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Research Article

Non-contrast enhanced MRI for efficiency evaluation of high-intensity focused ultrasound in adenomyosis ablation

, , , , , , & show all
Article: 2295813 | Received 13 Jun 2023, Accepted 12 Dec 2023, Published online: 17 Jan 2024

Abstract

Objective

To investigate the value of T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) in evaluating the therapeutic effect of high-intensity focused ultrasound (HIFU) in adenomyosis ablation.

Material and methods

One hundred eighty-nine patients with adenomyosis were treated with HIFU. The ablation areas on T2WI and DWI sequences were classified into different types: type I, relatively ill-defined rim or unrecognizable; subtype IIa, well-defined rim with hyperintensity; subtype IIb, well-defined rim with hypointensity. The volume of ablation areas on T2WI (VT2WI) and DWI (VDWI) was measured and compared with the non-perfused volume (NPV), and linear regression was conducted to analyze their correlation with NPV.

Results

The VT2WI of type I and type II (subtype IIa and subtype IIb) were statistically different from the corresponding NPV (p = 0.004 and 0.024, respectively), while no significant difference was found between the VDWI of type I and type II with NPV (p = 0.478 and 0.561, respectively). In the linear regression analysis, both VT2WI and VDWI were positively correlated with NPV, with R2 reaching 0.96 and 0.97, respectively.

Conclusions

Both T2WI and DWI have the potential for efficient evaluation of HIFU treatment in adenomyosis, and DWI can be a replacement for CE-T1WI to some extent.

Introduction

Adenomyosis is a common and benign uterine disease that affects women during their childbearing age. Its typical pathological findings are ectopic endometrial glands, stromal tissue in the myometrium, and hyperplasia of the peripheral smooth muscle [Citation1]. Adenomyosis can seriously impair the quality of life. About 2/3 of patients have symptoms of dysmenorrhea or menorrhea and some patients may experience infertility [Citation2, Citation3]. In addition to medication and surgery, high-intensity focused ultrasound (HIFU) ablation is a novel method for adenomyosis treatment. By focusing ultrasonic energy on the target tissue, HIFU treatment can cause coagulative necrosis and reduce the volume of the lesion [Citation4]. HIFU treatment contains the advantage of being highly efficient, noninvasive, and inexpensive [Citation5, Citation6].

To estimate the prognosis of the patients, the evaluation of treatment efficacy is necessary. MRI is one of the most important methods for efficacy evaluation post-treatment. The ablation rate, represented by the non-perfused volume ratio (NPVR), is the most widely used index for evaluating the short-term efficacy of HIFU. NPVR is defined as the ratio of the non-perfused volume (NPV) measured on post-treatment contrast-enhanced T1-weighted imaging (CE-T1WI) to the adenomyosis volume measured on pretreatment T2-weighted imaging (T2WI). It has been confirmed that NPVR has a significant positive correlation with the prognosis of the patients. Therefore, the NPVR has been the gold standard in the efficacy evaluation of HIFU treatment [Citation7–9]. However, the use of gadolinium-based contrast agents in CE-T1WI may increase money consumption and time costs. Furthermore, it may also pose potential risks to patient health, such as nephrogenic systemic fibrosis (NSF), contrast-induced nephropathy, and anaphylaxis [Citation10–12]. An MRI method that can quickly and effectively evaluate the efficacy of HIFU in adenomyosis treatment without the use of contrast agents may significantly improve its economy and safety.

T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) are MR sequences with fast imaging and without contrast agent use. Several studies have reported their value in the efficiency evaluation of HIFU treatment in leiomyomas [Citation13–15]. The signal change of micro hemorrhage on T2WI can make the boundary between ablation areas and fibroid tissue. Furthermore, Liao DF’s study found that a high-signal ring on DWI after HIFU ablation could help to measure the area of necrotic tissue and evaluate the success of the procedure. However, their value in efficiency evaluation for HIFU treatment in adenomyosis remains unknown.

