Non invasive visualization of enzyme activity with hyperpolarized MRI developing novel translational molecular imaging biomakers

Lead Research Organisation: University of Nottingham
Department Name: School of Medicine

Abstract

Non invasive visualization of enzyme activity with hyperpolarized MRI developing novel translational molecular imaging biomakers

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/R506394/1 01/11/2017 30/10/2021
1996456 Studentship BB/R506394/1 01/11/2017 30/10/2021 Andrea Torchi
 
Description By using Magnetic Resonance Spectroscopy (MRS) enhanced by Dynamic Nuclear Polarisation (DNP), we non-invasively measured the enzymatic conversion rates of pyruvate to lactate, alanine and bicarbonate in healthy human calf muscle under exercise. To the best of our knowledge, this is the first time that a clinical DNP study has been performed on skeletal muscle. We successfully completed the measurements in three volunteers and we saw differences in the conversion rates, that are potentially linked to the degree of endurance training of the volunteers and the intensity of the exercise.
Exploitation Route The main purposes of this study are:
1) to acquire skeletal muscle activity data in healthy controls, in order to measure the physiological response of the muscle to intense effort and to provide a comparison for future studies on pathological conditions affecting the muscle tissue.
2) to prepare for more complex (e.g. multi-voxel) DNP experiments in the new Nottingham DNP facility.



DNP-enhanced MRI could have a significant impact in the medical field, because of the possibility to quantify and localise different downstream metabolites in-vivo and in real time with a sensitivity and a resolution that are not obtainable without DNP hyperpolarisation. For instance, the ability of DNP to detect local lactate levels could potentially offer a radiation-free alternative to PET scans for some types of cancer therapy monitoring.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description School of Medicine Doctoral Programmes Committee Fund
Amount £596 (GBP)
Organisation University of Nottingham 
Sector Academic/University
Country United Kingdom
Start 07/2019 
End 10/2019
 
Description Student Travel Stipend for the World Molecular Imaging Congress 2019
Amount $650 (USD)
Organisation World Molecular Imaging Society 
Sector Learned Society
Country United States
Start 07/2019 
End 09/2019
 
Title Multisite metabolic model for analysis of DNP data 
Description This metabolic model describes the processes of perfusion of DNP hyperpolarised pyruvate from the bloodstream to the muscle, the conversion of pyruvate into lactate, alanine and bicarbonate, and the decay of the magnetic resonance signals of those metabolites due to T1 relaxation and radiofrequency pulses. The purpose of the model is to estimate the metabolic conversion rates from the measured metabolite signals, given an approximate knowledge of the T1 and flip angle values. 
Type Of Material Computer model/algorithm 
Year Produced 2019 
Provided To Others? No  
Impact This metabolic model allowed us to estimate the enzymatic conversion rates of pyruvate to lactate, alanine and bicarbonate in the three DNP clinical experiments that we completed so far. 
 
Description BBSRC-DTP Spring Conference, 9th-10th May 2019, Nottingham, UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact The BBSRC-DTP Spring School is a yearly event dedicated to PhD students funded by BBSRC, where they can share their research with other PhD students by presenting a talk or a poster. The event includes seminars from external speakers and training sessions as well.
In the 2019 BBSRC-DTP Spring School I presented a poster titled "In vivo non-invasive monitoring of muscle metabolism with Magnetic Resonance Spectroscopy", and I answered questions by other students about the research I was working on.
Year(s) Of Engagement Activity 2018,2019