Magnetic resonance elastography (MRE) for the evaluation of fibrosis in patients with benign uterine disorders: a systematic review

Benign uterine disorders encompass a heterogeneous group of gynaecological pathologies, including leiomyo - mas (fibroids) and adenomyosis. Leiomyomas represent the most prevalent uterine mass, reported to occur in over 70% of women by the onset of menopause [ 1]. Adenomyo- sis, characterized by the presence of endometrial glands and stroma within the myometrium, has an estimated prevalence ranging between 5 and 70%, depending on the diagnostic

applied [2], and is commonly associated with deep endometriosis (DE) [3]. Collectively, these disorders repre- sent a significant clinical burden, not only because of their impact on quality of life but also due to their implications for fertility and reproductive health [4–6]. Sabrine Q. Kol [email protected] Nienke P.M. Wassenaar [email protected] Robert A. de Leeuw [email protected] Shandra Bipat [email protected] 1 Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, Netherlands 2 Imaging and Biomarkers, Cancer Center Amsterdam, Amsterdam, Netherlands 3 Department of Obstetrics and Gynaecology, Amsterdam University Medical Centers, Amsterdam, Netherlands 4 Amsterdam Reproduction and Development (AR&D), Research Institute, Amsterdam, Netherlands

Objective To review magnetic resonance elastography (MRE) techniques and evaluate the feasibility of quantifying the extent of fibrosis in patients with benign uterine disorders.

A systematic search of the MEDLINE and EMBASE databases was performed for identifying rel - evant articles published between January 1, 2007, and September 2025. Studies meeting predefined inclusion criteria were selected. Two independent reviewers extracted data on study design, patient population, MRI protocol characteristics, MRE parameters and MRI/MRE features. Mean stiffness (kPa), including standard deviation were either extracted or calculated. The same reviewers also assessed the methodological quality of each study.

Six studies comprising a total of 162 patients (mean age range: 40.5 to 49 years) were included. Five studies focused on stiffness measurements in leiomyomas, while one study investigated the feasibility of stiffness measurements in patients with adenomyosis. All studies were classified as either pilot or feasibility studies. In studies reporting reproductive status, most patients were premenopausal (89 out of 125). The mean stiffness in evaluating leiomyomas ranged from 3.02 to 7.10 kPa across the included studies, resulting in a pooled mean stiffness of 4.72 ± 1.83 kPa. Uterine stiffness was higher in women with adenomyosis (2.93 kPa; range, 2.34–3.39 kPa) than in the healthy volunteer (2.04 kPa). Two studies correlated stiffness measurements with histopathological findings of fibrosis. All included studies were rated as having good methodological quality.

Despite the small number of studies, current findings suggest that MRE is a feasible imaging modality for measuring fibrosis.

Magnetic resonance imaging · Magnetic resonance elastography · Uterine leiomyomas · Adenomyosis · Benign uterine pathology · Systematic review Received: 12 November 2025 / Revised: 24 December 2025 / Accepted: 1 January 2026 © The Author(s) 2026 Magnetic resonance elastography (MRE) for the evaluation of fibrosis in patients with benign uterine disorders: a systematic review Sabrine Q. Kol1 · Nienke P .M. Wassenaar1,2 · Robert A. de Leeuw3,4 · Shandra Bipat1 1 3 Abdominal Radiology Although these benign uterine disorders differ in their pathogenesis and clinical presentation, they all are associ - ated with alterations in the extracellular matrix and increas- ing amounts of fibrosis. Leiomyomas are defined by smooth muscle proliferation within a fibrotic stroma [7], while ade- nomyosis results from the pathological invasion of endo - metrial tissue into the myometrium, which triggers smooth muscle hyperplasia and hypertrophy, ultimately leading to fibrotic remodeling [8, 9]. This fibrotic remodeling is driven by fibroblast activity and excessive extracellular matrix deposition, which play a critical role in symptomatology, including pain and abnormal uterine bleeding [ 10]. More- over, fibrotic changes can impair uterine contractility and increase the risk of obstetric complications, including uter - ine rupture, which has been reported to be more frequent in adenomyosis than in other uterine pathologies [ 11, 12]. Adenomyosis may develop from the endometrium outward or from the serosal surface inward, the latter form being strongly associated with deep endometriosis, which under - goes extensive fibrotic transformation contributing to its infiltrative behavior [13]. In leiomyomas, fibrosis not only contributes to lesion growth and symptom severity but also impacts treatment response, influencing outcomes of inter - ventions such as uterine artery embolization [ 14]. Across both conditions, the degree of fibrosis adds complexity to medical and surgical management, highlighting the impor - tance of incorporating fibrosis assessment into