Heat and sound: focused ultrasound in the clinic

In the current world financial climate, there is a drive towards more cost-effective, patient oriented treatments for many diseases. To this end there has been considerable interest in developing non-invasive therapies that have the potential to allow patients to be treated as day cases, thus reducing hospital in-patient costs. High intensity focused ultrasound (HIFU) represents one such therapy. The adoption of such techniques, which in themselves may be cheaper alternatives to those already existing, depends in large measure on the ability of healthcare providers to invest in the devices necessary to deliver these treatments.

In order to convince the clinical and administrative communities of the utility, cost-effectiveness and importance of a new procedure, it is important to provide an evidence base that comes from multi-centric prospective clinical trials. In this special issue, the growing evidence for the clinical utility of HIFU is presented, with papers coming from some of the foremost groups who are performing patient treatments.

High intensity focused ultrasound

A commonly used analogy for HIFU is that of a magnifying glass used to focus the sun’s rays to set light to dry tinder. This can only be achieved when the focus lies on the dry material, and in no other position in the beam produced by the lens. Ultrasound can also be brought to a tight focus, and it has been known for several decades that if the focus is placed at depth within tissue, localised thermal necrosis can be achieved with no damage to overlying or surrounding tissues. In practice, the thermal dose required to achieve thermal ablation (240 cumulative equivalent minutes) can be achieved in a few seconds (equivalent to temperatures of 56 °C for 1 s) [1].

HIFU is subject to many of the same constraints as diagnostic ultrasound. Since ultrasound will not propagate through gas or bone, tissue targets in the lung, or lying behind bone or the gas-filled bowel, are not readily accessible. As a rule of thumb, tissues that can be imaged with ultrasound can be targeted with HIFU, provided appropriate transducers (energy sources) are used. For tissue volumes that are accessible in this way, HIFU has the advantage that it is non-invasive since it can be delivered using an extra-corporeal source. This is not true of other thermal ablation techniques which require the insertion of a probe if deep-seated targets are to be ablated. It has been shown histologically that HIFU-induced thermal ablation is very selective with a margin between live and dead tissue that is only a few cells wide. In order to take full advantage of this precision, it is essential to use state of the art imaging techniques such as magnetic resonance imaging (MRI) or ultrasound (US) both for placing the focus, and for monitoring ablation. In this issue, clinical results are presented, with contributions from users of both ultrasound and magnetic resonance imaging guidance. Each method is associated with its own techniques, advantages and disadvantages.

Intuitively, it would seem most appropriate to use US for the imaging guidance since it might be expected to be comparatively simple to incorporate imaging and therapy into a single integrated treatment head, thus creating a stand-alone unit. Ultrasound imaging has the advantage of being real-time, but as yet no ultrasonically based method of determining temperature or thermal dose has been implemented clinically [2,3]. Instead, successful ablation is indicated by the appearance of bright echoes on the US scan, indicative of tissue water boiling. MRI has the advantage that thermometry sequences which allow quasi-real-time maps exist of temperature or thermal dose to be super-imposed on anatomical images during treatment [4]. The main disadvantage of MRgHIFU is that a treatment ties up a clinical scanner for a significant length of time. This can be a problem in a busy hospital whose scanner is also used for clinical imaging. Additionally, some tumours may prove inaccessible, simply because of the restricted space in the bore of a conventional MR scanner. If HIFU is to become more widespread, it may be that wide bore systems should be the MR scanners of choice.

To date, the most widely used application of extra-corporeal HIFU has been for the ablation of uterine fibroids [5,6], with more than 20,000 treatments having been carried out (FUF). The other non-cancer applications being explored clinically are in the eye (for the treatment of glaucoma [7], the brain (for example, for the treatment of essential tremor and other neurological conditions) and in the thyroid [8]. These applications are reviewed by O’Reilly & Hynynen in this issue [9]. The interest in using HIFU for cancer treatments is growing rapidly, with the organ that has been targeted most frequently being the liver. Despite the problems presented by passing the HIFU energy through the rib cage, and of abdominal motion, more than 10,000 patients with primary and secondary liver disease have been treated, almost exclusively under USgHIFU, and mostly outside a clinical trial setting. Motion compensation techniques are being developed to overcome the movement of abdominal organs caused by breathing and cardiac motion [10].

It has been recognised that, while ultrasound is highly attenuated by bone, the use of sophisticated techniques such as time reversal allows the recovery of the focus after the beam has been scattered during transit through the skull [11]. This means that focal ablation of selected regions in the brain, such as, for example, the ventral intermediate thalamus for the treatment of essential tremor, has become possible under MR guidance [12]. Here the non-invasive, highly localised ablation ability of HIFU really becomes a reality.

The strong reflection and high absorption of ultrasound by bone can also be used to therapeutic advantage since high temperatures can be achieved very locally at the periosteal surface. This is being used to cause neurolysis to palliate the pain caused by bone metastases [13,14]. More than 1000 such patients have now been treated [15]. Where it has broken through the cortex, ablative treatment of a bone tumour may also be possible.

It is not always necessary to use HIFU at full power. There is now a large body of evidence to show that not only can HIFU be used to induce hyperthermia, but also, when gas filled microbubbles are present, its mechanical action can enhance drug delivery and cause a temporary opening of the blood–brain barrier [9,16].

It is an exciting time for clinical HIFU. It appears that we are on the brink of many new applications that may lead to its far more widespread use. Once more clinical trial evidence has been accrued, and if the initial indications of benefit in terms of palliation, quality of life and overall survival can be proven, then it will be time to push those with spending power in the healthcare industries to take HIFU seriously and provide more facilities. According to the Focused Ultrasound Foundation, in 2013 there were 382 commercial sites around the world, 29 in the USA, 202 in Europe, 142 in Asia [15]. The number of manufacturers of devices had risen from five in 2000, to 22 (with seven in the USA, 10 in Europe and five in Asia) in that time. HIFU is on the move!

Declaration of interest

The author report no conflicts of interest. The authors alone are responsible for the content and writing of this article.