Abstract
Purpose
This study used contrast-enhanced MRI (CE-MRI) examination to assess the efficacy of high-intensity focused ultrasound (HIFU) for submucosal fibroids.
Methods
A total of 81 submucosal fibroids, including 33 cases of type 1, 29 cases of type 2, and 19 cases of type 2–5, treated by HIFU were retrospectively reviewed. CE-MRI was performed in all cases immediately after HIFU, the non-perfused volume ratio (NPVR) and the degree of endometrial impairment were recorded. Thereafter, CE-MRI was repeated in all cases after three months, and the change of fibroid volume shrinkage rate (FVSR), NPVR and the degree of endometrial impairment were recorded.
Results
The immediate NPVR was 86.4 ± 19.3% in type 1, 90.0 ± 13.3% in type 2 and 90.3 ± 7.2% in type 2–5. Among 81 fibroids, grades 0, 1, 2 and 3 endometrial impairments were observed in 38.3%, 16.1%, 14.8% and 30.9%, respectively. Three months later, NPVR was 68.0 ± 36.4% in type 1, 74.3 ± 27.7% in type 2 and 85.0 ± 16.1% in type 2–5. Grades 0, 1, 2 and 3 endometrial impairments were observed in 64.2%, 23.5%, 9.9% and 2.4%.FVSR was 49.0 ± 1.3% in type 1, 39.6 ± 1.7% in type 2 and 37.2 ± 2.1% in type 2–5. The FVSR in submucosal fibroid type 1 was superior to type 2 and type 2–5 (p < 0.05). The NPVR of submucosal fibroids in type 2–5 were higher than type 1 (p < 0.05) .There was no difference among different types of submucosal fibroids in endometrial impairment (p > 0.05) three months after HIFU.
Conclusions
At three months after HIFU, FVSR was better for submucosal fibroid type 1 than for type 2 and type 2–5. And there was no difference in endometrial impairment among the different types of submucosal fibroid groups.
1. Introduction
Fibroids are the most common benign tumors in gynecology, with at least 20–30% of women suffering from fibroids. They are classified into three subtype according to their locations in the uterus, including submucosal, intramural and subserosal fibroids. Submucosal fibroids, regardless of size, have more obvious clinical symptoms, which can lead to increased menstrual flow, dribbling, prolonged periods, dysmenorrhea, infertility and other symptoms, and need timely treatment. The current treatment methods for submucosal fibroids include hysteroscopic myomectomy, HIFU, laparotomy, laparoscopic myomectomy, uterine artery embolization, etc [Citation1,Citation2]. HIFU has been proven to be safe and effective in the treatment of submucosal fibroids [Citation3]. However, such reports are rare, especially for different types of submucosal fibroids. In this study, we evaluated the NPVR, the degree of mucosal damage, and the reduction rate of myoma in HIFU treatment of submucosal fibroids.
2. Material and methods
This retrospective study was approved by the ethics committee of our hospital (No. KS23145).
Written informed consent for the MRgHIFU procedure was obtained from all patients.
2.1. Patients
In this study, we retrospectively analyzed 81 submucosal fibroids in 72 women treated with HIFU ablation, between January 2018 and December 2021 at our hospital in , of which 33 were type 1, 29 were type 2, and 19 were type 2–5 according to the International Federation of Gynecology and Obstetrics (FIGO) [Citation4]. Exclusion criteria were as follows: Six patients of type 0 (easily removed by hysteroscopy), seven patients were complicated with adenomyosis, three patients with fibroid degeneration, four patients with a history of previous MRI-guided HIFU ablation. All HIFU therapy was performed using an ultrasound-guided HIFU tumor therapeutic system (JC200, Chongqing Haifu Medical Technology Co., Ltd., Chongqing, China).
Table 1. Baseline characteristics of the patients.
2.2. CE-MRI
CE-MRI examination was performed in all cases within one week before HIFU, immediately after HIFU and at three months after HIFU to observe and compare the changes in NPVR, endometrial impairment and FVSR. This examination was performed using GE1.5T MRI scanner, with sequences including axial T1WI (TR = 830 ms, TE = 11 ms), T2WI (TR = 3550 ms, TE = 70 ms), DWI (b = 800 s/mm2), sagittal compression lipid T2WI and contrast-enhanced scan. Gadopentetate glucosamine (Gd-TDPA) was used as the contrast agent for the enhancement scans at a dosage of 0.2 ml/kg, and LAVA was performed in the sagittal phase during the enhancement period, followed by the acquisition of transverse and coronal images in the delayed phase.
