Abstract
Measurement of vessel caliber by magnetic resonance imaging (MRI) is a valuable technique for in vivo monitoring of hemodynamic status and vascular development, especially in the brain. Here, we introduce a new paradigm in MRI termed vessel architectural imaging (VAI) that exploits an overlooked temporal shift in the magnetic resonance signal, forming the basis for vessel caliber estimation, and show how this phenomenon can reveal new information on vessel type and function not assessed by any other noninvasive imaging technique. We also show how this biomarker can provide new biological insights into the treatment of patients with cancer. As an example, we demonstrate using VAI that anti-angiogenic therapy can improve microcirculation and oxygen saturation and reduce vessel calibers in patients with recurrent glioblastomas and, more crucially, that patients with these responses have prolonged survival. Thus, VAI has the potential to identify patients who would benefit from therapies.
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Change history
20 September 2013
In the version of this article initially published, the labeling of Figure 2 was incorrect. The three top labels for arterioles should have read as follows (from bottom to top): “Rart = 7.5 μm,” “Rart = 10 μm” and “Rart = 20 μm,” respectively. The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
The authors thank T. Stylianopoulos (Department of Mechanical and Manufacturing Engineering, University of Cyprus) and J.W. Baish (Department of Mechanical and Biomedical Engineering, Bucknell University) for critical reading of this manuscript. This work was funded by the US Public Health Service (grants R21CA117079, S10RR023401, S10RR019307, S10RR019254, S10RR023043, S10RR021110, R01CA137254, R01CA129371, 5R01NS060918, K24CA125440, P01CA80124 and K25AG029415), by the US National Cancer Institute (http://www.clinicaltrials.gov/, NCT00035656); SAIC-Frederick Inc. grant 26XS263; Norwegian Research Council grant 191088/F20; South-Eastern Norway Regional Health Authority Grant 2013069; the Danish Research Foundation (Center of Functionally Integrative Neuroscience); the Ministry of Science, Innovation and Technology–Denmark (Investment Capital for University Research); the Sigrid Juselius Foundation; the Instrumentarium Research Foundation; the Academy of Finland; the Paulo Foundation; and the Finnish Medical Foundation. This work was conducted with support from Harvard Catalyst–Harvard Clinical and Translational Science Center (US National Institutes of Health Award nos. UL1 RR 025758 and M01-RR-01066 and financial contributions from Harvard University and its affiliated academic healthcare centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the US National Center for Research Resources or the US National Institutes of Health.
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K.E.E. wrote the manuscript. K.E.E., K.M., A.B., P.Y.W., P.I., T.T.B., B.R.R., R.K.J. and A.G.S. designed the study. D.J., B.R.R. and A.G.S. acquired all of the MRI data. P.Y.W. and T.T.B. acquired all of the clinical data. K.E.E. and A.B. performed the MatLab simulations. K.E.E., K.M., A.B., C.T.F., D.J., R.J.H.B., B.R.R., R.K.J. and A.G.S. analyzed and interpreted the simulations and human data. K.E.E. performed the statistical analysis. K.E.E., K.M., A.B., C.T.F., D.J., R.J.H.B., P.Y.W., P.I., T.T.B., B.R.R., R.K.J. and A.G.S. revised the manuscript critically. K.E.E., K.M., A.B., C.T.F., D.J., R.J.H.B., P.Y.W., P.I., T.T.B., B.R.R., R.K.J. and A.G.S. approved the final version of the manuscript.
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K.E.E. and A.B. have licensed patents with NordicNeuroLab AS. A.B. is a board member at NordicNeuroLab AS. P.Y.W. received research support from Merck, Sanofi-Aventis, Genentech, Novartis, Medimmune, AstraZeneca, Amgen, Vascular Biogenics and Genzyme. T.T.B. is on the consultant-advisory boards of Merck, Roche, Kirin Pharmaceuticals, Champions Biotechnology and Advance Medical and received grants from Pfizer, AstraZeneca and Millennium. B.R. is on the consultant-advisory board of Siemens Medical. R.K.J. received grant support from Dyax, MedImmune and Roche; is on the consultant-advisory board of Dyax, Noxxon Pharma and SynDevRx; and is on the board of directors of Xtuit. A.G.S. is the chief executive officer of Siemens HealthCare USA; received grant support from Sanofi-Aventis, Exelixis Inc., Schering-Plough and Takeda Pharmaceutical Company Ltd.; and is on the consultant-advisory board of Sanofi-Aventis, Bayer AG, Mitsubishi and Biogen Idec Inc.
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Emblem, K., Mouridsen, K., Bjornerud, A. et al. Vessel architectural imaging identifies cancer patient responders to anti-angiogenic therapy. Nat Med 19, 1178–1183 (2013). https://doi.org/10.1038/nm.3289
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DOI: https://doi.org/10.1038/nm.3289
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