High frequency ultrasound vibrational shear wave elastography for preclinical research.

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 anex vivotumour 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 tumoursin 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 tumoursin vivo.

Treatment monitoring and thermometry for therapeutic focused ultrasound.

Therapeutic ultrasound is currently enjoying increasingly widespread clinical use especially for the treatment of cancer of the prostate, liver, kidney, breast, pancreas and bone, as well as for the treatment of uterine fibroids. The optimum method of treatment delivery varies between anatomical sites, but in all cases monitoring of the treatment is crucial if extensive clinical acceptance is to be achieved. Monitoring not only provides the operating clinician with information relating to the effectiveness of treatment, but can also provide an early alert to the onset of adverse effects in normal tissue. This paper reviews invasive and non-invasive monitoring methods that have been applied to assess the extent of treatment during the delivery of therapeutic ultrasound in the laboratory and clinic (follow-up after treatment is not reviewed in detail). The monitoring of temperature and, importantly, the way in which this measurement can be used to estimate the delivered thermal dose, is dealt with as a separate special case. Already therapeutic ultrasound has reached a stage of development where it is possible to attempt real-time feedback during exposure in order to optimize each and every delivery of ultrasound energy. To date, data from MR imaging have shown better agreement with the size of regions of damage than those from diagnostic ultrasound, but novel ultrasonic techniques may redress this balance. Whilst MR currently offers the best method for non-invasive temperature measurement, the ultrasound techniques under development, which could potentially offer more rapid visualisation of results, are discussed.