Project

Back to overview

Multi-nuclear magnetic resonance spectroscopy (MRS) and imaging (MRI) on a clinical whole-body MR-system: Lipid organelles and mitochondria

English title Multi-nuclear magnetic resonance spectroscopy (MRS) and imaging (MRI) on a clinical whole-body MR-system: Lipid organelles and mitochondria
Applicant Boesch Chris
Number 149779
Funding scheme Project funding (Div. I-III)
Research institution Abt. Magnetresonanz-Spektroskopie u. Method. Departement für Klinische Forschung Universität Bern
Institution of higher education University of Berne - BE
Main discipline Physiology : other topics
Start/End 01.12.2013 - 31.12.2016
Approved amount 520'000.00
Show all

All Disciplines (2)

Discipline
Physiology : other topics
Endocrinology

Keywords (6)

Heart; Liver; Skeletal muscle; Insulin resistance; Magnetic resonance imaging; Magnetic resonance spectroscopy

Lay Summary (German)

Lead
Magnetresonanz-Spektroskopie (MRS) kann wichtige Zellorganellen im menschlichen Körper berührungsfrei charakterisieren.
Lay summary

Die Magnetresonanz Bildgebung (MRI) und Spektroskopie (MRS) erlauben die berührungsfreie und unschädliche Untersuchung von Anatomie und Stoffwechsel des menschlichen Körpers. Besonders die MRS von verschiedenen Typen von stabilen Atomkernen (1-Wasserstoff, 13-Kohlenstoff, 31-Phosphor) erlaubt dabei, eine Vielzahl von Stoffwechsel-Produkten im Körper zu beobachten. Zwar ist die Magnetresonanz nicht sehr sensitiv, da sie im Gegensatz zu den viel empfindlicheren nuklearmedizinischen Methoden mit nieder-energetischen Radiowellen arbeitet. Dies ist einerseits der Grund, dass die Magnetresonanz zu Recht als sehr sicher eingeschätzt wird, anderseits aber müssen die beobachteten Stoffwechselprodukte eine gewisse minimale Konzentration aufweisen. Trotz dieser Einschränkung können mit der 1H/13C/31P-MRS wichtige Substanzen wie z.B. Glykogen, ATP, Phosphokreatin, intrazelluläre Lipide usw. in verschiedenen Organen beobachtet werden.

Zwei wichtige Bausteine der menschlichen und tierischen Zelle sind im Fokus dieses Projektes: intrazelluläre Lipidtropfen und Mitochondrien. Diese benachbarten Zell-Organellen spielen bei Insulinresistenz und Diabetes eine wichtige Rolle. Mittels MRS können Stoffwechselvorgänge in diesen Organellen beobachtet werden und diese Studie versucht nun, über die Stoffwechselprodukte die Organellen selbst zu charakterisieren.

Die Studie zielt in einem ersten Schritt darauf, die Methodik zu verbessern, um reproduzierbare und aussagekräftige Resultate zu erhalten. In einem nächsten Schritt sollen die entwickelten und verbesserten Methoden in einer relativ kleinen Zahl von Versuchspersonen angewandt werden, um alltägliche Veränderungen zu dokumentieren (z.B. Frage: ist die MRS reproduzierbar und empfindlich genug, um Veränderungen des Leberstoffwechsels nach der Einnahme von verschiedenen Kohlenhydraten zu dokumentieren?). Auf dem aufbauend sollen dann Erkrankungen der Leber untersucht werden, welche heute noch die Entnahme einer Biopsie verlangen.

