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    ABSTRACT: The sampling schedule for chemical exchange saturation transfer imaging is normally uniformly distributed across the saturation frequency offsets. When this kind of evenly distributed sampling schedule is used to quantify the chemical exchange saturation transfer effect using model-based analysis, some of the collected data are minimally informative to the parameters of interest. For example, changes in labile proton exchange rate and concentration mainly affect the magnetization near the resonance frequency of the labile pool. In this study, an optimal sampling schedule was designed for a more accurate quantification of amine proton exchange rate and concentration, and water center frequency shift based on an algorithm previously applied to magnetization transfer and arterial spin labeling. The resulting optimal sampling schedule samples repeatedly around the resonance frequency of the amine pool and also near to the water resonance to maximize the information present within the data for quantitative model-based analysis. Simulation and experimental results on tissue-like phantoms showed that greater accuracy and precision (>30% and >46%, respectively, for some cases) were achieved in the parameters of interest when using optimal sampling schedule compared with evenly distributed sampling schedule. Hence, the proposed optimal sampling schedule could replace evenly distributed sampling schedule in chemical exchange saturation transfer imaging to improve the quantification of the chemical exchange saturation transfer effect and parameter estimation. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.
    No preview · Article · Nov 2013 · Magnetic Resonance in Medicine
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    ABSTRACT: The localization of microbubbles to a target site has been shown to be essential to their effectiveness in ultrasound mediated drug delivery and gene therapy. The incorporation of super paramagnetic nanoparticles into the microbubble coating enables them to be manipulated using an externally applied magnetic field. Magnetic microbubbles have been shown to be effective in therapeutic delivery both in vitro and in vivo in a mouse model. The aim of this experiment was to determine under what conditions in the human body magnetic microbubbles can be successfully imaged and targeted. Different flow rates and shear rates were generated in a tissue mimicking phantom and targeting was observed using a 9.4 MHz ultrasound imaging probe. For the highest shear rates, targeting was also observed optically. Results indicate that magnetic microbubbles can be successfully targeted at shear rates found in the human capillary system (>1000/s) and at flow rates found in the veins and smaller arteries (~200 ml/s). Successful retention was also demonstrated in a perfused porcine liver model simulating conditions in vivo. This study provides further evidence for the potential of magnetic microbubbles for targeted therapeutic delivery.
    No preview · Article · Nov 2013 · The Journal of the Acoustical Society of America
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    ABSTRACT: Encapsulation of cytotoxic drugs into liposomes enhances pharmacokinetics and improves passive accumulation in tumors. However, stable liposomes have limited drug release, and thus action, at the target site. This inefficient and unpredictable drug release is compounded by a lack of low-cost, non-invasive methods to map release in real time. We present a new liposomal vehicle that is exclusively triggered by inertial cavitation. Ultrasound exposure of these liposomes in the absence of SonoVue® provided no increase in drug release, whilst with SonoVue® at inertial cavitation pressure levels a substantial (30%) and significant (p < 0.001) increase was observed in vitro. A 16-fold increase in the level of drug release within tumors was similarly observed in the presence of inertial cavitation following intravenous delivery. Passive acoustic mapping of inertial cavitation sources during delivery was also found to correlate strongly with the presence of release. However, variability in tumor perfusion indicated that uneven distribution of micron-sized SonoVue® may limit this approach. Nano-scale cavitation nuclei, which may more readily co-localize with 140 nm liposomes, were thus developed and showed similar cavitation energies to SonoVue® in vitro. These nano-nuclei may ultimately provide a more reliable and uniform way to trigger drug release in vivo.
    No preview · Article · Nov 2013 · The Journal of the Acoustical Society of America
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