Ultrasound Dosimetry In The HIFU Ablation For Patients With Uterine Fibroids

Uterine fibroids are the most common tumor in the female reproductive system. High-intensity focused ultrasound (HIFU) induce the tissue coagulative necrosis by non-invasive focusing in areas of tumors. It results in tumor shrinkage and symptomatic relief and solution with uterus sparing。The Treatment Planning System (TPS) is the important unit in the HIFU ablation , which comprise with adjunctive treat methods, ultrasound transducer (frequency and focal length),3D conformal scanning regiem and dosimetry. Ultrasound ablation dosimetry for clinical treatment should base on the effectiveness, safety and efficiency. The dosimetry study is to clarify the relationship between ultrasound energy and treatment efficiency,defined ablation region and dosage of ultrasound。Ultrasound energy deposite in the tissue and induce biological focal region (BFR)。Tumor was thermal ablated by BFR moving,which is predictable theoretically. Energy efficiency factor (EEF) is a tool to quantitate the interaction of ultrasound energy and biological tissue. Apart from the acoustic characteristic of transducer, EEF be influenced with the distance from tumor depth to the skin surface,histological structure and functional condition, tissue acoustic environment, scanning mode and adjunctive therapy methods, etc.This study construct the dosage equations by analyzing the dosimetry data from the ultrasound ablation for the treatment of uterine fibroids, aimed to predict dosage according to the treat volume and to provide a basis for TPS clinical application. ObjectiveBased on the results of MR imaging, to establish multi linear regression model by analyzing the dosimetry data from the ultrasound ablation for the treatment of uterine fibroids, considering the safety and efficacy. Materials and Methods1. SubjectsFrom December 2006 to January 2009, 142 patients, aged 21 to 51 years old with a mean of 38.8 years old, were recruited in this prospective study.Inclusion criteria: (1)The diagnosis was confirmed by ultrasonography and magnetic resonance imaging (MRI); (2) Premenopausal women; (3) Patients desire to be treated for symptoms or psychological aims, refused to surgery treatment; (4)Uterine fibroids, maximum diameter exceed 1.5cm, is visible on ultrasound guided HIFU system; (5) Patients who were able to communicate with the nurse or physician for their sensations during the procedure; (6) A detailed written description of focused ultrasound ablation was provided to all patients, and written informed consent was obtained from each patient.Exclusion criteria: (1) Cervical fibroids; (2) Patients with gynecological disorder other than uterine fibroids ( inc. vaginitis, pelvic inflammatory disease, tumors, etc); (3) Women in menstrual period, pregnancy (HCG examination shows positive) or lactation; (4) Patients received radiotherapy with high-dose on lower abdomen or with connective tissue disease; (5) Patients with diabetes not controlled or on dialysis; (6) Patients with unstable cardiac status (inc. unstable angina pectoris on medication; documented myocardial infarction within six months of protocol entry; congestive heart failure requiring medication (other than diuretic); currently taking anti-arrhythmic drugs; severe hypertension (diastolic BP > 100 mmHg on medication); presence of cardiac pacemaker); (7) Patient has severe cerebrovascular disease (multiple CVA or CVA within six months); (8) Contraindication to MRI and sensitivity to gadolinium-DTPA.2. EquipmentJC Focused Ultrasound Tumor Therapeutic System [developed by Chongqing Haifu? (HIFU) Tech Co., Ltd., Chongqing, China], a 3.5 MHz B-mode ultrasonography (US) probe is integrated within the unit for real-time US monitoring. Therapeutic US transducer deliver the power with 0W-400W, work at a frequency of 0.8 MHz. The frequency of ultrasonography (US) is 3.5 MHz.Magnetom Symphony 1.5T MR Tim unit ( Siemens, Germany ). Body Matrx/large Loop coil. Gd-DTPA: Gadodiamid 0.5 mmol / ml (15-20 ml).3. Methods3.1Pre-treatment image evaluation A clinical imaging evaluation, including pelvic US and MRI, were completed before HIFU ablation. The vascular distribution of uterine fibroids classified to grade 0, gradeⅠ, gradeⅡ, gradeⅢ, gradeⅣ, according Adler grading methods. The T2WI sign intensity of uterine fibroids classified to type 1, low intensity; type 2, intermediate intensity; type 3, heterogeneous intensity; type 4, high intensity.3.2 Ultrasound ablation Preparation:①Bowel preparation: purgation 1 day before procedure, cleaning enema at operation day morning;②Skin preparation: shaved the hairs, degreased and degased on the skin in