Metabolic MR Imaging Group

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Research group

01.09.2017 -

A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences

Information People Publications

Leaders

Mikko Kettunen

Research Director

A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences

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

Biomedical MRI 01.01.1995 -

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

Leaders

Mikko Kettunen

Research Director

A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences

Post-doctoral Researchers

Jessica Rosa

Project Researcher

Institute of Biomedicine, School of Medicine, Faculty of Health Sciences

Doctoral Researchers

Aravinth Ravichandran

Project Researcher

A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences

Technicians

Maarit Pulkkinen

Senior Laboratory Technician

A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences

Supporting Staff

Taisto Kuosmanen

Project Controller

Financial Services, University Services

Publications

17 items

Refine your search

Metabolic MR Imaging Group

Leaders

Mikko Kettunen

Cooperation

Hyperpolarised MRI

Hyperpolarisation

Recent projects

Keywords

Leaders

Mikko Kettunen

Post-doctoral Researchers

Jessica Rosa

Doctoral Researchers

Aravinth Ravichandran

Technicians

Maarit Pulkkinen

Supporting Staff

Taisto Kuosmanen

Publications

Data-Driven Regularization Parameter Selection in Dynamic MRI

Metabolism of hyperpolarised [1-13C]pyruvate in awake and anaesthetised rat brains

Cyclodextrin-based organic radical contrast agents for in vivo imaging of glioma

Detection of lentiviral suicide gene therapy in C6 rat glioma using hyperpolarised [1-13 C]pyruvate

Assessment of the Relaxation-Enhancing Properties of a Nitroxide-Based Contrast Agent TEEPO-Glc with In Vivo Magnetic Resonance Imaging

Hyperpolarized MRI for Studying Tumor Metabolism

Analysis of 13 C and 14 C labeling in pyruvate and lactate in tumor and blood of lymphoma-bearing mice injected with 13 C- and 14 C-labeled pyruvate

Designed inorganic porous nanovector with controlled release and MRI features for safe administration of doxorubicin

Dynamic MRI reconstruction from undersampled data with an anatomical prescan

State estimation in dynamic MRI

Effects of fasting on serial measurements of hyperpolarized [1-13C]pyruvate metabolism in tumors

Tailored Dual PEGylation of Inorganic Porous Nanocarriers for Extremely Long Blood Circulation in Vivo

13C magnetic resonance spectroscopic imaging of hyperpolarized [1-13C, U-2H5] ethanol oxidation can be used to assess aldehyde dehydrogenase activity in vivo

13C magnetic resonance spectroscopy measurements with hyperpolarized [1-13C] pyruvate can be used to detect the expression of transgenic pyruvate decarboxylase activity in vivo

Hyperpolarized [U-2H, U-13C]Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells

MRI with hyperpolarised [1-13C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model

Detection of transgene expression using hyperpolarized 13 C urea and diffusion-weighted magnetic resonance spectroscopy