Resonance below 3T: Estimation Methods and Minimization Strategies.

The design of optimized radiofrequency (RF) coils is a fundamental task for maximizing the signal-to-noise ratio (SNR) in Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) applications. An efficient coil should be designed by minimizing the coil noise with respect to the sample noise, since coil conductor resistance affects data quality by reducing the SNR, especially for coils tuned to a low frequency. Such conductor losses strongly depend on the frequency (due to the skin effect) and on the conductor cross-sectional shape (strip or wire). This paper reviews the different methods for estimating conductor losses in RF coils for MRI/MRS applications, comprising analytical formulations, theoretical/experimental hybrid approaches and full-wave simulations. Moreover, the different strategies for minimizing such losses, including the use of Litz wire, cooled and superconducting coils, are described. Finally, recent emerging technologies in RF coil design are briefly reviewed.

Shaping and Focusing Magnetic Field in the Human Body: State-of-the Art and Promising Technologies.

In recent years, the usage of radio frequency magnetic fields for biomedical applications has increased exponentially. Several diagnostic and therapeutic methodologies exploit this physical entity such as, for instance, magnetic resonance imaging, hyperthermia with magnetic nanoparticles and transcranial magnetic stimulation. Within this framework, the magnetic field focusing and shaping, at different depths inside the tissue, emerges as one of the most important challenges from a technological point of view, since it is highly desirable for improving the effectiveness of clinical methodologies. In this review paper, we will first report some of the biomedical practices employing radio frequency magnetic fields, that appear most promising in clinical settings, explaining the underneath physical principles and operative procedures. Specifically, we direct the interest toward hyperthermia with magnetic nanoparticles and transcranial magnetic stimulation, together with a brief mention of magnetic resonance imaging. Additionally, we deeply review the technological solutions that have appeared so far in the literature to shape and control the radio frequency magnetic field distribution within biological tissues, highlighting human applications. In particular, volume and surface coils, together with the recent raise of metamaterials and metasurfaces will be reported. The present review manuscript can be useful to fill the actual gap in the literature and to serve as a guide for the physicians and engineers working in these fields.

Analysis, comparison and representation of occupational exposure to a static magnetic field in a 3-T MRI site.

The purpose of this study is to analyze exposure to the time-varying magnetic field caused by worker movements in a 3-T clinical magnetic resonance imaging (MRI) scanner. Measurements of the static magnetic field (B) in the proximity of the MRI scanner were performed to create a detailed map of the spatial gradient of B, in order to indicate the areas at high risk of exposure. Moreover, a personal exposure recording system was used in order to analyze and compare exposure to the static magnetic field during different routine procedures in MRI. We found that for all of the performed work activities, exposure was compliant with International Commission on Non-Ionizing Radiation Protection levels. However, our findings confirm that there is great variability of exposure between different workers and suggest the importance of performing personal exposure measurements and of detailed knowledge of the magnetic field spatial distribution.

Design, simulation, and test of surface and volume radio frequency coils for 13C magnetic resonance imaging and spectroscopy.

Hyperpolarized 13C Magnetic Resonance (MR) is a promising technique for in vivo non-invasive assessment of metabolism in humans. Despite the considerable signal increase provided by hyperpolarization techniques, the low molar concentration of derivate 13C metabolites gives rise to technological limits in terms of data quality. The development of dedicated radio frequency coils, capable of providing a large field of view with high signal-to-noise ratio data, is thus a fundamental task. This work describes the design, simulation, and test of a surface and a volume coil, both designed to be integrated with a clinical scanner for hyperpolarized 13C studies in small animal models, with the purpose to provide a detailed characterization and comparison of their performance. In particular, coil inductance was evaluated with analytical calculation, while the magnetostatic theory was employed for coils magnetic field pattern estimation. Workbench tests permitted us to characterize coil performance in terms of quality factor and efficiency. Additionally, this Tutorial summarizes the acquisition experience for the reconstruction of 13C spectroscopic maps in phantom using the two designed coils and a 3 T MR clinical scanner. We believe that this Tutorial could be interesting for graduate students and researchers in the field of magnetic resonance coil design and development, especially for 13C studies.

