My research concerns the application and development of novel multi-model biomedical imaging systems towards answering important and clinically relevant questions. I have a genuine passion for non-invasive imaging techniques that can be used across the entire patient age range. Once such method, MRI has found application across several medical research fields including Neuroimaging (including functional MRI), Oncology, Cardiovascular research, Musculoskeletal and Liver/Gastrointestinal imaging. However in the majority of cases an in-depth understanding of the complex MRI signal source in terms of the underlying physics, chemistry and biology is lacking. As such, my research strategy endeavours to take a multi-model imaging approach; using data to parameterise biophysical models. In turn data from these models can feedback to the laboratory helping further develop and refine the biomedical imaging techniques. Together this can help develop the imaging techniques for both improved diagnostics and novel therapeutics.
My research focuses on developing multi-modal imaging technology to investigate the underlying neural and haemodynamic mechanisms of the functional (f)MRI Blood Oxygenation Level Dependent (BOLD) signal (fig1a). The mechanisms of neurovascular coupling and not fully understood and therefore interpretation of BOLD fMRI signals is confounded; even in control conditions. My PhD thesis “Investigation of the haemodynamic response: fMRI techniques with concurrent optical measures of cerebral blood flow and volume” utilised different brain imaging methods, specifically fMRI, laser Doppler flowmetry and optical imaging spectroscopy in the animal model (Kennerley, A. J., et.al. (2005). Magn Reson Med. 54, 354-365; Kennerley, A.J., et.al. (2012) NeuroImage, 61 (1) , pp. 10-20). Evoked neural response data were acquired across different imaging modalities and data used to rigorously test published biophysical models and build/refine improved models of the BOLD fMRI signal. This included the development and parameterisation of Monte Carlo Simulations of MR signal attenuation to predict the BOLD fMRI signal changes from the underlying haemodynamics measured with optical imaging (Martindale, A. J., Kennerley, A. J., et.al., (2008). Magn Reson Med. 59(3) p607-18). Upon implementation of this approach it became clear that the light transport through tissue models used for optical imaging spectroscopy were limited; often assuming the brain as a homogeneous turbid media. For the first time in this field I used the high resolution 3 dimensional MRI data to parameterise a heterogeneous tissue model (fig1b) for optical imaging spectroscopy algorithms. This improved the accuracy of the resultant haemodynamic measures considerably (Kennerley, A. J., et.al. (2009). NeuroImage. 47(4):p1608-19). This technique has since been used to investigate the signal source of negative BOLD signals (Boorman, L.W., Kennerley, A.J., et.al. (2010) Journal of Neuroscience. 30(12): 4285-94) which often occur alongside more common increases in brain activity and could represent neuronal inhibition. The quality of my research was acknowledged at the British chapter of ISMRM where I won the prestigious Astra Zeneca (2010) and Mansfield (2013) prizes for innovative in-vivo fMRI research.
Figure 1 – Development of multi-modal fMRI and optical imaging; A) methods involved; B) using MCS to predict BOLD fMRI signal from the haemodynamics with a basic homogeneous tissue model and MRI parameterised heterogeneous tissue model. The latter shows a better fit to experimental data.
I am currently working on improvements to the optical recording from brain – implanting spatial frequency domain imaging to estimate changes in scattering which can be attributed to cellular swelling during activity. This imaging technique will be combined with diffusion weighted fMRI which is also related to microstructural changes in cell structure.
In preclinical models I have utilised hyperpolarised 13C NMR spectroscopy at high field to parameterise kinetic models of tumour metabolism (Kazan, S., et.al. (2012) Mag Res Med). I will continue this research developing methods for hyperpolarized MRI using the SABRE method as part of the CHyM research group collaborating with researchers from Biology in breast tumor models. My research in the oncology field will build on my research experience in the area of novel drug delivery mechanisms. As part of a multi-million pound EPSRC project - Engineering virus-like nano-particles for targeting the central nervous system; I used medical imaging techniques to quantify and track nano-vesicles (made from Gd or Rhodamine tagged hydrophilic/phobic polymers) in-vivo as a novel drug delivery system. More recently I have been working with Dr Staniland from the department of Chemistry in Sheffield quantifying the MRI properties of nano-sized megnetopolymersomes. These particles have properties which can be exploited for enhanced diagnostics (with magnetic resonance imaging) and therapeutics using magnetic hyperthermia induction (J Bain, et.al. (2015) Nano Letters. Under Review). Novel drug delivery mechanisms are currently a hot topic; a recent successful multidisciplinary research project I was profoundly involved in used Iron tagged macrophages to carry anti-cancer drugs to tumour sites within the body. I have shown by in vitro and in vivo that by pulsing the magnetic field gradients on an MRI system we can steer these labelled macrophages in a given direction (Fig 2). Thus when gradient targeting is applied towards tumour sites there is an increased uptake of the macrophage cells (upwards of 800% increase) and so the drug for improved therapy (A J Kennerley*, M Muthana*, et.al. (2015). Nature Coms doi: 10.1038/ncomms9009).
