Purpose The objective of this study was to determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEB) in normal swine liver and kidney following transcatheter arterial chemoembolization (TACE). The influence of bead size (70–150µm or 100–300µm) was compared with regard to tissue penetration and spatial distribution of the bead as well as eventual drug coverage (i.e., amount of tissue exposed to drug). Materials and Methods Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three dimensional tissue penetration of image-able DEB was investigated ex vivo with microCT. Drug penetration from the bead surface and drug coverage was evaluated with epi-fluorescence microscopy while cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with H&E. Results MicroCT demonstrated that 70–150µm DEB were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (~300µm) for both DEBs with a maximum tissue drug concentration at 1hr coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70–150µm DEBs resulted in ~2-fold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hr but increased at 24 and 168 hrs. Conclusions Smaller DEBs penetrated further into targeted tissue (macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (microscopic) in swine.
Purpose-To develop and characterize radiopaque embolization microspheres capable of in vivo detection with intra-procedural fluoroscopy and CT imaging and to evaluate their spatial distribution inside target tissues during and following transcatheter embolization.Materials and Methods-PVA hydrogel microspheres were loaded with lipiodol and examined for iodine content, stability of loading, and conspicuity with fluoroscopy and CT in vitro. Transcatheter embolization of swine liver and kidney was performed with the radiopaque microspheres and spatial distribution was evaluated with intra-procedural fluoroscopy and CT. Ex vivo evaluation was performed using light microscopy and micro-CT.Results-In vitro analyses demonstrated that radiopaque microspheres could be loaded with sufficient iodine content to be detected with routine fluoroscopy and CT imaging and that such loading was relatively stable. Radiopaque microspheres were visible in vivo with fluoroscopy and CT during transcatheter embolization. CT imaging during embolization procedures demonstrated a dose dependent relationship in the number and size of visualized embolized arteries. Imaging features of radiopaque microsphere distribution inside target tissues correlated well with ex vivo light microscopic and micro-CT evaluation of microsphere distribution.Conclusions-Radiopaque embolization microspheres are visualized during transcatheter embolization with routine intra-procedural fluoroscopy and CT. These radiopaque microspheres provided the three dimensional spatial distribution of embolic material inside target organs during the procedure, and therefore can provide real-time, intra-procedural feedback for the interventional
The consumption of unpasteurized goat cheese and goat's milk has been suggested as a risk factor for toxoplasmosis in humans. In the present study, detection and survival of Toxoplasma gondii in milk and cheese was studied by bioassay in mice (milk) and in cats (cheese). Eight goats were inoculated orally with 300 to 10,000 oocysts of T. gondii strain TgGoatUS26. Milk samples were collected daily up to 30 days postinoculation and bioassayed in mice and cats. For mouse bioassay, 50 ml of milk samples were centrifuged, and the sediment was inoculated subcutaneously into mice. Mice were tested for T. gondii infection by seroconversion and by the demonstration of parasites. By mouse bioassay, T. gondii was detected in milk from all eight goats. The T. gondii excretion in milk was intermittent. For cat bioassay, 400 ml (100 ml or more from each goat) of milk from four goats from 6 to 27 days postinoculation were pooled daily, and cheese was made using rennin. Ten grams of cheese was fed daily to four cats, and cat feces were examined for oocyst shedding. One cat fed cheese shed oocysts 7 to 11 days after consuming cheese. Attempts were made to detect T. gondii DNA in milk of four goats; T. gondii was detected by PCR more consistently, but there was no correlation between detection of viable T. gondii by bioassay in mice and T. gondii DNA by PCR. Results indicate that T. gondii can be excreted in goat's milk and can survive in fresh cheese made by cold-enzyme treatment. To prevent transmission to humans or animals, milk should not be consumed raw. Raw fresh goat cheese made by cold-enzyme treatment of unpasteurized milk also should not be consumed.
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