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

10 25 50
 
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