Mor-Miri Mishkovsky

Biography

I am a chemist, graduated Cum Laude in 2002 from Tel Aviv University in Israel. I obtained a PhD in Physical Chemistry from the Weizmann Institute of Science in Israel on the development of new technology for rapid detection of nuclear magnetic resonance (NMR) spectroscopic data aiming at reducing the measurement time from hours to a fraction of second with Prof. Lucio Frydman. My thesis “Methodological Developments in Ultrafast Multidimensional NMR” granted me the Auto Swartz excellence award in 2007. Since 2009 I am working with the Laboratory of Functional and Metabolic Imaging at the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, on the development of hyperpolarized (HP) magnetic resonance spectroscopy (MRS) methodologies for monitoring biochemical processes in real-time.My research is focused on the development of Magnetic Resonance (MR) Molecular Imaging by dissolution dynamic nuclear polarization (dDNP). HP agents to interrogate biochemical processes in real-time are applied in vivo in the healthy brain and disease models, aiming at improving our understanding of cerebral function and metabolism toward better clinical diagnostics and therapy.

Official source

https://people.epfl.ch/mor.mishkovsky

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The main goal of this course is to give the student a solid introduction into approaches, methods, and instrumentation used in biomedical research. A major focus is on Magnetic Resonance Imaging (MRI) and related methods, but other imaging modalities will be increasingly covered.

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People doing similar research (110)

People doing similar research

Hyperpolarized C-13-glucose magnetic resonance highlights reduced aerobic glycolysis in vivo in infiltrative glioblastoma

Jocelyne Bloch, Arnaud Comment, Cristina Ramona Cudalbu, Rolf Gruetter, Bernard Lanz, Mor-Miri Mishkovsky

Glioblastoma (GBM) is the most aggressive brain tumor type in adults. GBM is heterogeneous, with a compact core lesion surrounded by an invasive tumor front. This front is highly relevant for tumor recurrence but is generally non-detectable using standard imaging techniques. Recent studies demonstrated distinct metabolic profiles of the invasive phenotype in GBM. Magnetic resonance (MR) of hyperpolarized C-13-labeled probes is a rapidly advancing field that provides real-time metabolic information. Here, we applied hyperpolarized C-13-glucose MR to mouse GBM models. Compared to controls, the amount of lactate produced from hyperpolarized glucose was higher in the compact GBM model, consistent with the accepted "Warburg effect". However, the opposite response was observed in models reflecting the invasive zone, with less lactate produced than in controls, implying a reduction in aerobic glycolysis. These striking differences could be used to map the metabolic heterogeneity in GBM and to visualize the infiltrative front of GBM.

2021

Evaluating the potential of hyperpolarised [1-13C] L-lactate as a neuroprotectant metabolic biosensor for stroke

Lara Buscemi Estefanell, Jean-Noël Hyacinthe, Thanh Phong Kevin Lê, Mario Gaetano Lepore, Mor-Miri Mishkovsky

Cerebral metabolism, which can be monitored by magnetic resonance spectroscopy (MRS), changes rapidly after brain ischaemic injury. Hyperpolarisation techniques boost (13)C MRS sensitivity by several orders of magnitude, thereby enabling in vivo monitoring of biochemical transformations of hyperpolarised (HP) (13)C-labelled precursors with a time resolution of seconds. The exogenous administration of the metabolite L-lactate was shown to decrease lesion size and ameliorate neurological outcome in preclinical studies in rodent stroke models, as well as influencing brain metabolism in clinical pilot studies of acute brain injury patients. The aim of this study was to demonstrate the feasibility of measuring HP [1-(13)C] L-lactate metabolism in real-time in the mouse brain after ischaemic stroke when administered after reperfusion at a therapeutic dose. We showed a rapid, time-after-reperfusion-dependent conversion of [1-(13)C] L-lactate to [1-(13)C] pyruvate and [(13)C] bicarbonate that brings new insights into the neuroprotection mechanism of L-lactate. Moreover, this study paves the way for the use of HP [1-(13)C] L-lactate as a sensitive molecular-imaging biosensor in ischaemic stroke patients after endovascular clot removal.

2020

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The metabolic shift induced in human CD4+ T lymphocytes by stimulation is characterized by an upregulation of glycolysis, leading to an augmentation in lactate production. This adaptation has already been highlighted with various techniques and reported in several previous studies. We herein propose a method to rapidly and noninvasively detect the associated increase in flux from pyruvate to lactate catalyzed by lactate dehydrogenase using hyperpolarized 13C magnetic resonance, a technique which can be used for in vivo imaging. It was shown that the conversion of hyperpolarized 13C-pyruvate to 13C-lactate during the one-minute measurement increased by a mean factor of 3.6 in T cells stimulated for 5 days as compared to resting T cells. This method can be extended to other metabolic substrates and is therefore a powerful tool to noninvasively analyze T cell metabolism, possibly in vivo.

2020