Clinical Imaging xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
The utility of diffusion-weighted magnetic resonance imaging in differentiation of endometriomas from hemorrhagic ovarian cysts Mehtap Balaban a, Ilkay S. Idilman b, Huseyin Toprak c, Ozlem Unal b, Ali Ipek b, Ercan Kocakoc c,⁎ a b c
Fırat University, School of Medicine, Department of Radiology, Elazıg, Turkey Ankara Atatürk Education and Research Hospital, Department of Radiology, Ankara, Turkey Bezmialem Vakif University, School of Medicine, Department of Radiology, Istanbul, Turkey.
a r t i c l e
i n f o
Article history: Received 26 January 2015 Received in revised form 22 April 2015 Accepted 4 May 2015 Available online xxxx Keywords: Endometrioma Hemorrhagic ovarian cyst MRI DWI and ADC
a b s t r a c t The aim was to determine the utility of diffusion-weighted magnetic resonance imaging (DW MRI) and apparent diffusion coefficient (ADC) measurements in differentiation of endometrioma and hemorrhagic ovarian cyst. A total of 24 female patients who underwent pelvic MRI with an initial diagnosis of ovarian cyst were included in the study. The final diagnosis was endometrioma in 12 patients and hemorrhagic ovarian cyst in 12 patients. We observed significantly lower ADC values in endometriomas compared with hemorrhagic ovarian cysts in all b values. DW MRI with quantitative ADC measurements can be used for differentiation of endometrioma from hemorrhagic ovarian cysts. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Adnexa are anatomic regions between pelvic walls and uterine cornus. A mass in this region generally originates from ovaries, and many of them can mimic each other with similar imaging findings. Differentiation of endometrioma from hemorrhagic ovarian cyst can be challenging among ovarian pathologies. Endometriosis may contribute to pelvic pain and infertility. It was shown that patients with endometriosis have an increased risk of developing clear cell and endometrioid epithelial ovarian cancer [1]. Therefore, it becomes important to differentiate endometrioma that have coexistence with endometriosis from hemorrhagic ovarian cyst that spontaneously resolves with no associated malignancy risk. The role of magnetic resonance imaging (MRI) in evaluation of pelvic gynecologic pathologies increased in recent years [2]. Despite the usefulness of ultrasonography in characterization of adnexal masses, MRI is a superior imaging method with an accuracy rate over 90%, and it is generally used as a problem solver [2]. It was reported that MRI limits additional expense and invasive diagnostic and surgical applications and has advantages in terms of cost-effectiveness contrary to general belief [3].
⁎ Corresponding author. Bezmialem Vakif University, School of Medicine, Department of Radiology, Istanbul, Turkey. Tel.: +90 2124531700; fax: +90 2126318551. E-mail address: [email protected] (E. Kocakoc).
Diffusion-weighted (DW) MRI is a new technique that shows the molecular diffusion difference which is also known as Brownian motion. On DW MRI, image contrast is affected by Brownian motion of water molecules and gives information about microscopic level [4–6]. DW MRI also gives quantitative biophysical parameter of the water called apparent diffusion coefficient (ADC) [7,8]. By the way, DW imaging gives both qualitative and quantitative information that can be useful in differentiation of different lesions from each other. This is also an advantageous method which can be performed in a single breath hold period and without contrast administration. This technique was first described for early diagnosis of acute ischemic stroke in neuroradiology [9]. The usage of DW MRI in abdominal organs was also improved in conjuction with the development of fast MRI sequences such as echoplanar imaging. In the present study, we aimed to determine the utility of DW MRI and ADC measurements in differentiation of endometrioma from hemorrhagic ovarian cyst. 2. Material and methods A total of 24 female patients who were referred to our department for pelvic MRI with a suspected gynecologic mass between October 2007 and October 2008 were included in this study. All patients gave written informed consent for MRI examination. This study was approved by our institutional review board. From the study patients, 6 were operated and 18 were followed up. According to the histopathologic evaluation and
http://dx.doi.org/10.1016/j.clinimag.2015.05.003 0899-7071/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Balaban M, et al, The utility of diffusion-weighted magnetic resonance imaging in differentiation of endometriomas from hemorrhagic ovarian cysts, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.05.003
2
M. Balaban et al. / Clinical Imaging xxx (2015) xxx–xxx
Fig. 1. A histopathologically proven endometrioma with heterogenous appearence in left ovary is seen. It is hyperintense on fat-saturated T1W image (a) and hypointense on T2W image (b). DW MR image demonstrates hyperintense appearance in the cyst (c). ADC was measured as 1.5×10−3 mm2/s with b 600 (d).
