Water spin dynamics during apoptotic cell death in glioma gene therapy probed by T1rho and T2rho.
Longitudinal and transverse relaxations in the rotating frame, with characteristic time constants T1rho and T2rho, respectively, have potential to provide unique MRI contrast in vivo. On-resonance spin-lock T1rho with different spin-lock field strengths and adiabatic T2rho 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 T1rho and T2rho MR imaging are useful tools to quantify early changes in water dynamics reflecting treatment response during gene therapy.
Biomedical NMR Research Group, Department of Neurobiology and Biomedical Imaging Unit, A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, and Kuopio University Hospital, Kuopio, Finland.
A
A
Sierra
S
S
Michaeli
J-P
JP
Niskanen
P K
PK
Valonen
H I
HI
Gröhn
S
S
Ylä-Herttuala
M
M
Garwood
O H
OH
Gröhn
D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006561:Herpes Simplex / Q000201:enzymology; D016018:Least-Squares Analysis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009368:Neoplasm Transplantation; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D015774:Ganciclovir