Therapeutic dose and long-term efficacy of high-intensity focused ultrasound ablation for different types of uterine fibroids based on signal intensity on T2-weighted MR images

Figures & data

Figure 1. Flowchart of patient enrollment.

Figure 2. Classification of uterine fibroids on the basis of T2-weighted MR images. A1: heterogeneous extremely hypointense fibroids; A2: homogeneous extremely hypointense fibroids; B1: heterogeneous hypointense fibroids; B2: homogeneous hypointense fibroids; C1: heterogeneous isointense fibroids; C2: homogeneous isointense fibroids; D1: heterogeneous hyperintense fibroids; D2: homogeneous hyperintense fibroids.

Table 1. Comparison of baseline characteristics of patients with different types of uterine fibroids based on T2-weighted MR images.

	Extremely hypointensity (100)	Hypointensity (133)	Isointensity (104)	Hyperintensity (64)	p
Age (years)	38.8 ± 7.0	37.3 ± 6.6	38.7 ± 7.1	37.9 ± 6.6	.302
BMI (kg/m^2)	22.0 ± 2.4	21.7 ± 2.4	22.1 ± 2.8	22.5 ± 3.5	.224
Fibroid volume (cm^3)	113.1 (59.4–199.8)	84.0 (47.6–169.9)	161.6 (80.7–261.5)^b	148.8 (82.3–298.2)^b	<.001
Subcutaneous fat thickness (mm)	14.1 ± 5.7	13.4 ± 5.9	13.2 ± 6.0	13.1 ± 7.6	.637
Abdominal wall thickness (mm)	22.6 (18.6–26.4)	21.7 (17.3–26.2)	19.7 (15.1–24.3)^a	18.8 (15.6–28.8)	.015
Distance from posterior side of fibrosis to the sacrococcyx (mm)	19.7 (9.7–35.4)	18.8 (9.8–37.0)	14.2 (8.1–24.1)^b	15.2 (9.0–27.2)	.023
Distance from anterior side of fibroid to abdominal wall (mm)	40.2 (29.2–57.2)	43.4 (29.1–58.7)	37.0 (26.4–53.6)	35.5 (22.4–46.6)^b	.018
Type of fibroids (Sm/I/Ss)n/(%)	10/35/55 (10.0/35.0/55.0)	28/52/53 (21.1/39.1/39.8)	26/44/34 (25.0/42.3/32.7)	9/38/17 (14.1/59.4/26.6)	<.001
Location of fibroids (A/P/L/R/F)n/(%)	44/19/15/15/7 (44.0/19.0/15.0/15.0/7.0)	45/38/27/17/6 (33.8/28.6/20.3/12.8/4.5)	31/24/19/20/10 (29.8/23.1/18.3/19.2/9.6)	22/17/8/10/7 (34.4/26.6/12.5/15.6/10.9)	.436

Sm: submucosal; I: intramural; Ss: subserosal; A: anterior wall of the uterus; P: posterior wall of the uterus; L: left wall of the uterus; R: right wall of the uterus; F: fundus.

^a A significant difference between the group with extremely hypointense fibroids and each of the other group, p<.05.

^b A significant difference between the group with hypointense fibroids and the group with isointense fibroids, as well as the group with hyperintense fibroids, p<.05.

Table 2. Comparison of baseline characteristics of patients with heterogeneous uterine fibroids or homogeneous fibroids based on T2-weighted MR images.