Fig. 2. A hemorrhagic ovarian cyst in the left ovary is seen. The lesion is hyperintense on T1W (a), T2W (b), and DW MR (c) images. ADC was measured as 1.74×10−3 mm2/s with b 600 (d).
follow-up results, the final diagnosis was endometrioma for 12 lesions and hemorrhagic ovarian cyst for 12 lesions. 2.1. MR examination All patients underwent pelvic MRI with a 1.5-T MR unit (Signa Hispeed Excite; General Electric, Milwaukee, WI, USA). The patients were examined in supine position. Diffusion-weighted MR images were obtained by a four-channel phased-array coil for body using an echo planar imaging in the axial plane without breath holding in approximately 30 s. A three-plane gradient echo localizer sequence was performed at the beginning of the examination. Imaging parameters were repetition time (TR)/echo time (TE): 8000/80 ms; section thickness: 5 mm; intersection gap: 0; matrix size: 128×128; field of view: 300×300 mm; and water excitations with b values of 100, 600, and 1000 s/mm 2 for DWI. Axial T2-weighted spin-echo sequences (TR/ TE=4100/95, section thickness: 5 mm, intersection gap: 1 mm) were also performed for lesion detection. T2-weighted images were used for detection of lesion and lesion diameters. Color-coded ADC maps were automatically created by the diffusion difference between gradients b 100, b 600, and b 1000 s/mm2 and the b 0 gradient on a workstation (Advantage Windows, software version 2.0; General Electric Medical Systems). Monoexponential method was used in ADC measurements. A minimum mean square error estimator was used in the monoexponential method to minimize the mean square error of the fitted ADC values. The mean ADC values were calculated on images with all acquired b values. A round or elliptical region of interest (ROI) with an area range between 50 and 70 mm2 was placed by a radiologist (M.B., with 4 years of experience) on color-coded ADC maps of the detected lesions. The ROIs were placed in the center of pure cystic lesions or solid-like component of complex cystic lesions. Calculated ADC values for b values of 100, 600, and 1000 s/mm 2 were compared for groups.
2.2. Statistical analyses Data were summarized as mean±standard deviation for continuous variables and frequencies for categorical variables. Mann–Whitney U test was used for independent group comparisons depending on the distributional properties of the data. A P value b .05 was considered as statistically significant. In order to determine the diagnostic accuracy of ADC measurements, receiver operating characteristic (ROC) analysis was performed. Cutoff ranges were calculated around the optimal cutoff to maximize sensitivity and specificity for discrimination of endometrioma from hemorrhagic ovarian cyst. Youden index J values were used to compare diagnostic accuracy of ADC measurements in different b values. 3. Results A total of 24 female patients with ovarian lesions were included in this study. The final diagnosis was made according to the histopathologic evaluation (n=6) or follow-up results (n=18), which are based on follow-up ultrasound examinations. The diagnosis of five patients was endometrioma and one patient was hemorrhagic ovarian cyst according to the histopathologic evaluation. Other patients with endometrioma were treated with drugs. Lesions were divided into two groups: endometriomas (n=12) and hemorrhagic ovarian cysts (n=12). At the time of the imaging, the mean age of the patients was 33.4 years±10.8 (standard deviation; range, 18–58 years). The mean age of the patients with endometrioma was 37 years±12.8 (standard deviation; range, 22–58 years), and that of patients with hemorrhagic ovarian cysts was 30.1 years±7.3 (standard deviation; range, 18–40 years). The mean size of all lesions was 4.9 cm±2.1 (standard deviation; range, 2.5–11 cm), that of endometriomas was 4.5 cm±1.4 (standard deviation; range, 3–7.5 cm), and that of hemorrhagic ovarian cysts was 5.3 cm±2.7 (standard deviation; range, 2.5–11 cm). There was no difference observed in terms of patient age (P=.247) and size of the lesions (P=.560) between the two groups.
Please cite this article as: Balaban M, et al, The utility of diffusion-weighted magnetic resonance imaging in differentiation of endometriomas from hemorrhagic ovarian cysts, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.05.003
M. Balaban et al. / Clinical Imaging xxx (2015) xxx–xxx
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patient who had a hemorrhagic ovarian cyst diagnosis by histopathology with b values below the cutoff (Fig. 5). There was no false-negative patient. 4. Discussion
Fig. 3. Box plot shows ADC values of endometrioma and hemorrhagic ovarian cysts according to b 100, b 600, and b 1000.