Direct link to Lay Summary Last update: 21.11.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Postexercise repletion of muscle energy stores with fructose or glucose in mixed meals.
Rosset Robin, Lecoultre Virgile, Egli Léonie, Cros Jérémy, Dokumaci Ayse Sila, Zwygart Karin, Boesch Chris, Kreis Roland, Schneiter Philippe, Tappy Luc (2017), Postexercise repletion of muscle energy stores with fructose or glucose in mixed meals., in The American journal of clinical nutrition, [ePub ahead], N/A.
Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy.
Christ Emanuel R, Egger Andrea, Allemann Sabin, Buehler Tania, Kreis Roland, Boesch Chris (2016), Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy., in Scientific reports, 6, 19310-19310.
FISICO: Fast Image SegmentatIon COrrection.
Valenzuela Waldo, Ferguson Stephen J, Ignasiak Dominika, Diserens Gaëlle, Häni Levin, Wiest Roland, Vermathen Peter, Boesch Chris, Reyes Mauricio (2016), FISICO: Fast Image SegmentatIon COrrection., in PloS one, 11(5), 0156035-0156035.
Handbook of Magnetic Resonance Spectroscopy In Vivo, Chapter Muscle Studies by H-1 MRS
Boesch Chris, Kreis Roland (2016), Handbook of Magnetic Resonance Spectroscopy In Vivo, Chapter Muscle Studies by H-1 MRS, in Griffiths John and Bottomley Paul (ed.), John Wiley & Sons, WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA , 1097-1108.
Influence of muscle fiber orientation on water and metabolite relaxation times, magnetization transfer, and visibility in human skeletal muscle.
MacMillan Erin Leigh, Bolliger Christine Sandra, Boesch Chris, Kreis Roland (2016), Influence of muscle fiber orientation on water and metabolite relaxation times, magnetization transfer, and visibility in human skeletal muscle., in Magnetic resonance in medicine, 75(4), 1764-70.
Metabolic and hormonal response to intermittent high-intensity and continuous moderate intensity exercise in individuals with type 1 diabetes: a randomised crossover study.
Bally Lia, Zueger Thomas, Buehler Tania, Dokumaci Ayse S, Speck Christian, Pasi Nicola, Ciller Carlos, Paganini Daniela, Feller Katrin, Loher Hannah, Rosset Robin, Wilhelm Matthias, Tappy Luc, Boesch Chris, Stettler Christoph (2016), Metabolic and hormonal response to intermittent high-intensity and continuous moderate intensity exercise in individuals with type 1 diabetes: a randomised crossover study., in Diabetologia, 59(4), 776-84.
Methodological and physiological test-retest reliability of (13) C-MRS glycogen measurements in liver and in skeletal muscle of patients with type 1 diabetes and matched healthy controls.
Buehler Tania, Bally Lia, Dokumaci Ayse Sila, Stettler Christoph, Boesch Chris (2016), Methodological and physiological test-retest reliability of (13) C-MRS glycogen measurements in liver and in skeletal muscle of patients with type 1 diabetes and matched healthy controls., in NMR in biomedicine, 29(6), 796-805.
Motion-insensitive determination of B1+ amplitudes based on the bloch-siegert shift in single voxels of moving organs including the human heart.
Dokumaci Ayse Sila, Pouymayou Bertrand, Kreis Roland, Boesch Chris (2016), Motion-insensitive determination of B1+ amplitudes based on the bloch-siegert shift in single voxels of moving organs including the human heart., in Magnetic resonance in medicine, 75(5), 1867-74.
Regulation of fuel metabolism during exercise in hypopituitarism with growth hormone-deficiency (GHD).
Zueger Thomas, Loher Hannah, Egger Andrea, Boesch Chris, Christ Emanuel (2016), Regulation of fuel metabolism during exercise in hypopituitarism with growth hormone-deficiency (GHD)., in Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the Inte, 29, 39-44.