Ficoll as testing material for diffusion weighted imaging-quality assurance phantoms.

PURPOSE: The aim of this work is to test the use of aqueous solutions of Ficoll®**, a highly branched polymer displaying crowding properties, to build a phantom suitable for Diffusion Weighted Imaging (DWI) in Magnetic Resonance Imaging (MRI). METHODS: We developed a test object made of a cylindrical plastic container with a precise geometrical arrangement suitable for measuring several samples at the same time. The container was designed to host single vials with variable geometry and number, and to fit inside common commercial head coils for MRI scanners. In our experiments, vials were filled with 8 aqueous solutions of Ficoll 70 and Ficoll 400 spanning a range of polymer concentration from 5 to 30% by weight. Vials containing ultra-pure water were also used as reference. Experiments were performed on both 1.5 and 3 T clinical scanners (GE, Philips and Siemens), under the conditions of a standard clinical examination. RESULTS: The geometry of the phantom provided reduced imaging artifacts, especially image distortions at magnetic interfaces. We found that the Apparent Diffusion Coefficient (ADC) varied in the range of 0.00125-0.00223 mm2/s and decreased with Ficoll concentration. ADC vs Ficoll concentration exhibited a linear trend. Results were consistent over time and among different MRI clinical scanners, showing an average variability of 3% at 1.5 T and of 7.5% at 3 T. Moreover, no substantial difference was found between Ficoll 70 and 400. By varying Ficoll concentration, ADC can be modulated to approach tissue-mimicking values. Preliminary results for relaxation measurements proved that both T1 and T2 decreased with Ficoll concentration in the ranges 1.3-2.4 s and 150-800 ms respectively. CONCLUSIONS: In this work, we propose a 3D phantom design based on the widespread crowding agent Ficoll, which is suitable for DWI quality assurance purposes in MRI acquisitions. Aqueous Ficoll solutions provide good performance in terms of stability, ease of preparation, and safety.

Multivariate Curve Resolution for 2D Solid-State NMR spectra.

We present a processing method, based on the multivariate curve resolution approach (MCR), to denoise 2D solid-state NMR spectra, yielding a substantial S/N ratio increase while preserving the lineshapes and relative signal intensities. These spectral features are particularly important in the quantification of silicon species, where sensitivity is limited by the low natural abundance of the 29Si nuclei and by the dilution of the intrinsic protons of silica, but can be of interest also when dealing with other intermediate-to-low receptivity nuclei. This method also offers the possibility of coprocessing multiple 2D spectra that have the signals at the same frequencies but with different intensities (e.g.: as a result of a variation in the mixing time). The processing can be carried out on the time-domain data, thus preserving the possibility of applying further processing to the data. As a demonstration, we have applied Cadzow denoising on the MCR-processed FIDs, achieving a further increase in the S/N ratio and more effective denoising also on the transients at longer indirect evolution times. We have applied the combined denoising on a set of experimental data from a lysozyme-silica composite.

The Procedure for Quantitative Characterization and Analysis of Magnetic Fields in Magnetic Resonance Sites for Protection of Workers: A Pilot Study.

Concerning the occupational exposure in magnetic resonance imaging (MRI) facilities, the worker behavior in the magnetic resonance (MR) room is of such particular importance that there is the need for a simple but reliable method to alert the worker of the highest magnetic field exposure. Here, we describe a quantitative analysis of occupational exposure in different MRI working environments: in particular, we present a field measurement method integrated with a software tool for an accurate mapping of the fringe field in the proximity of the magnetic resonance bore. Three illustrative assessment studies are finally presented, compared and discussed, considering an example of a realistic path followed by an MRI worker during the daily procedure. The results show that the basic restrictions set by ICNIRP can be exceeded during standard procedure even in 1.5 T scanners. Using the described simplified metrics, it is possible to introduce behavioral rules on how to move around an MRI room that could be more useful than a numerical limit to aid magnetic field risk mitigation strategies.

