# Publications

(Papers and More!)

### 13C Pyruvate Transport Across the Blood-Brain Barrier in Preclinical Hyperpolarised MRI

There has been much controversy in the field about the rate of pyruvate transport across the blood-brain-barrier within the lifetime of the hyperpolarised experiment. Through of the use of spectroscopy, imaging and the permeablisation of the blood-brain-barrier both physiologically and pathophysiologically, we show in this work that the role of the BBB cannot be neglected. This fortunately seems to be a function of the anaesthetic used, and provides a further impetus to study humans, rather than animals.
In Scientific Reports

### Assessing the optimal preparation strategy to minimize the variability of cardiac pyruvate dehydrogenase flux measurements with hyperpolarized MRS

This work assesses variability in metabolic readings as determined by hyperpolarized magnetic resonance spectroscopy.
In NMR in Biomed.

### Hyperpolarized ketone body metabolism in the rat heart

Ketone bodies are often maligned as the ‘forgotten’ metabolic fuel source. In this work, we show that labelled acetoacetate can be simply synthesised, hyperpolarised, injected with no discernable toxicity in vivo, and their subsequent metabolic kinetics observed
In NMR in Biomed.

### Non-Invasive Immuno-Metabolic Cardiac Inflammation Imaging Using Hyperpolarized Magnetic Resonance

In this work we show that the role of the immune system in myocardial infaction can be measured using hyperpolarised Magnetic Resonance, and cannot be neglected. It is currently in press
In Circ. Res.

### Myocyte Metabolic Imaging with Hyperpolarised MRI

This invited chapter in a reference text covers in 70 or so short pages the physical origins of Dynamic Nuclear Polarisation, and applications and strategies for its applications. Unfortunately, despite my best efforts, it is not open access. Please contact me directly for assistance.
In Protocols and Methodologies in Basic Science and Clinical Cardiac MRI

### Hyperpolarized [1,4-13C2]Fumarate Enables Magnetic Resonance-Based Imaging of Myocardial Necrosis

In this work, we show that hyperpolarised fumarate enables the detection of cardiac necrosis directly following injury, which would be of significant clinical utility.
In JACC: CVI

### On the Metabolism of Exogenous Ketones in Humans

Ketone body metabolism is of considerable interest in humans, owing to the comparatively recent discovery of methods for creating ketotic states without starvation. This work shows that the consumption of exogenous ketone compounds achieves ketosis in humans, safely and effectively.
In Frontiers in Physiology

### Susceptibility-Induced Distortion Correction in Hyperpolarized Echo Planar Imaging

Magnetic susceptibility causes a number of artefacts in some MR experiments, particularly Echo Planar Imaging. This work describes a reconstruction method to substantially ameliorate such artefacts, using a physics-based algorithm. The code and example datasets are available online.
In Magon. Res. Med.

### Bounded rate constant estimation in hyperpolarised [1-13C]pyruvate experiments by a Delayed-rejection Adaptive Metropolis Markov-Chain Monte Carlo (DAM-MCMC) Method

In Proc. Intl. Soc. Magon. Res. Med. 2017

### Ferumoxytol as a blood-pool T2 relaxation agent for 7T phosphorus spectroscopy

In Proc. Intl. Soc. Magon. Res. Med. 2017

### Hyperpolarized [1,4-13C2]Fumarate is a probe of necrosis in myocardial infarction

In Proc. Intl. Soc. Magon. Res. Med. 2017

### The use of weighted averaging in spectroscopy studies improves statistical power

In Proc. Intl. Soc. Magon. Res. Med. 2017

### Transport across the blood-brain-barrier may be limiting for hyperpolarized [1- 13C]pyruvate neuro-oncology studies

In Proc. Intl. Soc. Magon. Res. Med. 2017

### Hyperpolarised MRI of cardiac inflammation and repair

The role of the immune system following a myocardial infarction is complex and not completely understood. Here we use hyperpolarized magnetic resonance to investigate lactate production and glycolysis in the heart, and showed that 2-deoxyglucose alters the pattern of disease following infarction.
In The Lancet

### Weighted averaging in spectroscopic studies improves statistical power

This work shows that the Cramér-Rao Lower Bound derived from spectral quantification algorithms is a sensible weight to chose for the propagation of uncertainty throughout the population.
In Magon. Res. Med.

