Cocrystalline Matrices for Hyperpolarization at Room Temperature Using Photoexcited Electrons.

We propose using cocrystals as effective polarization matrices for triplet dynamic nuclear polarization (DNP) at room temperature. The polarization source can be uniformly doped into cocrystals formed through acid-acid, amide-amide, and acid-amide synthons. The dense-packing crystal structures, facilitated by multiple hydrogen bonding and π-π interactions, result in extended T1 relaxation times, enabling efficient polarization diffusion within the crystals. Our study demonstrates the successful polarization of a DNP-magnetic resonance imaging molecular probe, such as urea, within a cocrystal matrix at room temperature using triplet-DNP.

Hyperpolarization of Biomolecules in Eutectic Crystals at Room Temperature Using Photoexcited Electrons.

The hyperpolarization of biomolecules at room temperature could facilitate highly sensitive magnetic resonance imaging for metabolic studies and nuclear magnetic resonance (NMR)-based screenings for drug discovery. In this study, we demonstrate the hyperpolarization of biomolecules in eutectic crystals using photoexcited triplet electrons at room temperature. Eutectic crystals composed of the domains of benzoic acid doped with the polarization source and analyte domains were prepared using a melting-quenching process. Spin diffusion between the benzoic acid and analyte domain was elucidated using solid-state NMR analysis, indicating that hyperpolarization was transferred from the domain of benzoic acid to the domain of the analyte.

Triplet-DNP in magnetically oriented microcrystal arrays.

We explore dynamic nuclear polarization using electron spins in the photo-excited triplet state (Triplet-DNP) in magnetically oriented microcrystal arrays (MOMAs) of pentacene-doped p-terphenyl, in which the individual crystallites are magnetically aligned and UV-cured. In contrast to the conventional approach to Triplet-DNP in powder, which suffers from reduced nuclear polarization due to the averaged electron polarization and the broadening of electron-spin resonance, Triplet-DNP of the MOMAs offers as high dynamic polarization as that attainable in single-crystals. In the case of pentacene-doped p-terphenyl, the enhanced 1H polarization in the one-dimensional MOMA, prepared simply by leaving the suspension in a stationary magnetic field before UV curation, can be higher than that attainable in the powder sample by an order of magnitude and comparable to that in single crystals and in the three-dimensional MOMA made using a modulational rotating field. Triplet-DNP of the MOMAs may find potential applications, such as the polarization of the co-doped target molecules and dissolution experiments.

Real-time monitoring of enzyme-catalyzed phosphoribosylation of anti-influenza prodrug favipiravir by time-lapse nuclear magnetic resonance spectroscopy.

Favipiravir (brand name Avigan), a widely known anti-influenza prodrug, is metabolized by endogenous enzymes of host cells to generate the active form, which exerts inhibition of viral RNA-dependent RNA polymerase activity; first, favipiravir is converted to its phosphoribosylated form, favipiravir-ribofuranosyl-5'-monophosphate (favipiravir-RMP), by hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Because this phosphoribosylation reaction is the rate-determining step in the generation of the active metabolite, quantitative and real-time monitoring of the HGPRT-catalyzed reaction is essential to understanding the pharmacokinetics of favipiravir. However, assay methods enabling such monitoring have not been established. 19 F- or 31 P-based nuclear magnetic resonance (NMR) are powerful techniques for observation of intermolecular interactions, chemical reactions, and metabolism of molecules of interest, given that NMR signals of the heteronuclei sensitively reflect changes in the chemical environment of these moieties. Here, we demonstrated direct, sensitive, target-selective, nondestructive, and real-time observation of HGPRT-catalyzed conversion of favipiravir to favipiravir-RMP by performing time-lapse 19 F-NMR monitoring of the fluorine atom of favipiravir. In addition, we showed that 31 P-NMR can be used for real-time observation of the identical reaction by monitoring phosphorus atoms of the phosphoribosyl group of favipiravir-RMP and of the pyrophosphate product of that reaction. Furthermore, we demonstrated that NMR approaches permit the determination of general parameters of enzymatic activity such as Vmax and Km . This method not only can be widely employed in enzyme assays, but also may be of use in the screening and development of new favipiravir-analog antiviral prodrugs that can be phosphoribosylated more efficiently by HGPRT, which would increase the intracellular concentration of the drug's active form. The techniques demonstrated in this study would allow more detailed investigation of the pharmacokinetics of fluorinated drugs, and might significantly contribute to opening new avenues for widespread pharmaceutical studies.

Room-temperature hyperpolarization of polycrystalline samples with optically polarized triplet electrons: pentacene or nitrogen-vacancy center in diamond?