2.3. Image analysis
The MRI data of all patients were analyzed by two experienced diagnostic imaging physicians on a dedicated GE workstation. The pre-operative lesion and post-operative non-perfused volume (NPV) were measured, and the ablation rate (non-perfused volume ratio, NPVR) was calculated, NPVR = NPV/lesion volume × 100%.
T2WI signal intensity typing: (1) Funaki I: submucosal fibroid signal is lower than skeletal muscle; (2) Funaki II: submucosal fibroid signal is lower than uterine smooth muscle but higher than skeletal muscle; (3) Funaki III: uterine fibroid signal is higher than uterine smooth muscle [Citation5].
Grading of contrast-enhancement impairment after HIFU ablation for submucosal uterine fibroids: Endometrial impairment was classified into grade 0 (normal endometrium), grade 1 (pin-point, full-thickness discontinuity of involved endometrium), grade 2 (between grade 1 and 3) or grade 3 (full-thickness discontinuity of involved endometrium >1 cm in size). Arrows indicate the extent of endometrial discontinuity in two of three orthogonal planes of contrast-enhanced T1-weighted MR images obtained immediately after treatment [Citation6].
2.4. Statistical analysis
All statistical analyses were performed using R software (https://www.r-project.org/, version 3.6.3). A P value < 0.05 was considered statistically significant. Shapiro-Wilk test for normality of continuous variables (all numerical variables do not meet normality, and median min-max here a column of data can be used when describing). Results in the trilinear table: Kruskal-Wallis H test. Comparison of treatment effects of different subtype: ordered logistics regression (independent variables were only fibroids type, Y was FVSR at three months after HIFU, NPVR at three months after HIFU, and endometrial impairment at three months after HIFU.
3. Results
3.1. Comparison of treatment efficacy
The average treatment time for submucosal fibroids was 972 ± 490s in type 1, 961 ± 506s in type 2, 996 ± 679s in type 2–5. The average treatment energy for submucosal fibroids was 410 ± 235kj in type 1, 398 ± 192kj in type 2, 470 ± 284kj in type 2–5. The average treatment power for submucosal fibroids was 383 ± 54.6w in type 1, 395 ± 19.5w in type 2, 396 ± 6.5w in type 2–5.The immediate NPVR was 86.4 ± 19.3% in type 1, 90.0 ± 13.3% in type 2 and 90.3 ± 7.2% in type 2–5. Three months later, NPVR was 68.0 ± 36.4% in type 1, 74.3 ± 27.7% in type 2 and 85.0 ± 16.1% in type 2–5. FVSR at 3 months was 49.0 ± 1.3% in type 1 (), 39.6 ± 1.7% in type 2 () and 37.2 ± 2.1% in type 2–5 () in .
Figure 1. Pre-HIFU, post-HIFU and follow-up MRI images obtained from a patient with type 1 submucosal fibroids. (A) The fibroids were located in the submucosa of the posterior wall of the uterus, with slightly high signal intensity on T2WI(Funaki III); (B) Moderate enhancement on T1WI; (C) 95% of the fibroids were ablated after HIFU, and there was no enhancement in the ablation area; Endometrium impairment grade 3(arrow); (D) Three months after HIFU, FVSR was 50%. Endometrium impairment grade 0(arrow).
Figure 2. Pre-HIFU, post- HIFU and follow up HIFU MRI images obtained from a patient with type 2 submucosal fibroid. (A) The fibroids were located under the mucosa of the anterior wall of the uterus, with low signal intensity on T2WI(Funaki II); (B) Significant enhancement on T1WI; (C) 100% of the fibroids were ablated after HIFU, there is no enhancement in the mucosa of the fibroids; Endometrium impairmen grade 3(arrow); (D) 3 months after HIFU, FVSR was 90%, 100% enhancement of mucosa in fibroids. Endometrium impairmen grade 0(arrow).
