Acute Vascular Imaging Centre for Oxford (OxAVIC)

Lead Research Organisation: University of Oxford
Department Name: Surgical Sciences

Abstract

This application is for a clinical research centre (CRC) that will allow the close monitoring of
patients as they receive treatments for acute vascular events, in a safe environment at the heart
of the John Radcliffe Hospital. Crucially the CRC will focus on investigating patients at the time
they are having strokes and heart attacks. It will take advantage of medical advances,
particularly in imaging, to improve our understanding of these illnesses and explore new
avenues to improve care and outcomes for patients. The novel aspect of this proposal is to
place this state-of-the-art imaging at the core of where acute clinical care is provided, namely,
the Accident and Emergency Department. Researchers still have a great many questions to
answer about why patients do not recover despite current treatment strategies, such as
angioplasties and the use of clot-busting drugs. Traditionally, such research facilities are either
unavailable or do not provide safe environments for patients at the time of the stroke or heart
attack. The CRC will provide a focus to bring together the research expertise from many
complimentary areas within Oxford University, to understand how we can develop new
treatments or improve on existing treatment for these common conditions.

Technical Summary

Support for a new multi-modal imaging facility including high-field 3T MRI and state-of-art angiogrphy suite adjacent to John Radcliffe A&E in a fully equipped new CRC that links efficiently with acute hospital services, community programmes and existing university research infrastructure.

To enable immediate investigation of patients presenting with acute stroke or coronary syndromes: the ultimate goal is to define and link ‘upstream‘ vascular events (eg plague instability, rupture inflammation, thrombosis, embolism) with ‘downstream‘ end-organ imaging (eg, perfusion, injury, repair, compensation in affected tissue, vascular leak, oedema, haemorrahage, angiogenesis in affeced vascular bed) with a view to gaining a better understanding of clinical emergencies and improved therapy. Develop new imaging methodologies for this clinical setting; Develop novel blood biomarkers to relate to acute imaging findings. In stroke programmes (major and monir stroke/TIA) assess acute intervention & prevention -investigate mechanisms underlying neurological deterioration. Seek to focus therapy on those who will benefit most, define surrogate enpoints that will optimise efficient therapeutic development and focus the design of large-scale clinical trials with mortality and morbidity end-points.

Publications

10 25 50
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Balami JS (2011) Neurological complications of acute ischaemic stroke. in The Lancet. Neurology

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Biasiolli L (2013) In-vivo quantitative T2 mapping of carotid arteries in atherosclerotic patients: segmentation and T2 measurement of plaque components. in Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance

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Dall'Armellina E (2012) Cardiovascular magnetic resonance by non contrast T1-mapping allows assessment of severity of injury in acute myocardial infarction. in Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance

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Dall'Armellina E (2013) Diagnostic value of pre-contrast T1 mapping in acute and chronic myocardial infarction. in JACC. Cardiovascular imaging

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Greenhalgh T (2017) Maximising value from a United Kingdom Biomedical Research Centre: study protocol. in Health research policy and systems

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Grunwald IQ (2012) Comparison of stent free cell area and cerebral lesions after unprotected carotid artery stent placement. in European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery

 
Description Project grant
Amount £122,100 (GBP)
Organisation The Henry Smith Charity 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2011 
End 06/2014
 
Description Transatlantic Network of Excellence
Amount £475,875 (GBP)
Organisation The Leducq Foundation 
Sector Charity/Non Profit
Country France
Start 10/2008 
End 09/2014
 
Title MRI 
Description Novel MRI techniques to assist outcome in human patients with acute vascular syndromes. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2011 
Provided To Others? Yes  
Impact A number of publications from the research groups, plus presentations at international conferences covering both heart and brain and MRI technology. 
 
Title NHS-OU integration 
Description Appointed two key posts to promote the establishment and running of an acute MI and an acute stroke cohort. Integrating with BRC structures; for clinical systems IT; sample storage; clinical and research governance 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact Prospective cohort in formation. 
 
