A Novel Ultrasound Modulated Optical Tomography System

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


Optical imaging of biological tissue is able to provide structural and functional information, which potentially enables early detection of abnormalities such as tumours and detection of tissue oxygenation. However, one disadvantage of such technique is the difficulty to image objects at depth. By comparison, ultrasound imaging is able to provide good image resolution at depth and is an established clinical imaging modality. However, ultrasound imaging is based on the detection of the mechanical properties in tissues which is not as sensitive as optical techniques in e.g. detecting tumours.Ultrasound-modulated optical tomography (UOT) is a new technique to take advantage of the combined strengths of the two imaging modalities. In UOT, light is transmitted into the target tissue and at the same time an ultrasonic wave is focused into the tissue to modulate the light. The scattered light from the tissue can be measured and images of tissue optical properties can be reconstructed, with a spatial resolution primarily defined by ultrasound. Studies of UOT as a medical imaging tool only began in the 90s. Although promising images have been produced with laboratory phantoms and excised tissues, a significant challenge of the current UOT technique is the weak optical modulation signal to be measured. A direct way to tackle the problem of weak optical signal is to maximise the ultrasonic modulation of all light passing through the ultrasound focus. Past studies show that simply increasing the ultrasound amplitude may not be sufficient and also has some adverse effects. In this project, we propose to develop a novel UOT system with dual-frequency ultrasound excitation to maximise the modulated light signal. In this pilot study both a computer simulation system and an experimental system will be developed and results compared with the conventional UOT system. This new system has the potential to significantly improve UOT image quality.

Planned Impact

Who will benefit? a) Patients with diseases resulting in changed tissue optical/EM properties or blood flow such as cancer and cardiovascular diseases. b) Clinicians who diagnose and treat the above patients c) Healthcare system d) Wider population and economy e) UOT research community f) Biomedical research community g) Biomedical Imaging industry h) Pharmaceutical companies What will these impacts be, and what is their importance? a) The patients and the clinicians will benefit from a new imaging technique which can help with the diagnosis and treatment. Such information is not available through current clinical means. b) The UOT research community will benefit from a new method to generate ultrasound modulated optical signals and a novel, publicly available, simulation software. c) Ultimately, both the biomedical research community and pharmaceutical companies will benefit from a new imaging technique which enables longitudinal studies in pre-clinical studies. d) Potential development of new products by commercial biomedical imaging companies to exploit and commercialise the new technique e) Economic impact through more effective disease management and treatment, resulting in shorter hospital stays and faster recovery time. Realistic timescales for the benefits to be realised This is a feasibility study and many of the potential benefits will require additional further research and development (~an additional 3 years). What research and professional skills will staff working on the project develop? The RA will further develop the following skills: a) Numerical: parallel computing, numerical simulation, programming, b) Experimental: making ultrasonic and laser measurements; making test objects/phantoms; operating common electronic equipments. c) Other: writing reports and papers, presentation skills, communication skills All the investigators involved in this project will learn from one another. As their backgrounds are each different in bio-optics, bio-photonics, medical ultrasonics, numerical simulation and signal processing they possess . What will be done to ensure that they benefit? This is a feasibility study and we plan at this early stage to do the following to ensure the impact of this research: 1) Dissemination of results through publications and conference presentations. This will draw attention from both academic and industrial beneficiaries; 2) Generation and update of a webpage dedicated for the project with the software generated through the project. This will provide a port for publicising this research; 3) Working with the college technology transfer company Imperial Innovations to identify and engage potential industrial partners as early as possible; 4) Engaging potential biological and clinical end users by giving presentations in various networks within the Imperial College Faculty of Medicine, NHS Trust and Academic Health Sciences Centre. Academic beneficiaries For other researchers in the field, firstly they will benefit from a novel UOT simulation tool which will be published on our webpage. No such public software exists. Secondly, they will benefit from a better understanding of how light and tissue interact with dual frequency ultrasound, how optical measurements vary under such conditions and the shear wave effects. As end users of this technique biomedical researchers working on pre-clinical models will benefit from a non-invasive functional imaging technique which allows longitudinal studies. This research is cross-disciplinary and the new knowledge generated will benefit both the ultrasound and optical imaging communities. The project involves researchers from the Faculties of Engineering, Natural Science and Medicine to bring in the skills needed to make an impact both in biophotonics and ultrasound.
Description Ultrasound-modulated optical tomography (UOT) is a new technique to take advantage of the combined strengths of optical and ultrasound imaging, providing tissue structural and functional information with good image resolution at depth. Such imaging system has great potential in the diagnosis and treatment monitoring of a wide range of clinical conditions such as cancer and cardiovascular diseases. Currently a significant challenge of the UOT technique is the weak signal to be measured. The main aim of this project is to establish the feasibility of a new UOT technique which uses acoustic radiation force (ARF), a localised force induced by ultrasound in tissue that can displace tissue by several micrometres, to improve the measured signal in UOT. The project has achieved and exceeded the initial goals set out in the proposal and a follow-on project proposal is in preparation. The specific achievements against the objectives are listed below:

