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Assessment of murine colorectal cancer by micro-ultrasound using three dimensional reconstruction and non-linear
Jessica L Freeling1, Khosrow Rezvani1
1Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota , Vermillion, South Dakota, USA.
Abstract:
The relatively low success rates of current colorectal cancer (CRC) therapies have led investigators to search for more specific treatments. Vertebrate models of colorectal cancer are essential tools for the verification of new therapeutic avenues such as gene therapy. The evaluation of colorectal cancer in mouse models has been limited due to the lack of an accurate quantitative and longitudinal noninvasive method. This work introduces a method of three-dimensional micro-ultrasound reconstruction and microbubble administration for the comprehensive and longitudinal evaluation of CRC progression. This approach enabled quantification of both tumor volume and relative vascularity using a well-established inducible murine model of colon carcinogenesis. This inducible model recapitulated the adenocarcinoma sequence that occurs in human CRC allowing systematic in situ evaluation of the ultrasound technique. The administration of intravenous microbubbles facilitated enhancement of colon vascular contrast and quantification of relative vascularity of the mid and distal colon of the mouse in three dimensions. In addition, two-dimensional imaging in the sagittal orientation of the colon using Non-Linear Contrast Mode enabled calculation of relative blood volume and perfusion as the microbubbles entered the colon microvasculature. Quantitative results provided by the outlined protocol represent a noninvasive tool that can more accurately define CRC development and progression. This ultrasound technique will allow the practical and economical longitudinal study of murine CRC in both basic and preclinical studies.
Insights
Researchers developed a novel 3D micro-ultrasound method with microbubbles to noninvasively track colorectal cancer (CRC) progression in mice. This technique accurately quantifies tumor volume and vascularity, aiding preclinical studies.
Area of Science:
- Medical imaging
- Oncology
- Preclinical research
Background:
- Current colorectal cancer (CRC) therapies have limited success rates, necessitating novel treatment strategies.
- Accurate, noninvasive, and longitudinal evaluation methods for CRC in animal models are crucial for therapeutic development.
- Existing methods for assessing CRC progression in mouse models lack quantitative and longitudinal capabilities.
Purpose of the Study:
- To introduce a novel 3D micro-ultrasound reconstruction and microbubble administration technique for comprehensive CRC evaluation in mice.
- To enable quantitative and longitudinal assessment of tumor volume and vascularity in a murine model of colon carcinogenesis.
- To validate the ultrasound technique's efficacy in a model that recapitulates human colorectal adenocarcinoma sequence.
Main Methods:
- Utilized a three-dimensional micro-ultrasound reconstruction and microbubble administration approach.
- Employed an inducible murine model of colon carcinogenesis that mimics human CRC progression.
- Administered intravenous microbubbles to enhance colon vascular contrast and enable 3D quantification of vascularity.
- Applied 2D imaging in sagittal orientation using Non-Linear Contrast Mode for blood volume and perfusion calculations.
Main Results:
- Successfully quantified tumor volume and relative vascularity in a murine CRC model.
- Demonstrated enhanced colon vascular contrast and 3D vascularity quantification using microbubbles.
- Enabled calculation of relative blood volume and perfusion via 2D imaging with microbubble contrast.
- Provided quantitative, noninvasive data for defining CRC development and progression.
Conclusions:
- The developed 3D micro-ultrasound technique with microbubbles offers a noninvasive method for longitudinal evaluation of CRC progression in mice.
- This approach accurately quantifies tumor volume and vascularity, crucial for preclinical studies.
- The technique facilitates practical and economical longitudinal studies of murine CRC, supporting basic and preclinical research.
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