Description Acute magnetic resonance imaging in cerebral ischaemia (AMICI) 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution The purpose of this study is to perform MRI in patients with acute stroke in taking advantage of the unique setting of AVIC.
Collaborator Contribution Expertise in stroke.
Impact This study has resulted in a number of publications and presentations at international conferences.
Start Year 2012
 
Description Adenosine cardioprotection in myocardial infarction 
Organisation University of Oxford
Department Division of Cardiovascular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Infarct size is an important determinant of outcome in ST-elevation myocardial infarction; hence reducing myocardial injury is the mainstay of therapy. This is best achieved by early reperfusion and presently primary percutaneous coronary intervention (pPCI) is the most effective modality. However, despite achieving infarct-related vessel patency and reperfusion, patients still sustain significant myocardial infarction. Attempts to improve outcomes by adjuvant mechanical treatments show inconsistent benefit. An alternative paradigm is to recruit innate protective mechanisms whereby cells can become resistant to injury if primed. Recent studies using a concept called local post-conditioning or targeting mitochondrial pathways with cyclosporine in myocardial infarction have been successful in reducing infarct size, but these have been in selective groups.
Collaborator Contribution Expertise in cardiovascular surgery
Impact We have shown that intermittent limb ischemia after the onset of myocardial ischemia, and prior to reperfusion (remote ischemic perconditioning, rIPerC) reduces infarct size in an animal model and now shown that it reduces the extent of myocardial damage in patients experiencing acute myocardial infarction ( Lancet, in press).
Start Year 2009
 
Description Biomarkers after heart attack 
Organisation John Radcliffe Hospital
Department Department of Cardiology
Country United Kingdom 
Sector Academic/University 
PI Contribution AVIC provides cath alb and equipment to undertake this study.
Collaborator Contribution Input of whole of clinical infrastructure. Univsersity-Biomedical Research Centre collaboration
Impact Cohort study. Approx 150 recruits to date. Biobank. Under evaluation.
Start Year 2011
 
Description Changes in perfusion MRI and functional imaging in relation to blood pressure after TIA and minor stroke 
Organisation University of Oxford
Department Nuffield Department of Clinical Neurosciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Blood pressure is the most important treatable risk factor for stroke, although the mechanism(s) by which raised blood pressure causes stroke are uncertain. Rothwell and colleagues have shown that labile blood pressure is a major risk factor for stroke and preliminary analyses of OXVASC data also suggest that variability in SBP is also strongly correlated with the development of vascular cognitive impairment after TIA and stroke. In order to understand the possible mechanisms underlying the association between variability of SBP and cerebral ischaemia, we are performing a detailed brain and vascular imaging protocol in patients presenting acutely with TIA and minor stroke, and who are also undergoing 24-hour ambulatory monitoring and central monitoring of home BP measurements. We aim to determine any global or regional perfusion abnormalities in the acute phase after TIA or minor stroke and compare these with repeat imaging during follow-up. We will also determine any abnormalities in functional activation patterns and the white-matter connectivity. These imaging parameters will be correlated with level and variability of SBP. Recruitment to this study was difficult last year, due to the non-availability of acute patient slots on the OCMR scanner. These difficulties have continued, it has not been possible to obtain imaging slots for patients within the first 24-48 hours.
Collaborator Contribution Expertise in Clinical Neurology
Impact Unfortunately, due to the delay in the opening of the Acute Vascular Imaging Centre (AVIC), we have not been able to recruit patients to this study. The opening of AVIC is now scheduled for April 2010, and we hope to resume recruitment then.
Start Year 2009
 
