Department of Radiology; Department of Neurosurgery
Cardiovascular Diseases | Enzymes and Coenzymes | Nervous System Diseases | Radiology
Progress in clinical development of magnetic resonance imaging (MRI) substrate-sensors of enzymatic activity has been slow partly due to the lack of human efficacy data. We report here a strategy that may serve as a shortcut from bench to bedside. We tested ultra high-resolution 7T MRI (microMRI) of human surgical histology sections in a 3-year IRB approved, HIPAA compliant study of surgically clipped brain aneurysms. microMRI was used for assessing the efficacy of MRI substrate-sensors that detect myeloperoxidase activity in inflammation. The efficacy of Gd-5HT-DOTAGA, a novel myeloperoxidase (MPO) imaging agent synthesized by using a highly stable gadolinium (III) chelate was tested both in tissue-like phantoms and in human samples. After treating histology sections with paramagnetic MPO substrate-sensors we observed relaxation time shortening and MPO activity-dependent MR signal enhancement. An increase of normalized MR signal generated by ultra-short echo time MR sequences was corroborated by MPO activity visualization by using a fluorescent MPO substrate. The results of microMRI of MPO activity associated with aneurysmal pathology and immunohistochemistry demonstrated active involvement of neutrophils and neutrophil NETs as a result of pro-inflammatory signalling in the vascular wall and in the perivascular space of brain aneurysms.
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DOI of Published Version
Sci Rep. 2018 May 16;8(1):7687. doi: 10.1038/s41598-018-25804-y. Link to article on publisher's site
Wadghiri, Youssef Z.; Hoang, Dung Minh.; Leporati, Anita M.; Gounis, Matthew J.; Rodriguez-Rodriguez, Aurora; Mazzanti, Mary L.; Weaver, John P.; Wakhloo, Ajay K.; Caravan, Peter; and Bogdanov, Alexei A. Jr, "High-resolution Imaging of Myeloperoxidase Activity Sensors in Human Cerebrovascular Disease" (2018). Radiology Publications and Presentations. 405.
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This work is licensed under a Creative Commons Attribution 4.0 License.