Local cerebral blood flow values as estimated with diffusible tracers: validity of assumptions in normal and ischemic...

A theoretical assessment is made of the validity of assumptions underlying the theory for estimating local cerebral blood flow with diffusible tracer in the tissue under normal and ischemic conditions. First, Kety's derivation of equations that have commonly been used for calculating local cerebral blood flow values is examined in order to define the problems and assumptions. Second, the brain:blood partition coefficient of diffusible tracer, lambda, and the diffusion-limited factor, m, under normal and ischemic conditions are reviewed. An examination of the literature suggested that contrary to common belief, lambda appears to change very little in ischemia if the tissue constituents remain unchanged, whereas m does change with ischemia if the diffusible tracer used is greatly diffusion-limited in the exchange between brain and blood. Even when a gas with an m value close to unity is used as the diffusible tracer, the prolonged mean transit time of blood through the ischemic tissue would make it difficult to maintain the exponential assumptions. As part of the ischemic tissue became infarcted, which is the case with most stroke patients, so the assumptions of homogeneous perfusion would become invalid. This inevitably renders it difficult to estimate local cerebral blood flow with diffusible tracer in ischemic tissue containing an infarcted mass.