Microbubble contrast agent SonoVue combined with oxytocin improves the efficiency of high-intensity focused ultrasound ablation for adenomyosis

Figures & data

Figure 1. The process of patient selection was shown, with the final number of patients as 330.

Table 1. Basic information and treatment data of patients.

Variables	Group A	Group B	Group C	Group D	Total/p
No. of patients	82	85	81	82	330
Dysmenorrhea	82	83	79	81	0.71
Hypermenorrhagia	72	76	71	70	0.65
Menostaxis	71	66	69	67	0.58
Age (y)	38.1 ± 6.9	37.0 ± 5.9	36.9 ± 3.8	37.9 ± 6.1	0.47
Thickness of adenomyosis (cm)	5.1 ± 0.9	5.7 ± 1.1	6.0 ± 1.7	5.2 ± 1.1	0.66
Location of uterus
Anteverted	49	53	48	47	0.39
Midposition	29	31	28	30	0.72
Retroverted	4	5	3	3	0.28
Location of disease
Anterior	27	31	26	29	0.43
Posterior	37	41	38	39	0.52
Fundus	10	13	11	9	0.61
Lateral	5	6	5	3	0.54
Ablation time(s)	633.7 ± 55.1	874.2 ± 65.6	936.3 ± 85.2	1303.2 ± 96.2	0.00
EEF(J/mm3)	4.7 ± 0.9	8.5 ± 0.6	8.9 ± 0.7	12.6 ± 1.8	0.01
VAS	6.1 ± 0.5	5.3 ± 0.8	4.4 ± 0.6	4.9 ± 1.1	0.43
NPVR (%)	90.4 ± 8.8%	88.7 ± 9.1%	89.4 ± 7.2%	80.5 ± 7.9%	0.25
Sonication power (W)	371.8 ± 29.3	383.8 ± 31.6	379.2 ± 26.4	390.1 ± 33.6	0.38

Unless otherwise noted, values are presented as mean ± standard deviation. NPVR: non-perfusion volume ratio; EEF: energy efficiency factor; VAS: Visual Analogue Scale.

Figure 2. Before HIFU ablation, the lesion of adenomyosis is in the posterior wall of uterus with low echo (A). After HIFU ablation, the echo of adenomyosis turns white(B); Before HIFU, the T2WI MRI shows the adenomyosis in the posterior wall of the uterus with hypointensity signal and hyperintensity pot sac signal (C); On contrast enhanced magnetic resonance imaging after treatment, the non-perfused volume (arrows) in the posterior wall is necrosis of the adenomyosis (D).

Figure 3. The high-intensity focused ultrasound (HIBU) ablation time, EEF (energy efficiency factor), NPVR (non-perfused volume ratio), and VAS (Visual Analogue Scale) were shown among four groups. (A) A significant (p < 0.05) difference existed in the HIFU ablation time between group A and each of the other three groups (*) or between groups B or C and group D (**). (B) A significant (p < 0.05) difference existed in EEF between group A and each of the other three groups (*) or between groups B or C and group D (**). (C) A significant (p < 0.05) difference existed in NPVR between group A and group D (*). (D) No significant (p > 0.05) difference was found in VAS among four groups. *Indicates a significant (p < 0.05) difference between group A and the other groups in figures A and B or between groups A and D in figure (C). ** indicates a significant (p < 0.05) difference between group B or C and group D.

Table 2. Tests of effects between subjects with ablation time as the dependent variable.

Source	Type III sum of squares	df	Mean square	F	Significance	Eta^2
Correct model	8836634.206a	3	2945544.735	2258.085	0.000	0.954
Intercept	245205105.363	1	245205105.363	187976.740	0.000	0.998
Oxytocin	6013368.565	1	6013368.565	4609.910	0.000	0.934
SonoVue	2746157.144	1	2746157.144	2105.232	0.000	0.866
Oxytocin* SonoVue	165863.649	1	165863.649	127.153	0.000	0.281
Error	423944.256	325	1304.444
Total	254766187.000	329
Corrected total	9260578.462	328

^aR²=0.954 (correct R²=0.954) synergy between oxytocin and SonoVue exist (p = 0.00).

Table 3. Complications of HIFU treatment for adenomyosis.

Variables	Group A	Group B	Group C	Group D	p Value
VAS	6.1 ± 0.5	5.3 ± 0.8	4.4 ± 0.6	4.9 ± 0.3	0.125
Lower abdominal pain (%)	69 (84.1%)	60 (70.6%)	65 (80.2%)	61 (74.4%)	0.271
Leg pain (%)	21 (25.6%)	16 (18.8)	18 (22.2%)	17 (20.7%)	0.103
Sacrum/buttock pain (%)	12 (14.6%)	10 (11.8%)	11 (13.6%)	9 (11.0%)	0.231
Groin pain (%)	2 (2.4%)	1 (1.2%)	1 (1.2%)	0	0.386
Fever (%)	0	1 (1.2%)	0	1 (1.2%)	0.388
Skin blister (%)	1 (1.2%)	0	1 (1.2%)	0	0.698
Nausea or vomiting (%)	4 (4.9%)	3 (3.5%)	2 (2.5%)	1 (1.2%)	0.657
Hematuresis (%)	1 (1.2%)	0	0	0	0.501
Flushed face (%)	1 (1.2%)	1 (1.2%)	0	0	0.301

VAS: Visual Analogue Scale; HIFU: high-intensity focused ultrasound.

Data availability statement

All data and materials analyzed in this study are included in the manuscript. The data used and/or analyzed in the current study are available from the corresponding author on reasonable request.