Abstract 1495: Quantification of blood perfusion in rhabdomyosarcoma xenograft in 3D using contrast-enhanced ultrasound imaging

Abstract

Abstract This study aims to estimate individual 3D perfusion maps using nonlinear contrast-enhanced ultrasound imaging (CEUS) over the volume of individual rhabdomyosarcoma xenograft tumors in CD1 nude mice. We implanted the tumors subcutaneously close to the right kidney. We administered MicroMarker® microbubbles via tail vein catheter and acquired images using VisualSonics VEVO 2100 imaging system. We used the burst-replenishment technique to image tumor perfusion. To maintain a steady concentration of microbubbles, we used a programmable pump to inject a small bolus followed by constant infusion, achieving a steady state in less than 1 min, significantly shorter than the commonly used constant infusion without an initial bolus. Our preliminary analysis showed that the nonlinear CEUS signal intensities of kidney cortex have less than 20% variation between mice. We used a custom program to acquire the CEUS perfusion images over a 3D volume that included the tumor and the right kidney. We used the kidney as a reference organ to normalize whole tumor perfusion data. We applied temporal clustering methods to identify regions with similar perfusion profiles. We fitted three perfusion models to each region: a) mono-exponential, b) lognormal, c) beam-specific. We compared the performance of the models based on their overall quality of fit (across all the regions) and their error in estimated pre-burst signal level. Our preliminary analysis showed that log-normal and multi-vessel beam-specific models provide better performance than the mono-exponential model. We estimated individual 3D perfusion maps based on the model fits. These perfusion maps over the entire tumor volume represent tumor perfusion more accurately than the commonly used methods based on a single 2D plane over a region of interest and without including a reference organ. Our approach quantifies intratumoral blood perfusion heterogeneity and enables comparison of perfusion across individuals. Our method is extensible to other animal models and cancer types provided they can be imaged using ultrasound and a reference tissue can be imaged reliably in tandem on a subset of planes containing the tumor. Citation Format: Abbas Shirinifard, Suresh Thiagarajan, András Sablauer. Quantification of blood perfusion in rhabdomyosarcoma xenograft in 3D using contrast-enhanced ultrasound imaging. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1495. doi:10.1158/1538-7445.AM2015-1495