High-resolution Imaging of Myeloperoxidase Activity Sensors in Human Cerebrovascular Disease

Scientific Reports
Youssef Z WadghiriAlexei A Bogdanov

Abstract

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 o...Continue Reading

References

Nov 5, 1999·Neurosurgery·D ChyatteD R Todor
Sep 22, 2000·Bioorganic & Medicinal Chemistry Letters·K P EisenwienerH R Mäcke
Oct 28, 2004·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·John W ChenAlexei Bogdanov
Mar 12, 2005·NMR in Biomedicine·Youssef Zaim WadghiriDaniel H Turnbull
Apr 23, 2005·Organic Letters·Manuel QuerolAlexei Bogdanov
Jan 18, 2006·Magnetic Resonance Imaging·Richard G SpencerMark P Mattson
Jan 28, 2006·Stroke; a Journal of Cerebral Circulation·Takuya MoriwakiNobuo Hashimoto
Apr 12, 2006·Laboratory Investigation; a Journal of Technical Methods and Pathology·Hye Won KangAlexei A Bogdanov
May 12, 2006·Organic & Biomolecular Chemistry·Manel QuerolAlexei A Bogdanov
Jun 9, 2006·Neurological Research·Tomoki HashimotoWilliam L Young
Oct 7, 2006·Journal of Magnetic Resonance Imaging : JMRI·Manuel Querol, Alexei Bogdanov
Apr 26, 2007·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Mark D MeadowcroftQing X Yang
May 19, 2007·Bioconjugate Chemistry·Alexei BogdanovAnna Yudina
May 30, 2007·Journal of Anatomy·Guido PielesWolfgang J Weninger
Aug 19, 2007·Chembiochem : a European Journal of Chemical Biology·Manuel QuerolAlexei Bogdanov
Nov 21, 2007·Circulation·Tomohiro AokiNobuo Hashimoto
Feb 7, 2008·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Felix W WehrliPeter J Snyder
Aug 30, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Christian A GleissnerKlaus Ley
Nov 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Michael O BreckwoldtRalph Weissleder
Jan 24, 2009·Stroke; a Journal of Cerebral Circulation·Tomohiro AokiNobuo Hashimoto
Dec 9, 2009·Journal of the American Chemical Society·Elisenda RodríguezJohn W Chen
Jun 1, 2010·Journal of Neurointerventional Surgery·Riikka TulamoMika Niemelä
Nov 3, 2011·Future Oncology·Marie-France PenetZaver M Bhujwalla
Jul 17, 2013·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Dung Minh HoangYoussef Zaim Wadghiri
Oct 15, 2013·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·David L PennE Sander Connolly
Dec 11, 2013·Translational Stroke Research·Nohra ChalouhiDavid Hasan
Apr 1, 2014·Expert Review of Clinical Immunology·Remo C RussoFlavio A Amaral
Apr 10, 2014·Stroke; a Journal of Cerebral Circulation·Matthew J GounisAlexei A Bogdanov
Sep 10, 2015·Stroke; a Journal of Cerebral Circulation·Matthew J GounisAlexei A Bogdanov
Mar 31, 2017·Seminars in Thrombosis and Hemostasis·Miguel Jiménez-AlcázarTobias A Fuchs

❮ Previous
Next ❯

Citations

Jul 25, 2019·Journal of Neurointerventional Surgery·Edgar A SamaniegoDavid Hasan
Jun 20, 2019·Biochemistry. Biokhimii︠a︡·A A BogdanovA P Savitsky
Oct 3, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christina H LiuPushpa Tandon
Oct 20, 2020·Investigative Radiology·Sergey ShuvaevPeter Caravan
Jun 26, 2021·Radiology. Imaging Cancer·Tobias BäuerleAlexei Bogdanov

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
fluorescence microscopy
light microscopy
light
electrophoresis

Software Mentioned

GraphPad
Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.