J Med Ultrasonics DOI 10.1007/s10396-016-0701-5
ORIGINAL ARTICLE
The utility of ultrasound elastography in differentiation of endometriomas and hemorrhagic ovarian cysts Abdussamet Batur1 • Alpaslan Yavuz1 • Mesut Ozgokce1 • Aydın Bora1 Mehmet Deniz Bulut1 • Harun Arslan1 • Muhammed Alpaslan1
•
Received: 11 November 2015 / Accepted: 14 January 2016 Ó The Japan Society of Ultrasonics in Medicine 2016
Abstract Purpose To investigate the feasibility of acoustic radiation force impulse imaging in differentiation of endometriomas and hemorrhagic ovarian cysts. Materials and methods We evaluated 84 ovarian cysts with high internal echogenicity diagnosed in 70 consecutive women. We excluded simple cysts and hemorrhagic cysts containing septations or mural nodules with detectable flow on Doppler ultrasonography. We obtained the elastographic shear wave velocity (SWV) value of the cysts that could be endometriomas or hemorrhagic ovarian cysts. Results Among the 78 ovarian cysts in 70 women without any septation or mural nodule, there were 42 endometriomas and 36 hemorrhagic ovarian cysts. Analysis of median SWV values of the ovarian cysts showed that the endometriomas had considerably higher levels of stiffness & Abdussamet Batur [email protected] Alpaslan Yavuz [email protected] Mesut Ozgokce [email protected] Aydın Bora [email protected] Mehmet Deniz Bulut [email protected] Harun Arslan [email protected] Muhammed Alpaslan [email protected] 1
Department of Radiology, Dursun Odabas Medical Center, Yuzuncuyil University, 65080 Van, Turkey
compared to the hemorrhagic ovarian cysts [median SWV 4.20 ± 0.42 vs 2.54 ± 1.04 m/s, p \ 0.001]. A SWV cutoff value greater than 3.81 m/s yielded sensitivity and specificity values of 82.1 and 79.2 % respectively, for differentiation of endometriomas from hemorrhagic ovarian cysts. Conclusion Sonoelastography is a novel imaging technique that enables us to evaluate the stiffness of adnexal lesions. The accurate discrimination of endometriomas and hemorrhagic ovarian cysts is important for avoiding unnecessary surgical procedures. ARFI imaging has a high sensitivity and specificity for distinguishing endometrioma from hemorrhagic ovarian cysts. Keywords Endometrioma Hemorrhagic ovarian cyst Elastography ARFI imaging
Introduction Ultrasonography is an important tool in the evaluation of adnexal cystic lesions. Many of these lesions, originating from the ovaries, can mimic each other with similar imaging findings. Therefore, preoperative characterization of them is crucial when choosing conservative or surgical treatment [1]. Differentiation of endometriomas from hemorrhagic ovarian cysts can be challenging [2]. The appearance of an endometrioma may be similar to a hemorrhagic ovarian cyst because both are cystic masses that contain blood of variable age [3]. Because there is a risk of malignancy in ovarian endometriosis and it may contribute to infertility, it becomes important to differentiate endometriomas from hemorrhagic ovarian cysts that spontaneously resolve [4–6].
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A recent ultrasound-based elastography technique, acoustic radiation force impulse (ARFI), provides elastograms and also defines some parameters of soft tissue such as peak displacement, period of time to reach peak displacement, and recovery time. This can be referred to as quantitative elastography [7]. One of the applications of ARFI imaging is virtual touch quantification (VTQ), a realtime elastographic method that displays results as colorcoded images and numeric values, which are significant for analysis of tissue stiffness. Further, VTQ is a quantitative, operator-independent, and reproducible technique. It is based on a combination of the radiation force induced in tissue by a US beam and an ultrafast imaging sequence capable of capturing the propagation of the resulting shear waves, which is impacted by the local viscoelastic properties of tissue, and it can be used to estimate tissue stiffness [8, 9]. Because of the bleeding characteristics of the different periods, grayscale imaging of endometriomas and hemorrhagic ovarian cysts may be similar and differentiation of them can be challenging. Whereas the bleeding in endometriomas is chronic, it results in high protein and iron accumulation. This pathophysiological mechanism that causes an increase in density and stiffness of the lesion showed that these two lesions could be distinguished from each other on diffusion-weighted images (DWI) [2]. In this study, we investigated the feasibility of elastography in differentiation of endometriomas and hemorrhagic ovarian cysts according to the same pathophysiological mechanism.
