High Intensity Focused Ultrasound (HIFU, focused ultrasound knife) was proposed by Lynn in the 1940s and was used in experiments to destroy target tissue in the nervous system of animals with the characteristics of rapid visualization and little damage to surrounding tissues. However, due to the limitations of engineering technology at the time, this technology was not developed further. In the last decade of the last century, with the rapid development of computer technology and high-definition imaging technology, once again set off a wave of HIFU research, and took the lead in China to complete the industrialization of the device, and now China is at the forefront of the clinical application of HIFU in the world. The HIFU system integrates image, positioning, control and focus in one, which firstly locates the tumor tissue by ultrasound probe and outlines its contour during the treatment. –Then, under the automatic control of the computer, the ultrasound transducer can precisely focus the ultrasound energy on the deep tumor tissue (3000W/cm2, equivalent to 30,000-50,000 times of the diagnostic ultrasound) to produce instant high temperature (≥65℃), thus causing immediate coagulation and necrosis of the tumor tissue. The HIFU system can adopt the “nibbling method” of superimposing dots into lines, lines into planes, and planes into body shapes according to the actual contour of tumor tissues, and cauterize tumors point by point under real-time monitoring. Experiments have proved that it only takes 0.25 seconds to kill any tumor cells at 65℃～70℃, so HIFU has softened the requirement of heat therapy on the temperature of the treatment area, and really achieved high temperature, high efficiency and non-invasive. I. Mechanism 1. Thermal effect: Thermal effect is the main effect of HIFU for tumor treatment. Ultrasound is a kind of mechanical wave with strong penetrating power, and after entering into the body, due to friction, viscous loss, heat conduction loss and molecular hesitation process, it continuously transforms part of the ordered ultrasonic vibration energy into disordered molecular thermal motion energy, which can produce instant high temperature at the focal point and inactivate the tissue; 2. tissue can make a large number of microbubbles, these microbubbles with the ultrasound cycle and rapid and violent expansion and compression, until the burst collapse, resulting in high temperature and high pressure, and issued a powerful shock wave, this is the cavitation effect. As the tissue damage caused by the cavitation effect is unpredictable and uncontrollable, the thermal effect damage must be accurately grasped during HIFU treatment to avoid the cavitation effect as much as possible. A large number of experimental studies and clinical practice have shown that HIFU treatment can be used as long as the target tissue temperature exceeds the lethal temperature, unrestricted increase in its absolute temperature is not only unnecessary, but harmful; 3, immune effect: HIFU can promote the release of some tumor antigens while inactivating tumor cells, thus promoting the specific and non-specific anti-tumor immunity of the host. II. Equipment The current HIFU devices are divided into transrectal type and in vitro type 1. Transrectal type: It is used for the treatment of prostate diseases (prostate cancer, BPH). The Sonablate 500 from Focus Sugery and the Ablatherm Integrated Imaging from Edap are of this type. This type of device is expensive, treats a single disease, and is mostly used in developed countries in Europe and the United States, and has a clearer efficacy on prostate cancer. 2.In vitro type: The ultrasound is focused on the tumor in vivo completely outside the body, and is divided into ultrasound-guided and magnetic co-core-guided according to the monitoring and guiding method. (1) Ultrasound-guided type: all the commercial machines are produced in China, and the ultrasound probe in the center of the treatment probe is like a rifle’s collimator, which is responsible for tumor localization. (1) JC series products of Chongqing Hefu Company adopt arc surface self-focusing combined with concave lens focusing method, with high acoustic power, obvious local effect, treatment completed at one time, real-time monitoring during treatment, but strong pain is produced during treatment and general anesthesia is required; (2) FEP-BY series products of Beijing Yuande Company adopt hundreds of small planar transducers arranged by arc surface and pulse emission, with no obvious pain during treatment and no anesthesia is required. The HIFUNIT9000 series of Shanghai Aishen Company adopts multi-faceted dual focus, the treatment probes can be freely combined, the focus efficiency is high, and for the first time in the world, the top-mounted dry treatment probe is used, the patient takes a comfortable lying position during treatment, the treatment can be monitored in real time, the patient has no obvious pain, and larger tumors can also be treated in stages. It is the first time in the world to adopt top-mounted dry treatment probe. Ultrasound-guided focused ultrasound is simple in structure and can take advantage of ultrasound dynamic observation, but its biggest limitation is that it cannot measure the immediate temperature of the target area without loss and accurately, and thus cannot quantify the degree of damage to the target area. (2) Magnetic resonance-guided (MRI-HIFU): The ExAblate2000 from Insightec, Israel, integrates 1.5T MRI and phased-array ultrasound transducer into one unit, and the temperature of the target area can be reflected by the temperature map of MRI during treatment [3], and it can be moved to the next focus if the treatment temperature has been reached, and continue to increase the temperature if the temperature is low. The ExAblate2000 has been approved by the United States for the treatment of uterine fibroids. Clinical application 1. Indications: At present, extracorporeal HIFU has been widely used in the treatment of solid tumors in the abdomen and pelvis, such as pancreatic cancer, liver cancer, kidney cancer, retroperitoneal tumors, uterine fibroids, ovarian cancer, prostate cancer, metastatic tumors in the abdomen and pelvis, breast cancer and osteosarcoma, which are more widely used in pancreatic cancer, retroperitoneal tumors and uterine fibroids; 2. The clinical application of HIFU is currently limited to the following Situations: (1) advanced tumors that cannot be surgically removed; (2) tumors that cannot tolerate surgery due to the patient’s advanced age, frailty or many comorbidities; (3) tumors that recur or metastasize after surgery and are not suitable for re-operation; (4) patients who firmly refuse surgery. 