Magnetic Resonance Imaging Parameters in Predicting the Treatment Outcome of High-intensity Focused Ultrasound Ablation of Uterine Fibroids With an Immediate Nonperfused Volume Ratio of at Least 90%

Rationale and Objectives

We aimed to investigate the role of magnetic resonance imaging parameters in predicting the treatment outcome of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids with a nonperfused volume (NPV) ratio of at least 90%.

Material and Methods

A total of 120 women who underwent HIFU treatment were divided into groups 1 ( n = 72) and 2 ( n = 48), comprising patients with an NPV ratio of at least 90% and less than 90%, respectively. Multivariate logistic regression analyses were carried out to investigate the potential predictors of the NPV ratio of at least 90%. The NPV ratios immediately post-treatment, therapeutic efficacy at 6 months’ follow-up, and safety in terms of adverse effects and changes in anti-Mullerian hormone level were assessed.

Results

By introducing multiple predictors obtained from multivariate analyses into a generalized estimating equation model, the results showed that the thickness of the subcutaneous fat layer in the anterior abdominal wall, peak enhancement of fibroid, time to peak of fibroid, and the ratio of area under the curve of fibroid to myometrium were statistically significant, except T2 signal intensity ratio of fibroid to myometrium, hence predicting an NPV ratio of at least 90%. No serious adverse effects and no significant difference between the anti-Mullerian hormone levels before or 6 months post-treatment were reported.

Conclusions

The findings in this study suggest that the achievement of NPV ratio of at least 90% in magnetic resonance imaging-guided HIFU treatment of uterine fibroids based on prediction model appears clinically possible without compromising the safety of patients.

Introduction

Uterine fibroids, also known as leiomyomas, represent the most common tumor in women. These fibroids disrupt the functions of the uterus and cause menorrhagia, dysmenorrhea, anemia, pelvic pressure or pain, urinary incontinence, recurrent pregnancy loss, and infertility. The lifetime prevalence of uterine fibroids ranges from 70% to 80% .

Magnetic resonance imaging (MRI)-guided high-intensity focused ultrasound (HIFU), which combines the anatomical and functional imaging of magnetic resonance (MR) with the thermal ablation possibilities of HIFU, is a promising minimally invasive therapy for the treatment of uterine fibroids. MRI is of great importance in HIFU treatments and not only contributes in patient selection, an essential step toward obtaining good treatment results, but also facilitates planning the treatment, monitoring the safety of the delivery, and verifying the outcome.

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Materials and Methods

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Patients

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MRI Sequences

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Assessment of T2W Images and Perfusion MRI

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MR-guided High-intensity Focused Ultrasound Treatment

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Therapeutic Efficacy and Safety Assessment

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Data Analysis and Statistics

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Results

Baseline Characteristics

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TABLE 1

Comparison of Baseline Characteristics According to the NPV Ratio of at Least 90% and Less Than 90%

Characteristics All Patients NPV Ratio ≥90% NPV Ratio <90%P Value Patients 120 72 48 Subcutaneous fat thickness (mm) 11.9 ± 4.3 (3.0–26.0) 11.0 ± 4.4 (3.0–25.0) 13.3 ± 3.8 (5.0–26.0) .004 ‡ Presence of abdominal scars Yes 31 17 14 .528 No 89 55 34 Uterus position .060 Anteverted 87 48 39 Retroverted 33 24 9 Diameter (cm) \* 7.1 ± 2.6 (2.4–15.1) 7.3 ± 3.0 (2.4–15.1) 6.8 ± 1.9 (3.0–11.8) .337 Distance (mm) † 94.5 ± 15.0 (57.0–133.0) 94.1 ± 15.6 (57.0–130.0) 95.2 ± 14.2 (59.0–133.0) .686 Fibroid types .526 Intramural 68 38 30 Subserosal 21 13 8 Submucosal 31 21 10

NPV, nonperfused volume.

Values in parentheses represent ranges.

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Characteristics of MRI-guided HIFU Treatment of Uterine Fibroids

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Analysis of Factors Influencing NPV Ratio of at Least 90%

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TABLE 2

Independent Factors of Each Group Associated With an NPV Ratio of at Least 90%: Multivariate Analysis

Parameters Multivariate Analysis Estimate 95% CI_P_ ValueBaseline parameters Intercept −3.025 −6.176 to 0.126 .060 Uterus position 0.879 −0.198 to 1.955 .110 Subcutaneous fat thickness (mm) 0.117 0.018–0.215 .021 \* Fibroid diameter (cm) −0.012 −0.030 to 0.006 .188 Distance (mm) \* 0.013 −0.017 to 0.043 .403 Fibroid type 0.480 −0.698 to 1.657 .424 T 2 SI parameters Intercept −1.978 −3.051 to −0.906 <.001 SI of uterine fibroids 0.004 −0.003 to 0.010 .257 SI ratio of fibroid to muscle 0.187 −0.150 to 0.525 .277 SI ratio of fibroid to myometrium 1.236 0.045–2.427 .042 † Semiquantitative perfusion MR parameters Intercept −6.055 −11.671 to −0.439 .035 Relative enhancement (in percentage) −0.001 −0.063 to 0.061 .971 Peak enhancement 0.006 0.00005 to 0.012 .048 † Relative peak enhancement (in percentage) −0.007 −0.071 to 0.058 .832 Time to peak (in seconds) −0.009 −0.017 to −0.001 .021 † Wash-in rate (per second) 0.093 −0.011 to 0.196 .079 Area under the curve −0.00001 −0.00003 to 0.000006 .220 Ratio of relative enhancement of fibroid to myometrium −1.099 −5.590 to 3.392 .632 Ratio of peak enhancement of fibroid to myometrium −3.096 −6.313 to 0.120 .059 Ratio of relative peak enhancement of fibroid to myometrium 3.108 −1.398 to 7.615 .176 Ratio of time to peak of fibroid to myometrium 0.381 −1.740 to 2.501 .725 Ratio of wash-in rate of fibroid to myometrium −0.261 −1.829 to 1.308 .745 Ratio of area under the curve of fibroid to myometrium 6.307 1.337–11.277 .013 †

CI, confidence interval; MR, magnetic resonance; NPV, nonperfused volume; SI signal intensity.

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Prediction Model

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y=e−6.958+0.143×1+0.189×2+0.008×3−0.015×4+4.785×51+e−6.958+0.143×1+0.189×2+0.008×3−0.015×4+4.785×5 y

−

6.958

0.143

0.189

0.008

−

0.015

4.785

−

6.958

0.143

0.189

0.008

−

0.015

4.785

for predicting an NPV ratio of at least 90% with five statistically significant predictors from multivariate analyses, where ×1 = thickness of the subcutaneous fat layer in the anterior abdominal wall (millimeters), ×2 = T2 SI ratio of fibroid to myometrium, ×3 = peak enhancement of fibroid, ×4 = time to peak of fibroid (in seconds), and ×5 = ratio of AUC of fibroid to myometrium. All the perfusion MRI parameters (ie, ×3, ×4, and ×5) and baseline parameter (ie, ×1) were statistically significant ( P < .05, Table 3 ), with the exception of T2 SI ratio of fibroid to myometrium (ie, ×2; P = .715, Table 3 ).

TABLE 3

Results of Generalized Estimating Equation (GEE) Analyses for Predicting the Treatment Outcome of MRI-guided HIFU Ablation With an NPV Ratio of at Least 90%

Parameters Estimate Standard Error 95% CI_P_ Value Intercept −6.958 2.385 −11.633 to −2.282 .004 Subcutaneous fat thickness (mm) 0.143 0.065 0.014–0.271 .030 \* SI ratio of fibroid to myometrium 0.189 0.518 −0.826 to 1.205 .715 Peak enhancement 0.008 0.002 0.003–0.012 .001 \* Time to peak (in seconds) −0.015 0.004 −0.023 to −0.007 .001 \* Ratio of area under the curve of fibroid to myometrium 4.785 1.666 1.519–8.051 .004 \*

CI, confidence interval; HIFU, high-intensity focused ultrasound; MRI, magnetic resonance imaging; NPV, nonperfused volume; SI, signal intensity.