Objective 1: To develop and initially evaluate a new ultrasound modulated tomography (UOT) simulation system with assistance of ARF;

This has been achieved and the results were presented at the SPIE Photonics conference, a major meeting in biomedical photonics. (R Li et al., Monte Carlo simulation study of light modulated by acoustic radiation force in elastic-viscous medium, SPIE Photonics West conference 2011)

Objective 2: To develop and initially evaluate a new ultrasound modulated tomography (UOT) experimental system with assistance of ARF;

Not only has this been fully achieved but the results went beyond what was initially proposed. Specifically:

1) A new ARF assisted UOT system has been developed in the laboratory and our experimental results on test phantoms have shown an improvement in the system signal amplitude by as much as 110%. Furthermore, the proposed system also improves the image spatial resolution by 40%, which is an achievement beyond our initial proposal. (R Li et al., Effects of acoustic radiation force and shear waves for absorption and stiffness sensing in ultrasound modulated optical tomography, OPTICS EXPRESS V19(8), P7299-7311,2011)

2) The ARF assisted UOT system is also capable of imaging the tissue mechanical properties (stiffness), which can be distinguished from the tissue optical properties. This is also an achievement beyond our initial proposal. (R Li et al., Effects of acoustic radiation force and shear waves for absorption and stiffness sensing in ultrasound modulated optical tomography, OPTICS EXPRESS V(8), P 7299-7311,2011)

3) The effects of a low-frequency oscillating acoustic radiation force (ARF) on UOT signals have been studied for the first time. It has been shown that the shear wave generated in tissue significantly affects the localization of UOT signals and should be avoided. (R Li et al., Parallel detection of AM ultrasound modulated optical signals, Optics Letters 2010 Vol. 35(15), pp. 2633-2635)

4) It has been shown for the first time that tissue stiffness can be measured by an UOT system, through tracking the ARF generated shear wave propagation in tissue. This offers a new tissue elastography technique and is also an achievement beyond our initial proposal.(journal paper in preparation)

Objective 3: To develop an UOT simulation software package for common use.

This has been fully achieved. An UOT simulation system has been developed and will soon appear online for free download(http://www3.imperial.ac.uk/people/mengxing.tang/research). This would offer the research community a useful tool for studying UOT and acousto-optic effect in general.

We also published two invited review papers:

DS. Elson et al., , Ultrasound-mediated optical tomography: a review of current methods, Interface Focus, doi:10.1098/rsfs.2011.0021

M-X Tang et al., PhotoacousticsPhotoacoustics, thermoacoustics, and acoustooptics for biomedical imaging, Proc. Inst. Mech. Eng. Part H: J. Eng. Med., 2010 Vol 224 (H2),p291-306
Exploitation Route We have developed a new way of sensing tissue stiffness and optical properties non-invasively. This is a short project (1 year) on feasibility study. In order to take the work forward further studies to fully evaluate the proposed method on patients would be required. Once clinically validated the method could have a broad implication in the management of a wide range of diseases including cancer.
Sectors Education,Healthcare