Non-proton Nuclei Research Articles

Frequency-independent dual-tuned cable traps for multi-nuclear MRI and MRS

Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) of non-proton nuclei (X-nuclei) typically require additional proton imaging for anatomical reference and B0 shimming. Therefore, two RF systems exist, necessitating cable traps to block the unwanted common-mode current at both Larmor frequencies of 1H and X-nuclei. This study introduces a frequency-independent dual-tuned cable trap that combines a standard solenoid cable trap with a float solenoid trap to independently tune high and low frequencies without compromising performance. The methods involved theoretical analysis, electromagnetic simulations, and bench tests. Two design approaches were evaluated: a float cable trap for 1H, a non-float cable trap for X-nuclei, and vice versa. Results showed that the design with the float trap for X-nuclei and non-float for 1H had superior performance, with high common-mode current suppression ability at both frequencies. Bench tests confirmed these findings, demonstrating effectiveness across various static fields and X-nuclei. The proposed frequency-independent dual-tuned cable trap provides a compact and efficient solution for multinuclear MRI and MRS, enhancing safety, image quality, and flexibility.

A double-tuned 1 H/31 P coil for rabbit heart metabolism detection at 3 T.

Magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS) employing proton nuclear resonance has emerged as a pivotal modality in clinical diagnostics and fundamental research. Nonetheless, the scope of MRI/MRS extends beyond protons, encompassing nonproton nuclei that offer enhanced metabolic insights. A notable example is phosphorus-31 (31 P) MRS, which provides valuable information on energy metabolites within the skeletal muscle and cardiac tissues of individuals affected by diabetes. This study introduces a novel double-tuned coil tailored for 1 H and 31 P frequencies, specifically designed for investigating cardiac metabolism in rabbits. The proposed coil design incorporates a butterfly-like coil for 31 P transmission, a four-channel array for 31 P reception, and an eight-channel array for 1 H reception, all strategically arranged on a body-conformal elliptic cylinder. To assess the performance of the double-tuned coil, a comprehensive evaluation encompassing simulations and experimental investigations was conducted. The simulation results demonstrated that the proposed 31 P transmit design achieved acceptable homogeneity and exhibited comparable transmit efficiency on par with a band-pass birdcage coil. In vivo experiments further substantiated the coil's efficacy, revealing that the rabbit with experimentally induced diabetes exhibited a lower phosphocreatine/adenosine triphosphate ratio compared with its normal counterpart. These findings emphasize the potential of the proposed coil design as a promising tool for investigating the therapeutic effects of novel diabetes drugs within the context of animal experimentation. Its capability to provide detailed metabolic information establishes it as an indispensable asset within this realm of research.

High-Grade Glioma Treatment Response Monitoring Biomarkers: A Position Statement on the Evidence Supporting the Use of Advanced MRI Techniques in the Clinic, and the Latest Bench-to-Bedside Developments. Part 2: Spectroscopy, Chemical Exchange Saturation, Multiparametric Imaging, and Radiomics.

ObjectiveTo summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and to highlight the latest bench-to-bedside developments.MethodsThe current evidence regarding the potential for monitoring biomarkers was reviewed and individual modalities of metabolism and/or chemical composition imaging discussed. Perfusion, permeability, and microstructure imaging were similarly analyzed in Part 1 of this two-part review article and are valuable reading as background to this article. We appraise the clinic readiness of all the individual modalities and consider methodologies involving machine learning (radiomics) and the combination of MRI approaches (multiparametric imaging).ResultsThe biochemical composition of high-grade gliomas is markedly different from healthy brain tissue. Magnetic resonance spectroscopy allows the simultaneous acquisition of an array of metabolic alterations, with choline-based ratios appearing to be consistently discriminatory in treatment response assessment, although challenges remain despite this being a mature technique. Promising directions relate to ultra-high field strengths, 2-hydroxyglutarate analysis, and the use of non-proton nuclei. Labile protons on endogenous proteins can be selectively targeted with chemical exchange saturation transfer to give high resolution images. The body of evidence for clinical application of amide proton transfer imaging has been building for a decade, but more evidence is required to confirm chemical exchange saturation transfer use as a monitoring biomarker. Multiparametric methodologies, including the incorporation of nuclear medicine techniques, combine probes measuring different tumor properties. Although potentially synergistic, the limitations of each individual modality also can be compounded, particularly in the absence of standardization. Machine learning requires large datasets with high-quality annotation; there is currently low-level evidence for monitoring biomarker clinical application.ConclusionAdvanced MRI techniques show huge promise in treatment response assessment. The clinical readiness analysis highlights that most monitoring biomarkers require standardized international consensus guidelines, with more facilitation regarding technique implementation and reporting in the clinic.

