28 May 2014

Histotripsy – surgery without a scalpel

Ultrasound cuts to the quick

Vladimir Koryagin, <url>How ultrasound can be used to perform surgical operations on a living organism without damaging the skin, scientists from the USA and Russia have found out in a joint work.

The lead author of the study, Tatiana Khokhlova, a graduate of the physics department of Moscow State University, now working in Seattle, told the newspaper.En" details of this work.

– You are the lead author of an article published recently in the journal Proceedings of the National Academy of Sciences on surgery using ultrasound (Khokhlova et al., Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model). What is the main conclusion of this work?

– In this work, we implemented for the first time the method of boiling histotripsy (from the Greek words histos (tissue) and tripsis (rubbing, crushing) – mechanical destruction of tissue during formation in it under the influence of ultrasound. - "Newspaper.Ru") on a live model – in a pig's liver.

It has been shown that local destruction of soft tissues by ultrasound into subcellular fragments is possible in a living organism, this is the main conclusion of the work.

In addition, it turned out that this process has selectivity by tissue type: structures with a high content of collagen (i.e. blood vessels, bile ducts, etc.) are more resistant to ultrasound than cellular components. This is extremely important both in the clinical implementation of this method for mechanical ablation (in medicine, the term "ablation", in fact, is an analogue of surgical removal. - "Newspaper.Ru") soft tissues – you can not be afraid of damage to, say, a large blood vessel directly bordering the area of destruction – and in bioengineering applications, because it provides a simple and convenient opportunity for decellularization (that is, the process of getting rid of parent cells. - "Newspaper.Ru") fabrics for the manufacture of biocompatible frames. The results of this work open up a fundamentally new direction in ultrasound surgery in particular and in therapeutic methods in general and have aroused great interest and enthusiasm among physicians.

– What methods were used in this case? What is your direct contribution?

– A special type of pulsed ultrasound exposure was used in the work, which we call boiling histotripsy: high-intensity, but very short (millisecond duration) shock wave ultrasonic pulses are focused inside the biological tissue, as a result of which local tissue boiling occurs in the focus, a millimeter-sized steam cavity is formed. The interaction of ultrasound with this cavity leads to the destruction of the biological tissue around it into subcellular components no larger than the cell nucleus. In our work, boiling histotripsy was used to create single destructions in live pig liver at different depths and at different distances from large blood vessels, after which liver samples containing destruction were processed for histological studies.


A snapshot from an article in PNAS – VM.

My contribution consists in the preparation and optimization of the irradiation protocol and the direct execution of the boiling histotripsy regime in this study, as well as in the analysis of histology results and the preparation of the article.

– How can ultrasound ablation be used? What are the pros and cons of using it?

– The main advantages of ultrasound ablation are the complete non-invasiveness of the method and the absence of ionizing effects. The disadvantages of thermal ablation are its high cost, due to the most commonly used method of monitoring such effects (MRI thermometry), as well as the danger of overheating of intermediate tissues - ribs and skin. The histotripsy method has not yet been introduced into clinical practice, but it can potentially solve many problems that exist in thermal ablation and be used in the same tasks. The monitoring method is ultrasound, since the formed vapor bubbles are clearly visible on ultrasound, it is much cheaper and easier than MRI. There is practically no thermal effect, so you don't have to worry about burns to the ribs or skin. Selectivity by tissue type I have already mentioned. I consider the most promising applications to be those in which the ground, liquid tissue can be removed from the body naturally, for example, during ablation of tumors in the kidneys or prostate gland.

The presence of subcellular components of the tumor in the body is very important for stimulating the immune response, which can contribute to healing, for example, resorption of metastases. This aspect of histotripsy opens up fundamentally new possibilities in cancer therapy, and now we are investigating the mechanism of such an immune response.

In addition, we are currently working on a method of non–invasive biopsy using histotripsy - point mechanical destruction of tissue in order to release biomarkers of cancer or other diseases into the circulation. Following such an impact, a blood test will allow you to diagnose the disease with high accuracy and, possibly, choose an effective treatment method.

As for the disadvantages, then, as in any non-invasive treatment, a reliable way is needed to confirm that all cells in the volume of tissue to be destroyed are indeed destroyed. In particular, our future works will be devoted to this.

– What are the prospects for the direction to which this work is devoted?

– I have already noted some medical areas in which the method of mechanical ultrasound ablation has advantages. There is also an important bioengineering direction – the creation of decellularized biocompatible skeletons from animal tissues. Due to the selectivity of histotripsy by tissue type and the preservation of structures with a high collagen content, it is possible to significantly simplify the decellularization of tissues for such skeletons simply by ultrasound ablation.

– Where were the surveys conducted? Did Russian institutions help you, or did you work only abroad?

– I graduated from the graduate school of Physics at Moscow State University, but now I work at Washington State University. Work in the field of ultrasound surgery and, in particular, histotripsy has been carried out for more than 15 years in close cooperation with the Department of Acoustics of the Faculty of Physics of Moscow State University. These are works on numerical modeling of the irradiation process, the development of methods for characterizing sources for ultrasonic ablation, the study of physical mechanisms, joint experiments.

Portal "Eternal youth" http://vechnayamolodost.ru28.05.2014

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