Figure 3. Pre-HIFU, post-HIFU and follow-up MRI images obtained from a patient with type 2–5 submucosal fibroids. (A) The fibroids were located under the mucosa of the anterior wall of the uterus, with low signal intensity on T2WI(Funaki I); (B) Slight to moderate enhancement after T1WI; (C) 100% of the fibroids were ablated after HIFU, there was no enhancement in the mucosa of the fibroids; Endometrium impairmen grade 3(arrow). (D) Three months after HIFU, FVSR was 50%. Excreted fibroid tissue was observed in the cervical canal. On the same day, the patient had abdominal pain and fibroid tissue was discharged through the vagina. Endometrium impairmen grade 3(arrow).
Table 2. Comparison of treatment efficacy.
3.2. Endometrial impairment
The immediate endometrial impairment grade 0 was in 31 fibroids(38.3%,31/81), grade 1 was in 13 fibroids(16.1%,13/81), grade 2 was in 12 fibroids(14.8%,12/81),grade 3 was in 25 fibroids(30.9%, 25/81). 3 months after HIFU endometrial impairment grade 0 was in 52 fibroids(64.2%, 52/81), grade 1 was in 19 fibroids(23.5%, 19/81), grade 2 was in 8 fibroids (9.9%, 8/81),grade 3 was in 2 fibroids(2.4%, 2/81) in .
3.3. Analysis of submucosal fibroids type (FIGO) in FVSR, NPVR and endometrium impairment at three months after HIFU
The NPVR of submucosal fibroids type 2–5 were higher than type 1 at three months after HIFU (p < 0.05). The FVSR result in submucosal fibroid type was type 1 > type 2–5, and type 1 > type 2 (p < 0.05), and there was no difference between type 2 and type 2–5 (p > 0.05). At three months after HIFU, there was no difference among different types of submucosal fibroids in endometrial impairment(p > 0.05)in .
Table 3. Analysis of submucosal fibroids type (FIGO) in FVSR, NPVR and endometrium impairment at three months after HIFU.
4. Discussion
4.1. FVSR
The evaluation methods for therapeutic effect of fibroids include the Uterine Fibroid Symptoms and Quality of Life questionnaire (UFS-QoL), symptom severity score (SSS) and FVSR. The first two evaluation methods are mostly used in clinic, and the last one is commonly used in imaging examination.
In the present study, FVSR was 49.0 ± 1.3% in type 1, 39.6 ± 1.7% in type 2 and 37.2 ± 2.1% in type 2–5. The average FVSR with the assistance of MR-guided high-intensity focused ultrasound was 49%-60% as reported by Funaki [Citation7] and 36.6 ± 29.6% shrinkage of fibroids in T1WI, 41.0 ± 24.2% shrinkage of fibroids in T2WI after three months of HIFU ablation as reported by Milka Marinova [Citation8]. In their study, few fibroids of Funaki III type were included. We had 18 cases of Funaki III, including nine cases in type 1, four cases in type 2, five cases in type 2–5. Kim et al. reported that evaluation of intracavitary fibroids should be more prudent because intracavitary fibroids with a low T2 signal intensity are often associated with very high levels of perfusion [Citation9]. In this study, there were 14 Funaki I fibroids in submucosal type 1, which had four high levels of perfusion. However, three fibroids had FVSR >90% because of discharge of fibroid tissue after three months of HIFU. Yang Wang and Ping Liao [Citation10,Citation11] reported that at around three months, some patients had vaginal discharge of fibroid tissue, which also occurred in five of our patients, three in submucosal type 1, one in submucosal type 2 and one in submucosal type 2–5. After the fibroid is ablated, coagulative necrosis occurs, and then new blood vessels appear around the necrotic fibroid after some time, leading to recurrence of the fibroid. Because most of the volume of submucosal type 1 fibroid is located under the mucosa, it is easier for the myoma tissue to be expelled, so even though type 1 myoma has high levels of perfusion, it is expelled before the formation of new blood vessels after ablation. Hence, FVSR in submucosal type 1 was better than in submucosal type 2 and type 2–5.
