MRI is playing an important and expanding role in the diagnosis and evaluation of acute stroke. In particular, the apparent diffusion coefficient (ADC) of water, as measured by diffusion-weighted MRI (DWI), provides a means to quickly evaluate ischemic stroke in a clinical setting. Although changes in the ADC of ischemic tissue are well documented and are already clinically useful, their full potential will not be realized until the underlying physiologic mechanisms responsible for such changes are better understood. The primary goal of this project is to develop and implement a perfused cell culture system (bioreactor) to investigate changes in MRI and MRS parameters due to model ischemia. Most work in the area of MRI and MRS investigations of model cerebral ischemia involves experimental stroke in animal models. These models provide extremely useful in vivo data but are complicated by unavoidable animal variability, tissue heterogeneity, lack of experimental control and spatial resolution. Bioreactor systems, on the other hand, allow cells to be grown to high density and studied in a relatively homogeneous and easily controlled environment. Perfusion constituents and flow rates in the bioreactor can be easily controlled, monitored and manipulated. Ischemic conditions can be experimentally induced within bioreactors and the cellular response can be studied in detail using MRI and magnetic resonance spectroscopy (MRS) methods. The bioreactor system will nicely fill a void that exist between simpler (non-perfused) cell cultures, and more complicated animal models. Within this project, ischemia induced changes in the ADC of water will be correlated with changes of in pH, ATP, PCr, Pi, Na+ and cell volume using MR methods. Initial studies will employ hollow fiber bioreactor (HFBR) cultures of rat C6 glials cells and will be compared to the ischemic response of normal rat brain. Further studies will the the ischemic response, in terms of MR observables, of human glial and neural cell lines. The consequences of hypoperfusion, pre-ischemic hyperglycemia, post-ischemic hypothermia will also be determined.
| Harkins, Kevin D; Galons, Jean-Philippe; Divijak, Joseph L et al. (2011) Changes in intracellular water diffusion and energetic metabolism in response to ischemia in perfused C6 rat glioma cells. Magn Reson Med 66:859-67 |
| Harkins, Kevin D; Galons, Jean-Philippe; Secomb, Timothy W et al. (2009) Assessment of the effects of cellular tissue properties on ADC measurements by numerical simulation of water diffusion. Magn Reson Med 62:1414-22 |
| Trouard, Theodore P; Harkins, Kevin D; Divijak, Joseph L et al. (2008) Ischemia-induced changes of intracellular water diffusion in rat glioma cell cultures. Magn Reson Med 60:258-64 |
| Galons, Jean-Philippe; Lope-Piedrafita, Silvia; Divijak, Joseph L et al. (2005) Uncovering of intracellular water in cultured cells. Magn Reson Med 54:79-86 |
