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Importance of Transvaginal Elastography in the Diagnosis of Uterine Fibroids


and Adenomyosis

Article  in  Ultraschall in der Medizin · August 2015


DOI: 10.1055/s-0035-1553266 · Source: PubMed

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Original Article 1

Importance of Transvaginal Elastography in the


Diagnosis of Uterine Fibroids and Adenomyosis
Stellenwert der transvaginalen Elastografie in der Diagnose
von uterinen Myomen und Adenomyose

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

Key words Abstract Zusammenfassung


● elastography
"
! !
● uterus
"
Purpose: To evaluate normal uterine tissue with Ziel: Evaluation von normalem Uterusgewebe mit
● uterine fibroids
"
special regard to age and the presence of uterine besonderem Hinblick auf das Alter und Beurtei-
● adenomyosis
"
fibroids and adenomyosis with transvaginal elas- lung des Vorliegens von Myomen und Adeno-
tography. myose mittels transvaginaler Elastografie.
Materials and Methods: In a prospective study Material und Methoden: In einer prospektiven
elastographic data of the uterus were obtained in Studie wurden bei 206 unselektierten Frauen
206 unselected women with transvaginal ultra- elastografische Daten des Uterus mit transva-
sound. Women who presented without any uter- ginalem Ultraschall erhoben. Frauen ohne uterine
ine pathology in ultrasonography were included Pathologie im Ultraschall wurden einer Kontroll-
in a control group, women with uterine fibroids gruppe zugeteilt, Frauen mit Myom oder Ade-
in a uterine fibroid group, and women with ade- nomyose einer Myom-bzw. Adenomyosegrup-
nomyosis in an adenomyosis group. In the control pe. In der Kontrollgruppe wurden Strain-Werte
group strain values were measured at two regions an zwei übereinander liegenden Bildbereichen
of interest (ROIs) placed one upon the other in the (ROIs) im vorderen unteren Uterinsegment ge-
anterior inferior uterine segment during a cycle of messen. Die während eines Kompressionszyklus-
compression. The maximum strain ratio (ROI1 / ses ermittelte maximale Strain-Ratio (ROI1 /
ROI2) was stored as the “age index”. In all groups ROI2) wurde als „Altersindex“ gesichert. In allen
strain values were measured at two ROIs placed Gruppen wurden Strain-Werte an zwei nebenei-
side by side in a uterine fibroid (uterine fibroid nander liegenden ROIs gemessen. Im Falle der
group) or adenomyosis (adenomyosis group) or Myom- und Adenomyosegruppe befand sich jew-
received 26.1.2015
accepted 4.5.2015 healthy homogeneous tissue (control group) and eils ein ROI innerhalb des Herdbefundes und ei-
adjacent healthy tissue. Maximum strain ratios ner in benachbartem gesundem Gewebe. In der
Bibliography (ROI3 / ROI4) were stored as the “lesion index”. Kontrollgruppe lagen beide ROIs in gesundem Ge-
DOI http://dx.doi.org/
Results: The “age index” was significantly negatively webe. Die maximale Strain-Ratio (ROI3 / ROI4)
10.1055/s-0035-1553266
correlated with the age of the women (r = –0.49, wurde als „Läsionsindex“ gesichert.
Published online: 2015
Ultraschall in Med 2015; 36: 1–6 p < 0.001). The median “lesion indices” were signifi- Ergebnisse: Der „Altersindex“ war signifikant
© Georg Thieme Verlag KG cantly (p < 0.001) different between the uterine fi- negativ mit dem Alter einer Frau korreliert
Stuttgart · New York · broid, adenomyosis and control groups. Median “le- (r = – 0,49, p < 0,001). Die medianen „Läsionsindi-
ISSN 0172-4614 sion indices” were 2.65, 0.44 and 1.19, respectively. ces“ der Myom-, Adenomyose- und Kontroll-
Conclusion: The “age index” shows that normal gruppe waren signifikant unterschiedlich (p <
Correspondence
Mareike Lea Frank uterine tissue has a certain age-dependent stiff- 0,001). Sie betrugen 2,65, 0,44 und 1,19.
Department of Obstetrics and ness that increases with age. The “lesion index” Schlussfolgerung: Der „Altersindex“ zeigt, dass
Gynecology, University Hospital allows for the assessment of the presence of a uter- normales Uterusgewebe eine gewisse Festigkeit
of Münster ine fibroid or adenomyosis and helps to differenti- aufweist, die mit dem Alter zunimmt. Der „Läsion-
Albert-Schweitzer-Campus 1 ate between both focal findings. Thus the use of sindex“ erlaubt die Beurteilung des Vorliegens von
Gebäude A1
elastography in addition to conventional ultra- Myomen und Adenomyose und hilft bei deren Dif-
48149 Münster
sound could help to diagnose uterine focal lesions ferenzierung. Somit könnte die zusätzliche Anwen-
Germany
Tel.: ++ 49/2 51/8 34 82 61 and may be useful in preoperative planning. dung von Elastografie zum konventionellen Ultra-
Fax: ++ 49■■■ schall bei der Diagnose uteriner Herdbefunde und
m_fran30@uni-muenster.de der präoperativen Planung helfen.
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Frank ML et al. Importance of Transvaginal … Ultraschall in Med 2015; 36: 1–6

