Feasibility study on QSM and R2* mapping for quantitative evaluation of iron deposition and ovarian function assessment in endometriotic ovarian cysts

Objectives To evaluate the feasibility of quantitative susceptibility mapping (QSM) and R2* mapping in assessing iron deposition in endometriotic ovarian cysts (EMO) and their potential implications for ovarian reserve.

This prospective study included 28 patients (33 lesions) with histopathologically confirmed EMO who underwent preoperative MRI examinations, including R2* mapping and QSM. Cyst fluid iron concentration ([Fe]) was measured via inductively coupled plasma optical emission spectrometry. Serum anti-Müllerian hormone (AMH) levels were quantified as a marker of ovarian reserve. Pearson correlation and regression analyses were performed to assess associations among AMH, [Fe], R2*, and QSM values.

In Group All Ages, AMH was negatively correlated with age (r = −0.74, p < 0.001) and [Fe] (r = −0.35, p = 0.048), while [Fe] showed moderate positive correlations with R2* (r = 0.55, p < 0.001) and QSM (r = 0.56, p < 0.001). In Group < 40 years, AMH exhibited moderate negative correlations with [Fe] (r = −0.45, p = 0.031), R2* (r = −0.48, p = 0.019), QSM (r = −0.49, p = 0.018). Multiple regression analyses confirmed that [Fe], R2*, QSM were significant predictors of AMH levels (p < 0.05). R2* and QSM were highly correlated (r = 0.72, p < 0.001), validating their consistency in assessing iron content.

R2* mapping and QSM reliably quantify iron deposition in EMO, with in vitro validation supporting their accuracy. Moreover, the potential link between iron deposition and ovarian reserve highlights the preliminary value of these methods in assessing ovarian function. Similar content being viewed by others

Mehedintu C, Plotogea MN, Ionescu S et al (2014) Endometriosis still a challenge. J Med Life 7(3):349–357 Bulun SE, Yilmaz BD, Sison C et al (2019) Endometriosis. Endocr Rev 40(4):1048–1079. https://doi.org/10.1210/er.2018-00242 Liu MN, Chen L, Xu TM et al (2022) Potential clinical implications of iron metabolism in ovarian endometriosis. J Trace Elem Med Biol 73:127017. https://doi.org/10.1016/j.jtemb.2022.127017 Wang Y, Nicholes K, Shih IM (2020) The origin and pathogenesis of endometriosis. Annu Rev Pathol 15:71–95. https://doi.org/10.1146/annurev-pathmechdis-012419-032654 Mori M, Ito F, Shi L et al (2015) Ovarian endometriosis-associated stromal cells reveal persistently high affinity for iron. Redox Biol 6:578–586. https://doi.org/10.1016/j.redox.2015.10.001 Ng SW, Norwitz SG, Taylor HS et al (2020) Endometriosis: the role of iron overload and ferroptosis. Reprod Sci 27(7):1383–1390. https://doi.org/10.1007/s43032-020-00164-z Liu MN, Chen L, Xu TM, Zhang K (2022) Potential clinical implications of iron metabolism in ovarian endometriosis. J Trace Elem Med Biol 73:127017. https://doi.org/10.1016/j.jtemb.2022.127017 Skarżyńska E, Wróbel M, Zborowska H et al (2023) The influence of lactoferrin in plasma and peritoneal fluid on iron metabolism in women with endometriosis. Int J Mol Sci 24(2):1619. https://doi.org/10.3390/ijms24021619 Chang HH, Chen MJ, Lu MY et al (2011) Iron overload is associated with low anti-müllerian hormone in women with transfusion-dependent β-thalassaemia. BJOG 118(7):825–831. https://doi.org/10.1111/j.1471-0528.2011.02927.x Kopeika J, Oyewo A, Punnialingam S et al (2019) Ovarian reserve in women with sickle cell disease. PLoS ONE 