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Assessment of 6 Months’ Follow-Up: Fibroid Volume and Symptom Changes

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TABLE 4

Comparison of Fibroid Tumor Volume and Symptom Changes Based on the NPV Ratio of at Least 90% and Less Than 90%

Treatment Outcome All Patients ( n = 120) NPV Ratio ≥90% ( n = 72) NPV Ratio <90% ( n = 48)P ValueFibroid volume (mL) \* Baseline .011 ‡ Mean ± SD 197.3 ± 155.7 226.7 ± 181.6 153.2 ± 90.7 Range 6.0–794.0 6.0–794.0 12.0–478.0 6 mo .004 ‡ Mean ± SD 113.2 ± 89.3 94.4 ± 70.8 141.4 ± 106.1 Range 4.0–578.0 4.0–400.0 10.0–578.0 Reduction ratio .001 ‡ Mean ± SD 0.38 ± 0.26 0.54 ± 0.13 0.14 ± 0.21 Range −0.21–0.84 0.30–0.84 −0.21 to 0.70Symptom severity score † Baseline .151 Mean ± SD 57.8 ± 16.0 56.1 ± 16.6 60.4 ± 14.9 Range 21.9–93.8 21.9–87.5 31.2–93. 6 mo .001 ‡ Mean ± SD 23.6 ± 26.3 8.0 ± 9.1 46.9 ± 26.5 Range 0.0–100.0 0.0–43.8 0.0–100.0 Improvement ratio .001 ‡ Mean ± SD 0.62 ± 0.39 0.86 ± 0.14 0.26 ± 0.37 Range −0.25–1.0 0.5–1.0 −0.25 to 1.0

NPV, nonperfused volume; SD, standard deviation.

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Safety Assessments

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TABLE 5

Complications and Adverse Effects of MRI-guided HIFU Treatment According to the NPV Ratio of at Least 90% and Less Than 90%

SIR Classification All Patients ( n = 120) NPV Ratio ≥90% ( n = 72) NPV Ratio <90% ( n = 48)P Value Class A Skin burn grade 1 3 (2.5) 0 (0) 3 (6.25) .062 Skin burn grade 2 1 (0.83) 0 (0) 1 (2.1) .400 Back pain 8 (6.7) 3 (4.2) 5 (10.4) .264 Pelvic pain 12 (10) 10 (13.9) 2 (4.2) .121 Leg pain 12 (10) 8 (11.1) 4 (8.3) .761 Nausea 6 (5) 6 (8.3) 0 (0) .080 Numbness 12 (10) 8 (11.1) 4 (8.3) .761 Vaginal discharge 13 (10.8) 10 (13.9) 3 (6.25) .154 Cystitis 1 (0.83) 1(1.4) 0 (0) 1.000

HIFU, high intensity focused ultrasound; MRI, magnetic resonance imaging; NPV, nonperfused volume; SIR, Society of Interventional Radiology.

Values in parentheses represent percentages.

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Discussion

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Conclusion

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References

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Magnetic Resonance Imaging Parameters in Predicting the Treatment Outcome of High-intensity Focused Ultrasound Ablation of Uterine Fibroids With an Immediate Nonperfused Volume Ratio of at Least 90%

Rationale and Objectives

Material and Methods

Results

Conclusions

Introduction

Materials and Methods

Patients

MRI Sequences

Assessment of T2W Images and Perfusion MRI

MR-guided High-intensity Focused Ultrasound Treatment

Therapeutic Efficacy and Safety Assessment

Data Analysis and Statistics

Results

Baseline Characteristics

Characteristics of MRI-guided HIFU Treatment of Uterine Fibroids

Analysis of Factors Influencing NPV Ratio of at Least 90%

Prediction Model

Assessment of 6 Months’ Follow-Up: Fibroid Volume and Symptom Changes

Safety Assessments

Discussion

Conclusion

References

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