Description Coronary Plaque Evaluation 
Organisation University of Oxford
Department Division of Cardiovascular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution This project aims to identify new biomarkers related to atherosclerotic plaque composition and rupture, through analysis of blood samples from patients undergoing coronary artery stenting. Enhanced specificity for biomarker discovery is achieved by detailed plaque characterisation by optical coherence tomography (OCT) to quantify fibrous cap, lipid core and thrombus) and comparison of within-patient matched blood samples in relation to time (pre-plaque disruption vs. time points after plaque disruption) and location (local coronary artery blood sampling immediately downstream from the plaque vs. peripheral blood). Enhanced sensitivity for biomarker discovery is achieved by analysis of coronary artery blood samples obtained during coronary stenting with occlusion of coronary blood flow with a balloon-occlusion
Collaborator Contribution Expertise in cardiovascular surgery
Impact Ethical approval and ORHT indemnity were granted in late 2008. The BRC Steering Committee approved the appointment of a clinical fellow to lead the project in April 2009. The post was advertised through the ORHT in May-June 2009 but no suitable appointees were shortlisted. The post was re-advertised through the University Dept. Cardiovascular Medicine in July-August 2009 and a highly suitable appointee was recruited, Dr. Regent Lee. Dr. Lee completed work permit and visa requirements and took up the post on 1 October 2009. At the time of this progress report, in the 5 weeks since Dr Lee's appointment, 12 patients have been recruited, and a recruitment rate of 2-3 patients/week is now anticipated, leading to >50 patients by the end of March 2010.
Start Year 2009
 
Description Datafusion Project 
Organisation Medtronic
Department Physiocontrol Division Medtronic
Country United States 
Sector Private 
PI Contribution AVIC is the clinical co-ordinating hub for this multidisciplinary study of telemedicine in acute MI
Collaborator Contribution Technology and technical support contribution
Impact >500 patients recruited. Data analysis ongoing
Start Year 2009
 
Description Index of Myocardial Resistance in Acute Myocardial Infarction 
Organisation University of Oxford
Department Division of Cardiovascular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Primary PCI reduces morbidity and mortality and is the treatment of choice for acute myocardial infarction. Recanalisation of the vessel using aspiration devices, percutaneous coronary angioplasty and implantation of a stent is usually successful resulting in resolution of chest pain, normalization of electrocardiographic (ECG) changes and restoring coronary flow. However, in around 30 % of patients these measures do not improve patient's symptoms and ECG changes and coronary flow remain slow despite a patent epicardial vessel. Distal embolization of atherothrombotic material leading to occlusion of intramyocardial arteries and microinfarctions has been identified to play a major role in microcirculatory dysfunction after PCI. Functional obstruction of the coronary microcirculation due to release of bioactive factors and reperfusion injury represent additional factors contributing to myocardial microcirculatory dysfunction in the setting of acute myocardial infarction. Dysfunction of the coronary microcirculation in acute myocardial infarction has been shown to be a powerful negative prognostic marker. The goal of this study is to evaluate the role of the coronary microcirculation after primary PCI for acute STEMI. We plan to use a relatively new catheter based technique, index of myocardial resistance (IMR), and compare it with findings at CMR as described below. Gathering additional knowledge on the role of coronary microcirculation during acute STEMI offers the opportunity to better understand pathophysiology and define measures to improve its function in the future.
Collaborator Contribution Expertise in cardiovascular surgery
Impact Milestones, expected Outputs (translation, impact etc): Q4 2009: Ethics submission Q1 2010: Commence study recruitment Q1- Q3 2010: study enrolment Q4 2010: report
Start Year 2009
 
Description MEASURES IN YOUNG AND AT RISK OF AORTIC DISTENSIBILITY - AN OxAVIC STUDY (MYRIAD) 
Organisation University of Oxford
Department Division of Cardiovascular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution This study will be a physiological investigation of the relation between aortic distensibility measured from direct assessment of central blood pressure in different aortic segments and peripherally assessed pressure, in groups with risk factors for cardiovascular disease. This will be possible because the study will use the unique OxAVIC facilities to perform simultaneous invasive arterial angiography and pressure measurements combined with cardiovascular magnetic resonance imaging. A broad range of studies, both observational and interventional, throughout the Heart Theme use regional aortic distensibility as a pathophysiological outcome measure to determine cardiovascular risk and disease development. Assessment of regional aortic distensibility is possible because of the ability of cardiovascular magnetic resonance to image directly the aorta with high spatial and temporal resolution. Determination of stiffness, however, also requires accurate assessment of the distending pressure within the aorta currently estimated from simple peripheral measures.
Collaborator Contribution Expertise in cardiovascular surgery
Impact MILESTONES • Completion of study protocol and ethics application Feb 2010 • Ethical approval obtained May 2010 • Recruitment commenced May 2010 • Data analysis 2011 • Publication 2011
Start Year 2009
 
