Feasibility Study Of Focused Ultrasound For Chronic Soft Tissue Injury And Preliminary Study On Its Mechanism

Background and objectives: Chronic soft tissue injury is human skeletal muscle, fascia ligament, joint capsule, periosteum, fat, and other soft tissue lesions damage. Its course of disease should generally be more than three weeks over. The main clinical manifestations of the disease is a partial intractable pain, as well as partial accompanied symptoms such as cold feeling, heavy feeling, aching pain, gas pains, and even different levels of local dysfunction. It is widespread in incidence of this disease, and difficult to cure. Traditional ultrasound therapy treatment of this disease has been more than 60 years, but in vain. In order to give full play to ultrasound characteristics and ultrasound effect we are trying to use focused ultrasound treatment of this disease. It is necessary to study for its safety, clinical feasibility and related mechanism.Methods:(1)30 rabbits were randomly divided into groupsⅠ～Ⅸunder single or multiple ultrasonic radiation, radiation dose and irradiation of different ways. Each rabbit bilateral hip symmetric region (soft tissue thickness of about 20 ~ 25 mm), is a part of ultrasonic irradiation. Rabbits are from prone position, limbs fixed for ease, and does not be provided sedatives, wait for the natural state of quiet to start ultrasonic irradiation. When animal struggling behavioral response happened in irradiation process, rabbits should be compelled to complete scheduled irradiation time. Focused ultrasound irradiation parameters are: frequency of 0.8 MHz, focus intensity of 30 W/cm2 and 40 W/cm2. The first time of rabbits struggle behavior should be record. After ultrasonic irradiation, TTC staining and histopathology were observed(.2)60 patients with chronic soft tissue injury were treated with a single use of focused ultrasound. The efficacy was evaluated after the treatment at different time point: 30 minutes after treatment, 3 days after treatment, 7 days after treatment, 14 days after treatment. The efficacy indices included pain, local tenderness and limitation of movement. Side effects were observed during the treatment and 2 weeks after treatment. (3)Experimental chronic soft tissue injury models were made on bilateral hip in 36 healthy adult rabbits by Zhou Guo Lin and Wu Jun's methods. 36 model rabbits were randomly divided into 3 groups: model group,control group and ultrasound group,each group twelve rabbits. Each group was subdivided into 3 subgroups according to different time points of observation after treatment: 30 minutes,3 and 7 days,each subgroup four rabbits, eight observation site. The ultrasound group underwent a single treatment of focused ultrasound with 0.8 MHz, focus intensity of 20 W/cm2, a continuous output wave, and fixed way for 20 seconds, 5 seconds interval, and moving way for 60 seconds. The control group was subjected to sham exposure. No treatment was given to the model group. The contents of PGE2 and pH value in injured muscle tissue were detected at the different time points,applying ELISA for PGE2. In the 3 and 7 days subgroup of ultrasound group and control group,the blood samples were drawn from ear veins of rabbits to test the mass concentrations ofβ-EP in plasma by radioimmunoassay before, 5 minutes and 24 hours after treatment.Results(:1)All single ultrasonic radiation groups of focus intensity of 30 W/cm2 had no animal struggling behavioral response and histological changes(skin appearance,TTC staining and histopathology had no abnormal changes). All groups of focus intensity of 40 W/cm2 had animal struggling behavioral response happen but no histological changes. All groups of multiple ultrasonic radiation had no histological changes.(2)The total efficacy rate were respectively 96.7%,53.3%,38.3%,23.3%,two patients had mild side effect, the side-effect rate was 3.3%.(3)The content of PGE2 was significantly decreased and pH value was significantly increased in ultrasound group compared with control group and model group 30 minutes after treatment (P < 0.01). The contents of PGE2 and pH value had no difference respectively among three groups 3 and 7 days after treatment (P > 0.05). In ultrasound group, the mass concentration ofβ-EP was significantly increased at 5 minutes after treatment compared with that before treatment (P < 0.01). There was no difference between that before treatment and 24 hours after treatment (P >0.05). The mass concentrations ofβ-EP had no difference within the control group at each time point (P > 0.05).Conclusions:(1)Focused ultrasound irradiated to rabbits on buttocks soft tissue ,when struggling behavioral response happened,histology had no changes. Behavioral response can be used as an early-warning standard to a dose that can not be tolerated,therefore focused ultrasound is a safe treatment(.2)Clinical study results show that focused ultrasound is safe and effective on chronic soft tissue injury treatment.(3)The effects of focused ultrasound on chronic soft tissue injury might be highly correlated with a decrease in PGE2, an increase in pH value in injured muscle tissue, and an increase in plasmaβ-EP.