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We present an application of spatial frequency-domain imaging (SFDI) to the wide-field imaging of drug delivery to brain tissue. Measurements were compared with values obtained by a previously validated variation of diffuse reflectance spectroscopy, the method of optical pharmacokinetics (OP). We demonstrate a cross-correlation between the two methods for absorption extraction and drug concentration determination in both experimental tissue phantoms and freshly extracted rodent brain tissue. These methods were first used to assess intra-arterial (IA) delivery of cationic liposomes to brain tissue in Sprague Dawley rats under transient cerebral hypoperfusion. Results were found to be in agreement with previously published experimental data and pharmacokinetic models of IA drug delivery. We then applied the same scheme to evaluate IA mitoxantrone delivery to glioma-bearing rats. Good correlation was seen between OP and SFDI determined concentrations taken from normal and tumor averaged sites. This study shows the feasibility of mapping drug/tracer distributions and encourages the use of SFDI for spatial imaging of tissues for drug/tracer-tagged carrier deposition and pharmacokinetic studies.

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.

The understanding of drug delivery to organs, such as the brain, has been hampered by the inability to measure tissue drug concentrations in real time. We report an application of an optical spectroscopy technique that monitors in vivo the real-time drug con- centrations in small volumes of brain tissue. This method will facilitate development of new protocols for delivery of drugs to treat brain can- cers. The delivery of many anticancer drugs to the brain is limited by the presence of the blood-brain barrier BBB. Mitoxantrone MTX is a water-soluble anticancer drug that poorly penetrates the BBB. It is preliminarily determined in an animal model that the brain tissue up- take of chemotherapy agents—in this demonstration, MTX—delivered intra-arterially is enhanced when the BBB is disrupted. © 2007 Society of