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Non-invasive cardiac metabolism assessment using ultra-high field (7T) MR Spectroscopy


   Radcliffe Department of Medicine


About the Project

My group at the Oxford Centre for Clinical Magnetic Resonance Research (OCMR) is focused on development of new methods for cardiac metabolism assessment using magnetic resonance spectroscopy (MRS). This project will utilize the increased signal-to-noise ratio of the ultrahigh field (7T) system, as well as its potential for cardio-respiratory motion detection and correction. Previously unexplored metabolic pathways can be investigated using ultrahigh field MRS in vivo and motion correction allows free-breathing acquisition essential for investigation of metabolism in patients with cardiovascular and metabolic disorders.

MRS is a technique capable of uncovering changes in tissue chemical composition and energy metabolism non-invasively in vivo. This is particularly attractive for organs where invasive biopsy is too risky, e.g., the heart. While most changes in metabolism occur in disease, there are also physiological changes that come naturally with ageing. To reliably quantify the level of metabolic impairment caused by the disease the underlying physiological changes need to be well described.

Our current focus is on the development of proton (1H)-MRS methods with high sensitivity to uncover variations in low concentration in the heart, i.e. creatine, acetyl-carnitine and carnosine that are essential for the creatine-kinase energy shuttle, acetyl-group buffering for the PDH cycle and pH-buffering in the heart, respectively. These methods will utilise motion tracking methods developed by Dr Aaron Hess (OCMR), based on the use the RF properties of array coils (coil-to-coil coupling) to track tissue. Ultimately, these techniques will be combined with our state-of-the-art methods for direct energy metabolism assessment using phosphorus (31P)-MRS.

The MRS methods my group develops are applied first in groups of healthy volunteers to uncover changes in cardiac metabolites, e.g., creatine, acetyl-carnitine or carnosine caused by lifestyle-interventions or normal physiological ageing. This is essential to unravel real disease-related impairments from physiological deviations.

The focus of this work will be on pulse sequences such as STEAM, Semi-LASER and CSI with water suppression cycling/or metabolite cycling scheme for improved frequency alignment. The collaboration with the group of Dr Hess will allow access to high-end motion tracking and correction techniques and my network of collaborators offers quick dissemination of the methodologies nationally and internationally. This DPhil is well suited to someone interested in the interface between biology and physics. Good software design skills, including C++ and Matlab are important, and an understanding of cardiac physiology is preferable.

The student will be trained in MRI pulse sequence programming and spectroscopy acquisition and analysis methods, they will be by the group in OCMR and will have also access to the graduate MR course organized by the Wellcome Centre for Integrative Neuroimaging (WIN).

Additional supervision will be provided by Dr Aaron Hess and Dr Jack JJ Miller.

Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide-range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division’s Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.


References

https://doi.org/10.3389/fphys.2020.00644

https://doi.org/10.21037/cdt.2019.12.13

https://doi.org/10.1002/mrm.27884

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