Conventional MR images of detected lesions were evaluated. T1weighted (T1W) and T2W MR images were heterogeneous for both lesions depending on the stage of the blood they contain. However, most of them were hyperintense on T1W images and hypo–mildly hyperintense on T2W images. On DW MR images, all lesions were hyperintense compared with the surrounding tissue (Figs. 1 and 2). The mean ADC values (× 10 −3 mm 2/s) of all lesions were 2.27±0.7 for b 100, 1.87± 0.7 for b 600, and 1.62±0.7 for b 1000. The mean ADC values (× 10 − 3 mm 2/s) of endometriomas were 1.84±0.5 for b 100, 1.42± 0.3 for b 600, and 1.15±0.2 for b 1000. The mean ADC values (× 10 − 3 mm 2/s) of hemorrhagic ovarian cysts were 2.70±0.7 for b 100, 2.32±0.6 for b 600, and 2.10±0.1 for b 1000. There were significantly lower ADC values in endometriomas in all b values (P=.004 for b 100, P= .001 for b 600, P= .001 for b 1000) (Fig. 3). The results are summarized in Table 1. The cutoff points of ADC value for differentiation of endometrioma from hemorrhagic ovarian cyst were 2.15×10 − 3 mm 2/s for b 100 [area under the curve, 0.847, 95% confidence interval (CI): 0.643–0.960, Youden index J: 0.6667] with a sensitivity of 83% and a specificity of 83%, 1.85×10−3 mm 2/s for b 600 (area under the curve, 0.903, 95% CI: 0.712–0.985, Youden index J: 0.8333) with a sensitivity of 100% and a specificity of 83%, and 1.54×10 − 3 mm 2/s for b 1000 (area under the curve, 0.17, 95% CI: 0.730–0.990, Youden index J: 0.9167) with a sensitivity of 100% and a specificity of 92% (Table 2). According to these analyses, ADC value at b 1000 was found to have the highest accuracy for differentiation of endometrioma from benign hemorrhagic ovarian cysts (Table 2, Fig. 4). There was only one false-positive
Endometriomas and hemorrhagic ovarian cysts are common ovarian pathologies, and differentiation of one from the other can be challenging. Endometriosis is the presence of endometrial gland and stroma outside the uterine cavity or myometrium [10], and the prevalence of it is approximately 5%–10% [11]. Endometriosis is a frequent cause of dysmenorrhea, pelvic pain, and infertility. The prevalence of endometriosis in the presence of infertility is about 20%, and there are varying degrees of infertility in 30%–50% of the women with endometriosis [11,12]. Ectopic endometrial tissue is sensitive to hormonal stimuli, and bloodfilled cysts occur due to the hemorrhages according to the menstrual cycle. The synonyms of these cysts are chocolate cysts and endometriotic cysts, and the wall of these cysts is thick and fibrotic. There are several treatment methods for endometrioma according to the symptoms of the patient. Medical treatments are focused on the hormonal alteration of the menstrual cycle and trying to produce a pseudopregnancy, pseudomenopause, or chronic anovulation [13]. However, medical therapy does not improve infertility in these patients. So, fertility can be achieved with surgical therapy including resection of obstructive masses and adhesions [13]. In contrast with endometriomas, hemorrhagic ovarian cysts occur due to the hemorrhage within the functional cysts and resorb spontaneously. By the way, differentiation of endometrioma from hemorrhagic ovarian cyst is important for appropriate treatment plan. It is especially important for patients with infertility to avoid unnecessary surgery. Imaging modalities can be useful in identification of gynecologic pathologies. Ultrasonography is preferred in the first step for this indication because of diagnostic efficiency, low cost, and practical usage. It is generally used for confirmation, characterization, and originating organ identification of a mass. However, it is dependent on practitioners’ experience [14]. Computed tomography can be helpful in detection of a mass. But it is not a superior imaging modality as it cannot show septa or papillary projections sufficiently and needs intravenous and oral contrast administration, patient preparation, and ionizing radiation. MRI has high soft tissue resolution and capability of multiplanar imaging, which make it a superior imaging modality in pelvic region. However, on conventional MRI, the differentiation of endometrioma from hemorrhagic ovarian cyst is quite difficult. DW MRI has been widely used for abdominopelvic region. Lesions in that region have high signal intensity in contrast with normal organs and tissues, and that eases detection of them. There are previous studies comparing ADC values of different ovarian lesions in the literature [15–17]. Katayama et al. did not find a significant difference between malignant and benign ovarian lesions [16]. However, Moteki and Ishizaka showed that DW MRI can discriminate malignant from benign ovarian tumors if the tumor size is smaller than 12 cm [15], and Nakayama et al. observed significant difference between malignant and benign ovarian tumors when they excluded mature cystic teratomas and endometrial cysts [17]. In both studies, researchers observed low ADC values in endometrial cysts [15,17]. However, there is no such study comparing ADC values of
Table 1 The details of detected 24 ovarian lesions in 24 patients
Patient age (years) Lesion size (cm) ADC values (10−3 mm2/s) b 100 ADC values (10−3 mm2/s) b 600 ADC values (10−3 mm2/s) b 1000
All lesions (n=24)
Endometrioma (n=12)
Hemorrhagic ovarian cyst (n=12)
P
33.4±10.8 4.9±2.1 2.27±0.7
37±12.8 4.5±1.4 1.84±0.5
30.1±7.3 5.3±2.7 2.70±0.7
.247 .560 .004
1.87±0.7
1.42±0.3
2.32±0.6
.001
1.62±0.7
1.15±0.2
2.10±0.1
.001
Data are mean±S.D.