Material and methods

Patients

Patients with symptomatic adenomyosis who underwent HIFU treatment (between June 2013 and September 2019) were enrolled in this study (). The inclusion criteria were as follows: (1) Adult women with symptomatic adenomyosis; (2) the patients should be completely autonomous and cooperate to complete HIFU treatment; and (3) the patients should undergo pelvic MRI scanning before and after HIFU treatment. The exclusion criteria were as follows: (1) age < 18 years, (2) inability to complete the treatment, (3) lack of clinical or imaging data, (4) other pelvic malignancies, and (5) acute pelvic inflammation and pregnancy.

Figure 1. The recruitment process of patients in this study.

Figure 1. The recruitment process of patients in this study.

HIFU treatment

The patient ingested liquid food three days before treatment and a single dose of intestinal preparation solution (2000 ml of composite polyethylene glycol electrolyte solution) in the afternoon before treatment. An enema was performed on the morning of the day of treatment. The treated area was shaved, degreased, and degassed in advance. The patient was prone on the operating table, and the anterior abdominal wall was in contact with degassed water. A catheter was inserted to control bladder volume by injecting saline, and a degassed water balloon was used to push away the intestine in the acoustic path.

The HIFU procedure was performed using a Focused Ultrasound Tumor Therapeutic System (Model-JC or Model-JC 200, Chongqing Haifu Medical Technology Co., Ltd.). The ultrasound parameters used in this study were as follows: a working frequency of 0.8 MHz, an acoustic power range of 300–400 W, and a focal area of 1.5 mm × 1.5 mm × 10 mm. The ultrasound device provided real-time monitoring during the HIFU procedure. The patient was treated under intravenous conscious sedation with fentanyl and midazolam hydrochloride. The ultrasonic energy was adjusted based on both patient’s feedback and changes in gray scale on ultrasonographic imaging during the treatment. The physician discontinued the treatment until the grayscale covered most of the lesion or the patient could not endure the pain of the procedure. When the treatment ended, the patient was asked to observe for 2 h before they returned to the ward.

MRI evaluation

All patients were scanned with 3.0 T MRI equipment (single HD excite, GE Healthcare, USA) before and after HIFU treatment. The eight-channel phased-array abdominal coil was fixed in a supine position. Patients were asked to breathe calmly and avoid body movements during the examination. The scanning parameters are presented in .

Table 1. MRI parameters.

The types of ablation areas, non-perfused volume (NPV), the ablation volume on T2WI (VT2WI), the ablation volume on DWI (VDWI), and the volume of adenomyosis were evaluated.

The types of ablation areas were classified independently by radiologists 1 and 2 (both with eight years of experience in MRI diagnosis). In cases of disagreement in classification between the two radiologists, the final decisions were made by radiologist 3 (10 years of experience in MRI diagnosis). All three radiologists were blinded to the patient’s information and post-treatment CE-T1WI images. The ablation areas on T2WI and DWI were respectively classified according to the following criteria (): (1) type I, the ablation area had a relatively ill-defined rim which was either hyperintensity or hypointensity or unrecognizable; (2) subtype IIa, the ablation area had a well-defined rim which was hyperintensity; (3) and subtype IIb, the ablation area had a well-defined peripheral rim which was hypointensity. When evaluating the ablation areas, the central slice that could manifest the largest part of the ablation area was used and pretreatment images were selected as a reference. The consistency of the classification of the ablation areas between the two radiologists was evaluated using the kappa consistency test.

Figure 2. T2WI (A1, B1, C1), DWI (A2, B2, C2), and CE-T2WI (A3, B3, C3) images post-treatment. As we can see, the subtype IIa and IIb ablation areas on T2WI or DWI had similar morphology with corresponding non-perfused area on CE-T1WI (B3 and C3).

Figure 2. T2WI (A1, B1, C1), DWI (A2, B2, C2), and CE-T2WI (A3, B3, C3) images post-treatment. As we can see, the subtype IIa and IIb ablation areas on T2WI or DWI had similar morphology with corresponding non-perfused area on CE-T1WI (B3 and C3).

