Water spin dynamics during apoptotic cell death in glioma gene therapy probed by T and T

A. Sierra, S. Michaeli, J. P. Niskanen, P. K. Valonen, H. I. Gröhn, S. Ylä-Herttuala, M. Garwood, Olli H. Gröhn

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Longitudinal and transverse relaxations in the rotating frame, with characteristic time constants T and T, respectively, have potential to provide unique MRI contrast in vivo. On-resonance spin-lock T with different spin-lock field strengths and adiabatic T with different radiofrequency- modulation functions were measured in BT4C gliomas treated with Herpes Simplex Virus thymidine kinase (HVS-tk) gene therapy causing apoptotic cell death. These NMR tools were able to discriminate different treatment responses in tumor tissue from day 4 onward. An equilibrium two-site exchange model was used to calculate intrinsic parameters describing changes in water dynamics. Observed changes included increased correlation time of water associated with macromolecules and a decreased fractional population of this pool. These results are consistent with destructive intracellular processes associated with cell death and the increase of extracellular space during the treatment. Furthermore, association between longer exchange correlation time and decreased pH during apoptosis is discussed. In this study, we demonstrated that T and T MR imaging are useful tools to quantify early changes in water dynamics reflecting treatment response during gene therapy.

Original languageEnglish (US)
Pages (from-to)1311-1319
Number of pages9
JournalMagnetic resonance in medicine
Volume59
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • Adiabatic
  • Apoptosis
  • Fast exchange
  • Gene therapy
  • Spin-lock
  • T
  • T

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