ABSTRACT Quantitative strain elastography (SE), referred to as E-Cervix (Samsung Medison), is a novel method for assessing parameters that indirectly describe the elasticity of the cervix.

This evaluation yields quantitative parameters based on the analysis of the elastographic map image, which represents a new approach in the context of SE. In our study, we aimed to examine

the reproducibility of this method in evaluating the cervix of non-pregnant women, the impact of basic demographic parameters of the patient on the results, and the responsiveness of the

method, i.e., the assessment of changes occurring in the results after the vaginal application of a 400 µg dose of misoprostol. We included 80 patients scheduled for hysteroscopy who

Coefficient) for intraobserver variability being good to excellent, ranging from 0.85 for ECI (Elasticity index) to 0.94 for IOS (Internal Os strain)/EOS (External Os strain) ratio. For

interobserver variability, ICC values ranged from 0.76 for ECI to 0.97 for IOS/EOS ratio. We observed no significant correlation between parameters such as height, weight, BMI (body mass

index), and the number of births in the patient’s history and the values of elastographic parameters. We found weak to moderate positive correlations between the day of the cycle in which

the patient was and ECI (rho = 0.28), EOS (rho = 0.41), IOS/EOS ratio (rho = 0.33). The study observed a significant increase in the median value of the HR (Hardness ratio) parameter after

the application of vaginal misoprostol (median difference = 5.32), an increase in EOS (difference of the medians = 0.04), and a significant decrease in IOS/EOS ratio (difference of medians =

− 0.05). In our study, we demonstrated high reproducibility and repeatability of E-Cervix parameters in non-pregnant women and showed a negligible influence of most demographic factors on

the study outcomes, as well as changes in parameter values under the influence of drugs affecting cervical elasticity. The method appears to be suitable for evaluating the cervix in

non-pregnant women. SIMILAR CONTENT BEING VIEWED BY OTHERS REPEATABILITY AND REPRODUCIBILITY OF QUANTITATIVE CERVICAL STRAIN ELASTOGRAPHY (E-CERVIX) IN PREGNANCY Article Open access 08

December 2021 MIDTRIMESTER CERVICAL ELASTOGRAPHY IN PREGNANT WOMEN WITH A HISTORY OF LOOP ELECTROSURGICAL EXCISION PROCEDURE (LEEP) Article Open access 02 June 2022 CLINICAL EXPERIENCE WITH

SHEAR WAVE ELASTOGRAPHY (SWE) FOR ASSESSING HEALTHY UTERUS IN A TRANSABDOMINAL APPROACH Article Open access 24 June 2024 INTRODUCTION Ultrasonographic elastography is finding increasingly

broad applications in medicine. It is conventionally used in liver and kidney diseases as well as in the diagnostics of breast tumors. Current research aims to extrapolate its use to new

branches of medicine. In terms of the physical basis of elastographic imaging, the two main methods used are shear wave elastography (SWE) and strain elastography (SE). These methods differ

in the type of stress applied to the tissue and the type of measurement performed. In SE, the elasticity of the tissue is measured through the correlation of radiofrequency echoes between

search windows where signal acquisition occurs during both compression and without tissue compression, while in SWE, the movement of particles perpendicular to the propagated wave is

measured, and the speed of this particle movement correlates with the shear modulus1. A definite advantage of SWE is its presentation of results in numerical form. SE, until now, had the

limitation of presenting images in the form of elastograms, or “color maps,” each color symbolizing the elasticity of the tissue. This is useful in the context of diagnosing focal changes in

organs, as it allows for the visualization of the elasticity of a focal change against the elasticity of the rest of the organ. However, this imaging creates a problem when it is necessary

to assess the entire organ. The cervix fits into this context, where in some situations, it is necessary to assess the organ as a whole, for example, during pregnancy or before procedures

related to the dilation of the cervical canal. Traditionally, the approach to assessing the elastogram was to visually evaluate the elasticity map through semi-quantitative assessment2.