pre-treatment planning [ 15, 16]. Consequently, non-invasive imaging techniques capable of evaluating tissue stiffness and detect- ing fibrosis in vivo, such as elastography, may offer valuable diagnostic and prognostic insights across the spectrum of benign uterine pathologies. Elastography is an imaging technique used to assess tis - sue stiffness and can be performed with either ultrasound or magnetic resonance imaging (MRI). Ultrasound elastog- raphy may be carried out using strain elastography, which is qualitative and operator-dependent, or shear wave elas - tography, which provides quantitative values but has tech - nical limitations [17]. Both techniques face reproducibility challenges, particularly due to the selection of the region of interest (ROI) in heterogeneous lesions. In benign gynae - cology, ultrasound elastography (USE) has been applied to the evaluation of the normal uterus, the myometrium (leio - myomas and adenomyosis), the endometrium (polyps), and pelvic endometriosis [18–22]. Acar et al. [19] demonstrated that myometrial stiffness measured with shear wave elas - tography (SWE) was significantly higher in adenomyosis than in healthy controls. Similarly, V ora et al. [20] reported increased stiffness in submucosal leiomyomas and focal adenomyomas. Magnetic resonance elastography (MRE) also provides quantitative measurements of tissue stiffness, achieved by applying low-frequency vibrations and tracking shear wave propagation with MRI. MRE is already used in clini - cal practice for liver fibrosis [ 23] and is being explored in areas such as pancreatic [ 24], cardiovascular [ 25], and neurological diseases [26]. The limitations of MRE include its high cost, limited availability, longer examination time, MRI-related contraindications, and the need for patients to remain still during image acquisition. Nevertheless, MRE offers several advantages over USE, including being able to assess whole organs (e.g. the uterus), not being as limited by depth or acoustic windows (e.g. body habitus, ascites), providing quantitative measurements and not being opera - tor dependent [ 27,28]. Furthermore, because MRE is per - formed within the context of an MRI examination, it also delivers high-resolution anatomical information along with tissue stiffness data. This study aims to systematically review MRE techniques and reported outcomes related to the use of MRE in quanti- fying fibrosis in patients with benign uterine disorders.

Study design This systematic review was conducted and reported in accordance with the Preferred Reporting Items for System - atic Reviews and Meta-analyses (PRISMA) guidelines: as outlined by Page et al. [29]. Search strategy A literature search was performed in the MEDLINE and EMBASE databases to identify relevant articles published from 2007 to date of search (Sept 1, 2025), as MRE was first introduced as a clinical test in 2007. The search strat - egy included the following search terms: “Magnetic Reso - nance Imaging” AND “Elastography” AND “Fibroids” OR “Leiomyomas” OR “Endometriosis” OR “ Adenomyosis”. The search strategy is described in detail in Supplement A. To identify additional articles, the citation indexes and the

lists of relevant articles were checked. Selection of relevant articles The title and/or abstract of all retrieved articles were screened for potential relevance by Reviewer 2 (X1), a methodolo - gist with extensive experience in systematic reviews. The following were excluded from further analysis: duplicates, conference abstracts, clinical registry entries, editorials, commentaries, letters-to-the-editor, non-relevant literature 1 3 Abdominal Radiology (e.g., not disease-related or involving other imaging tech - niques), narrative reviews, and case-reports. Inclusion criteria Subsequently, the full texts of the remaining articles were assessed by the same reviewer. The inclusion criteria were: 1) studies involving patients with a benign uterine disorder (including but not limited to: leiomyomas, deep endome - triosis and/or adenomyosis); 2) evaluation of fibrosis using MRE. All articles meeting these criteria were included for further data extraction. Data-extraction Data-extraction was performed independently by two reviewers, X1 and X2, the latter being an abdominal radiol- ogist with five years of dedicated experience in pelvic MRI. Any discrepancies between the reviewers were resolved through discussion. The following data were extracted: 1) Study characteristics, 2) Study population characteristics, 3) MRI protocol characteristics, 4) MRE parameters and main outcomes, 5) MRI and MRE features of leiomyomas, 6) Methodological quality of the included studies. Study characteristics The following data were extracted: 1) First author and year of publication, 2) Study period, 3) Country of origin, 4) Set- ting (academic or other), 5) Study type (pilot, feasibility or cohort), 6) Study design (single-center or multi-center, multi-center indicating involvement of authors from differ - ent institutions), 7) Department of first author, 8) Data col - lection method (retrospective or