Microimaging at 14 tesla using GESEPI for removal of magnetic susceptibility artifacts in T(2)(*)-weighted image contrast.

In magnetic resonance imaging (MRI), T(2)(*)-weighted contrast is significantly enhanced by extremely high magnetic field strength, offering broad potential applications. However, the T(2)(*)-weighted image contrast distortion and signal loss artifact arising from discontinuities of magnetic susceptibility within and around the sample are also increased, limiting utilization of high field systems for T(2)(*)-weighted contrast applications. Due to the B(0) dependence of the contrast distortions and signal losses, and the heterogeneity of magnetic susceptibility in biological samples, magnetic susceptibility artifacts worsen dramatically for in vivo microimaging at higher fields. Practical applications of T(2)(*)-sensitive techniques enhanced by higher magnetic fields are therefore challenged. This report shows that magnetic susceptibility artifacts dominate T(2)(*)-weighted image contrast at 14 T, and demonstrates that the GESEPI (gradient echo slice excitation profile imaging) technique effectively reduces or eliminates these artifacts at long TE in the highest field (14 T) currently available for (1)H imaging.

Improvements on an in vivo automatic shimming method [FASTERMAP].

Improvements on a localized, automatic shimming method described by Gruetter and Boesch (J. Magn. Reson. 96, 323-334 (1992)) and Gruetter (Magn. Reson. Med. 29, 804-811 (1993)) are presented. A spin-echo sequence employing a double sech refocusing scheme is used to acquire a field map along linear projections that improves the signal-to-noise ratio by at least a factor of two over the stimulated echo sequence previously used. To further improve the reliability of shim adjustments, a variance-weighted polynomial regression analysis is performed. This also extends the scope of application of this technique to global shimming. Localized 1H spectra of human brain shimmed by this method are presented.

A proposal for the conformation of loop E in Escherichia coli 5S rRNA.

A proposal is advanced for the conformation of the loop E region of prokaryotic 5S rRNAs based on spectroscopic data obtained from pAD3 RNA, a construct that includes helix IV, helix V, and loops D and E from Escherichia coli 5S rRNA. Even though loop E juxtaposes bases that cannot form Watson-Crick base pairs, it resembles an A-form double helix; its nucleotides relate to each other spectroscopically in a helix-like way and are in the anti conformation. The ends of loop E, which is palindromic, have the same conformation. Working in from either end towards the center of the loop, a closing GC is followed by a side-by-side GA and then by a reversed Hoogsteen AU, a pattern resembling that found at one end of eukaryotic loop E. The center of the loop consists of three nucleotide pairs, which appear to be an asymmetric GG pair, a Watson-Crick-like AG, and a GU stabilized by a single hydrogen bond.

Antithrombotic effects of a platelet fibrinogen receptor antagonist in a canine model of carotid artery thrombosis.

BACKGROUND AND PURPOSE: Platelet-fibrin thrombi in the lumen of atherostenotic carotid arteries may underlie transient ischemic attacks and cerebral infarction. For this reason, we investigated the antiplatelet and antithrombotic effects of a novel and potent platelet fibrinogen receptor (glycoprotein IIb/IIIa) antagonist (SK&F 106760). METHODS: The effects of 0.1-3.0 mg/kg i.v. SK&F 106760 on platelet aggregation were examined ex vivo in canine platelet-rich plasma (n = 20). In addition, the antithrombotic effects of SK&F 106760 were compared with those of aspirin in an acute canine model of extracranial carotid artery thrombosis with high-grade stenosis. Sham-operated (n = 4), vehicle-treated (n = 6), SK&F 106760-treated (n = 8), aspirin-treated (n = 9), and SK&F 106760+aspirin-treated (n = 5) dogs were examined. RESULTS: The intravenous administration of SK&F 106760 caused a dose-related inhibition of ex vivo platelet aggregation. In the carotid artery thrombosis model, an occlusive thrombus formed at stenotic sites in the region of the carotid bifurcation. The thrombogenic process caused a progressive reduction in carotid blood flow and reduced the cortical microvascular perfusion and electroencephalographic power. Based on nuclear magnetic resonance spectroscopy, the occlusive events depleted the stores of high-energy phosphates (adenosine triphosphate and phosphocreatine) and increased the lactate concentration in the forelimb somatosensory area of the parietal cortex. In this model, the administration of 1 mg/kg i.v. SK&F 106760 prevented thrombosis of the stenotic carotid artery. Consequently, neurophysiological, cerebral hemodynamic, and metabolic parameters were all improved significantly in the SK&F 106760-treated group. No dog receiving SK&F 106760 reoccluded during the 1-hour posttreatment observation period. In contrast, thrombosis of the carotid artery was associated with neurophysiological deterioration in six of the nine dogs treated with 5 mg/kg i.v. aspirin. Both spontaneous and evoked (increased carotid stenosis) aspirin-resistant thrombosis were abolished by SK&F 106760 treatment. CONCLUSIONS: These results suggest that antagonism of fibrinogen binding to platelet glycoprotein IIb/IIIa (the final common pathway for aggregation) may represent a new and more effective antithrombotic approach to the treatment of cerebral transient ischemic attacks and infarction associated with extracranial carotid artery disease.