We demonstrate room-temperature 13C hyperpolarization by dynamic nuclear polarization (DNP) using optically polarized triplet electron spins in two polycrystalline systems: pentacene-doped [carboxyl-13C] benzoic acid and microdiamonds containing nitrogen-vacancy (NV-) centers. For both samples, the integrated solid effect (ISE) is used to polarize the 13C spin system in magnetic fields of 350-400 mT. In the benzoic acid sample, the 13C spin polarization is enhanced by up to 0.12 % through direct electron-to-13C polarization transfer without performing dynamic 1H polarization followed by 1H-13C cross-polarization. In addition, the ISE has been successfully applied to polarize naturally abundant 13C spins in a microdiamond sample to 0.01 %. To characterize the buildup of the 13C polarization, we discuss the efficiencies of direct polarization transfer between the electron and 13C spins as well as that of 13C-13C spin diffusion, examining various parameters which are beneficial or detrimental for successful bulk dynamic 13C polarization.

High-field NMR with dissolution triplet-DNP.

Dissolution dynamic nuclear polarization (DNP) has wide variety of important applications such as real-time monitoring of chemical reactions and metabolic imaging. We construct DNP using photoexcited triplet electron spins (Triplet-DNP) apparatus combined with dissolution apparatus for solution NMR in a high magnetic field. Triplet-DNP enables us to obtain high nuclear polarization at room temperature. Solid-state samples polarized by Triplet-DNP are transferred to a superconducting magnet and dissolved by injecting aqueous solvents. The 13C polarization of 0.22% has been obtained for [caryboxy-13C]benzoic acid-d in the liquid state. Our results show that Triplet-DNP can be applied to real-time monitoring with solution NMR.

Dynamic nuclear polarization with photo-excited triplet electrons using 6,13-diphenylpentacene.

Dynamic nuclear polarization with photo-excited triplet electrons (Triplet-DNP) is demonstrated using 6,13-diphenylpentacene (DPPentacene). DPPentacene is soluble in various organic solvents, while pentacene, which is used in most of the triplet-DNP experiments, has limited solubility. An enhancement factor of 81 is obtained for 1H spins in the glass of ethanol-d6 : water = 80 : 20 (w/w) doped with 0.1 mM DPPentacene at 90 K in 0.67 T.

Acute Ischemic Stroke due to Undifferentiated Sarcoma: A Case Report and Literature Review.

Tumor emboli due to a sarcoma are usually confirmed by an autopsy or operative findings. A sarcoma embolus in an acute stroke patient is rare. We herein report a 37-year-old man with acute stroke caused by internal carotid artery occlusion who underwent embolectomy. A histopathological analysis of an embolus obtained with a mechanical retriever device was diagnosed as undifferentiated sarcoma. This is the first case of extracardiac sarcoma extraction via mechanical retrieval performed during intervention for acute ischemic stroke. A histopathologic evaluation with embolectomy is important for diagnosing tumor emboli.

Dynamic Nuclear Polarization using Photoexcited Triplet Electron Spins in Eutectic Mixtures.

Dynamic nuclear polarization using photoexcited triplet electrons (Triplet-DNP) is a method to significantly enhance nuclear spin polarization even in a low magnetic field and at room temperature. Pentacene has been practically used as an efficient polarizing agent for Triplet-DNP. In this study, we demonstrate room temperature 1H and 13C hyperpolarization of eutectic mixtures of deuterated benzoic acid doped with pentacene and a target molecule such as salicylic acid, nicotinic acid, or 2-naphthoic acid. These molecules are otherwise difficult to hyperpolarize by Triplet-DNP due to the low pentacene dopabilities of these molecules. The highest 1H polarization of 1.2% has been obtained for the eutectic mixture of salicylic acid in 0.39 T. The present sample preparation is a crucial method to widen the range of applications of Triplet-DNP to chemical and biomedical analyses.

Dissolution Dynamic Nuclear Polarization at Room Temperature Using Photoexcited Triplet Electrons.

Dissolution dynamic nuclear polarization (DNP) has recently gained attention as a method to enhance the sensitivity of liquid NMR spectroscopy and MRI. We demonstrate dissolution of the sample hyperpolarized by DNP using photoexcited triplet electrons in 0.38 T at room temperature. The achieved polarization of 0.8% is 6100 times as high as that at thermal equilibrium under the condition. The result is an important step for DNP using photoexcited triplet electrons to become widely used in chemical and biomedical research.

Hybrid stent device of flow-diverting effect and stent-assisted coil embolization formed by fractal structure.

