Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors

Background: A surrogate marker for treatment response that can be observed earlier than comparison of sequential magnetic resonance imaging (MRI) scan s, which depends on relatively slow changes in tumor volume, may improve su rvival of brain tumor patients by providing more time for secondary therape utic interventions. Previous studies in animals with the use of diffusion M RI revealed rapid changes in tumor water diffusion values after successful therapeutic intervention. Methods: The present study examined the sensitivi ty of diffusion MRI measurements in orthotopic rat brain tumors derived fro m implanted rat 9L glioma cells. The effectiveness of therapy for individua l brain cancer patients was evaluated by measuring changes in tumor volume on neuroimaging studies conducted 6-8 weeks after the conclusion of a treat ment cycle. Results: Diffusion MRI could detect water diffusion changes in orthotopic 9L gliomas after doses of 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU or carmustine) that resulted in as little as 0.2 log cell kill, a meas ure of tumor cell death. Mean apparent diffusion coefficients in tumors wer e found to be correlated with and highly sensitive to changes in tumor cell ularity (r = .78; two-sided P = .041). The feasibility of serial diffusion MRI in the clinical management of primary brain tumor patients was also dem onstrated. Increased diffusion values could be detected in human brain tumo rs shortly after treatment initiation. The magnitude of the diffusion chang es corresponded with clinical outcome. Conclusions: These results suggest t hat diffusion MRI will provide an early surrogate marker for quantification of treatment response in patients with brain tumors.