also excluded. These lesions were excluded because this study was designed to differentiate endometriomas from hemorrhagic ovarian cysts. We reevaluated the lesions with B-mode and elastographic ultrasonography 4 weeks after the initial assessment to see the possible changes in the size and/or configuration of the lesions. The lesions that showed no significant changes in size and configuration were evaluated as endometriomas (n = 49) and referred for surgery. A diagnosis of hemorrhagic cyst was made if the lesion had resolved on follow-up images (Fig. 1a, b). The final diagnosis was endometrioma for 42 lesions and hemorrhagic ovarian cyst for 36 lesions according to follow-up results and histopathological evaluation. Although there was no considerable change in size on follow-up sonographic examination, seven cases (*9 %) were diagnosed as hemorrhagic ovarian cysts histopathologically. We also examined the complete blood count for anemia research. We obtained the elastographic shear wave velocity (SWV) values of the cysts (n = 78) that could be endometriomas or hemorrhagic ovarian cysts. Five consecutive measurements were recorded for each lesion from the region identified as the region of interest (ROI), and the median of these measurements was recorded as the SWV value of the lesion. In VTQ, the shear wave speed is expressed in m/s. Only numerical results were taken into consideration. When lesion measurements of X.XX m/s were obtained, the measurements were considered invalid. Statistical analysis
Materials and methods This is a prospective study of 84 ovarian cysts with high internal echogenicity diagnosed in 70 consecutive premenopausal women. The study was approved by a local ethics committee, and each patient was informed and provided consent to participate in this study. The mean age of patients was 35 years, and the range was 17–52 years. The patients visited our center due to pelvic pain (n = 28), sterility (n = 14), or consultation for an ovarian cyst (n = 36). All patients underwent grayscale and elastographic ultrasound examination, which was performed using acoustic radiation force impulse (ARFI) imaging with virtual touch quantification (VTQ) with an ACUSON S2000 ultrasound system (Siemens, Mountain View, CA, USA) with a convex probe (4–9 MHz). B-mode ultrasonography was performed to characterize the adnexal masses morphologically. We excluded hemorrhagic cystic lesions containing septations or mural nodules with detectable flow on Doppler ultrasonography (n = 6). Simple cysts, which were defined as a sonolucent thin-walled (\3 mm thick) cyst larger than 3 cm in diameter without septations or papillary projections [10], were
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Descriptive statistics for studied variables (characteristics) were presented as mean, standard deviation, minimum, and maximum values. Student’s t test was used to compare two (control and patient) group means for the studied variables. Pearson correlation analysis was carried out to examine linear relationships among the variables. For discrimination of control and patient groups, cutoff values of SWV were determined by receiver operating characteristic (ROC) analysis. Statistical significance levels were considered as 5 %. The SPSS (ver. 13) statistical program was used for all statistical computations.
Results Among the 78 ovarian cysts in 70 women without any septations or mural nodules, there were 42 endometriomas and 36 hemorrhagic ovarian cysts. Mild anemia (with a hemoglobin level \11 g/dL) was present in as many as 38.88 % of patients (n = 14) with hemorrhagic ovarian cyst, and 26.19 % of patients (n = 11) with endometrioma. In one patient (2.77 %) with a hemorrhagic ovarian cyst,
J Med Ultrasonics
Fig. 1 A sonogram shows a a hemorrhagic cyst with a thick septation (arrow) during the patient’s initial examination, and b a 4-week follow-up image shows a reduction in lesion size with a leveling retracting clot (asterisk)
Table 1 The details of detected ovarian lesions Patient age (years)
All lesions (n = 78)
Endometrioma (n = 42)
Hemorrhagic cyst (n = 36) 28.96 ± 9.67
31.35 ± 10.36
33.39 ± 10.66
Lesion size (cm)
4.97 ± 1.00
5.10 ± 1.00
4.82 ± 1.00
Lesion depth (cm)
4.59 ± 1.11
4.45 ± 1.14
4.74 ± 1.08
there was severe anemia (with a hemoglobin level \8 g/ dL) due to cyst rupture into the abdomen. The final diagnosis was made according to the histopathologic evaluation (n = 49) or follow-up results (n = 29), which were based on follow-up ultrasonography. On the basis of the histologic diagnosis, 42 (54 %) of them were endometriomas and 7 (9 %) of them were hemorrhagic ovarian cysts. At the initial examination, the mean age of patients was 31.35 ± 10.36 years (range 16–52 years). The mean age of the patients with endometriomas was 33.39 ± 10.66 years (range 17–52 years), and that of the patients with hemorrhagic ovarian cysts was 28.96 ± 9.67 years (range 16–50 years). The mean size of all lesions was 4.97 ± 1.00 cm (range 3.5–7.3 cm), that of endometriomas was 5.10 ± 1.00 cm (range 3.7–7.3 cm), and that of hemorrhagic ovarian cysts was 4.82 ± 1.00 cm (range 3.5–7 cm). The mean depth of all lesions from the skin was 4.59 ± 1.11 cm (range 2.3–6.7 cm), that of endometriomas was 4.45 ± 1.14 cm (range 2.3–6.7 cm), and that of hemorrhagic ovarian cysts was 4.74 ± 1.08 cm (range 2.9–6.7 cm) (Table 1). There was no significant difference observed in terms of patient age (p = 0.125), size of the lesions (p = 0.338), and depth of the lesions (p = 0.357). The analysis of mean SWV values of ovarian cysts showed that endometriomas had considerably higher levels of stiffness compared to hemorrhagic ovarian cysts (median SWV: 4.20 ± 0.42 vs 2.54 ± 1.04 m/s, p \ 0.001).
