RT info:eu-repo/semantics/doctoralThesis T1 Realce de la placa de aterosclerosis intracraneal como marcador de su riesgo clínico y actividad inflamatoria A1 Gómez Vicente, Beatriz A2 Universidad de Valladolid. Escuela de Doctorado K1 Medicina K1 Resonancia magnética K1 Aterosclerosis K1 Atherosclerosis K1 Aterosclerosis K1 Intracranial K1 Intracraneal K1 Enhancement K1 Realce K1 3205 Medicina Interna AB IntroductionIntracranial atherosclerosis (ICAD) is a major cause of stroke worldwide. Patients affected by this condition are exposed to a very high risk of having future strokes, despite current preventive therapies. There is an unmet clinical need to develop prognostic markers to help stratify patients’ risk, in order to advance towards personalized stroke prevention. Post-contrast intracranial atherosclerotic plaque enhancement on high-resolution magnetic resonance imaging (HR-MRI) is among the most promising imaging markers of a high-risk plaque, although its long-term prognostic value is yet to be clarified. Besides, it remains unclear whether post-contrast enhancement is related to the inflammatory activity within the intracranial atheromatous plaque.ObjectivesWe aimed to (1) evaluate the capacity of intraplaque post-contrast enhancement to predict long-term risk of future stroke in symptomatic and asymptomatic subjects with ICAD, and (2) to analyze whether plaque and wall post-contrast enhancement is related to the distribution of circulating monocyte populations, specifically focusing on the proportion of monocytes expressing CCR5 receptor, which allows them penetrate into the atheromatous lesions. MethodologyWe designed two prospective, longitudinal, artery wall HR-MRI – based studies including symptomatic ICAD patients and asymptomatic subjects with ICAD. The first one was multi-centric and analyzed whether the HR-MRI features of ICAD plaques, including intraplaque post-contrast enhancement ratio, predicted the long-term risk of future strokes, using Cox regression model and Kaplan Meier survival analyses. The second investigation combined HR-MRI with flow cytometry performed on fresh blood samples extracted from symptomatic and asymptomatic participants on the same morning when MRI was performed. Symptomatic patients underwent a repeated protocol three months after the first one. Study subjects were classified according to the presence of enhancement in the following groups: no enhancement, arterial wall enhancement, and plaque enhancement. Flow cytometry was performed right away to identify monocyte populations Mon1, Mon2 and Mon3, using the following receptor markers CD14, CD16, HLA-DR, CCR2 and CCR5.ResultsThe first investigation included 48 symptomatic ICAD patients and 13 asymptomatic subjects with intracranial stenoses. During a follow-up period of 56.3 ± 16.9 months, 11 major cerebrovascular events occurred (seven ischemic strokes, two hemorrhagic strokes, two confirmed transient ischemic attacks). An intraplaque enhancement ratio > 1.77 (Hazard Ratio) HR, 3.632; 95% confidence interval (CI) (1.082-12.101) and brain microbleeds (HR 5.244; 95% CI, 1.476-18.629), emerged as independent predictors of future stroke risk. Survival analysis showed that proportion of patients free of future events was lower with a higher enhancement ratio (log-rank p < 0.05)The second investigation included 12 symptomatic ICAD patients and 34 asymptomatic individuals with a very high vascular risk. All symptomatic patients and 53% of asymptomatic subjects showed intracranial plaque and/or arterial wall post-contrast enhancement. Symptomatic patients showed a higher proportion of Mon2 and Mon3 expressing CCR5 receptor than asymptomatic subjects. Among asymptomatic individuals, a higher proportion of Mon3 CCR5+ was observed in those showing intraplaque or wall enhancement. In general, study participants with intraplaque or wall enhancement had a higher proportion of Mon3 CCR5+ than those with no enhancement. Finally, a significant correlation was found between Mon3 CCR5+ proportion and the number of intracranial arteries showing wall enhancement.ConclusionIntracranial plaque post-contrast enhancement is a predictor of a higher risk for future strokes in the long-term. If further validated by future studies, this imaging marker could have clinical applicability discriminating higher risk ICAD patients. Intracranial plaque and wall post-contrast enhancement is associated with a higher proportion of monocytes expressing CCR5 receptor in ICAD symptomatic patients and asymptomatic subjects. These findings suggest that post-contrast enhancement might reflect the inflammatory activity within intracranial atheromatous lesions, from the early stages (wall enhancement) to the advanced phases (plaque enhancement). YR 2022 FD 2022 LK https://uvadoc.uva.es/handle/10324/59744 UL https://uvadoc.uva.es/handle/10324/59744 LA spa NO Escuela de Doctorado DS UVaDOC RD 07-ago-2024