scholarly journals Non-invasive in Vivo Assessment of 11β-hydroxysteroid Dehydrogenase type 1 Activity by 19 F-magnetic Resonance Spectroscopy

2021 ◽  
Author(s):  
Gregorio Naredo-Gonzalez ◽  
Rita Upreti ◽  
Maurits A Jansen ◽  
Scott Semple ◽  
Oliver B Sutcliffe ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Limit Of Detection ◽  
Reductase Activity ◽  
Fluorine Content ◽  
Hydroxysteroid Dehydrogenase ◽  
Resonance Spectroscopy ◽  
Pharmacodynamic Biomarkers

Abstract 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies tissue glucocorticoid levels and is a pharmaceutical target in diabetes and cognitive decline. Clinical translation of inhibitors is hampered by lack of in vivo pharmacodynamic biomarkers. Our goal was to monitor substrates and products of 11β-HSD1 non-invasively in liver via 19 Fluorine magnetic resonance spectroscopy (19 F-MRS). Interconversion of mono/poly-fluorinated substrate/product pairs was studied in Wistar rats (male, n=6) and healthy men (n=3) using 7 T and 3 T MRI scanners, respectively. Here we show that the limit of detection, as absolute fluorine content, was 0.625 μmol in blood. Mono-fluorinated steroids, dexamethasone and 11-dehydrodexamethasone, were detected in phantoms but not in vivo in human liver following oral dosing. A non-steroidal polyfluorinated tracer, 2-(phenylsulfonyl)-1-(4-(trifluoromethyl)phenyl)ethanone and its metabolic product were detected in vivo in rat liver after oral administration of the keto-substrate, giving a readout of reductase activity. Administration of a selective 11β-HSD1 inhibitor in vivo in rats altered total liver 19 F-MRS signal. We conclude that there is insufficient sensitivity to measure mono-fluorinated tracers in vivo in man with current dosage regimens and clinical scanners. However use of a poly-fluorinated tracer allowed detection of hepatic reductase activity in rats and could be developed for translation to man.

19F-magnetic resonance spectroscopy as a tool to quantify 11[beta]-hydroxysteroid dehydrogenase activity in vivo

2013 ◽  
pp. 1-1
Author(s):  
Gregorio NaredoGonzalez ◽  
Maurits Jansen ◽  
Rita Upreti ◽  
Scott Semple ◽  
Gavin Merrifield ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Dehydrogenase Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Resonance Spectroscopy

scholarly journals Region-Specific Cerebral Metabolic Alterations in Streptozotocin-Induced Type 1 Diabetic Rats: An in vivo Proton Magnetic Resonance Spectroscopy Study

2015 ◽  
Vol 35 (11) ◽  
pp. 1738-1745 ◽  
Author(s):  
Hui Zhang ◽  
Mingming Huang ◽  
Lifeng Gao ◽  
Hao Lei
Keyword(s):  
Visual Cortex ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Brain Regions ◽  
Resonance Spectroscopy ◽  
Metabolic Disturbances ◽  
Metabolic Alterations ◽  
Neuronal Metabolism

Clinical and experimental in vivo1H-magnetic resonance spectroscopy (1H-MRS) studies have demonstrated that type 1 diabetes mellitus (T1DM) is associated with cerebral metabolic abnormalities. However, less is known whether T1DM induces different metabolic disturbances in different brain regions. In this study, in vivo1H-MRS was used to measure metabolic alterations in the visual cortex, striatum, and hippocampus of streptozotocin (STZ)-induced uncontrolled T1DM rats at 4 days and 4 weeks after induction. It was observed that altered neuronal metabolism occurred in STZ-treated rats as early as 4 days after induction. At 4 weeks, T1DM-related metabolic disturbances were clearly region specific. The diabetic visual cortex had more or less normal-appearing metabolic profile; while the striatum and hippocampus showed similar abnormalities in neuronal metabolism involving N-acetyl aspartate and glutamate; but only the hippocampus exhibited significant changes in glial markers such as taurine and myo-inositol. It is concluded that cerebral metabolic perturbations in STZ-induced T1DM rats are region specific at 4 weeks after induction, perhaps as a manifestation of varied vulnerability among the brain regions to sustained hyperglycemia.

Biological NMR Spectroscopy

1997 ◽  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Nmr Spectroscopy ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
State Of The Art ◽  
Critical Assessment ◽  
Resonance Spectroscopy ◽  
History Of ◽  
Structure Of Proteins

This book presents a critical assessment of progress on the use of nuclear magnetic resonance spectroscopy to determine the structure of proteins, including brief reviews of the history of the field along with coverage of current clinical and in vivo applications. The book, in honor of Oleg Jardetsky, one of the pioneers of the field, is edited by two of the most highly respected investigators using NMR, and features contributions by most of the leading workers in the field. It will be valued as a landmark publication that presents the state-of-the-art perspectives regarding one of today's most important technologies.

In vivo 2D J-resolved magnetic resonance spectroscopy of rat brain with a 3-T clinical human scanner

NeuroImage ◽  
2004 ◽  
Vol 22 (1) ◽  
pp. 381-386 ◽  
Author(s):  
E Adalsteinsson ◽  
R.E Hurd ◽  
D Mayer ◽  
N Sailasuta ◽  
E.V Sullivan ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Rat Brain ◽  
Resonance Spectroscopy

scholarly journals INSPECTOR: free software for magnetic resonance spectroscopy data inspection, processing, simulation and analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Martin Gajdošík ◽  
Karl Landheer ◽  
Kelley M. Swanberg ◽  
Christoph Juchem
Keyword(s):  
Magnetic Resonance ◽  
Quality Management ◽  
Magnetic Resonance Spectroscopy ◽  
Data Processing ◽  
Biomedical Research ◽  
Clinical Diagnostics ◽  
Resonance Spectroscopy ◽  
User Friendliness ◽  
Wide Range

AbstractIn vivo magnetic resonance spectroscopy (MRS) is a powerful tool for biomedical research and clinical diagnostics, allowing for non-invasive measurement and analysis of small molecules from living tissues. However, currently available MRS processing and analytical software tools are limited in their potential for in-depth quality management, access to details of the processing stream, and user friendliness. Moreover, available MRS software focuses on selected aspects of MRS such as simulation, signal processing or analysis, necessitating the use of multiple packages and interfacing among them for biomedical applications. The freeware INSPECTOR comprises enhanced MRS data processing, simulation and analytical capabilities in a one-stop-shop solution for a wide range of biomedical research and diagnostic applications. Extensive data handling, quality management and visualization options are built in, enabling the assessment of every step of the processing chain with maximum transparency. The parameters of the processing can be flexibly chosen and tailored for the specific research problem, and extended confidence information is provided with the analysis. The INSPECTOR software stands out in its user-friendly workflow and potential for automation. In addition to convenience, the functionalities of INSPECTOR ensure rigorous and consistent data processing throughout multi-experiment and multi-center studies.

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