{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T18:11:33Z","timestamp":1787249493180,"version":"build-2736575974"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T00:00:00Z","timestamp":1563753600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T00:00:00Z","timestamp":1563753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Uterine leiomyoma is the most common benign smooth muscle tumor in women pelvis, originating from the myometrium. It is caused by a disorder of fibrosis, with a large production and disruption of extracellular matrix (ECM). Medical treatments are still very limited and no preventative therapies have been developed. We supposed that synchrotron-based phase-contrast microtomography (PhC-microCT) may be an appropriate tool to assess the 3D morphology of uterine leiomyoma, without the use of any contrast agent. We used this technique to perform the imaging and the quantitative morphometric analysis of healthy myometrium and pathologic leiomyomas. The quantitative morphometric analysis of collagen bundles was coupled to the Roschger approach. This method, previously only used to evaluate mineralized bone density distribution, was applied here to study the fibrosis mass density distribution in healthy and pathologic biopsies from two patients. This protocol was shown to be powerful in studying uterine leiomyomas, detecting also small signs of the ECM alteration. This is of paramount importance not only for the follow-up of the present study, i.e. the investigation of different compounds and their possible therapeutic benefits, but also because it offers new methodologic possibilities for future studies of the ECM in soft tissues of different body districts.<\/jats:p>","DOI":"10.1038\/s41598-019-47048-0","type":"journal-article","created":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T10:02:40Z","timestamp":1563789760000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Advanced 3D Imaging of Uterine Leiomyoma\u2019s Morphology by Propagation-based Phase-Contrast Microtomography"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4177-7441","authenticated-orcid":false,"given":"Alessandra","family":"Giuliani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Greco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Pacil\u00e8","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Zannotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Delli Carpini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Tromba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano Raffaele","family":"Giannubilo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ciavattini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquapina","family":"Ciarmela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,22]]},"reference":[{"issue":"6","key":"47048_CR1","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1093\/humupd\/dmr031","volume":"17","author":"P Ciarmela","year":"2011","unstructured":"Ciarmela, P. et al. Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications. Human Reproduction Update 17(6), 772\u2013790 (2011).","journal-title":"Human Reproduction Update"},{"issue":"1","key":"47048_CR2","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1067\/mob.2003.99","volume":"188","author":"D Day Baird","year":"2003","unstructured":"Day Baird, D. et al. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. American Journal of Obstetrics and Gynecology 188(1), 100\u2013107 (2003).","journal-title":"American Journal of Obstetrics and Gynecology"},{"issue":"4","key":"47048_CR3","doi-asserted-by":"publisher","first-page":"484","DOI":"10.3109\/14767058.2014.921675","volume":"28","author":"A Ciavattini","year":"2015","unstructured":"Ciavattini, A. et al. Number and size of uterine fibroids and obstetric outcomes. J Matern Fetal Neonatal Med 28(4), 484\u20138 (2015).","journal-title":"J Matern Fetal Neonatal Med"},{"issue":"5","key":"47048_CR4","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1016\/j.fertnstert.2016.01.032","volume":"105","author":"A Ciavattini","year":"2016","unstructured":"Ciavattini, A. et al. Growth trend of small uterine fibroids and human chorionic gonadotropin serum levels in early pregnancy: an observational study. Fertil Steril 105(5), 1255\u20131260 (2016).","journal-title":"Fertil