Abstract
Here we describe the parametric response map (PRM), a voxel-wise approach for image analysis and quantification of hemodynamic alterations during treatment for 44 patients with high-grade glioma. Relative cerebral blood volume (rCBV) and flow (rCBF) maps were acquired before treatment and after 1 and 3 weeks of therapy. We compared the standard approach using region-of-interest analysis for change in rCBV or rCBF to the change in perfusion parameters on the basis of PRM (PRMrCBV and PRMrCBF) for their accuracy in predicting overall survival. Neither the percentage change of rCBV or rCBF predicted survival, whereas the regional response evaluations made on the basis of PRM were highly predictive of survival. Even when accounting for baseline rCBV, which is prognostic, PRMrCBV proved more predictive of overall survival.
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References
O'Connor, J.P., Jackson, A., Parker, G.J. & Jayson, G.C. DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents. Br. J. Cancer 96, 189–195 (2007).
Zahra, M.A., Hollingsworth, K.G., Sala, E., Lomas, D.J. & Tan, L.T. Dynamic contrast-enhanced MRI as a predictor of tumour response to radiotherapy. Lancet Oncol. 8, 63–74 (2007).
Cao, Y. et al. Clinical investigation survival prediction in high-grade gliomas by MRI perfusion before and during early stage of RT. Int. J. Radiat. Oncol. Biol. Phys. 64, 876–885 (2006).
Østergaard, L., Weisskoff, R.M., Chesler, D.A., Gyldensted, C. & Rosen, B.R. High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis. Magn. Reson. Med. 36, 715–725 (1996).
Rosen, B.R., Belliveau, J.W., Vevea, J.M. & Brady, T.J. Perfusion imaging with NMR contrast agents. Magn. Reson. Med. 14, 249–265 (1990).
Brix, G. et al. Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series. Magn. Reson. Med. 52, 420–429 (2004).
Hoffmann, U., Brix, G., Knopp, M.V., Hess, T. & Lorenz, W.J. Pharmacokinetic mapping of the breast: a new method for dynamic MR mammography. Magn. Reson. Med. 33, 506–514 (1995).
Tofts, P.S. Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J. Magn. Reson. Imaging 7, 91–101 (1997).
Degani, H., Gusis, V., Weinstein, D., Fields, S. & Strano, S. Mapping pathophysiological features of breast tumors by MRI at high spatial resolution. Nat. Med. 3, 780–782 (1997).
Galbraith, S.M. et al. Reproducibility of dynamic contrast-enhanced MRI in human muscle and tumours: comparison of quantitative and semi-quantitative analysis. NMR Biomed. 15, 132–142 (2002).
Hylton, N. Dynamic contrast-enhanced magnetic resonance imaging as an imaging biomarker. J. Clin. Oncol. 24, 3293–3298 (2006).
Thomas, A.L. et al. Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J. Clin. Oncol. 23, 4162–4171 (2005).
Xiong, H.Q. et al. A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Invest. New Drugs 22, 459–466 (2004).
Tofts, P.S. et al. Estimating kinetic parameters from dynamic contrast-enhanced T1-weighted MRI of a diffusable tracer: standardized quantities and symbols. J. Magn. Reson. Imaging 10, 223–232 (1999).
Eyal, E. & Degani, H. Model-based and model-free parametric analysis of breast dynamic-contrast-enhanced MRI. NMR Biomed. 22, 40–53 (2009).
Kiessling, F., Morgenstern, B. & Zhang, C. Contrast agents and applications to assess tumor angiogenesis in vivo by magnetic resonance imaging. Curr. Med. Chem. 14, 77–91 (2007).
Law, M. et al. Gliomas: predicting time to progression or survival with cerebral blood volume measurements at dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology 247, 490–498 (2008).
Law, M., Young, R., Babb, J., Pollack, E. & Johnson, G. Histogram analysis versus region of interest analysis of dynamic susceptibility contrast perfusion MR imaging data in the grading of cerebral gliomas. AJNR Am. J. Neuroradiol. 28, 761–766 (2007).
Young, R., Babb, J., Law, M., Pollack, E. & Johnson, G. Comparison of region-of-interest analysis with three different histogram analysis methods in the determination of perfusion metrics in patients with brain gliomas. J. Magn. Reson. Imaging 26, 1053–1063 (2007).
Hamstra, D.A. et al. Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma. Proc. Natl. Acad. Sci. USA 102, 16759–16764 (2005).
Lee, K.C. et al. A feasibility study evaluating the functional diffusion map as a predictive imaging biomarker for detection of treatment response in a patient with metastatic prostate cancer to the bone. Neoplasia 9, 1003–1011 (2007).
Lee, K.C. et al. An imaging biomarker of early treatment response in prostate cancer that has metastasized to the bone. Cancer Res. 67, 3524–3528 (2007).
Moffat, B.A. et al. Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response. Proc. Natl. Acad. Sci. USA 102, 5524–5529 (2005).
Moffat, B.A. et al. The functional diffusion map: an imaging biomarker for the early prediction of cancer treatment outcome. Neoplasia 8, 259–267 (2006).
Liu, G. et al. Dynamic contrast-enhanced magnetic resonance imaging as a pharmacodynamic measure of response after acute dosing of AG-013736, an oral angiogenesis inhibitor, in patients with advanced solid tumors: results from a phase I study. J. Clin. Oncol. 23, 5464–5473 (2005).
Morgan, B. et al. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two phase I studies. J. Clin. Oncol. 21, 3955–3964 (2003).
Mross, K. et al. Phase I clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumours. Eur. J. Cancer 41, 1291–1299 (2005).
O'Donnell, A. et al. A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points. Br. J. Cancer 93, 876–883 (2005).
Rugo, H.S. et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J. Clin. Oncol. 23, 5474–5483 (2005).
Wedam, S.B. et al. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J. Clin. Oncol. 24, 769–777 (2006).
Chan, J.L. et al. Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. J. Clin. Oncol. 20, 1635–1642 (2002).
Meyer, C.R. et al. Demonstration of accuracy and clinical versatility of mutual information for automatic multimodality image fusion using affine and thin-plate spline warped geometric deformations. Med. Image Anal. 1, 195–206 (1997).
Acknowledgements
This work was supported by the US National Institutes of Health research grants P01CA085878, U24CA083099 and P50CA093990.
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C.J.G. conducted data and statistical analyses and wrote the manuscript, T.L.C. acquired and post-processed the MRI data, C.R.M. registered the image data, D.A.H. acquired patient information, C.T., T.S.L. and L.J. accrued subjects and wrote the institutional review board protocol, P.C.S. performed image analysis, T.D.J. aided in the statistics, D.J.R. performed PRM and whole-tumor analysis, A.R. contributed to the design of the study and B.D.R. supervised the project including data analysis and manuscript preparation.
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C.J.G., T.L.C., C.R.M., A.R. and B.D.R. are entitled to royalties from the licensure of intellectual property studied in this research. This technology has been licensed to ImBio, LLC, a company in which A.R. and B.D.R. have a financial interest.
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Galbán, C., Chenevert, T., Meyer, C. et al. The parametric response map is an imaging biomarker for early cancer treatment outcome. Nat Med 15, 572–576 (2009). https://doi.org/10.1038/nm.1919
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DOI: https://doi.org/10.1038/nm.1919
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