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.

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.

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.

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.

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.

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.

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.

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.

Scalable spin amplification with a gain over a hundred.

We propose a scalable and practical implementation of spin amplification which does not require individual addressing nor a specially tailored spin network. We have demonstrated a gain of 140 in a solid-state nuclear spin system of which the spin polarization has been increased to 0.12 using dynamic nuclear polarization with photoexcited triplet electron spins. Spin amplification scalable to a higher gain opens the door to the single spin measurement for a readout of quantum computers as well as practical applications of nuclear magnetic resonance spectroscopy to infinitesimal samples which have been concealed by thermal noise.

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.

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.

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.

Development of biodegradable scaffolds based on patient-specific arterial configuration.

Biodegradable scaffolds are of great value in tissue engineering. We have developed a method for fabricating patient-specific vascular scaffolds from a biocompatible and biodegradable polymer, poly(L-lactide-co-epsilon-caprolactone). This method's usefulness is due to flexibility in the choice of materials and vascular configurations. Here, we present a way to fabricate scaffolds of human carotid artery by combining processes of rapid prototyping, lost wax, dip coating, selective dissolution, and salt leaching. The result was the successful development of porous biodegradable scaffolds, with mechanical strength covering the range of human blood vessels (1-3 MPa). Human umbilical vein endothelial cells were also cultured on the scaffolds and their biocompatibility was confirmed by cell growth. The Young's modulus of scaffolds could be controlled by changing polymer concentration and porosity. The wall thickness of the tubular scaffold was also controllable by adjusting polymer concentration and pull-up velocity during dip coating. We believe that this fabrication technique can be applied to patient-specific regeneration of blood vessels.

Usefulness of a simplified management scheme for paraclinoid aneurysms based on a modified classification.

BACKGROUND: Our objective was to set up a management-oriented classification for paraclinoid aneurysms, and then design and apply a simplified management scheme according to each group defined by this classification. METHODS: Paraclinoid aneurysms were classified as group I (supraophthalmic artery), group II (ophthalmic artery) and group III (infraophthalmic artery) aneurysms intradurally. Between January 2005 and December 2006, 86 cases with 89 paraclinoid aneurysms were treated. There were 35 (40.2%) aneurysms in group I (20 in group Ia, 15 in group Ib), 32 (36.8%) in group II and 20 (23%) in group III. RESULTS: In group I aneurysms, 20 (57.1%) were treated by clipping or/and wrapping, while 15 (42.9%) were managed by coiling. In group II aneurysms, 20 (62.5%) were treated by clipping and 12 (37.5%) by coiling. The contralateral approach was performed for 4 (6%) aneurysms in groups I and II. All 20 group III aneurysms were treated by coiling. The overall rate of permanent complications was 4.6%. The rate of complete occlusion was 92.5% in surgical cases and 55.6% in endovascular ones. The overall outcomes in the treatment of paraclinoid aneurysms were excellent (GOS = 5, 95.4%). CONCLUSION: Based on our modified classification of paraclinoid aneurysms, a simplified management scheme was designed and applied. For group I (supraophthalmic artery) and group II (ophthalmic artery) aneurysms, surgical clipping or/and wrapping should be the first choice of treatment, while for group III (infraophthalmic artery) aneurysms, endovascular coiling should be the best modality. Additionally, individualizing the treatment planning might contribute to better results.

The relationship between venous hypertension and expression of vascular endothelial growth factor: hemodynamic and immunohistochemical examinations in a rat venous hypertension model.

BACKGROUND: Venous hypertension is regarded as an important factor in the pathogenesis of dural arteriovenous fistula (DAVF). We investigate histologic reaction of dural sinus under the condition of venous hypertension using a rat venous hypertension model to present hemodynamic and immunohistochemical effect in the development of DAVF. METHODS: Twenty-four Sprague-Dawley male rats were divided into venous hypertension and control groups. Venous hypertension was induced with a left common carotid artery-external jugular vein anastomosis and an occlusion of a right posterior facial vein. Measurements of systemic mean arterial pressure, draining vein pressure (DVP), and cerebral perfusion pressure (CPP) were conducted on the next day, at 7 days, and at 28 days after surgery, and the rats were killed for histologic examinations. RESULTS: Postoperative DVP increased significantly in venous hypertension group compared to control group (35 +/- 5 vs 13 +/- 2 mm Hg, P < .05). Increased DVP remained above 30 mm Hg throughout the observation period. Postoperative CPP decreased significantly in venous hypertension group compared to control group (49 +/- 8 vs 86 +/- 9 mm Hg, P < .05). In venous hypertension group, there was a significant difference between days 1 and 28 (49 +/- 8 vs 64 +/- 8 mm Hg, P < .05). Histologic examination revealed thickening of connective tissues, proliferation of fibroblasts, and strong expression of vascular endothelial growth factor (VEGF) in endothelium under venous hypertension condition. Immunostained VEGF cells decreased significantly from day 7 to day 28 (100 +/- 16 vs 72 +/- 19 cells, P < .05). A positive correlation was observed between DVP and VEGF expression (Pearson correlation coefficient; r = 0.671, P = .0017). There was a negative correlation between CPP and immunostained VEGF cells (r = -0.702, P = .0089). CONCLUSIONS: These results suggest that venous hypertension is associated with increased expression of VEGF, and a decreased CPP may have a potential effect in VEGF expression under venous hypertension condition. These factors are speculated to play an important role in progression of DAVF.

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.

CT angiography with electrocardiographically gated reconstruction for visualizing pulsation of intracranial aneurysms: identification of aneurysmal protuberance presumably associated with wall thinning.

Electrocardiographically (ECG) gated multisection helical CT images were obtained in 23 patients with ruptured intracranial aneurysms. 4D-CTA (3D CT angiography plus phase data) images were generated by ECG-gated reconstruction. Four patients showed pulsation of an aneurysmal bleb. Clipping was performed in two of these patients, and the rupture site matched the pulsatile bleb seen in 4D-CTA.

Contralateral meningeal artery supply of paramedian meningiomas.

BACKGROUND: When resecting at falcine or parasagittal portion of paramedian meningiomas, intraoperative hemostasis often is difficult despite effective management of ipsilateral meningeal arteries. We attribute such difficulties to meningeal artery blood supply from the contralateral side. We retrospectively studied feeding arteries from both sides in case of paramedian meningioma in terms of patient and tumor characteristics. METHODS: Forty-three patients with paramedian meningiomas underwent selective internal and external carotid angiography. We investigated how contralateral meningeal arterial feeders related to patient profiles and imaging, histopathologic, and immunohistochemical findings. RESULTS: Contralateral meningeal supply existed for 14 of 25 falcine meningiomas and 6 of 18 parasagittal meningiomas. Patients with contralateral feeders were 8.5 years younger than the others (P=.027) and were more likely to have larger tumors (P=.028). These were histopathologically malignant (P=.048), while showing more proliferation followed by monoclonal antibody against the Ki-67 antigen index (P=.012) and angiogenetic potential associated with vascular endothelial growth factor expression (P=.0085). CONCLUSIONS: Contralateral meningeal supply may reflect strong angiogenetic recruitment from rapid tumor growth followed by high expression of vascular endothelial growth factor. This angiographical feature may predict the aggressive growth of paramedian meningiomas.