Fig. 2 The area under the receiver operating characteristic (ROC) curve for distinguishing endometriomas from hemorrhagic ovarian cysts using ARFI VTQ imaging was 0.863 (95 % CI 0.761–0.966, p \ 0.001)
The ROC curve for distinguishing endometriomas from hemorrhagic ovarian cysts is shown in Fig. 2. A SWV cutoff value greater than 3.81 m/s yielded sensitivity and
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Fig. 3 A sonogram shows a a homogeneous endometrioma with low-level echoes during the initial examination with a SWV value of 4.65 m/s, and b a 4-week follow-up image shows the same lesion with mild heterogeneity with a SWV value of 4.45 m/s, measured at the same level
specificity values of 82.1 and 79.2 % respectively, for differentiation of endometriomas from hemorrhagic ovarian cysts. The intraclass correlation coefficient for SWV measurement was 86.3 % (95 % CI 0.761–0.966). At the 4-week follow-up examination, the median SWV value for endometriomas (n = 42) was 4.02 ± 0.36 m/s (Fig. 3a, b), and no statistically significant difference between the initial value was observed. The features in seven cases, which showed no change in size on follow-up examination and were diagnosed as hemorrhagic ovarian cyst histopathologically, changed during follow-up because the lesions evolved into various stages of clot formation and clot retraction. The median SWV value for these lesions was 3.88 ± 0.24 m/s when measured from the clot areas, and was 0.80 ± 0.14 m/s when measured from the lysis areas. The median SWV value for these seven lesion during the initial examination was 2.56 ± 0.15 m/s.
Discussion Ultrasonography remains the method of choice for the initial evaluation of suspect ovarian lesions because it is relatively noninvasive, inexpensive, and widely available [1]. Among the ovarian pathologies, endometriomas and hemorrhagic ovarian cysts are common lesions, and differentiation of one from the other can be challenging [2]. Endometrioma is the presence of endometrial gland and stroma outside the uterine cavity or myometrium with a prevalence of approximately 5–10 %. It is a frequent cause of dysmenorrhea, pelvic pain, and infertility [11]. The classic appearance of an endometrioma is a homogeneous, hypoechoic lesion within the ovary with low-level echoes. However, the sonographic findings are highly variable, with a spectrum of appearance related to degradation of blood products over time because of the chronic nature and
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cyclic bleeding of these lesions [5]. For similar reasons, high concentrations of protein and iron in these cysts are observed [12]. Hemorrhagic ovarian cysts occur due to bleeding within the functional cysts that is resorbed spontaneously. An adnexal cyst resulting in bleeding is usually acutely painful [2, 13]. They tend to evolve slowly into various stages of acute hemorrhage, clot formation, and clot retraction, thus giving rise to changing sonographic appearances until they completely resolve in 6 weeks or decrease considerably in size and change in morphologic appearance [14]. In this study, however, seven cases showed no considerable change in size and morphologic appearance after 4 weeks of follow-up. We thought that this could be due to recurrent bleeding. Endometriomas can manifest a broad range in US appearance. Unfortunately, characteristics of hemorrhagic cysts may lead to confusion with ovarian neoplasms such as endometriomas [15]. The accurate diagnosis of endometriomas is important for avoiding unnecessary surgical procedures, because the treatment of choice for endometriosis is surgical resection, whereas hemorrhagic ovarian cysts almost completely resolve spontaneously [10, 14, 16]. Patel et al. reported that the presence of diffuse lowlevel internal echoes is the most important feature that helps to discriminate an endometrioma from other lesions. At the same time, they emphasized that hemorrhagic ovarian cysts can also demonstrate diffuse low-level internal echoes [15]. However, only three (8 %) of 40 endometriomas, according to their study findings, demonstrated features associated with acute hemorrhage. On the other hand, Holsbeke et al. [17] reported that almost 50 % of the endometriomas had ultrasound characteristics other than the typical ‘‘unilocular cyst with ground glass echogenicity of the cyst fluid’’. Also according to Patel