Please cite this article as: Balaban M, et al, The utility of diffusion-weighted magnetic resonance imaging in differentiation of endometriomas from hemorrhagic ovarian cysts, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.05.003
4
M. Balaban et al. / Clinical Imaging xxx (2015) xxx–xxx
the lesion. DW MRI with quantitative ADC measurements can be used for differentiation of endometrioma from hemorrhagic ovarian cysts.
Acknowledgments None of the authors have relevant conflict of interest.
References
Fig. 4. Graph shows ROC curve for discriminating endometrioma from hemorrhagic ovarian cyst.
endometriomas and hemorrhagic ovarian cysts available in the literature. In our study, we aimed to demonstrate ADC values of endometriomas and hemorrhagic cysts and to determine the utility of DW MRI in discriminating these two lesions. In our study, ADC values of endometriomas were 1.84± 0.5 10−3 mm2/s for b 100, 1.42±0.3 10−3 mm2/s for b 600, and 1.15±0.2 10−3 mm2/s for b 1000. ADC values of hemorrhagic ovarian cysts were 2.70 ±0.7 10−3 mm2/s for b 100, 2.32±0.6 10−3 mm2/s for b 600, and 2.10±0.1 10−3 mm2/s for b 1000. We observed significantly lower ADC values in endometriomas compared with hemorrhagic ovarian cysts in all b values (P=.001 for b 100, P=.001 for b 600, P=.001 for b 1000), with a higher sensitivity and specificity at b 1000. There were a few limitations of the present study. First, less T2 shinethrough effect can be the reason of lower ADC values obtained in endometriomas. Second, we have a small patient population. Extensive studies would be helpful to emphasize the efficiency of DW MRI in differentiation of these two entities. 5. Conclusions DW MRI is a noninvasive, fast, and effective diagnostic tool that does not require contrast material and gives quantitative information about
[1] Heidemann LN, Hartwell D, Heidemann CH, Jochumsen KM. The relation between endometriosis and ovarian cancer—a review. Acta Obstet Gynecol Scand 2014;93: 20–31. [2] Saini A, Dina R, McIndoe GA, Soutter WP, Gishen P, deSouza NM. Characterization of adnexial masses with MRI. AJR Am J Roentgenol 2005;184:1004–9. [3] Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43–66. [4] Le Bihan D, Turner R, Douek P, Patronas N. Diffusion MR imaging: clinical applications. AJR Am J Roentgenol 1992;159:591–9. [5] Garner EI. Advances in the early detection of ovarian carcinoma. J Reprod Med 2005; 50:447–53. [6] Matoba M, Tonami H, Kondou T, Yokota H, Higashi K, Toga H, et al. Lung carcinoma: diffusion-weighted MR imaging-preliminary evaluation with apparent diffusion coefficient. Radiology 2007;243:570–7. [7] Koyama T, Tamai K, Togashi K. Current status of body MR imaging: fast MR imaging and diffusion-weighted imaging. Int J Clin Oncol 2006;11:278–85. [8] Abou-El-Ghar ME, El-Assmy A, Refaie HF, El-Diasty T. Bladder cancer: diagnosis with diffusion weighted MR imaging in patients with gross hematuria. Radiology 2009; 251:415–21. [9] Lutsep HL, Albers GW, DeCrespigny A, Kamat GN, Marks MP, Moseley ME. Clinical utility of diffusion-weighted magnetic resonance imaging in the assessment of ischemic stroke. Ann Neurol 1997;41:574–80. [10] Bulletti C, De Ziegler D, Polli V, Del Ferro E, Palini S, Flamigni C. Characteristics of uterine contractility during menses in women with mild to moderate endometriosis. Fertil Steril 2002;77:1156–61. [11] Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am 1997;24:235–58. [12] Woodward PJ, Sohaey R, Mezzetti TP. Endometriosis: radiologic–pathologic correlation. Radiographics 2001;21:193–216. [13] Olive DL, Pritts EA. Treatment of endometriosis. N Engl J Med 2001;345:266–75. [14] Fleischer AC, James AE, Millis JB, Julian C. Differential diagnosis of pelvic masses by gray scale sonography. AJR Am J Roentgenol 1978;131:469–76. [15] Moteki T, Ishizaka H. Diffusion-weighted EPI of cystic ovarian lesions: evaluation of cystic contents using apparent diffusion coefficients. J Magn Reson Imaging 2000;12: 1014–9. [16] Katayama M, Masui T, Kobayashi S, Ito T, Sakahara H, Nozaki A, et al. Diffusionweighted echo planar imaging of ovarian tumors: is it useful to measure apparent diffusion coefficients? J Comput Assist Tomogr 2002;26:250–6. [17] Nakayama T, Yoshimitsu K, Irie H, Aibe H, Tajima T, Nishie A, et al. Diffusionweighted echo-planar MR imaging and ADC mapping in the differential diagnosis of ovarian cystic masses: usefulness of detecting keratinoid substances in mature cystic teratomas. J Magn Reson Imaging 2005;22:271–8.