Figure 2 – in-vitro demonstration of magnetic resonance targeting. The MR imaging gradients can be pulsed in a given direction to effectively ‘steer’ iron labelled particles in that direction. This can lead to a significant uptake of particles into a specific area – for example a tumour site to deliver therapy.
H-index = 16; i-10 index = 25 (as of 24th October 2017)
Mr Paolo R Dicarolo – Meyer Children’s Hospital, Florence.
For current PhD opportunities, see main York Chemistry pages.
Applications from self-funded PhD/PDRA level researchers and Erasmus students are welcomed; contact Aneurin directly for advice and details of current projects (email@example.com).
Aneurin is a keen advocate of public engagement in research. He has previously secured over £18,500 to develop a public engagement programs around neuro-imaging research.
His motivation stems from research by the Institute of Physics which showed that the uptake of Physics in higher education is on the increase (~5% per year with only a corresponding 0.6% increase in UK population). However, it is still viewed by many as a stereotypically dry subject for 'geeks' - perhaps an imprudent impression that leads to the worryingly high gender gap for the subject (23:87 female to male ratio http://www.iop.org/news/12/aug/page_56802.html). Topics within physics include electromagnetism, quantum theory, nuclear and particle physics; all 'theoretically heavy' subjects. With the current shortage of specialist physics teachers, it can be difficult to inspire students onto the next level - with many finding physics dull/boring and without real application.
Aneurin aims to dispel the myth that physics is dreary through fun and interactive workshop demonstrations of real-life applications of these complex physical ideas. He does this through the use of Magnetic Resonance Imaging (MRI) technology. MRI not only spans complex physical topics (e.g. Electromagnetism, Quantum theory ad nuclear spin physics) but when applied to brain imaging it bridges the scientific disciplines. Physics helps us understand 'how' the brain is imaged; Mathematics helps us interpret the data; chemistry/biology/psychology help us to understand the brain; and ultimately engineering helps design and build the systems to allow all this to happen.
Aneurin’s unique twist to pique interest and help introduce the science behind brain imaging involves pitting a mind-reader against functional (f)MRI technology. Mind-reading, perhaps through modern mentalists such as Derren Brown, has remained ever popular and intriguing. However, is mind reading really possible? Although science is yet to prove the ability of the brain to gain information about an object, person, or location through means other than the known senses, research using fMRI has provided demonstrations of thought identification; in some sense, mind reading. My events include live feats of mind reading performed on members of the public (old and young) to garner interest. Using this as a springboard, the science behind thought identification with fMRI is explained with interactive props (including a portable Earth Field MRI scanner), thus giving the audience a picture of how physics and engineering can help understand how the brain works and inspiring them to continue an education involving physics and engineering.
Aneurin is originally from Wolverhampton in the West Midlands (UK). He studied experimental Physics (MPhys) at the University of Newcastle upon Tyne specialising in particle physics. In 2002, he moved to the University of Sheffield to undertake a PhD in Neuroimaging under the supervision of Professor John Mayhew. His research involved the combination of MRI with optical imaging to investigate and model the heamodynamic response underlying the BOLD (his mom still thinks he works for a washing powder company) fMRI signal. He stayed in Sheffield to complete post-doctoral training before being appointed as a research fellow in charge of a multi-million-pound high field pre-clinical MRI facility at the University of Sheffield. His current research interest involves the application of imaging technologies to help answer burning bio-chemical questions.
He lives in South Yorkshire with his wife Natalie and their two sons Noah and Aled. Outside of his research Aneurin is an avid strategy board-gamer and painter. He set up and ran a city wide gaming club in Sheffield. He is also a sci-fi nerd and occasional moonlights as a mind reader. Ask him to read your mind!