Artifacts by Misalignment of Cardiac Magnetic Resonance Phased-array Coil Elements: From Simulation to In vivo Test.

BACKGROUND: Cardiac magnetic resonance evaluations generally require a radiofrequency coil setup comprising a transmit whole-body coil and a receive coil. In particular, radiofrequency phased-array coils are employed to pick up the signals emitted by the nuclei with high signal-tonoise ratio and a large region of sensitivity. METHODS: Literature discussed different technical issues on how to minimize interactions between array elements and how to combine data from such elements to yield optimum Signal-to-Noise Ratio images. However, image quality strongly depends upon the correct coil position over the heart and of one array coil portion with respect to the other. RESULTS: In particular, simple errors in coil positioning could cause artifacts carrying to an inaccurate interpretation of cardiac magnetic resonance images. CONCLUSION: This paper describes the effect of array elements misalignment, starting from coil simulation to cardiac magnetic resonance acquisitions with a 1.5 T scanner. Phased-array coil simulation was performed using the magnetostatic approach; moreover, phantom and in vivo experiments with a commercial 8-elements cardiac phased-array receiver coil permitted to estimate signal-to-noise ratio and B1 mapping for aligned and shifted coil.

Metabolic and Molecular Imaging with Hyperpolarised Tracers.

Since reaching the clinic, magnetic resonance imaging (MRI) has become an irreplaceable radiological tool because of the macroscopic information it provides across almost all organs and soft tissues within the human body, all without the need for ionising radiation. The sensitivity of MR, however, is too low to take full advantage of the rich chemical information contained in the MR signal. Hyperpolarisation techniques have recently emerged as methods to overcome the sensitivity limitations by enhancing the MR signal by many orders of magnitude compared to the thermal equilibrium, enabling a new class of metabolic and molecular X-nuclei based MR tracers capable of reporting on metabolic processes at the cellular level. These hyperpolarised (HP) tracers have the potential to elucidate the complex metabolic processes of many organs and pathologies, with studies so far focusing on the fields of oncology and cardiology. This review presents an overview of hyperpolarisation techniques that appear most promising for clinical use today, such as dissolution dynamic nuclear polarisation (d-DNP), parahydrogen-induced hyperpolarisation (PHIP), Brute force hyperpolarisation and spin-exchange optical pumping (SEOP), before discussing methods for tracer detection, emerging metabolic tracers and applications and progress in preclinical and clinical application.

Dual photoacoustic/ultrasound multi-parametric imaging from passion fruit-like nano-architectures.

Ultrasound (US) imaging is a well-established diagnostic technique to image soft tissues in real time, while photoacoustic (PA) is an emerging imaging technique employed to collect molecular information. Integration of PA and US imaging provides complementary information enhancing diagnostic accuracy without employing ionizing radiations. The development of contrast agents able to combine PA and US features is pivotal to improve the significance of PAUS imaging and for PAUS-guided treatment of neoplasms. Here, we demonstrate in relevant ex-vivo models that disassembling passion fruit-like nano-architectures (pfNAs) can be employed in PAUS imaging. pfNAs are composed by silica nanocapsules comprising aggregates of commercial NIR-dyes-modified polymers and ultrasmall gold nanoparticles. The intrinsic US and PA features of pfNAs have been fully characterized and validated in tissue-mimicking materials and in ex vivo preparations. Moreover, the application of a multi-parametric approach has allowed the increase of information extrapolated from collected images for a fine texture analysis.

Spectroscopic and photoacoustic characterization of encapsulated iron oxide super-paramagnetic nanoparticles as a new multiplatform contrast agent.

