RESUMEN
Parahydrogen-induced polarization (PHIP) is an inexpensive way to produce hyperpolarized molecules with polarization levels of >10 % in the solution-state, but is strongly limited in generality since it requires chemical reactions/ interactions with H2. Here we report a new method to widen the scope of PHIP hyperpolarization: a source molecule is produced via PHIP with high 13C polarization, and precipitated out of solution together with a target species. Spin diffusion within the solid carries the polarization onto 13C spins of the target, which can then be dissolved for solution-state applications. We name this method PHIP-SSD (PHIP with solid-state spin diffusion) and demonstrate it using PHIP-polarized [1-13C]-fumarate as the source molecule, to polarize different 13C-labelled target molecules. 13C polarizations of between 0.01 and 3 % were measured on [1-13C]-benzoic acid, depending on the molar ratio of fumarate:benzoate in the solid state. We also show that PHIP-SSD does not require specific co-crystallization conditions by grinding dry powders of target molecules together with solid fumarate crystals, and obtain 13C signal enhancements of between 100 and 200 on [13C,15N2]-urea, [1-13C]-pyruvate, and [1-13C]-benzoic acid. This approach appears to be a promising new strategy for facile hyperpolarization based on PHIP.
RESUMEN
Hyperpolarization techniques increase nuclear spin polarization by more than four orders of magnitude, enabling metabolic MRI. Even though hyperpolarization has shown clear value in clinical studies, the complexity, cost and slowness of current equipment limits its widespread use. Here, a polarization procedure of [1-13 C]pyruvate based on parahydrogen-induced polarization by side-arm hydrogenation (PHIP-SAH) in an automated polarizer is demonstrated. It is benchmarked in a study with 48 animals against a commercial dissolution dynamic nuclear polarization (d-DNP) device. Purified, concentrated (≈70-160 mM) and highly hyperpolarized (≈18%) solutions of pyruvate are obtained at physiological pH for volumes up to 2 mL within 85 s in an automated process. The safety profile, image quality, as well as the quantitative perfusion and lactate-to-pyruvate ratios, are equivalent for PHIP and d-DNP, rendering PHIP a viable alternative to established hyperpolarization techniques.
Asunto(s)
Hidrógeno , Ácido Pirúvico , Animales , Ácido Pirúvico/metabolismo , Isótopos de Carbono , Imagen por Resonancia Magnética/métodos , HidrogenaciónRESUMEN
Carbon-13 hyperpolarized pyruvate is about to become the next-generation contrast agent for molecular magnetic resonance imaging of cancer and other diseases. Here, efficient and rapid pyruvate hyperpolarization is achieved via signal amplification by reversible exchange (SABRE) with parahydrogen through synergistic use of substrate deuteration, alternating, and static microtesla magnetic fields. Up to 22 and 6% long-lasting 13C polarization (T1 = 3.7 ± 0.25 and 1.7 ± 0.1 min) is demonstrated for the C1 and C2 nuclear sites, respectively. The remarkable polarization levels become possible as a result of favorable relaxation dynamics at the microtesla fields. The ultralong polarization lifetimes will be conducive to yielding high polarization after purification, quality assurance, and injection of the hyperpolarized molecular imaging probes. These results pave the way to future in vivo translation of carbon-13 hyperpolarized molecular imaging probes prepared by this approach.
Asunto(s)
Imagen por Resonancia Magnética , Ácido Pirúvico , Espectroscopía de Resonancia Magnética/métodos , Isótopos de CarbonoRESUMEN
We present a versatile method for the preparation of hyperpolarized [1-13C]fumarate as a contrast agent for preclinical in vivo MRI, using parahydrogen-induced polarization (PHIP). To benchmark this process, we compared a prototype PHIP polarizer to a state-of-the-art dissolution dynamic nuclear polarization (d-DNP) system. We found comparable polarization, volume, and concentration levels of the prepared solutions, while the preparation effort is significantly lower for the PHIP process, which can provide a preclinical dose every 10 min, opposed to around 90 min for d-DNP systems. With our approach, a 100 mM [1-13C]-fumarate solution of volumes up to 3 mL with 13-20% 13C-hyperpolarization after purification can be produced. The purified solution has a physiological pH, while the catalyst, the reaction side products, and the precursor material concentrations are reduced to nontoxic levels, as confirmed in a panel of cytotoxicity studies. The in vivo usage of the hyperpolarized fumarate as a perfusion agent in healthy mice and the metabolic conversion of fumarate to malate in tumor-bearing mice developing regions with necrotic cell death is demonstrated. Furthermore, we present a one-step synthesis to produce the 13C-labeled precursor for the hydrogenation reaction with high yield, starting from 13CO2 as a cost-effective source for 13C-labeled compounds.
