{"paper_id":"e0e37267-1ce9-4f4b-a84f-8b6410538fe9","body_text":"The Benefit of Transvaginal Elastography in Detecting Deep\nEndometriosis: A Feasibility Study\nNutzen der transvaginalen Elastografie bei der Erkennung der tief\ninfiltrierenden Endometriose: Eine Machbarkeitsstudie\nAuthors\nAnjeza Xholli 1, Ambrogio P Londero 2\n , Elena Cavalli 1, Umberto Scovazzi 1, Mattia Francesco Ferraro 1, Ilaria Vacca 1,\nMaria Giulia Schiaffino 1, Francesca Oppedisano 1, Giorgio Sirito 1, Filippo Molinari 1,A n g e l oC a g n a c c i1, 2\nAffiliations\n1 Academic Unit of Obstetrics and Gynecology, IRCCS\nOspedale Policlinico San Martino, Genova, Italy\n2 DINOGMI, University of Genoa, Genova, Italy\nKey words\ndeep endometriosis, color score ratio, strain elastography,\nstrain ratio, endometriotic lesion\nreceived 19.11.2022\naccepted after revision 06.02.2023\naccepted manuscript online 06.02.2023\npublished online 13.04.2023\nBibliography\nUltraschall in Med 2024; 45: 69 –76\nDOI 10.1055/a-2028-8214\nISSN 0172-4614\n© 2023. Thieme. All rights reserved.\nGeorg Thieme Verlag KG, Rüdigerstraße 14,\n70469 Stuttgart, Germany\nCorrespondence\nAmbrogio P Londero\nDINOGMI, University of Genoa, Largo Paolo Daneo 3,\n16132 Genova, Italy\nambrogio.londero@gmail.com\nAdditional material is available at https://doi.org/\n10.1055/a-2028-8214.\nABSTRACT\nObjectives This study aimed to evaluate elastography fea-\ntures of deep infiltrating endometriosis (DIE), and to define\nwhether this technique may discriminate lesions from sur-\nrounding non-endometriotic tissue.\nMethods This was an exploratory observational study on\nwomen affected by DIE treated in a third-level academic hos-\npital gynaecology outpatient facility between 2020 and 2021.\nStrain elastography (SE) was conducted via transvaginal\nprobe. Tissue deformation of DIE and surr ounding tissue was\nexpressed as percentage tissue deformation or as subjective\ncolour score (CS; from blue = stiff to red = soft, assigned nu-\nmerical values from 0 to 3). Ratios of normal tissue/DIE were\ncompared to ratio of normal tissue/stiffer normal tissue area.\nResults Evaluations were performed on 46 DIE nodules and\nsurrounding tissue of the uterosacral ligaments (n = 21), para-\nmetrium (n = 7), rectum (n = 14), and recto-vaginal septum\n(n = 4). Irrespective of location, DIE strain ratio (3.09, IQR\n2.38 –4.14 vs. 1.25, IQR 1.11 –1.48; p < 0.001) and CS ratio\n(4.62, IQR 3.83 –6.94 vs. 1.13, IQR 1.06 –1.29; p < 0.001) was\nsignificantly higher than that of normal tissue. ROC AUC of CS\nratio was higher than ROC AUC of strain ratio (99.76 %, CI.95\n99.26 –100 % vs. 91.35 %, CI.95 85.23 –97.47 %; p = 0.007),\nand best ROC threshold for CS ratio was 1.82, with a sensitiv-\nity of 97.83 % (CI.95 93.48 –100 %) and a specificity of 100 %\n(CI.95 100 –100 %).\nConclusions Both strain and CS ratios accurately distinguish\nDIE nodules at various locations. Applications of elastography\nin improving the diagnosis DIE, in distinguishing different DIE\nlesions and in monitoring DIE evolution can be envisioned and\nare worthy of further evaluation.\nZUSAMMENFASSUNG\nZiel Ziel dieser Studie war es, die elastografischen Merkmale\nder tief infiltrierenden Endo metriose (TIE) zu untersuchen\nund festzustellen, ob diese Technik die Läsionen von umge-\nbendem nicht-endometriotischem Gewebe unterscheiden\nkann.\nMethoden Dies war eine explorative Beobachtungsstudie an\nFrauen mit TIE, die zwischen 2020 und 2021 in einer gynäko-\nlogischen Ambulanz eines Universitätskrankenhauses der Ter-\ntiärversorgung behandelt wurden. Die Strain-Elastografie (SE)\nwurde über eine transvaginale Sonde durchgeführt. Die Ge-\nwebedeformation der TIE und des umgebenden Gewebes\nwurde als prozentuale Gewebedeformation oder als subjek-\ntive Farbscala (CS; von blau = steif bis rot = weich, mit Zahlen-\nwerten von 0 bis 3) angegeben. Das Verhältnis Normalge-\nwebe/TIE wurde mit dem Verhältnis Normalgewebe/steiferes\nnormales Gewebe verglichen.