Abstract 2440: Glioblastoma molecular imaging in vivo using multi-spectral optoacoustic tomography
Authors: Burton Neal C. , Patel Manishkumar , Driessen Wouter H.P. , Shi Jing , Morscher Stefan , Zhao Fuqiang , Bednar Bohumil , Wiest Christian , Razansky Daniel , Ntziachristos Vasilis 
Published: August 2012

Abstract
Brain research has been revolutionized by imaging technologies. X-ray CT and MRI provide high spatial resolution, revealing anatomical anomalies indicative of disease. PET and optical imaging have target specificity, allowing the visualization of molecular events. Intravital microscopy has specificity and resolution, providing key information on pathological micro-events, but lacks penetration depth. Multi-spectral optoacoustic tomography (MSOT) combines high resolution, molecular specificity and depth to achieve non-invasive in vivo anatomical, functional and molecular imaging in deep tissue. MSOT illuminates tissue with light pulses at multiple wavelengths and detects the acoustic waves generated by the thermoelastic expansion following light absorption. Using spectral analysis of the data collected, MSOT can then differentiate the spectral signatures of endogenous biomarkers such as oxy-/deoxy-hemoglobin and of photo-absorbing agents and quantify their concentration. In this work we explore the potential of MSOT in cross-sectional imaging of the mouse brain and contrast these results with MRI and ex vivo brain imaging to validate the MSOT in vivo findings. 8 week old nude CD-1 mice were used for stereotactic implantation of U87 glioblastoma cells and for imaging of hemoglobin contrast and ICG biodistribution. In vivo MSOT of the intact mouse head yielded unprecedented performance in cross-sectional imaging of the mouse brain by visualizing the overall brain outline and anatomy, and imaging temporal arteries and blood vessels beneath the skull. Additionally, NIR probes were injected into the 3rd ventricle, with an excellent correlation between MSOT and fluorescence imaging of cryoslices, demonstrating the capacity of MSOT to localize NIR probes in the brain through intact skin and skull with high accuracy. In addition, spectral decomposition of hemoglobin confirmed the MSOT ability to visualize well perfused and ischemic brain conditions following a CO2 challenge. Additionally, MSOT accurately visualized ICG bio-distribution injected into the tail vein, and followed in real time the ICG kinetics and clearance. Finally, spectral decomposition of deoxygenated hemoglobin allowed the observation of hypoxia related to the growth of U87 tumor cells injected into the striatum. Multispectral processing allowed the visualization of the true organ distribution of IntegriSense and AngioSense in the brain, with planar fluorescence imaging used for a reference comparison. The application of MSOT in in vivo brain imaging is demonstrated. MSOT can be used to follow changes in blood oxygenation, as well as the distribution of near-infrared probes. With the advent of new molecular probes, MSOT could also track molecular features of neurological disease and cancer in mouse models.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2440. doi:1538-7445.AM2012-2440