Test-retest analysis of multiple (31) P magnetization exchange pathways using asymmetric adiabatic inversion.
Pouymayou Bertrand, Buehler Tania, Kreis Roland, Boesch Chris (2016), Test-retest analysis of multiple (31) P magnetization exchange pathways using asymmetric adiabatic inversion., in Magnetic resonance in medicine, [ePub ahead], N/A.
The Flexibility of Ectopic Lipids.
Loher Hannah, Kreis Roland, Boesch Chris, Christ Emanuel (2016), The Flexibility of Ectopic Lipids., in International journal of molecular sciences, 17(9), E1554.
Comparison of (31)P saturation and inversion magnetization transfer in human liver and skeletal muscle using a clinical MR system and surface coils.
Buehler Tania, Kreis Roland, Boesch Chris (2015), Comparison of (31)P saturation and inversion magnetization transfer in human liver and skeletal muscle using a clinical MR system and surface coils., in NMR in biomedicine, 28(2), 188-99.
Correction tool for Active Shape Model based lumbar muscle segmentation.
Valenzuela Waldo, Ferguson Stephen J, Ignasiak Dominika, Diserens Gaelle, Vermathen Peter, Boesch Chris, Reyes Mauricio (2015), Correction tool for Active Shape Model based lumbar muscle segmentation., in Conf Proc IEEE Eng Med Biol Soc., IEEE, New York, NY 10016-5997 USA.
Exercise efficiency relates with mitochondrial content and function in older adults.
Broskey Nicholas T, Boss Andreas, Fares Elie-Jacques, Greggio Chiara, Gremion Gerald, Schlüter Leo, Hans Didier, Kreis Roland, Boesch Chris, Amati Francesca (2015), Exercise efficiency relates with mitochondrial content and function in older adults., in Physiological reports, 3(6), e12418.
Hepatic and intramyocellular glycogen stores in adults with type 1 diabetes and healthy controls.
Bally L, Buehler T, Dokumaci A S, Boesch C, Stettler C (2015), Hepatic and intramyocellular glycogen stores in adults with type 1 diabetes and healthy controls., in Diabetes research and clinical practice, 109(1), 1-3.
Metabolic inflexibility and insulin resistance in obese adolescents with non-alcoholic fatty liver disease.
Lee SoJung, Rivera-Vega Michelle, Alsayed Hany Mohamed Abdel Aal, Boesch Chris, Libman Ingrid (2015), Metabolic inflexibility and insulin resistance in obese adolescents with non-alcoholic fatty liver disease., in Pediatric diabetes, 16(3), 211-8.
Proton diffusion tensor spectroscopy of metabolites in human muscle in vivo.
Brandejsky Vaclav, Boesch Chris, Kreis Roland (2015), Proton diffusion tensor spectroscopy of metabolites in human muscle in vivo., in Magnetic resonance in medicine, 73(2), 481-7.
Sugar- and artificially sweetened beverages and intrahepatic fat: A randomized controlled trial.
Campos Vanessa, Despland Camille, Brandejsky Vaclav, Kreis Roland, Schneiter Philippe, Chiolero Arnaud, Boesch Chris, Tappy Luc (2015), Sugar- and artificially sweetened beverages and intrahepatic fat: A randomized controlled trial., in Obesity (Silver Spring, Md.), 23(12), 2335-9.
Cardiac lipid levels show diurnal changes and long-term variations in healthy human subjects.
Ith Michael, Stettler Christoph, Xu Jian, Boesch Chris, Kreis Roland (2014), Cardiac lipid levels show diurnal changes and long-term variations in healthy human subjects., in NMR in biomedicine, 27(11), 1285-92.
Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training.
Broskey Nicholas T, Greggio Chiara, Boss Andreas, Boutant Marie, Dwyer Andrew, Schlueter Leopold, Hans Didier, Gremion Gerald, Kreis Roland, Boesch Chris, Canto Carles, Amati Francesca (2014), Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training., in The Journal of clinical endocrinology and metabolism, 99(5), 1852-61.

