Low-field NMR has emerged as a new analytical technique for the investigation of molecular structure and dynamics. Here, we introduce a highly integrated ultralow-frequency NMR spectrometer designed for the purpose of ultralow-field NMR polarimetry of hyperpolarized contrast media. The device measures 10 cm × 10 cm × 2.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
September 2024
It has recently been shown that a bolus of hyperpolarized nuclear spins can yield stimulated emission signals similar in nature to maser signals, potentially enabling new ways of sensing hyperpolarized contrast media, including most notably [1-C]pyruvate that is under evaluation in over 50 clinical trials for metabolic imaging of cancer. The stimulated NMR signal emissions lasting for minutes do not require radio-frequency excitation, offering unprecedented advantages compared to conventional MR sensing. However, creating nuclear spin maser emission is challenging in practice due to stringent fundamental requirements, making practical in vivo applications hardly possible using conventional passive MR detectors.
View Article and Find Full Text PDFWe present an integrated, open-source device for parahydrogen-based hyperpolarization processes in the microtesla field regime with a cost of components of less than $7000. The device is designed to produce a batch of C and N hyperpolarized (HP) compounds via hydrogenative or non-hydrogenative parahydrogen-induced polarization methods that employ microtesla magnetic fields for efficient polarization transfer of parahydrogen-derived spin order to X-nuclei (e.g.
View Article and Find Full Text PDFC hyperpolarized pyruvate is an emerging MRI contrast agent for sensing molecular events in cancer and other diseases with aberrant metabolic pathways. This metabolic contrast agent can be produced via several hyperpolarization techniques. Despite remarkable success in research settings, widespread clinical adoption faces substantial roadblocks because the current sensing technology utilized to sense this contrast agent requires the excitation of C nuclear spins that also need to be synchronized with MRI field gradient pulses.
View Article and Find Full Text PDFHyperpolarized [1-C]pyruvate is the leading hyperpolarized injectable contrast agent and is currently under evaluation in clinical trials for molecular imaging of metabolic diseases, including cardiovascular disease and cancer. One aspect limiting broad scalability of the technique is that hyperpolarized C MRI requires specialized C hardware and software that are not generally available on clinical MRI scanners, which employ proton-only detection. Here, we present an approach that uses pulse sequences to transfer C hyperpolarization to methyl protons for detection of the C-C pyruvate singlet, employing proton-only excitation and detection only.
View Article and Find Full Text PDFEfficient N-hyperpolarization of [N]metronidazole was reported previously using the Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) technique. This hyperpolarized FDA-approved antibiotic is a potential contrast agent because it can be administered in a large dose and because previous studies revealed long-lasting HP states with exponential decay constant values of up to 10 min. Possible hypoxia-sensing applications have been proposed using hyperpolarized [N]metronidazole.
View Article and Find Full Text PDFConventional nuclear magnetic resonance (NMR) enables detection of chemicals and their transformations by exciting nuclear spin ensembles with a radio-frequency pulse followed by detection of the precessing spins at their characteristic frequencies. The detected frequencies report on chemical reactions in real time and the signal amplitudes scale with concentrations of products and reactants. Here, we employ Radiofrequency Amplification by Stimulated Emission of Radiation (RASER), a quantum phenomenon producing coherent emission of C signals, to detect chemical transformations.
View Article and Find Full Text PDFEfficient C hyperpolarization of ketoisocaproate is demonstrated in natural isotopic abundance and [1-C]enriched forms via SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). Parahydrogen, as the source of nuclear spin order, and ketoisocaproate undergo simultaneous chemical exchange with an Ir-IMes-based hexacoordinate complex in CDOD. SABRE-SHEATH enables spontaneous polarization transfer from parahydrogen-derived hydrides to the C nucleus of transiently bound ketoisocaproate.
