Fig 1.
Physiological basis for compartmentalized transport models in TB granulomas.
Schematic depicting regions and consequences of compromised oxygen transport in idealized spherical granulomas, including 1) a vascularized region where convection dominates and plasma filtration from blood vessels occurs, and 2) an inner region lacking blood vessels where diffusion dominates, and hypoxia and necrosis result. (Adapted from [15]).
Fig 2.
Granuloma IFP estimates and comparisons to tumor data.
(A) Predicted dimensionless IFP profiles within granulomas from the uniform perfusion case for varying values of dimensionless granuloma size, α0 = 1–15. (B) Fitting the theoretical IFP estimates (Eq III with a fitted modulus [9], see S1 Text) to experimentally measured tumor IFP data (from human neuroblastoma tumor models grown in immunosuppressed rats, ~2 cm in diameter [9]) demonstrates the applicability of the uniform perfusion model to physiological IFP levels with a single fitted parameter.
Fig 3.
Granuloma IFV estimates and comparisons to tumor data.
(A) Predicted dimensionless IFV profiles within granulomas from the uniform perfusion case for varying values of dimensionless granuloma size, α0 = 1–15. (B) Fitting the theoretical IFV estimates (Eq IV with a fitted modulus [9], see S1 Text) to experimentally measured tumor IFV data [9] demonstrates the applicability of the uniform perfusion model to physiological IFV levels with a single fitted parameter.
Fig 4.
Granuloma convective zone thickness estimates and comparisons to experimental granuloma data.
Dimensionless convective zone thickness, λΔ (lines), as a function of dimensionless granuloma size (0 < α0 < 30) for varying values of dimensionless limiting perfusion velocity, (as defined in the S1 Text), in comparison to experimental data from rabbit TB granulomas [15] (gray dots).
Fig 5.
Granuloma oxygen and glucose profile estimates.
Dimensionless concentration, f, of oxygen (A) and glucose (B) as a function of dimensionless granuloma radius, ξ, for increasing values of dimensionless granuloma size (the modulus α0).
Fig 6.
Effect of tissue hydraulic conductivity on oxygen and glucose delivery.
(A) Oxygen and (B) glucose concentration profiles for base case parameter values (Eq S39, see S1 Text) of tissue hydraulic conductivity Kv increased by a factor of 10 for small (α0 = 3.5) and large (α0 = 20) granulomas.
Fig 7.
Estimates of drug delivery and comparisons to rifampicin and clofazimine distribution data in experimental granulomas.
Dimensionless concentration (lines), f, of rifampicin (A; RIF) and clofazimine (B; CFZ) as a function of dimensionless granuloma radius, ξ, for increasing values of dimensionless granuloma size (the modulus α0) in comparison to experimental data from mouse TB granulomas [17] (dots). The mean squared error (MSE, see Eq S44) between the theoretical and experimental results for rifampicin and clofazimine are 0.012 and 0.010, respectively (see S2 Table for all raw data, predicted data, and MSE values).