The ablation volume on T2WI (VT2WI), the ablation volume on DWI (VDWI), and NPV were measured on post-treatment T2WI, DWI (b = 800 m2/s) and CE-T1WI. Adenomyosis volume was measured on pretreatment T2WI. The volumes were measured by delineating all the slices of the target areas using the ITK-SNAP 3.4 software (Cognitica, Philadelphia, PA, USA) and the volumes were calculated automatically (). When measuring the type I ablation volumes, the regions with suspicious signal change at the rim should all be covered. For patients whose ablation areas were unrecognized, we defined the VT2WI or VDWI as 0 cm3. VT2WI and VDWI were compared to the corresponding NPV. Linear regression analysis was performed to assess their correlations.

Figure 3. The measurement of VT2WI, VDWI, NPV and volume of adenomyosis. A. Measurement of volume of adenomyosis on pretreatment T2WI; B. Measurement of VT2WI on post-treatment T2WI; C. Measurement of VDWI on post-treatment DWI; D. Measurement of NPV on post-treatment CE-T1WI.

Figure 3. The measurement of VT2WI, VDWI, NPV and volume of adenomyosis. A. Measurement of volume of adenomyosis on pretreatment T2WI; B. Measurement of VT2WI on post-treatment T2WI; C. Measurement of VDWI on post-treatment DWI; D. Measurement of NPV on post-treatment CE-T1WI.

Based on their ablation types on T2WI, the patients were divided into the T2WI-type I group and the T2WI-type II group, the T2WI-type II group was then divided into T2WI-subtype IIa group and T2WI-subtype IIb group. The patients were also classified into DWI-type I group, DWI-type II group, DWI-subtype IIa group, and DWI-subtype IIb group according to their ablation types on DWI. The clinical and treatment parameters were compared between the groups.

Statistical analysis

All analyses were performed using the SPSS software (SPSS 24.0 IBM Company, Armonk, NY, USA). Normally distributed data were reported as mean ± standard deviation, whereas non-normally distributed data were reported as medians and interquartile ranges. The t-test or rank sum test was used to compare differences in measurement data, and the chi-square test was used to compare differences in counting data. The interpretation of the Kappa value is based on the following criteria: a Kappa value < 0.2 indicates poor consistency; a Kappa value between 0.21 and 0.40 indicates fairly poor consistency; a Kappa value between 0.41 and 0.60 indicates moderate consistency; a Kappa value between 0.61 and 0.80 indicated fairly good consistency; and a Kappa value > 0.80 indicates good consistency. An intraclass correlation coefficient above 0.90 was classified as having good reliability. Statistical significance was set at p < 0.05.

Results

General characteristic

In total, 189 patients were enrolled in this study. The mean age was 41 ± 5 years, and the mean BMI was 32.1 ± 2.9. The median adenomyosis volume was 94.4 (53.5–196.2) cm³. The median NPV was 43.2 (23.7–78.8) cm³ and the median NPVR was 44.1 (30.9–62.3) %. The interval time between the HIFU procedure and post-treatment MRI scanning (IT) was 1 (1–3) days and 141 patients underwent MRI examination within 2 days.

The classification of ablation areas on T2WI and DWI

Of the 189 adenomyosis on T2WI, 31 of them presented type I ablation areas, 119 of them presented subtype IIa ablation areas and 39 of them presented subtype IIb ablation areas. In all 189 ablation areas on DWI, 15 of them were type I ablation areas, 121 of them were subtype IIa ablation areas, and 53 of them were subtype IIb ablation areas. The kappa value of the classification for the ablation area on T2WI was 0.627 (p < 0.001) between the two radiologists, and that on DWI was 0.651 (p < 0.001). Both reached fairly good consistency ().

Table 2. Inter-reader agreement in classifying ablation types on T2WI and DWI.