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et al. endometriomas were the only lesions misdiagnosed as hemorrhagic ovarian cysts with the use of fibrin strands as a diagnostic criterion. Because endometriomas enlarge by way of repetitive hemorrhage into the lumen, the sonographic observation of fibrin strands reflects an episode of recent hemorrhage leading to mimicking a hemorrhagic ovarian cyst [13]. Zhi et al. [18] reported that organized hemorrhagic content may increase the stiffness of the lesion in solid breast lesions. Similarly, in our study the mean SWV values measured from the clot areas of hemorrhagic ovarian cysts were compatible with stiffness of endometriomas, whereas the SWV values measured from the lysis areas were very low. However, the SWV values in any part of the lesions exhibited considerably higher levels of stiffness in endometriomas. Although B-mode US appearances can be stranded in the differentiation of endometriomas and hemorrhagic ovarian cysts, magnetic resonance imaging can be an excellent method for identifying the old hemorrhagic content that characterizes endometriomas [19]. Its mechanism (T2 shortening resulting in hypointensity) is based on the high concentration of protein and degraded blood products that result from the repeated hemorrhage [12]. Based on the same pathophysiological mechanism, we speculate that ultrasound elastography can play an important role as a new technique in the differentiation of endometriomas and hemorrhagic ovarian cysts. A growing number of applications of ultrasound elastography, including differentiation of malignant and benign lesions in the breast, prostate, lymph nodes, liver, gastrointestinal tract, cervix, and thyroid (7–9), are being explored; nevertheless, to our knowledge, there have been no studies evaluating the utility of elastography for hemorrhagic content in gynecological or other pathologies in routine practice. Although Xie et al. [20] reported a study evaluating the utility of elastography for the spectrum of serous ovarian carcinomas, they calculated the stiffness of only solid components. In the present study, we observed that an endometrioma can be distinguished easily from an hemorrhagic ovarian cyst by ultrasound elastography even if the grayscale characteristics are similar. Because both can have characteristics of recurrent bleeding periods, it causes difficulty in grayscale separation. In contrast, due to the high protein and iron concentration resulting from chronic bleeding in endometriomas, it shows increased density and stiffness. Based on the working principle of elastography, we can distinguish endometriomas from hemorrhagic ovarian cysts because of their different hardness and stiffness. Despite the lack of distinction in grayscale and on follow-up examination, as shown in the seven cases described above, a distinction can be made by showing the low SWV values (Fig. 4).
Fig. 4 A sonogram shows a homogeneous lesion with low-level echoes, which did not exhibit significant change in size and configuration on follow-up examination, compatible with typical features of an endometrioma. The SWV value of the lesion was 0.97 m/s, and the postoperative pathologic diagnosis was hemorrhagic ovarian cyst
One of the technical limitations of elastography in this study is related to the inclusion of deep lesions (the VTQ penetration depth is restricted to 8 cm in curved array transducers [21]), while another limitation may be the short follow-up period.
Conclusion Sonoelastography is a novel imaging technique that allows us to evaluate the stiffness of adnexal lesions. It is noninvasive, inexpensive, and nowadays widely available. We believe that SWV values of hemorrhagic cysts may contribute to the differentiation of endometriomas from hemorrhagic ovarian cysts. Compliance with ethical standards Conflict of interest of interest.
The authors declare that they have no conflict
Ethical statement All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.