However, such assessment was characterized by subjectivity. The solution to this problem appeared with the introduction of the E-Cervix software (Samsung Medison) into practice. It uses SE,

where the exciting factor is the pulse wave transmitted by surrounding tissues. As a result of its action, a colorful elastogram is obtained. The unique value of the software is the fact

that it provides quantitative parameters. These parameters arise as a result of the distribution of the number of pixels in each color on the obtained elastogram at specified points in the

region of interest (ROI). As a result, we obtain the following parameters: ECI (Elasticity Index): A measure of tissue heterogeneity. It informs about the average difference in color

intensity between neighboring pixels of the elastogram and adopts values from 0 to 81 (0—low heterogeneity, 81—high heterogeneity). HR (Hardness Ratio): The number of red pixels (defined as

the top 30% of the color intensity scale) among all the pixels in the ROI. This value is displayed as a percentage (0%—soft, 100%—hard). IOS (Internal Os Strain): Mean strain level of the

internal cervical os ROI [region of interest] (0—hard, 1—soft). EOS (External Os Strain): Mean strain level of the external cervical os ROI (0—hard, 1—soft). Ratio (IOS/EOS): Ratio of the

internal to the external cervical os mean strain. Additionally, the pressure of the probe is standardized through a reliability indicator with an auto-freeze option. After proper

stabilization of the vaginal probe, the motion bars appearing on the screen change color to green, and the image freezes automatically3. To date, research results available in the literature

mainly concern the examination of pregnant women’s cervixes using this module. This direction of research is intuitive, given the standard assessment of the cervix’s hardness by palpation

during pregnancy4. Good reproducibility and repeatability of this method in pregnancy have been proven5,6. We did not find any studies in the literature concerning the application of this

method in non-pregnant women. However, in this group, there is also potential for research into elastography for conditions such as neoplasms, infertility, or assessment before gynecological

procedures. In our study, we decided to evaluate the reproducibility of the E-Cervix software for quantitative elastogram assessment in non-pregnant women presenting to the clinic for

planned operative hysteroscopy, as well as to examine whether basic demographic parameters influence the parameters obtained in the E-Cervix analysis. The second aim of the study was to

assess the characteristics of elastogram changes 12–16 h after the application of vaginal misoprostol at a dose of 400 micrograms, which is standardly used before hysteroscopy procedures at

the center where the study was conducted. MATERIALS AND METHODS The study included patients presenting to the Department of the Provincial Hospital Complex in Kielce for a resectoscopy

procedure scheduled for the following day. Exclusion criteria were: women who had undergone cervical conization, those with Naboth cysts, cervical polyps, difficulty visualizing the internal

os of the cervix, and medical contraindications to the use of vaginal misoprostol (allergy to the drug, bronchial asthma). We utilized the Samsung Hera W10 device equipped with a 6 MHz

vaginal ultrasound transducer and E-Cervix software. Ethical approval for the study was obtained from the Bioethics Committee at Jan Kochanowski University in Kielce (approval number

22/2022). All methods were performed in accordance with the relevant local regulations and guidelines of the ethical commission. All enrolled patients expressed informed consent to

participate in the study. Upon admission, patients underwent transvaginal ultrasound assessment of the cervix according to a standard protocol (Table 1). The examination was performed twice,

with the removal of the probe from the vagina between examinations. The examination was conducted upon admission by the same operator, and the data obtained were used to assess

repeatability (intraobserver variability) and baseline correlation with various demographic parameters. On the same day, between 19:00 and 21:00, a physician administered 400 micrograms of

misoprostol in tablet form vaginally to the patient. Then, following the same protocol, the cervix was assessed the next day between 07:00 and 09:00 (10–12 h after medication

administration). The second examination was also performed twice using the same protocol, but by two operators (JP & JM); the values obtained in the second examination were used to

assess reproducibility (interobserver variability). After calculating the arithmetic means from the two primary measurements and the two post-misoprostol measurements, we compared the change

in individual parameters obtained in the study. Ultrasonographic examinations were performed by two operators (JM, JP) with four years of experience using the E-Cervix software. STATISTICAL

