THE APPLICATION OF POROUS-MEDIA THEORY TO THE INVESTIGATION OF TIME-DEPENDENT DIFFUSION IN IN-VIVO SYSTEMS

Recent developments in solid-boundary porous-media theory have shown t hat useful structural information can be extracted from the time-depen dent diffusion coefficient, D(t), of the fluid filling the interstitia l space, This theoretical framework provides a basis from which to und erstand the results from diffusion experiments performed in other type s of systems (e.g. biological). Structural information about porous me dia can be obtained from the short-time behavior of D(t) in the form o f the ratio of the surface area to pore volume, S/V The long-time beha vior of D(t) in porous media provides an indirect measure of the macro scopic structure, In this case, the longtime diffusion coefficient, D- eff, reflects the tortuosity, T, of the medium; a property of both the connectivity of the diffusion paths and the volume fraction of the sa mple. Measurements of D(t) were performed in RIF-1 tumors, using both spectroscopy and imaging, and the data were used to calculate S/V and T, The results were compared with histological sections in order to co rrelate S/V and T with differences in tissue structure (i.e. necrotic vs nonnecrotic tumor tissue), Based on spectroscopic measurements, the re is a trend towards decreasing S/V and T with increasing tumor volum e, consistent with the interpretation that water in necrotic tissue Is experiencing relatively fewer restricting barriers (as compared to no n-necrotic tumor tissue). Based on D(t) maps generated from RIF-1 tumo rs, D-eff, and hence T appears to be much more sensitive than S/V in d ifferentiating between necrotic and nonnecrotic tissue, In addition to characterizing diseased tissue, S/V and particularly T appear to be s ensitive to structural changes that would accompany tumor treatment an d should therefore provide a useful tool for monitoring the progress o f therapeutic interventions.