Ultrafast contrast enhanced ultrasound for imaging and quantifying flow and tissue perfusion

Lead Research Organisation: Imperial College London
Department Name: Dept of Bioengineering


Imaging and quantifying blood flow and perfusion are critical to the diagnosis and management of a range of major diseases including coronary heart disease, valvular heart disease, carotid, cerebral and peripheral vascular diseases, cancer, and chronic inflammation, all of which manifest themselves with abnormalities in flow and perfusion. Existing imaging and quantification techniques have numerous limitations. Ultrasound imaging is one of the most widely used clinical imaging methods, offering safety, real-time imaging, low cost and excellent accessibility. Recent advances in ultrafast ultrasound techniques can increase ultrasound imaging speed by up to two orders of magnitude and have resulted in exciting developments in non-contrast enhanced ultrasound applications, including soft tissue elastography, brain functional imaging and cardiac imaging. If combined with advances in contrast enhanced ultrasound (CEUS) using microbubble contrast agents, the ultrafast techniques have the potential to improve the conspicuity of the contrast agent by up to 10 times and greatly extend the field of view or the dynamic range of blood flows that can be tracked through ultrasound; these hitherto unrealised improvements could dramatically impact the ability to image and quantify flow and perfusion. In this project we propose to develop and evaluate novel ultrafast CEUS methodologies and systems for this purpose, building on our extensive research experiences on microbubble contrast agent imaging. They have the potential to become the next generation ultrasound tools for pre-clinical and clinical imaging of blood flow and tissue perfusion, giving unprecedented performance in terms of accuracy, SNR, sensitivity, specificity and resolution.

Planned Impact

The proposed project will develop and evaluate new ultrasound tools for imaging and quantification of flow and perfusion. Flow and perfusion are biomarkers for a number of major diseases including coronary heart diseases, cancer, carotid and peripheral vascular diseases, chronic inflammation and valvular heart disease. Patients with these major diseases comprise a very significant fraction of the population. The tools to be developed would be highly valuable for the detection, diagnosis and staging of these diseases and also monitoring of progression and treatment of these diseases. Specifically:
* Patients with the above diseases can benefit from this clinical imaging tool which is safe and easy to access and could lead to fast and better diagnosis, more informed treatment planning, and improved treatment monitoring/evaluation.
* Clinicians can benefit from new imaging tools which offers quantitative vascular information for patient diagnosis and management.
* NHS could benefit from this powerful and affordable imaging tool for assisting the diagnosis and management of patients.
* Microbubble and ultrasound manufacturing industry can benefit from this technique through wider and increased use of microbubbles and ultrasound imaging in hospitals.
* Finally researchers interested in studying the above diseases would also benefit from the new imaging tools for imaging flow and perfusion.


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Christensen-Jeffries K (2020) Super-resolution Ultrasound Imaging. in Ultrasound in medicine & biology

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Christensen-Jeffries K (2017) Microbubble Axial Localization Errors in Ultrasound Super-Resolution Imaging. in IEEE transactions on ultrasonics, ferroelectrics, and frequency control

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Christensen-Jeffries K (2017) 3-D In Vitro Acoustic Super-Resolution and Super-Resolved Velocity Mapping Using Microbubbles. in IEEE transactions on ultrasonics, ferroelectrics, and frequency control

Description - We have developed methodologies and system for acquiring contrast enhanced ultrasound images at frame rates 1-2 orders of magnitude higher than existing technologies;
- We have developed image tracking techniques for mapping arterial flow velocities
- We have developed methodologies for quantifying tissue perfusion/microcirculation
- We have demonstrated the applications of the above developed technologies in vivo. These technologies have great potential in improved diagnosis and patient management of a wide range of diseases including cardiovascular diseases and cancer.
Exploitation Route We are currently working with clinicians to evaluate the technologies on patients. If successful the technologies could change current clinical practice.
Sectors Healthcare

Description BHF Project Award
Amount £179,389 (GBP)
Funding ID PG/16/95/32350 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2017 
End 06/2020
Description CRUK MDA
Amount £485,213 (GBP)
Funding ID C53470/A22353 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2016 
End 05/2020
Description EPSRC Impact Acceleration Account Funding
Amount £75,118 (GBP)
Funding ID EP/R511547/1 
Organisation Imperial College London 
Sector Academic/University
Country United Kingdom
Start 04/2019 
End 03/2020
Description Collaboration with Hammersmith 
Organisation Hammersmith Hospital
Department Renal Unit, Hammersmith Hospital
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution We have developed HFR CE technologies ready for in vivo feasibility study.
Collaborator Contribution A first in human feasibility study of the technologies was co-organised by the partner and my group.
Impact A joint paper in JACC CVI has been published.
Start Year 2016
Title Acoustic sub-aperture processing for ultrasound imaging 
Description A new method, Acoustic Sub-Aperture Processing (ASAP), has been developed to improve the signal to noise ratio and contrast of an ultrasound image. The method splits the ultrasound aperture and takes advantages of the fact that signals are common between sub-apertures but noises are not. So a correlation between the sub-aperture signals could generate much improved image quality. The method could have an impact on a wide range of clinical applications. 
IP Reference GB2551376 
Protection Patent application published
Year Protection Granted 2017
Licensed No
Impact The method is shown to be able to significantly improve image quality and if adopted clinical could have an impact on a wide range of clinical applications and benefit the patients and clinical professionals.
Description Imperial Festival 
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 Public/other audiences
Results and Impact We have a presentation booth as part of the Imperial Festival with the theme "Seeing with sound to treat cancer and heart diseases ". The booth has been visited by >100 from the general public.
Year(s) Of Engagement Activity 2015
URL http://www.imperial.ac.uk/be-inspired/festival/
Description Presentation at Pint of Science 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I was invited to give a presentation for Pint of Science. I used the opportunity to present the science of using bubbles in medical ultrasound imaging.
Year(s) Of Engagement Activity 2017
URL https://pintofscience.co.uk