Challenges for Molecular Magnetic Resonance Imaging (original) (raw)
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Magnetization and diffusion effects in NMR imaging of hyperpolarized substances
Magnetic Resonance in Medicine, 1997
The special magnetization characteristics of hyperpolarized noble gases have led to an interest in using these agents for new MRI applications. In this note, the magnetization effects and NMR signal dependence of two noble gases, 3He and '=Xe, are modeled across a range of gradient-echo imaging parameters. Pulse-sequence analysis shows a wide variation in optimum flip angles between imaging of gas (e.g., 3He or '"Xe) in air spaces (e.g., trachea and lung) and in blood vessels. To optimize imaging of the air spaces, it is also necessary to reduce the otherwise substantial signal losses from diffusion effects by increasing voxel size. The possibility of using hyperpolarized '"Xe for functional MRI (fMRI) is discussed in view of the results from the blood flow analysis. The short-lived nature of the hyperpolarization opens up new possibilities, as well as new technical challenges, in its potential application as a blood-flow tracer.
Hyperpolarization Methods for MRS
eMagRes, 2015
Chekmenev). Co-authored >30 peer-reviewed articles covering advanced MR detection hardware and utilizing hyperpolarization techniques to enable MR contrast agents for in vivo molecular imaging for improved human health.
A hyperpolarized equilibrium for magnetic resonance
Nature Communications, 2013
Nuclear magnetic resonance spectroscopy and imaging (MRI) play an indispensable role in science and healthcare but use only a tiny fraction of their potential. No more than E10 p.p.m. of all 1 H nuclei are effectively detected in a 3-Tesla clinical MRI system. Thus, a vast array of new applications lays dormant, awaiting improved sensitivity. Here we demonstrate the continuous polarization of small molecules in solution to a level that cannot be achieved in a viable magnet. The magnetization does not decay and is effectively reinitialized within seconds after being measured. This effect depends on the long-lived, entangled spin-order of parahydrogen and an exchange reaction in a low magnetic field of 10 À 3 Tesla. We demonstrate the potential of this method by fast MRI and envision the catalysis of new applications such as cancer screening or indeed low-field MRI for routine use and remote application.
ChemistryOpen, 2018
Fluorinated ligands have a variety of uses in chemistry and industry, but it is their medical applications as F-labelled positron emission tomography (PET) tracers where they are most visible. In this work, we illustrate the potential of using F-containing ligands as future magnetic resonance imaging (MRI) contrast agents and as probes in magnetic resonance spectroscopy studies by significantly increasing their magnetic resonance detectability through the signal amplification by reversible exchange (SABRE) hyperpolarization method. We achieve F SABRE polarization in a wide range of molecules, including those essential to medication, and analyze how their steric bulk, the substrate loading, polarization transfer field, pH, and rate of ligand exchange impact the efficiency of SABRE. We conclude by presenting F MRI results in phantoms, which demonstrate that many of these agents show great promise as future F MRI contrast agents for diagnostic investigations.
15 N Hyperpolarization of Dalfampridine at Natural Abundance for Magnetic Resonance Imaging
Chemistry – A European Journal, 2019
Signal Amplification by Reversible Exchange (SABRE) is a promising method for NMR signal enhancement and production of hyperpolarized molecules. As nuclear spin relaxation times of heteronuclei are usually much longer than those of protons, SABRE-based hyperpolarization of heteronuclei in molecules is highly important in the context of biomedical applications. In this work, we demonstrate that the SLIC-SABRE technique can be successfully used to hyperpolarize 15 N nuclei in dalfampridine. The high polarization level of ca. 8% achieved in this work allowed us to acquire 15 N MR images at natural abundance of the 15 N nuclei for the first time.
