Development of contrast enhanced ultrasonography using the sheep ovarian model of microvascular regulation

Lead Research Organisation: Heriot-Watt University
Department Name: Sch of Engineering and Physical Science

Abstract

A large number of diseases, including cancer, infertility, heart and pregnancy abnormalities, depend on changes to the blood flow in the area of the disease. In cancer generally there is more blood flow generated by the cancer cells, while in heart attacks there is an area in the heart that almost has no blood supply. The seriousness of the disease is also linked to small blood flow changes. The ovary is a tissue where blood flow changes occur naturally during the menstrual cycle. Thus this tissue can simulate a range of diseases and can be used as a system for setting up an accurate blood flow measuring tool. Ultrasound imaging combined with contrast agents that are injected into the blood stream to assess the blood supply of small areas, would be a major advance in the diagnosis and treatment of many different diseases. We plan to develop the tools to do this by focussing on a small tissue in which the blood supply changes from very small to very large in a predictable reproducible way. We can also use drugs to change the blood supply to this tissue. This tissue is in the sheep ovary and if we can use this to create tools to measure normal and abnormal blood flow we can then take this tool directly into the clinic to measure the important changes to blood flow in a variety of important human diseases.

Technical Summary

The ability for the real-time detection and monitoring of microvascular tissue perfusion would be a major advance in the detection of pelvic pathology. In addition microvascular changes are central to a wide range of diseases such as inflammation, cancer and cardiovascular disease. Although blood flow can be measured in large vessels, the measurement of capillary flow is its infancy. This research aims to use the ovine ovary model of angiogenesis and its manipulation to develop and refine contrast enhanced ultrasonography of the microvasculature for future use in the clinic. Microbubble enhanced sonography will be developed using the ovine corpus luteum, the structure in the body with the most marked microvascular circulation. This gland undergoes predictable phases of marked angiogenesis and vascular regression, representing a minimal and maximal perfusion, and the vascular development can be manipulated in vivo. Quantitative microvascular assessment will be performed initially on the normal as well as the chemically regressed ovary, and will lead to the development of an intravaginal probe for real-time ovarian contrast imaging. The results will be compared with endocrinological and histological data. A 3D perfusion imaging technique will be finally developed as means of an objective real time histology tool. The research will translate into clinical diagnostic applications during pelvic sonography for the detection of abnormal microvascular networks such as seen in endometriosis, adenomyosis, pelvic inflammatory disease and ectopic pregnancy.

Publications

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Buchoux A (2015) Manufacturing of microcirculation phantoms using rapid prototyping technologies. in Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference

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Butler M (2011) On the acoustic response of microbubbles in arteriole sized vessels in Applied Physics Letters

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Butler Mairead (2010) Single microbubble acoustics in small tubes. in Proceedings of 20th International Congress on Acoustics

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Butler MB (2014) A setup for the assessment of the effect of tubular confinement on the acoustic response of microbubbles. in Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference

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Perperidis A (2014) Automatic dissociation between microvasculature and larger vessels for ultrasound contrast imaging. in Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference

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Sboros V (2010) The assessment of microvascular flow and tissue perfusion using ultrasound imaging. in Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine

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Sboros V (2011) Imaging of the ovine corpus luteum microcirculation with contrast ultrasound. in Ultrasound in medicine & biology

 
Description British Heart Foundation project grant
Amount £180,000 (GBP)
Funding ID PG/10/021/28254 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2011 
End 09/2019
 
Description CLASP award
Amount £274,489 (GBP)
Funding ID ST/M007804/1 
Organisation Science and Technologies Facilities Council (STFC) 
Sector Public
Country United Kingdom
Start 06/2016 
End 08/2018
 
Description Distance Education Initiative
Amount £238,650 (GBP)
Organisation University of Edinburgh 
Sector Academic/University
Country United Kingdom
Start 07/2012 
End 06/2014
 
Description James Watt sholarship
Amount £50,000 (GBP)
Organisation Heriot-Watt University 
Sector Academic/University
Country United Kingdom
Start 10/2012 
End 01/2016
 
Title image analysis software 
Description the software improves the resolution, sensitivity and reproducibility of micro-vascular imaging. It utilizes data from any commercial ultrasound imaging systems and it can be used offline 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact We believe that this software may have commercial potential, as it is a new application that may improve clinical diagnosis. We, thus, consider generating further funding to refine and validate it in order to explore its potential. 
 