\nErgebnisse Es wurden 46 TIE-Knoten und das sie umgebende\nGewebe von Ligamentum sacrouterinum (n = 21), Parame-\ntrium (n = 7), Rectum (n = 14) und Septum rectovaginale\n(n = 4) ausgewertet. Unabhängig von der Lokalisation waren\ndie Strain-Ratio (3,09; IQR 2,38 –4,14 vs. 1,25; IQR 1,11 –\nOriginal Article\n69Xholli A et al. The Benefit of … Ultraschall in Med 2024; 45: 69 –76 | © 2023. Thieme. All rights reserved.\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\nAccepted Manuscript online: 2023-02-06   Article published online: 2023-04-13\n\n1,48; p < 0,001) und CS-Ratio (4,62; IQR 3,83 –6,94 vs. 1,13;\nIQR 1,06–1,29; p < 0,001) der TIE signifikant höher als bei Nor-\nmalgewebe. Die ROC-AUC der CS-Ratio war höher als die\nROC-AUC der Strain-Ratio (99,76 %; 95 % CI = 99,26 –100 vs.\n91,35; 95 % CI = 85,23 –97,47; p = 0,007), und der optimale\nROC-Schwellenwert für die CS-Ratio betrug 1,82 bei einer\nSensitivität von 97,83 % (95 %CI = 93,48 –100) und einer Spezi-\nfität von 100 % (95 % CI = 100 –100).\nSchlussfolgerung Sowohl die Strain- als auch die CS-Ratio er-\nmöglichen eine genaue Differenzierung von TIE-Knoten an\nverschiedenen Stellen. Der Einsatz der Elastografie zur Verbes-\nserung der TIE-Diagnose, zur Unterscheidung verschiedener\nTIE-Läsionen und zur Überwachung der TI E-Entwicklung kann\nin Betracht gezogen werden und sollte weiter untersucht wer-\nden.\nIntroduction\nEndometriosis is a common chronic inflammatory disease charac-\nterized by ectopic endometrial tissue outside the uterine cavity [1,\n2, 3]. Its prevalence is roughly 5 –10 % in the general female popu-\nlation but reaches 71 –87 % in women with pelvic pain [2, 3]. Endo-\nmetriosis can be characterized by superficial implants on the ab-\ndominal serous membrane or distant organs (e. g., pleura or\npericardium) [3, 4, 5]. In the pelvis, endometriosis can lead to\ndeeper lesions affecting the bladder, rectum, sigmoid tract, rec-\ntovaginal septum, parametrium and/or uterosacral ligaments [5].\nThese lesions are commonly aggregated under deep infiltrating\nendometriosis (DIE) [5, 6], which often requires extensive surgery\nleading to severe morbidity [7]. Several studies have now shown\nthat transvaginal sonography (TVS) performed by an expert sono-\ngrapher can be regarded as being an accurate method in defining\nDIE nodules and their extension, as magnetic resonance imaging\n(MRI) [5, 8, 9]; although, accurate diagnosis of nodules of the\nuterosacral ligaments and parametrium remains problematic [5].\nStrain elastography (SE) measures tissue stiffness/elasticity and is\ncommonly used to characterize lesions of the breast and other or-\ngans [10, 11]. DIE lesions are stiffer than normal surrounding tis-\nsue, but few studies have applied SE to their characterization [12,\n13]. Hence, the aim of this study was to assess whether SE discri-\nminates DIE from surrounding non-endometriotic tissue. The sec-\nondary objective was to evaluate if the capabilities of elastography\nin distinguishing DIE lesions differed by location.\nMethods\nDesign and participates\nThis observational study was conducted between October 2020\nand December 2021 in a third-level academic hospital gynaecolo-\ngy outpatient facility. The study did not involve any intervention\nbeyond standard clinical practice. Publication of the results was\napproved by the Ethics Committee of IRCCS Ospedale Policlinico\nSan Martino, Genoa (CER Liguria n. 19/2022). Each participant\nsigned informed written consent for the anonymous use of their\ndata in clinical research.