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Convection-Enhanced Drug Delivery: Increased Efficacy and Magnetic Resonance Image Monitoring

¹ Advanced Technology Center, ² Neurosurgery Department, ³ Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Ramat Gan; ⁴ Neurosurgery Department, Sourasky Medical Center, Tel Aviv, Israel; ⁵ School of Physics and Astronomy, ⁶ Sackler School of Medicine, Tel-Aviv University; and ⁷ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Yael Mardor, The Advanced Technology Center, Sheba Medical Center, Tel Hashomer, Ramat Gan 52621, Israel. Phone: 972-3-5302993, 972-52-6667274; Fax: 972-3-5303146; E-mail: yael.mardor{at}sheba.health.gov.il.

Convection-enhanced drug delivery (CED) is a novel approach to directly deliver drugs into brain tissue and brain tumors. It is based on delivering a continuous infusion of drugs via intracranial catheters, enabling convective distribution of high drug concentrations over large volumes of the target tissue while avoiding systemic toxicity. Efficient formation of convection depends on various physical and physiologic variables. Previous convection-based clinical trials showed significant diversity in the extent of convection among patients and drugs. Monitoring convection has proven to be an essential, yet difficult task. The current study describes the application of magnetic resonance imaging for immediate assessment of convection efficiency and early assessment of cytotoxic tissue response in a rat brain model. Immediate assessment of infusate distribution was obtained by mixing Gd-diethylenetriaminepentaacetic acid in the infusate prior to infusion. Early assessment of cytotoxic tissue response was obtained by subsequent diffusion-weighted magnetic resonance imaging. In addition, the latter imaging methodologies were used to establish the correlation between CED extent and infusate's viscosity. It was found that low-viscosity infusates tend to backflow along the catheter track, whereas high-viscosity infusates tend to form efficient convection. These results suggest that CED formation and extent may be significantly improved by increasing the infusate's viscosities, thus increasing treatment effects.

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