the acoustic pathway;③Bladder preparation: insert and place the urinary catheter. Conscious-sedation: fentanyl and Midazolam for ramsy grade 3-4 analgesic to control the pain scale less than 4 scores.Protocal of HIFU ablation:①Treat region limited within pseudo-capsule: 15 mm distance to endometria; 5 mm distance to pseudo-capsule; 15 mm distance to depth of fibroids near to sacrum; 10 mm distance to front surface of fibroids near to abdominal wall; slice-slice distance: 5 mm; point-point distance: 5 mm;②HIFU ablation procedure: patient lies down in the prone position on the treatment system with the anterior abdominal wall placed above the transducer in a sealed tank of degassed water. Real-time guiding ultrasonography was used to determine the location of fibroid and avoid to damage the non-targeted structures, such as the intestinal tract. The therapeutic energy was regulated based on the tolerance of patients and the feedback from the gray scale in ultrasonography. Sonications were exposured by point scanning and line scanning. Hyperechoic regions appear on the ultrasound image and covered the planning treatment region. After the procedure, all of the patients were observed in a recovery room for 2 hours before they are discharged .Document data:①Dose parameters: treatment time, sonication time and ultrasonic power;②Acceptability: pain scoring for sensation during sonications;③Safety evaluation: side effects and complications.3.3 Post-treatment image evaluation Enhanced MR imaging was performed 0-3 months after the treatment for each patient according to imaging parameter pre-treatment used.3.4 Complications SIR grading system was used to categorize the severity.3.5 Dosimetry analysisEnergy effect factor(EEF) was used as quantitative unit for dose. The equation as follows: ηis focus coefficient ( = 0.7); P is ultrasonic power (W); t is sonication time; V is non-perfusion volume (NPV) (mm3); EEF is dosage for a unit tissue ablation.3.6 Statistical Analysis SPSS 13.0 Statistical software package and Microsoft Excel statistical function was used to analyze the data. Statistical significance is defined as a P value less than 0.05.Results1. Ablation technical results One hundred forty-two patients with 168 fibroids underwent single HIFU ablation procedure. The mean size of uterine fibroids was 4.4±1.6 (range: 1.5 to 12.3) cm and mean volume was 62.57±85.87 (range: 1.9 to 747.1) cm3. The mean treatment time was 2.7±1.3 hours (range: 14 to 471) mins and mean sonication time was 33±19 (range: 2 to 79) mins. Overall, follow-up MR imaging was obtained in 139 patients with 165 fibroids within 3 months after treatment. The mean ratio of NPV is 84.70±22.96%.2. AcceptabilityEight-five patients tolerate the procedure well with 0-4 pain scores.3. ComplicationsForty-seven (33.10%) patients experienced side-effects and complications. 94.92% events are SIR classification A-B. No SIR classification D-F events occurred. One woman experienced skin burnⅡgrade in the groin area, typical protection was administrated. Two women experienced axillary temperature measurement more than 38.5℃, recovery in 48 hours after treatment. One woman underwent catheterization for urinary retention, resolved within 48 hours.4. Results of dosimetryThe ultrasonic dose are linear correlation with the size, location, and vascular distribution and T2WI sign intensity of uterine fibroids. There is no correlation relationship between ultrasonic ablation dose and abdominal wall thickness.Conclusions1. Sufficient treat volume for uterine fibroids ablation is feasibility using fentanyl and Midazolam for conscious-sedation.2. Energy efficiency factor (EEF), a direct reflection of relationship between ultrasound energy and ablation efficacy for uterine fibroids. It could be used as a quantitative measurement.3. In the clinical practice, the size, location, vascular distribution and T2WI sign intensity of uterine fibroids could be used as measures for prediction of ultrasound ablation dose.4. Prediction equation of ultrasound ablation dose for uterine fibroids as follows:(1) Prediction equation based on CDFI and MRI images (χ1 is the location,χ2 is the size,χ3 is 1 plus Adler classification of vascular distribution andχ4 is T2WI sign intensity of uterine fibroids.)(2) Prediction equation based on CDFI images (χ1 is the location,χ2 is the size andχ3 is 1 plus Adler classification of vascular distribution of uterine fibroids.)(3) Prediction equation based on MRI images ?y? =3.052+6.095?x1 ?0.383?x2+2.827?x3+5.135?x4?y? =6.202+5.557?x1 ?0.180?x2+2.144?x3?y? =8.759+6.816?x1 ?0.332?x2+4.881?x3 (χ1 is the location,χ2 is the size andχ3 is T2WI sign intensity of uterine fibroids.)...