Design and Comparison of Different Types of Dual-Frequency Matching Networks Used in Double-Tuned Coils for Multinuclear Magnetic Resonance Imaging and Spectroscopy

Multi-resonant RF coils are often used in multinuclear MR imaging and/or spectroscopy experiments, and a large variety of strategies for multi-tuning coils exist. However, designing a multi-tuned coil with good performance is challenging, and improvements in sensitivity are always desirable - particularly on the X-nucleus coil due to the intrinsically lower MR sensitivity of non-proton nuclei. In this work, various dual-frequency matching networks in double-tuned coils are compared, and their effect on the coil performance is investigated. Four different dual-frequency matching networks were designed and constructed with frequency-splitting or -blocking traps, which enable exploration of both proton-1 ( <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> H) and sodium-23 ( <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">23</sup> Na) nuclei. Two single-frequency matching networks were also built without any additional lossy components as a reference, and their matchings were set to either the <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> H or the <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">23</sup> Na frequency. The initial evaluation was conducted on the bench using a network analyser to examine the scattering (S)-parameters and quality factors of the connected RF coils. The performance of the attached matching networks was then further evaluated by measuring the corresponding signal-to-noise ratio (SNR) based on images obtained at a 7 T clinical MRI scanner. It was found that even though the tuning and matching conditions were nearly impeccable in the S-parameters, the actual <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> H SNR decreased significantly due to the inserted traps, whereas the SNRs of the <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">23</sup> Na frequency were nearly maintained with the added traps and the losses were much less. The dual-frequency matching networks create additional sensitivity loss, which is dependent on the actual implementation of the matching circuit. This is in agreement with previously reported results associated with the evaluation of inserted double-tuning traps for RF coils.

Perspectives of X-nuclei magnetic resonance imaging in neuro-oncology

X‑nuclei magnetic resonance imaging (MRI) yields abroad spectrum of metabolic and functional imaging techniques with increasing clinical feasibility. Current X‑nuclei techniques in (neuro)oncology with emphasis on potential clinical applications of sodium and oxygen MRI are described and discussed. Review with discussion of state-of-the-art literature on X‑nuclei imaging. X‑nuclei MRI employs NMR-sensitive nonproton nuclei to enable both anatomical visualization as well as noninvasive imaging and quantification of physiological processes in the human body. At the moment, sodium MRI represents the most common application of X‑nuclei MRI because of its comparatively high NMR signal. Moreover, its sensitivity to pathological cellular proliferation renders sodium MRI agood candidate for oncological imaging, yielding additional biochemical information to proton MRI. Oxygen MRI is currently primarily investigational, requiring high technical efforts and costs. However, preliminary results show ahuge potential of this technique for metabolic characterization of tumors. X‑nuclei MRI is arapidly evolving field in metabolic and functional imaging. In coming years, sodium MRI is expected to be increasingly used as an additional clinical tool in oncology to enhance diagnostic accuracy.

