Complementarity of ultrasound and fluorescence imaging in an orthotopic mouse model of pancreatic cancer

Abstract

BackgroundPancreatic cancer is a devastating disease characterized by dismal 5-year survival rates and limited treatment options. In an effort to provide useful models for preclinical evaluation of new experimental therapeutics, we and others have developed orthotopic mouse models of pancreatic cancer. The utility of these models for pre-clinical testing is dependent upon quantitative, noninvasive methods for monitoring in vivo tumor progression in real time. Toward this goal, we performed whole-body fluorescence imaging and ultrasound imaging to evaluate and to compare these noninvasive imaging modalities for assessing tumor burden and tumor progression in an orthotopic mouse model of pancreatic cancer.MethodsThe human pancreatic cancer cell line XPA-1, engineered for stable, high-level expression of red fluorescent protein (RFP), was implanted into the pancreas of nude mice using orthotopic implantation. The tumors were allowed to grow over a period of one to several weeks during which time the mice were imaged using both fluorescence imaging and ultrasound imaging to measure tumor burden and to monitor tumor growth.ResultsWhole-body fluorescence imaging and ultrasound imaging both allowed for the visualization and measurement of orthotopic pancreatic tumor implants in vivo. The imaging sessions were well-tolerated by the mice and yielded data which correlated well in the quantitative assessment of tumor burden. Whole-body fluorescence and two-dimensional ultrasound imaging showed a strong correlation for measurement of tumor size over a range of tumor sizes (R2 = 0.6627, P = 0.003 for an exposure time of 67 msec and R2 = 0.6553, P = 0.003 for an exposure time of 120 msec).ConclusionOur findings suggest a complementary role for fluorescence imaging and ultrasound imaging in assessing tumor burden and tumor progression in orthotopic mouse models of human cancer.

Imaging Enzymes at Work: Metabolic Mapping by Enzyme Histochemistry

“…invasive imaging modalities are available for this purpose, such as bioluminescence imaging (BLI) (Klerk et al 2007), fluorescence imaging (FLI) (Hoffman 2004;Joyce et al 2004;Hoffman and Yang 2006), magnetic resonance imaging (MRI) (Mook et al 2008), computed tomography (Koo et al 2006), ultrasonography (Snyder et al 2009), single photon emission computed tomography (Lewis et al 2002;Sadaghiani et al 2007), and positron emission tomography (Lyons 2005;Sadaghiani et al 2007). …”

High-frequency Ultrasound Imaging of Mouse Cervical Lymph Nodes

“…HFUS has been used to visualize diseased mouse lymph nodes within the main body cavity, demonstrating parallel utility of this technology to clinical practice. In particular, inflammatory and metastatic visceral lymph node alterations have been observed in mouse models of cancer harboring breast 12,13 , pancreatic 14 , colorectal 15 and lung 16 tumors, as well as fibrous histocytomas…”

Ultrasound guided fluorescence tomography

“…Finally, ultrasound imaging, with the advantages of low cost and non-invasiveness, has been employed as a complement to fluorescence imaging. For example, C. Snyder et al employed US imaging to assess tumor size in mice to provide guidance for fluorescence imaging [6]. Also, Zhu et al used 2D US structural prior for a better fluorescence reconstruction in terms of localization and quantification [7].…”