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Focal enhancement is frequently encountered in unruptured aneurysms, but its implication for risk stratification and patient management remains unclear. This study investigates the association of focal wall enhancement with hemodynamic and morphological risk factors and histologic markers of wall inflammation and degeneration.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Patients with an unruptured middle cerebral artery aneurysm who underwent 3D rotational angiography and 3T MR vessel wall imaging showing focal wall enhancement were included. Hemodynamic parameters were calculated based on flow simulations and compared between enhanced regions and the entire aneurysm surface. Morphological parameters were semiautomatically extracted and quantitatively associated with wall enhancement. Histological analysis included detection of vasa vasorum, CD34, and myeloperoxidase staining in a subset of patients.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Twenty-two aneurysms were analyzed. Enhanced regions were significantly associated with lower AWSS, lower maxOSI, and increased LSA. In multivariate analysis, higher ellipticity index was an independent predictor of wall enhancement. Histologic signs of inflammation and degeneration and higher PHASES score were significantly associated with focal enhancement.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Focal wall enhancement is colocalized with hemodynamic factors that have been related to a higher rupture risk. It is correlated with morphological factors linked to rupture risk, higher PHASES score, and histologic markers of wall destabilization. The results support the hypothesis that focal enhancement could serve as a surrogate marker for aneurysm instability.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s00234-020-02498-6","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T20:03:36Z","timestamp":1595016216000},"page":"1627-1635","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Multimodal validation of focal enhancement in intracranial aneurysms as a surrogate marker for aneurysm instability"],"prefix":"10.1007","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8782-8278","authenticated-orcid":false,"given":"Naomi","family":"Larsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2615-0616","authenticated-orcid":false,"given":"Charlotte","family":"Fl\u00fch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7002-7917","authenticated-orcid":false,"given":"Sylvia","family":"Saalfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9757-7564","authenticated-orcid":false,"given":"Samuel","family":"Vo\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Hille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Trick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1413-2699","authenticated-orcid":false,"given":"Fritz","family":"Wodarg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0427-6832","authenticated-orcid":false,"given":"Michael","family":"Synowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7330-1942","authenticated-orcid":false,"given":"Olav","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4140-6771","authenticated-orcid":false,"given":"Philipp","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,17]]},"reference":[{"key":"2498_CR1","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/nrneurol.2016.150","volume":"12","author":"N Etminan","year":"2016","unstructured":"Etminan N, Rinkel GJ (2016) Unruptured intracranial aneurysms: development, rupture and preventive management. 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