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Expression of cyclooxygenase 2 (COX-2) in the wall of human cerebral aneurysms and correlation to MRI
Expression von Cyclooxygenase 2 (COX-2) in der Wand zerebraler Aneurysmen in Korrelation zur MRT-Bildgebung
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Veröffentlicht: | 26. Juni 2020 |
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Objective: The pathophysiology of development, growth and rupture of cerebral aneurysms is only partially understood. Cyclooxygenase 2 (COX-2) converts arachidonic acid to PGH2 which in turn is isomerized to PGE2. COX-2 plays an important role in the inflammatory pathway of the human body. Expression of COX-2 seems to be related to aneurysm instability and might serve as a future target for medical treatment and rupture prevention. The aim of this feasibility study was to investigate COX-2 expression in the wall of cerebral aneurysms and correlation to image features in clinical (1-3 Tesla) MRI and ultra-high field 7 Tesla MRI.
Methods: The study group comprised 5 patients with partly thrombosed saccular intracranial Aneurysms (IAs), one ruptured, 4 unruptured which underwent microsurgical treatment. Formaldehyde fixed paraffin embedded samples were immunohistochemically (IHC) stained with a monoclonal antibody against COX-2 (DAKI, Clone: CX-294). Perls’s Prussian blue staining and MRI images were correlated to the IHC, that was analysed with the "Trainable Weka Segmentation" (doi:10.1093/bioinformatics/btx180).
Results: Aneurysm dome size ranged between5 to 40 millimetres. Proportion of COX-2 positive cells ranged between 3.7 % to 79.98 %. The expression of COX-2 correlated positively with aneurysm size, but in the smallest aneurysm which had a relatively high expression of 47.85 % COX-2 positive cells. At all field strength, MRI shows a wall hypointensity due to iron deposition (Figure 2 A, B).
Figure 1 [Fig. 1]
Figure 2 [Fig. 2]
Conclusion: As COX-2 could be a future molecular target for aneurysm treatment the hypointense signal patterns in TOF and SWI have a potential to serve as a biomarker for treatment stratification and treatment response monitoring.