O-014 Modelling Unstable Brain Aneurysms: MR Molecular Imaging of Myeloperoxidase in the Aneurysm Wall and Correlation with Human Pathology

Introduction An imaging approach identifying patients who benefit from treatment of unruptured intracranial aneurysms (UIA) is desired. We investigate a potential biomarker of UIA instability, myeloperoxidase (MPO), in human aneurysm tissue and in parallel develop a MPO molecular imaging approach in experimental models. Materials and Methods We harvested 20 aneurysms from 17 patients during surgical clipping. Angiograms were evaluated for: 1. maximum diameter, 2. blebs, 3. surface architecture (berry/irregular), and 4. single-lobe or multilobular. The tissue samples were stained against human MPO. MRI sequence insensitive to complex intra-aneurysmal flow was optimised in vitro. A silicone vascular replica of a rabbit elastase aneurysm was built 1 and embedded in coconut oil. Flow was generated by a pulsatile pump simulating the rabbit aortic waveform1 using a blood analogue matching T1- and viscosity of blood. At 3T, we acquired motion-sensitised driven-equilibrium (MSDE) (TE=10ms, variable TR and FA) and optimised the flow velocity encoded gradient echo imaging parameter (VENC, 1–8cm/s), while using spectral pre-saturation inversion recovery (SPIR) fat suppression. Saccular aneurysm model in white New Zealand rabbits (n=8) was created 2 . The animals were imaged using the MRI protocol optimised in-vitro. Naive aneurysms were imaged before and 3 hours after injecting MPO-specific contrast agent. Animals returned to the surgical suite 1-week later for lipopolysaccharide (LPS)-induced inflammation of the aneurysm wall 3 . Two-days after the LPS administration, the MRI study was repeated before and after MPO-specific contrast agent infusion. The animals were euthanised and the aneurysms explanted for histology. Results Ten human aneurysms were positive for MPO. All ruptured aneurysms (n=3) were positive for MPO. UIAs described as irregular/complex had a positive trend for MPO infiltration (p=0.087). Aneurysms were more likely to be positive for MPO in patients who had a family history of subarachnoid haemorrhage (p In the phantom experiment we confirmed that the MSDE sequence with VENC of 1 cm/s and SPIR eliminated the signal from blood flow and adjacent fat, respectively, yet provided sufficient contrast to image a representative amount of the MPO-contrast. The optimised MSDE sequence was used in the rabbit aneurysm model. Significant motion artifact required respiratory-triggering. Consequently, T1-weighting was lost. An inversion pulse was added to the sequence as to gain T1-sensitivity by inversion recovery (IR, IR delay optimised to 800ms). As compared to the naive aneurysm, there was a 40-fold increase in the SNR change from pre to post-contrast MSDE imaging in the inflamed aneurysm model (p Conclusion Human aneurysms with associated risk factors for rupture or that have ruptured contain MPO within the aneurysm wall; suggesting that MPO could be a valuable biomarker for assessment of aneurysm propensity for rupture. A diagnostic MR imaging protocol has been optimised in vitro and applied for detection of an MPO-specific contrast agent in an animal model of aneurysms. Disclosures M. Gounis: 1; C; NIH. I. van der Bom: None. A. Wakhloo: None. S. Zheng: None. J. Weaver: None. A. Puri: None. A. Kuhn: None. A. Bogdanov: 1; C; NIH. References Seong, et al. Biorheology 2005;42:345–361 Cloft, et al. Radiology 1999;213:223–228 DeLeo, et al. Radiology 2009;252:696–703