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A1690
October 22, 2008 9:00 AM - 11:00 AM Room Hall E2-Area G, |
| Non Invasive, Real-Time Optical Measurement of Brain Tissue Rhodamine Concentrations in Vivo |
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Mei Wang, M.P.H., Shailendra Joshi, M.D., Jane Zhang, M.S., Irving Bigio, Ph.D. Anesthesiology, Columbia University, New York, NY |
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Introduction: Optical pharmacokinetics (OP) is a form of diffuse reflectance spectrometry that permits real time measurements of tissue drug concentrations. The technique is uniquely suited to assess the rapid changes in tissue drug concentrations after intra-arterial delivery. Rhodamine-B (RB) is a lipid soluble tracer that can cross the blood brain barrier that can be detected by real- time OP in Vivo. It's light absorption spectrum is distinct from hemoglobin and oxyhemoglobin therefore its tissue concentrations can be measured by optical means.The aim of this experiment was to assess such feasibility of OP measurement by brain tissue RB concentrations so as to understand the complex and ultra-fast kinetics of intraarterial lipid soluble drugs. Methods: After approval by the IACUC, the experiments were conducted on New Zealand white rabbits. For the experiment the animals were anesthetized with intramuscular ketamine and thereafter the anesthesia was maintained with intravenous infusion of propofol (10-20 mg/kg/hr) with mechanical ventilation. Surgical preparation included venous, femoral arterial and selective internal carotid arterial cannulations. The skull was carefully milled to the inner table. The laser Doppler and the OP probes were placed to measure cerebral blood flow and drug concentration measurements. The animals received increasing doses of RB in the dose range of (0.001-1 mg). Optical measurements were made using commercially available tissue spectroscope (Optimum Technologies Inc. Boston MA). The spectral analysis was done using the Mathlab-7 software. Results: Hemodynamic parameters remained stable during RB injections. There was a correlations between the drug injection dose and injection and optically measured peak concentrations as well as the area under the concentration time curve between and within animals.[figure1]OP technique permitted us to record real-time concentration of RB in the brain tissue.[figure2]Discussion: In previous experiments we had observed that tissue drug concentration of mitoxantrone, a water soluble anticancer drug, can be measured in virtual real-tine by the OP method. In this experiments we observed a dose dependent increase in brain tissue concentrations after intra-arterial injection of lipid soluble RB. Figure 2 illustrates the power of OP technologies, each RB concentration-time curve had 240 data points and would have taken several animals or dialysate samples if conventional tissue biopsy or microdialysis were used. The ability to measure tissue brain tissue concentrations and similar optical tracers in real-time could help improve drug delivery protocols, for example the delivery of drug bearing liposomes could be tracked by RB tagging. Anesthesiology 2008; 109 A1690 |
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