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Authors M. L. Frank1, S. D. Schäfer1, M. Möllers1, M. K. Falkenberg1, J. Braun1, U. Möllmann1, F. Strube1, A. Fruscalzo2, S. Amler3,
W. Klockenbusch1, R. Schmitz1
1
Affiliations Department of Obstetrics and Gynecology, University Hospital of Münster, Germany
2
Department of Obstetrics and Gynecology, St. Franziskus-Hospital, Münster, Germany
3
Institute of Biostatistics and Clinical Research, University of Münster, Germany
The “sickle sign” was assessed in the whole group on the basis of Results
a scale of 0 to 2 points. 0 points were given if no “sickle sign” !
could be seen, 1 point if a thin red line was observed and 2 points 206 women fulfilled the study criteria and were analyzed. 143
if a “sickle sign” as defined above was seen. The “sickle sign” was women presented without any uterine pathology, 41 with uter-
approved by a second operator. ine fibroids and 22 with adenomyosis. Elastographic data analy-
Motion compensation was activated and two quadratic 5 mm sis was feasible in all cases.
ROIs were placed one upon the other in the anterior inferior uter- Patient age ranged from 16 to 81 years. The mean ±SD age of the
ine segment at the moment of maximal relaxation. The first ROI whole study population was 44.7 ± 16.1. The mean ages of the
(ROI1) was placed close to the probe, and the second ROI (ROI2) group without abnormalities, the uterine fibroid group and the
adjacent to the endometrium. In order to standardize the meas- adenomyosis group were 44.3 ± 16.8, 50.4 ± 14.8 and 36.9 ± 8.9,
urement as much as possible, they were situated in extension of respectively.
the probe axis, with a maximum deviation of 20 degrees. Strain The mean ±SD frame rate of the records was 14.8 ± 0.7. The mean
values were measured at the two ROIs and their ratio was calcu- frame rates in the control group, uterine fibroid group and ade-
lated during a cycle of tissue compression and relaxation (ROI1 / nomyosis group were 14.9 ± 0.7, 14.7 ± 0.8 and 14.6 ± 0.8, respec-
ROI2). The maximum of the ratio was stored and named the “age tively. There was no significant difference between the frame
index”. rates in the three groups (p = 0.227).
Second, elastographic data of all groups were analyzed to assess In the elastogram, the average uterus of a young woman was
the presence of a uterine fibroid or adenomyosis. mostly colored in blue, with smaller contents of green, at the mo-
Again two quadratic 5 mm ROIs were chosen, and motion com- ment of maximal relaxation. When compression began, the color
pensation was activated. In the control group, ROIs were placed phenomenon that was previously defined as the “sickle sign” oc-
side by side in the anterior inferior uterine segment between curred. The red sickle-shaped form in the anterior inferior uter-
the probe and the endometrium in homogeneous tissue. In the ine segment near the ultrasound probe expanded with increas-
uterine fibroid and adenomyosis group, the first (ROI3) was ing compression (● " Fig. 1a). The average uterus of an older
placed in healthy homogeneous tissue, and the second (ROI4) woman was also mostly colored in blue, with smaller contents
was placed on an equal level in a myoma or an area of adenomyo- of green, before pressure was applied to it. The composition bare-
sis. The ROIs were placed at the same distance from the probe be- ly changed during the following cycle of compression (● " Fig. 1b).
cause a comparable amount of pressure reaches the same depth A significant difference was found for the mean ages between the
of the tissue. Strain values were measured, and their ratio was group with the “sickle sign” and without the “sickle sign” and be-
calculated during a cycle of tissue compression (ROI3 / ROI4). tween the group with a thin red line and without the “sickle sign”
The maximum ratio was stored as the “lesion index”. (p < 0.001). The group with a thin red line was older by trend than
All strain measurements were performed three times, and mean the group with the “sickle sign”, but the difference was not signif-
values of the stored maxima were calculated to achieve more re- icant (p = 0.058). The mean ages of the group with the “sickle
liable data. sign”, with a thin red line and without the “sickle sign” were
To assess intra- and interobserver reliability, 10 cases were selec- 34.5 ± 12.9, 41.8 ± 14.5 and 56.6 ± 13.9 years, respectively.
ted and strain ratios were measured two times by the operator A negative correlation was found between age and “age index”
and independently another time by a second operator. (r = –0.49, p < 0.001). ●
" Fig. 2 shows how the maximum strain ra-
tio declines with age. The median “age index” was 2.4.
