**6. Guiding/monitoring of therapy**

Therapy guidance is the key for a safe and effective HIFU. Guidance is accomplished mainly with two imaging methods which are US and MRI. Imaging techniques are used with HIFU therapy not only for therapeutic guidance but it allows also therapy planning and targeting, monitoring, controlling and assessing the treatment response and follow-up [22].

#### **6.1. Ultrasound monitoring**

causes no significant heating, but cavitation caused by this type of waves are used in some circumstances like enhancing a drug delivery or the transient opening of the blood-brain

The technique is based on the generation of focused ultrasound field. The focused ultrasound field is generated by a piezoelectric transducer with a center frequency of 1 to 7 MHz. The field is coupled into the body and aimed into a target region. Ultrasound waves are absorbed by tissues throughout their propagation and the acoustic energy will be converted to heat with a high energy density inside the focal zone [22]. The result is a temperature rise in the target zone within seconds to a level exceeding the threshold level of protein denaturation which is around 60 degrees. The result will be protein coagulation and coagulative necrosis [22-24]. In contrast there is a low acoustic energy density in the surrounding structures which keep them

Between sonication a pause is necessary to prevent boiling and bubbles formations which can reflects and distort the ultrasound field and the consequence is unpredictable lesion growth and lesion formation in unwanted areas. So to ablate a large solid tumor it can take several hours. Thus HIFU is a very time consuming procedure [22]. HIFU has the advantage over other thermal ablative techniques of being a mini-invasive and non-ionizing with no long-term cumulative effects which means that it could be safely repeated. Further more it is interesting non invasive surgical tool because it can cause cell death in a tissue that is distant from the

There are two main types of transducers used for HIFU. In general HIFU needs a high power ultrasound transducer. Such kind of transducers is made of low loss piezoceramic materials or piezocomposites working in resonant mode. The two major types are the self- focusing spherical shaped piezoceramic transducers with fixed aperture and fixed focal length which is the simplest, and the phased array transducers made up of a large number of separate transducer elements. Thereby each element is driven by a separate electric radio frequency signal with an individual phase, frequency and amplitude. The advantages of phased arrays are the possibility for an adaptive selection of elements, the fast electronic beam steering and the beam forming capability. Such transducers are much more expensive and the number of

On the other hands we can divide the transducers into extracorporeal used for the treatment of cutaneous and abdominal tumors, transrectal as those used for the prostate, and interstitial

elements in such transducers can reach thousands in some special cases [22].

and endoscopic ones used for the treatment of biliary or esophageal lesions [24].

. Larger volume can be

**4. Mechanisms of action of high intensity focused ultrasound**

spared. This will create elliptical small volume lesions of 50-300 mm3

ablated without gaps by combining single lesions.

barrier [22].

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source of US [23].

**5. Clinical devices in use**

This is the case of most today's HIFU treatment. In general the divergent field of the diagnostic transducer and the field of therapeutic source are superposed and arranged in parallel so that the diagnostic imager provides the beam view. This eases the positioning of the therapeutic source and the identification of organ at risk [22]. Real-time visualization of the targeted volume is feasible with decoupling of US image and focused US.

US are able to detect cloud of gas bubbles that are formed as results of cavitation and tissue heating. The detection of bubble could be an indication for the position of the thermal focus, but this cannot be used to assess and control lesion formation.

US are not able to perform temperature mapping. Some try to use some parameters such as speed of sound, or attenuation or reflection coefficient as indicators for temperature variations, but with modest success.

The major advantages of US are, first they share same physical mechanism so a good assess‐ ment of the beam pass is possible. Then it allows the use of conventional materials for the therapy unit so that the diagnostic US transducer can be easily integrated in the therapeutic source that allows for a small and flexible devices with lower prices [22].

#### **6.2. MR-monitoring**

The advantages of MRI over US are the capacity of giving a morphological image for planning, targeting and thermal monitoring. It can also assess the shape and size of the induced tissue lesion at the end of therapy. Contrast enhanced T1 imaging are employed. The induced lesions prove hypointense reflecting the loss of perfusion. Major disadvantage is the need for an MR compatible HIFU therapy unit and the cost of the MR scanner. Limitations are the confined space for patient access and the need of a complex and expensive technology [22].

#### **6.3. MR thermometry**

A different method exists to measure the temperature related changes with the MR. Mainly four methods have been described: T1, diffusion, proton density, and proton resonance frequency shift. The most frequently used method is the proton resonance frequency shift (PRFS). The proton resonance frequency shift can be measured directly or by phase mapping which consists of observing the phase shift induced by temperature change. Phase mapping is easier to do than direct assessment. Therefore phase mapping is the most common approach used for temperature mapping [22].
