Dataset Information

Imaging Fast-Acting Drug Effects in Humans Using ¹H-MRS.

ABSTRACT: Proton magnetic spectroscopy (¹H-MRS) is a noninvasive imaging technique that allows for the quantification of neurometabolic compounds at millimolar concentrations in the living human brain. This technique has been most often used to assess long-term changes in human brain metabolism in psychiatric disorders, pharmacological treatment, chronic drug use, and alcohol dependence. In contrast, the capacity of ¹H-MRS to evaluate the biochemical changes in the minutes to hours following drug consumption, which contribute to fast-acting drug-induced changes in perception, mood, cognition, and behavior, is largely unexplored. This Viewpoint highlights the utility of ¹H-MRS imaging for revealing neural mechanisms of rapid drug action in the human brain, with implications for phasic, in vivo changes in biosynthetic and catabolic pathways after drug exposure. Drawing from examples of psychostimulant drug effects, neuromodulatory input and drug-induced mood, we present strategies to optimize ¹H-MRS for noninvasively imaging fast-acting drug effects and other rapid phenomena within the living human brain. These approaches could provide powerful tools for both basic research and drug development.

SUBMITTER: White TL

PROVIDER: S-EPMC7478238 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Imaging Fast-Acting Drug Effects in Humans Using 1H-MRS.

White Tara L TL Gonsalves Meghan A MA

ACS chemical neuroscience 20200825 17

Proton magnetic spectroscopy (1H-MRS) is a noninvasive imaging technique that allows for the quantification of neurometabolic compounds at millimolar concentrations in the living human brain. This technique has been most often used to assess long-term changes in human brain metabolism in psychiatric disorders, pharmacological treatment, chronic drug use, and alcohol dependence. In contrast, the capacity of 1H-MRS to evaluate the biochemical changes in the minutes to hours f ...[more]

PMID: 32840110

Similar Datasets

Project description:PurposeNon-invasive imaging is a key clinical tool for detection and treatment monitoring of infections. Existing clinical imaging techniques are frequently unable to distinguish infection from tumors or sterile inflammation. This challenge is well-illustrated by prosthetic joint infections that often complicate joint replacements. D-methyl-11C-methionine (D-11C-Met) is a new bacteria-specific PET radiotracer, based on an amino acid D-enantiomer, that is rapidly incorporated into the bacterial cell wall. In this manuscript, we describe the biodistribution, radiation dosimetry, and initial human experience using D-11C-Met in patients with suspected prosthetic joint infections.Methods614.5 ± 100.2 MBq of D-11C-Met was synthesized using an automated in-loop radiosynthesis method and administered to six healthy volunteers and five patients with suspected prosthetic joint infection, who were studied by PET/MRI. Time-activity curves were used to calculate residence times for each source organ. Absorbed doses to each organ and body effective doses were calculated using OLINDA/EXM 1.1 with both ICRP 60 and ICRP 103 tissue weighting factors. SUVmax and SUVpeak were calculated for volumes of interest (VOIs) in joints with suspected infection, the unaffected contralateral joint, blood pool, and soft tissue background. A two-tissue compartment model was used for kinetic modeling.ResultsD-11C-Met was well tolerated in all subjects. The tracer showed clearance from both urinary (rapid) and hepatobiliary (slow) pathways as well as low effective doses. Moreover, minimal background was observed in both organs with resident micro-flora and target organs, such as the spine and musculoskeletal system. Additionally, D-11C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUVmax and SUVpeak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P < 0.01). Furthermore, higher distribution volume and binding potential were observed in suspected infections compared to the unaffected joints.ConclusionD-11C-Met has a favorable radiation profile, minimal background uptake, and fast urinary extraction. Furthermore, D-11C-Met showed increased uptake in areas of suspected infection, making this a promising approach. Validation in larger clinical trials with a rigorous gold standard is still required.

Project description:Newer antidepressants are needed for the many individuals with major depressive disorder (MDD) that do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent evidence from clinical trials shows that the NMDA antagonist ketamine is a revolutionary novel antidepressant because it acts rapidly and is effective for treatment-resistant patients. A single infusion of ketamine alleviates depressive symptoms in treatment-resistant depressed patients within hours and these effects may be sustained for up to 2 weeks. Although the discovery of ketamine's effects has reshaped drug discovery for antidepressants, the psychotomimetic properties of this compound limit the use of this therapy to the most severely ill patients. In order to develop additional antidepressants like ketamine, adequate preclinical behavioral screening paradigms for fast-acting antidepressants need to be established and used to identify the underlying neural mechanisms. This review examines the preclinical literature attempting to model the antidepressant-like effects of ketamine. Acute administration of ketamine has produced effects in behavioral screens for antidepressants like the forced swim test, novelty suppression of feeding and in rodent models for depression. Protracted behavioral effects of ketamine have been reported to appear after a single treatment that last for days. This temporal pattern is similar to its clinical effects and may serve as a new animal paradigm for rapid antidepressant effects in humans. In addition, protracted changes in molecules mediating synaptic plasticity have been implicated in mediating the antidepressant-like behavioral effects of ketamine. Current preclinical studies are examining compounds with more specific pharmacological effects at glutamate receptors and synapses in order to develop additional rapidly acting antidepressants without the hallucinogenic side effects or abuse potential of ketamine.

Dataset Information

Imaging Fast-Acting Drug Effects in Humans Using ¹H-MRS.

Publications

Imaging Fast-Acting Drug Effects in Humans Using <sup>1</sup>H-MRS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets