Proton magnetic resonance spectroscopy of lymphocytes: An historical perspective

Proton magnetic resonance spectroscopy can be used to elucidate alterations to cellular chemistry associated with specific biological functions. It became apparent that this type of information was present in the magnetic resonance spectra from intact viable lymphocytes in the late 1970s. It was not until the 1980s, however, that one-dimensional multipulse sequences were used to filter the large signal contributions from water and fat, which had until then masked weaker signals from other molecules. When this technology was combined with two-dimensional spectroscopy, unambiguous assignment of the biologically relevant chemical species became possible. In vitro activated, stimulated, transformed, and malignant lymphocytes, as well as embryonic fibroblasts and malignant cells of epithelial origin, all gave rise to a strong triglyceride spectrum and resonances from a multitude of cellular metabolites. Two-dimensional spectroscopy and the analyses of highly purified membranes determined that the triglyceride signals originated, at least in part, from the plasma membrane. Based on physicochemical data, a new model for the structural arrangement of plasma membrane lipid in these cells was proposed. While differences exist between the proton magnetic resonance spectra of stimulated lymphocytes and malignant cells in vitro, they share a high-resolution lipid spectrum. In tissue, however, the presence of activated lymphocytes does not always produce the lipid spectrum, particularly in the vicinity of tumors