High-Resolution Low-Field Molecular Magnetic Resonance Imaging of Hyperpolarized Liquids
Analytical Chemistry, 2014
We demonstrate the feasibility of microscale molecular imaging using hyperpolarized proton and carbon-13 MRI contrast media and low-field (47.5 mT) preclinical scale (38 mm i.d.) 2D magnetic resonance imaging (MRI). Hyperpolarized proton images with 94 × 94 μm 2 spatial resolution and hyperpolarized carbon-13 images with 250 × 250 μm 2 in-plane spatial resolution were recorded in 4−8 s (largely limited by the electronics response), surpassing the inplane spatial resolution (i.e., pixel size) achievable with micropositron emission tomography (PET). These hyperpolarized proton and 13 C images were recorded using large imaging matrices of up to 256 × 256 pixels and relatively large fields of view of up to 6.4 × 6.4 cm 2. 13 C images were recorded using hyperpolarized 1-13 C-succinate-d 2 (30 mM in water, %P 13C = 25.8 ± 5.1% (when produced) and %P 13C = 14.2 ± 0.7% (when imaged), T 1 = 74 ± 3 s), and proton images were recorded using 1 H hyperpolarized pyridine (100 mM in methanol-d 4 , %P H = 0.1 ± 0.02% (when imaged), T 1 = 11 ± 0.1 s). Both contrast agents were hyperpolarized using parahydrogen (>90% para-fraction) in an automated 5.75 mT parahydrogen induced polarization (PHIP) hyperpolarizer. A magnetized path was demonstrated for successful transportation of a 13 C hyperpolarized contrast agent (1-13 C-succinate-d 2 , sensitive to fast depolarization when at the Earth's magnetic field) from the PHIP polarizer to the 47.5 mT low-field MRI. While future polarizing and low-field MRI hardware and imaging sequence developments can further improve the low-field detection sensitivity, the current results demonstrate that microscale molecular imaging in vivo is already feasible at low (<50 mT) fields and potentially at low (∼1 mM) metabolite concentrations.
NMR hyperpolarization techniques for biomedicine
Chemistry (Weinheim an der Bergstrasse, Germany), 2015
Recent developments in NMR hyperpolarization have enabled a wide array of new in vivo molecular imaging modalities, ranging from functional imaging of the lungs to metabolic imaging of cancer. This Concept article explores selected advances in methods for the preparation and use of hyperpolarized contrast agents, many of which are already at or near the phase of their clinical validation in patients.
Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology, 2017
Superparamagnetic nanoparticles are used as contrast agents in magnetic resonance imaging and allow, for example, the detection of tumors or the tracking of stem cells in vivo. By producing magnetic inhomogeneities, they influence the nuclear magnetic relaxation times, which results in a darkening, on the image, of the region containing these particles. A great number of studies have been devoted to their magnetic properties, to their synthesis and to their influence on nuclear magnetic relaxation. The theoretical and fundamental understanding of the behavior of these particles is a necessary step in predicting their efficiency as contrast agents, or to be able to experimentally obtain some of their properties from a nuclear magnetic resonance measurement. Many relaxation models have been published, and choosing one of them is not always easy, many parameters and conditions have to be taken into account. Relaxation induced by superparamagnetic particles is generally attributed to an...
Singlet-contrast magnetic resonance imaging: unlocking hyperpolarization with metabolism
Hyperpolarization-enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as 13C, 15N, or 129Xe due to their long spin‑polarization lifetimes and the absence of a proton‑background signal from water and fat in the images. Here we present a novel type of 1H imaging, in which hyperpolarized spin order is locked in a nonmagnetic long-lived correlated (singlet) state, and is only liberated for imaging by a specific biochemical reaction. In this work we produce hyperpolarized fumarate via chemical reaction of a precursor molecule with para-enriched hydrogen gas, and the proton singlet order in fumarate is released as antiphase NMR signals by enzymatic conversion to malate in D2O. Using this model system we show two pulse sequences to rephase the NMR signals for imaging and suppress the background signals from water. The hyperpolarization-enhanced 1H‑imaging modality presented here can allow for hyperpolarized imaging...