4.2. NPVR
NPVR is also an important technical parameter that is positively correlated with clinical success in HIFU, with a high success rate indicated by NPVR > 80% [Citation12]. The immediate NPVR was 86.4 ± 19.3% in type 1, 90.0 ± 13.3% in type 2 and 90.3 ± 7.2% in type 2–5. To protect the endometrium, the treatment was stopped when the fibroid grayscale changes were observed at 5 mm near the endometrium in type 1, so the ablation effect was affected. There were 18 cases of Funaki III type, including 9 cases in type 1, 4 cases in type 2, 5 cases in type 2–5. These cases had a higher smooth muscle content relative to collagen fibers (i.e. cellular fibroids), and usually had a middle-high level of tissue perfusion which equal to or high than uterine smooth muscle [Citation9,Citation13,Citation14]. There was neovascularization around the ablation foci in Funaki III type, so the 3-month NPVR after HIFU was not as high as the immediate NPVR [Citation15–19].
Xie reported in 2015 that immediate NPVR was higher in type 2 submucosal fibroids compared to type 1 submucosal fibroids for HIFU treatment using the same power and same treatment time, and hence they concluded that type 2 submucosal fibroids are more sensitive than type 1 to HIFU treatment [Citation20]. In the current study, type 2–5 was superior to type 1 in the 3-month NPVR group after HIFU, which was similar with the findings of Xie.
The volume of type 2 fibroids located in the myometrium was >50% and type 2–5 throughout the whole uterus in clinical operation in uterine type. The volume of fibroids located in the myometrium was higher in both groups compared to type 1 submucosal fibroids [Citation4]. The target point was relatively far from the endometrium and plasma layer, so more heat can be released during ablation, and the volume of fibroids that can ablate necrosis was relatively large. Park MJ reported that patients with NPVR ≥80% had a significantly higher 3-month FVSR than NPVR < 80%, although there was no significant difference in the decrease in SSS. This conclusion was reached in cases with no differentiation of fibroid type [Citation21]. Submucosal fibroids type alone have not been reported. For type 1 fibroids ablation is easier to drain necrotic tissue than type 2 and 2–5, and clinical symptoms improve more significantly. Type 2 and 2–5 may have higher NPVR, but more necrosis does not necessarily result in more drainage, and volume reduction is not necessarily greater in submucosal fibroids. Therefore, longer follow-up is needed to correlate the NPVR and FVSR in submucosal fibroids.
4.3. Endometrial impairment
Kim et al. reported that after ablation of submucosal fibroids by HIFU, endometrial strengthening was intact or mildly injured or impaired in most cases, and immediate endometrial impairment correlated with the degree of protrusion of the fibroid into the uterine cavity [Citation6]. In this study, in the immediate contrast-enhanced T1-weighted images, endometrial impairment was assessed as grade 0 in 38.3% (31/81), grade 1 in 16.0% (13/81), grade 2 in 14.8% (12/81) and grade 3 in 30.8% (25/81) of the patients. The grade 3 rate was much higher than previously reported [Citation6]. There was 60%(15/25) in type 1, 16%(4/25) in type 2, 25%(6/25) in type 2–5 of grade 3.However, at the 3-month follow-up, overall endometrial impairment was grade 0 in 64.2% (52/81), grade 1 in 23.5% (19/81), grade 2 in 9.9% (8/81) and grade 3 in 2.4% (2/81).The rate of grade 0 was close to previously reported [Citation6]. There was only 2 cases in type 2–5 of grade 3. As mentioned above, type 2–5 had a higher NPVR. That was not conducive to the recovery of endometrial blood supply. Most cases of endometrial impairment in this study could recover well and spontaneously after HIFU ablation. Moreover, there was no difference among different types of submucosal fibroids in endometrial impairment three months after HIFU. This also indicated that the endometrium can be repaired well after HIFU, without being affected by the degree of protrusion into the uterine cavity. In other words, the enhancement defect of endometrium does not represent the real damage of endometrium.
4.4. Limitation
This is a retrospective study. More cases of different types of submucosal fibroids will be collected. And long-term effects in patients treated with HIFU ablation for symptomatic uterine fibroids are needed.
5. Conclusion
The rate of fibroid shrinkage at three months after HIFU was better for type 1 than for type 2 and 2–5. NPVR at three months after HIFU was better for type 2–5 than for type 1. There was no difference in endometrial impairment comparison among different types of submucosal fibroids at three months after HIFU.
Disclosure statement
No potential conflict of interest was reported by the author(s).
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References
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