Patent Document ID: 9406119
Application ID: 13992358
Patent Flag: 1

Claim One:
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 ] - k on ɛ ⁡ [ C ] ⁡ [ Ag ] + k off ⁡ [ B ] ∂ [ B ] ∂ t = k on ɛ ⁡ [ C ] ⁡ [ Ag ] - k off ⁡ [ B ] - k e , B ⁡ [ B ] ∂ [ Ag ] ∂ t = R s - k on ɛ ⁡ [ C ] ⁡ [ Ag ] + k off ⁡ [ B ] - k e , Ag ⁡ [ Ag ] ∂ [ I ] ∂ t = k e [ B } - k resid ⁡ [ I ] ∂ [ C ] ∂ r ⁢ | r = R = 0 ⁢ - D ⁢ ∂ [ C ] ∂ r ⁢ | r = R cap = P ⁡ ( [ C ] p - [ C ] ɛ ) ⁢ [ C ] ⁢ | t = 0 = 0 ⁢ [ B ] ⁢ | t = 0 = 0 ⁢ [ Ag ] ⁢ | t = 0 = Ag 0 ⁢ [ 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, k on denotes the CA/antigen association rate constant, k off denotes the CA/antigen dissociation rate constant, ε denotes the CA void fraction in the tissue, k e,B denotes the internalization rate constant of the CA/antigen bound complex, k e,Ag denotes the internalization rate constant of the antigen, k resid denotes the rate of release of CA or CA signal from the intracellular compartment, R S denotes the antigen synthesis rate, R denotes the Krogh cylinder radius, R cap denotes the capillary radius, P denotes the tumor capillary permeability, Ag 0 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.