Mapping of oxygen tension and cell distribution in a hollow‐fiber bioreactor using magnetic resonance imaging

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“…For example in a CHO cell line it has been shown that the specific oxygen consumption rate can be reduced by 50% with no effect on cell growth rate (Lin et al, 1993) and in a number of cell lines glucose consumption rate has been shown to be influenced by glucose concentration (Ljunggren et al, 1994;Neermann et al, 1996, and references cited therein). The dissociation of nutrient uptake rate from cell mass is likely to be even greater in intensive reactor systems where there may be significant heterogeneity in nutrient concentrations (Chresand et al, 1988;Drury et al, 1988;Piret et al, 1990a;Piret et al, 1990b;Williams et al, 1997). By comparing bioreactor glucose consumption rate with cell mass, estimated from MR measurements of cell volume or ATP content, we have shown that the specific glucose consumption rate declines during the culture and that this correlates with the decline in media glucose concentration.…”

“…The diffusion-weighted image shows water with a low ADC, i.e. intracellular water (van Zijl et al, 1991;Callies et al, 1994;Williams et al, 1997), giving a map of cell growth over the reactor. High signal intensity in this image corresponds Figure 2.…”

“…Non-invasive magnetic resonance imaging and spectroscopy techniques have been used previously to investigate the growth and metabolism of mammalian cells in intensive bioreactor systems, in particular the hollow-fiber bioreactor (HFBR) (Gillies et al, 1991;Mancuso, 1990). We have shown previously that diffusion-weighted 1 H MRI can be used to monitor the distribution of CHO-K1 cells growing in an HFBR (Callies et al, 1994) and that 19 F MRI measurements of dissolved oxygen distribution, using a perfluorocarbon probe molecule, can be used to investigate the relationship between the distribution of cells and dissolved oxygen (Williams et al, 1997). We have shown here that diffusion-weighted 1 H MR imaging and spectroscopy can be used to monitor the distribution and growth of CHO-K1 cells in a fixed-bed bioreactor composed of macroporous carriers.…”

“…Magnetic resonance spectroscopy (MRS) and imaging (MRI) are non-invasive techniques which have already been used to monitor cellular metabolism (Gillies et al, 1989), cell density (Mancuso et al, 1990;Gillies et al, 1991;Barry et al, 1993), cell and dissolved oxygen distribution (Callies et al, 1994;Williams et al, 1997) and medium flow rates in HF-BRs (Hammer et al, 1990;Donoghue et al, 1992), (Reviewed in Fernandez, 1996;Brindle 1998). Mancuso et al (1990) used 23 Na and 31 P MR measurements of reactor sodium and ATP content respectively to estimate cell concentration in an HFBR and compared these measurements with measurements of oxygen consumption rate.…”

New advances in MR‐compatible bioartificial liver

“…19 F MRI has been demonstrated to image oxygen concentrations within a coaxial hollow fiber bioreactor 51, but has not yet been performed with BALs. This method perfuses a perfluorinated hydrocarbon into the bioreactor, and T 1 maps are obtained across the bioreactor in order to obtain the oxygen concentration.…”