{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T04:45:06Z","timestamp":1770180306619,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Extracellular matrix (ECM) and collagen remodeling contribute to chronic kidney disease (CKD) progression and vascular access dysfunction. Conventional histological techniques rely on staining and provide limited sensitivity for detecting early or subtle ECM alterations. Nonlinear optical imaging modalities, including second-harmonic generation (SHG), third-harmonic generation (THG), and multiphoton fluorescence (MPF) microscopy, enable label-free, high-resolution visualization of fibrillar collagen and may offer additional structural information. This study aimed to evaluate the added value of nonlinear imaging beyond conventional histology for assessing ECM remodeling in renal and vascular tissues. Materials and Methods: A systematic literature review was conducted in accordance with the PRISMA 2020 guidelines. PubMed and Web of Science were searched for studies published between 1 January 2015, and 4 April 2025, investigating ECM or collagen remodeling in renal or vascular tissues using SHG, THG, or MPF microscopy. After screening 115 records, 10 studies were included in the qualitative synthesis. In addition, representative SHG, THG, and MPF images of excised human arteriovenous fistula (AVF) tissue were acquired as illustrative feasibility examples to demonstrate the application of these imaging modalities. The use of human tissue was approved by the Vilnius Regional Biomedical Research Ethics Committee (approval No. 2022\/6-1443-917). Results: The included studies demonstrated that nonlinear microscopy enables label-free assessment of collagen density, organization, and fiber orientation. SHG imaging differentiated healthy from diseased tissues and has been reported to support fibrosis assessment and staging in preclinical and selected clinical studies and revealed microstructural remodeling patterns not readily detected by conventional histology. The illustrative AVF images demonstrated collagen disorganization consistent with patterns reported in the reviewed literature and are presented solely to demonstrate imaging feasibility, without implying disease phenotype or clinical outcome associations. Conclusions: Nonlinear optical microscopy provides complementary structural information on ECM organization that is not accessible with standard histological techniques. Further validation and methodological standardization are required to support its broader application in clinical nephrology and vascular medicine.<\/jats:p>","DOI":"10.3390\/medicina62020317","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T16:46:28Z","timestamp":1770137188000},"page":"317","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nonlinear Microscopy of ECM Remodeling in Renal and Vascular Tissues: A Systematic Review Integrating Human AVF Imaging"],"prefix":"10.3390","volume":"62","author":[{"given":"Vilt\u0117 Gabriel\u0117","family":"Samson\u0117","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 01513 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielius","family":"Samsonas","sequence":"additional","affiliation":[{"name":"Laser Research Centre, Faculty of Physics, Vilnius University, 01513 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5850-1129","authenticated-orcid":false,"given":"Laurynas","family":"Rim\u0161evi\u010dius","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 01513 Vilnius, Lithuania"},{"name":"Nephrology Centre, Vilnius University Hospital Santaros Klinikos, 08406 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mykolas","family":"Ma\u010diulis","sequence":"additional","affiliation":[{"name":"Laser Research Centre, Faculty of Physics, Vilnius University, 01513 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Osteikait\u0117","sequence":"additional","affiliation":[{"name":"Laser Research Centre, Faculty of Physics, Vilnius University, 01513 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birut\u0117","family":"Vai\u0161nyt\u0117","sequence":"additional","affiliation":[{"name":"Centre of Cardiology and Angiology, Clinic of Cardiac and Vascular Diseases, Vilnius University Hospital Santaros Klinikos, 08406 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edvardas","family":"\u017durauskas","sequence":"additional","affiliation":[{"name":"State Pathology Center, Vilnius University Hospital Santaros Klinikos, 08406 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginijus","family":"Barzda","sequence":"additional","affiliation":[{"name":"Laser Research Centre, Faculty of Physics, Vilnius University, 01513 Vilnius, Lithuania"},{"name":"Department of Chemical and Physical Sciences, University of Toronto Mississauga, Toronto, ON L5L 1C6, Canada"},{"name":"Department of Physics, University of Toronto, Toronto, ON M5S 1A1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0017-468X","authenticated-orcid":false,"given":"Marius","family":"Miglinas","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 01513 Vilnius, Lithuania"},{"name":"Nephrology Centre, Vilnius University Hospital Santaros Klinikos, 08406 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1364\/BOE.411501","article-title":"Three-Dimensional Characterization of Collagen Remodeling in Cell-Seeded Collagen Scaffolds via Polarization Second Harmonic Generation","volume":"12","author":"Xydias","year":"2021","journal-title":"Biomed. 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