High-resolution Imaging of Myeloperoxidase Activity Sensors in Human Cerebrovascular Disease
| Autor: | Dung Minh Hoang, Aurora Rodríguez-Rodríguez, Alexei A. Bogdanov, Peter Caravan, Youssef Zaim Wadghiri, Matthew J. Gounis, Anita M. Leporati, Mary L. Mazzanti, John P. Weaver, Ajay K. Wakhloo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Gadolinium DTPA Male Pathology medicine.medical_specialty Adolescent Gadolinium Contrast Media chemistry.chemical_element lcsh:Medicine Inflammation Biosensing Techniques Article 030218 nuclear medicine & medical imaging Young Adult 03 medical and health sciences 0302 clinical medicine Image Processing Computer-Assisted medicine Humans Prospective Studies Perivascular space lcsh:Science Aged Peroxidase Multidisciplinary biology medicine.diagnostic_test Phantoms Imaging business.industry lcsh:R Magnetic resonance imaging Histology Middle Aged Magnetic Resonance Imaging Imaging agent 3. Good health Cerebrovascular Disorders medicine.anatomical_structure chemistry Myeloperoxidase biology.protein Immunohistochemistry Female lcsh:Q medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-25804-y |
| Popis: | 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 (µMRI) of human surgical histology sections in a 3-year IRB approved, HIPAA compliant study of surgically clipped brain aneurysms. µMRI 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 µMRI 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. |
| Databáze: | OpenAIRE |
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