This paper presents a novel hybrid medical stent device. This hybrid stent device formed by fractal mesh structures provides a flow-diverting effect and stent-assisted coil embolization. Flow-diverter stents decrease blood flow into an aneurysm to prevent its rupture. In general, the mesh size of a flow-diverter stent needs to be small enough to prevent blood flow into the aneurysm. Conventional flow-diverter stents are not available for stent-assisted coil embolization, which is an effective method for aneurysm occlusion, because the mesh size is too small to insert a micro-catheter for coil embolization. The proposed hybrid stent device is capable of stent-assisted coil embolization while simultaneously providing a flow-diverting effect. The fractal stent device is composed of mesh structures with fine and rough mesh areas. The rough mesh area can be used to insert a micro-catheter for stent-assisted coil embolization. Flow-diverting effects of two fractal stent designs were composed to three commercially available stent designs. Flow-diverting effects were analyzed using computational fluid dynamics (CFD) analysis and particle image velocimetry (PIV) experiment. Based on the CFD and PIV results, the fractal stent devices reduce the flow velocity inside an aneurism just as much as the commercially available flow-diverting stents while allowing stent-assisted coil embolization.

A Ku band pulsed electron paramagnetic resonance spectrometer using an arbitrary waveform generator for quantum control experiments at millikelvin temperatures.

We present a 17 GHz (Ku band) arbitrary waveform pulsed electron paramagnetic resonance spectrometer for experiments down to millikelvin temperatures. The spectrometer is located at room temperature, while the resonator is placed either in a room temperature magnet or inside a cryogen-free dilution refrigerator; the operating temperature range of the dilution unit is from ca. 10 mK to 8 K. This combination provides the opportunity to perform quantum control experiments on electron spins in the pure-state regime. At 0.6 T, spin echo experiments were carried out using γ-irradiated quartz glass from 1 K to 12.3 mK. With decreasing temperatures, we observed an increase in spin echo signal intensities due to increasing spin polarizations, in accordance with theoretical predictions. Through experimental data fitting, thermal spin polarization at 100 mK was estimated to be at least 99%, which was almost pure state. Next, to demonstrate the ability to create arbitrary waveform pulses, we generate a shaped pulse by superposing three Gaussian pulses of different frequencies. The resulting pulse was able to selectively and coherently excite three different spin packets simultaneously-a useful ability for analyzing multi-spin system and for controlling a multi-qubit quantum computer. By applying this pulse to the inhomogeneously broadened sample, we obtain three well-resolved excitations at 8 K, 1 K, and 14 mK.

Room temperature hyperpolarization of nuclear spins in bulk.

Dynamic nuclear polarization (DNP), a means of transferring spin polarization from electrons to nuclei, can enhance the nuclear spin polarization (hence the NMR sensitivity) in bulk materials at most 660 times for (1)H spins, using electron spins in thermal equilibrium as polarizing agents. By using electron spins in photo-excited triplet states instead, DNP can overcome the above limit. We demonstrate a (1)H spin polarization of 34%, which gives an enhancement factor of 250,000 in 0.40 T, while maintaining a bulk sample (∼ 0.6 mg, ∼ 0.7 × 0.7 × 1 mm(3)) containing >10(19) (1)H spins at room temperature. Room temperature hyperpolarization achieved with DNP using photo-excited triplet electrons has potentials to be applied to a wide range of fields, including NMR spectroscopy and MRI as well as fundamental physics.

In vitro simulator with numerical stress analysis for evaluation of stent-assisted coiling embolization in cerebral aneurysm treatments.

BACKGROUND: There are several complications associated with Stent-assisted Coil Embolization (SACE) in cerebral aneurysm treatments, due to damaging operations by surgeons and undesirable mechanical properties of stents. Therefore, it is necessary to develop an in vitro simulator that provides both training and research for evaluating the mechanical properties of stents. METHODS: A new in vitro simulator for three-dimensional digital subtraction angiography was constructed, followed by aneurysm models fabricated with new materials. Next, this platform was used to provide training and to conduct photoelastic stress analysis to evaluate the SACE technique. RESULTS: The average interaction stress increasingly varied for the two different stents. Improvements for the Maximum-Likelihood Expectation-Maximization method were developed to reconstruct cross-sections with both thickness and stress information. CONCLUSIONS: The technique presented can improve a surgeon's skills and quantify the performance of stents to improve mechanical design and classification. This method can contribute to three-dimensional stress and volume variation evaluation and assess a surgeon's skills.

Strongly driven electron spins using a K(u) band stripline electron paramagnetic resonance resonator.

This article details our work to obtain strong excitation for electron paramagnetic resonance (EPR) experiments by improving the resonator's efficiency. The advantages and application of strong excitation are discussed. Two 17 GHz transmission-type, stripline resonators were designed, simulated and fabricated. Scattering parameter measurements were carried out and quality factor were measured to be around 160 and 85. Simulation results of the microwave's magnetic field distribution are also presented. To determine the excitation field at the sample, nutation experiments were carried out and power dependence were measured using two organic samples at room temperature. The highest recorded Rabi frequency was rated at 210 MHz with an input power of about 1 W, which corresponds to a π/2 pulse of about 1.2 ns.