	Extremely hypointensity		Hypointensity		Isointensity
	Heterogeneous (66)	Homogeneous (34)	Heterogeneous (89)	Homogeneous (44)	Heterogeneous (83)	Homogeneous (21)
Age (years)	39.5 ± 7.1	37.5 ± 6.6	38.3 ± 6.6	35.3 ± 6.1	39.3 ± 6.8	36.3 ± 7.9
BMI (kg/m^2)	22.0 ± 2.4	22.1 ± 2.5	21.8 ± 2.2	21.5 ± 2.6	22.3 ± 2.8	21.4 ± 2.9
Fibroid volume (cm^3)	141.1 (85.0–229.3)	74.3^a (40.1–142.6)	103.1 (54.3–207.8)	50.6^b (31.8–100.3)	173.9 (92.0–298.0)	132.7^c (23.0–208.3)
Subcutaneous fat thickness (mm)	14.3 ± 5.4	13.9 ± 6.3	12.9 ± 5.4	14.3 ± 6.7	13.2 ± 5.8	13.0 ± 6.6
Abdominal wall thickness (mm)	22.8 ± 7.0	23.1 ± 6.8	21.6 ± 6.4	24.5 ± 7.9	20.6 ± 7.3	19.9 ± 6.7
Distance from posterior side of fibroids to sacrococcyx (mm)	19.7 (9.6–31.3)	21.6 (10.0–38.2)	18.8 (9.8–32.9)	20.0 (9.8–41.0)	13.8 (8.1–20.9)	19.5 (7.7–24.6)
Distance from anterior side of fibroids to abdominal wall (mm)	37.9 (26.2–57.6)	41.6 (33.8–56.7)	38.8 (28.0–56.7)	51.1^b (34.4–63.8)	34.0 (26.4–50.4)	45.4^c (25.8–69.5)
Type of fibroids (Sm/I/Ss)n/(%)	7/23/36 (10.6/34.8/54.5)	3/12/19 (8.8/35.3/55.9)	20/30/39 (22.5/33.7/43.8)	8/22/14 (18.2/50.0/31.8)	20/35/28 (24.1/42.2/33.7)	6/9/6 (28.6/42.9/28.6)
Location of fibroids (A/P/L/R/F)n/(%)	24/12/13/11/6 (36.4/18.2/19.7/16.7/9.1)	20/7/2/4/1 (58.8/20.6/5.9/11.8/2.9)	30/21/22/11/5 (33.7/23.6/24.7/12.4/5.6)	15/17/5/6/1 (34.1/38.6/11.4/13.6/2.3)	26/17/16/16/8 (31.3/20.5/19.3/19.3/9.6)	5/7/3/4/2 (23.8/33.3/14.3/19.0/9.5)

Fibroid type (Sm: submucosal; I: intramural; Ss: subserosal); fibroid location (A: anterior wall of the uterus; P: posterior wall of the uterus; L: left wall of the uterus; R: right wall of the uterus; F: fundus).

^a A significant difference between the heterogeneous group and the homogeneous group in patients with extremely hypointense fibroids, p<.05.

^b A significant difference between the heterogeneous group and the homogeneous group in patients with hypointense fibroids, p<.05.

^c A significant difference between the heterogeneous group and the homogeneous group in patients with isointense fibroids, p<.05.

Table 3. Comparison of HIFU treatment results between different types of uterine fibroids based on T2-weighted MR images.

	Extremely hypointensity (100)	Hypointensity (133)	Isointensity (104)	Hyperintensity (64)	p
Power (W)	400 (400–400)	400 (400–400)	400 (400–400)	400 (400–400)	.165
Treatment time (min)	52.5 (37.3–75.0)	67.0 (48.0–100.0)^a	81.0 (58.3–116.5)^a	91.0 (71.0–130.5)^a,b	<.001
Sonication time (s)	497.5 (330.8–720.0)	575.0 (401.0–982.5)	900.0 (560.8–1200.0)^a,b	1000.0 (740.0–1289.0)^a,b	<.001
Treatment intensity (s/h)	569.0 ± 156.4	567.4 ± 183.4	649.2 ± 179.5^a,b	637.1 ± 135.9^a,b	<.001
Total energy (kJ)	199.0 (122.8–281.3)	230.0 (160.2–393.0)^a	360.0 (223.9–480.0)^a,b	400.0 (296.0–515.6)^a,b	<.001
Treatment efficiency (mm^3/s)	175.3 (95.5–301.8)	93.0 (48.3–205.9)^a	129.9 (50.7–261.4)^a	110.3 (60.9–237.3)^a	<.001
EEF (J/mm^3)	1.5 (0.9–2.9)	3.0a (1.3–5.8)	2.2 (1.0–5.5)^a	2.5 (1.2–4.6)^a	<.001
NPV ratio (%)	75.2 ± 14.6	71.1 ± 15.6	68.2 ± 17.3^a,b	67.8 ± 16.6^a,b	.006

^a A significant difference between the group with extremely hypointense fibroids and each of the other group, p<.05.

^b A significant difference between the group with hypointense fibroids and the group with isointense fibroids, as well as the group with hyperintense fibroids, p<.05.

Table 4. Comparison of HIFU treatment results between heterogeneous uterine fibroids and homogeneous fibroids in different groups based on T2-weighted MR images.