### Simultaneous in vivo assessment of cardiac and hepatic metabolism in the diabetic rat using hyperpolarized MRS

We show here that multiple-slice spectroscopy combined with hyperpolarized pyruvate forms a powerful tool of diabetic metabolism
In NMR in Biomedicine

### Fast Padé Transform Accelerated CSI for Hyperpolarized MRS

Here we show that the use of Padé approximants (rational polynomial approximating functions, in contrast with the linear polynomials more typically encountered) can be used to form an alternative reconstruction method for CSI data. This may be of utility in a hyperpolarized context.
In Tomography

### Assessment of Metformin-Induced Changes in Cardiac and Hepatic Redox State Using Hyperpolarized [1-13C]Pyruvate

Here we show that Metformin has a profound effect on visible lactate production in the myocardium, which is consistent with a hypothesis that it changes the cellular redox state. This is a significant finding in the context of diabetes care, as diabetic cardiomyopathy is a common cause of death for diabetic patients.
In Diabetes

### Assessment of Metformin induced changes in cardiac redox state using hyperpolarized[1-13C]pyruvate

Here, we investigated the effect of a first-line anti-diabetic drug, Metformin, on cardiac metabolism.
In Proc. Soc. Card. Magon. Res.

### Mapping of intracellular pH in the in vivo rodent heart using hyperpolarized [1-13C]pyruvate

One of a series of Lau, Miller and Tyler papers, here we show that hyperpolarized pyruvate can be used a probe of intracellular pH through the use of a spectrally-selective excitation pulse that excites CO2 and bicarbonate with a large flip angle.
In Magon. Res. Med.

### Simultaneous assessment of cardiac metabolism and perfusion using copolarized [1-13C]pyruvate and 13C-urea

One of a series of Lau, Miller and Tyler papers, here we show that hyperpolarized pyruvate can be co-polarized with urea, and used as a combination perfusion/metabolism probe.
In Magon. Res. Med.

### Simultaneous assessment of cardiac metabolism and perfusion using co-polarized [1-13C]pyruvate and 13C-urea

In Proc. Intl. Soc. Magon. Res. Med. 2016

### Cardiac perfusion imaging using hyperpolarized 13C urea using flow sensitizing gradients

One of a series of Lau, Miller and Tyler papers, here we show that hyperpolarized urea can be used as an effective quantitative probe of perfusion, and one that is potentially able to detected conditions such as balanced ischaemia that are traditionally not visible to first-pass perfusion imaging with gadolinium
In Magon. Res. Med.

### In vivo assessment of cardiac metabolism and function in the abdominal aortic banding model of compensated cardiac hypertrophy.

Here the authors demonstrate that cardiac energetics are changed in heart failure, a major cause of death in the western world.
In Cardiovasc. Res.

### Robust and high resolution hyperpolarized metabolic imaging of the rat heart at 7T with 3D spectral-spatial EPI

This publication represents the first major piece of work from my PhD, a high resolution and robust imaging sequence that was able to image cardiac metabolism at (for the time) world-leading spatial resolution.
In Magon. Res. Med.

### Ferroportin regulates cardiac iron homeostasis

In Proc. Intl. Soc. Magon. Res. Med. 2015

### Flow-sensitizing gradients for first-pass perfusion imaging using hyperpolarized 13C urea

In Proc. Intl. Soc. Magon. Res. Med. 2015

### High resolution hyperpolarized metabolic imaging with three-dimensional spectral-spatial EPI at 7T

In Proc. Intl. Soc. Magon. Res. Med. 2015

### Hyperpolarized ketone body metabolism in the in vivo rat heart

In Proc. Intl. Soc. Magon. Res. Med. 2015

### The acute effects of metformin on cardiac and hepatic metabolism: a hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy study

In Proc. Intl. Soc. Magon. Res. Med. 2015

### Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function.

