Research Papers: Sensing

Noninvasive in vivo optical assessment of blood brain barrier permeability and brain tissue drug deposition in rabbits

[+] Author Affiliations
Aysegul Ergin, Jane Zhang

Boston University, Department of Biomedical Engineering, 44 Cummington Street, Boston, Massachusetts 02215

Mei Wang, Shailendra Joshi

College of Physicians and Surgeons of Columbia University, Department of Anesthesiology, P&S Box 46, 630 West 168th Street, New York, New York 10032

Irving Bigio

Boston University, Department of Biomedical Engineering, Electrical Engineering, Physics and Medicine, 44 Cummington Street, Boston, Massachusetts 02215

J. Biomed. Opt. 17(5), 057008 (May 21, 2012). doi:10.1117/1.JBO.17.5.057008
History: Received August 18, 2011; Revised February 28, 2012; Accepted March 1, 2012
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Abstract.  Osmotic disruption of the blood brain barrier (BBB) by intraarterial mannitol injection is sometimes the key step for the delivery of chemotherapeutic drugs to brain tissue. BBB disruption (BBBD) with mannitol, however, can be highly variable and could impact local drug deposition. We use optical pharmacokinetics, which is based on diffuse reflectance spectroscopy, to track in vivo brain tissue concentrations of indocyanine green (ICG), an optical reporter used to monitor BBBD, and mitoxantrone (MTX), a chemotherapy agent that does not deposit in brain tissue without BBBD, in anesthetized New Zealand white rabbits. Results show a significant increase in the tissue ICG concentrations with BBBD, and our method is able to track the animal-to-animal variation in tissue ICG and MTX concentrations after BBBD. The tissue concentrations of MTX increase with barrier disruption and are found to be correlated to the degree of disruption, as assessed by the ICG prior to the injection of the drug. These findings should encourage the development of tracers and optical methods capable of quantifying the degree of BBBD, with the goal of improving drug delivery.

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© 2012 Society of Photo-Optical Instrumentation Engineers

Citation

Aysegul Ergin ; Mei Wang ; Jane Zhang ; Irving Bigio and Shailendra Joshi
"Noninvasive in vivo optical assessment of blood brain barrier permeability and brain tissue drug deposition in rabbits", J. Biomed. Opt. 17(5), 057008 (May 21, 2012). ; http://dx.doi.org/10.1117/1.JBO.17.5.057008


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