Cancer angiogenesis is a key focal point in biomedical research. However, lack of a high resolution and portable imaging technique that helps in non-invasive, real-time quantification of various parameters is a huge challenge facing cancer research studies in animals.
In cancer research, scientists need to visualize the tumor in real time, to study the effects of drugs on the tumor and aid in further drug discovery. In order to achieve this, they need imaging techniques that help them visualize tumor angiogenesis in a non-invasive manner in real time. Traditional methods including dissection and histology are not of much help in this regard. This is where micro-ultrasound tool is of great use to researchers.
Micro-ultrasound uses intravenous contrast agents and very high frequency probes to image tissues in fine detail. It is a promising technique for studying angiogenesis and monitoring therapy. Angiogenesis research is usually performed on mice, as they are easily available in many strains and are also easy to handle. Micro-ultrasound is particularly useful in this application due to the small size of the mice.
Several cancer research groups have used micro-ultrasound successfully in angiogenesis visualization. They reported the advantages of using micro-ultrasound as compared to conventional imaging tools such as CT, MRI, SPECT, and PET.
These systems have significant drawbacks including complicated operating requirements. None of them provide real-time visualization like micro-ultrasound, which can provide images at 300 frames per second, which helps analyze blood flow and perfusion. A study by Loveless et al showed that micro-ultrasound can be combined with MRI in order to validate results from both the tools.
Micro-ultrasound using contrast agents
Contrast agents used in micro-ultrasound improves imaging. These are materials which have optical or acoustic properties that are different from those of the target tissues, and are injected into the bloodstream.
Mechanism of drug action
New tools have emerged in the past decade for the targeted treatment of patients with metastatic lung, breast and renal cancer. However, understanding the mechanism of action of these drugs and identifying the category of patients that they benefit the most has been a challenge.
Also, there is a lack of biomarkers that can be used to track response to therapy as well as resistance to treatment. Micro-ultrasound is ideal for studying these aspects in preclinical models.
Tumor volume and changes
Micro-ultrasound provides a non-invasive way of repeatedly monitoring changes in a tumor over a long period of time. The same animal can be monitored, and acts as its own control. This boosts the accuracy of the study and reduces the number of animals required.
Using micro-ultrasound, tumors can be continuously monitored and measured right from initiation of therapy, through different stages of their growth, and during metastases to other organs, tissues and lymph nodes.
It has been shown by several studies that the use of micro-ultrasound enables accurate monitoring of tumor size. Images from 3D micro-ultrasound closely correlated with histology images and also precisely confirmed the tumor size and shape in vivo.
Other studies reported that 3D micro-ultrasound can not only be used for non-invasive monitoring of tumor volume and growth, but also for evaluating possible chemotherapeutic agents in murine cancer models.
Micro-ultrasound systems from Vevo and VisualSonics
A novel micro-ultrasound system developed by VisualSonics seems to be a promising solution to this problem. The revolutionary new technique allows collection of a large amount of data over the entire lifespan of the animals studied, thus reducing the number of animals required. The new system helps rapidly quantify tumor vascularity, 3D tumor volume, and tissue perfusion.
Vevo MicroMarker® contrast agents help in visualizing capillaries and monitoring the expression of VEGF and other such endothelial cell markers. Vevo® micro-ultrasound systems are widely used by cancer researchers. Olive et al. used the Vevo high-resolution micro-ultrasound system to create images of normal and diseased tissue in mice as part of a pancreatic cancer study. The researchers also successfully used the Vevo MicroMarker microbubbles to see tumor perfusion.
Reviewed by Liji Thomas, MD