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2 Original Article

Introduction Material and Methods


! !
In the manual transvaginal examination, the normal uterus pre- Study population
sents itself as a relatively soft and equally easy to deform organ in In a prospective and cross-sectional study, between March 2013
younger women, whereas it appears as a stiffer and less deform- and August 2014, elastographic data of the uterus were collected
able organ in older women. in 206 unselected women who underwent transvaginal ultra-
Differences from these palpatory findings are suspicious of pa- sound during routine examination in the department of obste-
thology. For example, myomas can often be identified as stiff no- trics and gynecology of the University Hospital Münster. Women
dules or a uterus myomatosus as a non-specific solidification of who presented without any uterine pathology, with uterine
the uterus. The described tissue characteristics seem to be well fibroids or with adenomyosis in ultrasonography were included
accepted. Nevertheless, to date, published data about the charac- in the study. Myomas were defined as concentric, round and
terization of normal uterine tissue are scarce [1]. sharply defined lesions, whereas adenomyosis was defined as an
Uterine fibroids and adenomyosis are frequent uterine patholo- elliptical lesion, with poorly defined borders. These conventional
gies. Fibroids are the most common benign tumors of the female ultrasound diagnosis criteria served as the gold standard in our
genital tract [2], with a cumulative incidence that ranges about study. Women with pregnancy, uterine infection, previous uter-
70 – 80 % by age 50 [3]. ine surgery or specific hormonal therapy were excluded. In-
Adenomyosis is defined as the presence of ectopic endometrial formed consent was obtained from all patients and the study
mucosa within the myometrium. Its prevalence varies widely, was approved by the institutional ethics board.
from 5 to 70 %, with a mean of 20 – 30 % in surgical findings [4].
Both pathologies can cause substantial morbidity. Fibroids, for Ultrasound examination
example, are shown to be associated with a morbidity of nearly Transvaginal elastography was performed with an IU22 and
40 % of women during their reproductive years and sometimes EPIQ7C Ultrasound System (Philips Medical Systems, Andover,
even after menopause [5]. As a consequence, uterine fibroids MA, USA) using the C10 – 3v PureWave 10 MHz vaginal probe.
and adenomyosis may require medical treatment or surgery. Elastographic scanning (elastographic dual-mode scanning in
Therefore, there is considerable interest in improving their diag- real-time) followed regular B-mode scanning of the uterus. Data
nosis and achieving detailed information about their exact loca- acquisition was performed independently of uterus position and
tion and extent, especially with regard to an upcoming surgical size. External compression was applied to the tissue by the ultra-
intervention. sound probe causing its deformation that was measured as
Transvaginal ultrasound is the most important imaging tech- strain. One cycle of gentle compression and relaxation was per-
nique in the assessment of gynecological findings [6]. Its impor- formed by an experienced gynecologist. The probe was gently
tance in the diagnosis, follow-up and delivery of pre-surgical in- moved against the lower uterine segment followed by slow de-
formation of gynecological pathologies is due to its accessibility compression. Movements were realized along the axis of the
and relatively low cost. transducer and the elastographic sample box was placed in the
Elastography is a new ultrasound tool that delivers information same axis. The measured strain values were color coded and dis-
about the elasticity of tissue. By its use, tissue stiffness can be played as an elastogram.
quantified [7]. The elastogram could be seen in real-time next to the regular
The normal ultrasound allows for the application of elastography B-mode image on the screen.
within routine examination. Elastograms are colored with an ascending color scale that ranges
In the past few years a multitude of studies have been published from blue over green and yellow to red. Blue indicates stiff tissue,
evaluating the application of elastography in different organs such green moderately stiff tissue, yellow moderately soft tissue and
as the breast, liver, prostate and thyroid gland [8 – 11]. Recommen- red soft tissue. They were superimposed on B-mode images to
dations on its clinical use have been published recently [12]. permit better interpretation.
The results are promising and it can be assumed that elastogra- Tissue stiffness is assessed in comparison with the adjacent tis-
phy will be established as a diagnostic tool in the future. sue. In consequence, the calculated strain values and correspond-
Among others, elastography has been shown to improve the dif- ing colors are relative indicators for tissue stiffness.
ferentiation of benign and malignant breast lesions [8, 13] and
nowadays 21 % of German breast ultrasound specialists are ap- Elastography data analysis
plying sonoelastography in the diagnosis of breast lesions [14]. Elastographic raw data were analyzed offline with QLAB Ad-
The first studies have just been published on the assessment of vanced Quantification Software 9 and 10 (Philips Medical Sys-
cervical stiffness in pregnancy and the related risk of preterm tems, Andover, MA, USA). The operator was not involved in the
birth [15, 16]. previous acquisition of the raw dataset and was previously su-
The aim of our study was to assess normal uterine tissue stiffness pervised in elastographic data analysis. Women who presented
with special regard to age with transvaginal elastography. Fur- without any uterine pathology were included in a control group,
thermore, we evaluate the difference of stiffness between uterine women with uterine fibroids in a uterine fibroid group and wom-
fibroids, adenomyosis and normal uterine tissue with transvagi- en with adenomyosis in an adenomyosis group.
nal elastography. Color patterns and strain values were evaluated to collect semi-
Assuming that elastography delivers additional information quantitative and quantitative information.
about normal uterine tissue, uterine fibroids and adenomyosis, First, elastographic data of the control group were studied to as-
it could be a helpful tool in the diagnosis of uterine pathologies sess normal uterine tissue.
and in preoperative planning. A recurrent color phenomenon in younger uteri, a red sickle-
shaped form that was located in the anterior inferior uterine seg-
ment near the probe, was defined as the “sickle sign”.
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Original Article 3