Recently, a number of photoacoustic (PA) agents with increased tissue penetration and fine spatial resolution have been developed for molecular imaging and mapping of pathophysiological features at the molecular level. Here, we present bio-conjugated near-infrared light-absorbing magnetic nanoparticles as a new agent for PA imaging. These nanoparticles exhibit suitable absorption in the near-infrared region, with good photoacoustic signal generation efficiency and high photo-stability. Furthermore, these encapsulated iron oxide nanoparticles exhibit strong super-paramagnetic behavior and nuclear relaxivities that make them useful as magnetic resonance imaging (MRI) contrast media as well. Their simple bio-conjugation strategy, optical and chemical stability, and straightforward manipulation could enable the development of a PA probe with magnetic and spectroscopic properties suitable for in vitro and in vivo real-time imaging of relevant biological targets.

Biomolecular imaging of 13C-butyrate with dissolution-DNP: Polarization enhancement and formulation for in vivo studies.

Magnetic Resonance Spectroscopy of hyperpolarized isotopically enriched molecules facilitates the non-invasive real-time investigation of in vivo tissue metabolism in the time-frame of a few minutes; this opens up a new avenue in the development of biomolecular probes. Dissolution Dynamic Nuclear Polarization is a hyperpolarization technique yielding a more than four orders of magnitude increase in the 13C polarization for in vivo Magnetic Resonance Spectroscopy studies. As reported in several studies, the dissolution Dynamic Nuclear Polarization polarization performance relies on the chemico-physical properties of the sample. In this study, we describe and quantify the effects of the different sample components on the dissolution Dynamic Nuclear Polarization performance of [1-13C]butyrate. In particular, we focus on the polarization enhancement provided by the incremental addition of the glassy agent dimethyl sulfoxide and gadolinium chelate to the formulation. Finally, preliminary results obtained after injection in healthy rats are also reported, showing the feasibility of an in vivo Magnetic Resonance Spectroscopy study with hyperpolarized [1-13C]butyrate using a 3T clinical set-up.

Smart assembly of Mn-ferrites/silica core-shell with fluorescein and gold nanorods: robust and stable nanomicelles for in vivo triple modality imaging.

Herein we report the synthesis of a resilient nanosystem based on silica-coated magnetic MnFe2O3 nanoparticles conjugated to fluorescein and PEGylated gold nanorods embedded in polymeric micelles (MnFe2O4@SiO2@GNRs@PMs), for magnetic-photoacoustic-optical triple-modality imaging. The magnetic relaxivity of the nanosystem has been evaluated, revealing high r2/r1 ratios that suggest the effectiveness of the nanosystem as the T2-contrast agent. In addition, contrast-based fluorescence imaging has been tested both in vitro and ex vivo, showing that the nanosystem exhibits the suitable optical properties of fluorescein, with contrast intensities comparable with previously reported results. Finally, photoacoustic, due to gold nanorods, performances of the nanosystem have been evaluated, revealing good linearity between concentration and photoacoustic response in the 25-250 nM concentration under irradiation at 690 nm. The results showed a contrast-to-noise ratio (CNR) as high as 60 in a mouse leg subcutaneously injected with the nanosystem. Biocompatibility studies revealed no hemolytic effect induced by the nanoconstruct, revealing the applicability of the studied diagnostic tool for medical studies.

A radiofrequency system for in vivo hyperpolarized 13 C MRS experiments in mice with a 3T MRI clinical scanner.

Hyperpolarized carbon-13 magnetic resonance spectroscopy (MRS) is a powerful tool to explore tissue metabolic state, by permitting the study of intermediary metabolism of biomolecules in vivo. However, a number of technological problems still limit this technology and need innovative solutions. In particular, the low molar concentration of derivate metabolites give rise to low signal-to-noise ratio (SNR), which makes the design and development of dedicated radiofrequency (RF) coils a fundamental task. In this article, the authors describe the simulation and the design of a RF coils configuration for MR experiments in mice, constituted by a 1 H whole body volume RF coil for imaging and a 13 C single circular loop surface RF coil for performing 13 C acquisitions. After the building, the RF system was employed in an in vivo experiment in a mouse injected with hyperpolarized [1-13 C]pyruvate by using a 3 T clinical MR scanner. SCANNING 38:710-719, 2016. © 2016 Wiley Periodicals, Inc.

