Pulsed ultrasound exposures (sonications) were performed in the brains of rabbits
under monitoring by MRI. BBB disruption was confirmed with contrast-enhanced MR images. Whole brain histologic examination was performed using staining for ischemic neurons and TUNEL staining for apoptosis. Tiny regions of extravasated red blood cells scattered around the sonicated locations, indicated capillaries. Despite these vasculature effects, only a few cells in some of the sonicated areas showed evidence of apoptosis or ischemia. The authors found that ultrasound-induced BBB disruption is possible without inducing substantial vascular damage that would result in ischemic Inhibitors,research,lifescience,medical or apoptotic death to neurons . The method Inhibitors,research,lifescience,medical could find application in the delivery of large therapeutic molecules that do not normally permeate the BBB. Herceptin
(trastuzumab), a humanized anti-human epidermal growth factor receptor 2 (HER2/c-erbB2) monoclonal antibody, was delivered locally and noninvasively into the mouse central nervous system Inhibitors,research,lifescience,medical through the blood-brain barrier under image guidance by using an MRI-guided focused ultrasound. The amount of herceptin delivered to the target tissue was selleck chemicals correlated with the extent of the MRI-monitored barrier opening, making it possible to estimate indirectly the amount of Herceptin delivered. The method could be used to treat breast cancer metastases to the brain . It was further shown that dopamine D(4) receptor-targeting antibody could
also be delivered using the same technique Inhibitors,research,lifescience,medical in the brain [65, 66]. Delivery of small molecules can also be enhanced with the use of HIFU cavitation disruption of the BBB. Treat et al. demonstrated relatively high concentrations of doxorubicin in the brain with minimal healthy tissue damage effects. The authors observed that doxorubicin accumulation in nontargeted contralateral Inhibitors,research,lifescience,medical brain tissue remained significantly lower. MRI signal enhancement in the sonicated region correlated strongly with tissue doxorubicin concentration, suggesting that contrast-enhanced MRI could perhaps indicate drug penetration during image-guided interventions . Konofagou and coworkers assessed the spatial permeability of the BBB-opened science region using dynamic contrast-enhanced MRI (DCE-MRI) in mice. The authors processed DCE-MR images using the general kinetic model and the reference region model. Permeability maps were generated and the Ktrans (the transfer rate constant from the intravascular system to the extracellular extravascular space) values were calculated for a predefined volume of interest in the sonicated and the control area for each mouse. The results demonstrated that Ktrans in the BBB-opened region was at least two orders of magnitude higher when compared to the contralateral (control) side .