Vessel architectural imaging identifies cancer patient responders to anti-angiogenic therapy
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, 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
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.
Trial registration: ClinicalTrials.gov NCT00035656.
Conflict of interest statement
CONFLICTS OF INTERESTS
KEE: Licensed patents: NordicNeuroLab AS.
KM: No potential conflicts of interest
AB: Board member: NordicNeuroLab AS. Licensed patents: NordicNeuroLab AS.
CTF: No potential conflicts of interest
DJ: No potential conflicts of interest
RJHB: No potential conflicts of interest
PYW: Research Support: Merck, Sanofi-Aventis, Genentech, Novartis, Medimmune, AstraZeneca, Amgen, Vascular Biogenics, Genzyme
PI: No potential conflicts of interest
TTB: Consultant/Advisory boards: Merck & Co., Inc., Roche, Kirin Pharmaceuticals, Champions Biotechnology, Advance Medical. Grant support: Pfizer, Astra Zeneca, Millenium
BR: Consultant/Advisory Board: Siemens Medical
RKJ: Grant support: Dyax, MedImmune, Roche. Consultant/Advisory boards: Dyax, Noxxon Pharma, SynDevRx. Equity and Board of Directors: Xtuit.
AGS: CEO, Siemens HealthCare USA. Grant support: Sanofi-aventis, Exelixis, Inc, Schering-Plough, Takeda Pharmaceutical Company Limited. Consultant/Advisory boards: Sanofi-aventis, Bayer AG, Mitsubishi, Biogen Idec Inc.
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Source: PubMed