The measurement of ablation volume on T2WI and DWI

The median VT2WI of type I and type II ablation area were 15.0 (5.3–33.5) cm³ and 50.4 (23.2–114.8) cm³, both of which were significantly different (p = 0.004 and p = 0.024, respectively) with their corresponding NPV, which were 21.2 (8.7–42.8) cm³ and 49.1 (27.9–94.9) cm³, respectively. And the VDWI of type I and type II ablation area were 9.4 (3.7–24.6) cm³ and 57.1 (33.5–122.3) cm³, both of which with no significant difference (p = 0.078 and p = 0.561) with their corresponding NPV, which were 13.9 (6.3–26.6) cm³ and 58.8 (30.1–118.4) cm³. Seven patients got invisible ablation areas on T2WI, their largest NPV and NPVR were 18.5 cm3 and 17.7% and their smallest NPV and NPVR were 2.2 cm3 and 2.0%. Five patients had completely invisible ablation areas on DWI, their largest NPV and NPVR were 6.3 cm3 and 13.8% and their smallest NPV and NPVR were 2.2 cm3 and 2.0%. The ICC of the measurement for VT2WI was 0.951 in the type I group and that was 0.990 in type II group. The ICC of the measurement for VDWI was 0.947 in type I group and that was 0.975 in type II group. All achieved good consistency ().

Table 3. Inter-reader agreement in measuring VT2WI and VDWI.

In the linear regression analysis, both VT2WI and VDWI showed significant correlations with the NPV. The linear equation between VT2WI and NPV was NPV = 0.98 VT2WI + 1.32 (R2 = 0.96, p < 0.001). The linear equation between VDWI and NPV was NPV = 0.96 VT2WI + 1.07 (R2 = 0.97, p < 0.001) ().

Figure 4. Linear correspondence between VT2WI and NPV and VDWI and NPV. A. The scatter diagram of correspondence betweenVT2WI and NPV; B. The scatter diagram of correspondence between VDWI and NPV.

Figure 4. Linear correspondence between VT2WI and NPV and VDWI and NPV. A. The scatter diagram of correspondence betweenVT2WI and NPV; B. The scatter diagram of correspondence between VDWI and NPV.

Clinical and treatment parameters of the different groups

The age, BMI, adenomyosis volume, adenomyosis type, uterus position, NPV, sonication power, treatment time, sonication time, sonication dose, energy efficiency factor (EEF, defined as the ultrasound energy delivered for ablating 1 mm3 of the adenomyotic lesion tissue), NPVR, and IT of the different groups were compared. The NPV in the T2WI-type I group was 21.2 (8.7–42.8) cm³, while the NPV was 49.1 (27.9–94.9) cm³ in the T2WI-type II group (p < 0.01). The NPVR in the T2WI-type I group was 27.2 (17.4–44.7)%, while that was 54.6 (42.0–73.9)% in the T2WI-type II group (p < 0.01). The NPV in the DWI-type I group was 13.9 (6.3–26.6) cm³, and that was 58.8 (30.1–118.4) cm³ in the DWI-type II group (p < 0.01). The same difference was found between the NPVR in the DWI-type I and DWI-type II group (32.5 (13.4–48.5)% vs. 43.0 (30.0–68.7)%, p < 0.001). The EEF in the DWI-type I group was 4.1 (2.5–6.8) kJ/cm³, and the EEF in the DWI-type II group was 2.0 (1.4–4.3) kJ/cm³ (p = 0.044). And the volume of adenomyosis in the DWI-type I group was smaller than that in the DWI-type II group (68.7 (33.6–93.9) cm³ vs. 148.2 (76.3–266.1) cm³, p = 0.001). The results are shown in and Citation5.

Table 4. Comparison of clinical and treatment parameters between T2WI-type I and T2WI- type II group.

Table 5. Comparison of clinical and treatment parameters between DWI-type I and DWI-type II group.