prospective), 9) Funding information, 10) Ethical approval status (No, Yes – whether informed consent was waived or obtained), and 11) Disclo- sure of conflict of interest. Study population characteristics The following study population-related data were obtained: 1) Inclusion and exclusion criteria, 2) Number of included patients, 3) Age (reported as mean ± standard deviation (SD) and/or range), 4) Body Mass Index (BMI) (reported as mean ± SD or median and range), 5) Menopausal status (premenopausal, perimenopausal or postmenopausal), 6) Symptoms, 7) Ethnicity, and 8) Type of surgery performed. MRI protocol characteristics The following technical aspects of MRI were extracted: 1) MRI vendor, 2) Magnetic field strength, 3) Type of coil used (body, phased array, or other), 4) MRI sequences performed (e.g., fat-saturated T1, post-contrast T1, T2-weighted, T2 HASTE, diffusion-weighted imaging (DWI) and/or dynamic contrast-enhanced (DCE) imaging). MRE parameters The summarized technical aspects of MRE included: 1) Mechanical wave frequency (in Hertz), 2) Method used to define the region of interest (ROI), 3) MRE post process - ing method, 4) Stiffness measurements reported for benign uterine disorder. MRI and MRE features of leiomyomas The following data were extracted: 1) Leiomyoma vol - ume (cm 3), 2) Leiomyomadiameter (cm), 3) Number of leiomyomas, 4) Location of leiomyoma in uterus wall, 5) Leiomyoma characteristics on T2-WI, 6) Leiomyoma char- acteristics on post-contrast imaging and, 7) MRE data of stiffness of leiomyoma in kPa (mean ± SD and/or median with ranges). In case MRE data were presented for any sub- groups, these data were also extracted. Statistical analysis Due to the expected small number of studies and limited patient cohorts, mostly originating from pilot and feasibility investigations, a formal meta-analysis was not conducted. Instead, pooled means and pooled standard deviations were estimated by weighting each study according to its sample size, mean, and standard deviation, thereby giving greater influence on studies with larger population. Details on pool- ing of the means and the standard deviations are given in Supplement B. Methodological quality assessment The methodological quality of the included studies was eval- uated based using the National Institutes of Health (NIH) quality Assessment Tool for Case Series Studies ( h t t p s : / / w w w . n h l b i . n i h . g o v / h e a l t h - t o p i c s / s t u d y - q u a l i t y - a s s e s s m e n t - t o o l s) (Supplement C). As all articles described cross-sectional studies (no cohort with exposure, no diagnosis with refer - ence standard and no treatment), we choose a checklist for cross-sectional studies to assess the methodological qual - ity. And as these cross-sectional studies were predominantly pilot or feasibility studies, we choose the NIH checklist for case series (low number of patients in each study) [30]. This tool consists of several questions addressing key domains of bias including, selection bias, performance bias, detection bias and attrition bias (i.e., lost to follow-up). 1 3 Abdominal Radiology in leiomyomas, while one study investigated the feasibil - ity of stiffness measurements in patients with adenomyosis. Additional study details are summarized in Table 1. Study population characteristics A total of 162 patients were included across all studies: 157 patients underwent MRE to assess fibrosis in uterine leio - myomas, 4 underwent MRE for the evaluation of fibrosis in adenomyosis, and one was a healthy volunteer. The reported mean age ranged from 40.5 to 49 years. In the studies where reproductive status was documented, most patients were premenopausal (89 out of 125). Other patient characteristics are listed in Table 2. MRI protocol characteristics & MRE parameters Four out of the six studies used a 1.5-T MRI, and 2 studies used a 3-T MRI. All patients were placed in supine posi - tion in the MRI scanner for image acquisition. None of the studies reported the use of spasmolytics or other prepara - tion protocols as part of their imaging procedures. MRE was performed using phased-array coils to ensure adequate sig - nal reception across the pelvic region. A passive driver was placed on the lower abdomen, directly over the uterus, and secured with a belt in three studies [33, 35, 36]. Aphinives et al. [35] reported using a soft pad placed beneath the passive driver to decrease patient vibrating sensations. The passive driver was connected via a flexible tube to an active driver, which was located outside the MRI suite, typically in the equipment room. The active drivers generated mechanical Each question was rated with “yes”, “no”, “other” (“cannot determine” (CD), “not applicable” (NA), or “not reported” (NR)). Finally, overall quality was determined based on the outcomes of the questions. If 6–8 questions were answered with YES, the quality rating of the study was assessed as “Good”. If 4–5 questions were answered with YES, the quality of the study was assessed as “Fair’’. In all of the other cases the quality was assessed as “Poor”.

