Abstract 4338: Monitoring radiation response in tumor vasculature using intravital photoacoustic imaging in a murine window chamber model in vivo
Authors: Sun John , Maeda Azusa , Stapleton Shawn , Chen Yonghong , Heinmiller Andrew , Bate Dave , McGrath Theresa , Needles Andrew , Theodoropoulos Catherine , DaCosta Ralph 
Published: August 2012

Abstract
VisualSonics has recently developed a preclinical photoacoustic (PA) imaging system called the VevoLAZR that combines the sensitivity of optical imaging and the high resolution of micro-ultrasound. The system incorporates a 40 MHz (centre frequency) ultrasound transducer linear array probe (LZ550) and a tuneable 680-970 nm nanosecond pulsed-laser. We used this system to study in vivo changes in tumor oxygen saturation and haemoglobin density caused by exposure to radiation therapy (RT). For this, DsRed-Me180 human cervical tumors were grown in a nude mouse dorsal skinfold window chamber model until they reached 2.5 mm in diameter. Specifically, we investigated the system's sensitivity and dynamic range to measure relative changes in oxygen saturation in tumor and surrounding healthy tissues 10 days after treatment. Tumors (∼2.5 mm diameter) were focally irradiated with a single dose of 30 Gy using a small animal microirradiator (XRAD225, Precision XRay Inc., North Branford, CT). To measure the dynamic range and stability of our setup for measuring oxygen saturation in vivo, we altered the anesthetised animal's inhaled oxygen from 100% to 7% for 1 min during PA imaging. This test showed that blood oxygen saturation in the healthy dorsal skinfold tissue decreased from 82% to 8% and confirmed the linearity of the measurement technique. Furthermore, we compared vascular morphology obtained by photoacoustic imaging and intravital fluorescent microscopy using FITC-Dextran (2 MDa, injected 20 mins prior). This comparison showed good correlation and confirms that PA imaging can provide important structural information of vascularity. Photoacoustic imaging was performed before and 10 days after irradiation to assess changes in tumour volume, relative blood oxygen saturation, relative tissue oxygen saturation, and relative hemoglobin density. Ten days after irradiation, PA imaging showed that the tumour volume increased from 5.7 to 14.2 mm3, relative blood oxygen saturation decreased from 75.3 to 48.2%, relative tissue oxygen saturation decreased from 40.7 to 0.1%, and hemoglobin density decreased from 18457 to 3253 a.u. These data illustrate the capability of PA imaging to simultaneously measure multiple radiobiological response metrics from a single imaging scan. Pilot results demonstrate: i) the compatibility of the VisualSonics small animal VevoLAZR photoacoustic imaging system with intravital murine tumor models, ii) the sensitivity of the system to detect RT-induced changes in tumor vascular oxygen saturation non-invasively, in real time and in vivo, and iii) a new preclinical application of PA imaging for longitudinal monitoring of tumor response to RT in vivo.
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 4338. doi:1538-7445.AM2012-4338