Statistical analysis Uterine myomas could be identified as blue rounded areas. They
Statistical analyses were performed using IBM SPSS® Statistics 22 appear to be darker than the surrounding tissue and are often set
for Windows (IBM Corporation, Somers, NY, USA). off from the surrounding tissue by a green border (● " Fig. 1c).
Descriptive statistics were performed to characterize the study Areas of adenomyosis had a spotted, irregular color pattern and
population. The results are shown as mean ± standard deviation appeared brighter than the adjacent normal myometrium. Often
(SD) or as median with interquartile range (IQR). foci of adenomyosis with a red center surrounded by a yellow and
To compare the age between the three independent groups with a green irregular border could be seen (● " Fig. 1 d).
the “sickle sign”, with a thin red line, and without the “sickle The median “lesion indices” of the uterine fibroid group, the ade-
sign”, analysis of variance for normally distributed data was per- nomyosis group and the control group were shown to be signifi-
formed. cantly different (p < 0.001). The median “lesion index” indicative
The Spearman‘s rank correlation coefficient was chosen to assess for a myoma was 2.65 [2.12; 3.34] and the one indicative for ade-
the correlation between age and “age index”. nomyosis was 0.44 [0.36; 0.46]. Healthy homogeneous uterine
To compare the “lesion indices” and the frame rates of the three tissue had a median “lesion index” of 1.19 [1.07; 1.34] (● " Fig. 3).
independent groups without abnormalities, with uterine fibroids A suitable cut-off value predictive for uterine fibroids was 1.785,
and with adenomyosis, the Kruskal-Wallis test for non-normally with a sensitivity of 88 % and a specificity of 95 %. The area under
distributed data was conducted. the curve value was 0.955 (95 % confidence interval (CI): 0.919 –
To adjust for multiple testing, Bonferroni-post hoc tests were per- 0.992). A suitable cut-off value predictive for adenomyosis was
formed. 0.505, with a sensitivity and specificity of 86 % and 100 %, respec-
The area under the receiver operating characteristic (ROC) curve tively. The area under the curve value was 1. The ROC curves of
(AUC) analysis was performed to determine “lesion index” cut-off the “lesion indices” for uterine fibroids and adenomyosis are
values that predict with a high sensitivity and specificity the shown in ● " Fig. 4, 5.
presence of a uterine fibroid or adenomyosis. Intra- and interobserver reliability of strain measurements were
Intra- and interobserver reliability of strain measurements was shown to be excellent [17]. The interobserver reliability was
determined using the intraclass correlation coefficient. 0.983 (95 % CI: 0.933 – 0.996; p < 0.001) and the intraobserver re-
P-values were considered significant in case of p ≤ 0.05. liability was 0.987 (95 % CI: 0.948 – 0.997; p < 0.001).
