Institute of Cellular Medicine

Staff Profile

Dr Kieren Hollingsworth

Senior Lecturer in Magnetic Resonance Physics

Background

Introduction

I am a scientist who applies physics to quantify pathological processes in human organs and tissues (such as the liver, skeletal muscle, the knee, the heart and the pancreas) to allow early detection of disease, and to provide sensitive biomarkers to use in longitudinal studies of therapy. 


My work as a principal investigator concentrates on creating and clinically validating methods of accelerating quantitative MRI to reduce costs and improve the patient experience. You can read more about these activities on the "Research" tab and in research papers from my group available here and here.

 

I collaborate with other principal investigators to design, develop and implement quantitative methods and apply them to clinical research questions or genuine importance.

 

My methods for quantifying the amount of fat stored in the liver and pancreas are playing a key role in Newcastle research to reverse type 2 diabetes through very low calorie diets (available here). 

 

I have developed and led the physics behind a multicentre trial to prove that MRI is a more sensitive way of tracking disease progression, compared to conventional functional measurements (available here).


Recent work has also included using quantitative MRI to track the effectiveness of anti-inflammatory treatments in juvenile idiopathic arthritis.

 

I have also collaborated to use quantitative MRI to identify and quantify early sub-clinical changes in cardiac function through the use of strain and torsion measurements, and assessments of cardiac energetics. I have applied these to situations including:

(i) showing the unusual pathological mechanisms of limb girdle muscular dystrophy 2I on the heart, published in European Journal of Heart Failure (available here). 

(ii) the detection of subclinical differences in physically active and inactive women of different ages, published in Circulation: Cardiovascular Imaging (available here).     

(iii) the early detection of cardiac impairment in mitochondrial disease which cannot be detected by conventional ultrasound, published in European Journal of Cardiology, Cardiovascular Imaging (available here). 

 

Background

I first trained in Magnetic Resonance Physics at the Department of Chemical Engineering, University of Cambridge under Dr Mike Johns, presenting a Ph.D. thesis entitled "Emulsion characterisation using magnetic resonance methods".

As a result of this work, I developed an interest in applying magnetic resonance methods to problems of human disease. In January 2004 I took up a post-doctoral position at the Department of Radiology, University of Cambridge.

In February 2006, I moved to the Newcastle Magnetic Resonance Centre to lead the development of MR physics method across a range of metabolic and genetic dieases, and collaborating with a large number of internationally-renowned clinical groups at the University. With further appointments as a Senior Staff Scientist in 2009, Lecturer in 2012 and Senior Lecturer in 2016 I have combined this with leading my own independent MR physics research, which will provide the next generation of quantitative MR methods for clinical research.  

Qualifications

M.A. (Hons), M.Eng. (Hons), Ph.D. (Cantab)

Positions Held

Senior Lecturer in Magnetic Resonance Physics, Institute of Cellular Medicine, Newcastle University, from August 2016

Lecturer in Magnetic Resonance Physics (Grade G), Institute of Cellular Medicine, Newcastle University, from August 2012 to July 2016

Senior Staff Scientist (Grade G) in Magnetic Resonance Physics, Institute of Cellular Medicine, Newcastle University, March 2009-July 2012 

Research Associate in Magnetic Resonance Physics,  Institute of Cellular Medicine, Newcastle University, Feb 2006 to Feb 2009

Research Associate in Magnetic Resonance Physics, Radiology, University of Cambridge, Jan 2004 to Feb 2006

Research Fellow, Hughes Hall, University of Cambridge, Jan 2004 to Feb 2006

Memberships

Member of the International Society for Magnetic Resonance in Medicine

Honours and Awards

Danckwerts-Pergammon prize for best Ph.D. dissertation, Department of Chemical Engineering, University of Cambridge

Languages

French, German

Research

My Google Scholar Page can be found at https://scholar.google.co.uk/citations?user=14q5fz4AAAAJ . As of 5th June 2018, my Google Scholar statistics were 3765 citations with a h-index of 33.