\nThe sample comprised all consecutive patients of 18 to 45\nyears of age complaining of endometriosis symptoms referred to\nthe specialist outpatient facility during the study period with a\nprevious or current diagnosis of DIE. Demographic and clinical\ndata were collected for each. Presence of pain at menstruation, in-\ntermenstrual pain, and pain at intercourse was recorded [14, 15,\n16]. The intensity of each type of pain was estimated individually\non a 100-mm visual analogue scale (VAS) [3]. Each woman under-\nwent standard bimanual vaginal examination to assess for the\npresence of stiff nodules, tenderness and mobility of pelvic or-\ngans. Transvaginal sonography was then performed by an expert\nqualified practitioner (A.X.). The presence of gynaecological dis-\neases such as uterine myomas and adenomyosis was assessed\nusing the MUSA criteria [17]. Ovarian endometriosis and DIE of\nthe posterior and anterior compartments was diagnosed based\non the IDEA consensus opinion and in accordance with recent\nguidelines [9, 18]. Women with a clinical and sonographic diagno-\nsis of DIE were further evaluated by SE. Some of these women had\npreviously received a surgical d iagnosis of endometriosis, and\nsome underwent surgery afterwards if clinically indicated [19].\nWhen surgery was performed, endometriosis was confirmed by\nhistology.\nSonographic Measurements\nA sole operator performed all ultrasound assessments using a\nVoluson E6 General Electric (GE Medical System, Zipf, Austria)\ninstrument. The ultrasound examinations were conducted with\na transvaginal wideband 5 –9 Mhz transducer and dedicated\nelastography software (GE Medical System, Zipf, Austria). Volume\n(cm3) of endometriotic nodules identified in B-mode was evaluat-\ned by the ellipsoid formula (3 mai n diameters × 0.5223). Tissue\nstiffness/elasticity was evaluated by SE, which measures tissue de-\nformation or displacement provoked by an applied pressure [10,\n12, 13]. The strain value can be depicted using colored shading\nsuperimposed on the B-mode image. The strain of different re-\ngions of interest (ROI) can be conc omitantly evaluated, and the\nstrain ratio, a measure of the discrepancy in the elasticity of differ-\nent tissues, can be used to improve SE accuracy [10, 20, 21]. For\nimage acquisition in B-mode, the vaginal probe was positioned in\nthe region of the endometriotic nodule. Afterwards, the sonogra-\npher performed a series of approximately 5 compression-decom-\npression cycles in the elastography modality, revealing the co-\nlored shading superimposed on the B-mode image. The\ncompression and decompression process were achieved using\nsub-centimetric motions perpendicular to the axis of the endome-\ntriotic lesion. A feedback contro l bar in the ultrasound real-time\nelastography program was used to check and maintain optimal\ncompression force ( ▶ Fig. 1). The dynamic elastography acquisi-\ntion process was recorded on video, to be analyzed afterward off-\nline ( ▶ Video 1). The offline analyst was blinded to patient data.\n70 Xholli A et al. The Benefit of … Ultraschall in Med 2024; 45: 69 –76 | © 2023. Thieme. All rights reserved.\nOriginal Article\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\nThe endometriotic nodule was well characterized under SE as a\nhomogenous blue area distinct from surrounding tissue. Three\nROIs (circular areas of 7.06 mm2), placed at an equal distance\nfrom the probe, were: the endometriotic nodule, the surrounding\nnon-endometriotic tissue on the left of the nodule, and the sur-\nrounding non-endometriotic tissue on the right ( ▶ Fig. 1). The\nstrains and the colour scores were computed at optimal compres-\nsion. For each of the three ROIs, the SE software provided the nu-\nmerical value of the strain as the percentage of tissue deforma-\ntion. The CS (purple/blue as low elasticity, yellow/green as\nintermediate, and red as high) was also coded as follows: from\n0 = blue/purple to 3.0 = red [20, 21]. The mean value of three\nmeasurements was used. Raw values for strain and CS were used\nto calculate the respective ratios. Strain or CS ratio of the endo-\nmetriotic