Search strategy, selection and inclusion The initial search of the MEDLINE and EMBASE data - bases yielded 116 records (Fig. 1). After screening titles and abstracts, 108 studies were excluded for not meeting the inclusion criteria. The full texts of the remaining eight articles were reviewed in detail, resulting in the exclusion of two additional studies. Ultimately six articles were included for data extraction, five evaluating MRE in patients with leiomyomas [ 31–35] and one evaluating MRE in patients with adenomyosis [36]. Study characteristics All included studies were conducted in academic settings and were classified as either feasibility (2 studies) or pilot studies (4 studies). Five out of six studies were prospectively performed and all had received ethical approval. Further - more, 5 of the 6 studies focussed on stiffness measurements Fig. 1 Search, selection and inclu- sion of relevant articles 1 3 Abdominal Radiology et al.[ 31] additionally presented histograms of stiffness distributions. None of the studies reported any adverse events during the MRE examination. The MRI protocol characteristics and MRE technical features are summarized in Supplements D and E respec - tively. Additional MRE parameters and outcomes are listed in Table 3. Leiomyomas MRI and MRE features of leiomyomas Three of the five studies (Jondal et al. n = 102, Ichikawa et al. n = 11, and Aphinives et al. n = 26) reported that most of the patients, ranging from 62 to 100% had multiple leiomyomas [32, 33, 36]. Among the studies reporting on leiomyoma size (Stewart et al. n = 6, Jondal et al. n = 102 and Obrzut et al. n = 12), the diameter ranged from 4 cm to 22.5 cm [31, 32, 34]. The mean stiffness of leiomyomas ranged from 3.02 to 7.10 kPa across all the included studies. vibrations all at the frequency of 60 Hz, which was transmit- ted through the tube to the passive driver and subsequently propagated through the abdominal wall to the uterus. Shear wave imaging was evaluated in three studies [ 31, 32, 34] using a modified two-dimensional (2D) gradient- recalled echo–based elastography pulse sequence. In a subset of patients in the Jondal et al. [ 32] study, additional three-dimensional (3D) multi-slice spin-echo–based planar imaging sequences were acquired, while Jain et al. [ 36] employed a 3D EPI MRE approach. Following image acquisition, ROIs were selected. In three studies, the person responsible for delineating the ROIs was specified: in two studies ([ 31, 33], a radiologist performed this task, while in Aphinives et al. [ 35], an MRI technician was responsible. Additionally, three studies reported using the T2-weighted images as a guide when defining the ROIs, to avoid areas of degeneration in the leiomyoma, identified by T2 hyperintense areas. Stiffness values were reported across studies using a combination of mean, median, standard deviation, and, in some cases, minimum and maximum values (kPa). Stewart Table 1 Study characteristics of included articles Leiomyoma Author Department of first authors Country of origin Study type Study design Study Setting Study period Data collection Information on funding Information on ethical approval Con- flict of interest Stewart@, [ 31] Obstetrics Gynecology U.S.A Feasibility Single-center Academic Apr. 2008- Mar. 2009 Prospective Yes, with funding disclosed Approved and informed consent obtained None declared Jondal@, [32] Radiology U.S.A Pilot Single-center Academic N. A.* Prospective Yes, with funding disclosed Approved and informed consent obtained Yes, declared Ichikawa, [33] Radiology Japan Pilot Multi-center# Academic Feb. 2013- Dec. 2014 Retrospective Not reported Approved and informed consent obtained None declared Obrzut, [34] Biophysics Poland Pilot Multi-center# Academic Sept. 2016- Feb. 2017 Prospective Yes, with funding disclosed Approved and informed consent obtained Not reported Aphini- ves, [35] Radiology Thailand Pilot Single-center Academic Sept. 2020- Oct. 2021 Prospective Yes, with funding disclosed Approved and informed consent obtained None declared Adenomyosis Author Department of first authors Country of origin Study type Study design Study Setting Study period Data collection Information on funding Information on ethical approval Con- flict of interest Jain, [36] Centre for Reproduc- tive Health United Kingdom Feasibility Multi-center# Academic N. A.