Table 2 Diagnostic accuracy of ADC measurements for differentiation of endometrioma from hemorrhagic ovarian cyst Patients Cutoff value
AUC
Sensitivity (95% CI)
Specificity (95% CI)
PPV (95% CI)
NPV (95% CI)
P value
b 100 ≤2.15×10−3 s/mm2 b 600 ≤1.85×10−3 s/mm2 b 1000 ≤1.54×10−3 s/mm2
0.847 (0.643–0.960) 0.903 (0.712–0.985) 0.917 (0.730–0.990
0.83 (0.52–0.98) 1.00 (0.74–1.00) 1.00 (0.74–1.00)
0.83 (0.52–0.98) 0.83 (0.52–0.98) 0.92 (0.62–1.00)
0.83 (0.52–0.98) 0.86 (0.57–0.98) 0.92 (0.64–1.00)
0.83 (0.52–0.98) 1.00 (0.69–1.00) 1.00 (0.72–1.00)
=.0002 b.0001 b.0001
AUC, area under the curve; NPV, negative predictive value; PPV, positive predictive value.
Fig. 5. A hemorrhagic cyst with a b value below the cutoff. The lesion is hyperintense on T1W (a), T2W (b), and DW MR (c) images.
Please cite this article as: Balaban M, et al, The utility of diffusion-weighted magnetic resonance imaging in differentiation of endometriomas from hemorrhagic ovarian cysts, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.05.003
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
The utility of diffusion-weighted magnetic resonance imaging in differentiation of endometriomas from hemorrhagic ovarian cysts Mehtap Balaban a, Ilkay S. Idilman b, Huseyin Toprak c, Ozlem Unal b, Ali Ipek b, Ercan Kocakoc c,⁎ a b c
Fırat University, School of Medicine, Department of Radiology, Elazıg, Turkey Ankara Atatürk Education and Research Hospital, Department of Radiology, Ankara, Turkey Bezmialem Vakif University, School of Medicine, Department of Radiology, Istanbul, Turkey.
a r t i c l e
i n f o
Article history: Received 26 January 2015 Received in revised form 22 April 2015 Accepted 4 May 2015 Available online xxxx Keywords: Endometrioma Hemorrhagic ovarian cyst MRI DWI and ADC
a b s t r a c t The aim was to determine the utility of diffusion-weighted magnetic resonance imaging (DW MRI) and apparent diffusion coefficient (ADC) measurements in differentiation of endometrioma and hemorrhagic ovarian cyst. A total of 24 female patients who underwent pelvic MRI with an initial diagnosis of ovarian cyst were included in the study. The final diagnosis was endometrioma in 12 patients and hemorrhagic ovarian cyst in 12 patients. We observed significantly lower ADC values in endometriomas compared with hemorrhagic ovarian cysts in all b values. DW MRI with quantitative ADC measurements can be used for differentiation of endometrioma from hemorrhagic ovarian cysts. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Adnexa are anatomic regions between pelvic walls and uterine cornus. A mass in this region generally originates from ovaries, and many of them can mimic each other with similar imaging findings. Differentiation of endometrioma from hemorrhagic ovarian cyst can be challenging among ovarian pathologies. Endometriosis may contribute to pelvic pain and infertility. It was shown that patients with endometriosis have an increased risk of developing clear cell and endometrioid epithelial ovarian cancer [1]. Therefore, it becomes important to differentiate endometrioma that have coexistence with endometriosis from hemorrhagic ovarian cyst that spontaneously resolves with no associated malignancy risk. The role of magnetic resonance imaging (MRI) in evaluation of pelvic gynecologic pathologies increased in recent years [2]. Despite the usefulness of ultrasonography in characterization of adnexal masses, MRI is a superior imaging method with an accuracy rate over 90%, and it is generally used as a problem solver [2]. It was reported that MRI limits additional expense and invasive diagnostic and surgical applications and has advantages in terms of cost-effectiveness contrary to general belief [3].
⁎ Corresponding author. Bezmialem Vakif University, School of Medicine, Department of Radiology, Istanbul, Turkey. Tel.: +90 2124531700; fax: +90 2126318551. E-mail address: [email protected] (E. Kocakoc).
