This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The primary goal of this proposal is to overcome the confounding effects of a leaky blood brain barrier by using a novel CT contrast agent, iodinated liposome. Liposomes are microscopic spherical vesicles constructed of phospholipid bilayers that can encapsulate the iodinated contrast agent. Specific features such as vesicle size, chemical affinity and thermal (or pH) sensitivities can be engineered. The agent we will use is a polyethylene glycol (PEG)-coated liposome with an intravascular circulation half-life on the order of 6-8 hours. These characteristics allow blood pool imaging for several hours after a simple IV injection, and should also decrease the rate of extravasation of the agent into the tumor interstitium.Non-invasive evaluation of cerebral blood volume (CBV) and permeability (PS) is a method for grading tumors as well as evaluating treatment effect. Positron emission tomography (PET) based CBV and PS methods suffer from significant disadvantages due to: (1) the leakage of tracer from the intravascular space into the tumor bed, and (2) the relatively low spatial resolution. Advantages of computed tomography (CT) methods are the high spatial resolution, the direct linear relationship between signal intensity and contrast agent concentration, and the lack of vulnerability to blood product artifact. With both CT and PET (and MR), a leaky blood brain barrier produces errors and requires the use of a deconvolution algorithm to derive CBV and PS.
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