3. Contraindications: Due to the physical characteristics and focusing principle of ultrasound, tumors in the following organs or parts are not suitable for HIFU treatment: tumors of gas-containing cavity organs, such as lung cancer and intestinal cancer; tumors of the central nervous system; tumors less than 1 cm from the epidermis or tumors that have infiltrated the epidermis, in addition, if the on-board ultrasound cannot clearly show the tumor, or if there is bone or gas-containing tissue in the ultrasound beam incidence channel, they are also not suitable for HIFU treatment. Hepatocellular carcinoma: Most of the liver is under the obstruction of the rib cage, and only part of the left lobe of the liver is not obstructed. Since it is difficult for ultrasound to pass through bone tissue, if HIFU is used to treat right lobe liver cancer, the few ultrasound waves that pass through the rib cage are not enough to produce a focused heating effect, and the rib cage will be in severe pain due to the high-energy ultrasound waves. Some physicians adopt the method of removing part of the rib to increase the acoustic window, although the operation itself is not very traumatic, but still difficult for patients to accept. Some scholars have reported that HIFU treatment after TACE for liver cancer can achieve higher survival than TACE alone because the tumor blood vessels are closed first and its heat dissipation function is reduced. It is generally believed that there are many other minimally invasive ablation methods for hepatocellular carcinoma, all of which have clear efficacy, and HIFU does not exert its own advantages compared with it. Pancreatic cancer: It is an indisputable fact that the surgical resection rate of pancreatic cancer is low and the efficacy of conventional treatment is extremely poor. when HIFU treats pancreatic tumors, not only the tumor image can be clearly displayed, but also the important blood vessels around the tumor are protected from damage because of the heat dissipation function of blood flow. most pancreatic cancers lack blood supply, so it is conducive to heat accumulation. while treating pancreatic tumors, the ultrasound beam can thermally close the posterior abdominal plexus, which has obvious The ultrasound beam can thermally seal the posterior abdominal nerve plexus while treating pancreatic tumors, which has obvious pain relief effect. The Center of Focused Ultrasound Knife of East China Hospital of Fudan University treated more than 1300 cases of pancreatic cancer with HIFU in 2 years from 2005 to 2007, all of which were inoperable advanced tumors or postoperative recurrence in situ, with a pain relief rate of 75% and an average survival rate of 6.6 months, among which those who did not undergo surgery had significantly better results than those who underwent surgery, and none of them had serious complications (such as pancreatitis, pancreatic leakage, jaundice). In the treatment of posterior peritoneal tumors, HIFU gives full play to the advantages of strong ultrasound penetration and accurate focusing, which truly reflects high efficiency, safety, and repeatability. The mechanism of HIFU treatment is functional inactivation of tumor cells. Since the high temperature closes the nutrient vessels around the tumor, the absorption of tumor coagulation and necrosis is a long process, therefore, the conventional method of judging the efficacy by the volume and length of tumor is not suitable for HIFU treatment. 1.Imaging evaluation: It is generally believed that the local efficacy of HIFU should be judged mainly by imaging evaluation, mainly to determine whether there is coagulative necrosis in the tissues of the treatment target area and the extent of necrosis. Ultrasound, color Doppler, ultrasonography, CT, MRI and even PET-CT can reflect the blood supply in the target area, so as to infer whether the tumor is inactivated or not; 2.Comprehensive clinical evaluation includes clinical symptoms, signs, laboratory tests, tumor markers, pathological histology and quality of survival (QOL); 3.Clinical follow-up: the local regression of treatment, the presence of distant metastasis, the patient’s Survival. In a large number of HIFU treatment practices, it has been found that many advanced tumors have no obvious local imaging changes after HIFU treatment, but they do have good clinical efficacy, and the tumors stop growing for a long period of time or grow very slowly; on the contrary, many cases with significant imaging changes have metastases in other sites after HIFU treatment. In view of the fact that nowadays it is considered that tumor, especially advanced tumor, is not a localized disease or a static disease and cannot be cured with the existing treatments. Therefore, controlling the disease progression, reducing the trauma and complications caused by treatment and improving the survival quality of tumor patients are more practical strategies for cancer treatment. In the HIFU treatment of intermediate and advanced tumors, the practice of using imaging changes in the target area as the only criterion to judge the local efficacy of HIFU and at the cost of increasing the risk of treatment deserves to be reflected. V. Prospect As a green treatment for tumor in the 21st century, HIFU has attracted great attention worldwide, and its basic research and clinical application have made exciting breakthroughs. The defects of current ultrasound-guided HIFU that cannot measure temperature in real time will be compensated by the new generation of MRI-guided HIFU that can measure temperature, and the development of some small therapeutic probes for specific organs (such as treatment of thyroid gland, axillary lymph nodes, intracavitary treatment of gynecological diseases and special transducers for intraoperative applications) will significantly broaden the indications for HIFU treatment. The improvement of HIFU technology will eventually bring a real technological revolution in the field of local tumor treatment.