Diffusion-weighted (DW) MRI is a new technique that shows the molecular diffusion difference which is also known as Brownian motion. On DW MRI, image contrast is affected by Brownian motion of water molecules and gives information about microscopic level [4–6]. DW MRI also gives quantitative biophysical parameter of the water called apparent diffusion coefficient (ADC) [7,8]. By the way, DW imaging gives both qualitative and quantitative information that can be useful in differentiation of different lesions from each other. This is also an advantageous method which can be performed in a single breath hold period and without contrast administration. This technique was first described for early diagnosis of acute ischemic stroke in neuroradiology [9]. The usage of DW MRI in abdominal organs was also improved in conjuction with the development of fast MRI sequences such as echoplanar imaging. In the present study, we aimed to determine the utility of DW MRI and ADC measurements in differentiation of endometrioma from hemorrhagic ovarian cyst. 2. Material and methods A total of 24 female patients who were referred to our department for pelvic MRI with a suspected gynecologic mass between October 2007 and October 2008 were included in this study. All patients gave written informed consent for MRI examination. This study was approved by our institutional review board. From the study patients, 6 were operated and 18 were followed up. According to the histopathologic evaluation and
http://dx.doi.org/10.1016/j.clinimag.2015.05.003 0899-7071/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Balaban M, et al, The utility of diffusion-weighted magnetic resonance imaging in differentiation of endometriomas from hemorrhagic ovarian cysts, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.05.003
2
M. Balaban et al. / Clinical Imaging xxx (2015) xxx–xxx
Fig. 1. A histopathologically proven endometrioma with heterogenous appearence in left ovary is seen. It is hyperintense on fat-saturated T1W image (a) and hypointense on T2W image (b). DW MR image demonstrates hyperintense appearance in the cyst (c). ADC was measured as 1.5×10−3 mm2/s with b 600 (d).
Fig. 2. A hemorrhagic ovarian cyst in the left ovary is seen. The lesion is hyperintense on T1W (a), T2W (b), and DW MR (c) images. ADC was measured as 1.74×10−3 mm2/s with b 600 (d).
follow-up results, the final diagnosis was endometrioma for 12 lesions and hemorrhagic ovarian cyst for 12 lesions. 2.1. MR examination All patients underwent pelvic MRI with a 1.5-T MR unit (Signa Hispeed Excite; General Electric, Milwaukee, WI, USA). The patients were examined in supine position. Diffusion-weighted MR images were obtained by a four-channel phased-array coil for body using an echo planar imaging in the axial plane without breath holding in approximately 30 s. A three-plane gradient echo localizer sequence was performed at the beginning of the examination. Imaging parameters were repetition time (TR)/echo time (TE): 8000/80 ms; section thickness: 5 mm; intersection gap: 0; matrix size: 128×128; field of view: 300×300 mm; and water excitations with b values of 100, 600, and 1000 s/mm 2 for DWI. Axial T2-weighted spin-echo sequences (TR/ TE=4100/95, section thickness: 5 mm, intersection gap: 1 mm) were also performed for lesion detection. T2-weighted images were used for detection of lesion and lesion diameters. Color-coded ADC maps were automatically created by the diffusion difference between gradients b 100, b 600, and b 1000 s/mm2 and the b 0 gradient on a workstation (Advantage Windows, software version 2.0; General Electric Medical Systems). Monoexponential method was used in ADC measurements. A minimum mean square error estimator was used in the monoexponential method to minimize the mean square error of the fitted ADC values. The mean ADC values were calculated on images with all acquired b values. A round or elliptical region of interest (ROI) with an area range between 50 and 70 mm2 was placed by a radiologist (M.B., with 4 years of experience) on color-coded ADC maps of the detected lesions. The ROIs were placed in the center of pure cystic lesions or solid-like component of complex cystic lesions. Calculated ADC values for b values of 100, 600, and 1000 s/mm 2 were compared for groups.
2.2. Statistical analyses Data were summarized as mean±standard deviation for continuous variables and frequencies for categorical variables. Mann–Whitney U test was used for independent group comparisons depending on the distributional properties of the data. A P value b .05 was considered as statistically significant. In order to determine the diagnostic accuracy of ADC measurements, receiver operating characteristic (ROC) analysis was performed. Cutoff ranges were calculated around the optimal cutoff to maximize sensitivity and specificity for discrimination of endometrioma from hemorrhagic ovarian cyst. Youden index J values were used to compare diagnostic accuracy of ADC measurements in different b values. 3. Results A total of 24 female patients with ovarian lesions were included in this study. The final diagnosis was made according to the histopathologic evaluation (n=6) or follow-up results (n=18), which are based on follow-up ultrasound examinations. The diagnosis of five patients was endometrioma and one patient was hemorrhagic ovarian cyst according to the histopathologic evaluation. Other patients with endometrioma were treated with drugs. Lesions were divided into two groups: endometriomas (n=12) and hemorrhagic ovarian cysts (n=12). At the time of the imaging, the mean age of the patients was 33.4 years±10.8 (standard deviation; range, 18–58 years). The mean age of the patients with endometrioma was 37 years±12.8 (standard deviation; range, 22–58 years), and that of patients with hemorrhagic ovarian cysts was 30.1 years±7.3 (standard deviation; range, 18–40 years). The mean size of all lesions was 4.9 cm±2.1 (standard deviation; range, 2.5–11 cm), that of endometriomas was 4.5 cm±1.4 (standard deviation; range, 3–7.5 cm), and that of hemorrhagic ovarian cysts was 5.3 cm±2.7 (standard deviation; range, 2.5–11 cm). There was no difference observed in terms of patient age (P=.247) and size of the lesions (P=.560) between the two groups.