Description MRI in ischaemic myocardium 08/H0603/26 
Organisation University of Oxford
Department Division of Cardiovascular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution MR determination of oedema will provide the Oxford Acute Vascular Imaging Centre (AVIC) with a tool to identify hyper-acutely injured myocardium and, in quantitative fashion, to determine the volume of myocardium 'at risk' after transient ischemia. Image acquisition for myocardial oedema imaging at 3T has been established in our hands as part of an accelerated 'acute' protocol that also characterises myocardial function; perfusion ± volume of infarction. These techniques will provide the most comprehensive assessment of 'downstream' myocardial injury, and we have now established a robust and reproducible protocol that can be accomplished in an appropriately swift manner.
Collaborator Contribution Expertise in the field of cardiovascular imaging
Impact We have evaluated patients with both NSTEMI and STEMI - those representing the two ends of the ACS spectrum, and now have data on approximately 40 patients derived from ~120 MRI scans. By imaging at multiple (3) time points, we have been able to define the quantitative changes in myocardial oedema. This is a new and important parameter but we needed to define the variability and time course of change that will be essential for the design of future studies.
Start Year 2009
 
Description MRI perfusion in patients with symptomatic vertebral or basilar artery stenosis 
Organisation University of Oxford
Department Nuffield Department of Clinical Neurosciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Rothwell and colleagues have shown that the risk of recurrent stroke in patients with posterior circulation TIA or minor stroke is higher than that in patients with carotid territory events (Brain 2003;126:1940-54; Cerebrovascular Dis 2006; 219: 6) due to a greater prevalence of significant large artery stenosis in patients with posterior circulation events (Brain. 2009;132:982-8). While vertebral stenting may improve prognosis in such patients, this has a significant procedural risk. It is therefore important to identify patients whose risk of stroke is highest without treatment. Angiographic studies by Rothwell and Kuker suggest that the extent of collateral flow is a key prognostic factor. MR arterial spin labelling (ASL) is a non-invasive way to assess cerebral perfusion, and it may be a useful tool in determining the degree to which flow and perfusion in the posterior circulation are compromised.
Collaborator Contribution Expertise in Clinical Neurology
Impact In 2008 we obtained ethics committee approval and scanned 17 patients/controls using the OCMR MRI scanner. This year, we have continued patient recruitment, although this was hampered due to the delayed opening of the Acute Vascular Imaging Centre, which is now scheduled for April 2010, and to very limited availability of scanning time on the OCMR scanner. We have up to now scanned a total of 29 patients / controls. First results of this study have been submitted to the International Society in Magnetic Resonance in Imaging (ISMRM) 2010 and will be submitted to the European Stroke Conference in May 2010.
Start Year 2009
 
Description Magnetic resonance inaging of early brain injury after subarachnoid haemorrhage (SAH) 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution The purpose of this study uses state-of-the-art MRI technology to investigate mechanisms of delayed cerebral ischaemia following SAH.
Collaborator Contribution Expertise in SAH.
Impact No outputs yet.
Start Year 2012
 
Description Myocardial Injury following Coronary Artery Surgery versus Angioplasty (MICASA) 
Organisation University of Oxford
Department Division of Cardiovascular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution This project has been completed. 80 patients were randomised to either complex revascularisation with coronary stents or coronary bypass surgery. Three MRI scans were performed at different time points.
Collaborator Contribution Expertise in cardiovascular imaging
Impact The initial results show that less invasive revascularisation with stents is at least as safe as coronary bypass surgery with no increase in the damage to the heart muscle that is sustained during the procedure. The initial paper is under peer review by the Journal American College Cardiology. Additional analyses are planned using this data including measures of perfusion and detailed assessment of changes in cytokines.
Start Year 2009
 