ANALYSIS All parameters obtained in the E-Cervix study are continuous variables. To describe the groups, we used the median as the measure of central tendency for distributions deviating

from normality (_p_ < 0.05 in the Shapiro-Wilk test) and the arithmetic mean for distributions approximating normality. As measures of dispersion corresponding to these values, we

presented the interquartile range and standard deviation, respectively. To assess the correlation between demographic data and parameters obtained in the E-Cervix analysis, we used

Spearman’s rank correlation coefficient. The strength of the correlation was interpreted using J. Guilford’s scale8. To evaluate the change in parameters obtained in the E-Cervix study after

the application of misoprostol, the change was calculated using the non-parametric Wilcoxon test for variables with a distribution close to normal, and the t-test for dependent samples was

used (only one variable—cervical length had a normal distribution). To assess intra- and interobserver variability of parameters obtained in the study, we calculated interclass correlation

coefficients (ICC). For each parameter obtained in the study, we presented Bland-Altman plots. On these plots, for each parameter, we illustrated the mean difference as well as the limits of

agreement (LoA), defined as the mean difference ± 1.96 times the standard deviation. Additionally, for each parameter, we reported the percentage of measurements that fall outside the LoA.

The minimal sample size was calculated for the assessment of reproducibility and repeatability based on the work of Bujang et al.9 and on a preliminary study10. Assuming the null hypothesis

that the ICC equals 0.5, with two observations per patient included in the study and a power of 80%, the data available in the study indicated a minimal sample size of 63 subjects. The ICC

values were interpreted as follows: > 0.9—excellent reproducibility, 0.75–0.9—good reproducibility, 0.5–0.75—moderate reproducibility, and < 0.5—poor reproducibility. The statistical

analysis was performed using SPSS version 27.0.1.0 (IBM Company) and Statistica version 13.1 (Tibco Software). Differences were considered significant at _p_ < 0.05. RESULTS The study

included 80 patients. Upon admission, patients underwent the examination twice by the same ultrasonographer, and the examination the next day after the application of the misoprostol dose

was performed by both ultrasonographers consecutively. The demographic analysis of patients included in the study is presented in Table 2. Basic data concerning the patients were correlated

with the parameters obtained in the E-Cervix study. The results of the correlation analysis are placed in Table 3. We obtained statistically significant positive correlations between the day

of the menstrual cycle and ECI, EOS, and the IOS/EOS ratio; in all cases, the strength of these correlations ranged from weak to moderate. We also found negative correlations between the

length of the cervix and parameters such as age, height, BMI, the number of prior births regardless of the mode, and the day of the menstrual cycle; in all cases, the strength of the

correlations was weak. Table 4 presents the analysis of reproducibility and repeatability of the values obtained in the E-Cervix study. All obtained parameters fell within the range of good

and excellent reproducibility, with the highest values characterizing the measurement of the cervix. Figures 1 and 2 present intraobserver and interobserver variability, respectively, on

Bland-Altman plots with marked mean differences between measurements and ± 1.96 SD (LoA). In Table 5, we reported the percentage of measurement pairs that fell outside the LoA. For none of

the parameters did the number of measurement pairs outside the LoA exceed 8.75%. In Table 6, we present the changes in individual parameters obtained in the study after the application of

the vaginal dose of misoprostol. We observed a statistically significant increase in the HR parameter (difference of the medians = 5.317) and an increase in EOS (difference of the medians = 

0.0425), as well as a decrease in the IOS/EOS ratio (difference of medians = − 0.05313). For the remaining parameters, we did not obtain statistical significance in terms of changes.