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).
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4 Original Article

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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Frank ML et al. Importance of Transvaginal … Ultraschall in Med 2015; 36: 1–6

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Original Article 5

the presence of uterine fibroids and adenomyosis and helps in


the differentiation between both focal findings.
A possible limitation of our study is that the applied force during
the elastographic examination could not be standardized. The
deformation of tissue depends on its characteristics but also on
the amount of the stress applied. In order to minimize its impact
as a possible confounder on the measured tissue elasticity, the ra-
tio between two ROIs was calculated. In addition, the QLAB soft-
ware calculates and displays the course of the ratio during the re-
cord. Strikingly, the course was regularly displayed as a curve
with a maximum. We stored that maximum as we suspect it to
be tissue-specific and relatively force-independent.
Moreover, standardization of the placement of ROIs was limited
as the position of the uterus in reference to the probe varies in
each woman. Nevertheless, following our standardized maxi-
mum strain ratio measurements, intra- and interobserver relia-
bility were shown to be excellent.
Another limitation could be that QLAB software 9 and 10 was not
specifically developed and not yet customized for gynecological
ultrasound.
Furthermore, conventional ultrasound diagnosis served as the
gold standard in our study, and the diagnosis was not verified by
Fig. 4 ROC curve of the “lesion index” for uterine fibroids.
histopathology. The assessed uterine pathologies can be hidden
Abb. 4 ROC-Kurve des „Läsionsindex“ für Myome.
due to untypical presentation.
Now there are a growing number of studies about the use of elas-
tography within the field of gynecology but data is still rare. Only
a few studies have been published about the assessment of uter-
ine myomas and adenomyosis with elastography.
In a feasibility study Ami et al. observed 10 women with uterine
fibroids with transvaginal elastosonography. They calculated
strain ratios and concluded that this technique offers comple-
mentary diagnostic information [18].
In a pilot study Tessarolo et al. evaluated 30 women with sus-
pected adenomyosis with standard B-mode and elastosonogra-
phy. Based on color evaluation, they found that adenomyotic
areas present more softness than the surrounding uterine tissue
and considered elastosonography as a possible useful tool in the
diagnosis of adenomyosis [19].
Stoelinga et al. defined specific sonoelastographic characteristics
of the myometrium, fibroids and adenomyosis. Their findings
were also based on color evaluation. Elastography-based diagno-
ses were compared with histology and/or MRI-based diagnoses
and showed excellent agreement [20].
Recently our group assessed deep infiltrating endometriosis
using transvaginal elastography. Schiffmann et al. showed that
the strain ratio between two ROIs in the Douglas’s cul-de-sac is
associated with the presence of an endometriotic lesion [21].
Fig. 5 ROC curve of the “lesion index” for adenomyosis. In conclusion, our study has shown that transvaginal elastogra-
Abb. 5 ROC-Kurve des „Läsionsindex“ für Adenomyose. phy can be used to evaluate uterine tissue. “Age index” and “le-
sion index” deliver information about uterine tissue stiffness.
Uteri with a stiffness differing from the mean stiffness at their
age could be associated with a manifest or developing pathology.
sis < 1, emphasizing that uterine fibroids are stiffer and adeno- An untypically stiff young or soft old uterus could be further ex-
myosis is softer than the surrounding tissue. amined. For example cases of infection or cancer screening could
The calculated ratios show that elastography is able to quantify be investigated.
these focal findings. The use of elastography in addition to conventional ultrasound
To simplify, uterine fibroids are more than twice as stiff as heal- could allow for easier identification of focal lesions and it may
thy uterine tissue and adenomyosis is about half as stiff or twice also be possible to obtain more detailed information about their
as soft as healthy tissue. exact location and extent which could be especially helpful in
To our knowledge, this is the first study showing that the elasto- preoperative planning.
graphic calculation of strain ratios allows for the assessment of The influence of the use of hormones on strain could also be an
interesting target for clinical research. Moreover in future studies
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Frank ML et al. Importance of Transvaginal … Ultraschall in Med 2015; 36: 1–6

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6 Original Article

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