Please cite this article as: Balaban M, et al, The utility of diffusion-weighted magnetic resonance imaging in differentiation of endometriomas from hemorrhagic ovarian cysts, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.05.003
M. Balaban et al. / Clinical Imaging xxx (2015) xxx–xxx
3
patient who had a hemorrhagic ovarian cyst diagnosis by histopathology with b values below the cutoff (Fig. 5). There was no false-negative patient. 4. Discussion
Fig. 3. Box plot shows ADC values of endometrioma and hemorrhagic ovarian cysts according to b 100, b 600, and b 1000.
Conventional MR images of detected lesions were evaluated. T1weighted (T1W) and T2W MR images were heterogeneous for both lesions depending on the stage of the blood they contain. However, most of them were hyperintense on T1W images and hypo–mildly hyperintense on T2W images. On DW MR images, all lesions were hyperintense compared with the surrounding tissue (Figs. 1 and 2). The mean ADC values (× 10 −3 mm 2/s) of all lesions were 2.27±0.7 for b 100, 1.87± 0.7 for b 600, and 1.62±0.7 for b 1000. The mean ADC values (× 10 − 3 mm 2/s) of endometriomas were 1.84±0.5 for b 100, 1.42± 0.3 for b 600, and 1.15±0.2 for b 1000. The mean ADC values (× 10 − 3 mm 2/s) of hemorrhagic ovarian cysts were 2.70±0.7 for b 100, 2.32±0.6 for b 600, and 2.10±0.1 for b 1000. There were significantly lower ADC values in endometriomas in all b values (P=.004 for b 100, P= .001 for b 600, P= .001 for b 1000) (Fig. 3). The results are summarized in Table 1. The cutoff points of ADC value for differentiation of endometrioma from hemorrhagic ovarian cyst were 2.15×10 − 3 mm 2/s for b 100 [area under the curve, 0.847, 95% confidence interval (CI): 0.643–0.960, Youden index J: 0.6667] with a sensitivity of 83% and a specificity of 83%, 1.85×10−3 mm 2/s for b 600 (area under the curve, 0.903, 95% CI: 0.712–0.985, Youden index J: 0.8333) with a sensitivity of 100% and a specificity of 83%, and 1.54×10 − 3 mm 2/s for b 1000 (area under the curve, 0.17, 95% CI: 0.730–0.990, Youden index J: 0.9167) with a sensitivity of 100% and a specificity of 92% (Table 2). According to these analyses, ADC value at b 1000 was found to have the highest accuracy for differentiation of endometrioma from benign hemorrhagic ovarian cysts (Table 2, Fig. 4). There was only one false-positive
Endometriomas and hemorrhagic ovarian cysts are common ovarian pathologies, and differentiation of one from the other can be challenging. Endometriosis is the presence of endometrial gland and stroma outside the uterine cavity or myometrium [10], and the prevalence of it is approximately 5%–10% [11]. Endometriosis is a frequent cause of dysmenorrhea, pelvic pain, and infertility. The prevalence of endometriosis in the presence of infertility is about 20%, and there are varying degrees of infertility in 30%–50% of the women with endometriosis [11,12]. Ectopic endometrial tissue is sensitive to hormonal stimuli, and bloodfilled cysts occur due to the hemorrhages according to the menstrual cycle. The synonyms of these cysts are chocolate cysts and endometriotic cysts, and the wall of these cysts is thick and fibrotic. There are several treatment methods for endometrioma according to the symptoms of the patient. Medical treatments are focused on the hormonal alteration of the menstrual cycle and trying to produce a pseudopregnancy, pseudomenopause, or chronic anovulation [13]. However, medical therapy does not improve infertility in these patients. So, fertility can be achieved with surgical therapy including resection of obstructive masses and adhesions [13]. In contrast with endometriomas, hemorrhagic ovarian cysts occur due to the hemorrhage within the functional cysts and resorb spontaneously. By the way, differentiation of endometrioma from hemorrhagic ovarian cyst is important for appropriate treatment plan. It is especially important for patients with infertility to avoid unnecessary surgery. Imaging modalities can be useful in identification of gynecologic pathologies. Ultrasonography is preferred in the first step for this indication because of diagnostic efficiency, low cost, and practical usage. It is generally used for confirmation, characterization, and originating organ identification of a mass. However, it is dependent on practitioners’ experience [14]. Computed tomography can be helpful in detection of a mass. But it is not a superior imaging modality as it cannot show septa or papillary projections sufficiently and needs intravenous and