In this publication, I wrote a $T_{2}^{*}$ mapping sequence and analysis pipeline to help quantify iron levels in mice with profoundly altered iron homeostasis through magnetic resonance. This was technically challenging owing to the high level of iron in some tissues within each individual, and various electrodynamic interactions that arose due to the relatively high field (7T) magnet used.

### Mechanisms of cell migration in the adult brain: modelling subventricular neurogenesis

Another paper mathematically modelling adult neurogenesis, in which we further investigate the previously proposed model.
In Comput. Methods. Biomech. Biomed. Engin.

### A mathematical model of adult subventricular neurogenesis

This work describes a set of PDEs to describe a neurological process in the adult brain, computationally solves them, and then performs a sensitivity analysis. I wrote most of it as a third year undergraduate student on a Nuffield Foundation sponsored placement. My supervisors were the first and last authors.
In J. Roy. Soc. Interface

# Recent Posts

### An IBM Spectrum Protect / HFS Backup / TSM client size limiting script

In my university we have hte ability to use IBM Spectrum Protect aka HFS Backup aka Tivoli Storage Manager for backing up large amounts of experimental data. Unfortunately, due to local rules this fails if the amount of data to be sent is more than 200 GiB and we have to email the central team and ask them to let us back it up again. The below script (just about) automatically stops the process if it’s going to bust a pre-determined size limit.

### NMR Variable Temperature Control, the Bruker BVT3000, and Eurotherm 902/904 series temperature control

A common problem in spectroscopy experiments is variable temperature control. One of the giant companies in the field, Bruker, has made a device that blows hot or cold air at samples to regulate their temperature. The device that blows air and runs the show has gone through several iterations over the years, but one variant is called the Bruker BVT3000 variable temperature controller. It has a little microcontroller, and talks to a commercially available (at the time) PID controller called the Eurotherm 902 series.

### A simple keep-alive script for OpenVPN

su echo 1 > /proc/sys/net/ipv4/ip_forward #Enable NAT iptables -t nat -A POSTROUTING -o eth1 -j MASQUERADE #Set up DNAT iptables -A FORWARD -i eth1 -o tap0 -m state --state RELATED,ESTABLISHED,NEW -j ACCEPT #Enable connections from the private subnet S1 out iptables -A FORWARD -i tap0 -o eth1 -j ACCEPT #Enable connections from the tunnel to the the private subnet, i.e. from S2 to S1 #Bring up the tunnel: ifconfig tap0 up #Configure the tunnel as you like: ifconfig tap0 192.

### Vector-Based Table of the Nuclides

The NZ Plot The N-Z plot, also known as the Plot of the Nuclides, is a standard plot in which one shows $N$, the number of nucleons in an isotope, against $Z$, its proton number. For low $A=N+Z$, this is approximately a straight line along which stable nuclei exist. As an medical physicist, I perpetually find myself wishing to refer to the NZ plot occasionally, in order to find out if a given nuclide is either (a) NMR visible (that is, $I\neq0$), (b) radioactive with a decent activitiy, or occasionally both.

### How to effectively use SSH as a port-forwarding tunnel

The problem: You have an expensive piece of bespoke hardware box, $A$, on a private subnet $S_1$. Your computer of interest, $C$, is sat on a different subnet, $S_2$. There is a linux router between the two, $B$, running sshd. You wish $C$ (or a virtual machine thereon) to talk to $A$, but don’t want the rest of $S_1$ to be accessible to all of $S_2$ or vice-versa. In short, you want something on $C$ to use a specific (virtual) network interface to go $C\rightarrow B\rightarrow A$.

# Projects

#### VarianTools and other MRI utilities

Sources and utilities for common MR problems on the Varian/Agilent platform

#### DPhil Thesis

Online copies of my DPhil [PhD] thesis.

# Teaching

I have taught the following courses:

### Department of Physics

• Year 1: Classical Mechanics, Special Relativity, Circuit Theory, Electromagnetism, Optics

• Year 2: Electromagnetism, Quantum Mechanics

• Year 3: Biophysics

### Department of Biochemistry

• Year 1: Mathematics, Statistics (Four very basic lectures on statistics can be found here: 1 2 3 4 )