John Civale

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.

Quality assurance for clinical high intensity focused ultrasound fields.

Abstract As the use of HIFU in the clinic becomes more widespread there is an ever increasing need to standardise quality assurance protocols, an important step in facilitating the wider acceptance of HIFU as a therapeutic modality. This article reviews pertinent aspects of HIFU treatment delivery, encompassing the closely related aspects of quality assurance and calibration. Particular attention is given to the description and characterisation of relevant acoustic field parameters and the measurement of acoustic power. Where appropriate, recommendations are made.

Attenuation Estimation and Temperature Imaging Using Backscatter for Extracorporeal HIFU Treatment Planning

For HIFU to be widely applicable in the clinic, problems relating to treatment planning, delivery and monitoring need to be resolved. The characterisation of the acoustic and thermal properties of specific tissues is an important pre‐requisite to determining the optimal exposure parameters for individual treatments. We describe a preliminary evaluation of two methods that may be of use in deriving such planning information prior to HIFU. Both methods have been implemented on a diagnostic ultrasound scanner. One is backscatter attenuation estimation (BAE), which uses pulse‐echo data and an axial beam translation substitution method to estimate the average attenuation coefficient of tissue overlying the region to be treated. The second method is backscatter temperature imaging (BTI) applied to a non‐lesioning test exposure, which is normally used to determine the focal position but here the observed peak temperature rise is employed to provide an estimate of all case‐specific losses involved in delivering a...

Noninvasive high-intensity focused ultrasound treatment of twin-twin transfusion syndrome: A preliminary in vivo study

High-intensity focused ultrasound can ablate blood flow in the sheep placenta and may be translatable to human twin-twin transfusion syndrome. Splitting the babies Twin-twin transfusion syndrome is a complication of some twin pregnancies, where abnormal connections between the twins’ placental blood vessels result in unequal sharing of blood flow, with potentially lethal consequences. Although it is possible to separate the twins’ vasculature using fetoscopic laser occlusion of the connecting blood vessels, it is an invasive treatment with a high risk of complications. Shaw et al. used a sheep model of pregnancy to demonstrate the feasibility and relative safety of using high-intensity focused ultrasound to ablate blood flow through individual placental vessels. The authors used only healthy pregnant sheep, and the procedure still required surgical intervention to reach the uterus, but this approach may eventually offer a safer treatment alternative for human patients. We investigated the efficacy, maternofetal responses, and safety of using high-intensity focused ultrasound (HIFU) for noninvasive occlusion of placental vasculature compared to sham treatment in anesthetized pregnant sheep. This technique for noninvasive occlusion of placental vasculature may be translatable to the treatment of conditions arising from abnormal placental vasculature, such as twin-twin transfusion syndrome (TTTS). Eleven pregnant sheep were instrumented with maternal and fetal arterial catheters and time-transit flow probes to monitor cardiovascular, acid-base, and metabolic status, and then exposed to HIFU (n = 5) or sham (n = 6) ablation of placental vasculature through the exposed uterine surface. Placental vascular flow was occluded in 28 of 30 targets, and histological examination confirmed occlusion in 24 of 30 targets. In both HIFU and sham exposures, uterine contact reduced maternal uterine artery flow, but delivery of oxygen and glucose to the fetal brain remained normal. HIFU can consistently occlude in vivo placental vessels and ablate blood flow in a pregnant sheep model. Cardiovascular and metabolic fetal responses suggest that the technique is safe in the short term and potentially translatable to human pregnancy.

Optimising HIFU Lesion Formation with Backscatter Attenuation Estimation (BAE)

Ultrasound attenuation is an important dosimetric factor for HIFU treatments of soft tissue tumours. During clinical HIFU treatments ultrasound attenuation in the tissue overlying the focal volume leads to a loss in intensity. In clinical treatments at the Royal Marsden Hospital (UK), ultrasound attenuation is currently estimated using published tissue attenuation coefficients and the thickness of tissue layers determined from diagnostic ultrasound images. This method gives an inaccurate estimate of attenuation. Therefore to improve the delivery of HIFU, a better measurement of attenuation is required. Methods have been investigated for eventual clinical use in estimating the attenuation coefficient of the liver in vivo, immediately prior to HIFU treatment, using backscattered ultrasound pulses. Radio frequency (RF) echo signals were acquired using a clinical ultrasound scanner working with a linear array probe. The data required for diffraction correction of these estimates is a set of RF images obtained...

Quality assurance and field characterisation for MRgHIFU treatments: their need and the challenges presented

In our drive to increase the clinical recognition of HIFU treatments, it is important that we pay attention to other comparable, but more widely accepted, therapeutic techniques, and match their rigorous quality assurance and calibration practices. Well validated Quality Assurance (QA) and field characterisation techniques are important in order that treatments can be planned and simulated, and so they may be compared between patients, between centres and between machines. There is still some discussion as to which the most relevant parameters for such comparisons are. While the pressure distribution and total power can be measured with reasonable accuracy in the laboratory, the presence of the high magnetic fields in the vicinity of an MR scanner render many of the current equipment unuseable. It is therefore important to develop techniques appropriate for MRgHIFU systems that work within the restricted space available.