DISCUSSION Elastography is a dynamically developing branch of ultrasonography that is being extrapolated to new areas. In fundamental research on a new diagnostic method, it is crucial to

verify whether the obtained results are reproducible and whether there are any phenotypic traits of the patient that could interfere with the study outcome. In our study, we identified

certain relationships between the parameters obtained in the examination and demographic characteristics. The only parameter that partially correlated with the values obtained in E-Cervix

and indicated a tendency towards a more elastic cervix in terms of the external os was the day of the cycle. This result is consistent with physiological data suggesting that the consistency

of the cervix changes with the menstrual cycle phase11. However. the correlation was low. Literature also indicates that some E-Cervix parameters correlate with demographic data of

participants. Studies conducted in the third trimester of pregnancy observed a correlation with parameters such as the number of previous cesarean sections, BMI, weight, and the age of the

examined woman. However. in each of these cases. the correlation was very weak. with absolute values lower than 0.25,12. The difference in the impact of confounding factors can be explained

by the changing anatomy of the pelvis and abdominal cavity during pregnancy and the greater effect of intra-abdominal pressure on the large surface of the pregnant uterus, which in effect

may be transferred to the cervix, affecting its compression. In the literature, we did not find any other studies of this type conducted on non-pregnant women. In our opinion, due to the low

strength of the correlations. the obtained values do not significantly affect the outcomes of the measured values. The only significant correlation of E-Cervix parameters with a phenotypic

factor of the patient outside of pregnancy was the day of the cycle. We observed, of course, that other factors correlated with CL, which is an additional parameter obtained in the study.

but it does not interest us strictly speaking. as it is not an elastographic value. but appears as a result of the study after delineating the ROI. In our study, we observed very high

reproducibility of the parameters obtained. The ICC values obtained are higher than those obtained during studies on pregnant women5,12. This may be due to several factors. Firstly, the

elasticity of the cervical neck during pregnancy exhibits greater interindividual variability, and moreover. it changes as pregnancy progresses. which intensifies the interindividual

variability among women even during the same trimester. Studies available in the literature show variability in the parameters obtained in the study with the duration of pregnancy when the

examination is performed on the same pregnant patient at different times13. Secondly, during pregnancy. there are more factors that can disrupt the results of examinations even performed

within a short time interval, such as the positioning and movements of the child in the uterus. This may explain the higher ICC values obtained in our study compared to women who are not

pregnant. In our study, we showed that some E-Cervix parameters are responsive to the action of vaginal misoprostol. This is a synthetic prostaglandin used for inducing labor, inducing

abortion, as well as before performing procedures requiring dilation of the cervical canal. This prostaglandin affects the elasticity of the cervix and the width of its canal. Demonstrating

the responsiveness of this method may open up new diagnostic avenues. A natural area of potential application could be the assessment of the cervix before a planned hysteroscopy procedure

and qualification for the possible administration of misoprostol before the procedure. Hysteroscopy is a diagnostic and therapeutic procedure, usually performed with the aim of removing

changes inside the uterine cavity such as polyps. fibroids. uterine septa, etc. The total outer diameter of hysteroscopes varies significantly and mainly depends on the sheath size.

Introducing hysteroscopes with a diameter greater than 5 mm usually requires the operator to mechanically dilate the cervix. Cervical dilation is the most painful element of the procedure

from the patient’s point of view, which is particularly important in the case of local analgesia14. In a randomized study involving women before the insertion of an intrauterine device,

where half received 3 mg of dinoprostone vaginally 12 h before the procedure, patients receiving prostaglandins had lower pain scores during all subsequent steps necessary for IUD insertion,

and reported higher satisfaction with the procedure, while operators reported that the procedure was technically easier15. Having an objective method for assessing the cervix before the

procedure, such as elastography, could allow us to appropriately qualify patients both for the administration of misoprostol and for the administration of an additional dose in case of

inefficacy before the start of the procedure, which could increase patient satisfaction with the procedure by reducing pain discomfort. One of the mechanical complications of hysteroscopy is

uterine perforation. This complication occurs during resectoscopy at a frequency of about 1% of cases16,17. It is a complication associated with potential damage to abdominal cavity organs.

