Quantifying Fluid Infusions and Tissue Expansion in Brain

The technique of direct infusions into brain tissue of therapeutic molecules that would otherwise not adequately cross the blood-brain barrier (BBB) continues to be used in clinical trials. As part of our research into understanding the transport of fluids and molecules in brain tissue, we performed infusions of a saline solution of the magnetic resonance (MR) marker Gadodiamide( Omniscan) into porcine brains. We use quantitative concentration measurements of contrast reagents from MR images to both measure the distribution profile of the infusate and to elucidate important determinants of fluid flow during infusions into brain parenchyma. Based on this, and from other MRI data collected during infusion, we give preliminary results for the quantification of the expansion of the volume fraction of the interstitium particularly in white matter regions of brain during infusion-induced edema. We claim this expansion, rather than an anisotropy of fluid conductivity, makes white matter tracts a preferred pathway for flow. We also comment briefly on other determinants that are currently being pursued such as the influence of the cerebrospinal fluid and perivascular spaces that may be elucidated with quantitative tracking of tracer, but which need further studies.