A remarkable statistical significance was found between the ITs in the T2WI-subtype IIa and T2WI-subtype IIb groups (1 (1–2) days vs. 5 (2–7) days, p < 0.001), and the same difference was also found between the DWI-subtype IIa and IIb groups (1 (1–3) days vs. 6 (3-6) days, p < 0.001). The EEF and sonication time [2.4 (1.5–7.8) kJ/cm³ and 597 (397–1213) s] in the T2WI-subtype IIa group were smaller than those [2.9 (1.9–4.6) kJ/cm³ and 912 (489–1200) s] in the T2WI-subtype IIb group. The treatment time in the T2WI-subtype IIa group was 52 (35–93) min, which was smaller than the treatment time of 88 (61–102) min in the T2WI-subtype IIb group. And the NPV and NPVR in the DWI-subtype IIb group were larger than those in the DWI-subtype IIa group [54.6 (19.3–83.2) cm³ vs. 52.6 (21–113.5) cm³, p = 0.026 and 67.7 (35.2–79.5)% vs 44.1 (35.8–68.5)%, p = 0.013). Furthermore, the sonication power was slightly higher in the DWI-subtype IIa group (400 (373-400) W vs. 398 (371–400) W, p = 0.013). The results are shown in and Citation7.

Table 6. Comparison of clinical and treatment parameters between T2WI-subtype IIa and T2WI-subtype IIb group.

Table 7. Comparison of clinical and treatment parameters between DWI-subtype IIa and DWI-subtype IIb group.

Discussion

The ultrasound energy in HIFU ablation leads to an interruption of blood flow in the ablation tissue. As a result, the treated tissue appears as the non-perfused area on CE-T1WI [Citation16]. At present, the NPVR has become the gold standard for efficient evaluation of HIFU treatment since it has a positive correlation with the patient’s prognosis [Citation7–9]. However, the use of gadolinium-based contrast agents is time- and money-consuming and may pose potential risks. Therefore, it is more economical and safer to use the non-contrast MRI technique for efficacy evaluation. In leiomyomas, the value of T2WI and DWI in the efficacy evaluation of HIFU treatment has been revealed [Citation13–15]. However, their potential for evaluating HIFU treatment in adenomyosis remains unknown.

According to the image features of the ablation area on T2WI or DWI, they were classified into type I (with an ill-defined rim) and type II (with a well-defined rim). The main differences in treatment parameters between the type I group and the type II group were their NPV and NPVR. Adenomyosis patients with type I ablation areas on T2WI or DWI were associated with lower NPV and NPVR, indicating that a type I ablation area on T2WI or DWI may suggest relatively poor treatment efficiency. Previous studies have also found that lesion volume and EEF are related to NPVR [Citation17, Citation18], which may explain why EEF and lesion volume were also different between type I and type II.

The type II ablation areas on T2WI and DWI were further classified into subtypes IIa and IIb on the basis of the signal intensity of their rims. Sixty-three percent (119/189) of the ablation areas on T2WI belonged to subtype IIa, while 64.0% (121/189) of the ablation areas on DWI belonged to subtype IIa. Each of them had a core of heterogeneous signal intensity and a rim of hyperintensity that delineated the edge of the ablation area. This distinctive appearance may be due to the difference in energy distribution in the ablation area [Citation19, Citation20]. The central part absorbed more ultrasonic energy and resulted in coagulative necrosis, while the peripheral part absorbed less ultrasonic energy. Its pathological change was cytotoxic edema, which presented high intensity on T2WI and DWI. This phenomenon was also observed in previous studies [Citation21, Citation22].

