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

T Liimatainen, JM Hakumäki, RA Kauppinen, M Ala-Korpela

Research output: Contribution to journalArticle (Academic Journal)

33 Citations (Scopus)

Abstract

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 (1)H 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 (1)H MRS-visible lipids, the fatty acid --CH==CH-- groups and cholesterol compounds showed the strongest associations with water diffusion (r(2) = 0.30; P <0.05 and r(2) = 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 (1)H 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 (1)H 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 (1)H MRS resonances of mobile lipids alone can no longer give a reliable estimate of tissue conditions.
Original languageEnglish
Pages (from-to)272 - 279
Number of pages8
JournalNMR in Biomedicine
Volume22
Issue number3
Early online date13 Nov 2008
DOIs
Publication statusPublished - Apr 2009

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