Reducing the cost and patient burden of MRI in clinical trials: acceleration of quantitative MRI using novel reconstruction techniques.

MRI is not just a powerful tool for radiologists to visualise diseased tissue, but rather it can be used to accurately measure the disease state of tissue or the function of an organ, and this has informed my research over the last decade. Applications include tracking disease progression in muscular dystrophy, or examining the lipid content of the liver and pancreas and type 2 diabetes.

However, MRI examinations typically require the patient to lie still for many minutes at a time, and a whole examination can take an hour or more. This is a lot for a patient to tolerate within the contect of other visits in a clinical trial protocol and MRI scanning time is costly (~£500/hr in the UK). There are now active trials in Duchenne muscular dystrophy, a muscle wasting disease that affects young boys as young as 4-5 years old, who find it particularly challenging to keep still in the scanner. 

My research as Principal Investigator, funded by the MRC, is to develop and validate highly accelerated MRI measurements by acquiring less data and using a new reconstruction technique. To date, I have demonstrated that we can speed up the scanning by a factor of 5 times to measure the progressing disease in muscular dystrophy.

The clinical validation work was published in the leading international journal Radiology, available here. The technical exploration of how to find the most robust method for doing this was published in Magnetic Resonance in Medicine and is available here.

My present activity as part of this grant is to validate similar accelerations in the heart, and in the liver and pancreas of patients with type 2 diabetes. 

 

Quantitative MRI for clinical trials

My main research interests involve finding new ways to quantify early functional impairment or tissue change in diseases, preferably before the disease becauses overt or symptomatic. These measures permit the tissue or organ state to be tracked across time.

Examples of this include the early detection of cardiac disease in neuromuscular diseases and diabetes, and the tracking of liver and pancreas stored lipid in response to very low calorie diets

 

Postgraduate Supervision

I place great importance on the supervision and training of research students, both clinical and non-clinical, and other post-doctoral workers. I supervise 4 MD and 3 PhD students, with informal but substantial supervision of 2 further PhD students. Evidence of success in this supervisory activity is shown by the timely submission of theses for these students at the appropriate stage (2 PhD and 1 MD) and the successful award of the one PhD and one MD examined to date.

In addition, I have run two four-month research placements for NHS Medical Physics Trainees and three undergraduate research projects. 

Esteem Indicators

Grant reviewer for the Wellcome Trust, Canada Research Chairs program 2012, MRC MRC Experimental Medicine call, 2008 and British Renal Society research awards.

External PhD examiner for University of Cambridge and Universite de Paris Sud.

internal chair of examiners for Newcastle University. 

Reviewer for journals: Heart, Circulation: Cardiovascular Imaging, Journal of Toxicology, Journal of Neurology, Neurosurgery and Psychiatry, NMR in Biomedicine, Magnetic Resonance in Medicine, Journal of Magnetic Resonance Imaging, Neuromuscular Disorders, Journal of Biomedical Research.


Funding

Principal Investigator (100%), MRC New Investigator Research Grant (G1100160, 2012-2015), £301k, “Highly accelerated quantitative MRI of skeletal and cardiac muscle in muscular dystrophy and type 2 diabetes”.

Principal Investigator (85%), MRC Confidence in Concept Award (2017-2018), £53k, “Quantitative Magnetic Resonance Imaging in Juvenile Idiopathic Arthritis to Measure Suppression of Intra-Articular Inflammation”.

Principal Investigator (100%), ImagingDMD subcontract for Summit Pharmaceuticals (2016-2018), £187k, “A Phase 2 Clinical Study to Assess the Activity and Safety of Utrophin Modulation with SMT C1100 in Ambulatory Male Subjects with DMD”.

Co-applicant (25%), Diabetes UK (2017-2020), £516k, “Reversal of Type 2 Diabetes upon Normalisation of Energy Intake in Non-Obese People (ReTUNE)”.