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12. Corwin MT, Gersovich EO, Lamba R, et al. Differentiation of ovarian endometriomas from hemorrhagic cysts at MR imaging: utility of T2 dark spot sign. Radiology. 2014;271:126–32. 13. Patel MD, Feldstein VA, Filly RA. The likelihood ratio of sonographic findings for diagnosis of hemorrhagic ovarian cysts. J Ultrasound Med. 2005;24:607–14. 14. Jain KA. Sonographic spectrum of hemorrhagic ovarian cysts. J Ultrasound Med. 2002;21:879–86. 15. Patel MD, Feldstein VA, Chen DC, et al. Endometriomas: diagnostic performance of US. Radiology. 1999;210:739–45. 16. Chamie LP, Blasbalg R, Pereira RMA, et al. Findings of pelvic endometriosis at transvaginal US, MR imaging, and laparoscopy. Radiographics. 2011;31:E77–100. 17. Holsbeke CV, Calster BV, Guerriero S, et al. Endometriomas: their ultrasound characteristics. Ultrasound Obstet Gynecol. 2010;35:730–40. 18. Zhi H, Ou B, Luo BM, et al. Comparison of ultrasound elastography, mammography, and sonography in the diagnosis of solid breast lesions. J Ultrasound Med. 2007;26:807–15. 19. Togashi K, Nishimura K, Kimura I, et al. Endometrial cysts: diagnosis with MR imaging. Radiology. 1991;180:73–8. 20. Xie M, Zhang X, Zhan J, et al. Application of real-time ultrasound elastography for discrimination of low- and high-grade serous ovarian carcinoma. J Ultrasound Med. 2013;32:257–62. 21. Xie J, Zou L, Yao M, et al. A preliminary investigation of normal pancreas and acute pancreatitis elasticity using virtual touch tissue quantification (VTQ) imaging. Med Sci Monit. 2015;21:1693–9.
ORIGINAL ARTICLE
The utility of ultrasound elastography in differentiation of endometriomas and hemorrhagic ovarian cysts Abdussamet Batur1 • Alpaslan Yavuz1 • Mesut Ozgokce1 • Aydın Bora1 Mehmet Deniz Bulut1 • Harun Arslan1 • Muhammed Alpaslan1
•
Received: 11 November 2015 / Accepted: 14 January 2016 Ó The Japan Society of Ultrasonics in Medicine 2016
Abstract Purpose To investigate the feasibility of acoustic radiation force impulse imaging in differentiation of endometriomas and hemorrhagic ovarian cysts. Materials and methods We evaluated 84 ovarian cysts with high internal echogenicity diagnosed in 70 consecutive women. We excluded simple cysts and hemorrhagic cysts containing septations or mural nodules with detectable flow on Doppler ultrasonography. We obtained the elastographic shear wave velocity (SWV) value of the cysts that could be endometriomas or hemorrhagic ovarian cysts. Results Among the 78 ovarian cysts in 70 women without any septation or mural nodule, there were 42 endometriomas and 36 hemorrhagic ovarian cysts. Analysis of median SWV values of the ovarian cysts showed that the endometriomas had considerably higher levels of stiffness & Abdussamet Batur [email protected] Alpaslan Yavuz [email protected] Mesut Ozgokce [email protected] Aydın Bora [email protected] Mehmet Deniz Bulut [email protected] Harun Arslan [email protected] Muhammed Alpaslan [email protected] 1
Department of Radiology, Dursun Odabas Medical Center, Yuzuncuyil University, 65080 Van, Turkey
compared to the hemorrhagic ovarian cysts [median SWV 4.20 ± 0.42 vs 2.54 ± 1.04 m/s, p \ 0.001]. A SWV cutoff value greater than 3.81 m/s yielded sensitivity and specificity values of 82.1 and 79.2 % respectively, for differentiation of endometriomas from hemorrhagic ovarian cysts. Conclusion Sonoelastography is a novel imaging technique that enables us to evaluate the stiffness of adnexal lesions. The accurate discrimination of endometriomas and hemorrhagic ovarian cysts is important for avoiding unnecessary surgical procedures. ARFI imaging has a high sensitivity and specificity for distinguishing endometrioma from hemorrhagic ovarian cysts. Keywords Endometrioma Hemorrhagic ovarian cyst Elastography ARFI imaging
Introduction Ultrasonography is an important tool in the evaluation of adnexal cystic lesions. Many of these lesions, originating from the ovaries, can mimic each other with similar imaging findings. Therefore, preoperative characterization of them is crucial when choosing conservative or surgical treatment [1]. Differentiation of endometriomas from hemorrhagic ovarian cysts can be challenging [2]. The appearance of an endometrioma may be similar to a hemorrhagic ovarian cyst because both are cystic masses that contain blood of variable age [3]. Because there is a risk of malignancy in ovarian endometriosis and it may contribute to infertility, it becomes important to differentiate endometriomas from hemorrhagic ovarian cysts that spontaneously resolve [4–6].
