© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 24, 2029-2036,
December 20, 2000
© 2000 Oxford University Press
REPORT |
Diffusion Magnetic Resonance Imaging: an Early Surrogate Marker of Therapeutic Efficacy in Brain Tumors
Affiliations of authors: T. L. Chenevert (Department of Radiology), L. D. Stegman, B. D. Ross (Departments of Radiology and Biological Chemistry), J. M. G. Taylor (Departments of Biostatistics and Radiation Oncology), P. L. Robertson (Departments of Pediatrics and Neurology), H. S. Greenberg (Department of Neurology), A. Rehemtulla (Department of Radiation Oncology), University of Michigan Medical School, Ann Arbor.
Correspondence to: Brian D. Ross, Ph.D., Center for Molecular Imaging, University of Michigan, 1150 West Medical Center Dr., 9303 MSRB III, Ann Arbor, MI 48109–0648 (e-mail: bdross{at}umich.edu).
Background: A surrogate marker for treatment response that can be observed earlier than comparison of sequential magnetic resonance imaging (MRI) scans, which depends on relatively slow changes in tumor volume, may improve survival of brain tumor patients by providing more time for secondary therapeutic interventions. Previous studies in animals with the use of diffusion MRI revealed rapid changes in tumor water diffusion values after successful therapeutic intervention. Methods: The present study examined the sensitivity of diffusion MRI measurements in orthotopic rat brain tumors derived from implanted rat 9L glioma cells. The effectiveness of therapy for individual brain cancer patients was evaluated by measuring changes in tumor volume on neuroimaging studies conducted 6–8 weeks after the conclusion of a treatment 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 measure of tumor cell death. Mean apparent diffusion coefficients in tumors were found to be correlated with and highly sensitive to changes in tumor cellularity (r = .78; two-sided P = .041). The feasibility of serial diffusion MRI in the clinical management of primary brain tumor patients was also demonstrated. Increased diffusion values could be detected in human brain tumors shortly after treatment initiation. The magnitude of the diffusion changes corresponded with clinical outcome. Conclusions: These results suggest that diffusion MRI will provide an early surrogate marker for quantification of treatment response in patients with brain tumors.
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