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Even asymptomatic unilateral stenosis can induce subclinical cerebrovascular changes, potentially affecting both hemispheres through collateral circulation. This study aimed to systematically assess cerebral perfusion in asymptomatic individuals with unilateral carotid artery stenosis by comparing ipsilateral and contralateral hemispheres with healthy controls, challenging the assumption that the contralateral hemisphere remains unaffected. Materials and Methods: This cross-sectional study included 114 participants, comprising 54 asymptomatic individuals (mean age 65.5) with significant unilateral carotid stenosis and 60 age-matched controls (mean age 64.8). Cerebral perfusion was assessed using 1.5T Magnetic Resonance Imaging (MRI) with pseudo-continuous arterial spin labeling (pCASL). CBF was measured bilaterally in four predefined middle cerebral artery (MCA) regions: precentral gyrus, lentiform nucleus, insular cortex, and temporal cortex. Statistical analyses included multivariate analysis of variance (MANOVA), analysis of variance (ANOVA), paired t-tests, and discriminant analysis (DA). Results: Significant bilateral reductions in CBF were observed in individuals with carotid stenosis compared to controls (MANOVA and ANOVA, p &lt; 0.001). The greatest perfusion deficit was in the ipsilateral insular cortex (49.88 \u00b1 10.83 mL\/100 g\/min), followed by intermediate contralateral perfusion (51.49 \u00b1 8.86 mL\/100 g\/min) and higher control values (58.78 \u00b1 10.44 mL\/100 g\/min). DA indicated the insular cortex as the region with the highest discriminative contribution (64.7%). Conclusions: Unilateral carotid artery stenosis in asymptomatic individuals is associated with significant bilateral cerebral hypoperfusion, suggesting widespread hemodynamic effects. Pronounced perfusion deficits in the insular cortex underline its vulnerability. The observed contralateral perfusion reductions challenge the traditional use of the contralateral hemisphere as a reference standard, underscoring the need for comprehensive perfusion assessment in carotid artery disease.<\/jats:p>","DOI":"10.3390\/medicina61050771","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T03:17:32Z","timestamp":1745291852000},"page":"771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bilateral Cerebral Hypoperfusion in Asymptomatic Unilateral Carotid Artery Stenosis: An Arterial Spin Labeling MRI Study"],"prefix":"10.3390","volume":"61","author":[{"given":"Nikola","family":"Dacic","sequence":"first","affiliation":[{"name":"Center for Radiology, University Clinical Center of Vojvodina, 21000 Novi Sad, Serbia"},{"name":"Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srdjan","family":"Stosic","sequence":"additional","affiliation":[{"name":"Center for Radiology, University Clinical Center of Vojvodina, 21000 Novi Sad, Serbia"},{"name":"Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivera","family":"Nikolic","sequence":"additional","affiliation":[{"name":"Center for Radiology, University Clinical Center of Vojvodina, 21000 Novi Sad, Serbia"},{"name":"Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9103-1280","authenticated-orcid":false,"given":"Zoran D.","family":"Jelicic","sequence":"additional","affiliation":[{"name":"Department of Computing and Control, Faculty of Technical Sciences, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1900-3733","authenticated-orcid":false,"given":"Aleksandra Dj","family":"Ilic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"},{"name":"Neurology Clinic, University Clinical Center of Vojvodina, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2034-3401","authenticated-orcid":false,"given":"Mirna N.","family":"Radovic","sequence":"additional","affiliation":[{"name":"Department of Computing and Control, Faculty of Technical Sciences, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2303-7979","authenticated-orcid":false,"given":"Jelena","family":"Ostojic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.21037\/atm-20-7490","article-title":"A Narrative Review of the Pathophysiology of Ischemic Stroke in Carotid Plaques: A Distinction Versus a Compromise Between Hemodynamic and Embolic Mechanism","volume":"9","author":"Mechtouff","year":"2021","journal-title":"Ann. 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