Non-invasive Mapping of Oxygen Extraction Fraction in Human: Development of Novel Multi-Parametric Magnetic Resonance Relaxometry Imaging Methods

Supervisors: Jiabao He, Tanja Gagliardi, Yazan Masannat, Ehab Husain, Matthew Clemence

Project description:

This project aims to translate, optimise and extend quantitative oxygen extraction fraction mapping based on oxygen enriched air inspiration and magnetic resonance (MR) relaxometry imaging for human application. This underpinning bioimaging method will be pivotal in the non-invasive assessment of mitochondrial function and abnormal metabolism, fundamental in the understanding and treatment of fatigue, cancer and combating frailty.

Oxygen is essential to the aerobic energy production, while anaerobic energy production is employed under insufficient oxygen supply. The anaerobic pathway is not only inefficient in terms of amount of energy produced, but also alters the pH affecting skeletal muscle performance. Musculoskeletal disorders associated with fatigue, present compromised skeletal muscle energy regulation and abnormal pH handling. Our previous work has shown that single dose of dietary nitrate (in the form of 7cl concentrated beetroot juice) can reduce skeletal muscle oxygen deficit1, underscoring its sports performance enhancement function.

MR imaging is a promising powerful non-invasive method for assessing tissue oxygen level. Since deoxyhaemoglobin is paramagnetic, generating local field disturbance inside MR scanner, both the rate of signal dissipation (R2*) and the rate of tissue re-magnetisation (R1*) increases with the concentration of deoxyhaemoglobin (Figure 1). However, these methods are qualitative in nature, with R1* measurement influenced by hardware imperfection. Recently, a method based on the employment of inspiration of oxygen enriched air in conjunction with the observation of R1* was successfully developed and demonstrated in animal model, allowing quantitative assessment of oxygen extraction fraction2. However, R1* measurement is lengthy compared to R2* assessment, and humans can only be exposed to oxygen enriched air for a limited time. While several acceleration methods are available (namely Look-Locker, fast reordering and DESPOT1 methods)3.

We are seeking a highly motivated student, with a background in quantitative discipline, to join our vibrant multidisciplinary team. The successful candidate will conduct literature review, three main workpackages and thesis writing. The workpackages include:

  • development and optimisation of R1* and R2* acquisition schemes to estimate sensitivity and specificity,
  • development and optimisation of data feature extraction algorithms for the effective combination of R1* and R2* data,
  • implementation and validation of this new acquisition approach on our clinical MR scanner.

Aberdeen has a long tradition in medical imaging, and has the infrastructure for human imaging with sophisticated experimental setup. The multidisciplinary investigation team has extensive experience and strong track record in the development and application of novel MR methods, human imaging application, cellular biology, and scanner hardware analysis and programming. The successful candidate will be guided by Dr Jiabao He and supported by the multidisciplinary team, while benefiting from strong infrastructure and industrial partner.

The student will receive training in:

  • theory of MRI and relaxometry, a rapidly expanding area essential for in vivo human translational biological research,
  • implementation of imaging acquisition methodologies and analysis approaches, highly sought after skillsets,
  • large data management, visualisation and information extraction, critical in modern biology,
  • mitochondrial function and the oxygen consumption pathways,
  • generic skills of academic writing, presentation and project management.

Figure 1: Pilot data showing the R2*(top) and T1=1/R1 (bottom) acquired on a piece of freshly excised breast tumour specimen submerged in formalin. The three images in each row are the orthogonal images across the centre of the tumour, as indicated by blue cross. These parameters are influenced by the concentration of deoxyhaemoglobin, and subsequently oxygen extraction fraction can be obtained by modulating the blood oxygen level through the inspiration of oxygen enriched air.

References:

  1. Bentley, R., Gray, S. R., Schwarzbauer, C., et al. (2014). Dietary nitrate reduces skeletal muscle oxygenation response to physical exercise: a quantitative muscle functional MRI study. Physiological Reports, 2(7), e12089–e12089.
  2. Beeman, S. C., Shui, Y.-B., Perez-Torres, C. J., Engelbach, J. A., Ackerman, J. J. H., & Garbow, J. R. (2016). O2 -sensitive MRI distinguishes brain tumor versus radiation necrosis in murine models. Magnetic Resonance in Medicine, 75(6), 2442–2447.
  3. Eldeniz, C., Finsterbusch, J., Lin, W., & An, H. (2016). TOWERS: T-One with Enhanced Robustness and Speed. Magnetic Resonance in Medicine, 76(1), 118–126.
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