Development of Multi-Nuclear In Vivo Magnetic Resonance Spectroscopy for Metabolic Phenotyping of Mouse Hearts
Lead Research Organisation:
University of Oxford
Department Name: RDM Cardiovascular Medicine
Abstract
Magnetic Resonance Imaging and Spectroscopy (MRI and MRS) are ideally suited for the non-invasive assessment of cardiac anatomy, function and metabolism in models of cardiovascular disease. However, while MRI for assessing global cardiac function is becoming routine in rodents, methods are lacking to assess the metabolic changes that occur in models of disease, or as a consequence of specific gene changes. Developing these methods will be highly relevant as a growing body of evidence implicates changes in energy metabolism is important in the development of heart failure, and the ability to study cardiac physiology allows the dissection of the molecular pathways involved. We have obtained funding to develop novel, multi-nuclear MRS techniques on our new 9.4 T MR system to non-invasively investigate cardiac energy metabolism and ion homeostasis experimentally. Our results should not only lead to a better understanding of cardiac pathophysiology, but will also provide the basis for more comprehensive, multi-parametric tools for future basic and translational cardiac research.
Technical Summary
Magnetic Resonance Imaging and Spectroscopy (MRI and MRS) are ideally suited for the non-invasive assessment of cardiac anatomy, function and metabolism in rodent models of cardiovascular disease. However, while MRI for assessing global cardiac function is becoming routine in rodents, methods are lacking to assess the metabolic changes that occur in surgical models of disease, or as a consequence of specific gene modifications. Developing these methods will be highly relevant as a growing body of evidence implicates changes in energy metabolism as important in the development of heart failure, and the ability to study cardiac physiology in the mouse allows the dissection of molecular pathways in a way that is not possible in humans. Therefore, we propose to develop novel, multi-nuclear MRS techniques on our new 9.4 T experimental MR system to non-invasively investigate the energy metabolism and ion homeostasis of mouse hearts in vivo. Our results should not only lead to a better understanding of cardiac pathophysiology, but will also provide the basis for more comprehensive, multi-parametric tools for future basic and translational cardiac research.
Publications
Zhang W
(2008)
Abnormal cardiac morphology, function and energy metabolism in the dystrophic mdx mouse: an MRI and MRS study.
in Journal of molecular and cellular cardiology
Yavari A
(2017)
Mammalian ?2 AMPK regulates intrinsic heart rate.
in Nature communications
Phillips D
(2010)
Mice over-expressing the myocardial creatine transporter develop progressive heart failure and show decreased glycolytic capacity.
in Journal of molecular and cellular cardiology
Maguire, ML
(2008)
Development of 31P In Vivo MRS for Metabolic Phenotyping of Mouse Hearts
Maguire, ML
(2010)
In vivo T1 mapping of 31P metabolites at short TR
Maguire ML
(2014)
Assessment of compressed sensing for high resolution in vivo mouse cardiac 23Na chemical shift imaging
in Proc ISMRM
Maguire ML
(2015)
Compressed sensing to accelerate magnetic resonance spectroscopic imaging: evaluation and application to 23Na-imaging of mouse hearts.
in Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
Lygate CA
(2013)
Investigating cardiac energetics in heart failure.
in Experimental physiology
Bohl S
(2009)
Refined approach for quantification of in vivo ischemia-reperfusion injury in the mouse heart.
in American journal of physiology. Heart and circulatory physiology
Bohl S
(2009)
Advanced methods for quantification of infarct size in mice using three-dimensional high-field late gadolinium enhancement MRI.
in American journal of physiology. Heart and circulatory physiology
Aksentijevic D
(2010)
High-energy phosphotransfer in the failing mouse heart: role of adenylate kinase and glycolytic enzymes.
