Monitoring of gliomas in vivo by diffusion MRI and 1H MRS during gene therapy-induced apoptosis: interrelationships between water diffusion and mobile lipids


  • Timo Liimatainen,

    Corresponding author
    1. A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland
    2. Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, USA
    • Center for Magnetic resonance Research, University of Minnesota, 2021 6th Street SE, 2021 6th Street SE, Minneapolis MN 55455, USA.
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  • Juhana M. Hakumäki,

    1. Department of Radiology, Kuopio University Hospital, Finland
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  • Risto A. Kauppinen,

    1. Biomedical NMR Research Center, Dartmouth Medical School, Dartmouth, NH, USA
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  • Mika Ala-Korpela

    1. Computational Medicine Research Group, Department of Biomedical Engineering and Computational Science, Helsinki University of Technology, Finland
    2. Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Finland
    3. Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Finland
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The measurement of water diffusion by diffusion-weighted MRI (DWI) in vivo offers a non-invasive method for assessing tissue responses to anti-cancer therapies. The pathway of cell death after anti-cancer treatment is often apoptosis, which leads to accumulation of mobile lipids detectable by 1H MRS in vivo. However, it is not known how these discrete MR markers of cell death relate to each other. In a rodent tumour model [i.e. ganciclovir-treated herpes simplex thymidine kinase (HSV-tk) gene-transfected BT4C gliomas], we studied the interrelationships between water diffusion (Trace{D}) and mobile lipids during apoptosis. Water diffusion and water-referenced concentrations of mobile lipids showed clearly increasing and interconnected trends during treatment. Of the accumulating 1H MRS-visible lipids, the fatty acid [BOND]CH[DOUBLE BOND]CH[BOND] groups and cholesterol compounds showed the strongest associations with water diffusion (r2 = 0.30; P < 0.05 and r2 = 0.48; P < 0.01, respectively). These results indicate that the tumour histopathology and apoptotic processes during tumour shrinkage can be interrelated in vivo by DWI of tissue water and 1H MRS of mobile lipids, respectively. However, there is considerable individual variation in the associations, particularly at the end of the treatment period, and in the relative compositions of the accumulating NMR-visible lipids. The findings suggest that the assessment of individual treatment response in vivo may benefit from combining DWI and 1H MRS. Absolute and relative changes in mobile lipids may indicate initiation of tumour shrinkage even when changes in tissue water diffusion are still small. Conversely, greatly increased water diffusion probably indicates that substantial cell decomposition has taken place in the tumour tissue when the 1H MRS resonances of mobile lipids alone can no longer give a reliable estimate of tissue conditions. Copyright © 2008 John Wiley & Sons, Ltd.