Advanced 3D Imaging of Uterine Leiomyoma’s Morphology by Propagation-based Phase-Contrast Microtomography

Abstract

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. Uterine leiomyoma (myoma or fibroid) is the most common benign smooth muscle tumor in women pelvis causing significant morbidity in a large segment of reproductive-aged women 1,2 , including significant impact on the reproductive healthy status and on the pregnancy outcome of affected patients 3,4. Fibroids remain the leading indication for hysterectomy 5,6 especially during the peri-menopause period, although the assumption that leiomyoma symptoms will resolve with the onset of the menopause is too simplistic and may not be always valid 7. Medical treatments for leiomyoma are still very limited and no preventative therapies have been developed 8. The precise pathogenesis of uterine leiomyoma is not well understood. Genetic alterations, epigenetic mechanisms, steroids, growth factors, cytokines and chemokines provide the clue of initiators and promoters of leiomyoma growth 9. Uterine myoma is thought to be a consequence of myofibroblasts activation and extracellular matrix (ECM) production, following an improper inflammatory response inside the myometrium 10-12. Excessive accumulation of ECM components including collagens, fibronectin and proteoglycans are the major structural part of leiomyoma tissue that are abnormally orientated modifying mechanical stress on cells and leading to activation of internal mechanical signaling and dynamic reciprocity 13-15. The ECM stiffness causes the rigid structure of the leiomyoma and it is thought to be a cause of abnormal bleeding and pelvic pressure and pain 16. The role of inflammation and reparative processes as well as the effect of some potential therapeutic compounds (tranilast, strawberry extracts, omega-3 fatty acids, g...

The Symmetric 3D Organization of Connective Tissue around Implant Abutment: A Key-Issue to Prevent Bone Resorption

“…SR-PhC-microCT was successful in detecting, with high spatial resolution, the 3D structural organization of ECM within bioscaffolds, supporting the understanding of how the presence of cells modified the construct arrangement [19,20]. Moreover, we recently performed SR-PhC-microCT on uterine leiomyomas, demonstrating the capability of this method to discriminate healthy and pathologic collagen distribution in this district without using contrast agents [21].…”

Influence of abutment macro‐ and micro‐geometry on morphologic and morphometric features of peri‐implant connective tissue

“…Moreover, an evaluation exclusively based on the thickness of the connective tissue (vertical and/or transversal) is a not sufficient information to ensure the stability of the soft tissue. In fact, numerous studies stated that large quantities of collagen, without directionality or with uncontrolled connectivity, create dysfunctional fibrotic structures (Belloni et al, 2022; Giuliani et al, 2019; Rockey et al, 2015).…”

Sphingosine 1-phosphate signaling in uterine fibroids: implication in activin A pro-fibrotic effect

“…Uterine fibroids are considered fibrotic disorders because they contain 50% more ECM proteins than the corresponding myometrium (15,49); therefore, considering the well recognized fibrotic phenotype of this disease, is crucial to understand the molecular mechanisms underly-ing the fibrotic process. The alteration of the ECM organization in uterine fibroids has been pointed out by means of X-ray phase-contrast imaging revealing higher mass collagen density distribution, higher collagen bundle thickness and fiber number, lower collagen fiber specific surface, and lower mean collagen bundles in leiomyoma tissues compared with myometrial tissues (50).…”