* Prospective Yes, with funding disclosed Approved and informed consent obtained Not reported *N.A. Not available, #Multi-center indicating involvement of authors from different institutions; @ studies performed at the same institute 1 3 Abdominal Radiology Table 2 Study population characteristics of included articles Leiomyoma Author Inclusion/ exclusion criteria No. of patients Age (years) BMI (kg/m2) Reproductive status (Pre-/peri-/ post-menopausal) Symptoms Ethnicity Treatment (# of patients) Stewart, [31] Planned for surgical excision of uterine leiomyomas 6 Mean: 42 ± 10 Range: 34–60 Mean: 28.9 ± 6.2 Range: 23–38 Pre: 5 Post: 1 Enlarged uterus/ fibroid: 3 Menorrhagia: 11 Bulk symptoms: 1 Degenerating fibroid & preterm labor: 1 Caucasian: 3 Asian: 2 African- American: 1 Hysterectomy: 3 Myomectomy: 2 Diagnostic hys- teroscopy: 1 Jondal, [32] Patients between 18 and 89 years sched- uled for a pelvic MRI for uterine fibroids or other uterine problems® 102 Mean: 44 ± 8.8 N.R Pre: 68 Peri: 29 Post: 5 Menorrhagia: 89 Dysmenorrhea: 37 Increased urinary frequency: 51 Pain or pressure in abdomen/back: 65 Caucasian: 82 African- American: 11 Other: 9 None: 39 FUS: 13 UAE: 15 Surgery: 35 Ichikawa, [33] Patients who under- went MRgFUS for uterine fibroids 11 Mean: 45.5 ± 4.4 range 38–52 N.R N.R Hypermenorrhoea: 8 Abdominal tight- ness: 2 Increased urinary frequency: 1 N.R MRgFUS: 26* Obrzut, [34] Patients with symp- tomatic leiomyomas, who underwent surgical treatment 12 Mean 40.5 range 26–61 Median 22.45 range 19.16– 27.24 Pre: 11 Post: 1 N.R N.R Hysterectomy: 7 Myomectomy: 5 Aphini- ves, [35] > 18 years old, diag- nosed with myoma uteri, and requested for pelvic MRI Excluded: patients with pregnancy or emergency medical conditions 26 Mean: 49 range 26–70 N.R N.R N.R N.R N.A Adenomyosis Author Inclusion/ exclusion criteria Num- ber of patients Age (years) BMI (kg/m2) Reproductive status (Pre-/peri-/post-menopausal) Symptoms Ethnicity Treatment (# of patients) Jain, [36] Patients with sus- pected adenomyosis and heavy menstrual bleeding diagnosed by TVUS 5α N.R N.R Pre: 5 Heavy men- strual bleeding: 4 None: 1α N.R Hysterec- tomy: 2 N.R.: not reported, N.A.: not applicable, FUS: Focused Ultrasound Surgery, UAE: Uterine artery embolization, TVUS: transvaginal ultra - sound, MRgFUS: Magnetic Resonance-guided Focused Ultrasound Surgery ®: all patients included had uterine leiomyomas, *: refers to number of leiomyomas treated not number of patients α: including 1 healthy volunteer 1 3 Abdominal Radiology Association between leiomyoma stiffness and histological composition Obrzut et al. ( n = 12) examined the relationship between mean stiffness and histological composition. Surgical speci- mens were stained to differentiate muscle fibers, collagen fibers, and nuclei, and were categorized based on the per - centage of connective tissue content. Leiomyomas con - taining more than 30% fibrous tissue exhibited a higher median stiffness (6.15 kPa) compared to those with up to 15% fibrous content (4.46 kPa) and between 15 and 30% (5.78 kPa) [34]. Association between leiomyoma stiffness and treatment outcome Ichikawa et al. ( n =11) compared treatment stiffness values in patients undergoing MR-guided focused ultrasound and found that patients who experienced a substantial volume reduction had significantly higher pre-treatment stiffness values (mean 8.3 kPa, range 6.9–10.3) compared to patients without substantial volume reduction (mean 6.1 kPa, range 5.2–8.0) [33]. The pooled mean with pooled SD was 4.72 ± 1.83 (Fig.2). Other features are listed in Table 4. Association between leiomyoma stiffness and T2 weighted signal intensity or contrast enhancement In the study conducted by Stewart et al., 50% of the patients (3 out of 6) demonstrated homogenously hypointense leio - myomas on T2-WI, which corresponded with higher mean stiffness values. Conversely, one patient with a heterog - enous leiomyoma on T2-WI showed the lowest mean stiff - ness [31]. Similarly, Jondal et al. ( n = 102) found a correlation between T2 signal characteristics and stiffness values. Their study reported that hyperintense leiomyomas on T2-WI had significant lower stiffness than hypointense, minimally heterogenous leiomyomas. The mean stiffness difference between the two groups was 2.38 kPa: hyperin- tense leiomyomas had a mean stiffness of 2.88 ± 0.98 kPa, whereas hypointense leiomyomas measured 5.27 ± 2.16 kPa (p = 0.0147). Notably, mean stiffness did not differ signifi - cantly across varying contrast enhancement patterns [32]. Author Wave Fre- quency (Hz) Region of Interest (ROI) Placement Stiffness Measurements Reported (kPa) Main Outcome of Study Stewart, [31] 60 ROIs were manually drawn by radiologists within the uterine leio- myoma using the stiffness maps Mean stiffness, SD and histo- grams of tissue stiffness Assess the in vivo stiff- ness of uterine leiomyo- mas using MRE Jondal, [32] 60 ROIs were manually drawn on the largest