Blood flow studies in normal and diseased arteries in relation to early vascular changes and paediatric obesity
Lead Research Organisation:
University of Strathclyde
Department Name: Biomedical Engineering
Abstract
Paediatric obesity has recently taken epidemic proportions worldwide, becoming one of this century's major challenges. Originally a high-income countries' problem, obesity at young age is now prevailing also in low- and middle-income countries. Increased levels of blood cholesterol and early cardiovascular diseases (CVDs) are-among other health problems-, the first clinical symptoms that disparate overweight from normal-weight children. In addition, the likelihood of overweight children to remain obese in adulthood is high, along with an associated increased propensity for developing high-risk CVDs and other chronic non-communicable diseases, which in turn may increase the risk for premature death. Tackling paediatric obesity is a priority in recent UK policies, in line with European and worldwide strategic priorities.
Primarily a dietary disease, obesity is believed to accelerate the initiation and progression of endothelial dysfunction, one of the early biological markers for atherosclerotic lesions that underlie most cardiovascular diseases. Lesion distribution varies in space within the arterial network and it is yet unclear why the endothelium is at times prone or immune to disease, particularly with increasing age. Evidence of lipid accumulation can first be detected at the intima layer of the systemic arteries as early as the age of three. Well-established medical imaging modalities, such as high-resolution ultrasonography and magnetic resonance imaging, allow for the non-invasive assessment of fatty streak deposition in paediatric practice. Several markers have been proposed to help the clinical assessment of endothelial damage in high-risk patients. In obese children, arterial changes can painlessly be evaluated with measurements of the aortic and carotid intima-media thickness (IMT) and flow-mediated dilatation (FMD) of the brachial, radial and femoral arteries. Pulse wave analysis is additionally utilised to assess arterial stiffness, distensibility and compliance.
In this research project, both experimental and mathematical modelling methods will be used to assess early vascular changes in paediatrics, in relation to childhood obesity. The information from these studies will be examined and the data between normal and diseased arteries will then be compared. This will later allow patient-specific numerical simulations to be performed and the quality of blood flow through arterial vessels to be analysed. This diagnostic tool will be fundamental in monitoring obesity-induced vascular changes in the young population.
The project is highly multi-disciplinary within the broad fields of Biomedical Engineering, Fluid Mechanics, and Paediatric Medicine. The named candidate will gain expertise in biofluid dynamics methods and be in close collaboration with paediatric cardiac surgeons from the Royal Hospital for Children, Glasgow, who have an extended and proven experience in working with engineers for the development of new medical technologies.
Primarily a dietary disease, obesity is believed to accelerate the initiation and progression of endothelial dysfunction, one of the early biological markers for atherosclerotic lesions that underlie most cardiovascular diseases. Lesion distribution varies in space within the arterial network and it is yet unclear why the endothelium is at times prone or immune to disease, particularly with increasing age. Evidence of lipid accumulation can first be detected at the intima layer of the systemic arteries as early as the age of three. Well-established medical imaging modalities, such as high-resolution ultrasonography and magnetic resonance imaging, allow for the non-invasive assessment of fatty streak deposition in paediatric practice. Several markers have been proposed to help the clinical assessment of endothelial damage in high-risk patients. In obese children, arterial changes can painlessly be evaluated with measurements of the aortic and carotid intima-media thickness (IMT) and flow-mediated dilatation (FMD) of the brachial, radial and femoral arteries. Pulse wave analysis is additionally utilised to assess arterial stiffness, distensibility and compliance.
In this research project, both experimental and mathematical modelling methods will be used to assess early vascular changes in paediatrics, in relation to childhood obesity. The information from these studies will be examined and the data between normal and diseased arteries will then be compared. This will later allow patient-specific numerical simulations to be performed and the quality of blood flow through arterial vessels to be analysed. This diagnostic tool will be fundamental in monitoring obesity-induced vascular changes in the young population.
The project is highly multi-disciplinary within the broad fields of Biomedical Engineering, Fluid Mechanics, and Paediatric Medicine. The named candidate will gain expertise in biofluid dynamics methods and be in close collaboration with paediatric cardiac surgeons from the Royal Hospital for Children, Glasgow, who have an extended and proven experience in working with engineers for the development of new medical technologies.
