Glioma cell density in a rat gene therapy model gauged by water relaxation rate along a fictitious magnetic field

Longitudinal and transverse rotating-frame relaxation time constants, T_1ρ and T_2ρ, have previously been successfully applied to detect gene therapy responses and acute stroke in animal models. Those experiments were performed with continuous-wave irradiation or with frequency-modulated pulses operating in an adiabatic regime. The technique called Relaxation Along a Fictitious Field (RAFF) is a recent extension of frequency-modulated rotating-frame relaxation methods. In RAFF, spin locking takes place along a fictitious magnetic field, and the decay rate is a function of both T_1ρ and T_2ρ processes. In this work, the time constant characterizing water relaxation with RAFF (T _RAFF) was evaluated for its utility as a marker of response to gene therapy in a rat glioma model. To investigate the sensitivity to early treatment response, we measured several rotating-frame and free-precession relaxation time constants and the water apparent diffusion coefficients, and these were compared with histological cell counts in 8 days of treated and control groups of animals. T_RAFF was the only parameter exhibiting significant association with cell density in three different tumor regions (border, intermediate, and core tissues). These results indicate that T_RAFF may provide a marker to identify tumors responding to treatment.