| 摘要 |
A method is provided for estimating a parameter of physiological significance. One or more images are provided of a tissue in a subject to whom a dose of a contrast agent (CA) has been administered, using a computer equipped with image processing software, the concentration or relative concentration of the agent in a region or regions of interest in the tissue is determined, thus generating concentration data. The time-based behavior of concentrations of CA within the tissue is determined using a pharmacokinetic model that is based on a set of pharmacokinetic model parameters. Using computer code, the pharmacokinetic model is fit to the concentration data, varying one or more parameters, such that a best fit estimate of a parameter of physiological significance is provided. |
| 主权项 |
1. A method of estimating a parameter of physiological significance, the method comprising:
(a) providing one or more images of a tissue in a subject to whom a dose of a contrast agent (CA) has been administered; and (b) determining, using a computer equipped with image processing software, the concentration or relative concentration of the agent in a region or regions of interest in the tissue, thereby generating concentration data; (c) describing the time-based behavior of concentrations of CA within the tissue using a pharmacokinetic model that is based on a set of pharmacokinetic model parameters; and (d) fitting, using computer code, the pharmacokinetic model to the concentration data, varying one or more parameters, wherein the best fit estimates a parameter of physiological significance, wherein the pharmacokinetic model for performing the analysis is a distributed model, and wherein the distributed model is based on the Krogh cylinder given by the following equations:∂[C]∂t=D∇2[C]-konɛ[C][Ag]+koff[B]∂[B]∂t=konɛ[C][Ag]-koff[B]-ke,B[B]∂[Ag]∂t=Rs-konɛ[C][Ag]+koff[B]-ke,Ag[Ag]∂[I]∂t=ke[B}-kresid[I]∂[C]∂r|r=R=0-D∂[C]∂r|r=Rcap=P([C]p-[C]ɛ)[C]|t=0=0[B]|t=0=0[Ag]|t=0=Ag0[I]|t=0=0 wherein ∇2 denotes the Laplacian in cylindrical coordinates, [C] denotes the free CA concentration, [B] denotes the bound CA/antigen concentration, [Ag] denotes the unbound antigen concentration, [I] denotes the concentration of intracellular CA, D denotes the CA diffusion coefficient in tissue, kon denotes the CA/antigen association rate constant, koff denotes the CA/antigen dissociation rate constant, ε denotes the CA void fraction in the tissue, ke,B denotes the internalization rate constant of the CA/antigen bound complex, ke,Ag denotes the internalization rate constant of the antigen, kresid denotes the rate of release of CA or CA signal from the intracellular compartment, RS denotes the antigen synthesis rate, R denotes the Krogh cylinder radius, Rcap denotes the capillary radius, P denotes the tumor capillary permeability, Ag0 denotes the initial antigen density, and [C]P denotes the plasma concentration of the contrast agent as a function of time, also sometimes called an arterial input function. |
