Background and Purpose:The pathophysiology of development, growth, and rupture of intracranial aneurysms (IAs) is only partly understood. Cyclooxygenase 2 (COX-2) converts arachidonic acid to prostaglandin H₂, which, in turn, is isomerized to prostaglandin E₂. In the human body, COX-2 plays an essential role in inflammatory pathways. This explorative study aimed to investigate COX-2 expression in the wall of IAs and its correlation to image features in clinical (1.0T, 1.5T, and 3.0T) magnetic resonance imaging (MRI) and ultra-high-field 7T MRI.Methods:The study group comprised 40 patients with partly thrombosed saccular IAs. The cohort included 17 ruptured- and 24 unruptured IAs, which had all been treated microsurgically. Formaldehyde-fixed paraffin-embedded samples were immunohistochemically stained with a monoclonal antibody against COX-2 (Dako, Santa Clara, CA; Clone: CX-294). We correlated Perls Prussian blue staining, MRI, and clinical data with immunohistochemistry, analyzed using the Trainable Weka Segmentation algorithm.Results:Aneurysm dome size ranged between 2 and 67 mm. The proportion of COX-2 positive cells ranged between 3.54% to 85.09%. An upregulated COX-2 expression correlated with increasing IA dome size (P=0.047). Furthermore, there was a tendency of higher COX-2 expression in most ruptured IAs (P=0.064). At all field strengths, MRI shows wall hypointensities due to iron deposition correlating with COX-2 expression (P=0.022).Conclusions:Iron deposition and COX-2 expression in IAs walls correlate with signal hypointensity in MRI, which might, therefore, serve as a biomarker for IA instability. Furthermore, as COX-2 was also expressed in small unruptured IAs, it could be a potential target for specific medical treatment.

中文翻译：

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颅内动脉瘤的病理生理学：COX-2表达，动脉瘤壁中的铁沉积以及与磁共振成像的相关性。

背景与目的：仅部分了解颅内动脉瘤（IAs）的发育，生长和破裂的病理生理学。环氧合酶2（COX-2）将花生四烯酸转化为前列腺素H ₂，然后将其异构化为前列腺素E ₂。在人体中，COX-2在炎症途径中起着至关重要的作用。这项探索性研究旨在调查IAs壁中COX-2的表达及其与临床（1.0T，1.5T和3.0T）磁共振成像（MRI）和超高场7T MRI图像特征的相关性。 ：研究组包括40例部分血栓性囊状IA的患者。该队列包括17例破裂的IA和24例未破裂的IA，均已接受显微手术治疗。用针对COX-2的单克隆抗体（Dako，Santa Clara，CA; Clone：CX-294）对甲醛固定的石蜡包埋的样品进行免疫组织化学染色。我们将Perls普鲁士蓝染色，MRI和临床数据与免疫组织化学相关联，并使用可训练的Weka分割算法进行了分析。结果：动脉瘤穹顶的大小在2到67 mm之间。COX-2阳性细胞的比例在3.54％至85.09％之间。COX-2表达上调与IA穹顶大小增加相关（P = 0.047）。此外，在大多数破裂的IAs中有较高的COX-2表达趋势（P = 0.064）。在所有场强下，MRI均显示出铁沉积引起的壁低强度与COX-2表达相关（P = 0.022）。结论：IAs壁的铁沉积和COX-2表达与MRI中的信号低强度相关，因此可能有用作为IA不稳定的生物标记。此外，由于COX-2也在未破裂的小型IAs中表达，因此可能成为特定药物治疗的潜在靶标。