Design and evaluation of a 1H/31P double-resonant helmet coil for 3T MRI of the brain

Proton magnetic resonance imaging (MRI) can be combined with signals from non-proton nuclei (X-nuclei) to provide metabolic information. Double-resonant coils are often used for X-nuclei MR studies where the proton element is employed for scout imaging and B0 shimming. This work describes the development of a new double-resonant coil capable of operating at both proton and X-nuclei frequencies.The proposed design extends the wheel-and-spoke coil, which allows for quadrature drive, by adding an extra ring outside the coil to achieve double-resonance. Furthermore, in order to maximise SNR by increasing the filling factor, the shape of the coil has been modified to a helmet style making it suitable for brain applications.The performance of the double-resonant helmet coil was evaluated by simulation and MR measurements. The helmet coil was successfully tuned to the 1H/31P resonance frequencies of a 3T MR scanner, with high isolation between the two quadrature ports. MR measurements of a phantom were carried out, and the averaged sensitivity of the double-resonant helmet coil over the whole phantom was found to be higher than that of the conventional double-tuned birdcage coil at both frequencies.

Trap Design and Construction for High-Power Multinuclear Magnetic Resonance Experiments.

Performing multinuclear experiments requires one or more radiofrequency (RF) coils operating at both the proton and second-nucleus frequencies; however, inductive coupling between coils must be mitigated to retain proton sensitivity and coil tuning stability. The inclusion of trap circuits simplifies placement of multinuclear RF coils while maintaining inter-element isolation. Of the commonly investigated non-proton nuclei, perhaps the most technically demanding is carbon-13, particularly when applying a proton decoupling scheme to improve the resulting spectra. This work presents experimental data for trap circuits withstanding high-power broadband proton decoupling of carbon-13 at 7 T. The advantages and challenges of building trap circuits with various inductor and capacitor components are discussed. Multiple trap designs are evaluated on the bench and utilized on an RF coil at 7 T to detect broadband proton-decoupled carbon-13 spectra from a lipid phantom. A particular trap design, built from a coaxial stub inductor and high-voltage ceramic chip capacitors, is highlighted owing to both its performance and adaptability for planar array coil elements with diverse spatial orientations.

Ultra-High-Field MR Neuroimaging.

At ultra-high magnetic fields, such as 7T, MR imaging can noninvasively visualize the brain in unprecedented detail and through enhanced contrast mechanisms. The increased SNR and enhanced contrast available at 7T enable higher resolution anatomic and vascular imaging. Greater spectral separation improves detection and characterization of metabolites in spectroscopic imaging. Enhanced blood oxygen level-dependent contrast affords higher resolution functional MR imaging. Ultra-high-field MR imaging also facilitates imaging of nonproton nuclei such as sodium and phosphorus. These improved imaging methods may be applied to detect subtle anatomic, functional, and metabolic abnormalities associated with a wide range of neurologic disorders, including epilepsy, brain tumors, multiple sclerosis, Alzheimer disease, and psychiatric conditions. At 7T, however, physical and hardware limitations cause conventional MR imaging pulse sequences to generate artifacts, requiring specialized pulse sequences and new hardware solutions to maximize the high-field gain in signal and contrast. Practical considerations for ultra-high-field MR imaging include cost, siting, and patient experience.