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A recent ultrasound-based elastography technique, acoustic radiation force impulse (ARFI), provides elastograms and also defines some parameters of soft tissue such as peak displacement, period of time to reach peak displacement, and recovery time. This can be referred to as quantitative elastography [7]. One of the applications of ARFI imaging is virtual touch quantification (VTQ), a realtime elastographic method that displays results as colorcoded images and numeric values, which are significant for analysis of tissue stiffness. Further, VTQ is a quantitative, operator-independent, and reproducible technique. It is based on a combination of the radiation force induced in tissue by a US beam and an ultrafast imaging sequence capable of capturing the propagation of the resulting shear waves, which is impacted by the local viscoelastic properties of tissue, and it can be used to estimate tissue stiffness [8, 9]. Because of the bleeding characteristics of the different periods, grayscale imaging of endometriomas and hemorrhagic ovarian cysts may be similar and differentiation of them can be challenging. Whereas the bleeding in endometriomas is chronic, it results in high protein and iron accumulation. This pathophysiological mechanism that causes an increase in density and stiffness of the lesion showed that these two lesions could be distinguished from each other on diffusion-weighted images (DWI) [2]. In this study, we investigated the feasibility of elastography in differentiation of endometriomas and hemorrhagic ovarian cysts according to the same pathophysiological mechanism.
also excluded. These lesions were excluded because this study was designed to differentiate endometriomas from hemorrhagic ovarian cysts. We reevaluated the lesions with B-mode and elastographic ultrasonography 4 weeks after the initial assessment to see the possible changes in the size and/or configuration of the lesions. The lesions that showed no significant changes in size and configuration were evaluated as endometriomas (n = 49) and referred for surgery. A diagnosis of hemorrhagic cyst was made if the lesion had resolved on follow-up images (Fig. 1a, b). The final diagnosis was endometrioma for 42 lesions and hemorrhagic ovarian cyst for 36 lesions according to follow-up results and histopathological evaluation. Although there was no considerable change in size on follow-up sonographic examination, seven cases (*9 %) were diagnosed as hemorrhagic ovarian cysts histopathologically. We also examined the complete blood count for anemia research. We obtained the elastographic shear wave velocity (SWV) values of the cysts (n = 78) that could be endometriomas or hemorrhagic ovarian cysts. Five consecutive measurements were recorded for each lesion from the region identified as the region of interest (ROI), and the median of these measurements was recorded as the SWV value of the lesion. In VTQ, the shear wave speed is expressed in m/s. Only numerical results were taken into consideration. When lesion measurements of X.XX m/s were obtained, the measurements were considered invalid. Statistical analysis
Materials and methods This is a prospective study of 84 ovarian cysts with high internal echogenicity diagnosed in 70 consecutive premenopausal women. The study was approved by a local ethics committee, and each patient was informed and provided consent to participate in this study. The mean age of patients was 35 years, and the range was 17–52 years. The patients visited our center due to pelvic pain (n = 28), sterility (n = 14), or consultation for an ovarian cyst (n = 36). All patients underwent grayscale and elastographic ultrasound examination, which was performed using acoustic radiation force impulse (ARFI) imaging with virtual touch quantification (VTQ) with an ACUSON S2000 ultrasound system (Siemens, Mountain View, CA, USA) with a convex probe (4–9 MHz). B-mode ultrasonography was performed to characterize the adnexal masses morphologically. We excluded hemorrhagic cystic lesions containing septations or mural nodules with detectable flow on Doppler ultrasonography (n = 6). Simple cysts, which were defined as a sonolucent thin-walled (\3 mm thick) cyst larger than 3 cm in diameter without septations or papillary projections [10], were
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Descriptive statistics for studied variables (characteristics) were presented as mean, standard deviation, minimum, and maximum values. Student’s t test was used to compare two (control and patient) group means for the studied variables. Pearson correlation analysis was carried out to examine linear relationships among the variables. For discrimination of control and patient groups, cutoff values of SWV were determined by receiver operating characteristic (ROC) analysis. Statistical significance levels were considered as 5 %. The SPSS (ver. 13) statistical program was used for all statistical computations.
