Low spin-lock field T1 relaxation in the rotating frame as a sensitive MR imaging marker for gene therapy treatment response in rat glioma.
OBJECTIVE
To prospectively assess the effectiveness of T1 relaxation in the rotating frame (T1 rho) dispersion and the low spin-lock radiofrequency field (B(1)) T1 rho magnetic resonance (MR) imaging relaxation time in noninvasive monitoring of gene therapy response in BT4C glioma in rats.


METHODS
All animal studies were approved by the ethical committee of the National Laboratory Animal Center. Rats with BT4C gliomas (n=9) were treated with herpes simplex virus thymidine kinase gene therapy and were compared with untreated rats (n=5). Absolute T1 rho at a B(1) range of 2.0 x 10(-6) to 1.4 x 10(-4) T, T1, T2, and apparent diffusion constant were measured at 4.7 T during treatment. Statistical significance was tested by using repeated-measures analysis of variance.


RESULTS
A significant (P<.05) lengthening of T1 rho was observed beginning on the 4th day of treatment, and T1 rho values increased to be approximately 80% higher than values observed before treatment. These changes preceded T1 and T2 changes and resembled those of water diffusion. The T1 rho was associated with a treatment-induced decrease in cell density; this was the only measured MR imaging property that provided significant (P<.05) Pearson correlation with cell density in the tumor border. T1 rho relaxation dispersion, however, did not offer additional benefits over those offered in one B(1) experiment in the early phase of treatment.


CONCLUSIONS
T1 rho with low B(1) is an excellent MR imaging marker of early gene therapy response in gliomas. The low B(1) approach is not limited by specific absorption rate restrictions; this finding suggests that spin-lock methods could be applicable in clinical settings. (
Kettunen
Mikko I
MI
Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland. mik21@mole.bio.cam.ac.uk
Sierra
Alejandra
A
Närväinen
M Johanna
MJ
Valonen
Piia K
PK
Ylä-Herttuala
Seppo
S
Kauppinen
Risto A
RA
Gröhn
Olli H J
OH
D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011379:Prognosis; D051381:Rats; D015203:Reproducibility of Results; D012399:Rotation; D012680:Sensitivity and Specificity; D013113:Spin Labels; D016896:Treatment Outcome
D013113:Spin Labels