Micro-ultrasound is a miniaturized version of ultrasound with a wider range of applications, especially in research pertaining to small animal models. Smaller versions of imaging techniques boost the efficacy of the techniques, and also reduce the number of animals required for a particular study.

The micro-ultrasound imaging tool has evolved over the past decade as a relatively inexpensive technique for studying small animal models. This in turn helps to analyze diseases in humans. Recent approaches have made it possible to capture images at higher frequencies, thus enabling a host of new uses. The micro-ultrasound technique is widely utilized in various applications in cancer, developmental biology, and cardiovascular disease.

Principles of micro-ultrasound

In micro-ultrasound systems, sound waves are generated from transducers and then propagated through living tissues. Tissues reflect these sound waves which then come back to the transducer. The sound waves are then translated into two- and three-dimensional images. Micro-ultrasound techniques are very useful for research on small animals in frequency ranges of 15 to 80 MHz.

Applications of micro-ultrasound

• Helps study processes that occur over a period of time, for example, tumor volume changes and angiogenesis
• Dedicated platform for monitoring heart rate, ECG, respiration, and body temperature of animals
• Screening modality helps early detection of tumor of diameter 50 µm or above
• Helps to monitor tumor perfusion and velocity of blood flow
• Enables the micro-injection of drugs, stem cells, and other probes into tumors
• Observation of flow and capillaries in neoangiogenesis
• Targeted molecular imaging with the help of agents such as integrins and VEGFR
• Detection and measurement of cardiotoxicity as a result of cancer therapy

Strengths of micro-ultrasound

• Micro-ultrasound is a rapid, real time technique that captures data at a speed of around 1000 frames per second
• Micro-ultrasound units are portable and relatively cost-effective
• Using micro-ultrasound, it is possible to visualize high speed events in mice such as in vivo blood flow and cardiac function.
• It allows imaging resolution of up to 30 µm – thus making it possible to visualize tiny tumor vasculature
• There is no risk of radiation side-effects
• With the help of contrast agents, it is possible to increase image resolution to 3-5 µm
• A combination of microbubbles and markers enables visualization at the molecular level
• Its range of applications is on par with that of dual imaging techniques such as micro-MRI/PET.
• Micro-ultrasound devices enable access to raw data, which is usually not possible with commercial ultrasound systems

Weaknesses of micro-ultrasound

• The penetration depth of micro-ultrasound is limited compared to similar techniques such as micro-MRI, micro-PET, micro-CT, and micro-SPECT.
• The imaging depth decreases with increasing frequency; typical imaging depth of micro-ultrasound is about 3 cm under the skin, which is still adequate for small animals such as rats and mice.
• It is generally thought that ultrasound imaging quality depends on operator skills, but the more user-friendly devices available nowadays claim that this is not true.
• Contrast agents used in the micro-ultrasound technique usually cannot diffuse out of the tiny tumor vasculature, which is mostly a disadvantage. In some situations, it can be a good thing, as in angiogenesis and tumor perfusion imaging.

Commercial availability

Several micro-ultrasound devices are commercially available for research uses. For example, the ExactVu™ micro-ultrasound system from Exact Imaging is suitable for non-invasive, real-time, high-resolution prostate imaging and biopsy. According to the Exact Imaging’s president, the resolution of ExactVu is 300% more compared to conventional ultrasound platforms, as well as enabling imaging at 29 MHz during, for instance, transrectal biopsies.

Vevo Imaging systems also offers Vevo LAZR micro-ultrasound units that use photoacoustics for in vivo imaging of tiny animal models. LAZR micro-ultrasound is designed to work at a frequency range of 30–70 MHz. With a resolution of 30 µm, these may be ideal for long-term studies of rat and mice cancer angiogenesis.

References

1. https://www.exactimaging.com/videos/exactvu-micro-ultrasound-a-true-revolution-in-resolution
2. http://www.nature.com/app_notes/nmeth/2015/151404/pdf/nmeth.f.381.pdf
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262267/

Further Reading

• All Micro-Ultrasound Content
• Micro-Ultrasound in Cancer Research

Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.