Results Among the 78 ovarian cysts in 70 women without any septations or mural nodules, there were 42 endometriomas and 36 hemorrhagic ovarian cysts. Mild anemia (with a hemoglobin level \11 g/dL) was present in as many as 38.88 % of patients (n = 14) with hemorrhagic ovarian cyst, and 26.19 % of patients (n = 11) with endometrioma. In one patient (2.77 %) with a hemorrhagic ovarian cyst,
J Med Ultrasonics
Fig. 1 A sonogram shows a a hemorrhagic cyst with a thick septation (arrow) during the patient’s initial examination, and b a 4-week follow-up image shows a reduction in lesion size with a leveling retracting clot (asterisk)
Table 1 The details of detected ovarian lesions Patient age (years)
All lesions (n = 78)
Endometrioma (n = 42)
Hemorrhagic cyst (n = 36) 28.96 ± 9.67
31.35 ± 10.36
33.39 ± 10.66
Lesion size (cm)
4.97 ± 1.00
5.10 ± 1.00
4.82 ± 1.00
Lesion depth (cm)
4.59 ± 1.11
4.45 ± 1.14
4.74 ± 1.08
there was severe anemia (with a hemoglobin level \8 g/ dL) due to cyst rupture into the abdomen. The final diagnosis was made according to the histopathologic evaluation (n = 49) or follow-up results (n = 29), which were based on follow-up ultrasonography. On the basis of the histologic diagnosis, 42 (54 %) of them were endometriomas and 7 (9 %) of them were hemorrhagic ovarian cysts. At the initial examination, the mean age of patients was 31.35 ± 10.36 years (range 16–52 years). The mean age of the patients with endometriomas was 33.39 ± 10.66 years (range 17–52 years), and that of the patients with hemorrhagic ovarian cysts was 28.96 ± 9.67 years (range 16–50 years). The mean size of all lesions was 4.97 ± 1.00 cm (range 3.5–7.3 cm), that of endometriomas was 5.10 ± 1.00 cm (range 3.7–7.3 cm), and that of hemorrhagic ovarian cysts was 4.82 ± 1.00 cm (range 3.5–7 cm). The mean depth of all lesions from the skin was 4.59 ± 1.11 cm (range 2.3–6.7 cm), that of endometriomas was 4.45 ± 1.14 cm (range 2.3–6.7 cm), and that of hemorrhagic ovarian cysts was 4.74 ± 1.08 cm (range 2.9–6.7 cm) (Table 1). There was no significant difference observed in terms of patient age (p = 0.125), size of the lesions (p = 0.338), and depth of the lesions (p = 0.357). The analysis of mean SWV values of ovarian cysts showed that endometriomas had considerably higher levels of stiffness compared to hemorrhagic ovarian cysts (median SWV: 4.20 ± 0.42 vs 2.54 ± 1.04 m/s, p \ 0.001).
Fig. 2 The area under the receiver operating characteristic (ROC) curve for distinguishing endometriomas from hemorrhagic ovarian cysts using ARFI VTQ imaging was 0.863 (95 % CI 0.761–0.966, p \ 0.001)
The ROC curve for distinguishing endometriomas from hemorrhagic ovarian cysts is shown in Fig. 2. A SWV cutoff value greater than 3.81 m/s yielded sensitivity and
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Fig. 3 A sonogram shows a a homogeneous endometrioma with low-level echoes during the initial examination with a SWV value of 4.65 m/s, and b a 4-week follow-up image shows the same lesion with mild heterogeneity with a SWV value of 4.45 m/s, measured at the same level
specificity values of 82.1 and 79.2 % respectively, for differentiation of endometriomas from hemorrhagic ovarian cysts. The intraclass correlation coefficient for SWV measurement was 86.3 % (95 % CI 0.761–0.966). At the 4-week follow-up examination, the median SWV value for endometriomas (n = 42) was 4.02 ± 0.36 m/s (Fig. 3a, b), and no statistically significant difference between the initial value was observed. The features in seven cases, which showed no change in size on follow-up examination and were diagnosed as hemorrhagic ovarian cyst histopathologically, changed during follow-up because the lesions evolved into various stages of clot formation and clot retraction. The median SWV value for these lesions was 3.88 ± 0.24 m/s when measured from the clot areas, and was 0.80 ± 0.14 m/s when measured from the lysis areas. The median SWV value for these seven lesion during the initial examination was 2.56 ± 0.15 m/s.