nodule was defined as the ratio between the mean of\nthe two non-endometriotic tissue ROIs as the nominator, divided\nby the value obtained from the endometriotic nodule ROI as the\ndenominator. The resulting value was compared to the strain or\nCS ratio of the non-endometrioti c tissue; this was calculated as\nthe ratio between the mean of the two non-endometriotic tissue\nROIs as the nominator, and the minimum value between the two\nROIs from surrounding non-endometriotic tissue as the denomi-\nnator. This yielded ratios with a scale starting from 1, and progres-\nsively increasing values that correspond to tissue of greater con-\nsistency.\nSample size assessment\nThe sample size was calculated according to preliminary data col-\nlected from six patients to find any difference in strain ratio for dif-\nferent DIE locations paired with normal tissue using a nonpara-\nmetric test. The target sample size was therefore 4 pairs,\nsufficient to detect differences in the median strain ratio between\nendometriosis and normal tissue in every DIE assessed, with pow-\ner 80 % and a 0.05 significance level on two-sided testing.\nData analysis\nData were analyzed using the statistical package R [22] (version\n3.6.3; R Core Team (2020). Kolmogorov –Smirnov was used to\ntest the normal distribution of data. A Wilcoxon test or t-test was\napplied to the continuous variables, as appropriate (the endome-\ntriotic lesion and the paired nor mal tissue were tested using a\npaired test). Dichotomic variab les were tested using the chi-\nsquared or Fisher ’se x a c tt e s t .C o n t i n u o u sd a t aa r ep r e s e n t e da s\nthe median and interquartile range (IQR) or mean and standard\ndeviation. Categorical variables are expressed as frequencies, ab-\nsolute values, and percentages. Intra-operator variability was as-\nsessed via the intraclass correlation coefficient (ICC) and its 95 %\nconfidence interval (CI.95). The performance of strain and CS ra-\ntios in determining the presence of an endometriotic nodule was\nevaluated by generating the receiver operating characteristic\n(ROC) curves. ROC curves are presented with their area under\nthe curve (AUC) and relative CI.95. The DeLong test was used to\ncompare AUCs of different ROC curves. For all analyses, a two-\ntailed p-value < 0.05 was considered significant.\n▶ Fig. 1 Endometriotic nodule (white arrow) under B-mode elastography, showing colored shading superimposed on the image (Panel A), and\nexample of tissue strain elastography (Panel B). The yellow circular region of interest (ROI) is located on the endometriotic nodule, and the other\ntwo ROIs (blue and purple) on the left and right surrounding tissue.\nOP-VIDEO\n▶ Video 1 Dynamic elastography acquisition.\n71Xholli A et al. The Benefit of … Ultraschall in Med 2024; 45: 69 –76 | © 2023. Thieme. All rights reserved.\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\nResults\nPopulation\nThe study examined 46 DIE nodules from 32 women. Mean age at\ndiagnosis was 37.31 ± 8.43 years. ▶ Table 1 shows the characteris-\ntics of participants. 18.7 % of them had had a surgical diagnosis of\nendometriosis within the previous 24 months. A subsequent his-\ntological evaluation of the nodule detected at sonography was\nobtained in 32.1 % of the nodules.\nTransvaginal elastography\nIn a preliminary assessment of 6 nodules in 6 different subjects,\nthe intra-operator variability for strain ratio was 0.841 (CI.95\n0.516–0.966), and for CS ratio it was 0.925 (CI.95 0.816 –0.980).