14(2):e0213024. https://doi.org/10.1371/journal.pone.0213024 Jihad A, Sarhat E (2023) Altered levels of anti-mullerian hormone and hepcidin as potential biomarkers for polycystic ovary syndrome. Georgian Med News 339:47–51 Moolhuijsen LME, Visser JA (2020) Anti-Müllerian hormone and ovarian reserve: update on assessing ovarian function. J Clin Endocrinol Metab 105(11):3361–3373. https://doi.org/10.1210/clinem/dgaa513 Shigetomi H, Imanaka S, Kobayashi H (2021) Effects of iron-related compounds and bilirubin on redox homeostasis in endometriosis and its malignant transformations. Horm Mol Biol Clin Investig 43(2):187–192. https://doi.org/10.1515/hmbci-2021-0065 Li A, Ni Z, Zhang J et al (2020) Transferrin insufficiency and iron overload in follicular fluid contribute to oocyte dysmaturity in infertile women with advanced endometriosis. Front Endocrinol (Lausanne) 11:391. https://doi.org/10.3389/fendo.2020.00391 Hayashi S, Nakamura T, Motooka Y et al (2020) Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice. Redox Biol 37:101726. https://doi.org/10.1016/j.redox.2020.101726 Wyatt J, Fernando SM, Powell SG et al (2023) The role of iron in the pathogenesis of endometriosis: a systematic review. Hum Reprod Open 2023(3):hoad033. https://doi.org/10.1093/hropen/hoad033 Kido A, Himoto Y, Moribata Y et al (2022) MRI in the diagnosis of endometriosis and related diseases. Korean J Radiol 23(4):426–445. https://doi.org/10.3348/kjr.2021.0405 Yan S, Dong X, Ding D et al (2023) Iron deposition in ovarian endometriosis evaluated by magnetic resonance imaging R2* correlates with ovarian function. Reprod Biomed Online 47(3):103231. https://doi.org/10.1016/j.rbmo.2023.05.003 Pyatigorskaya N, Sanz-Morère CB, Gaurav R et al (2020) Iron imaging as a diagnostic tool for Parkinson’s disease: a systematic review and meta-analysis. Front Neurol 11:366. https://doi.org/10.3389/fneur.2020.00366 Calle-Toro JS, Barrera CA, Khrichenko D et al (2019) R2 relaxometry based MR imaging for estimation of liver iron content: a comparison between two methods. Abdom Radiol 44(9):3058–3068. https://doi.org/10.1007/s00261-019-02074-4 Sethi SK, Sharma S, Gharabaghi S et al (2022) Quantifying brain iron in hereditary hemochromatosis using R2* and susceptibility mapping. AJNR Am J Neuroradiol 43(7):991–997. https://doi.org/10.3174/ajnr.A7560 Mao D, Li Y, Liu P et al (2018) Three-dimensional mapping of brain venous oxygenation using R2* oximetry. Magn Reson Med 79(3):1304–1313. https://doi.org/10.1002/mrm.26763 Chang S, Park J, Yang YJ et al (2022) Myocardial T2* imaging at 3T and 1.5T: a pilot study with phantom and normal myocardium. J Cardiovasc Dev Dis 9(8):271. https://doi.org/10.3390/jcdd9080271 Kritsaneepaiboon S, Ina N, Chotsampancharoen T et al (2018) The relationship between myocardial and hepatic T2 and T2* at 1.5T and 3T MRI in normal and iron-overloaded patients. Acta Radiol 59(3):355–362. https://doi.org/10.1177/0284185117715285 Schweser F, Deistung A, Reichenbach JR (2016) Foundations of MRI phase imaging and processing for quantitative susceptibility mapping (QSM). Z Med Phys 26(1):6–34. https://doi.org/10.1016/j.zemedi.2015.10.002 Pyatigorskaya N, Santin MD (2021) QSM as a new powerful tool for clinical practice in neuroimaging. J Neuroradiol 48(1):25–27. https://doi.org/10.1016/j.neurad.2021.01.005 Eskreis-Winkler S, Zhang Y, Zhang J et al (2017) The clinical utility of QSM: disease diagnosis, medical management, and surgical planning. NMR