Collaboration

Group / person Country
Types of collaboration
F.Amati, Physiology, University Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
E.Canet-Soulas et al. INSERM U630, University of Lyon France (Europe)
- Publication
M.A.Thomas, David Geffen School of Medicine at UCLA, Los Angeles CA United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
T.Stellingswerff, J.Decombaz, Nestle Research Center, Lausanne Switzerland (Europe)
- Publication
H.Hoppeler et al., Systematic Anatomy, University Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
P Carlier, C.Wary, Institut de Myologie, AIM – CEA, Paris France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel
J.Machann, Dept. of Diagnostic Radiology, Eberhard-Karls-University Tübingen Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
S.J. Lee, S.Arslanian, Children's Hospital, University of Pittsburgh School of Medicine United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ESMRMR Annual Meeting, Magn Reson Mater Phys Biol Med 2016 29 (Suppl 1):S507 Poster Towards a model-free separation of intra- and extra-myocellular lipids (IMCL/EMCL) 29.09.2016 Vienna, Austria Pouymayou Bertrand; Kreis Roland; Boesch Chris;
Annual Meeting of ISMRM, Plenary Lecture Talk given at a conference MR of Lipids in Biological Processes & Disease States 09.05.2016 Suntec, Singapore, Singapore Boesch Chris;
Annual Meeting of ISMRM, Proc Intl Soc Magn Reson Med 2016;24:1105 Talk given at a conference Observation of 31P magnetization transfer at 3 Tesla using asymmetric adiabatic inversion and two different fitting strategies 09.05.2016 Suntec Singapore, Singapore Kreis Roland; Bühler Tania; Boesch Chris; Pouymayou Bertrand;
Annual Meeting of ISMRM, Proc Intl Soc Magn Reson Med 2016;24:0720 Talk given at a conference Ingestion of Carbohydrate Solutions of Glucose-Fructose Versus Glucose-Alone During a Prolonged Exercise in Individuals with Type 1 Diabetes 09.05.2016 Singapore, Singapore Boesch Chris; Dokumaci Ayse Sila; Bühler Tania;
ESMRMR Annual Meeting, Magn Reson Mater Phys Biol Med 2015;28 Suppl.1:271 Talk given at a conference Simultaneous observation and analysis of multiple 31P magnetization exchange pathways using asymmetric adiabatic inversion 01.10.2015 Edinburgh, Great Britain and Northern Ireland Pouymayou Bertrand; Kreis Roland; Bühler Tania; Boesch Chris;
51st Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), DIABETOLOGIA, 58: S286-S287 (2015) Poster Glucose metabolism under differing exercise conditions in type 1 diabetes 14.09.2015 Stockholm, Sweden Boesch Chris; Bühler Tania; Tappy Luc; Dokumaci Ayse Sila;
Annual Meeting of ISMRM, Proc Intl Soc Magn Reson Med 2015;23:4082 Poster Quantification of hepatic and myocellular glycogen after two days of diet and activity standardization: a 13C MRS reproducibility study in individuals with type 1 diabetes and matched healthy controls 30.05.2015 Toronto, Canada Bühler Tania; Dokumaci Ayse Sila; Boesch Chris;
Annual Meeting of ISMRM, Proc Intl Soc Magn Reson Med 2015;23:489 Talk given at a conference Motion-insensitive sequence for single-voxel determination of B1+ by Bloch-Siegert shift in moving organs including the human heart 30.05.2015 Toronto, Canada Dokumaci Ayse Sila; Kreis Roland; Pouymayou Bertrand; Boesch Chris;
Annual Meeting of ISMRM, Proc Intl Soc Magn Reson Med 2015;23:800 Talk given at a conference Carbohydrate requirements during intermittent high intensity exercise compared to continuous moderate intensity exercise in individuals with type 1 diabetes 30.05.2015 Toronto, Canada Bühler Tania; Dokumaci Ayse Sila; Boesch Chris;
Annual Meeting ISMRM, invited educational lecture (COMBINED EDUCATIONAL & SCIENTIFIC SESSION: Diabetes & Muscle Imaging) Talk given at a conference MR Imaging & Spectroscopy of the Influence of Insulin Resistance 15.05.2014 Milano, Italy Boesch Chris;
Annual Meeting ISMRM, Proc.Intl.Soc.Magn.Reson.Med. 2014; 22: 0826. Talk given at a conference Proton Diffusion Tensor Spectroscopy of Metabolites in Human Muscle In Vivo 10.05.2014 Milano, Italy Kreis Roland; Boesch Chris;
61st Annual Meeting of the American-College-of-Sports-Medicine, MEDICINE AND SCIENCE IN SPORTS AND EXERCISE 46 (5): 753 Poster Do Skeletal Muscle Mitochondria Play A Role In Making Us More Efficient For Endurance Exercise? 01.04.2014 Atlanta GA, United States of America Kreis Roland; Boesch Chris;


