First Steps towards Localized Opening of the Blood-Brain-Barrier by IR Laser Illumination Through the Rodent Skull

Abstract

Glioblastoma, an aggressive malign tumor of the brain, is one of the most shattering diagnoses due to its very poor prognosis and limited treatment options. These options mainly consist of surgical or radiation therapeutic removal of as much tumor mass as possible, which unfortunately is almost always incomplete. Even worse, chemotherapy is of little use, as the special setup of the brain′s vessels severely limits the transit into the parenchyma of elsewhere efficient cytostatica. This Blood-Brain-Barrier (BBB) is for quite some time the target of sophisticated and nano-particle based transport mechanisms, however it is reported, that a boost of permeability for most of the brain can be achieved based on moderate temperature increase. One means to locally and reversibly increase the brain′s temperature and thus potentially opening the BBB may be achieved by illuminating the skull with infrared laser light, thus causing punctual heating and heat diffusion into the cortex. In extension of the common laser light guiding by glass fibres, we use a micro-positioned simple optics to focus a 1470 nm laser beam of approximately 500 µm in diameter on the skull. The apparent opening of the BBB is evidenced by the localized spread of Evans Blue injected into the tail vein of said rat, binding to Albumin (64,6 kDa) in the body. This marker molecule is usually blocked from passing through the intact BBB, but under IR illumination for half a minute, it appeared in post mortem visible blobs. Temperature profiles and potential tissue damage are now under investigation by high speed thermal camera and post mortem histology.

Keywords

• blood brain barrier opening
• infrared laser illumination
• evans blue