\nElastography of DIE nodules and surrounding tissue is depicted\nin ▶ Fig. 1. The strain ratio of DIE nodules (3.09, IQR 2.38 –4.14)\nwas significantly higher than that of normal tissue (1.25, IQR\n1.11–1.48) (p < 0.001). Similarly, the CS ratio of DIE nodules was\nsignificantly higher (4.62, IQR 3.83 –6.94) than that of normal tis-\nsue (1.13, IQR 1.06 –1.29) (p < 0.001). The distributions of strain\nand CS ratios of DIE nodules was well distinguished from those of\nnormal tissue ( ▶ Fig. 2). ROC plots present strain and CS ratio ac-\ncuracy in defining DIE implants ( ▶ Fig. 2); the best threshold for\nstrain ratio ROC was 1.68, with a sensitivity of 91.3 % (CI.95\n82.61 –97.83 %) and a specificity of 82.61 % (CI.95 71.74 –\n93.48 %), while the best threshold for CS ratio ROC was 1.82,\nwith a sensitivity of 97.83 % (CI.95 93.48 –100 %) and a specificity\nof 100 % (CI.95 100 –100 %). CS ratio AUC (99.76 %, CI.95 99.26 –\n100 %) was higher than strain ratio AUC (91.35 %, CI.95 85.23 –\n97.47 %) (p = 0.007).\nStrain ratio and CS ratio of different DIE locations\nStrain ratio and CS ratio were not significantly different among the\ndifferent DIE locations. Similarly, the difference between endome-\ntriosis and normal tissue strain a nd CS ratios was consistently\nshown in all the locations investigated, even though, for a low\nnumber of cases in the recto-vaginal septum, it did not reach sta-\ntistical significance ( ▶ Table 2). Strain and CS ratios of nodules\nwith histological diagnosis of endometriosis were also calculated\nseparately. Data were not diff erent from those obtained when\nconsidering all nodules ( ▶ Table 2).\nThe accuracy of the strain and CS ratios in distinguishing endo-\nmetriotic nodules in different locations was evaluated by\nROC plots ( ▶ Fig. 3). Data were similar among locations. At the\nuterosacral ligaments, the stra in ratio AUC was 89.91 % (CI.95\n81.49 –98.33 %) and the CS ratio AUC 100 % (CI.95 100 –100 %),\nthe difference between the two being significant (p = 0.019). At\nthe parametrium, the strain ratio AUC was 90.99 % (CI.95 82.6 –\n99.39 %) and the CS ratio AUC 100 % (CI.95 100 –100 %), the differ-\nence between the two being significant (p = 0.036). At the\nrectum, the strain ratio AUC was 92.31 % (CI.95 85.46 –99.16 %)\nand the CS ratio AUC 99.22 % (CI.95 97.57 –100 %), the difference\nbetween the two being close to significant (p = 0.056). At the rec-\nto-vaginal septum, the strain ratio AUC was 96.2 % (CI.95 90.77 –\n100 %) while the CS ratio AUC was 100 % (CI.95 100 –100 %); this\ndifference was not significant, probably due to the limited num-\nber of cases in the sample (p = 0.169). Separate ROC curves for\nDIE nodules confirmed by histology were also calculated. Data\nwere comparable to those reported for all nodules considered to-\ngether ( Supplemental Figure 1 ).\n▶ Table 1 Characteristics of the population.\nWomenʼs background characteristics\nand therapy\nWomen (n.) 32\nAge (years) 37.31 (± 8.43)\nNulliparity 31.25 % (10/32)\nActual surgery 34.38 % (11/32)\nPrevious surgery 18.75 % (6/32)\nMedical therapy 34.38 % (11/32)\n▪ Progesterone 28.12 % (9/32)\n▪ COC 6.25 % (2/32)\nWomenʼs symptoms\nDysmenorrhea 68.75 % (22/32)\n▪ Dysmenorrhea VAS 5 (0 –8)\nOvulation pain 37.5 % (12/32)\n▪ O v u l a t i o np a i nV A S 0( 0 –5)\nChronic pelvic pain 62.5 % (20/32)\n▪ Chronic pelvic pain VAS 3.5 (0 –6.25)\nDyspareunia 46.88 % (15/32)\n▪ D y s p a r e u n i aV A S 0( 0 –7.25)\nDyschezia 25 % (8/32)\n▪ D y s c h e z i aV A S 0( 0 –1)\nBack pain 43.75 % (14/32)\n▪ Back pain VAS 0 (0 –5.25)\nInguinal pain 9.38 % (3/32)\nEndometriotic nodules characteristics\nNumber 46\nVolume (cm³) 0.62 (0.35 –1.01)\nNodules per women 1 (1 –2)\nLocations\n▪ Uterosacral ligaments 45.65 % (21/46)\n▪ Parametrium 15.22 % (7/46)\n▪ Rectum 30.43 % (14/46)\n▪ Recto-vaginal septum 8.7 % (4/46)\nAcronyms: COC = Combined oral contraceptives; VAS = Visual Analogue\nScale.\n72 Xholli A et al. The Benefit of … Ultraschall in Med 2024; 45: 69 –76 | © 2023. Thieme. All rights reserved.\nOriginal Article\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\nDiscussion\nPrincipal findings\nAt SE analysis, strain and CS ratios for DIE lesions and normal tis-\nsue were significantly different, irrespective of nodule location.