Validation of a combined ultrasound and bioluminescence imaging system with magnetic resonance imaging in orthotopic pancreatic murine tumors

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.

Innovative Experimental Ultrasound and US-Related Techniques Using the Murine Model in Pancreatic Ductal Adenocarcinoma: A Systematic Review

“…Based on our selection criteria, 13 of those studies were excluded, while 88 studies met our inclusion criteria. The included studies could be divided into seven main topics: ultrasound in pancreatic cancer diagnosis and progression (21 papers) [3][4][5][6][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]; dynamic contrast-enhanced ultrasound (DCE-US) (five papers) [6,[42][43][44][45]; microbubble ultrasound-mediated drug delivery (18 papers) [7,[46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]; focused ultrasound (23 papers) [43,; sonodynamic therapy (SDT) (seven papers) [58,69,…”

Application and Development Prospect of Nanoscale Iron Based Metal-Organic Frameworks in Biomedicine

“…To be specific, chemically and thermally stable Fe-MOFs are employed in drug delivery, biosensors, biocatalysts, and other fields, and they exhibit excellent optical and photothermal properties. Besides, they have been commonly adopted as imaging agents for magnetic resonance imaging (MRI) 130 and photoacoustic imaging (PAI). 131 Furthermore, they serve as a photothermal agent and carrier for photothermal therapy (PTT) 132 and photodynamic therapy (PDT).…”

“… 134 Because Fe 3+ is a paramagnetic metal ion, Fe-MOF has become an excellent candidate for MRI imaging, as shown in Figure 11 . 130 The existence of numerous paramagnetic metal centers makes Fe-MOFs tend to exhibit higher relaxation than small molecular contrast agents (CA). In general, a higher relaxation value will help to improve the sensitivity and specificity of contrast media.…”

“…Creative Commons. 130 ( D ) PAI images and ( E ) Photothermal photographs of doxorubicin@MIL-100 compound. Reprinted from Zhiming H, Caina X, Liang Y, et al Multifunctional drug delivery nanoparticles based on MIL-100 (Fe) for photoacoustic imaging-guided synergistic chemodynamic/chemo/photothermal breast cancer therapy.…”

Validation of dual energy X-ray absorptiometry for longitudinal quantification of tumor burden in a murine model of pancreatic ductal adenocarcinoma

“…Furthermore, as BLI signal intensity is a function of tumor metabolism rather than tumor size, it must be used in conjunction with another outcome measure that directly assesses tumor mass [ 9 ]. Thus far, the focus in preclinical models of PDAC has been ultrasound and magnetic resonance imaging (MRI), which have sensitivity and specificity strengths, but suffer from high costs at low throughput [ 6 ]. To overcome this, we developed a dual energy X-ray absorptiometry (DEXA) approach to quantify PDAC-induced skeletal muscle wasting using a non-metastatic model of PDAC [ 10 ].…”