Abstract 1955: A preclinical ultrasound platform for widefield 3D imaging of rodent tumors
Authors: Czernuszewicz Tomasz , Papadopoulou Virginie , Rojas Juan D. , Rajamahendiran Rajalekha , Perdomo Jonathan , Butler James , Harlacher Max , O'Connell Graeme , Zukic Dzenan , Dayton Paul A. , Aylward Stephen , Gessner Ryan C. 
Published: August 2019

Abstract
Background: Preclinical ultrasound (US) and contrast-enhanced ultrasound (CEUS) imaging have long been used in oncology to noninvasively measure tumor volume and vascularity. While the value of preclinical US has been repeatedly demonstrated, these modalities are not without several key limitations that make them unattractive to cancer researchers, including: high user-variability, low throughput, and limited imaging field-of-view (FOV). Herein, we present a novel robotic preclinical US/CEUS system that addresses these limitations and demonstrates its use in evaluating tumors in 3D in a rodent model.
Methods: The imaging system was designed to allow seamless whole-body 3D imaging, which requires rodents to be imaged without physical contact between the US transducer and the animal. To achieve this, a custom dual-element transducer was mounted on a robotic carriage, submerged in a hydrocarbon fluid, and the reservoir sealed with an acoustically transmissive top platform. Eight NOD/scid/gamma (NSG) female mice were injected subcutaneously in the flank with 8×109 786-O human clear-cell renal cell carcinoma (ccRCC) cells. Weekly imaging commenced after tumors reached a size of 150 mm3 and continued until tumors reached a maximum size of 1 cm3 (∼4-5 weeks). An additional six nude athymic female mice were injected subcutaneously in the flank with 7 × 105 SVR angiosarcoma cells to perform an inter-operator variability study. Imaging consisted of 3D B-mode (conventional ultrasound) of the whole abdomen (&lt; 1 min), as well as contrast-enhanced acoustic angiography (&lt; 10 min) to measure blood vessel density (BVD). Tumors were manually segmented in 3D (&lt; 2 min) and inter-operator and inter-reader reliability was assessed with Krippendorff’s alpha.
Results: Wide-field US images reconstructed from 3D volumetric data showed superior FOV over conventional US. Several anatomical landmarks could be identified within each image surrounding the tumor, including the liver, small intestines, bladder, and inguinal lymph nodes. Tumor boundaries were clearly delineated in both B-mode and BVD images, with BVD images showing heterogeneous microvessel density at later timepoints suggesting tumor necrosis. Excellent agreement was measured for both inter-reader and inter-operator experiments, with alpha coefficients of 0.914 (95% CI: 0.824-0.948) and 0.959 (0.911-0.981), respectively.
Conclusion: We have demonstrated a novel preclinical US imaging system that can accurately and consistently evaluate tumors in rodent models. The system leverages cost-effective robotic technology, and a new scanning paradigm that allows for easy and reproducible data acquisition to enable wide-field, 3D, multi-parametric ultrasound imaging.
Note: This abstract was not presented at the meeting.
Citation Format: Tomasz Czernuszewicz, Virginie Papadopoulou, Juan D. Rojas, Rajalekha Rajamahendiran, Jonathan Perdomo, James Butler, Max Harlacher, Graeme O'Connell, Dzenan Zukic, Paul A. Dayton, Stephen Aylward, Ryan C. Gessner. A preclinical ultrasound platform for widefield 3D imaging of rodent tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1955.