Description | In girls and women with Turner syndrome (TS), congenital abnormalities, alongside an underlying predisposition to obesity and hypertension, contribute to an increased risk of cardiovascular disease and ultimately reduced life expectancy. We observe that children with TS present a greater variance in aortic arch morphology than their healthy counterparts, and hypothesise that their haemodynamics is also different. In this research period, computational fluid dynamic (CFD) simulations were performed for five TS girls, and one age-matched healthy girl, using patient-specific inlet velocity profiles, extracted from phase-contrast MRI data. The visualisation of multidirectional blood flow and wall shear stress (WSS) revealed increased vortical flow in the arch, descending aorta, and supra-aortic branches, and a highly heterogenous pattern of higher WSS in the TS geometries. The correlation between the presence of aortic abnormalities, and disturbed flow with elevated WSS, suggests that the risk of cardiovascular disease in TS may be increased as a result of the abnormal blood flow patterns induced by anatomical variations in the thoracic aorta. |
Exploitation Route | The analysis of haemodynamic parameters of patient-specific aortic models that are difficult to measure in vivo can improve our understanding of cardiovascular disease processes, thus enhancing diagnostic capabilities, and progressing toward patient-specific precision medicine. TS girls and women face a lifelong battle with a broad spectrum of cardiovascular concerns, from congenital heart abnormalities, to an increased risk of hypertension, ultimately reducing life expectancy. The current management of cardiovascular conditions in TS is the same as in the general population, due to a lack of understanding of the developmental origins of the cardiovascular manifestations seen specifically in TS. The key clinical question is whether any of the cardiovascular risk in TS patients is modifiable. Currently known modifiable risk factors are hypertension and obesity and therefore the treatment of hypertension and avoidance of being overweight and obesity is necessary in this group of patients. Would this alter the flow dynamics more favourably too? In this study, the anatomical abnormalities observed in the aorta of young TS girls were accompanied by abnormal flow patterns and highly non-uniform distribution of wall shear stresses, which may promote the development of cardiovascular diseases. The type of analysis presented in this study could be used clinically to predict patients at higher risk and therefore be more pro-active in lifestyle measures. Considering the excess of morbidity and mortality, the early diagnosis of cardiovascular changes associated with Turner syndrome is essential, and given the advantages of computational fluid dynamics (CFD) in monitoring these changes, this method should be used alongside the standard Doppler echocardiography and magnetic resonance imaging in the clinical assessment of these patients. |
Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
Description | UK-Canada Globalink Doctoral Exchange Scheme |
Amount | £12,737 (GBP) |
Funding ID | NE/T014113/1 |
Organisation | Natural Environment Research Council |
Sector | Public |
Country | United Kingdom |
Start | 05/2021 |
End | 08/2021 |
Title | Computational models of Turner syndrome aorta |
Description | Retrospective cardiac MRI data for paediatric Turner syndrome patients was obtained through our collaboration with the Queen Elizabeth University Hospital. From these MRI images, three-dimensional computational models were created of the aortic arch for a small (n<10) patient group. With the recruitment of more patients, this database of Turner syndrome models will be expanded on. |
Type Of Material | Computer model/algorithm |
Year Produced | 2020 |
Provided To Others? | No |
Impact | The development of computational Turner syndrome aorta models was used to simulate the patient-specific blood flow and the haemodynamic results were analysed and are in the process of being published. |
Description | Collaboration with Queen Elizabeth University Hospital |
Organisation | Queen Elizabeth University Hospital |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | We have provided our partners at the hospital with our expertise in computational fluid dynamics, and the processing of patient data using these methods to reveal interesting results which we are in the process of joint publishing. |
Collaborator Contribution | Throughout this collaboration with both the Department of Radiology and the Department of Paediatric Endocrinology at Royal Hospital for Children, Queen Elizabeth University Hospital (Glasgow, UK), our partners have provided us with anonymous retrospective patient data, and their clinical expertise. |
Impact | A joint publication is in the process and will be submitted early 2021. This collaboration is multi-disciplinary as it includes the Department of Paediatric Endocrinology, as the patient group we are interested in are children with Turner syndrome, the Department of Cardiology, as we are studying the cardiovascular health of these patients, and the the Department of Radiology, as the patient data we obtain is cardiac MRI data. |
Start Year | 2018 |
Description | Collaboration with University of Toronto (UKRI-Canada Globalink Doctoral Exchange Scheme) |
Organisation | University of Toronto |
Country | Canada |
Sector | Academic/University |
