Confocal fluorescence optical microscopy and magnetic resonance microscopy are each used to study live cells in a minimally invasive way. Both techniques provide complementar3, information. Therefore, by examining cells simultaneously with both methodologies, more detailed information is obtained than is possible with each microscope individually. In this paper two configurations of a combined confocal and magnetic resonance microscope are described. The first configuration is capable of studying large single cells or three-dimensional cell agglomerates, whereas the second configuration is designed for the investigation of monolayers of mammalian cells. In both cases the sample compartment is part of a temperature regulated perfusion system. Images obtained with the combined system ate shown for Xenopus laevis oocytes, model JB6 tumor spheroids, anda single layer of Chinese hamster ovary cells. Finally, potential applications of the combined microscope are discussed.
lntroductionConfocal fluorescence optical microscopy (OM) and magnetic resonance microscopy (MRM) are extensively used to study living cells in a minimally or noninvasive way [I-4]. Both methods have their advantages and disadvantages and provide complementary information. With OM, images can be obtained with a high spatial resolution (1 ~tm or less) in a short time (seconds). These images can be used to detect small concentrations of biochemicals within a cell or to determine its morphology. This technique, however, requires the use of fluorescent labels and is limited to transparent samples. In contrast, the images obtained with MRM are considerably less well-resolved (10-30 ~tm for ah image of the water distribution), and take a long time to acquire (often several minutes to hours). Despite these shortcomings, MRM is still very useful since it can be used irrespective of the opacity of the sample. Furthermore, MRM provides a wealth of additional biophysical and biochemical information such as the N M R T~ and NMR T 2 relaxation rates, the diffusion coefficient of intra-and extracellular water, and the concentrations of mobile, low-molecular-weight cellular metabolites [3][4][5].