Description Microbubble agents 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution n/a
Collaborator Contribution Microbubble agent materials for in vivo experiments
Impact multidiscipline further funding (material science, in vitro physics experimentation, medical imaging, fluid mechanics, acoustics)
Start Year 2011
 
Description Microbubble agents 
Organisation University of Virginia (UVa)
Country United States 
Sector Academic/University 
PI Contribution n/a
Collaborator Contribution Microbubble agent materials for in vivo experiments
Impact multidiscipline (material science, in vitro physics experimentation, medical imaging, acoustics)
Start Year 2012
 
Description Microbubble physics 
Organisation Erasmus MC
Department Department of Biomedical Engineering
Country Netherlands 
Sector Academic/University 
PI Contribution in vitro experimental investigation, supervision
Collaborator Contribution hardware and software access, supervision, management
Impact 2 publcations. Disciplinear involved are optics, acoustics, fluid dynamics.
Start Year 2010
 
Description Tracer kinetics modelling 
Organisation University of Cyprus
Country Cyprus 
Sector Academic/University 
PI Contribution In vivo data
Collaborator Contribution Software with mathematical models
Impact publication (mathematical modelling, electrical engineering, in vivo experimentation)
Start Year 2008
 
Description Vascular physiology 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Physics experimental data
Collaborator Contribution Scientific advice
Impact further funding (physiology, in vivo experimentation, medical imaging)
Start Year 2011
 
Description computational fluid mechanics 
Organisation University of Thessaly
Department Department of Mechanical Engineering
Country Greece 
Sector Academic/University 
PI Contribution data sharing, supervision
Collaborator Contribution hardware, software
Impact 2 publications. Disciplines involved: Fluid mechanics, mathematical simulations, in vitro experimentation.
Start Year 2011
 
Description 'Let's talk about sex and babies' public lectures 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact more than 100 people attended and questions on the impact of our research were posed.

The public appreciated the need to do animal experiments in order to improve much needed technology for humans. The general impression was that there is an increasingly positive feedback on such experiments.
Year(s) Of Engagement Activity 2010,2011,2012,2013,2014,2015,2016
 
Description ESRC public information day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 250 members of public attended

The event was designed to raise public awareness
Year(s) Of Engagement Activity 2012
 
Description Edinburgh Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact More than 1000 members of the general public. An interest was expressed in hands on tools that enable live imaging for parts of the human body.

Awareness and understanding of the general public of the technologies that are available to them by the Health Services. As a consequence the public appreciated that more research is required to improve public health.
Year(s) Of Engagement Activity 2010,2011,2014,2015,2016
 
Description Nexxus 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The Scottish Life Science Network, Nexxus, featured the Institute of Biological Chemistry, Biophysics and Bioengineering on its front cover of its quarterly magazine, highlighting the new inter-disciplinary biomedical research being established at Heriot Watt University.


It is possible to monitor the impact of this
Year(s) Of Engagement Activity 2012
 
Description School Visits 
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 It is estimated around 500 pupils have attended our workshop and were attracted by tools that allow them to create their own medical images. An ultrasound scanner is available in this workshop and children are keen to use it.

Pupils that were exposed to the workshop appreciated the need for technolgical developments in order to improve public health. In addition, our workshop improves the public image that Basic Sciences have in children by removing the fear especially expressed for Physics and Mathematics. Children have expressed interest to follow a career path in Medical Imaging.
Year(s) Of Engagement Activity 2010,2011,2014,2015
 
Description School visit 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Local
Primary Audience Schools
Results and Impact 30 local children attended

The activity received excellent feedback as it engaged children in a sophisticated scientific research activity.
Year(s) Of Engagement Activity 2012