Quantifying tumour microvasculature with optical coherence angiography and intravoxel incoherent motion diffusion MRI.

Abstract

Intravoxel Incoherent Motion (IVIM) MRI is a contrast-agent-free microvascular imaging method finding increasing use in biomedicine. However, there is uncertainty in the ability of IVIM-MRI to quantify tissue microvasculature given MRI's limited spatial resolution (mm scale). Nine NRG mice were subcutaneously inoculated with human pancreatic cancer BxPC-3 cells transfected with DsRed, and MR-compatible plastic window chambers were surgically installed in the dorsal skinfold. Mice were imaged with speckle variance optical coherence tomography (OCT) and colour Doppler OCT, providing high resolution 3D measurements of the vascular volume density (VVD) and average Doppler phase shift (Δϕ) respectively. IVIM imaging was performed on a 7T preclinical MRI scanner, to generate maps of the perfusion fraction f, the extravascular diffusion coefficient Dslow, and the intravascular diffusion coefficient Dfast. The IVIM parameter maps were coregistered with the optical datasets to enable direct spatial correlation. A significant positive correlation was noted between OCT's VVD and MR's f (Pearson correlation coefficient r = 0.34,p < 0.0001). Surprisingly, no significant correlation was found between Δϕ and Dfast. This may be due to larger errors in the determined Dfast values compared to f, as confirmed by Monte Carlo simulations. Several other inter- and intra-modality correlations were also quantified. Direct same-animal correlation of clinically applicable IVIM imaging with preclinical OCT microvascular imaging support the biomedical relevance of IVIM-MRI metrics, for example through f's relationship to the VVD.