oral contrast administration, patient preparation, and ionizing radiation. MRI has high soft tissue resolution and capability of multiplanar imaging, which make it a superior imaging modality in pelvic region. However, on conventional MRI, the differentiation of endometrioma from hemorrhagic ovarian cyst is quite difficult. DW MRI has been widely used for abdominopelvic region. Lesions in that region have high signal intensity in contrast with normal organs and tissues, and that eases detection of them. There are previous studies comparing ADC values of different ovarian lesions in the literature [15–17]. Katayama et al. did not find a significant difference between malignant and benign ovarian lesions [16]. However, Moteki and Ishizaka showed that DW MRI can discriminate malignant from benign ovarian tumors if the tumor size is smaller than 12 cm [15], and Nakayama et al. observed significant difference between malignant and benign ovarian tumors when they excluded mature cystic teratomas and endometrial cysts [17]. In both studies, researchers observed low ADC values in endometrial cysts [15,17]. However, there is no such study comparing ADC values of
Table 1 The details of detected 24 ovarian lesions in 24 patients
Patient age (years) Lesion size (cm) ADC values (10−3 mm2/s) b 100 ADC values (10−3 mm2/s) b 600 ADC values (10−3 mm2/s) b 1000
All lesions (n=24)
Endometrioma (n=12)
Hemorrhagic ovarian cyst (n=12)
P
33.4±10.8 4.9±2.1 2.27±0.7
37±12.8 4.5±1.4 1.84±0.5
30.1±7.3 5.3±2.7 2.70±0.7
.247 .560 .004
1.87±0.7
1.42±0.3
2.32±0.6
.001
1.62±0.7
1.15±0.2
2.10±0.1
.001
Data are mean±S.D.
Please cite this article as: Balaban M, et al, The utility of diffusion-weighted magnetic resonance imaging in differentiation of endometriomas from hemorrhagic ovarian cysts, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.05.003
4
M. Balaban et al. / Clinical Imaging xxx (2015) xxx–xxx
the lesion. DW MRI with quantitative ADC measurements can be used for differentiation of endometrioma from hemorrhagic ovarian cysts.
Acknowledgments None of the authors have relevant conflict of interest.
References
Fig. 4. Graph shows ROC curve for discriminating endometrioma from hemorrhagic ovarian cyst.
endometriomas and hemorrhagic ovarian cysts available in the literature. In our study, we aimed to demonstrate ADC values of endometriomas and hemorrhagic cysts and to determine the utility of DW MRI in discriminating these two lesions. In our study, ADC values of endometriomas were 1.84± 0.5 10−3 mm2/s for b 100, 1.42±0.3 10−3 mm2/s for b 600, and 1.15±0.2 10−3 mm2/s for b 1000. ADC values of hemorrhagic ovarian cysts were 2.70 ±0.7 10−3 mm2/s for b 100, 2.32±0.6 10−3 mm2/s for b 600, and 2.10±0.1 10−3 mm2/s for b 1000. We observed significantly lower ADC values in endometriomas compared with hemorrhagic ovarian cysts in all b values (P=.001 for b 100, P=.001 for b 600, P=.001 for b 1000), with a higher sensitivity and specificity at b 1000. There were a few limitations of the present study. First, less T2 shinethrough effect can be the reason of lower ADC values obtained in endometriomas. Second, we have a small patient population. Extensive studies would be helpful to emphasize the efficiency of DW MRI in differentiation of these two entities. 5. Conclusions DW MRI is a noninvasive, fast, and effective diagnostic tool that does not require contrast material and gives quantitative information about
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Table 2 Diagnostic accuracy of ADC measurements for differentiation of endometrioma from hemorrhagic ovarian cyst Patients Cutoff value
AUC
Sensitivity (95% CI)
Specificity (95% CI)
PPV (95% CI)
NPV (95% CI)
P value
b 100 ≤2.15×10−3 s/mm2 b 600 ≤1.85×10−3 s/mm2 b 1000 ≤1.54×10−3 s/mm2
0.847 (0.643–0.960) 0.903 (0.712–0.985) 0.917 (0.730–0.990
0.83 (0.52–0.98) 1.00 (0.74–1.00) 1.00 (0.74–1.00)
0.83 (0.52–0.98) 0.83 (0.52–0.98) 0.92 (0.62–1.00)
0.83 (0.52–0.98) 0.86 (0.57–0.98) 0.92 (0.64–1.00)
0.83 (0.52–0.98) 1.00 (0.69–1.00) 1.00 (0.72–1.00)
=.0002 b.0001 b.0001
AUC, area under the curve; NPV, negative predictive value; PPV, positive predictive value.
Fig. 5. A hemorrhagic cyst with a b value below the cutoff. The lesion is hyperintense on T1W (a), T2W (b), and DW MR (c) images.
Please cite this article as: Balaban M, et al, The utility of diffusion-weighted magnetic resonance imaging in differentiation of endometriomas from hemorrhagic ovarian cysts, Clin Imaging (2015), http://dx.doi.org/10.1016/j.clinimag.2015.05.003