leiomyoma, guided by cor- responding T2-weighted images Mean stiffness and SD of the ROIs Correlate fibroid MRE stiffness with MRI characteristics Ichikawa, [33] 60 Two radiologists placed ROIs within the uterine fibroid on stiff- ness maps, guided by T2-weighted images, avoiding areas of degeneration Mean stiff- ness pre-and posttreatment Evaluate usefulness of MRE for predicting treatment outcomes of patients receiving MRgFUS* Obrzut, [34] 60 ROIs were manually drawn on the largest leiomyoma, guided by cor- responding T2-weighted images Mean stiffness and SD were reported Investigated stiffness of leiomyomas in correla- tion with histopatho- logic composition Aphinives, [35] 60 ROIs for the whole uterus were drawn manually on axial FFE images by an MRI technologist Average, median, minimum, maxi- mum stiffness and SD Assess the feasibility of MRE in evaluating uterine fibroid stiffness in Thai patients Jain, [36] 60 ROI demarcating the whole uterus as appeared on T2-WI and trans- ferred and superimposed on the relevant stiffness map Global estimated uterine stiffness Asses the feasibility to measure uterine stiffness in adenomyosis and a healthy volunteer, and correlate findings with histology in 2 cases Table 3 MRE Parameters and Main Outcomes *MRgFUS: MRI Guided Focused Ultrasound, FFE: fast field echo 1 3 Abdominal Radiology Adenomyosis In one study MRE was evaluated in four patients with sus - pected adenomyosis (diffuse n = 3; focal n = 1) and one healthy volunteer (Jain 2025) [36]. Two patients underwent hysterectomy, and histologic analysis of the tissue samples was performed. Uterine stiffness was higher in women with adenomyosis (2.93 kPa; range, 2.34–3.39 kPa) than in the healthy volunteer (2.04 kPa). Methodological quality assessment All included studies were either pilot or feasibility stud - ies and were rated as having good methodological quality according to the National Institutes of Health (NIH) quality Assessment Tool for Case Series Studies. Table 5.

This systematic review identified four pilot studies and two feasibility studies investigating the use of MRE for evaluat- ing fibrosis in benign uterine disorders, specifically leiomy- omas and adenomyosis [ 31–36]. Despite their small scale, findings suggest that MRE is a technically feasible imaging modality to assess fibrosis. Table 4 MRI and MRE Features of Leiomyomas Author Leiomyoma volume (cm3) Leiomyoma diameter (cm) Number of leiomyomas Location of leiomyoma in uterus wall Leiomyoma charac- teristics on T2-WI Leiomyoma characteristics on post-contrast Stiffness on MRE Mean ± SD /median, range (kPa) Stewart, [31] N.R Mean: 13.86*∅ Range 4.5–22.5∅ N.R N.R Dark: 4 Heterogenous: 1 N.A.: 1 Heterogenous: 1 Homogenous: 3 No enhancement: 1 N.A.: 1 Mean 5.09 ± 1.01* Range 3.95–6.68 Jondal, [32] Mean: 283.0 ± 398.0 Range 4.5—22.5 Single: 21 Multiple: 81 Submucosal: 17 Intramural: 75 Subserosal: 6 Pedunculated: 4 Dark min. heteroge- neity: 69 Dark substantial heterogeneity: 20 Iso/Hyperintense: 13 Greater/equal^: 59 Less^: 31 None^:7 No Gd adminis- tered: 5 Mean 4.81 ± 2.12 Ichikawa#, [33] Mean: 412.1 Range 29.3 −864.6) N.R Single:0 Multiple:11 (Mean 8 Range 2–17) Submucosal: 5 Intramural: 12 SI ratio of leiomy- oma-to-muscle: mean 1.23, range (0.81–1.84) N.R Mean 7.3 ± 1.60* Range 5.2–10.3 Obrzut, [34] N.R Median: 6.851∅ Range 4 −10.9∅ N.R N.R N.R N.R Mean 5.09 ± 0.96* Median 4.9 Range 3.7–6.9 Aphinives, [35] Mean: 237.74 ± 187.63 Range 56.24—716.35# N.R Single: 10 Multiple: 16 N.R N.R N.R Mean 3.02 ± 0.79 Range 1.83–5.06 N.R. Not recorded, SI Signal intensity, * mean and SD calculated using available data, ^ enhancement compared to myometrium, ∅ measure - ment corresponds to largest leiomyoma, # in case of multiple leiomyomas, the total was summation of all leiomyomas Fig.  2 Mean stiffness (kPa) per study and pooled results in patients with leiomyomas 1 3 Abdominal Radiology and quantify fibrosis in adenomyosis, with potential impli - cations for diagnosis and monitoring. A major strength of this review is the inclusion of studies that employed quantitative stiffness measurements, provid - ing objective data on uterine tissue properties. Across the available evidence, a consistent MRE set-up was used, with all studies applying the same driver system (a passive driver over the lower abdomen and an active driver producing 60 Hz vibrations), which supports technical comparability. To our knowledge, this is the first systematic review to spe- cifically evaluate MRE for fibrosis in benign uterine disor - ders, namely leiomyomas and adenomyosis. However, this systematic review highlights several important limitations in the current evidence