Expression of Cyclooxygenase 2 (COX-2) in the Wall of Human Cerebral Aneurysms and Correlation to MRI

Jan Rodemerk1; Andreas Junker2; M.D.; Bixia Chen1, M.D.; Daniela Pierscianek1, M.D.; Philipp Dammann1, M.D.; Alexander Radbruch4, M.D.; Stefan Maderwald3, PhD; Yuan Zhu1, PhD; Ramazan Jabbarli1, M.D.; Ulrich Sure1, M.D.; Karsten H. Wrede1, M.D.

1Department of Neurosurgery, University Hospital Essen, Essen, Germany
2Clinic for Neuropathology, University Hospital Essen, Essen, Germany
3Erwin L. Hahn Institute for Magnetic Resonance Imaging, University Duisburg-Essen, Essen, Germany
4Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany

DOI: 10.3205/20dgnc113

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 between 5 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).

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.

Figure 1. 27-millimetre Aneurysm. A, Circulus 3T TOF-MRI shows a hypointensity surrounding the aneurysm, asterisk indicating the aneurysm wall. B in situ. C, 0.5x magnification IHC COX-2 staining (48.54 % coverage of positive cells), asterisk indicating in both slides positive stained aneurysm wall. D, 0.5x magnification Perls‘s Prussian blue
Figure 2. Largest (40-millimetre) aneurysm. SWI MRI at 1T a with hypointensity (A), not as strong as in the SWI 7T MRI (B), asterisk indicating the aneurysm wall. This hypointensity correlates with the high iron deposition in the Perls‘s Prussian blue staining (C, 40x magnification). COX-2 positive cells cover 79.98 % of the 40x magnification IHC slide (D).