The remaining ablation areas on T2WI and DWI were classified as subtype IIb, and they had apparent rims of hypointensity. It is noteworthy that the median IT of patients with subtype IIb ablation areas on T2WI and DWI was longer. The IT of some patients in our study exceeded 2 days. Generally, MRI scans within 2 days after the HIFU treatment would allow physicians to better understand the success of the procedure. We still enrolled these patients in our study because we found the IT may somehow impact the image features of the ablation area on T2WI and DWI. When the IT was long enough, the local micro-hemorrhage would gradually transform into paramagnetic material, such as deoxyhemoglobin or methemoglobin, which could appear as low signal intensity on T2WI and DWI [Citation23, Citation24]. In the meantime, the local cytotoxic edema also faded over time [Citation21]. The MR findings of subtype IIb on T2WI and DWI were not observed in previous reports [Citation13, Citation25, Citation26]. This difference might be caused by the different objects and IT in various studies. The EEF, treatment time, and sonication time between the T2WI-subtype IIa group and the T2WI-subtype IIb group showed statistical differences. While, the NPVR, NPV, and sonication power between the DWI-subtype IIa group and the DWI-subtype IIb group also showed statistical differences. The results above showed that the HIFU parameters and treatment difficulty of adenomyosis may affect the appearance of lesions on T2WI and DWI to some extent. However, the specific mechanism remained unclear.

Both VT2WI and VDWI presented high correlations with NPV, which may imply that T2WI and DWI have the potential to be optional methods for evaluating the efficiency of HIFU treatment for adenomyosis. The VT2WI of types I and II were statistically different from their corresponding NPV. Neither VDWI of type I nor VDWI type II VDWI differed significantly from their corresponding NPV. Even though most type I ablation areas on DWI were relatively ill-defined, their outlines were still visible, and their VDWI was comparable with NPV. For patients whose ablation areas were unrecognized, we defined their VDWI as 0 cm3. However, no difference was found between their VDWI and NPV. Because they had rather low NPV (less than 10 cm3). For these reasons, DWI has high accuracy in the volume measurement of ablation areas of all types. However, T2WI is not suitable for evaluating the efficiency of HIFU treatment for adenomyosis independently, considering the limited accuracy of volume measurement for ablation areas. The classification of ablation area types on T2WI and DWI between two radiologists reached “fairly good” standards (κ = 0.627 and 0.651) in Kappa consistency tests. This meant that a “gray zone” existed in the classification of area types on DWI. However, it may have little effect on the value of DWI in efficiency evaluation, because DWI achieved high accuracy in the measurement of ablation areas of both type I and type II. Based on the above analysis, we believe that DWI may replace CE-T1WI in NPVR measurements and calculations to some extent.

There are still some limitations in this study: first, it is a retrospective study, and bias is inevitable; furthermore, the interval time of MRI reexamination post-treatment for some patients exceeded 2 days, which may have some impact on the results; and finally, patients were treated by physicians with different seniorities.

Conclusions

Both T2WI and DWI have the potential to evaluate the efficiency of high-intensity focused ultrasound in adenomyosis ablation, and DWI may be an alternative to CE-T1WI.

Author contributions

Si Ma: manuscript writing, data management, and analysis. Mingmei Tang, Xueke Qiu, and Yang Liu (third author): Classification and ROI delineation. Chunmei Gong: Conceptualization. Yan Hu: chart drawing. Fajin Lv and Yang Liu: project development and administration.

Ethical approval

The protocol of this retrospective study was approved by the Ethics Committee, and the requirement for informed consent was waived (ethics approval number K2023-115). All patient data were anonymized for reporting purposes.

Abbreviations
HIFU=

high-intensity focused ultrasound

NPV=

non-perfused volume

NPVR=

non-perfused volume ratio

VT2WI=

ablation volume on T2WI

VDWI=

ablation volume on DWI

ICC=

intraclass correlation coefficient

MRI=

magnetic resonance image

T2WI=

T2-weighted imaging

DWI=

diffusion-weighted imaging

CE-T1WI=

contrast-enhanced T1WI

BMI=

body mass index

IT=

interval time between HIFU procedure and MRI scanning post-treatment

EEF=

energy efficiency factor

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that data supporting the findings of this study are available upon request from the corresponding author. The data are not publicly available because they contain information that can compromise the privacy of the research participants.

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