Response

We agree with de Vocht and Kromhout that vital sign and cognitive ability measurements from 25 subjects are not sufficient to validate human safety at 9.4 T. However, we strongly disagree with their comment that a “firm conclusion” regarding human safety was reached. Both the abstract and the conclusion of the article state that the data suggest (rather than demonstrate) that human exposure to a 9.4-T static magnetic field does not represent an immediate and readily demonstrated safety concern. Obviously, additional data are required to make a firm conclusion of human safety at 9.4 T. However, such data will become available at a slow rate due to the limited number of ultra-high-field human MR scanners currently in existence. It is important that initial experimental data are presented to remove any theoretical fears that would halt future safety testing. Our initial experimental data do suggest that any effects that may be present will require a large number of subjects but do indicate that such safety testing can proceed. Contrary to the unfounded accusation of de Vocht and Kromhout, no participant comments or reported sensations were ignored at any time during this study. As stated in the manuscript, “Volunteers reporting any unusual sensations or discomforts were encouraged [emphasis added] to give a detailed account of the experience.” Specifically, we comment that “[v]olunteers indicated that these sensations [vertigo or light-headedness] were primarily experienced when being moved through the static magnetic field of the 9.4T scanner and that the sensations did not persist once they were stationary for several minutes” and that “[n]o volunteers reported any experienced discomforts persisting outside of the magnet room.” We found that all experienced discomforts and sensations, including vertigo, were consistent with those previously reported. Additional data on the distributions of the measured vital sign and cognitive data were included in table and figure form in an earlier version of the manuscript. At the request of the editor and the reviewers, these data were removed from the final version. These data were, however, peer reviewed. Staff working near the 9.4-T MR scanner are rarely exposed to a static magnetic field larger than 400 mT. During a typical human experiment, staff will be in a field greater than 0.5 mT only when moving the subject into, and out of, the magnet. This process takes approximately five minutes total. As members of the small group of personnel working with a human scanner above the U.S. Food and Drug Administration (FDA) 8 T limit, we are naturally interested in any safety implications for ultra-high-field MR personnel. The improved sensitivity at ultra-high-field enables imaging of nonproton nuclei within times acceptable to human subjects. Even though many of the required frequencies are close to that of protons at lower fields (e.g., 17-O at 9.4 T is 54 MHz, 1-H at 1.5 T is 64 MHz), imaging frequency must still be considered a parameter to be explored with respect to human safety. Therefore, although we are in the process of collecting additional safety data, we suspect that it will be some time before any firm conclusion about the safety of human exposure to 9.4 T can be made. Ian C. Atkinson PhD*, Keith R. Thulborn MD, PhD*, * Center for MR Research, University of Illinois at Chicago, Chicago, Illinois, USA.

Finite-difference time-domain simulations of radio frequency electromagnetic fields and signal inhomogeneities in ultrahigh-field magnetic resonance imaging systems

Severe inhomogeneities of radio frequency electromagnetic fields arise in ultrahigh-field magnetic resonance imaging (MRI) systems. The purpose of this study is to estimate the distribution of electromagnetic fields, magnetic resonance signals, and the specific absorption ratio (SAR) in the human head. Numerical simulations were carried out using the finite-difference time-domain method. An increase in frequency resulted in severe inhomogeneities in the magnetic resonance signals and the SAR. A reduction in the duty ratio is required to meet safety standards for the SAR. The results indicate the importance of developing coils and image-processing methods to compensate for the signal inhomogeneities in proton images. On the other hand, ultrahigh-field MRI systems are particularly useful for quantitative measurements of nonproton nuclei.

Hyperpolarized C‐13 spectroscopic imaging of the TRAMP mouse at 3T—Initial experience

The transgenic adenocarcinoma of mouse prostate (TRAMP) mouse is a well-studied murine model of prostate cancer with histopathology and disease progression that mimic the human disease. To investigate differences in cellular bioenergetics between normal prostate epithelial cells and prostate tumor cells, in vivo MR spectroscopic (MRS) studies with non-proton nuclei, such as (13)C, in the TRAMP model would be extremely useful. The recent development of a method for retaining dynamic nuclear polarization (DNP) in solution permits high signal-to-noise ratio (SNR) (13)C MRI or MRSI data to be obtained following injection of a hyperpolarized (13)C agent. In this transgenic mouse study, this method was applied using a double spin-echo (DSE) pulse sequence with a small-tip-angle excitation RF pulse, hyperbolic-secant refocusing pulses, and a flyback echo-planar readout trajectory for fast (10-14 s) MRSI of (13)C pyruvate (pyr) and its metabolic products at 0.135 cm(3) nominal spatial resolution. Elevated (13)C lactate (lac) was observed in both primary and metastatic tumors, demonstrating the feasibility of studying cellular bioenergetics in vivo with DNP hyperpolarized (13)C MRSI.

