In magnetic resonance imaging (MRI), cerebral blood volume (CBV) quantification is dependent on the MRI sequence and on the properties of the contrast agents (CAs). By using the rapid steadystate T 1 method, we show the potential of gadolinium per (3,6-anhydro) a-cyclodextrin (Gd-ACX), a new MRI paramagnetic CA (inclusion complex of Gd 3 + with per (3,6-anhydro)-a-cyclodextrin), for the CBV quantification in the presence of blood-brain barrier lesions. After biocompatibility and relaxivity experiments, in vivo experiments on rats were performed on a C6 tumor model with 0.05 mmol Gd-ACX/kg ( < 1/10 of the median lethal dose) injected at a 25 mmol/L concentration, inducing neither nephrotoxicity nor hemolysis. On T 1 -weighted images, a signal enhancement of 170% appeared in vessels after injection, but not in the tumor (during the 1 h of observation), in contrast to the 90% signal enhancement obtained with Gd-DOTA (a clinical MRI CA) injected at a T 1 isoefficient dose. This result shows the absence of Gd-ACX extravasation into the tumor tissue and its confinement to the vascular space. Fractional CBV values were found similar to Gd-ACX and Gd-DOTA in healthy brain tissue and in the contralateral hemisphere of tumor-bearing rats, whereas only Gd-ACX was appropriate for CBV quantification in tumor regions.
Although the interactions of sulfur mustard (HD) with nucleic acids and proteins have been well studied, the toxic interactions with the membrane matrix and specially the phospholipid bilayer have so far been poorly investigated. We have used several NMR techniques to study these interactions: 1H NMR to observe the localization of HD in membranes of small unilamellar vesicles (SUV) of lecithin; 31P NMR to verify the hypothesis of pore formation in membranes of large unilamellar vesicles (LUV); and pseudo solid state 31P and 2H NMR to analyze the dynamic consequences of the presence of HD in multilayer dispersions of dimyristoylphosphatidylcholine (DMPC). Immediate and late modifications of the DMPC-HD complexes have been observed at the macroscopic and microscopic levels. After intoxication, HD is spontaneously incorporated into the membrane and locates at the level of the chain methylene groups. This incorporation occurs without formation of pores in the membrane. The presence of HD in the phospholipid dispersion differentially increases the membrane fluidity depending upon the level involved. Weak at the superficial level (phosphate group), this increase is dose-dependent on progression into the membrane. This increase is related to a lowering of transition temperature when measured at the chain level. Macroscopically, HD induces dose- and time-dependent modifications of the DMPC-HD complexes, leading to the formation of an optically transparent gel. This gel formation is confirmed at a microscopic level, where all structures disappear after intoxication.
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