Co-applicant (20%), Diabetes UK Strategic Research Initiative (2013-2018), £1.2million, “Reversal of T2DM using non-surgical weight management with Low-Energy-Liquid-Diet and long-term maintenance, within routine NHS care (DiRECT)”.

Co-applicant (5%), European Union Horizon 2020 (2016-2020), £1.8m, “VISION-DMD - Phase 2 Clinical Trials of VBP15: An Innovative Steroid-like Intervention for Duchenne Muscular Dystrophy.”

Co-applicant (15%), Academy of Medical Sciences and Newcastle Healthcare Charity (2012-2015), £108k, “A 4D flow sensitive magnetic resonance study of patent foramen ovale in cryptogenic stroke”.

Co-applicant (50%), Newcastle Healthcare Charity (2015-2016), “Pancreas morphology in type 2 diabetes following reversal of diabetes”, £36.5k.

Co-applicant (25%), Pfizer (2010-2012), “The role of skeletal muscle function and energetics in the symptoms of growth hormone disease”, £83k.

Co-applicant (40%), Diabetes UK (2009-2010), “Effect of change in pancreas and liver fat content upon beta cell function”, £127k.

Teaching

POSTGRADUATE TEACHING

Although my career is mostly research focussed, high quality teaching should flow naturally from research and I contribute teaching to the following courses: 

(1) MSc Clinical Science (Medical Physics)

I provide teaching, examination and assessment for the following modules, which are targetted at the training needs of prospective NHS Medical Physicists, whether or not they intend to specialise in Imaging with Non-Ionising Radiation in the first year (MPY8001, MSC8001) and to those who wish to take specialist modules in their 2nd and 3rd years (MPY8011, MPY8012, MSC8004).


MPY8001 : Introduction to Medical Physics

I am the theme lead for this 1st year course, which is taken by all medical physicist trainees. It considers the physical origins of the magnetic resonance effect, considers the different types of echo and the encoding of these echoes to produce images. Later contributions to the course include basic sequences, quality assurance and an introduction to clinical MRI.


MPY8011 : Imaging with non-ionising radiation 1

Teaching topics include Parallel Imaging, Physics of Image Artefacts* and the hands-on practical, Linking Theory to Practice*


MPY8012 : Imaging with non-ionising radiation 2

Teaching topics include Magnetic Resonance Angiography

 

(2) MRes contributions

I provide lectures and/or seminar materials for the following MRes modules where quantitative MRI can play an important part:

CVR8007 “Diagnostic Approaches and Current Treatment of Cardiovascular Disorders”

MMB8037 “Cardiovascular Science in Health and Disease”

MMB8035 “Diabetes”  


(3) FRCR Part 1 

I provide teaching in MR Physics to specialist trainees in Radiology in the North East towards the FRCR Part 1 examination.

RESEARCH PROJECTS FOR BSc BIOMEDICAL SCIENCES AND MSc MEDICAL SCIENCES

I regularly supervise final year BSc research projects for students reading Biomedical Sciences and dissertation projects for those reading the MSc in Medical Sciences. It is important that the students have a genuine immersive research experience, and that as far as possible they are able to co-author a publication while working in my group. Previous projects have included:

"Accelerating magnetic resonance imaging in type 2 diabetes and muscular dystrophy" - 2014

"Investigating Magnetic Resonance Imaging as a Method of Measuring Organ Lipid Infiltration in Type 2 Diabetes" - 2013

"Effect of age and physical activity on muscle and cardiac metabolism" - 2011

"White matter lesions and their relationship to autonomic dysfunction in primary biliary cirrhosis"- 2008  

 

UNDERGRADUATE TUTORING

 I am a Personal Tutor to undergraduates reading the BSc/MSci in Biomedical Sciences, being responsible for providing personal induction advice and meeting regularly with them to provide academic and pastoral support throughout their course.  

 

PROPOSING PhD PROJECTS/VACATION PROJECTS

While I am willing to be contacted about proposals for PhD projects/vacation projects, it should be noted that deadlines for funding are early and often very competitive. 

Publications