In vitro strain measurements in cerebral aneurysm models for cyber-physical diagnosis.

BACKGROUND: The development of new diagnostic technologies for cerebrovascular diseases requires an understanding of the mechanism behind the growth and rupture of cerebral aneurysms. To provide a comprehensive diagnosis and prognosis of this disease, it is desirable to evaluate wall shear stress, pressure, deformation and strain in the aneurysm region, based on information provided by medical imaging technologies. METHODS: In this research, we propose a new cyber-physical system composed of in vitro dynamic strain experimental measurements and computational fluid dynamics (CFD) simulation for the diagnosis of cerebral aneurysms. A CFD simulation and a scaled-up membranous silicone model of a cerebral aneurysm were completed, based on patient-specific data recorded in August 2008. In vitro blood flow simulation was realized with the use of a specialized pump. A vision system was also developed to measure the strain at different regions on the model by way of pulsating blood flow circulating inside the model. RESULTS: Experimental results show that distance and area strain maxima were larger near the aneurysm neck (0.042 and 0.052), followed by the aneurysm dome (0.023 and 0.04) and finally the main blood vessel section (0.01 and 0.014). These results were complemented by a CFD simulation for the addition of wall shear stress, oscillatory shear index and aneurysm formation index. Diagnosis results using imaging obtained in August 2008 are consistent with the monitored aneurysm growth in 2011. CONCLUSION: The presented study demonstrates a new experimental platform for measuring dynamic strain within cerebral aneurysms. This platform is also complemented by a CFD simulation for advanced diagnosis and prediction of the growth tendency of an aneurysm in endovascular surgery.

Delayed rupture of a basilar artery aneurysm treated with coils: case report and review of the literature.

Delayed rupture of a previously unruptured cerebral aneurysm after uneventful saccular coil packing is rare, particularly when the quality of aneurysm occlusion is appropriate (neck remnant or total occlusion). The present report describes the case of a 70-year-old woman with an incidentally detected, asymptomatic, small basilar tip non-thrombosed aneurysm who experienced rupture of the aneurysm 2 years after coiling. Cerebral angiography taken on the day of rupture revealed only small recanalization of the aneurysm neck with no dome-filling. This is the first report of delayed rupture due to minor recurrence of a previously unruptured small asymptomatic cerebral aneurysm after saccular coil packing. A literature review of 26 reports of late bleeding after coil embolization of previously unruptured cerebral aneurysms showed that dome-filling after coil embolization, symptomatic aneurysms and large/giant aneurysms all increase the risk of delayed rupture in previously unruptured aneurysms after saccular coil packing.

Technical skills measurement based on a cyber-physical system for endovascular surgery simulation.

BACKGROUND: Quantification of medical skills is a challenge, particularly simulator-based training. In the case of endovascular intervention, it is desirable that a simulator accurately recreates the morphology and mechanical characteristics of the vasculature while enabling scoring. METHODS: For this purpose, we propose a cyber-physical system composed of optical sensors for a catheter's body motion encoding, a magnetic tracker for motion capture of an operator's hands, and opto-mechatronic sensors for measuring the interaction of the catheter tip with the vasculature model wall. Two pilot studies were conducted for measuring technical skills, one for distinguishing novices from experts and the other for measuring unnecessary motion. RESULTS: The proficiency levels were measurable between expert and novice and also between individual novice users. The results enabled scoring of the user's proficiency level, using sensitivity, reaction time, time to complete a task and respect for tissue integrity as evaluation criteria. Additionally, unnecessary motion was also measurable. CONCLUSION: The development of cyber-physical simulators for other domains of medicine depend on the study of photoelastic materials for human tissue modelling, and enables quantitative evaluation of skills using surgical instruments and a realistic representation of human tissue.

Development of biodegradable scaffolds based on magnetically guided assembly of magnetic sugar particles.

Biodegradable scaffolds with controlled pore layout and porosity have great significance in tissue engineering for cell penetration, tissue ingrowth, vascularization, and nutrient delivery. Porogen leaching has been commonly used to control pore size, pore structure and porosity in the scaffold. In this paper we focus on the use/development of two magnetically guided porogen assembly methods using magnetic sugar particles (MSPs) for scaffold fabrication. First, a patterning device is utilized to align MSPs following designed templates. Then a magnetic sheet film is fabricated by mixing poly(vinyl alcohol, PVA) and NdFeB powder for steering the MSPs. After poly(l-lactide-co-ɛ-caprolactone) (PLCL) casting and removal of the sugar template, a scaffold with spherical pores is obtained. The surface and the inner structure of the scaffolds are evaluated using light and electron micrographs showing their interconnection of pores, pore wall morphology and porosity. Single layer scaffolds with the size of 8mm in width and 10mm in length were constructed with controllable pore diameters in the ranges of 105-150 µm, 250-300 µm and 425-500 µm.