	Extremely hypointensity		Hypointensity		Isointensity
	Heterogeneous (66)	Homogeneous (34)	Heterogeneous (89)	Homogeneous (44)	Heterogeneous (83)	Homogeneous (21)
Power (W)	400 (400–400)	400 (400–400)	400 (400–400)	400 (400–400)	400 (400–400)	400 (400–400)
Treatment time (min)	54.0 (43.3–76.3)	48.0 (33.0–67.5)	65.0 (48.5–100.5)	74.5 (44.5–99.3)	86.0 (60.0–122.0)	75.0^c (54.0–82.0)
Sonication time (s)	512.5 (393.5–763.5)	412.0^a (260.0–571.0)	592.0 (413.5–999.5)	551.0 (360.3–947.0)	900.0 (578.0–1245.0)	750.0 (425.0–1152.5)
Treatment intensity (s/h)	596.7 ± 157.9	515.2 ± 140.5^a	585.3 ± 192.3	531.2 ± 160.1	646.6 ± 174.2	659.5 ± 203.3
Total energy (kJ)	205 (151.4–305.4)	164.8^a (104.0–224.7)	236.8 (164.0–399.8)	210.8 (144.1–378.8)	360.0 (231.2–490.4)	300.0 (170.0–461.0)
Treatment efficiency (mm^3/s)	197.2 (116.3–320.9)	162.6 (65.4–274.4)	122.0 (64.3–254.2)	59.6^b (35.5–145.2)	133.2 (50.7–262.4)	123.0 (37.8–234.9)
EEF (J/mm^3)	1.3 (0.9–2.4)	1.7 (1.0–4.3)	2.3 (1.1–4.4)	4.7^b (2.0–7.9)	2.1 (1.0–5.3)	2.3 (1.2–7.6)
NPV ratio (%)	74.2 ± 13.1	77.0 ± 17.2	70.6 ± 15.5	72.2 ± 15.9	66.4 ± 17.4	75.3 ± 14.8c

^a A significant difference between the heterogeneous group and the homogeneous group in patients with extremely hypointense fibroids, p<.05.

^b A significant difference between the heterogeneous group and the homogeneous group in patients with hypointense fibroids, p<.05.

^c A significant difference between the heterogeneous group and the homogeneous group in patients with isointense fibroids, p<.05.

Table 5. Univariate analysis related to NPV ratio.

	NPV ratio < 60% n/n%	60%≤NPV ratio < 80% n/n%	NPV ratio ≥ 80% n/n%	p
Age (years)				.523
≤37 years	56 (25.3%)	105 (47.5%)	60 (27.2%)
>37 years	38 (21.1%)	86 (47.8%)	56 (31.1%)
BMI (kg/m^2)				.074
≤21.63 kg/m^2	38 (18.7%)	104 (51.2%)	61 (30.1%)
>21.63 kg/m^2	56 (28.3%)	87 (43.9%)	55 (27.8%)
Fibroid volume (cm^3)				.155
≤84.49 cm^3	54 (26.9%)	87 (43.3%)	60 (29.9%)
>84.49 cm^3	40 (20.0%)	104 (52.0%)	56 (28.0%)
Ablation volume of fibroids (cm^3)				<.001
≤85.13 cm^3	69 (34.3%)	85 (42.3%)	47 (23.4%)
>85.13 cm^3	25 (12.5%)	106 (53.0%)	69 (34.5%)
Signal intensity on T2WI				.054
Extremely hypointensity	12 (12.0%)	52 (52.0%)	36 (36.0%)
Hypointensity	31 (23.3%)	62 (46.6%)	40 (30.1%)
Isointensity	31 (29.8%)	48 (46.2%)	25 (24.0%)
Hyperintensity	20 (31.3%)	29 (45.3%)	15 (23.4%)
Subcutaneous fat thickness (mm)				.095
≤11.85 mm	40 (19.9%)	106 (52.7%)	55 (27.4%)
>11.85 mm	54 (27.0%)	85 (42.5%)	61 (30.5%)
Abdominal wall thickness (mm)				.260
≤21.65 mm	42 (20.7%)	96 (47.3%)	65 (32.0%)
>21.65 mm	52 (26.3%)	95 (48.0%)	51 (25.8%)
Distance from posterior side of fibroids to sacrococcyx (mm)				.388
≤14.05 mm	36 (17.9%)	96 (47.8%)	69 (34.3%)
>14.05 mm	58 (29.0%)	95 (47.5%)	47 (23.5%)
Distance from anterior side of fibroids to abdominal wall (mm)				.009
≤38.8 mm	48 (23.7%)	90 (44.6%)	64 (31.7%)
>38.8 mm	46 (23.1%)	101 (50.8%)	52 (26.1%)
Type of fibroids				.019
Submucosal	18 (24.7%)	42 (57.5%)	13 (17.8%)
Intramural	46 (27.2%)	66 (39.1%)	57 (33.7%)
Subserosal	30 (18.9%)	83 (52.2%)	46 (28.9%)
Location of fibroids				.054
Anterior wall of the uterus	21 (14.8%)	67 (47.2%)	54 (38.0%)
Posterior wall of the uterus	29 (29.6%)	47 (48.0%)	22 (22.4%)
Left wall of the uterus	19 (27.5%)	36 (52.2%)	14 (20.3%)
Right wall of the uterus	18 (29.0%)	27 (43.5%)	17 (27.4%)
Fundus	7 (23.3%)	14 (46.7%)	9 (30.0%)
Treatment time (min)				<.001
≤71 min	25 (12.4%)	103 (51.0%)	74 (36.6%)
>71 min	69 (34.7%)	88 (44.2%)	42 (21.1%)
Sonication time (s)				<.001
≤680 s	30 (14.7%)	106 (52.0%)	68 (33.3%)
>680 s	64 (32.5%)	85 (43.1%)	48 (24.4%)

