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Metabolic MR Imaging Group´s Profile image

Metabolic MR Imaging Group

Research group
01.09.2017 -
A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences
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Our group is interested in the development of novel metabolic imaging using hyperpolarised MRI to gain a better understanding of potential biomarkers for metabolic diseases in brain and in other organs such as heart. Pathological processes, such as inflammation and injury, affect the metabolic balance of brain and other organs. Often the metabolic changes precede structural alterations in tissue and therefore give an early warning sign of the developing disease. Among the common pre-clinical and clinical imaging modalities, MR-based methods are unique in that they allow a non-invasive spatial and chemical separation of a range of tissue metabolites. Furthermore, Dissolution dynamic nuclear polarisation (dDNP) method increases sensitivity of 13C-labelled metabolite markers >10,000-fold making real-time in vivo metabolic MR imaging possible. Our group is interested in the development of novel metabolic MR imaging methods and combining them with advanced 1H MRI to gain a better understanding of potential biomarkers for CVD related metabolic diseases in brain and in other organs.

Cooperation

  • Hyperpolarisation

    MR signal can be amplified up to 100% signal levels (normal signal is around 0.01% even at highest used magnetic fields) using hyperpolarisation techniques. This signal boost can be used study real-time metabolism. Dissolution Dynamic Nuclear (Hyper)Polarisation (dDNP) has so far shown most promise in the translation to in vivo use.

    The DNP technique is based on microwave-driven transfer of polarisation from free electrons to the target nuclei (e.g. 13C, 15N) at high magnetic field and low temperature (~1.4 K). During the experiment, the marker (usually a small molecular weight molecule, e.g. [1-13C]pyruvic acid) is mixed with a radical, and if necessary a glass forming agent (e.g. glycerol). It is then placed into a dedicated hyperpolariser system and exposed to microwaves for an expended period of time (e.g. 30min to 24h depending on the sample) to build up the signal. After build-up, the sample will be dissolved using a hot buffer yielding a sample that can be injected to in vitro or in vivo samples, or to a patient in clinical settings. The system is flexible in terms of the polarised molecules and also allows different nuclei (e.g. 13C, 29Si, 1H.

    In UEF, we have a prototype SpinAligner system operating at 3.35T, 6.7T or 10T (https://polarize.dk/), developed in the Technical University of Denmark by Prof. Jan Henrik Ardenkjaer-Larsen (https://hypermag.dtu.dk/).

  • Metabolic responses in the brain

    We are interested to better understand cerebral metabolic responses to hyperpolarised markers. E.g. anaesthesia is known to have systemic effects that can cause profound alterations in apparent metabolism. In our recent studies, we have explored to effects of anaesthetics on apparent metabolism of [1-<sup>13</sup>C]pyruvate. Marked differences are observed between anaesthetised and awake animals highlighting the need for careful control of anaesthesia during pre-clicinal studies.

    More info : https://pubmed.ncbi.nlm.nih.gov/34672399/

    Metabolic response to gene therapy

    Hyperpolarised [1-13C]pyruvate MRI has shown promise in monitoring therapeutic efficacy in a number of cancers including glioma. In this study together with <a href=”https://uefconnect.uef.fi/en/group/molecular-medicine/”>Molecular Medicine</a> research group, we assessed the pyruvate response to the lentiviral suicide gene therapy of herpes simplex virus-1 thymidine kinase with the prodrug ganciclovir (HSV-TK/GCV) in C6 rat glioma and compared it with traditional MR therapy markers.

    HSV-TK/GCV gene therapy was accompanied by an apparent tumour growth arrest, but no changes in water diffusion or relaxation parameters in treated animals. Treated animals also showed decreased in lactate-to-pyruvate ratio between therapy weeks, whereas the ratio was increased in control animals.

    More info : https://pubmed.ncbi.nlm.nih.gov/31909530/

    Hyperpolarised water

    Hyperpolarised water can be used to enhance signal in e.g. in vitro experiments. Currently final samples contain 2-3M water in D2O polarised to about 5-10%. The signal lifetime in mainly D2O environment is around one minute. The transfer of technique to in vivo is possible although the signal lifetime is much shorter at around 5 sec.

    The large signal increase obtained with hyperpolarised water can be used to study e.g. molecular exchange at lower magnetic fields. In our collaboration with NMR Research Unit (University of Oulu) we studied water transport in yeast using a portable 0.35 T magnet.

    More info : https://pubmed.ncbi.nlm.nih.gov/35499690/

    Hyperpolarised silicon

    Silicon-based markers can have signal lifetimes of up to an hour. Therefore they may be suitable for perfusion imaging. We have been investigating hyperpolarisation of porous nanoparticles in collaboration with Department of Applied Physics.

Keywords

brain cancer contrast agents heart hyperpolarisation magnetic resonance imaging (MRI) metabolism

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