Steril"},{"issue":"3","key":"47048_CR5","doi-asserted-by":"publisher","first-page":"211. e1","DOI":"10.1016\/j.ajog.2011.12.002","volume":"206","author":"ER Cardozo","year":"2012","unstructured":"Cardozo, E. R. et al. The estimated annual cost of uterine leiomyomata in the United States. American journal of obstetrics and gynecology 206(3), 211. e1\u2013211. e9 (2012).","journal-title":"American journal of obstetrics and gynecology"},{"issue":"1","key":"47048_CR6","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.ejogrb.2010.05.012","volume":"152","author":"E Downes","year":"2010","unstructured":"Downes, E. et al. The burden of uterine fibroids in five European countries. European Journal of Obstetrics, Gynecology, and Reproductive Biology 152(1), 96\u2013102 (2010).","journal-title":"European Journal of Obstetrics, Gynecology, and Reproductive Biology"},{"issue":"3","key":"47048_CR7","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.maturitas.2014.04.011","volume":"78","author":"P Ciarmela","year":"2014","unstructured":"Ciarmela, P. et al. Management of leiomyomas in perimenopausal women. Maturitas 78(3), 168\u201373. (2014).","journal-title":"Maturitas"},{"issue":"3","key":"47048_CR8","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1210\/jc.2012-3237","volume":"98","author":"MS Islam","year":"2013","unstructured":"Islam, M. S. et al. Uterine leiomyoma: available medical treatments and new possible therapeutic options. Journal of Clinical Endocrinology & Metabolism 98(3), 921\u2013934 (2013).","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"issue":"1","key":"47048_CR9","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.fertnstert.2013.03.007","volume":"100","author":"MS Islam","year":"2013","unstructured":"Islam, M. S. et al. Complex networks of multiple factors in the pathogenesis of uterine leiomyoma. Fertility and Sterility 100(1), 178\u2013193 (2013).","journal-title":"Fertility and Sterility"},{"key":"47048_CR10","doi-asserted-by":"crossref","unstructured":"Leppert, P., M. Fouany & J. H. Segars Understanding uterine fibroids, in Fibroids, J.H. Segars, Editor. 2013, John Wiley & Sons, Ltd: Oxford. p. 1\u201310.","DOI":"10.1002\/9781118456996.ch1"},{"key":"47048_CR11","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s00441-015-2324-3","volume":"364","author":"O Protic","year":"2016","unstructured":"Protic, O. et al. Possible involvement of inflammatory\/reparative processes in the development of uterine fibroids. Cell & Tissue Research 364, 415\u2013427 (2016).","journal-title":"Cell & Tissue Research"},{"issue":"6","key":"47048_CR12","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1055\/s-0037-1607265","volume":"35","author":"O Protic","year":"2017","unstructured":"Protic, O. et al. Activin A in Inflammation, Tissue Repair, and Fibrosisossible Role as Inflammatory and Fibrotic Mediator of Uterine Fibroid Development and Growth. Semin Reprod Med 35(6), 499\u2013509 (2017).","journal-title":"Semin Reprod Med"},{"key":"47048_CR13","doi-asserted-by":"publisher","first-page":"783289","DOI":"10.1155\/2014\/783289","volume":"2014","author":"PC Leppert","year":"2014","unstructured":"Leppert, P. C., Jayes, F. L. & Segars, J. H. The extracellular matrix contributes to mechanotransduction in uterine fibroids. Obstet Gynecol Int 2014, 783289 (2014).","journal-title":"Obstet Gynecol Int"},{"issue":"1","key":"47048_CR14","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1095\/biolreprod.114.121368","volume":"92","author":"JT Thorne","year":"2015","unstructured":"Thorne, J. T. et al. Dynamic reciprocity between cells and their microenvironment in reproduction. Biol Reprod 92(1), 25 (2015).","journal-title":"Biol Reprod"},{"issue":"6","key":"47048_CR15","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1055\/s-0037-1607268","volume":"35","author":"S Rafique","year":"2017","unstructured":"Rafique, S., Segars, J. H. & Leppert, P. C. Mechanical Signaling and Extracellular Matrix in Uterine Fibroids. Semin Reprod Med 35(6), 487\u2013493 (2017).","journal-title":"Semin Reprod Med"},{"issue":"1","key":"47048_CR16","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1093\/humupd\/dmx032","volume":"24","author":"MS Islam","year":"2018","unstructured":"Islam, M. S. et al. Extracellular matrix in uterine leiomyoma pathogenesis: a potential target for future therapeutics. Hum Reprod Update 24(1), 59\u201385 (2018).","journal-title":"Hum Reprod Update"},{"issue":"8","key":"47048_CR17","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1002\/mnfr.201400134","volume":"58","author":"Md Soriful Islam","year":"2014","unstructured":"Islam, M. S. et al. Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: Promising options for prevention and treatment of uterine fibroids? Molecular nutrition & food research 58(8), 1667\u20131684 (2014).","journal-title":"Molecular Nutrition & Food Research"},{"issue":"2","key":"47048_CR18","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.fertnstert.2014.05.013","volume":"102","author":"MS Islam","year":"2014","unstructured":"Islam, M. S. et al. Tranilast, an orally active antiallergic compound, inhibits extracellular matrix production in human uterine leiomyoma and myometrial cells. Fertility and sterility 102(2), 597\u2013606 (2014).","journal-title":"Fertility and sterility"},{"issue":"5","key":"47048_CR19","first-page":"321","volume":"2","author":"MS Islam","year":"2012","unstructured":"Islam, M. S. et al. Antiproliferative effect of tranilast on human myometrial and leiomyoma cells. Biological and Biomedical Reports 2(5), 321\u2013327 (2012).","journal-title":"Biological and Biomedical Reports"},{"issue":"2017","key":"47048_CR20","first-page":"57","volume":"69","author":"MS Islam","year":"2016","unstructured":"Islam, M. S. et al. Dietary phytochemicals for possible preventive and therapeutic option of uterine fibroids: Signaling pathways as target. Pharmacological Reports 69(2017), 57\u201370 (2016).","journal-title":"Pharmacological Reports"},{"issue":"17","key":"47048_CR21","doi-asserted-by":"publisher","first-page":"3583","DOI":"10.1080\/10408398.2016.1245649","volume":"57","author":"MS Islam","year":"2017","unstructured":"Islam, M. S. et al. Molecular targets of dietary phytochemicals for possible prevention and therapy of uterine fi broids: Focus on fi brosis. Critical Reviews in Food Science and Nutrition 57(17), 3583\u20133600 (2017).","journal-title":"Critical Reviews in Food Science and Nutrition"},{"issue":"14","key":"47048_CR22","doi-asserted-by":"publisher","first-page":"23575","DOI":"10.18632\/oncotarget.15333","volume":"8","author":"MS Islam","year":"2017","unstructured":"Islam, M. S. et al. An anthocyanin rich strawberry extract induces apoptosis and ROS while decreases glycolysis and fibrosis in human uterine leiomyoma cells. Oncotarget 8(14), 23575\u201323587 (2017).","journal-title":"Oncotarget"},{"issue":"9","key":"47048_CR23","doi-asserted-by":"publisher","first-page":"7143","DOI":"10.1002\/jcp.26537","volume":"233","author":"MS Islam","year":"2018","unstructured":"Islam, M. S. et al. Omega-3 fatty acids modulate the lipid profile, membrane architecture, and gene expression of leiomyoma cells. J Cell Physiol 233(9), 7143\u20137156 (2018).","journal-title":"J Cell Physiol"},{"key":"47048_CR24","doi-asserted-by":"crossref","unstructured":"Giampieri, F. et al. Romina: A powerful strawberry with in vitro efficacy against uterine leiomyoma cells. J Cell Physiol (2018).","DOI":"10.1002\/jcp.27524"},{"key":"47048_CR25","doi-asserted-by":"crossref","unstructured":"Castro, L. et al. A High Concentration of Genistein Induces Cell Death in Human Uterine Leiomyoma Cells by Autophagy. Expert Opin Environ Biol, 5(Suppl 1) (2016).","DOI":"10.4172\/2325-9655.S1-003"},{"issue":"4","key":"47048_CR26","first-page":"281","volume":"44","author":"X Di","year":"2012","unstructured":"Di, X. et al. A high concentration of genistein down-regulates activin A, Smad3 and other TGF-\u03b2 pathway genes in human uterine leiomyoma cells. Experimental & molecular medicine 44(4), 281\u2013292 (2012).","journal-title":"molecular medicine"},{"issue":"8","key":"47048_CR27","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.1093\/humrep\/den087","volume":"23","author":"X Di","year":"2008","unstructured":"Di, X. et al. A low concentration of genistein induces estrogen receptor-alpha and insulin-like growth factor-I receptor interactions and proliferation in uterine leiomyoma cells. Hum Reprod 23(8), 1873\u201383 (2008).","journal-title":"Hum Reprod"},{"issue":"10","key":"47048_CR28","doi-asserted-by":"publisher","first-page":"2623","DOI":"10.1093\/humrep\/dem185","volume":"22","author":"AB Moore","year":"2007","unstructured":"Moore, A. B. et al. Stimulatory and inhibitory effects of genistein on human uterine leiomyoma cell proliferation