Development of a Hybrid Magnetic Resonance and Ultrasound Imaging System

A system which allows magnetic resonance (MR) and ultrasound (US) image data to be acquired simultaneously has been developed. B-mode and Doppler US were performed inside the bore of a clinical 1.5 T MRI scanner using a clinical 1–4 MHz US transducer with an 8-metre cable. Susceptibility artefacts and RF noise were introduced into MR images by the US imaging system. RF noise was minimised by using aluminium foil to shield the transducer. A study of MR and B-mode US image signal-to-noise ratio (SNR) as a function of transducer-phantom separation was performed using a gel phantom. This revealed that a 4 cm separation between the phantom surface and the transducer was sufficient to minimise the effect of the susceptibility artefact in MR images. MR-US imaging was demonstrated in vivo with the aid of a 2 mm VeroWhite 3D-printed spherical target placed over the thigh muscle of a rat. The target allowed single-point registration of MR and US images in the axial plane to be performed. The system was subsequently demonstrated as a tool for the targeting and visualisation of high intensity focused ultrasound exposure in the rat thigh muscle.

Cavitation Detection Using a Fibre‐Optic Hydrophone: A Pilot Study

A fibre‐optic hydrophone has been used to detect broadband acoustic emissions associated with inertial cavitation activity. Its potential for this application has been investigated in tap water and in agar gels, and compared with signals from a passive cavitation detector (PCD) and a microphone detecting audible frequency emissions. Processing of the fibre‐optic hydrophone data to find the total RMS voltage over an integrated frequency range of 15–20 MHz gives a high signal to noise ratio, comparable with that of the PCD. The sensitivity and effective field of view of the fibre tip appear sufficient for detecting even low level cavitation activity, however the precise directional response has yet to be assessed. Emissions from acoustic cavitation in tap water and agar gel from peak negative pressures reaching 5.8 and 3.5 MPa respectively were detectable when the fibre was up to 20 mm and 2 mm respectively from the acoustic axis, whilst retaining a high signal to noise ratio.

On measurement of the acoustic nonlinearity parameter using the finite amplitude insertion substitution (FAIS) technique

The acoustic nonlinearity parameter, B/A, is an important parameter which defines the way a propagating finite amplitude acoustic wave progressively distorts when travelling through any medium. One measurement technique used to determine its value is the finite amplitude insertion substitution (FAIS) method which has been applied to a range of liquid, tissue and tissue-like media. Importantly, in terms of the achievable measurement uncertainties, it is a relative technique. This paper presents a detailed study of the method, employing a number of novel features. The first of these is the use of a large area membrane hydrophone (30 mm aperture) which is used to record the plane-wave component of the acoustic field. This reduces the influence of diffraction on measurements, enabling studies to be carried out within the transducer near-field, with the interrogating transducer, test cell and detector positioned close to one another, an attribute which assists in controlling errors arising from nonlinear distortion in any intervening water path. The second feature is the development of a model which estimates the influence of finite-amplitude distortion as the acoustic wave travels from the rear surface of the test cell to the detector. It is demonstrated that this can lead to a significant systematic error in B/A measurement whose magnitude and direction depends on the acoustic property contrast between the test material and the water-filled equivalent cell. Good qualitative agreement between the model and experiment is reported. B/A measurements are reported undertaken at (20 ± 0.5) °C for two fluids commonly employed as reference materials within the technical literature: Corn Oil and Ethylene Glycol. Samples of an IEC standardised agar-based tissue-mimicking material were also measured. A systematic assessment of measurement uncertainties is presented giving expanded uncertainties in the range ±7% to ±14%, expressed at a confidence level close to 95%, dependent on specimen details.

A Comparison of Real‐time Feedback and Tissue Response to Ultrasound‐Guided High Intensity Focused Ultrasound (HIFU) Ablation using Scanned Track Exposure Regimes

Real time ultrasound monitoring of tissue ablation in clinical HIFU treatments currently depends on the observation of the appearance of new hyperechoic regions within the target volume, allowing visually directed treatment. These grey‐scale changes are attributed to the formation of gas or vapour bubbles. In this study, scanned track lesions have been formed in ex vivo bovine liver samples at a range of ablative intensities (free field spatial peak intensities 7 – 47 kW cm−2), and tracking speeds (1–2 mms−1). Their appearance on conventional B‐mode ultrasound images has been assessed using digital imaging techniques over the first 60 seconds following HIFU exposure. The size of the lesion as seen on the ultrasound scan is compared to the macroscopic size of the lesion at dissection. It is seen that the lesion size is highly dependent on the intensity and scanning speed of the transducer. Reliable lesions can be created using scanned tracks at the lowest powers, with increased numbers of cycles, and grey‐...