Simulation of heterogeneous molecular delivery in tumours using μCT reconstructions and MRI validation

Utilizing the detailed vascular network obtained from micro-computed tomography (μCT) to establish a mathematical model of the temporal molecular distribution within a murine C3H mammary carcinoma.

Female CDF1 mice with a C3H mammary carcinoma on the right rear foot were used in this study. Dynamic information for each tumour was achieved by Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) on a 16.4 T system. Detailed morphologic information on the tumour vasculature was obtained by ex vivo μCT and compared to CD34 immunohistochemical staining of tissue sections. The reconstructed vascular network served as origin for the diffusion (described by the apparent diffusion coefficient) within the tumour (the restricted volume described by the interstitial volume fraction derived from DCE-MRI). The resulting partial differential equation was solved using Finite-Element and a combined mathematical graph describing molecular distribution within the tumour was obtained.

The established molecular distribution model predicted a heterogeneous distribution throughout the tumour related to the layout of the vascular network. Central tumour section concentration-time curves estimated from the established molecular distribution model were compared with physical measurements obtained by DCE-MRI of the same tumours and showed excellent correlation.

A mathematical model describing temporal molecular distribution based on detailed vascular network structures was established and compared to DCE-MRI. The improved morphological insight will enhance future studies of heterogeneous tumours.