are influenced by the concentration. Hum Reprod 22(10), 2623\u20132631 (2007).","journal-title":"Hum Reprod"},{"issue":"52","key":"47048_CR29","doi-asserted-by":"publisher","first-page":"e5698","DOI":"10.1097\/MD.0000000000005698","volume":"95","author":"Andrea Ciavattini","year":"2016","unstructured":"Ciavattini, A. et al. Hypovitaminosis D and \u201csmall burden\u201d uterine fibroids: Opportunity for a vitamin D supplementation. Medicine (Baltimore) 95(52), e5698 (2016).","journal-title":"Medicine"},{"issue":"4","key":"47048_CR30","first-page":"821","volume":"26","author":"MZ Hossain","year":"2017","unstructured":"Hossain, M. Z. et al. A Comparative Study of Magnetic Resonance Imaging and Transabdominal Ultrasonography for the Diagnosis and Evaluation of Uterine Fibroids. Mymensingh Med J 26(4), 821\u2013827 (2017).","journal-title":"Mymensingh Med J"},{"issue":"5","key":"47048_CR31","doi-asserted-by":"publisher","first-page":"537 e1","DOI":"10.1016\/j.ajog.2008.12.037","volume":"200","author":"ED Levens","year":"2009","unstructured":"Levens, E. D. et al. Magnetic resonance imaging and transvaginal ultrasound for determining fibroid burden: implications for research and clinical care. Am J Obstet Gynecol 200(5), 537 e1\u20137 (2009).","journal-title":"Am J Obstet Gynecol"},{"issue":"1","key":"47048_CR32","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1007\/BF02924588","volume":"13","author":"SM Ascher","year":"1991","unstructured":"Ascher, S. M. & Silverman, P. M. Applications of computed tomography in gynecologic diseases. Urol Radiol 13(1), 16\u201328 (1991).","journal-title":"Urol Radiol"},{"issue":"1","key":"47048_CR33","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1088\/0031-9155\/58\/1\/R1","volume":"58","author":"A Bravin","year":"2013","unstructured":"Bravin, A., Coan, P. & Suortti, P. X-ray phase-contrast imaging: from pre-clinical applications towards clinics. Phys Med Biol 58(1), R1\u201335 (2013).","journal-title":"Phys Med Biol"},{"issue":"12","key":"47048_CR34","doi-asserted-by":"publisher","first-page":"5486","DOI":"10.1063\/1.1146073","volume":"66","author":"A Snigirev","year":"1995","unstructured":"Snigirev, A. et al. On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation. Review of Scientific Instruments 66(12), 5486\u20135492 (1995).","journal-title":"Review of Scientific Instruments"},{"issue":"905","key":"47048_CR35","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1259\/bjr\/32889803","volume":"76","author":"RA Lewis","year":"2003","unstructured":"Lewis, R. A. et al. X-ray refraction effects: application to the imaging of biological tissues. Br J Radiol 76(905), 301\u20138 (2003).","journal-title":"Br J Radiol"},{"issue":"4","key":"47048_CR36","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/nm0496-473","volume":"2","author":"A Momose","year":"1996","unstructured":"Momose, A. et al. Phase-contrast X-ray computed tomography for observing biological soft tissues. Nat Med 2(4), 473\u20135 (1996).","journal-title":"Nat Med"},{"issue":"1","key":"47048_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29841-5","volume":"8","author":"LCP Croton","year":"2018","unstructured":"Croton, L. C. P. et al. In situ phase contrast X-ray brain CT. Sci Rep 8(1), 11412 (2018).","journal-title":"Sci Rep"},{"issue":"4","key":"47048_CR38","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1016\/j.neuroimage.2012.03.029","volume":"61","author":"BR Pinzer","year":"2012","unstructured":"Pinzer, B. R. et al. Imaging brain amyloid deposition using grating-based differential phase contrast tomography. Neuroimage 61(4), 1336\u201346 (2012).","journal-title":"Neuroimage"},{"key":"47048_CR39","doi-asserted-by":"publisher","first-page":"769","DOI":"10.3389\/fphys.2017.00769","volume":"8","author":"A Giuliani","year":"2017","unstructured":"Giuliani, A. et al. Synchrotron Phase Tomography: An Emerging Imaging Method for Microvessel Detection in Engineered Bone of Craniofacial Districts. Front Physiol 8, 769 (2017).","journal-title":"Front Physiol"},{"issue":"1","key":"47048_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06251-7","volume":"7","author":"A Cedola","year":"2017","unstructured":"Cedola, A. et al. X-Ray Phase Contrast Tomography Reveals Early Vascular Alterations and Neuronal Loss in a Multiple Sclerosis Model. Sci Rep 7(1), 5890 (2017).","journal-title":"Sci