A team of scientists at The Institute of Cancer Research, London, has developed a repeatable three-dimensional (3D) imaging technique that could transform preclinical cancer studies. The researchers have demonstrated that a specialised form of ultrasound imaging, which maps tissue stiffness, can reliably measure mechanical changes in cancerous lesions, even under challenging real‑world conditions.
Increased tissue stiffness is associated with cancer, and tumours often become stiffer both as they grow and as their internal structure transforms. These mechanical changes can influence how cancers respond to treatment and how they spread.
For years, researchers have sought imaging tools sensitive enough to detect subtle differences in stiffness in animal models. The new study confirms that a technique called vibrational shear wave elastography (VSWE), which is being developed at The Institute of Cancer Research (ICR), may meet that need.
The study findings, published in the journal Physics in Medicine & Biology, could pave the way for more consistent use of biomechanical imaging in the early testing of cancer therapies. This research was supported by Cancer Research UK.
Why tumour stiffness matters in cancer research
When tumours stiffen, it is often because the extracellular matrix – the dense scaffold surrounding cancer cells – becomes thicker or more crosslinked. These changes can reduce the delivery of oxygen and anti‑cancer drugs, impede immune cell movement and, ultimately, make tumours more aggressive. Being able to measure stiffness non‑invasively allows researchers to understand these processes over time and to assess whether treatments are successfully reversing harmful mechanical changes.
Ultrasound shear wave elastography has become a mainstay technique in human medicine, where it is used to evaluate liver disease and breast lesions. However, applying the method to preclinical research is much more challenging. Small tumours – often only a few millimetres across – sit close to the skin and move with every breath the animal takes. These factors can affect measurement repeatability.
The team behind the new study sought to address this by using continuous harmonic vibrations delivered externally, rather than traditional ultrasound-generated “push” pulses. This external vibration approach offers better control of frequency and amplitude, making it potentially more reliable in tiny structures.
Testing consistency across real‑world conditions
The researchers implanted human breast cancer cells into the flanks of four mice. Once tumours reached about 500 cubic millimetres in size, each mouse underwent a series of imaging sessions across three consecutive days. During each session, the team varied three key conditions that could affect repeatability: vibration frequency, tumour orientation and type of anaesthesia (both of which can affect breathing motion).
The aim was to test not only how repeatable the measurements were, but also how much each practical variable altered the results.
To obtain 3D images, a high-frequency ultrasound probe was moved across the tumour, capturing a “stack” of slices that could be reconstructed into a full volumetric map of shear wave speed (SWS). Higher wave speeds indicate stiffer tissue.
Vibration frequency strongly influenced the results
Across the 138 datasets collected, the researchers found several notable patterns.
Firstly, they noted that measurements at 500 Hz showed the lowest variability and most consistent penetration of shear waves. At 1,000 Hz, variability increased substantially because the higher-frequency waves attenuated too quickly, reducing data quality.
The other two variables – anaesthesia and tumour orientation – had less effect on repeatability, and the researchers were able to conclude that differences in these factors did not significantly affect the stiffness measurements.
Importantly, the study showed that stiffness differences between tumours were clear and consistent. A statistical analysis confirmed significant variations in stiffness between different tumours, meaning that VSWE was able to repeatedly detect differences rather than image distortions caused by environmental interference.
In addition, the method produced highly correlated 3D maps across multiple days when scanning the same tumour under similar conditions. Spatial patterns remained stable despite growth in tumour size, confirming the technique’s reliability for longitudinal studies.
What this means for future cancer research
The study provides compelling evidence that VSWE can be used reliably to monitor how tumours respond to treatment over time. The technique’s resilience to breathing motion is particularly encouraging, as this is difficult to control perfectly in animal studies.
The findings also highlight the value of using the external vibration in preclinical elastography. Although higher frequencies promise greater spatial resolution, lower frequencies are better suited to tumour tissues that attenuate shear waves more strongly.
A promising tool for the preclinical imaging toolkit
As researchers increasingly focus on the mechanical environment of tumours – both as a biomarker and as a therapeutic target – the need for reliable, repeatable biomechanical imaging grows. The new findings suggest that VWSE, with its tuneable vibration frequencies, may become a cornerstone method for tracking how tumours evolve and respond in vivo.
First author John Civale, Senior Scientific Officer in the Division of Radiotherapy and Imaging at the ICR, said: “We were reassured to see just how robust the method proved to be. Despite the complexities of imaging tiny tumours in living animals, the day‑to‑day consistency of the measurements was remarkably strong.
“We’re now looking at ways to incorporate more sophisticated image‑registration methods that account for changes in tumour size and shape. This will help us detect even more subtle biomechanical changes during treatment.”
Senior author Dr Emma Harris, Group Leader of the Imaging for Radiotherapy Adaptation Group at the ICR, said:
“This study represents an advance on other repeatability studies where usually only mean values of shear weave speed are reported. Our results therefore provide a benchmark for other elastography studies.
“Once further refined, our technique could, if adopted more widely, accelerate the development of treatments aimed at altering tumour stiffness, improving drug delivery and ultimately improving outcomes for patients."
Image credit: Pete Linforth from Pixabay