High frequency ultrasound vibrational shear wave elastography for preclinical research

Abstract

Preclinical evaluation of novel therapies using models of cancer is an important tool in cancer research, where imaging can provide non-invasive tools to characterise the internal structure and function of tumours. The short propagation paths when imaging tumours and organs in small animals allow the use of high frequencies for both ultrasound and shear waves, providing the opportunity for high-resolution shear wave elastography and hence its use for studying the heterogeneity of tissue elasticity, where heterogeneity may be a predictor of tissue response. Here we demonstrate vibrational shear wave elastography (VSWE) using a mechanical actuator to produce high frequency (up to 1000 Hz) shear waves in preclinical tumours, an alternative to the majority of preclinical ultrasound SWE studies where an acoustic radiation force impulse is required to create a relatively low-frequency broad-band shear-wave pulse. We implement VSWE with a high frequency (17.8 MHz) probe running a focused line-by-line ultrasound imaging sequence which as expected was found to offer improved detection of 1000 Hz shear waves over an ultrafast planar wave imaging sequence in a homogenous tissue-mimicking phantom. We test the VSWE in an ex vivo tumour xenograft, demonstrating the ability to detect shear waves up to 10 mm from the contactor position at 1000 Hz. By reducing the kernel size used for shear wave speed estimation to 1 mm we are able to produce shear wave speed images with spatial resolution of this order. Finally, we present VSWE data from xenograft tumours in vivo, demonstrating the feasibility of the technique in mice under isoflurane sedation. Mean shear wave speeds in the tumours are in good agreements with those reported by previous authors. Characterising the frequency dependence of shear wave speed demonstrates the potential to quantify the viscoelastic properties of tumours in vivo.