Abstract
Preclinical mouse solid tumor models are widely used to evaluate efficacy of novel cancer therapeutics. Recent reports have highlighted the need for utilizing orthotopic implantation to represent clinical disease more accurately, however the deep tissue location of these tumors makes longitudinal assessment challenging without the use of imaging techniques. The purpose of this study was to evaluate the performance of a new multi-modality high-throughput in vivo imaging system that combines bioluminescence imaging (BLI) with robotic, hands-free ultrasound (US) for evaluating orthotopic mouse models. Long utilized in cancer research as independent modalities, we hypothesized that the combination of BLI and US would offer complementary advantages of detection sensitivity and quantification accuracy, while mitigating individual technological weaknesses. Bioluminescent pancreatic tumor cells were injected into the pancreas tail of C57BL/6 mice and imaged weekly with the combination system and magnetic resonance imaging (MRI) to serve as a gold standard. BLI photon flux was quantified to assess tumor activity and distribution, and US and MRI datasets were manually segmented for gross tumor volume. Robotic US and MRI demonstrated a strong agreement (R2 = 0.94) for tumor volume measurement. BLI showed a weak overall agreement with MRI (R2 = 0.21), however, it offered the greatest sensitivity to detecting the presence of tumors. We conclude that combining BLI with robotic US offers an efficient screening tool for orthotopic tumor models.
Highlights
Preclinical mouse solid tumor models are widely used to evaluate efficacy of novel cancer therapeutics
We explore the performance of a combined US and bioluminescence imaging (BLI) system, using magnetic resonance imaging (MRI) as a gold standard
The imaging studies were divided into 2 sub-analyses: Robotic US vs MRI to test the ability of US to accurately measure orthotopic tumor volume, and BLI vs MRI to assess the relationship between tumor radiance and tumor volume
Summary
Preclinical mouse solid tumor models are widely used to evaluate efficacy of novel cancer therapeutics. Magnetic resonance imaging (MRI) and positron emission tomography (PET) are widely considered to be the gold standard imaging modalities for deep orthotopic tumor evaluation, exhibiting the highest degree of soft tissue anatomical contrast and molecular sensitivity for deep tissue targets, respectively[4]. These modalities incur high operational cost, long acquisition times, limited access from high user demand, and Scientific Reports | (2022) 12:102. US images, in principle, can be acquired without obstructing the path of photons to a BLI camera positioned above the animal, substantially improving the practicality of a combined US and BLI system
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