Quantification in Hyperpolarized NMR
Quantitative aspects of hyperpolarized NMR are analyzed in the present work, and it is shown theoretically and experimentally that measured " apparent " signal enhancements could deviate significantly from real enhancements of polarization. Expressions are given as a function of spin count to deduce real enhancements from measured " apparent " enhancements, and vice versa. While the findings are of particular relevance to high-field work employing high-Q probes, and to analytical applications of hyperpolarized NMR whose objective is the measurement of spin count, our experiments demonstrate their significance even for low-and moderate-field work with probes of moderate Q-factor. H yperpolarized NMR is currently witnessing vigorous research activity and renewed popularity because it seeks to address the Achilles heel of NMR, viz., poor sensitivity, without seriously compromising its core strength, viz., high resolution. This opens up a number of chemical applications. Perhaps the earliest polarization enhancement technique in NMR was dynamic nuclear polarization (DNP), 1−3 otherwise known as the Overhauser effect (OE, or ODNP), and related techniques in the solid state, including the solid effect (SE). 4 It was subsequently shown that hyperpolarization could be achieved by suitable techniques that harness the high spin order in parahydrogen, yielding parahydrogen induced polarization (PHIP). 5−10 More recently, PHIP has received a significant boost by the avoidance of a chemical reaction across a multiple bond as originally required, relying instead on a catalyst to bind both parahydrogen and the " substrate " species of interest, accomplishing polarization transfer by spin exchange and NMR signal enhancement in the bulk phase by subsequent chemical exchange; this technique is termed signal amplification by reversible exchange (SABRE). 11−13 While signal enhancement was often the prime motivation in early ODNP studies (which were performed in continuous wave (cw) NMR mode), quantitative measurements for elucidation of the mechanism of the Overhauser effect resulted in the recognition that continuous wave ODNP studies reveal a peculiar effect which results in the deviation of the measured (or " apparent ") enhancement from its real value. 14−16 In this report, we argue that this effect could play a vital role in the time domain measurements typical of modern hyperpolarized NMR, including ODNP, as well as SABRE/PHIP. We give a quantitative relation between the apparent and real enhancement factors, which would aid quantitative analysis based on hyperpolarized NMR spectra. We also demonstrate this effect experimentally in pulsed mode at a moderately low NMR frequency. The basic phenomenon that gives rise to " false " enhancements may be termed the Q-enhancement effect. 14−16 It is to be noted especially that this is a fundamental effect that is unrelated to questions of sample transfer, arising as it does from the fact that the probe circuit quality factor, Q, changes with the sample polarization. In simple terms, the NMR probe which houses the sample under investigation has a quality factor Q that is governed by the coil inductance, L 0 , and effective serial resistance, R 0. Near the resonance condition, this is changed substantially by the NMR characteristics of the sample, viz., the radiofrequency susceptibility, χ, of the spin ensemble, and leads to measurable, even strong, effects under conditions of high spin polarization, especially for high-Q probes and high-frequency measurements. The effect may be modeled in a straightforward manner. The NMR coil impedance, Z, is given in SI units by ω ϕ χ ω ω ϕχ ω χ ω = + + = + ′ − ″ + Z L R L R i [1 ()] i [1 (() i ())] 0 0 0 0 0 0 0 0 0 (1) Here i is the unit imaginary, ϕ the filling factor, and ω 0 the angular frequency at which resonance occurs (i.e., ν 0 Hz). The contribution of the real part of the spin susceptibility, χ′, being zero on resonance, we find for the coil impedance on resonance ω ω ϕχ ω = + ″ + Z L L R i () 0 0 0 0 0 0 (2) For the quality factor of the NMR probe, we thus find that it changes from Q = ω 0 L 0 /R 0 far off resonance to Q′ = ω 0 L 0 / [ω 0 L 0 ϕχ″(ω 0)+R 0 ] on resonance. We may write the measured