Vascular Disruptive Agent (VDA) is a new strategy for slowing down tumor growth by interfering with angiogenesis. Traditionally, dynamic contrast enhanced MRI and T2/T2* measures were used to infer perfusion and oxygenation changes, respectively. However they are not quantitative and not specific. To understand the time-course perturbation of tumor perfusion and oxygenation by VDA we applied quantitative arterial spin labelling (ASL) perfusion MRI and oxy-haemoglobin mapping using multi-spectral optoacoustic tomography (MSOT) on an orthotopic glioma model in mouse.Orthotopic model was developed by stereotaxic injection of U87MG glioma cells in the brain of nude mice. MRI and MSOT imaging were done before and after tumor implantation. MRI was acquired on a 7T (Bruker Biospin GmbH, 72 mm volume coil with a phase array mouse brain coil) scanner which included T2 weighted fast spin echo imaging for tumor volume (TR/TE=2300/33 ms), T2* mapping obtained using multi-echo gradient echo sequence (TR=900 ms/TE=2.3/NE=12). T1 mapping by inversion recovery single-shot SE-EPI with 7 inversion times (TIs) ranging from 10 to 8000 ms (TR/TE = 10000/20 ms), and pseudo-continuous ASL (pCASL) with a labelling offset = 12 mm, labelling duration = 1600 ms, a post-labelling delay (PLD) of 50 ms. Perfusion was quantified by a kinetic model together with T1 map ^{1, 2}. MSOT (iThera Medical GmbH) was used to detect the oxy-haemoglobin (HbO2) and deoxy-hemoglobin (Hb) in the infra-red range. Vascular disruptive agent (CA4P) was injected at a dose of 30 mg/Kg intravenous and the treatment response was monitored for 1 hour continuously and 6 hours afterward to determine the hypoxic effect.ASL perfusion revealed a core/rim configuration of the growing tumor (Figure A,B,C) , with greater perfusion forming the rim of the tumor and gradually decreased towards the core (Figure D,E,F). Similarly, the sO2 (oxygen saturation), calculated as HbO2/ (HbO2+Hb), was higher in the rim of the tumor, showing a coupling of perfusion and sO2 (Figure B,C,F). After VDA treatment, tumor perfusion increased especially at the rim of tumor (Figure G,H). 6 h after the treatment, perfusion was reduced and became hypoxic as determined from the MSOT (Figure H inset).In this work, we demonstrated coupling of tumor perfusion and oxygenation before and after VDA treatment. The acute increase of perfusion surrounding the glioma (Figure G,H) may be indicative of a hyperaemia process due to vascular disruption ³, followed by an haemorrhage in tumor resulting in hypoxia. Nonetheless, DCE-MRI suggested that perfusion returned to normal 24h after the CA4P treatment while metabolism remained reduced ⁴. Therefore, it will be interesting to evaluate whether there is uncoupling in perfusion and metabolism in longer time frame. Recently, Rich et al ⁵ reported BOLD signal changes correlated with optoacoustic imaging. Our perfusion and T2* measure was also consistent with the Hb measure by MSOT, suggesting that multimodal imaging approach may serve as a surrogate indicator of oxygenation.Multi-modal molecular imaging using MRI and optoacoustic tomography can provide quantitative information on macroscopic changes in treatment response. This will facilitate our understanding of the drug mechanisms and translation in human.