Yb-DTPA, a novel contrast agent in magnetic resonance imaging: application to rat kidney.

We have developed a novel contrast agent, ytterbium-diethylenetriamine pentaacetic acid (Yb-DTPA), for magnetic resonance imaging (MRI) and its mechanism of action is predominantly by the susceptibility mechanism. We have applied this contrast agent for renal MRI studies. We also demonstrate that Yb-DTPA has a renal clearance similar to that of inulin in rats and may therefore be useful for the estimation of glomerular filtration rate.

9.4-T NMR microimaging studies of hepatic metastases of human colorectal tumors in nude mice.

We have applied NMR microimaging at 9.4 T to detect metastatic deposits in the liver of nude mice noninvasively, using an animal model for metastatic colon cancer that mimics several aspects of the human disease. Images were obtained with a resolution of 100 x 100 x 900 microns and the tumor deposits were clearly distinguished from the normal liver tissue with excellent contrast. Comparison of NMR images with corresponding histologic sections indicates that lesions as small as 900 microns were detected.

A study of the conformation of 5S RNA by 31P NMR.

Only a small number of resolved, single phosphorous, phosphodiester resonances are observed in the 31P spectrum of the 5S rRNA from E. coli. Its spectrum is much simpler than that of a tRNA (Gueron, M. and Shulman, R.G. (1975) Proc. Natl. Acad. Sci. 72, 3482-3484), which suggests that 5S RNA does not have a tightly folded, tRNA-like, tertiary structure. The resolved resonances in the 5S spectrum originate in loops D and E, near bases 88 and 76, respectively.

Ultraviolet irradiation of nucleic acids: formation, purification, and solution conformational analyses of the cis-syn and trans-syn photodimers of UpU.

Uridylyl(3'-5')uridine (UpU) is subjected to aqueous acetone photosensitized radiation with sunlamps. These irradiation conditions form only cyclobutane-type photodimers. Purification of a specific configurational photodimer is accomplished by using C-18 reverse-phase high-performance liquid chromatography. Multinuclear NMR analysis is used to analyze photoproduct formation and to determine conformational features of these photodimers. Four photodimers are identified, with the cis-syn isomer predominant. The cis-syn and trans-syn photodimers of UpU exhibit markedly different furanose and exocyclic bond conformations. A comparison of the properties of the cis-syn dimers of UpU with those of dTpdT reveal many similar conformational features but also some that are different.

Ultraviolet irradiation of nucleic acids: formation, purification, and solution conformational analyses of oligothymidylates containing cis-syn photodimers.

Acetone-photosensitized UV irradiation of three thymine oligomers, d(TpT), d(TpTpT), and d(TpTpTpT), forms predominantly cis-syn cyclobutyl photodimers. C-18 reverse-phase high-performance liquid chromatography is used to purify the following positional isomers: d(TpT[p]T), d(T[p]TpT), d(TpTpT[p]T), d(TpT[p]TpT), d(T[p]TpTpT), and d(T[p]TpT[p]T), where T[p]T represents the cis-syn photodimer. Conformational properties of the cis-syn dimers and adjacent thymine nucleotides have been investigated in solution by using 1H, 13C, and 31P NMR spectroscopy. These studies show that (1) the photodimer conformation in longer oligothymidylates is similar to that in the dinucleoside monophosphate and (2) the cis-syn dimer induces alterations to a greater degree on the 5' side than on the 3' side of the photodimer. Specifically, the photodimer distorts the exocyclic bonds epsilon(C3'-O3') in Tp- and gamma(C5'-C4') in -pT[p]- on the 5' side and slightly alters the furanose equilibrium of the -pT nucleotide on the 3' side of the dimer.

UV irradiation of nucleic acids: formation, purification and solution conformational analysis of the '6-4 lesion' of dTpdT.

Irradiation of dTpdT with 300 kJ/m2 of 254 nm produces numerous photo-products, one of which labeled dT6pd4T[1] was purified by HPLC. dT6pd4T has a UV spectrum (H20, pH 7) with lambda max = 326 nm and lambda min = 265 nm, and a P-31 NMR resonance at -3.46 ppm (normal dTpdT occurs at -4.01 ppm; TMP, 30 degrees C). 2-D COSY NMR spectra facilitated proton resonance assignments and 2-D NOESY spectra aided analysis of spatial orientation. Carbon-13 and proton-coupled P-31 NMR spectra of dT6pd4T were also obtained. These analyses indicate: C5=C6 of dT6p- is saturated and the -pd4T base is more aromatic; the dT6p- base possesses a configuration of 5R, 6S; dT6p- and -pd4T have anti-type glycosidic conformations; furanose conformation of dT6p- is mainly C3'-endo and that of -pd4T exists in a C3'-endo in equilibrium C3'-exo; exocyclic bonds gamma (C5'-C4'), beta (05'-C5') and epsilon (C3'-03') are non-classical rotamers; dihedral angle about epsilon (C3'-03') is smaller relative to dTpdT.