Neuroscience and Therapeutics and Head of the Division of Brain Sciences in the
Department of Medicine of Imperial College London. Prior to this
appointment, he was a Vice President in Pharmaceuticals Research and
Development for GlaxoSmithKline, where he led their Clinical Imaging Centre,
Discovery Clinical Genetics and a medicine development programme. Before that, he was MRC Clinical Research
Professor and Head of the Department of Clinical Neurology in the University of
Oxford. Through these roles, he became the founding
Director of the Oxford Centre for Functional Magnetic Resonance of the Brain
(FMRIB) and founding Head of the GSK Clinical Imaging Centre in London (now known
as Imanova, Ltd.).
Professor Paul McMahan Matthews
Visiting Professor (Honorary)
Early work as a post-graduate student
and post-doctoral fellow provided a foundation for Blood Oxygenation Leven Dependent
(BOLD) functional imaging with a quantitative model for the dependence of the in vivo MRI signal on blood oxygenation
with Keith Thulborn and John Waterton.
In Professor Sir George Radda’s Oxford laboratory, Prof Matthews, along
with Doug Arnold , also conducted amongst the first in vivo phosphorus magnetic resonance spectroscopy (MRS)
studies. After moving to McGill
University in his first faculty position, Prof Matthews and Doug Arnold later
led in establishing MRS for the diagnosis and monitoring of mitochondrial
They also demonstrated the
substantial, widespread axonal degeneration and loss in patients with multiple
sclerosis (MS) using proton MRS methods. In a series of subsequent reports over
several years, Prof Matthews’ group (at that time in the Department of
Neurology in Oxford) confirmed it neuropathologically and demonstrated that the
damage extends outside of lesions into the conventionally “normal appearing”
white matter, progresses through the disease course and is a primary mechanism
of disability. They extended these observations
of axonal pathology with novel evidence for early and progressive
neurodegeneration, and the selective vulnerability of specific populations of
neurons. These discoveries have contributed influentially to the new focus on
neuroprotective and reparative therapies for this and related neuroinflammatory
To explain the potential for
clinically complete recovery of patients in the relapsing-remitting phase of MS
despite irreversible neuroaxonal loss, Prof Matthews proposed that intrinsic
brain plasticity enables brain functional adaptation to damage and provided
first demonstrations of underlying mechanisms using functional MRI (fMRI). He then showed how both pharmacological and
behavioural interventions can modulate this both in MS and after subcortical
ischaemic stroke. This work has contributed to a fundamental paradigm shift in
MS and other white matter diseases, shifting attention from focal lesions to
the integrity of the preserved brain.
To enable these discoveries, Prof Matthews
led the FMRIB group with Steve Smith and his colleagues who made major
methodological contributions with development of automated methods for precise
assessment of brain atrophy (SIENA), white matter connectivity (probabilistic
tractography, TBSS, FLIRT) and connectivity-based parcellation of grey matter,
as well as robust paradigms for the analysis and interpretation of fMRI data,
particularly in the resting state. These
tools are part of the FSL software package from FMRIB, now perhaps the most
widely used image analysis software “toolbox” world-wide.
work has pioneered applications of imaging in therapeutics development. Over the last few years, he has worked to
promote research imaging data harmonisation and sharing, and large population
imaging. Contributing to this, Prof Matthews
serves in several external leadership roles, including as Steering Committee Member
and Chair of the Imaging Work Group for the UK Biobank, Executive Member and Chair
of the Dementias Platform UK MRI-PET Network, and one of the UK representatives
for the Interim Board of Euro-Bioimaging.
has been a member of the Nuffield Council of Bioethics Biological and Health
Data Working Party, chaired or served on MRC, Canadian Institutes of Healthcare
Research, Finnish Academy of Science and other grants councils. Amongst honours received, in 1997, Prof Matthews
was made a Fellow by Special Election in St Edmund Hall, Oxford, in 2008, Prof
Matthews was awarded an OBE for services to neuroscience and, in 2014, he was
elected as a Fellow of the Academy of Medical Sciences.
in Prof Matthews’ laboratory focuses on understanding mechanisms by which
inflammatory processes promote and protect the brain from
neurodegeneration. This work includes
the development and exploitation of molecular imaging of innate immune
responses in people with multiple sclerosis or early Alzheimer’s disease, as
well as experimental medicine studies of innate immune responses using a range
of ‘omics methods. A specific focus has
been on understanding mechanisms by which the 18kD mitochondrial translocator
protein modulates microglial immune responses.
Tools include in vivo MRI and
PET imaging, along with transcriptomics and metabolomics of accessible cell
populations. Increasing emphasis is
being placed on inter-disciplinary work with data scientists to develop
approaches for quantitative analyses and for molecular epidemiological study of
these phenomena in large populations.
Thulborn KR, Waterton JC, Matthews PM, Radda GK. 1982. Oxygenation dependence of the transverse relaxation
time of water protons in whole blood at high
field. Biochim Biophys Acta. 714(2):265‑270.
DL, Matthews PM, Radda GK. 1984.
Metabolic recovery after exercise and the assessment of mitochondrial
function in vivo in human skeletal muscle by means
of 31P NMR. Magn Reson. Med
Arnold DL, Matthews PM, Francis G., Antel J. 1990. Proton magnetic resonance spectroscopy of
human brain in vivo in the evaluation of multiple sclerosis: assessment of the
load of disease. Magn Reson Med.
DeStefano N, Matthews PM, Fu L, Narayanan S, Stanley J,
Francis G, Antel J, Arnold DL.1998.
Axonal damage correlates with disability in patients with relapsing-
remitting multiple sclerosis. Results of
a longitudinal magnetic resonance spectroscopy study. Brain. 121(Pt
Evangelou N, Esiri MM, Smith S, Palace J, Matthews PM.
2000. Quantitative pathological evidence
for axonal loss in normal-appearing white matter in multiple sclerosis. Ann Neurol. 47(3):391-395.
Cifelli Cifelli A, Arridge M,
Jezzard P, Esiri MM, Palace J. Matthews PM. 2002. Thalamic neurodegeneration in
multiple sclerosis. Ann Neurol. 52(5):650-653.
Lee M, Reddy H, Johansen-Berg H, Pendlebury S, Jenkinson
M, Smith S, Palace J, Matthews PM. 2000.
The motor cortex shows adaptive functional changes to brain injury from
multiple sclerosis. Ann Neurol. 47(5):606-13.
Johansen-Berg H, Rushworth MFS, Bogdanovic MD,
Kischka U, Wimalaratna S, Matthews PM.
2002. The role of ipsilateral
premotor cortex in hand movement after stroke.
Proc Natl Acad Sci. 99(22):14518-23.
SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins
KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TE. 2006.
Tract-based spatial statistics:
voxelwise analysis of multi-subject diffusion data. Neuroimage. 31(4):1487-505.
Owen DR, Yeo AJ, Gunn RN,
Song K, Wadsworth G, Lewis A, Rhodes C, Pulford DJ, Bennacef I, Parker CA,
Stjean PL, Cardon LR, Mooser VE, Matthews
PM, Rabiner EA, Rubio JP.
2012. An 18-kDa translocator
protein (TSPO) polymorphism explains differences in binding affinity of the PET
radioligand PBR28. J Cereb Blood Flow Metab. 32(1):1-5.
http://www.imperial.ac.uk/people/p.matthews; https://www.seh.ox.ac.uk/users/paulmatthews and http://www.acmedsci.ac.uk/fellows/fellows-directory/ordinary-fellows/professor-paul-matthews/