Associated projects

Number Title Start Funding scheme
170062 The aging mitochondria, dynamic and protective adaptations of exercise 01.12.2016 Project funding (Div. I-III)
156952 Magnetic resonance techniques to determine metabolite levels: extending scope and clinical robustness 01.12.2014 Project funding (Div. I-III)
138150 Advanced multi-modal MR Imaging and Spectroscopy for Comprehensive Characterization of Renal Function in Native and Transplanted Kidneys. 01.03.2012 Project funding (Div. I-III)
132935 Multi-nuclear magnetic resonance spectroscopy (MRS) and imaging (MRI) on a clinical whole-body MR-system: insulin resistance, ageing, and physical activity 01.12.2010 Project funding (Div. I-III)
135743 Magnetic Resonance Techniques to Investigate Human Brain Physiology: Acquisition and Postprocessing Tools to Advance Spectroscopy at Clinical and High Magnetic Fields 01.06.2011 Project funding (Div. I-III)
156167 Role of hepatic de novo lipogenesis in metabolic and brain responses to sucrose overfeeding 01.10.2014 Project funding (Div. I-III)
138428 Modulation of fructose's metabolic effects by environmental factors 01.10.2011 Project funding (Div. I-III)
157744 Magnetic Resonance (MR) - Elastography for Characterization of Liver Disease 01.12.2014 R'EQUIP

Abstract

Background:Insulin resistance (IR) is a common denominator of a complex of endemic diseases. This includes obesity, the “metabolic syndrome”, and overt Type 2 diabetes mellitus, all with severe cardiovascular consequences. The related non-alcoholic fatty liver disease (NAFLD) can lead to steatohepatitis (NASH) and subsequently to hepatocellular carcinoma. Lipotoxicity, mitochondrial impairment, inflammation, and oxidative stress are possible culprits leading to IR. Since most of these mechanisms are related to the complex of lipid droplets and mitochondria, these organelles are increasingly studied. In particular lipid organelles are organized to a higher degree and perform more complex functions than assumed previously.Magnetic resonance spectroscopy (MRS) is a non-invasive, non-ionizing tool for in vivo studies in humans and animals that is related to high-resolution nuclear magnetic resonance (HR-NMR) and magic angle spinning (HR-MAS). It can provide information on the complex of lipid droplets and mitochondria and is thus an attractive tool to validate hypotheses in vivo that have been generated in well-defined systems of extracts, cells, and excised tissue.Hypotheses:This proposal includes three sub-projects:1) Characterization of lipid organelles (lipid composition).2) ATP synthase flux measured by 31P-MRS saturation transfer.3) Multinuclear MRS of liver diseases (NAFLD, NASH).We hypothesize that in vivo MRS is sensitive enough to detect:A) Changes of composition of ectopic lipids in muscle, liver, and heart with exercise, diet, and under influence of IR.B) Influences of diet, exercise, and IR on the flux of ATP synthase measured by 31P-MRS saturation transfer.C) Differences between NAFLD and NASH in vivo using multinuclear MRS.Methodology:A feasibility study has shown that in vivo MRS is able to follow changes of liver metabolism (lipid content, glycogen, high-energy phosphates, and ATP synthase flux) in a cohort of healthy subjects. However, it needs further development to overcome the inherently low signal-to-noise-ratio and to distinguish the distinct lipid resonances to determine lipid composition. In addition, in vivo single-voxel MRS will be complemented with 2-(spectral)-dimensional MRS and it will be correlated with HR-MAS of excised tissue from muscle and (clinically indicated) liver biopsies. In a proof-of-principle with small cohorts, effects of exercise, diet, and IR will be shown.Importance and impact:Our network of MR-group, physiologists, and clinicians is working continuously on the development and - equally important - the application of in vivo MRS methods. The truly translational nature of HR-NMR, HR-MAS, and in vivo MRS in animals and humans allows for a stepwise increment of complexity of the examined system. This grant proposal will combine and foster the combination of HR-MAS in excised yet intact tissue with in vivo MRS in human subjects. This will have impact on the understanding of IR and will allow for a validation of hypotheses from well-defined systems in the complex environment of the human body.
-