Quantitative density profiling with pure phase encoding and a dedicated 1D gradient

A new centric scan imaging methodology for density profiling of materials with short transverse relaxation times is presented. This method is shown to be more robust than our previously reported centric scan pure phase encode methodologies. The method is particularly well suited to density imaging of low gyro-magnetic ratio non-proton nuclei through the use of a novel dedicated one-dimensional magnetic field gradient coil. The design and construction of this multi-layer, water cooled, gradient coil is presented. Although of large diameter (7.62 cm) to maximize sample cross section, the gradient coil has an efficiency of several times that offered by conventional designs (6 mT/m/A). The application of these ideas is illustrated with high resolution density-weighted proton ( 1H) images of hazelnut oil penetration into chocolate, and lithium ion ( 7Li) penetration into cement paste. The methods described in this paper provide a straightforward and reliable means for imaging a class of samples that, until now, have been very difficult to image.

13C imaging—a new diagnostic platform

The evolution of magnetic resonance imaging (MRI) has been astounding since the early 1980s, and a broad range of applications has emerged. To date, clinical imaging of nuclei other than protons has been precluded for reasons of sensitivity. However, with the recent development of hyperpolarization techniques, the signal from a given number of nuclei can be increased as much as 100,000 times, sufficient to enable imaging of nonproton nuclei. Technically, imaging of hyperpolarized nuclei offers several unique properties, such as complete lack of background signal and possibility for local and permanent destruction of the signal by means of radio frequency (RF) pulses. These properties allow for improved as well as new techniques within several application areas. Diagnostically, the injected compounds can visualize information about flow, perfusion, excretory function, and metabolic status. In this review article, we explain the concept of hyperpolarization and the techniques to hyperpolarize 13C. An overview of results obtained within angiography, perfusion, and catheter tracking is given, together with a discussion of the particular advantages and limitations. Finally, possible future directions of hyperpolarized 13C MRI are pointed out.

Theory and simulation of vibrational effects on structural measurements by solid-state nuclear magnetic resonance

Vibrational effects on structural parameters obtained by solid-state NMR are studied by theoretical calculations and molecular-dynamics simulations. The structural parameters treated contain internuclear distances between directly bonded or remote nuclei including nonproton pairs in a molecule and bond and dihedral angles. In addition to the intramolecular normal mode vibrations, the libration of the whole molecule is considered in the theory. It is shown that the molecular libration as well as the intramolecular vibrations reduce dipolar interactions, and consequently lengthen the internuclear distances obtained from the dipolar interactions (RNMR). In contrast, the internuclear distances obtained by single crystal x-ray or neutron diffraction (Rcor) are proved to be shortened by the molecular libration. Molecular-dynamics simulations for glycine molecules in the crystal at room temperature reveal that RNMR are 1%–4% longer than Rcor, confirming the theoretical results. It is also demonstrated that the effect of the molecular libration on distances between nonproton nuclei is dominant over that of the intramolecular vibrations. Especially for long distances, the molecular libration is shown to be an almost unique vibrational effect and to give differences of 1% to 2% between RNMR and Rcor. On the other hand, the theoretical calculations on the vibrational effects on bond and dihedral angles determined by correlating two dipolar tensors show very little angular deviations, and it is confirmed by molecular-dynamics simulations for glycine molecules.

Volume selective 1H NMR spectroscopy with solvent suppression

Until recently, molecular imaging using magnetic resonance (MR) has been limited by the modality's low sensitivity, especially with non-proton nuclei. The advent of hyperpolarized (HP) MR overcomes this limitation by substantially enhancing the signal of certain biologically important probes through a process known as external nuclear polarization, enabling real-time assessment of tissue function and metabolism. The metabolic information obtained by HP MR imaging holds significant promise in the clinic, where it could play a critical role in disease diagnosis and therapeutic monitoring. This review will provide a comprehensive overview of the developments made in the field of hyperpolarized MR, including advancements in polarization techniques and delivery, probe development, pulse sequence optimization, characterization of healthy and diseased tissues, and the steps made towards clinical translation.