■ Proof copy for correction only. All forms of publication, duplication or distribution prohibited under copyright law. ■
Fig. 1 Transvaginal elastography: The elastogram can be seen in real-time Abb. 1 Transvaginale Elastografie: Das Elastogramm wird in Echtzeit ne-
next to the regular B-mode image on the screen. a Uterus of a 19-year-old ben dem regulären B-Mode-Bild abgebildet. a Uterus einer 19-jährigen Frau
woman with “sickle sign”. The red sickle-shaped form that is located in the mit „Sichel-Zeichen“. Die rote sichelförmige Figur, die sich im vorderen un-
anterior inferior uterine segment near to the probe is a recurrent color teren Uterinsegment nahe des Ultraschallkopfes befindet, ist ein wieder-
phenomenon in younger uteri. b Uterus of a 73-year-old woman without kehrendes Farbphänomen in jüngeren Uteri. b Uterus einer 73-jährigen Frau
“sickle sign”. c Uterine fibroid. d Adenomyosis. Both focal findings (marked ohne „Sichel-Zeichen“. c Myom. d Adenomyose. Beide Herdbefunde (durch
with an *) are good to distinguish from the surrounding healthy tissue on ein * markiert) sind im farbkodierten Elastografie-Bild gut vom umgeben-
the color-coded elasticity image. den gesunden Gewebe abzugrenzen.
Fig. 2 Scatter plot showing the correlation of “age index” (y-axis) and Fig. 3 Box-and-whisker plot showing the distribution of the “lesion index”
age of a woman in years (x-axis). The correlation is moderately negative in the control group, uterine fibroid group and adenomyosis group. The
(r = –0.49, p < 0.001). median “lesion indices” are significantly different between the three
Abb. 2 Das Streudiagramm zeigt die Korrelation von „Altersindex“ groups (p < 0.001).
(Y-Achse) und Alter in Jahren (X-Achse) an. Die Korrelation ist moderat Abb. 3 Der Box-Whisker-Plot zeigt die Verteilung des „Läsionsindex“ in
negativ (r = –0,49, p < 0,001). der Kontrollgruppe, Myomgruppe und Adenomyosegruppe. Die medianen
„Läsionsindices“ sind zwischen den drei Gruppen signifikant unterschied-
lich (p < 0,001).
Discussion
!
Our study has shown that uterine tissue can be evaluated with tissue are low, the measured strain value at the first ROI was high
transvaginal elastography. Uterine tissue stiffness was able to be and the second low. In consequence, the ratio was high if a “sickle
illustrated and was measurable using this new imaging tool. sign” existed and low in case of its absence. According to the di-
The “age index” shows that the normal uterus has a certain age- minution of the “sickle sign” with age, the ratio between the two
dependent stiffness and that this stiffness increases with age. The measuring points declined with increasing age. In all groups two
“lesion index” allows for the assessment of the presence of a uter- ROIs were placed side by side in the uterine tissue. The first was
ine fibroid or adenomyosis. always placed in healthy tissue, the second was placed in a focal
In the control group two ROIs were first placed one above the finding or in homogeneous tissue.
other, the first adjacent to the probe and the second adjacent The ratios of normal uterine tissue ranged around 1, emphasizing
to the endometrium. As a result, in most cases of a “sickle sign”, that normal uterine tissue is relatively homogeneous. The mean
the first ROI was placed in it and the second above it. Because ratio of uterine fibroids was > 1 and the mean ratio of adenomyo-
strain values of soft tissue are high, whereas strain values of stiff
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with a larger number of cases, a possible influence of the size and 09 Friedrich-Rust M, Ong MF, Martens S et al. Performance of transient
elastography for the staging of liver fibrosis: a meta-analysis. Gastro-
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The nearer focal findings, especially myomas, were located close tion of prostate cancers: a meta-analysis. BJU Int 2012; 110: E614 –
to the probe and the more they were compressed in the direction E620
of the applied force, the better they could be depicted. Prospec- 11 Bojunga J, Herrmann E, Meyer G et al. Real-time elastography for the
differentiation of benign and malignant thyroid nodules: a meta-anal-
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dominal pressure, manually applied by the gynecologist during mendations on the clinical use of ultrasound elastography. Part 2: Clin-
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elasticity and BIRADS scoring. Breast Cancer Res Treat 2012; 133:
firmation and correlation and customized software are required 23 – 35
to evaluate the value of our findings. 14 Wojcinski S, Degenhardt F, Peisker U et al. Sonoelastography usage
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15 Fruscalzo A, Londero AP, Frohlich C et al. Quantitative Elastography of
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