Rep"},{"issue":"1","key":"47048_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29344-3","volume":"8","author":"W Vagberg","year":"2018","unstructured":"Vagberg, W. et al. Cellular-resolution 3D virtual histology of human coronary arteries using x-ray phase tomography. Sci Rep 8(1), 11014 (2018).","journal-title":"Sci Rep"},{"issue":"10","key":"47048_CR42","doi-asserted-by":"publisher","first-page":"e109562","DOI":"10.1371\/journal.pone.0109562","volume":"9","author":"A Velroyen","year":"2014","unstructured":"Velroyen, A. et al. X-ray phase-contrast tomography of renal ischemia-reperfusion damage. PLoS One 9(10), e109562 (2014).","journal-title":"PLoS One"},{"key":"47048_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/srep41054","volume":"7","author":"I Bukreeva","year":"2017","unstructured":"Bukreeva, I. et al. Quantitative 3D investigation of Neuronal network in mouse spinal cord model. Sci Rep 7, 41054 (2017).","journal-title":"Sci Rep"},{"issue":"7","key":"47048_CR44","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1097\/RLI.0b013e3181e193bd","volume":"45","author":"P Coan","year":"2010","unstructured":"Coan, P. et al. Characterization of osteoarthritic and normal human patella cartilage by computed tomography X-ray phase-contrast imaging: a feasibility study. Invest Radiol 45(7), 437\u201344 (2010).","journal-title":"Invest Radiol"},{"issue":"9","key":"47048_CR45","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1097\/RLI.0000000000000063","volume":"49","author":"A Horng","year":"2014","unstructured":"Horng, A. et al. Cartilage and soft tissue imaging using X-rays: propagation-based phase-contrast computed tomography of the human knee in comparison with clinical imaging techniques and histology. Invest Radiol 49(9), 627\u201334. (2014).","journal-title":"Invest Radiol"},{"issue":"5","key":"47048_CR46","doi-asserted-by":"publisher","first-page":"e97101","DOI":"10.1371\/journal.pone.0097101","volume":"9","author":"S Grandl","year":"2014","unstructured":"Grandl, S. et al. Visualizing typical features of breast fibroadenomas using phase-contrast CT: an ex-vivo study. PLoS One 9(5), e97101 (2014).","journal-title":"PLoS One"},{"issue":"8","key":"47048_CR47","doi-asserted-by":"publisher","first-page":"3099","DOI":"10.1364\/BOE.6.003099","volume":"6","author":"S Pacile","year":"2015","unstructured":"Pacile, S. et al. Clinical application of low-dose phase contrast breast CT: methods for the optimization of the reconstruction workflow. Biomed Opt Express 6(8), 3099\u2013112 (2015).","journal-title":"Biomed Opt Express"},{"issue":"3","key":"47048_CR48","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1089\/ten.tec.2008.0270","volume":"15","author":"G Albertini","year":"2009","unstructured":"Albertini, G. et al. Organization of extracellular matrix fibers within polyglycolic acid-polylactic acid scaffolds analyzed using X-ray synchrotron-radiation phase-contrast micro computed tomography. Tissue Eng Part C Methods 15(3), 403\u201311 (2009).","journal-title":"Tissue Eng Part C Methods"},{"issue":"4","key":"47048_CR49","first-page":"699","volume":"71","author":"H Noda","year":"1972","unstructured":"Noda, H. Partial specific volume of collagen. J Biochem 71(4), 699\u2013703 (1972).","journal-title":"J Biochem"},{"issue":"11","key":"47048_CR50","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1016\/j.jbiomech.2004.10.001","volume":"38","author":"SR Ward","year":"2005","unstructured":"Ward, S. R. & Lieber, R. L. Density and hydration of fresh and fixed human skeletal muscle. J Biomech 38(11), 2317\u201320 (2005).","journal-title":"J Biomech"},{"issue":"Pt 1","key":"47048_CR51","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1046\/j.1365-2818.2002.01010.x","volume":"206","author":"D Paganin","year":"2002","unstructured":"Paganin, D. et al. Simultaneous phase and amplitude extraction from a single defocused image of a homogeneous object. J Microsc 206(Pt 1), 33\u201340 (2002).","journal-title":"J Microsc"},{"issue":"7","key":"47048_CR52","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat Methods 9(7), 676\u201382 (2012).","journal-title":"Nat Methods"},{"issue":"3","key":"47048_CR53","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.bone.2007.10.021","volume":"42","author":"P Roschger","year":"2008","unstructured":"Roschger, P. et al. Bone mineralization density distribution