Asunto(s)
Fumaratos , Imagen por Resonancia Magnética , Ratones , Animales , Espectroscopía de Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Hidrogenación , Medios de ContrasteRESUMEN
Magnetic resonance imaging of 13C-labeled metabolites enhanced by parahydrogen-induced polarization (PHIP) enables real-time monitoring of processes within the body. We introduce a robust, easily implementable technique for transferring parahydrogen-derived singlet order into 13C magnetization using adiabatic radio frequency sweeps at microtesla fields. We experimentally demonstrate the applicability of this technique to several molecules, including some molecules relevant for metabolic imaging, where we show significant improvements in the achievable polarization, in some cases reaching above 60% nuclear spin polarization. Furthermore, we introduce a site-selective deuteration scheme, where deuterium is included in the coupling network of a pyruvate ester to enhance the efficiency of the polarization transfer. These improvements are enabled by the fact that the transfer protocol avoids relaxation induced by strongly coupled quadrupolar nuclei.
RESUMEN
The ultra-diffuse galaxies DF2 and DF4 in the NGC 1052 group share several unusual properties: they both have large sizes1, rich populations of overluminous and large globular clusters2-6, and very low velocity dispersions that indicate little or no dark matter7-10. It has been suggested that these galaxies were formed in the aftermath of high-velocity collisions of gas-rich galaxies11-13, events that resemble the collision that created the bullet cluster14 but on much smaller scales. The gas separates from the dark matter in the collision and subsequent star formation leads to the formation of one or more dark-matter-free galaxies12. Here we show that the present-day line-of-sight distances and radial velocities of DF2 and DF4 are consistent with their joint formation in the aftermath of a single bullet-dwarf collision, around eight billion years ago. Moreover, we find that DF2 and DF4 are part of an apparent linear substructure of seven to eleven large, low-luminosity objects. We propose that these all originated in the same event, forming a trail of dark-matter-free galaxies that is roughly more than two megaparsecs long and angled 7° ± 2° from the line of sight. We also tentatively identify the highly dark-matter-dominated remnants of the two progenitor galaxies that are expected11 at the leading edges of the trail.
RESUMEN
Nuclear spin hyperpolarization provides a promising route to overcome the challenges imposed by the limited sensitivity of nuclear magnetic resonance. Here we demonstrate that dissolution of spin-polarized pentacene-doped naphthalene crystals enables transfer of polarization to target molecules via intermolecular cross-relaxation at room temperature and moderate magnetic fields (1.45 T). This makes it possible to exploit the high spin polarization of optically polarized crystals, while mitigating the challenges of its transfer to external nuclei. With this method, we inject the highly polarized mixture into a benchtop NMR spectrometer and observe the polarization dynamics for target 1H nuclei. Although the spectra are radiation damped due to the high naphthalene magnetization, we describe a procedure to process the data to obtain more conventional NMR spectra and extract the target nuclei polarization. With the entire process occurring on a time scale of 1 min, we observe NMR signals enhanced by factors between -200 and -1730 at 1.45 T for a range of small molecules.
RESUMEN
3-Aryl-1-(trifluoromethyl)prop-2-yn-1-iminium triflate salts represent a novel, highly reactive class of acetylenic iminium salts. Herein we present several reactions which are based on the electron-poor acetylenic bond and on the high electrophilicity of the CF3-substituted iminium group. These salts were found to be highly reactive dienophiles in Diels-Alder reactions with cyclopentadiene, 2,3-dimethylbutadiene and even anthracene. At higher temperature, the cycloadducts undergo an intramolecular SE(Ar) reaction leading to condensed carbocycles incorporating a 1-(trifluoromethyl)-1-(dimethylamine)indene ring system. With styrenes and some substituted styrenes, cascade reactions take place, which likely include cyclobutene and several cationic intermediates and mainly yield 2-(1-phenylvinyl)indenes. In a similar reaction cascade, a fulvene derivative was obtained with 1,4-diphenylbutadiene as the substrate.
RESUMEN
OBJECTIVES: To update a previous clinical practice guideline on suctioning in adult patients, published in the Canadian Respiratory Journal in 2001. METHODS: A primary search of the MEDLINE (from 1998), CINAHL, EMBASE and The Cochrane Library (all from 1996) databases up to November 2007, was conducted. These dates reflect the search limits reached in the previous clinical practice guideline. A secondary search of the reference lists of retrieved articles was also performed. Two reviewers independently appraised each study before meeting to reach consensus. Study quality was evaluated using the Jadad and PEDro scales. When sufficient data were available, a meta-analysis was conducted using a random effects model. Data are reported as ORs, weighted mean differences and 95% CIs. When no comparisons were possible, qualitative analyses of the data were completed. RESULTS: Eighty-one studies were critically appraised from a pool of 123. A total of 28 randomized controlled trials or randomized crossover studies were accepted for inclusion. Meta-analysis was possible for open versus closed suctioning only. Recommendations from 2001 with respect to hyperoxygenation, hyperinflation, use of a ventilator circuit adaptor and subglottic suctioning were confirmed. New evidence was identified with respect to indications for suctioning, open suction versus closed suction systems, use of medications and infection control. CONCLUSIONS: While new evidence continues to be varied in strength, and is still lacking in some areas of suctioning practice, the evidence base has improved since 2001. Members of the health care team should incorporate this evidence into their practice.