High-amplitude ultrasound waves, generated outside the body, can be focused deep within tissue onto a region about the size of a grain of rice. In that region, conversion of the mechanical energy carried by the ultrasound wave into heat can lead to cell death by thermal necrosis, whilst leaving tissue outside the HIFU focal region unaffected. The potential of this technique to destroy deep-seated tumours non-invasively is currently being explored in the Clinical HIFU Unit at the Churchill Hospital in Oxford.
Contrast MR of a large tumour in the left kidney (left) and 12 days following HIFU treatment (right). Photo courtesy of the Clinical HIFU Unit, Churchill Hospital, Oxford.
The research being carried out in the IBME is aimed at further improving the speed, resolution, targeting and real-time monitoring of HIFU treatments, as applied to cancer therapy and to a range of novel HIFU applications. The laboratory is involved in research at all levels, ranging from the basic science of understanding cell death by ultasound-induced heating, to the clinical trials (in collaboration with the clinical HIFU unit) of novel methods for improved treatment delivery and treatment monitoring. The thermal dose that results in cell death, changes in the material properties of tissue in response to heating and ablation, and method.
One area of research is related to acoustic cavitation, a phenomenon that occurs when high amplitude acoustic waves propagating through tissue spontaneously nucleate and excite small, micrometre-sized bubbles. The presence of such bubbles at the HIFU focus has been shown to greatly enhance the local rate of heating. This excess heating can be exploited to reduce treatment times or, through the use of cavitation promoting agents, increase the specificity of HIFU therapy. In addition, the acoustic emissions associated with cavitation can be used to provide additional monitoring during a treatment. Work performed in excised tissue has shown that spatial localisation of cavitation events through a technique called passive acoustic mapping (PAM) provides a better means of discriminating whether or not a lesion has been formed. This is being utilized in several of the projects ongoing in BUBBL with the aim of enabling faster, safer procedures to be performed.
Ex-vivo Inertial cavitation mapping during 1.1 MHz HIFU using a commercial ultrasound probe (L10-5, Zonare Medical Systems). A lesion was formed whose location was well correlated with passive acoustic maps reconstructed from both the broadband and harmonic parts of the spectrum. These are considered to be representative of two regimes of cavitation, inertial and stable. In contrast, conventional assessment through detection of B-mode hyper-echo did not detect the lesion.
Lesions of different shapes and sizes created by a HIFU transducer in a polyacrylamide-BSA tissue-mimicking material.
A further area of interest pertains to the development of our understanding of heat-induced cell death. In 1984, Sapareto and Dewey proposed the thermal dose cumulative equivalent minutes (CEM) metric as a means of quantifying cell damage induced by mild heating. Even though the model provides a good descriptor at the temperatures and rates of heating encountered in mild hyperthermia (5-10 C above body temperature), its applicability in the context of the very high rates of heating and high temperatures achieved during ultrasound-induced ablation has yet to be demonstrated. Through the development of a broad range of cell-embedding tissue-mimicking materials, research carried out in BUBBL aims at acquiring a basic understanding of the limitations of the CEM model and at the development of adequate means of quantifying heat-induced damage under conditions relevant to HIFU therapy.
A third area of interest involves monitoring tissue ablation by tracking changes in material properties of the tissue. The current state of the art is MR guided HIFU but this involves delivering HIFU within an MR system, which is both expensive and technically challenging. Properties that are known to change when tissue is heated or ablated include its sound speed, acoustic attenuation, stiffness, optical and electromagnetic scattering, absorption and dielectric constants. We are developing various ultrasound or dual-wave modalities for imaging the changes in these properties such that ablation can be monitored in real time.