The NPV ratio was used as the dependent variable and the patients were divided into three groups according to NPV ratio. In the independent variables, the median value was used to classify the continuous numerical variables.

Table 6. Multivariate ordered logistic regression analysis for NPV ratio.

	B	SE	Wald	p	Exp (B)	95%CI
Ablation volume of fibroids (cm^3)
≤85.13 cm^3 >85.13 cm^3	–0.907	0.225	16.235	<.001	0.404	0.260–0.628
Distance from anterior side of fibroids to abdominal wall (mm)
≤38.8 mm >38.8 mm	0.131	0.215	3.497	.061	0.609	0.748–1.737
Type of fibroids
Submucosal	–0.496	0.265	3.497	.061	0.609	0.362–1.024
Intramural Subserosal	–0.019	0.214	0.008	.930	0.981	0.645–1.493
Treatment time (min)
≤71 min >71 min	0.872	0.286	9.309	.002	2.391	1.366–4.186
Sonication time (s)
≤680 s >680 s	0.296	0.288	1.052	.305	1.344	0.764–2.365

The NPV ratio was used as the dependent variable and the patients were divided into three groups according to NPV ratio. In the independent variables, the median value was used to classify the continuous numerical variables.

Table 7. Comparison of adverse effects among different types of uterine fibroids based on T2-weighted MR images.

	Extremely hypointensity (n = 100)	Hypointensity (n = 133)	Isointensity (n = 104)	Hyperintensity (n = 64)	p
Leg pain (n, %)	9 (9.0)	20 (15.0)	25 (24.0)	18 (28.1)	.004
Sciatic or buttock pain (n, %)	32 (32.0)	64 (48.1)	45 (43.3)	29 (45.3)	.091
Skin burning sensation (n, %)	22 (22.0)	36 (27.1)	35 (33.7)	23 (35.9)	.157
Treated area pain (n, %)	12 (12.0)	16 (12.0)	18 (17.3)	11 (17.2)	.531
Groin pain (n, %)	4 (4.0)	4 (3.0)	3 (2.9)	1 (1.6)	.848

Table 8. Comparison of re-intervention rate between different types of uterine fibroids based on T2-weighted MR images.

	Extremely hypointensity (100)	Hypointensity (133)	Isointensity (104)	Hyperintensity (64)	Total (401)	p
Number of follow-up cases	43	81	56	35	215	.674
Number of re-intervention cases	6	11	10	3	30
Cumulative re-intervention rate (%)	8.4	10.3	12.5	6.1	9.7

The cumulative reintervention rate was calculated using the correction formula: CI=I/(N – W/2), where I=number of re-interventions during the observation period, W=number of lost visits during the observation period and N=number of originating observations.