\nThe accuracy of discriminating endometriotic tissue from normal\ntissue was high in all areas examined.\nResults in the context of what is known\nThe value of tissue stiffness obtained by SE is variable and opera-\ntor dependent [23, 24]. Accordingly, it is not feasible to appropri-\nately define absolute stiffness by this method. Usually, the stiff-\nness ratio of sites of interest and adjacent tissue is more\nappropriate to eliminate inter-operator variability, as the com-\npression and decompression exerted by the operator similarly af-\nfect the two areas [10, 25, 26]. In this study, the stiffness ratio of\ntwo areas of the same tissue surrounding the nodule was compar-\ned with the stiffness of the nodule. DIE nodules were always stiffer\nthan surrounding tissue, and the ratio of non-endometriotic/DIE\nnodule was consistently above 1. We aimed to evaluate whether\nSE analysis expressed in this way can be used to differentiate DIE\nfrom surrounding tissue. To achieve this goal, we calculated the\nnormal tissue ratio as the ratio between the mean stiffness of the\ntwo areas surrounding the nodule as the numerator, divided by\nthe value of the stiffer area of the two. In this case too, the ratio\nwas consistently above 1. It emerged that the distribution of both\nstrain and CS ratios of DIE nodules was markedly different from\nthose of surrounding tissue. Cut-off values differentiating nodule\nfrom surrounding tissue were similar for strain and CS ratios, and\nboth showed high sensitivity and specificity. For CS ratio, a cut-off\nvalue of 1.82 was associated with sensitivity and specificity close\n▶ Fig. 2 Distribution of strain ratio (panel A) and color score (CS) ratio (Panel B) values in endometriosis versus normal tissue. ROC plot showing\naccuracy of strain ratio (Panel C) and CS ratio (Panel D) values in distinguishing endometriosis nodule from non-endometriotic tissue.\n73Xholli A et al. The Benefit of … Ultraschall in Med 2024; 45: 69 –76 | © 2023. Thieme. All rights reserved.\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\nto 100 %. Results were similar for any location of DIE, as previously\nreported for shear-wave elastography [27]. Similar results were\nobtained when considering DIE nodules with a histological diag-\nnosis separately.\nClinical implications\nSE has previously been applied to DIE in Douglas ’s cul-de-sac. Al-\nthough greater tissue stiffness was found in women with DIE, no\nattempt was performed to evaluate the sensitivity of this tech-\nnique [12]. In a recent article, share wave elastography proved to\nbe capable of detecting DIE nodules [27]. Share-wave elastogra-\nphy is more reproducible than SE and gives an absolute tissue\nstiffness value. However, we demonstrate herein that SE detects\nDIE, from surrounding non-endometriotic tissue, with high sensi-\ntivity and specificity when appropriate ROIs are used for calculat-\ning strain or CS ratio. In particular, the distribution curves of strain\nand CS ratios of normal versus endometriotic tissue had minimal if\nany superimposition. In normal tissue the curve was narrow, while\nin DIE it was broader and flatter, indicating a large variability of\nDIE nodule stiffness, probably due to the different proportions of\nfibrotic tissue [27].\nStrengths and limitations\nOne of the limitations of this stu dy is that SE is operator-depen-\ndent. To minimize this bias, we used three different strategies: a\nsingle experienced operator performed all the elastography eva-\nluations; strain values were analyzed at optimal tissue compres-\nsion, as indicated by the elastography software; strain or CS values\nwere not considered as an absolute value but as the ratio of ROIs\nvalues. Yet, we acknowledge that the inter-observer reproducibil-\nity of our analysis needs to be tested in further studies. Some\nwomen had undergone surgery before our evaluation and post-\nsurgical