Diffusion-Weighted MRI (DWMRI) has been useful in the clinical evaluation of neurological disease, such as stroke. A significant decrease in the apparent diffusion coefficient (ADC) is observed in the areas effected by ischemic stroke. More recently, the ADC has been used as an early predictor of response to chemotherapy in cancer. Despite the clinical utility of DWMRI the biophysical mechanisms underlying ADC are not completely understood.

Bioreactor Cell Cultures
We have developed a hollow-fiber bioreactor (HFBR) cell culture system to further explore these underlying mechanisms. Cells are grown in the extrafiber spaces of the bioreactor, while nutrients are delivered via media flowing through the lumen of the porous hollow fibers. A picture of the HFBR is shown below

Infusing Gd-DTPA causes the water signal to split into three peaks which correspond to the intracellular water, water inside the fiber wall, and intraluminal + extracellular water. This novel cell system allows us to exclusively investigate the the role of intracellular water in DWMRI.

Computational Modeling
To aid in the interpretation of DWMRI data, we have developed a finite difference model of diffusion. The model calculates the diffusion of water in a 3D geometry of cubic cells. Physical and experimental parameters such as cell size, cell volume fraction, membrane permeability, diffusion time, TE, and compartment specific diffusion and T2 coefficients are used to calculate water concentration distributions, which can be converted to clinically relevant ADCs. The model allows us to correlate changes in physical parameters with changes in the calculated ADC.

Relevant Publications
Galons et. al, Uncovering of intracellular water in cultured cells. MRM 2005