PI Contribution | The student's participation in the Globalink scheme at the University of Toronto will strengthen Canada's research capacity in the field of cardiovascular disease with specific contributions to female cardiovascular health. A unique opportunity is presented to exchange data, resources and expertise between two world-leading universities. The student will disseminate results obtained both during her first two years of PhD research in Scotland, and bring in expertise on the biomedical applications of the open-source software OpenFOAM. This would provide the UofT team with an alternative tool to simulate the haemodynamic environment in congenital heart disease patients. |
Collaborator Contribution | Due to the full affiliation between the University of Toronto and the Toronto General Hospital, the partners will provide the student with access to anonymised retrospective medical data from healthy and Turner syndrome patients. The partners at UofT will also provide the student with expertise in computational fluid dynamics and training in software not currently used by the student at their home university. |
Impact | Following the internship with Mitacs Globalink, the University of Strathclyde will have formed a new strategic partnership with the University of Toronto, providing the Biofluids Group at Strathclyde with connections to internationally renowned experts from the top institution in Canada. The proposed work will be used in the student's PhD thesis, fulfilling her first objective to investigate both children and adults with Turner syndrome, and will be published in high-impact academic journals jointly co-authored between the UK and Canadian researchers. |
Start Year | 2020 |
Description | 4D Flow workshop presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Oral presentation (titled "A numerical investigation of blood flow through patient-specific aortae of children with Turner syndrome") to healthcare professionals (doctors, nurses, SINAPSE representatives) at a workshop on 4D flow held at the Queen Elizabeth University Hospital. |
Year(s) Of Engagement Activity | 2019 |
Description | BioMedEng presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Poster presentation at the annual BioMedEng conference (titled "Blood Flow Simulations in the Aortic Arch in relation to Haemodynamic Wall Shear Stress and Obesity-induced Vascular Changes") held at Imperial College London. |
Year(s) Of Engagement Activity | 2019 |
Description | CMALS: One Health presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Poster presentation at the Centre for Mathematics Applied in the Life Sciences (CMALS): One Health workshop held at the University of Strathclyde. |
Year(s) Of Engagement Activity | 2019 |
Description | Cardiovascular Journal Club (Queen Elizabeth University Hospital) presentation |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Virtual oral presentation to the cardiovascular practitioners at the Queen Elizabeth University Hospital. |
Year(s) Of Engagement Activity | 2020 |
Description | Endocrinology Journal Club (Queen Elizabeth University Hospital) presentation |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Oral presentation to the Endocrinology doctors at the Queen Elizabeth University Hospital. |
Year(s) Of Engagement Activity | 2020 |
Description | International multilateral symposium of Biomedical Engineering presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Oral presentation (titled "Blood flow in an intracranial aneurysmal artery with a dual-layer stent") at Beihang university, Beijing, China for their International multilateral symposium of Biomedical Engineering with predominanlty postgraduate students and academic staff. Additional panel talk with the Undergraduate students at Beihang university. |
Year(s) Of Engagement Activity | 2018 |
Description | Meet the Researcher Showcase Event |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Exhibit hosted at the "Meet the Researcher Showcase" event, Dundee Science centre, for school children. Event hosted by Medical Research Scotland. |
Year(s) Of Engagement Activity | 2020 |
Description | Science Communication (primary school) volunteering |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Volunteering in science commincation at a local primary school. In partnership with the University of Glasgow, Undergraduate Medical School. |
Year(s) Of Engagement Activity | 2020 |
Description | Scottish Fluids Mechanics Meeting Presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Poster presentation at the annual Scottish Fluid Mechanics Meeting (titiled "Blood Flow Simulations in the Human Aortic Arch in Relation to Obesity") hosted by the Fluid Mechanics Research Group in the School of Science and Engineering at the University of Dundee. |
Year(s) Of Engagement Activity | 2019 |
Description | The Scottish Cardiovascular Forum presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Poster presentation at the Scottish Cardiovascular Forum meeting hosted by SIPBS, University of Strathclyde. |
Year(s) Of Engagement Activity | 2020 |
Description | World Congress in Computational Mechanics (WCCM) presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Virtual oral presentation and live panel participation (titled "Computational mechanics in pediatric medicine"), at the annual WCCM conference with 3000+ participants. |
Year(s) Of Engagement Activity | 2020 |
Description | Young WEIR-WISE - Discovering Engineering with S2 Girls (volunteering) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Volunteering at the Young WEIR-WISE programme which is a week long program designed to inspire young female students (s2 girls) to discover the excitement and personal satisfaction behind a career in engineering through participation in hands-on challenges at the University of Strathclyde. |
Year(s) Of Engagement Activity | 2019,2020 |