Measurement of bioreactor perfusion using dynamic contrast agent-enhanced magnetic resonance imaging

Dynamic magnetic resonance imaging was used to monitor solute diffusion thr ough aggregates of Chinese hamster ovary cells growing on macroporous carri ers in a fixed-bed bioreactor. Diffusion-weighted H-1 magnetic resonance im aging (MRI) and scanning electron microscopy demonstrated that cell growth in the bioreactor was heterogeneous, with the highest cell densities being found at the periphery of the carriers. T-1-weighted magnetic resonance ima ging measurements of the inflow of a commonly used magnetic resonance contr ast agent, gadolinium-diethylenetriaminopentaacetic acid (Gd-DTPA), showed that migration of the agent through the peripheral cell masses could be exp lained by diffusion. However, appearance of the contrast agent in the cente r of the carriers was too fast to be explained by simple diffusion and indi cated that these regions were perfused by convective flow. The average diff usivity of Gd-DTPA through the cell mass was found to be (2.4 +/- 0.2) x 10 (-10) m(2) sec(-1) (mean +/- SEM). This technique will be useful in the cha racterization and development of high-cell-density bioreactor systems, in w hich solute transport plays a critical role in cell growth and physiology. (C) 2001 John Wiley & Sons, Inc.