NMR hyperpolarization techniques for biomedicine (original) (raw)
Related papers
2002
Based on the principle of nuclear magnetic resonance (NMR), magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are widely used methods in medical diagnostic imaging and biological research. Clinical MRI has been restricted to imaging of protons, for reasons of sensitivity. In recent years, hyperpolarization techniques have emerged that can increase the NMR signal by 5-6 orders of magnitude. The increased signal from hyperpolarized substances enables investigation of non-proton nuclei, and thus makes novel kinds of examinations possible, e.g., imaging of the lungs and respiratory airways after inhalation of hyperpolarized gas. In this work, applications related to vascular imaging and lung function were investigated, using three hyperpolarized nuclei: 129 Xe, 13 C, and 3 He. In addition, practical aspects regarding the handling and utilization of hyperpolarized substances were evaluated. The potential of angiography using echo-planar imaging (EPI) was investigated using dissolved 129 Xe in a phantom model. Long relaxation times were achieved in the in vitro experiments, allowing images of reasonable quality to be acquired within a scan time of 44 ms. Under in vivo conditions, severe limitations are expected, which are mainly due to short transverse relaxation times. A novel 13 C substance with favorable properties for angiography was investigated using an optimized true fast imaging w it h st e ad y-s ta te pr ec es s io n (t r ue FIS P) pul s e se que nc e. L o ng re la xa t io n t im es we r e o bt a in ed al so u n de r in vi vo co nd it i on s (T 1 ≈ 4 0 s, T 2 ≈ 2 s), which permitted the acquisition of angiograms in live rats with a signal-to-noise ratio (SNR) as high as ~500. To investigate regional pulmonary ventilation, a technique was developed in an initial study, that was based on inhalation of 3 He gas. A quantitative measurement of gas replacement was calculated from the signal buildup after repeated inspirations of 3 He. The relative replacement of gas was close to 1 in the trachea and the major airways, and decreased to ~0.15 in the most peripheral parts of the lung. In a second study, regional ventilation was found to be increased in the inferior parts of the lung as compared with the superior parts, with the subject in supine position, whereas a uniform ventilation was measured in prone position. From measurements of the dynamic uptake of 129 Xe from the alveolar gas spaces to the pulmonary blood vessels, several physiological parameters could be derived, including the thickness of the respiratory membrane and the pulmonary perfusion. The method was employed to compare healthy control animals with animals with inflammatory lung injury. A significantly increased membrane thickness (10.0 µm vs. 8.6 µm) was measured in the latter group, whereas the pulmonary perfusion remained unaltered. By using hyperpolarized substances, novel possibilities of gaining physiological information arise, which may complement existing MRI and MRS techniques.
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...
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.
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.
Hyperpolarized [15N]nitrate as a potential long lived hyperpolarized contrast agent for MRI
Journal of Magnetic Resonance, 2019
Reports on gadolinium deposits in the body and brains of adults and children who underwent contrastenhanced MRI examinations warrant development of new, metal free, contrast agents for MRI. Nitrate is an abundant ion in mammalian biochemistry and sodium nitrate can be safely injected intravenously. We show that hyperpolarized [ 15 N]nitrate can potentially be used as an MR tracer. The 15 N site of hyperpolarized [ 15 N]nitrate showed a T 1 of more than 100 s in aqueous solutions, which was prolonged to more than 170 s below 20°C. Capitalizing on this effect for polarization storage we obtained a visibility window of 9 min in blood. Conversion to [ 15 N]nitrite, the bioactive reduced form of nitrate, was not observed in human blood and human saliva in this time frame. Thus, [ 15 N]nitrate may serve as a long-lived hyperpolarized tracer for MR. Due to its ionic nature, the immediate applications appear to be perfusion and tissue retention imaging.
Communications Chemistry, 2021
Magnetic Resonance Imaging combined with hyperpolarized 13C-labelled metabolic contrast agents produced via dissolution Dynamic Nuclear Polarization can, non-invasively and in real-time, report on tissue specific aberrant metabolism. However, hyperpolarization equipment is expensive, technically demanding and needs to be installed on-site for the end-user. In this work, we provide a robust methodology that allows remote production of the hyperpolarized 13C-labelled metabolic contrast agents. The methodology, built on photo-induced thermally labile radicals, allows solid sample extraction from the hyperpolarization equipment and several hours’ lifetime of the 13C-labelled metabolic contrast agents at appropriate storage/transport conditions. Exemplified with [U-13C, d7]-D-glucose, we remotely produce hyperpolarized 13C-labelled metabolic contrast agents and generate above 10,000-fold liquid-state Magnetic Resonance signal enhancement at 9.4 T, keeping on-site only a simple dissolutio...
In vivo hyperpolarized 13C MR spectroscopic imaging with 1H decoupling
Journal of Magnetic Resonance, 2009
Application of 13 C MRS in vivo on whole body MR system has been limited due to the low static field (and consequent low signal to noise ratio-SNR) of these scanners; thus there have been few reports of 1 H decoupled 13 C MRS in vivo using a clinical MR platform. The recent development of techniques to retain highly polarized spins in solution following DNP in a solid matrix has provided a mechanism to use endogenous pre-polarized 13 C labeled substrates to study real time cellular metabolism in vivo with high SNR. In a recent in vivo hyperpolarized metabolic imaging study using 13 C pyruvate, it has been demonstrated that the line shape (signal decay) of the resonances observed are greatly affected by J CH coupling in addition to inhomogeneous broadening. This study demonstrates the feasibility of improving hyperpolarized 13 C metabolic imaging in vivo by incorporating 1 H decoupling on a clinical whole body 3 T MR scanner. No reduction of T1 of a prepolarized 13 C substrate ([1-13 C] lactate) in solution was observed when 1 H decoupling was applied with WALTZ16 sequence. Narrower linewidth for the [1-13 C] lactate resonance was observed in hyperpolarized 13 C MRSI data in vivo with 1 H decoupling.
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.
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.