Phosphocholine-decorated superparamagnetic iron oxide nanoparticles: defining the structure and probing in vivo applications.

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are performing contrast agents for Magnetic Resonance Imaging (MRI). A functionalization strategy for SPIONs based on hydrophobic interactions is a versatile approach easily extendable to several kinds of inorganic nanoparticles and suitable for obtaining stable and biocompatible systems. Here we report on the original preparation of functionalized SPIONs with an 8 nm radius exploiting the hydrophobic interaction between a phosphocholine and an inner amphiphilic. With respect to other similarly functionalized SPIONs, characterized by the typical nanoparticle clustering that leads to large aggregates, our phosphocholine-decorated SPIONs are demonstrated to be monodisperse. We report the in vitro and in vivo study that proves the effective applicability of phosphocholine-decorated SPIONs as MRI contrast agents. The versatility of this functionalization approach is highlighted by introducing on the SPION surface a ruthenium-based potential antitumoral drug, named ToThyCholRu. Even if in this case we observed the formation of SPION clusters, ascribable to the presence of the amphiphilic ruthenium complex, interesting and promising antiproliferative activity points at the ToThyCholRu-decorated SPIONs as potential theranostic agents.

The effect of Gd on trityl-based dynamic nuclear polarisation in solids.

In dynamic nuclear polarisation (DNP) experiments performed under static conditions at 1.4 K we show that the presence of 1 mM Gd(iii)-DOTAREM increases the (13)C polarisation and decreases the (13)C polarisation buildup time of (13)C-urea dissolved in samples containing water/DMSO mixtures with trityl radical (OX063) concentrations of 10 mM or higher. To account for these observations further measurements were carried out at 6.5 K, using a combined EPR and NMR spectrometer. At this temperature, frequency swept DNP spectra of samples with 5 or 10 mM OX063 were measured, with and without 1 mM Gd-DOTA, and again a (13)C enhancement gain was observed due to the presence of Gd-DOTA. These measurements were complemented by electron-electron double resonance (ELDOR) measurements to quantitate the effect of electron spectral diffusion (eSD) on the DNP enhancements and lineshapes. Simulations of the ELDOR spectra were done using the following parameters: (i) a parameter defining the rate of the eSD process, (ii) an "effective electron-proton anisotropic hyperfine interaction parameter", and (iii) the transverse electron spin relaxation time of OX063. These parameters, together with the longitudinal electron spin relaxation time, measured by EPR, were used to calculate the frequency profile of electron polarisation. This, in turn, was used to calculate two basic solid effect (SE) and indirect cross effect (iCE) DNP spectra. A properly weighted combination of these two normalized DNP spectra provided a very good fit of the experimental DNP spectra. The best fit simulation parameters reveal that the addition of Gd(iii)-DOTA causes an increase in both the SE and the iCE contributions by similar amounts, and that the increase in the overall DNP enhancements is a result of narrowing of the ELDOR spectra (increased electron polarisation gradient across the EPR line). These changes in the electron depolarisation profile are a combined result of shortening of the longitudinal and transverse electron spin relaxation times, as well as an increase in the eSD rate and in the effective electron-proton anisotropic hyperfine interaction parameter.

Dissolution dynamic nuclear polarization of non-self-glassing agents: spectroscopy and relaxation of hyperpolarized [1-13C]acetate.

The intrinsic physicochemical properties of the sample formulation are the key factors for efficient hyperpolarization through dissolution dynamic nuclear polarization (dissolution-DNP). We provide a comprehensive characterization of the DNP process for Na-[1-(13)C]acetate selected as a model for non-self-glassing agents: the solid-state polarization dynamics of different formulations and the effect of the paramagnetic agent (trityl radical) on the pattern of polarization and the relaxation profile were extensively analyzed. We quantified the effects of the glassing agent and Gd(3+)-chelate on DNP performance. The results reported here describe the constraints of the acetate formulation useful for future studies in this field with non-self-glassing enriched molecules.