in health and disease. Bone 42(3), 456\u201366 (2008).","journal-title":"Bone"},{"issue":"2","key":"47048_CR54","doi-asserted-by":"publisher","first-page":"e88481","DOI":"10.1371\/journal.pone.0088481","volume":"9","author":"B Hesse","year":"2014","unstructured":"Hesse, B. et al. Alterations of mass density and 3D osteocyte lacunar properties in bisphosphonate-related osteonecrotic human jaw bone, a synchrotron microCT study. PLoS One 9(2), e88481 (2014).","journal-title":"PLoS One"},{"key":"47048_CR55","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.oraloncology.2018.04.026","volume":"82","author":"A Giuliani","year":"2018","unstructured":"Giuliani, A. et al. Bisphosphonate-related osteonecrosis of the human jaw: A combined 3D assessment of bone descriptors by histology and synchrotron radiation-based microtomography. Oral Oncol 82, 200\u2013202 (2018).","journal-title":"Oral Oncol"},{"issue":"Pt 4","key":"47048_CR56","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1107\/S0909049511002895","volume":"18","author":"T Weitkamp","year":"2011","unstructured":"Weitkamp, T. et al. ANKAphase: software for single-distance phase retrieval from inline X-ray phase-contrast radiographs. J Synchrotron Radiat 18(Pt 4), 617\u201329. (2011).","journal-title":"J Synchrotron Radiat"},{"issue":"5728","key":"47048_CR57","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1126\/science.1112063","volume":"308","author":"CL Walker","year":"2005","unstructured":"Walker, C. L. & Stewart, E. A. Uterine fibroids: the elephant in the room. Science 308(5728), 1589\u20131592 (2005).","journal-title":"Science"},{"issue":"2","key":"47048_CR58","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.ajog.2005.12.059","volume":"195","author":"PC Leppert","year":"2006","unstructured":"Leppert, P. C., Catherino, W. H. & Segars, J. H. A new hypothesis about the origin of uterine fibroids based on gene expression profiling with microarrays. Am J Obstet Gynecol 195(2), 415\u2013420 (2006).","journal-title":"Am J Obstet Gynecol"},{"issue":"3","key":"47048_CR59","first-page":"900","volume":"79","author":"EA Stewart","year":"1994","unstructured":"Stewart, E. A. et al. Relative overexpression of collagen type I and collagen type III messenger ribonucleic acids by uterine leiomyomas during the proliferative phase of the menstrual cycle. Journal of Clinical Endocrinology & Metabolism 79(3), 900\u2013906 (1994).","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"issue":"12","key":"47048_CR60","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1177\/1933719109343310","volume":"16","author":"JM Norian","year":"2009","unstructured":"Norian, J. M. et al. Transforming growth factor beta3 regulates the versican variants in the extracellular matrix-rich uterine leiomyomas. Reproductive Sciences 16(12), 1153\u20131164 (2009).","journal-title":"Reproductive Sciences"},{"issue":"5","key":"47048_CR61","doi-asserted-by":"publisher","first-page":"E775","DOI":"10.1210\/jc.2013-2623","volume":"99","author":"MS Islam","year":"2014","unstructured":"Islam, M. S. et al. Role of activin-A and myostatin and their signaling pathway in human myometrial and leiomyoma cell function. Journal of Clinical Endocrinology & Metabolism 99(5), E775\u2013E785 (2014).","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"issue":"Suppl 3","key":"47048_CR62","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1016\/j.fertnstert.2004.04.030","volume":"82","author":"PC Leppert","year":"2004","unstructured":"Leppert, P. C. et al. Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium. Fertility and Sterility 82(Suppl 3), 1182\u20131187 (2004).","journal-title":"Fertility and Sterility"},{"issue":"10","key":"47048_CR63","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1093\/humrep\/deq222","volume":"25","author":"O Yoshino","year":"2010","unstructured":"Yoshino, O. et al. Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids. Hum Reprod 25(10), 2475\u20139 (2010).","journal-title":"Hum Reprod"},{"issue":"1","key":"47048_CR64","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jmig.2011.09.010","volume":"19","author":"O Yoshino","year":"2012","unstructured":"Yoshino, O. et al. Myomectomy decreases abnormal uterine peristalsis and increases pregnancy rate. J Minim Invasive Gynecol 19(1), 63\u20137 (2012).","journal-title":"J Minim Invasive Gynecol"},{"issue":"5","key":"47048_CR65","doi-asserted-by":"publisher","first-page":"596 e1","DOI":"10.1016\/j.ajog.2016.05.006","volume":"215","author":"FL Jayes","year":"2016","unstructured":"Jayes, F. L. et al. Loss of stiffness in collagen-rich uterine fibroids after digestion with purified collagenase Clostridium histolyticum. Am J Obstet Gynecol 215(5), 596 e1\u2013596 e8 (2016).","journal-title":"Am J Obstet Gynecol"},{"key":"47048_CR66","doi-asserted-by":"publisher","first-page":"2968410","DOI":"10.1155\/2016\/2968410","volume":"2016","author":"AP da Silva","year":"2016","unstructured":"da Silva, A. P. et al. Histopathological and Digital Morphometrical Evaluation of Uterine Leiomyoma in Brazilian Women. Obstet Gynecol Int 2016, 2968410 (2016).","journal-title":"Obstet Gynecol Int"},{"key":"47048_CR67","first-page":"528376","volume":"2013","author":"GP Flake","year":"2013","unstructured":"Flake, G. P. et al. The natural history of uterine leiomyomas: light and electron microscopic studies of fibroid phases, interstitial ischemia, inanosis, and reclamation. Obstet Gynecol Int 2013, 528376 (2013).","journal-title":"Obstet Gynecol Int"},{"issue":"4","key":"47048_CR68","doi-asserted-by":"publisher","first-page":"e0215646","DOI":"10.1371\/journal.pone.0215646","volume":"14","author":"FL Jayes","year":"2019","unstructured":"Jayes, F. L. et al. Evidence of biomechanical and collagen heterogeneity in uterine fibroids. PLoS One 14(4), e0215646 (2019).","journal-title":"PLoS One"},{"issue":"2","key":"47048_CR69","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1002\/jor.1100120213","volume":"12","author":"TJ Mommersteeg","year":"1994","unstructured":"Mommersteeg, T. J. et al. Nonuniform distribution of collagen density in human knee ligaments. J Orthop Res 12(2), 238\u201345 (1994).","journal-title":"J Orthop Res"},{"issue":"5","key":"47048_CR70","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1093\/humupd\/4.5.496","volume":"4","author":"JJ Brosens","year":"1998","unstructured":"Brosens, J. J., Barker, F. G. & de Souza, N. M. Myometrial zonal differentiation and uterine junctional zone hyperplasia in the non-pregnant uterus. Hum Reprod Update 4(5), 496\u2013502 (1998).","journal-title":"Hum Reprod Update"},{"key":"47048_CR71","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1155\/2013\/173184","volume":"2013","author":"A Ciavattini","year":"2013","unstructured":"Ciavattini, A. et al. Uterine Fibroids: Pathogenesis and Interactions with Endometrium and Endomyometrial Junction. Obstetrics and Gynecology International 2013, 11 (2013).","journal-title":"Obstetrics and Gynecology International"},{"issue":"1","key":"47048_CR72","doi-asserted-by":"publisher","DOI":"10.1186\/s40679-016-0036-8","volume":"3","author":"F Brun","year":"2017","unstructured":"Brun, F. et al. SYRMEP Tomo Project: a graphical user interface for customizing CT reconstruction workflows. Adv Struct Chem Imaging 3(1), 4 (2017).","journal-title":"Adv Struct Chem Imaging"},{"issue":"7","key":"47048_CR73","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9(7), 671\u20135 (2012).","journal-title":"Nat Methods"},{"issue":"6","key":"47048_CR74","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1002\/jbmr.5650020617","volume":"2","author":"AM Parfitt","year":"1987","unstructured":"Parfitt, A. M. et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2(6), 595\u2013610 (1987).","journal-title":"J Bone Miner Res"},{"issue":"6","key":"47048_CR75","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.bone.2010.08.023","volume":"47","author":"M Doube","year":"2010","unstructured":"Doube, M. et al. BoneJ: Free and extensible bone image analysis in ImageJ. Bone 47(6), 1076\u20139 (2010).","journal-title":"Bone"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47048-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47048-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47048-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T11:44:07Z","timestamp":1671277447000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47048-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,22]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["47048"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-47048-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,22]]},"assertion":[{"value":"13 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"10580"}}