View Article and Find Full Text PDFHyperpolarized [1-C]pyruvate is a revolutionary molecular probe enabling ultrafast metabolic MRI scans in 1 min. This technology is now under evaluation in over 30 clinical trials, which employ dissolution Dynamic Nuclear Polarization (d-DNP) to prepare a batch of the contrast agent; however, d-DNP technology is slow and expensive. The emerging SABRE-SHEATH hyperpolarization technique enables fast (under 1 min) and robust production of hyperpolarized [1-C]pyruvate via simultaneous chemical exchange of parahydrogen and pyruvate on IrIMes hexacoordinate complexes.
View Article and Find Full Text PDFThe feasibility of Carbon-13 Radiofrequency (RF) Amplification by Stimulated Emission of Radiation (C-13 RASER) is demonstrated on a bolus of liquid hyperpolarized ethyl [1- C]acetate. Hyperpolarized ethyl [1- C]acetate was prepared via pairwise addition of parahydrogen to vinyl [1- C]acetate and polarization transfer from nascent parahydrogen-derived protons to the carbon-13 nucleus via magnetic field cycling yielding C-13 nuclear spin polarization of approximately 6 %. RASER signals were detected from samples with concentration ranging from 0.
View Article and Find Full Text PDFDespite great successes in oncology, patient outcomes are often still discouraging, and hence the diagnostic imaging paradigm is increasingly shifting toward functional imaging of the pathology to better understand individual disease biology and to personalize therapies. The dissolution Dynamic Nuclear Polarization (d-DNP) hyperpolarization method has enabled unprecedented real-time MRI sensing of metabolism and tissue pH using hyperpolarized [1-C]pyruvate as a biosensor with great potential for diagnosis and monitoring of cancer patients. However, current d-DNP is expensive and suffers from long hyperpolarization times, posing a substantial translational roadblock.
View Article and Find Full Text PDFα-Ketoglutarate is a key biomolecule involved in a number of metabolic pathways─most notably the TCA cycle. Abnormal α-ketoglutarate metabolism has also been linked with cancer. Here, isotopic labeling was employed to synthesize [1-C,5-C,D]α-ketoglutarate with the future goal of utilizing its [1-C]-hyperpolarized state for real-time metabolic imaging of α-ketoglutarate analytes and its downstream metabolites .
View Article and Find Full Text PDFPetrographic and geochemical studies were undertaken on the Paleocene-Eocene limestones of the Ewekoro Formation in order to infer the depositional and post-depositional imprints on the limestone. Thin section petrographic studies revealed three distinct microfacies; grainstone, packstone and wackestone, and there were variations in the depositional environments from meteoric vadose to shallow marine environments with evidences of post-depositional processes of compaction, micritization and dolomitization. The total rare earth element concentration (ƩREE) of the limestone samples ranged from 39.
View Article and Find Full Text PDFMolecular metabolic imaging in humans is dominated by positron emission tomography (PET). An emerging nonionizing alternative is hyperpolarized MRI of C-pyruvate, which is innocuous and has a central role in metabolism. However, similar to PET, hyperpolarized MRI with dissolution dynamic nuclear polarization (d-DNP) is complex costly, and requires significant infrastructure.
View Article and Find Full Text PDFSignal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) is investigated to achieve rapid hyperpolarization of C spins of [1- C]pyruvate, using parahydrogen as the source of nuclear spin order. Pyruvate exchange with an iridium polarization transfer complex can be modulated via a sensitive interplay between temperature and co-ligation of DMSO and H O. Order-unity C (>50 %) polarization of catalyst-bound [1- C]pyruvate is achieved in less than 30 s by restricting the chemical exchange of [1- C]pyruvate at lower temperatures.
View Article and Find Full Text PDFA novel series of polyamine/CNT composites were synthesized via a single step polycondensation reaction of melamine, paraformaldehyde, various alkyldiamines and chlorinated carbon nanotubes (CNT) at optimized reaction conditions in the presence of N, N-Dimethyl formamide as a solvent. Chlorinated carbon nanotubes synthesized by reacting acidified CNT and thionyl chloride was used. The pure polymer (MFDH) and the functionalized composites (MFDH1, MFDH2, MFDH3 and MFDH4) having 0.
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