Multimodal investigation of endometriosis by using LA-ICP-MS and QCL-based infrared microscopy

Abstract Endometriosis affects millions of women worldwide. It is linked to severe pain and leads to high socio-economic costs. Endometriosis is characterized by the growth of tissue resembling the endometrium outside the uterus, with the cause still unclear. This study demonstrates how multimodal bioimaging methods can provide new insights into the elemental and molecular processes of endometriosis at the macroscopic level. By using multimodal bioimaging techniques, the role of trace elements (TE) and changes in molecular composition were investigated in human endometriosis biopsies and compared with TE concentrations in serum and peritoneal fluid during the disease. As an element-specific bioimaging technique, laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS) was utilized to analyze the TE profile in human biopsies with high sensitivity. Additionally, a quantum cascade laser-based infrared microspectroscopy generated complementary spatial molecular information of the affected tissue. The chemometric processing of the molecular data was made by using uniform manifold approximation and projection (UMAP). To validate the results obtained, TE levels in body fluids were quantified by using ICP-MS and microassays. Our study demonstrates that differences in the TE profile and at the protein level, in terms of mucin expression, can be detected in lesion areas. The TE changes in the tissue differed from those in the body fluids. The presence of mucins in the lesion areas was additionally confirmed by immunohistochemistry. These results highlight the potential of imaging methods in the field of endometriosis research and offer a promising avenue for further studies. Competing Interest Statement The authors have declared no competing interest. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of Charite - University Medical Centre gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present work are contained in the manuscript.