Delivery of imaging agents into brain

Delivery of diagnostic agents to the central nervous system (CNS) poses sev eral challenges as a result of the special features of CNS blood vessels an d tissue fluids. Diffusion barriers exist between blood and neural tissue, in the endothelium of parenchymal vessels (blood-brain barrier, BBB), and i n the epithelia of the choroid plexuses and arachnoid membrane (blood-CSF b arriers), which severely restrict penetration of several diagnostic imaging agents. The anatomy of large vessels can be imaged using bolus injection o f X-ray contrast agents to identify sites of malformation or occlusion, and blood flow measured using MRT and CT, while new techniques permit analysis of capillary perfusion and blood volume. Absolute quantities can be derive d, although relative measures in different CNS regions may be as useful in diagnosis. Local blood flow, blood volume, and their ratio (mean transit ti me) can be measured with high speed tomographic imaging using MRT and CT. I ntravascular contrast agents for MRI are based on high magnetic susceptibil ity agents such as gadolinium, dysprosium and iron. Steady-state imaging us ing agents that cross the BBB including I-123- and Tc-99m-labelled lipophil ic agents with SPECT, gives a 'snapshot' of perfusion at the time of inject ion. Cerebral perfusion can also be measured with PET, using (H2O)-O-15, C- 11- or O-15-butanol, and F-18-fluoromethane, and cerebral blood volume meas ured with (CO)-O-15. Recent advances in MRI permit the non-invasive 'labell ing' of endogenous water protons in flowing blood, with subsequent detectio n as a measure of blood flow. Imaging the BBB most commonly involves detect ing disruptions of the barrier, allowing contrast agents to leak out of the vascular system. Gd-DTPA is useful in imaging leaky vessels as in some cer ebral tumors, while the shortening of T-1 by MR contrast agents can be used to detect more subtle changes in BBB permeability to water as in cerebral ischemia. Techniques for imaging the dynamic activity of the brain parenchy ma mainly involve PET, using a variety of radiopharmaceuticals to image glu cose transport and metabolism, neurotransmitter binding and uptake, protein synthesis and DNA dynamics. PET methods permit detailed analysis of region al function by comparing resting and task-related images, important in impr oving understanding of both normal and pathological brain function. (C) 199 9 Elsevier Science B.V. All rights reserved.