base on MRE for benign uterine disorders. A key constraint across the included studies is the absence of large cohort data, which significantly limits the generalizability of the findings. Moreover, the small number of studies, heterogeneity in uterine pathologies investigated (five on leiomyomas and one on adenomyosis), and variability in outcome measures precluded the performance of a meta-analysis. Also, the studies fail to elaborate on the criteria for patient selection, which may have introduced selection bias. The reported mean age ranged from 40.5 to 49 years, and among the 120 patients for whom reproductive status was reported, 24.2% were perimenopausal and 5.8% were post- menopausal. This is noteworthy, as leiomyomas are gener - ally most clinically significant in women of reproductive age, particularly in those with a desire to conceive. Technical variability further complicates interpretation. The studies applied different MRI acquisition sequences; MRE in leiomyomas- For leiomyomas, the studies sug - gest that MRE-derived stiffness could serve as a biomarker of fibrosis. Jondal et al. [ 32]and Stewart et al. [ 31] found that T2-hypointense leiomyomas showed higher stiffness values, consistent with Oguchi et al. [ 37], who linked low T2 signal with reduced proliferative activity and increased fibrosis. Obrzut et al. [ 34] confirmed this relationship his - tologically, showing significantly higher stiffness in leio - myomas with > 30% fibrous content (6.15 kPa) compared to less fibrotic lesions (4.46 kPa). Aphinives et al. [ 35]. also reported leiomyoma stiffness exceeding that of normal myometrium, while Stewart et al. [31] noted values compa- rable to fibrotic liver disease. MRE may also help predict treatment outcomes. Ichikawa et al. [ 33] suggested that leiomyomas with high stiffness respond better to MR-guided focused ultrasound, while those with high T2 signal and high-water content may resist ablation. This likely reflects treatment mechanisms: thermal ablation is more effective in dense fibrotic tissue, whereas embolization depends on vascular supply and may be less effective in poorly perfused leiomyomas. Consistent with this, Chung et al. [ 38] reported that leiomyomas with high T2 signal intensity were more likely to respond favor - ably to uterine artery embolization (UAE). MRE in adenomyosis- For adenomyosis, evidence is more limited. In Jain et al. [ 36], regions of increased stiff - ness on MRE corresponded with adenomyotic areas on MRI and with histological fibrosis in hysterectomy specimens, strengthening the hypothesis that MRE reflects disease- related remodeling. While preliminary, these results indi - cate that MRE may provide a non-invasive means to detect Table 5 Methodological quality assessment of included articles Author Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Overall quality Stewart, [31] YES YES NR NO YES YES YES YES Good Jondal, [32] YES YES NR YES YES YES YES YES Good Ichikawa, [33] YES NO YES YES YES YES YES YES Good Obrzut, [34] YES YES NR YES YES YES YES YES Good Aphinives, [35] YES NO NR YES YES YES YES YES Good Juan, [36] YES NO NR YES* YES YES YES YES Good Q1. Was the study question or objective clearly stated? Yes, if clearly described in the introduction Q2. Was the study population clearly and fully described? Yes, if inclusion and exclusion criteria, patient age, and menstrual status are clearly stated Q3. Were the cases consecutive? Yes, if clearly mentioned in the methods Q4. Were the subjects comparable? Yes, if only patients with either leiyomomas, deep endometriosis or adenomyosis were included Q5. Was the intervention clearly described? Yes, provided that MRE techniques are clearly defined Q6. Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants? Yes, if MRE evaluation was done in all patients in the same way to calculate stiffness Q7. Were the statistical methods well-described? Yes, if it is reproducible and all details are mentioned Q8. Were the results well-described? Yes, if all results matched the method section Quality Rating. If 6–8 questions were answered with YES, the quality rating is assessed as “Good”. If 4–5 questions were answered with YES, the quality was assessed as ‘Fair’’. All other cases were assessed as poor quality NR: Not reported; *Feasibility study including a healthy volunteer 1 3 Abdominal Radiology Recommendations Future research should aim to move the technique beyond experimental use toward clinical applicability (e.g. for differentiation between symptomatic and asymptomatic leiomyomas, and for guiding the choice between surgical, embolization, and ablative therapies). Prospective studies should be designed: 1) including all patients undergoing MRI in routine clini- cal practice, rather than focusing solely on those scheduled for surgery, to ensure representative and generalizable find- ings. In this case, the time and accompanying costs of the additional MRE could be limited. 2) with standardization of MRE acquisition protocols, as different algorithms will have effect on measurements and with standardization of fibrosis assessment methods, as different way of ROI placements will also have effect on measurements. 3) with incorporation of normal myometrial measure - ments as reference values (e.g. as additional sequence in patient undergoing pelvic MRI for other conditions) and also reporting other factors such as tissue cellularity, vas - cularity, edema, hormonal status, as intrinsic heterogeneity of uterus masses will also have effect on quantifying tissue properties (fibrosis). 4) to validate MRE-derived stiffness measurements against histopathological results or to assess its added value alongside conventional imaging modalities, particularly in relation to disease progression, symptom severity, treatment planning, and patient-reported outcomes. Such studies may help establish the potential of MRE as a clinically valuable tool for assessing fibrosis in benign uterine disease. Supplementary Information The online version contains supplementary material available at h t t p s : / / d o i . o r g / 1 0 . 1 0 0 7 / s 0 0 2 6 1 - 0 2 6 - 0 5 3 7 4 - 8. Author Contribution All authors made substantial contributions to all of the following: (1) the conception and design of the study, or acqui - sition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be submitted. Funding The authors did not receive support from any organization for the submitted work. Data availability All extracted data are available in tables and supple- mentary files. Details on the search results is available on request (end- note files). Declarations Competing interests The authors declare no competing interests. 2D gradient-recalled echo (GRE) and spin echo–echo pla - nar imaging (SE-EPI)—which have been reported to differ in technical reliability at various field strengths. Kim et al. [39] showed that GRE had higher failure rates at 3 T com- pared to 1.5 T, while SE-EPI performed more reliably at 3 T. Reflecting this, Resoundant, a Mayo Clinic–founded company supporting MRE technology, recommends GRE at 1.5 T and SE-EPI at 3 T; most studies in this review fol - lowed these guidelines, suggesting appropriate sequence selection despite heterogeneity. Although all studies used the same MRE system, details of the inversion algorithms used to calculate stiffness maps were not reported, limiting comparability, as different algo- rithms can affect stiffness measurements. Only three of the six studies specified who placed ROIs, however none of the studies reported inter or intra-observer variability, and reproducibility seems to be major limitation in imaging studies; different way of ROI placements can also affect stiffness measurements. Furthermore, none of the studies included a reference ROI in the normal myometrium, so normal values are missing. Scan times were generally short (< 1 min in most stud - ies), suggesting feasible integration into MRI workflows. However, variability remains (e.g., Jain et al.) and the addi- tional time needed for post-processing and interpretation is not well quantified, highlighting the need for workflow optimization [36].

of this review itself include the small pool of eligible studies and the inability to perform a meta-analysis. These reflect the early stage of research in this field rather than shortcomings of the review methodology.

Despite the limited number of available studies, current findings suggest that MRE is a feasible imaging modality for measuring fibrosis in benign uterine disorders. Clinical relevance However, at this stage, these data cannot be translated to clinical practice, due to small number of studies performed (pilot and feasibility studies), missing data on normal stiff - ness values, technical heterogeneity (different algorithms), different interpretation aspects (ROI placement variability) of uterine stiffness by MRE and missing data on time and costs. 1 3 Abdominal Radiology 13. Vissers G, Giacomozzi M, Verdurmen W, Peek R, Nap A (2024) The role of fibrosis in endometriosis: a systematic review. Hum Reprod Update 30:706-750 h t t p s : / / d o i . o r g / 1 0 . 1 0 9 3 / h u m u p d / d m a e 0 1 8 14. Özen M, Patel R, Hoffman M, Raissi D (2023) Update on endo - vascular therapy for fibroids and adenomyosis. 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