Abstract
Proton MRS detection of cellular lipid accumulation has been suggested as a noninvasive method for detecting apoptosis or programmed cell death (PCD) in vivo. The spectral changes that have been observed in apoptotic cells include a general increase in lipid signals and a specific increase in the ratio of the lipid methylene‐to‐methyl peak intensities. These changes were investigated here following drug‐induced apoptosis, both in vitro with a murine lymphoma cell line (EL‐4) and in vivo following implantation of these cells to form subcutaneous tumors. Fluorescence microscopy and flow cytometric measurements with a lipophilic dye revealed an accumulation of cytoplasmic lipid droplets in isolated EL‐4 cells undergoing etoposide‐induced apoptosis. ^1^H MR spectra (both diffusion‐weighted (DW) and unweighted) showed an increase in lipid signals. However, the methylene/methyl peak ratio showed only minimal changes. Localized in vivo spectroscopy of EL‐4 tumors also showed an increase in lipid signals, including a signal from polyunsaturated lipid at 2.8 ppm, after 16–24 h of drug treatment. Again there was no significant change in the methylene/methyl peak ratio. This study confirms that MRS‐detectable lipids accumulate in tumor cells undergoing apoptosis, and therefore may be usable as a marker for the noninvasive detection of tumor cell apoptosis in the clinic. Magn Reson Med 54:43–50, 2005. © 2005 Wiley‐Liss, Inc.