MODELING UNSTABLE BRAIN ANEURYSMS: MR MOLECULAR IMAGING OF MYELOPEROXIDASE IN VASCULAR WALL AND CORRELATION WITH HUMAN PATHOLOGY

摘要

Brain aneurysm bleeding is associated with high rates of fatality or permanent neurological impairment. Despite the low risk of bleeding of an unruptured cerebral aneurysm (UCA) [1,2], the dismal outcome of aneurysmal rupture has led to the aggressive treatment of these aneurysms. In 2008, approximately 60,000 UCAs were treated in the USA [3]. The rate of morbidity and mortality from treatment is high: approximately 5 and 14% for coil embolization and surgical clipping, respectively [3]. The risk-benefit analysis does not support treatment of all UCAs and in an era of significant attention to healthcare economics, considerable expense for treatment of unruptured aneurysms may not be justified. Thus, there is a strong clinical need to identify asymptomatic patients with UCA who would benefit from preventative interventional or surgical procedures. We previously demonstrated that the enzymatic activity of neutrophilic myeloperoxidase (MPO) can be used as a highly selective and sensitive target for detecting inflammation using MRI [4]. Our rabbit model studies validated the use of a gadolinium(III)-chelate MPO activity-sensing MR imaging agent as a probe for the detection and localization of lipopolysaccharide (LPS)-induced inflammation in an animal aneurysm model. Although these results are promising, several key issues remain before the relevance of an MPO imaging approach can begin to be evaluated for use in patients with UCA. 1. Direct evidence of the presence of MPO in human aneurysm tissues must be established, and 2, MR protocols (specifically for axial black blood imaging) have to be optimized to detect the presence of MPO within a human aneurysm, especially given the complexity of intra-aneurysmal flow and its attenuation of the MR signal. Here we describe studies carried out to ascertain the presence of MPO in human aneurysm tissue and to optimize a clinical MR protocol for detecting an MPO-specific contrast agent in the wall of saccular aneurysms.