Biomed. https://doi.org/10.1002/nbm.3668 Rolla E (2019) Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment. F1000Res 8:529. https://doi.org/10.12688/f1000research.14817.1 Yamaguchi K, Mandai M, Toyokuni S et al (2008) Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress. Clin Cancer Res 14(1):32–40. https://doi.org/10.1158/1078-0432.CCR-07-1614 Tehrani FR, Mansournia MA, Solaymani-Dodaran M, Azizi F (2014) Age-specific serum anti-Müllerian hormone levels: estimates from a large population-based sample. Climacteric 17(5):591–597. https://doi.org/10.3109/13697137.2014.912262 Zhang J, Wang X, Ren Z et al (2021) Impact of age and menopausal stage on serum anti-Müllerian hormone levels in middle-aged women. Climacteric 24(6):618–623. https://doi.org/10.1080/13697137.2021.1965114 Lv PP, Jin M, Rao JP et al (2020) Role of anti-Müllerian hormone and testosterone in follicular growth: a cross-sectional study. BMC Endocr Disord 20(1):101. https://doi.org/10.1186/s12902-020-00569-6 Laur N, Kinscherf R, Pomytkin K et al (2020) ICP-MS trace element analysis in serum and whole blood. PLoS ONE 15(5):e0233357. https://doi.org/10.1371/journal.pone.0233357 Li Y, Lu X, Chen L et al (2023) Identification of ovarian endometriotic cysts in cystic lesions of the ovary by amide proton transfer weighted imaging and R2* mapping. Clin Radiol 78:e106–e112. https://doi.org/10.1016/j.crad.2022.09.117 Defrère S, Lousse JC, González-Ramos R et al (2008) Potential involvement of iron in the pathogenesis of peritoneal endometriosis. Mol Hum Reprod 14(7):377–385. https://doi.org/10.1093/molehr/gan033 Lousse JC, Defrère S, Van Langendonckt A et al (2009) Iron storage is significantly increased in peritoneal macrophages of endometriosis patients and correlates with iron overload in peritoneal fluid. Fertil Steril 91(5):1668–1675. https://doi.org/10.1016/j.fertnstert.2008.02.103 Lu X, Ma Y, Chang EY et al (2018) Simultaneous quantitative susceptibility mapping (QSM) and for high iron concentration quantification with 3D ultrashort echo time sequences: an echo dependence study. Magn Reson Med 79(4):2315–2322. https://doi.org/10.1002/mrm.27062 Imanaka S, Yamada Y, Kawahara N et al (2021) Validation of magnetic resonance relaxometry R2 value and cyst fluid iron level for diagnosis of ovarian endometrioma. Redox Rep 26(1):105–110. https://doi.org/10.1080/13510002.2021.1937456 Rahmanzadeh R, Galbusera R, Lu PJ et al (2022) A new advanced MRI biomarker for remyelinated lesions in multiple sclerosis. Ann Neurol 92(3):486–502. https://doi.org/10.1002/ana.26441 Ruetten PPR, Gillard JH, Graves MJ (2019) Introduction to quantitative susceptibility mapping and susceptibility weighted imaging. Br J Radiol 92(1101):20181016. https://doi.org/10.1259/bjr.20181016 Li J, Lin H, Liu T et al (2018) Quantitative susceptibility mapping (QSM) minimizes interference from cellular pathology in R2* estimation of liver iron concentration. J Magn Reson Imaging 48(4):1069–1079. https://doi.org/10.1002/jmri.26019 La Marca A, Sighinolfi G, Radi D et al (2010) Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update 16(2):113–130. https://doi.org/10.1093/humupd/dmp036 Hale GE, Robertson DM, Burger HG (2014) The perimenopausal woman: endocrinology and management. J Steroid Biochem Mol Biol 142:121–131. https://doi.org/10.1016/j.jsbmb.2013.08.015 Meuleman C, Vandenabeele B, Fieuws S et al (2009) High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril 92(1):68–74. https://doi.org/10.1016/j.fertnstert.2008.04.056 