in European journal of heart failure
| Title | MRS Postprocessing |
| Description | Development of a new post-processing tool to analyse MR spectroscopy data. This is a collaboration with Newcastle University. |
| Type Of Material | Physiological assessment or outcome measure |
| Year Produced | 2006 |
| Provided To Others? | Yes |
| Impact | This software was / is being used to analyse 23Na- & 31P-MRS chemical shift imaging data, which would have not been possible to be analysed. |
| Title | MRS-hardware |
| Description | Development of dedicated actively decoupled surface receive coil (to be used in conjunction with commercial volume transmit coil) to improve sensitivity of MRS experiment, developed for 31P and 23Na |
| Type Of Material | Physiological assessment or outcome measure |
| Year Produced | 2012 |
| Provided To Others? | Yes |
| Impact | Substantially improved spatial resolution of experiments within physiological acceptable scan times due to increased sensitivity |
| Title | MRS-method |
| Description | Implementation of slice-selective, 1D/2D/3D acquisition-weighted double-gated chemical shift imaging sequences. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2009 |
| Provided To Others? | Yes |
| Impact | Improved spatial localization; work is in progress to demonstrate the impact on absolute metabolite quantification |
| Description | Development of a novel post-processing framework for MRS data |
| Organisation | Newcastle University |
| Department | MRC Centre for Brain Ageing and Vitality |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Development of a graphical user interface and data handling framework Validation on in vivo data |
| Collaborator Contribution | Development of the numerical fitting algorithm |
| Impact | This project had already major impact locally in both research groups and we expect a countable output (i.e. publication, licensable software) within the next one-two years. This collaboration only involves two MR physicists at present. |
| Description | Oslo |
| Organisation | University of Oslo |
| Department | Institute for Experimental Medical Research |
| Country | Norway |
| Sector | Academic/University |
| PI Contribution | We have shared MR sequences to aid cardiac MRI and MRS at their preclinical MR system. |
| Collaborator Contribution | Oslo has shared some post-processing, which we are in the process of integrating and utilising for our research. |
| Impact | Oslo has published two peer-reviewed papers, which I have co-authored |
| Start Year | 2009 |
| Description | BC_ISMRM_2017 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Invited keynote lecture on preclinical cardiac MRI; sparked interest and discussions |
| Year(s) Of Engagement Activity | 2017 |
| Description | CRE_MLM_2011 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Participants in your research and patient groups |
| Results and Impact | Researchers stopped by at the poster presentation to discuss the science No long-term impact |
| Year(s) Of Engagement Activity | 2011 |
| Description | CRE_MLM_2012 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Participants in your research and patient groups |
| Results and Impact | Researchers stopped by at the poster presentation to discuss the science No long-term impact |
| Year(s) Of Engagement Activity | 2012 |
| Description | InAug_Lect_2017 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | Inaugural lecture as Chair in Biomedical Imaging |
| Year(s) Of Engagement Activity | 2017 |
| Description | LICAMM_Seminar_2016 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was an invited seminar at the Leeds Institute for Cardiovascular and Metabolic Medicine, which was attended by local scientists. This sparked an increased interest in preclinical (cardiac) MR. |
| Year(s) Of Engagement Activity | 2016 |
| Description | LICAMM_Seminar_2017 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | Seminar on preclinical cardiac MR & MRS; sparked interest and discussion in this subject |
| Year(s) Of Engagement Activity | 2017 |
| Description | Leeds_CBiol_Seminar_2017 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | Invited Seminar on preclinical cardiac MR; sparked interest and discussion in this modality. |
| Year(s) Of Engagement Activity | 2017 |
| Description | MedIm_Oslo_15_JES |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited Lecture at MedIm Conference for PhD Students, Oslo, November 16&17, 2015 |
| Year(s) Of Engagement Activity | 2015 |
| Description | RDM_MLM_2013 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | poster presentation |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Researchers stopped by at the poster presentation to discuss the science No long-term impact |
| Year(s) Of Engagement Activity | 2013 |
| Description | RDM_MLM_2014 |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Type Of Presentation | poster presentation |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Researchers stopped by at the poster presentation to discuss the science No long-term impact |
| Year(s) Of Engagement Activity | 2014 |
| Description | Stavanger_0317 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited lecture on cardiac MRS at the NORHEART course 'Cardiac Imaging in Research'; NORHEART is a Norwegian PhD School for heart research |
| Year(s) Of Engagement Activity | 2017 |
| Description | Wuerzburg_2018 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited Seminar at the University of Wuerzburg, Department of Experimental Radiology, which sparked discussion and interest |
| Year(s) Of Engagement Activity | 2018 |