Description Periprocedural Myocardial Injury Following Contemporary Rotational Atherectomy PCI for Heavily Calcified Coronary Lesions 
Organisation University of Oxford
Department Division of Cardiovascular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Periprocedural myocardial injury is not an uncommon event following percutaneous coronary intervention (PCI). It occurs in up to 30% of all PCI procedures and the rate is higher in treatment of complex lesions. Although often clinically silent, it is an adverse long term prognosticator. Heavily calcified coronary lesions are difficult to treat and often lead to increased procedural times, increased radiation exposure, and either unsatisfactory PCI or procedural failure altogether. Rotational atherectomy (Rotablation) facilitates PCI of these cases and is currently the preferred adjunctive treatment. It uses a diamond-tipped burr rotating at high speed to grind away calcific deposits and modify the lesion - thus enabling stent delivery, and also optimal stent expansion and deployment. Improved procedural results are reported with this technique, however concern exists regarding irreversible myocardial injury due to downstream embolisation of calcific debris. Previous small studies have instead postulated myocardial stunning or a non-embolic slow flow phenomenon to occur after rotablation. The incidence, mechanism and prevention of myocardial injury following rotablation requires further study. Contemporary rotational atherectomy is now performed at lower burr speeds (150 000 rpm) and shorter run times to minimise complications. There is no study of contemporary rotational atherectomy in heavily calcified coronary lesions to investigate the incidence, degree and pattern of periprocedural injury. The aim of this study is to investigate the degree and pattern of periprocedural myocardial injury following rotablation for heavily calcified coronary lesions, as defined by biomarkers and cardiac MRI (cMR). The relationship between the change in plaque content and volume (as measured by IVUS) and the extent and pattern of new myocardial injury will also be analysed to study the hypothesis that new myocardial injury is mainly a result of distal embolisation of calcific debris. This research will help us understand the mechanism of periprocedural injury in this group of patients, and will assist in developing preventative and therapeutic strategies. It is also envisioned that this will be a pilot study to assist in design of a randomised trial assessing potential preventative/treatment strategies for periprocedural myocardial injury in this group of patients. The frequency and known timing of myocardial injury in this study would also provide an excellent opportunity to study the release kinetics of novel biochemical markers of periprocedural myocardial injury and inflammation.
Collaborator Contribution Expertise in cardiovascular surgery
Impact Milestones, expected Outputs (translation, impact etc): Q4 2009: Ethics submission Q1 2010: Commence study recruitment Q1 2010 - Q2 2011: study enrolment Q4 2011: report
Start Year 2009
 
Description BRC Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact As part of the BRC Open Day, there were four organised tours of AVIC for the public. The facilities in AVIC were demonstrated and the research carried out in the facility was explained and shown how this can have an impact on future healthcare. There were a number of questions from the attendees at the time and postivie feedback was received afterwards.

None
Year(s) Of Engagement Activity 2013
URL http://oxfordbrc.nihr.ac.uk/event/discover-the-future-of-healthcare-at-our-open-day/
 
Description Oxford Open Doors 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact We gave a demonstration of the facility and described the range of research which is undertaken. This was followed by a Q&A session.

None
Year(s) Of Engagement Activity 2014
 
Description TV interview (ITV Meridian) 2012 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact This was a broadcast interview and demonstration of the AVIC facility and would have been of general information / education of the regional area covered by the TV area.

none
Year(s) Of Engagement Activity 2012
URL http://vimeo.com/51148834
 
Description TV interview (South Today, BBC) 2012 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact This was a broadcast interview and demonstration of the AVIC facility and would have been of general information / education of the regional area covered by the TV area.

None
Year(s) Of Engagement Activity 2012