Abstract LB-297: Vessel architectural imaging identifies cancer patient responders to anti-angiogenic therapy.
Authors: Emblem Kyrre E. , Mouridsen Kim , Bjornerud Atle , Farrar Christian T. , Jennings Dominique , Borra Ronald J.H , Wen Patrick Y. , Ivy Percy , Batchelor Tracy T. , Rosen Bruce R. , Jain Rakesh K. , Sorensen A. Gregory 
Published: August 2014

Abstract
Purpose: Traditional magnetic resonance imaging (MRI) of cancer in vivo is confounded by heterogeneous vessel architecture with stochastic perfusion. Here, we present a new imaging method coined as vessel architectural imaging (VAI), exploiting an overlooked temporal shift in the MRI signal used in vessel caliber estimation. We show that VAI identifies glioblastoma patients who respond to anti-VEGF therapy by improved microcirculation and prolonged survival [1].
Materials & Methods: In this IRB-approved phase II study of cediranib (NCT00305656), an oral pan-VEGF receptor kinase inhibitor [2], 30 patients with recurrent glioblastoma were imaged monthly during therapy, using a simultaneously acquired gradient-echo and spin-echo contrast enhanced perfusion MRI sequence for VAI [1]. When visualized in a scatter plot, the resulting point-by-point temporal gradient-echo and spin-echo tissue-concentration curves will form a vortex of a certain shape and traverse in a clockwise or counter-clockwise direction depending on tissue type. Typically, a clockwise vortex direction reflects the presence of smaller-caliber, fast-inflow arteriole vessels and capillaries only, whereas a counter-clockwise vortex direction is observed if the tissue also includes a larger-caliber, slow-inflow venule component. The vortex direction effect is attributed to the level of deoxygenated blood in the tissue and the corresponding size of the vortex area is proportional to the relative arteriole-to-venule oxygen saturation (SO2) levels of the tissue [1].
Results: Collectively, patients showed a significant increase in tumoral image voxels with a clockwise vortex direction during therapy (pair-wise Wilcoxons; P &lt; 0.05), mimicking the direction ratios and vessel branching architecture of healthy tissue [1]. Ten responding patients, showing the biggest relative increase in image voxels with a clockwise vortex direction during therapy, also had reduced vessel calibers, improved SO2 levels and prolonged overall survival compared to 12 non-responders (341 days versus 146 days, Cox regression with time dependent covariates; P &lt; 0.01) [1].
Discussion: Using VAI we were able to obtain novel information not provided by traditional MRI, including vessel architecture and SO2 levels. Our results indicate that VAI is a different and potentially more sensitive biomarker for anti-VEGF therapy response.
[1] Emblem KE et al. Nature Med. 2013; In press.
[2] Batchelor TT et al. J Clin Oncol. 2010; 28(17):2817-23.
Citation Format: Kyrre E. Emblem, Kim Mouridsen, Atle Bjornerud, Christian T. Farrar, Dominique Jennings, Ronald J.H Borra, Patrick Y. Wen, Percy Ivy, Tracy T. Batchelor, Bruce R. Rosen, Rakesh K. Jain, A. Gregory Sorensen. Vessel architectural imaging identifies cancer patient responders to anti-angiogenic therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-297. doi:10.1158/1538-7445.AM2013-LB-297