Water spin dynamics during apoptotic cell death in glioma gene therapy probed by T1ρ and T2ρ

Longitudinal and transverse relaxations in the rotating frame, with characteristic time constants T1ρ and T2ρ, respectively, have potential to provide unique MRI contrast in vivo. On-resonance spin-lock T1ρ with different spin-lock field strengths and adiabatic T2ρ 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 T1ρ and T2ρ MR imaging are useful tools to quantify early changes in water dynamics reflecting treatment response during gene therapy. Magn Reson Med 59:1311–1319, 2008. © 2008 Wiley-Liss, Inc.