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Studying low-concentration metabolites in the brain with CEST-linescan


NeuroSpin researchers, in collaboration with Iramis and the Università Statale di Milano, have developed a CEST magnetic resonance spectroscopy sequence that allows them to detect and confirm the presence of three dipeptides in the brain and skeletal muscle of adult rats and thus to consider future studies of their physiological role. 

Published on 15 November 2022

CEST for in vivo studying metabolites

There is a growing need to study the presence and fate of metabolites during pathophysiological processes. This information provides information on the mechanisms involved in these processes and, above all, can reveal signatures that can be used as tools for diagnosis, monitoring of disease progression and/or response to treatment. Large-scale methods, such as metabolomics, are the methods of choice. But other methods can be particularly useful.

The CEST (Chemical Exchange Saturation Transfer) magnetic resonance spectroscopy modality allows the detection and quantification of metabolites in vivo. It is based on the exchange of protons of the metabolite under study with those of water. The CEST technique has already demonstrated its interest in detecting certain important metabolites such as glucose or glutamate and in replacing other MRI modalities that require the injection of a contrast agent that can cause undesirable effects. However, it is still difficult with this technique to quantify molecules that are less abundant and/or for which the proton exchange rate is very slow.

In vivo Detection OF CARNOSINE AND ITS TWO DERIVATIVES

In collaboration with a team from Iramis and the Università Statale di Milano in Italy, a team from BAOBAB (NeuroSpin department) has developed a CEST sequence optimised for the detection of a dipeptide, carnosine, and its two derivatives, anserine and homocarnosine. Carnosine is present in skeletal muscle but also in the olfactory bulb. Present in the brain but at very low concentrations, it is known to be involved in the cellular response to high levels of inflammation and is a potential target for new therapies to prevent strokes. Moreover, it is a particularly sensitive molecule to measure via blood samples in rodents and humans, increasing the demand for non-invasive and accurate measurements.

Their method, CEST-linescan (CEST-LS), significantly reduces the acquisition time compared to a conventional CEST, thus increasing signal stability while maintaining an equivalent signal-to-noise ratio.

With CEST-linescan, the researchers detected carnosine and its two derivatives in vivo in the brain and skeletal muscle of adult rats. CEST-linescan could be useful for non-invasively studying the (patho)-physiological roles of these three molecules.

Contact Joliot :

Luisa Ciobanu (luisa.ciobanu@cea.fr

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