Benaglia L, Paffoni A, Mangiarini A et al (2015) Intrafollicular iron and ferritin in women with ovarian endometriomas. Acta Obstet Gynecol Scand 94(6):646–653. https://doi.org/10.1111/aogs.12647 Ni Z, Li Y, Song D et al (2022) Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity. Cell Death Dis 13(7):579. https://doi.org/10.1038/s41419-022-05037-8 Guo SW, Ding D, Shen M et al (2015) Dating endometriotic ovarian cysts based on the content of cyst fluid and its potential clinical implications. Reprod Sci 22(7):873–883. https://doi.org/10.1177/1933719115570907 Nelson SM, Davis SR, Kalantaridou S et al (2023) Anti-Müllerian hormone for the diagnosis and prediction of menopause: a systematic review. Hum Reprod Update 29(3):327–346. https://doi.org/10.1093/humupd/dmac045 Koninckx PR, Fernandes R, Ussia A et al (2021) Pathogenesis based diagnosis and treatment of endometriosis. Front Endocrinol (Lausanne) 12:745548. https://doi.org/10.3389/fendo.2021.745548 Becker CM, Bokor A, Heikinheimo O et al (2022) ESHRE guideline: endometriosis. Hum Reprod Open 2022(2):hoac009. https://doi.org/10.1093/hropen/hoac009 Moreno-Sepulveda J, Romeral C, Niño G et al (2022) The effect of laparoscopic endometrioma surgery on anti-müllerian hormone: a systematic review of the literature and meta-analysis. JBRA Assist Reprod 26(1):88–104. https://doi.org/10.5935/1518-0557.20210060 Nankali A, Kazeminia M, Jamshidi PK et al (2020) The effect of unilateral and bilateral laparoscopic surgery for endometriosis on anti-Mullerian hormone (AMH) level after 3 and 6 months: a systematic review and meta-analysis. Health Qual Life Outcomes 18(1):314. https://doi.org/10.1186/s12955-020-01561-3 Funding Not applicable. Author information Authors and Affiliations Contributions Dawei Ding and Lingyu Chang contribute equally to this article and should be considered co-first authors. Dawei Ding: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing—review & editing. Lingyu Chang: Conceptualization, Formal analysis, Investigation, Project administration, Software, Writing—original draft. Xuemei Wang: Conceptualization, Methodology, Resources, Supervision, Writing—original draft. Ying Xu: Data curation, Formal analysis, Investigation, Writing—original draft. Bo Yang: Data curation, Visualization, Writing—original draft. Dmytro Pylypenko: Software, Supervision, Writing—review & editing. Tianyong Xu: Software, Supervision, Writing—review & editing. Jingtao Wang: Conceptualization, Methodology, Resources, Supervision, Writing—review & editing. Dexin Yu: Conceptualization, Methodology, Resources, Supervision, Writing—review & editing. Fang Wang: Conceptualization, Methodology, Resources, Supervision, Writing—review & editing. Final manuscript approved by all authors. Corresponding author Ethics declarations Conflict of interest The authors have no relevant fnancial or non-fnancial interests to disclose. Ethical approval The study was approved by the institutional review board of Qilu Hospital of Shandong University. Written informed consent was obtained from all patients. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Ding, D., Chang, L., Wang, X. et al. Feasibility study on QSM and R2* mapping for quantitative evaluation of iron deposition and ovarian function assessment in endometriotic ovarian cysts. Radiol med 131, 386–394 (2026). https://doi.org/10.1007/s11547-025-02152-2 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11547-025-02152-2