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DOI: 10.1148/radiol.2433052077
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(Radiology 2007;243:796-803.)
© RSNA, 2007

Molecular Imaging

Low Spin-Lock Field T1 Relaxation in the Rotating Frame as a Sensitive MR Imaging Marker for Gene Therapy Treatment Response in Rat Glioma1

Mikko I. Kettunen, PhD, Alejandra Sierra, PhD, M. Johanna Närväinen, PhD2, Piia K. Valonen, PhD, Seppo Ylä-Herttuala, MD, PhD, Risto A. Kauppinen, MD, PhD, and Olli H. J. Gröhn, PhD

1 From the Departments of Biotechnology and Molecular Medicine (M.I.K., P.K.V., S.Y.) and Neurobiology (M.J.N., O.H.J.G.), A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland; Laboratorio de Imagen y Espectroscopia por Resonancia Magnética, Instituto de Investigaciones Biomédicas "Alberto Sols" Consejo Superior De Investigaciones Cientificas/Universidad Autonoma De Madrid, Madrid, Spain (A.S.); and School of Sport and Exercise Sciences, University of Birmingham, Birmingham, England (R.A.K.). Received December 20, 2005; revision requested February 15, 2006; revision received April 28; accepted May 31; final version accepted September 13. Supported by the Academy of Finland, the Sigrid Juselius Foundation, the Finnish Cancer Foundation, the Finnish Cultural Foundation, and the Research Foundation of Leiras. Address correspondence to M.I.K., Department of Biochemistry, University of Cambridge, Old Addenbrookes Site, 80 Tennis Court Rd, Cambridge CB2 1GA, England (e-mail: mik21{at}mole.bio.cam.ac.uk).

Purpose: To prospectively assess the effectiveness of T1 relaxation in the rotating frame (T1{rho}) dispersion and the low spin-lock radiofrequency field (B1) T1{rho} magnetic resonance (MR) imaging relaxation time in noninvasive monitoring of gene therapy response in BT4C glioma in rats.

Materials and 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 B1 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 B1 experiment in the early phase of treatment.

Conclusion: T1{rho} with low B1 is an excellent MR imaging marker of early gene therapy response in gliomas. The low B1 approach is not limited by specific absorption rate restrictions; this finding suggests that spin-lock methods could be applicable in clinical settings.

© RSNA, 2007


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Is There a Role for MR Imaging in Monitoring Gene Therapy Response?
Diana Lindquist
Radiology 2007 243: 611-612. [Full Text] [PDF]



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D. Lindquist
Is There a Role for MR Imaging in Monitoring Gene Therapy Response?
Radiology, June 1, 2007; 243(3): 611 - 612.
[Full Text] [PDF]