Discussion Ultrasonography remains the method of choice for the initial evaluation of suspect ovarian lesions because it is relatively noninvasive, inexpensive, and widely available [1]. Among the ovarian pathologies, endometriomas and hemorrhagic ovarian cysts are common lesions, and differentiation of one from the other can be challenging [2]. Endometrioma is the presence of endometrial gland and stroma outside the uterine cavity or myometrium with a prevalence of approximately 5–10 %. It is a frequent cause of dysmenorrhea, pelvic pain, and infertility [11]. The classic appearance of an endometrioma is a homogeneous, hypoechoic lesion within the ovary with low-level echoes. However, the sonographic findings are highly variable, with a spectrum of appearance related to degradation of blood products over time because of the chronic nature and
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cyclic bleeding of these lesions [5]. For similar reasons, high concentrations of protein and iron in these cysts are observed [12]. Hemorrhagic ovarian cysts occur due to bleeding within the functional cysts that is resorbed spontaneously. An adnexal cyst resulting in bleeding is usually acutely painful [2, 13]. They tend to evolve slowly into various stages of acute hemorrhage, clot formation, and clot retraction, thus giving rise to changing sonographic appearances until they completely resolve in 6 weeks or decrease considerably in size and change in morphologic appearance [14]. In this study, however, seven cases showed no considerable change in size and morphologic appearance after 4 weeks of follow-up. We thought that this could be due to recurrent bleeding. Endometriomas can manifest a broad range in US appearance. Unfortunately, characteristics of hemorrhagic cysts may lead to confusion with ovarian neoplasms such as endometriomas [15]. The accurate diagnosis of endometriomas is important for avoiding unnecessary surgical procedures, because the treatment of choice for endometriosis is surgical resection, whereas hemorrhagic ovarian cysts almost completely resolve spontaneously [10, 14, 16]. Patel et al. reported that the presence of diffuse lowlevel internal echoes is the most important feature that helps to discriminate an endometrioma from other lesions. At the same time, they emphasized that hemorrhagic ovarian cysts can also demonstrate diffuse low-level internal echoes [15]. However, only three (8 %) of 40 endometriomas, according to their study findings, demonstrated features associated with acute hemorrhage. On the other hand, Holsbeke et al. [17] reported that almost 50 % of the endometriomas had ultrasound characteristics other than the typical ‘‘unilocular cyst with ground glass echogenicity of the cyst fluid’’. Also according to Patel
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et al. endometriomas were the only lesions misdiagnosed as hemorrhagic ovarian cysts with the use of fibrin strands as a diagnostic criterion. Because endometriomas enlarge by way of repetitive hemorrhage into the lumen, the sonographic observation of fibrin strands reflects an episode of recent hemorrhage leading to mimicking a hemorrhagic ovarian cyst [13]. Zhi et al. [18] reported that organized hemorrhagic content may increase the stiffness of the lesion in solid breast lesions. Similarly, in our study the mean SWV values measured from the clot areas of hemorrhagic ovarian cysts were compatible with stiffness of endometriomas, whereas the SWV values measured from the lysis areas were very low. However, the SWV values in any part of the lesions exhibited considerably higher levels of stiffness in endometriomas. Although B-mode US appearances can be stranded in the differentiation of endometriomas and hemorrhagic ovarian cysts, magnetic resonance imaging can be an excellent method for identifying the old hemorrhagic content that characterizes endometriomas [19]. Its mechanism (T2 shortening resulting in hypointensity) is based on the high concentration of protein and degraded blood products that result from the repeated hemorrhage [12]. Based on the same pathophysiological mechanism, we speculate that ultrasound elastography can play an important role as a new technique in the differentiation of endometriomas and hemorrhagic ovarian cysts. A growing number of applications of ultrasound elastography, including differentiation of malignant and benign lesions in the breast, prostate, lymph nodes, liver, gastrointestinal tract, cervix, and thyroid (7–9), are being explored; nevertheless, to our knowledge, there have been no studies evaluating the utility of elastography for hemorrhagic content in gynecological or other pathologies in routine practice. Although Xie et al. [20] reported a study evaluating the utility of elastography for the spectrum of serous ovarian carcinomas, they calculated the stiffness of only solid components. In the present study, we observed that an endometrioma can be distinguished easily from an hemorrhagic ovarian cyst by ultrasound elastography even if the grayscale characteristics are similar. Because both can have characteristics of recurrent bleeding periods, it causes difficulty in grayscale separation. In contrast, due to the high protein and iron concentration resulting from chronic bleeding in endometriomas, it shows increased density and stiffness. Based on the working principle of elastography, we can distinguish endometriomas from hemorrhagic ovarian cysts because of their different hardness and stiffness. Despite the lack of distinction in grayscale and on follow-up examination, as shown in the seven cases described above, a distinction can be made by showing the low SWV values (Fig. 4).
Fig. 4 A sonogram shows a homogeneous lesion with low-level echoes, which did not exhibit significant change in size and configuration on follow-up examination, compatible with typical features of an endometrioma. The SWV value of the lesion was 0.97 m/s, and the postoperative pathologic diagnosis was hemorrhagic ovarian cyst
One of the technical limitations of elastography in this study is related to the inclusion of deep lesions (the VTQ penetration depth is restricted to 8 cm in curved array transducers [21]), while another limitation may be the short follow-up period.
Conclusion Sonoelastography is a novel imaging technique that allows us to evaluate the stiffness of adnexal lesions. It is noninvasive, inexpensive, and nowadays widely available. We believe that SWV values of hemorrhagic cysts may contribute to the differentiation of endometriomas from hemorrhagic ovarian cysts. Compliance with ethical standards Conflict of interest of interest.
The authors declare that they have no conflict
Ethical statement All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.
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