scars may have modified tissue stiffness. We did not ob-\nserve relevant differences between women with and without a\nprevious surgery, but the number of subjects was limited, and ad-\nditional studies are necessary to investigate this possible con-\nfounding. Elastography was app lied after nodule identification,\nand in this condition, both strain and CS ratios discriminated no-\ndules from normal tissue. It remains to be seen whether elastogra-\nphy may help less-skilled sonographers to distinguish DIE from\nsurrounding tissue, becoming an additional tool for achieving an\naccurate diagnosis of DIE.\nResearch implications\nProspective studies should help determine whether our method is\na sensitive and specific tool for diagnosing DIE, particularly in\nareas where ultrasonography is less accurate, such as the uterosa-\ncral ligaments and the parametrium [5]. The stiffness of DIE no-\ndules varies widely, and whether these differences are related to\na different DIE composition is suggestive but unproven. A differ-\nent stiffness may identify an active DIE, which can be more symp-\ntomatic and responsive to medical treatment.\nConclusions\nSE expressed as both strain and CS ratio highly accurately distin-\nguishes DIE nodules at various locations from surrounding non-\nendometriotic tissue. Pending validation and reproducibility test-\ning of our findings by prospective studies, elastography may re-\npresent an important tool for diagnosing DIE and possibly moni-\ntoring its evolution either spontaneous or in response to\ntreatment.\n▶ Table 2 Strain ratio and CS ratio divided by location and tissue type (endometriosis/normal tissue). Analysis on nodules confirmed by histological\ndiagnosis is also separately reported.\nA) All endometriotic nodules Uterosacral ligaments (21) Parametrium (7) Rectum (14) Recto-vaginal septum (4)\nStrain ratio endometriosis 3.09 (2.10 –4.00) 3.00 (2.42 –3.50) 3.47 (2.64 –4.83) 3.75 (3.08 –4.38)\nStrain ratio normal tissue 1.16 (1.07 –1.32) 1.24 (1.17 –1.26) 1.34 (1.15 –1.56) 1.82 (1.44 –2.65)\np-value (*) < 0.001 0.016 0.003 0.125\nCS ratio endometriosis 5.17 (4.50 –7.75) 3.83 (2.56 –6.00) 4.50 (3.80 –6.94) 4.00 (3.34 –5.38)\nCS ratio normal tissue 1.10 (1.05 –1.26) 1.11 (1.07 –1.16) 1.22 (1.09 –1.30) 1.52 (1.36 –1.64)\np-value (*) < 0.001 0.016 0.001 0.125\nB) Nodules with histology Uterosacral ligaments (6) Parametrium (3) Rectum (5) Recto-vaginal septum (1)\nStrain endometriosis 3.34 (2.14 –4.00) 3.00 (2.50 –3.46) 3.83 (2.67 –4.30) –\nStrain control 1.30 (1.10 –1.61) 1.24 (1.12 –1.25) 1.15 (1.07 –1.33) –\np-value (*) < 0.001 0.016 0.003 –\nCS endometriosis 4.69 (4.50 –9.09) 6.25 (4.44 –9.38) 4.50 (4.50 –7.00) –\nCS control 1.18 (1.07 –1.28) 1.17 (1.13 –1.21) 1.17 (1.13 –1.27) –\np-value (*) < 0.001 0.016 0.001 –\n(*) Differences between endometriosis and normal tissue in each location (paired Wilcoxon test).\nAcronyms: CS = color score.\n74 Xholli A et al. The Benefit of … Ultraschall in Med 2024; 45: 69 –76 | © 2023. Thieme. All rights reserved.\nOriginal Article\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\nConflict of Interest\nThe authors declare that they have no conflict of interest.\nReferences\n[1] Bulun SE, Yilmaz BD, Sison C et al. Endometriosis. Endocr Rev 2019; 40:\n1048–1079. doi:10.1210/er.2018-00242\n[2] Mariuzzi L, Domenis R, Orsaria M et al. Functional Expression of Aryl Hy-\ndrocarbon Receptor on Mast Cells Populating Human Endometriotic Tis-\nsues. Lab Invest 2016; 96: 959 –971. doi:10.1038/labinvest.2016.74\n[3] Xholli A, Filip G, Previtera F et al. Modification of Endometrioma Size dur-\ning Hormone Therapy Containing Dienogest. Gynecol Endocrinol 2020;\n36: 545 –549. doi:10.1080/09513590.2019.1703942\n[4] Takigawa Y, Mizuno D, Iga N et al. Catamenial Pneumothorax Due to\nHeterotopic Endometriosis in the Pericardium. 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