In up to 50% of perforation cases, it occurs in instances of difficulty passing through the cervical canal17. This means that with appropriate qualification, this complication could be

avoided. Other complications associated with difficulty passing through the cervical canal include the creation of a false passage, cervical tears, and the cancellation of the procedure due

to difficulty penetrating the cervical canal17. Besides the clinical potential of the method, it has significant potential to objectify scientific research. One such field may be studies

assessing methods of preparing the cervix for procedures requiring passage through the cervical canal (misoprostol, dinoprostone, laminaria). However, there is a problem in the literature

with reporting outcomes of such studies. Many criteria are subjective, such as the subjective ease of performing the procedure, the time needed to dilate the cervix, the size of the dilator

that passes through the cervical canal before the procedure (in such a case, it is necessary to check patency before applying the method of preparing the cervix, which is an invasive

element). Other measures, such as the rate of perioperative complications, seem more objective but can also depend on manual skills18. Future studies should assess the correlations between

the aforementioned outcome measures and the parameters obtained in the E-Cervix study, possibly establishing a direct relationship between the parameter values and outcome measures, and over

time allow for their interchangeable use. A limitation of the study is the lack of reference to the hysteroscopy procedure; we did not assess the relationship between the study outcomes and

the outcomes of hysteroscopy, nor the direct relationship of measured parameters in absolute values with hysteroscopy results. We also did not assess patients by categorizing them based on

the type of pathology they presented with, and we do not know whether such pathology affects the results. The strength of the study lies in its innovativeness. So far, we have not found

studies in the literature where the cervix was assessed using this method in non-pregnant women. We also did not find studies attempting to link elastographic examination with the

“preparation” of the cervix for hysteroscopy procedures. CONCLUSION Elastographic examination of the cervix in non-pregnant women is characterized by high repeatability. There is a low

sensitivity of the results to the phenotypic factors of the patients. The study shows reactivity to the modeling of the cervix under the influence of prostaglandins. DATA AVAILABILITY The

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before operative hysteroscopy. _Cochrane Database Syst. Rev._ 2015 (4), CD005998 (2015). Download references ACKNOWLEDGEMENTS This publication was co-financed by the KOPIPOL Association’s

Creators Fund. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Collegium Medicum, Jan Kochanowski University in Kielce, Kielce, Poland Jakub Mlodawski, Justyna Plusajska, Grzegorz Swiercz 

& Marta Mlodawska * Clinic of Obstetrics and Gynecology, Provincial Combined Hospital in Kielce, Kielce, Poland Jakub Mlodawski, Justyna Plusajska, Karolina Detka, Grzegorz Swiercz &

 Marta Mlodawska Authors * Jakub Mlodawski View author publications You can also search for this author inPubMed Google Scholar * Justyna Plusajska View author publications You can also

search for this author inPubMed Google Scholar * Karolina Detka View author publications You can also search for this author inPubMed Google Scholar * Grzegorz Swiercz View author

publications You can also search for this author inPubMed Google Scholar * Marta Mlodawska View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS

J.M.—conception, original draft, result interpretation, sonographic examinations; J.P.—ultrasonographic examination, , K.D.—data collection, G.S.—results interpretation, M.M. —original

draft, supervision. CORRESPONDING AUTHOR Correspondence to Jakub Mlodawski. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ADDITIONAL INFORMATION

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Reproducibility of quantitative cervical strain elastography in nonpregnant patients and the effect of vaginal misoprostol on measured parameters. _Sci Rep_ 15, 16857 (2025).

https://doi.org/10.1038/s41598-025-01249-y Download citation * Received: 28 March 2024 * Accepted: 05 May 2025 * Published: 15 May 2025 * DOI: https://doi.org/10.1038/s41598-025-01249-y

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