A hybrid optical and ultrasound system to measure localized oxygenation, blood flow and oxygen consumption in the human body

Lead Research Organisation: University College London
Department Name: Medical Physics and Biomedical Eng

Abstract

A patient's health is in great danger when there is a prolonged lack of oxygen delivery to meet the metabolic demand of the tissue. This will eventually lead to cell death and organ failure. Therefore, it is very important for clinicians to monitor oxygenation in the body especially in critically ill patients or those undergoing major surgery. For example a measure of the oxygen levels in the venous system (venous oxygen saturation) has been shown to be very useful in reducing the death rate of patients with severe symptoms of whole body infection (sepsis). Also, measurements of venous oxygen saturation have been shown to be a good predictor of post-operative complications. Currently, clinical monitoring of venous oxygen saturation involves inserting an invasive catheter into a vein near the neck to perform measurements directly on the blood. However, the invasive procedures required to make these measurements demand considerable surgical skill and are associated with risk such as infection and bleeding. These procedures are only carried out in patients deemed sick enough to justify the risk, e.g. patients in the intensive care unit. These practicalities preclude many patients who can potentially benefit from the diagnostic value of the venous oxygen saturation measurement. The main objective of this work is to develop a new clinical monitor which can measure venous oxygen saturation non-invasively by combining optical and ultrasound technologies. The new clinical monitor has a probe containing both optical and ultrasound components which can be placed on the skin surface over the measurement site and target a localised region beneath. For example, it can be placed over the chest and measure the venous oxygen saturation in the pulmonary artery which contains the blood that has circulated through the whole body. This non-invasive venous oxygen saturation measurement can replace its invasive catheter based counterpart for clinical monitoring. The new monitor can also be used to target a vein draining the blood from the brain (jugular vein) so that the condition of the brain can be monitored. Other applications include the monitoring of limbs with poor circulation, recovery after surgery and the functioning of transplanted organs. Apart from venous oxygen saturation, the new monitor can also be used to measure blood flow and oxygen consumption, which indicates oxygen delivery to the tissue and the amount of oxygen used up by the tissue respectively. The principle of the new monitor is based on the phenomenon that ultrasound waves can cause periodic movement within a specific tissue region changing the way light travels through it. When light passes through this region, the intensity of the light will be altered and can be detected by a surface mounted optical detector. In other words, the light is tagged by the ultrasound waves which are the strongest in the target region. The detected tagged light is known as the acousto-optic signal and can be used to derive localized oxygenation, blood flow and oxygen consumption.In this work, different ways of combining the optical and ultrasound techniques will be systematically investigated, including the enhancement of the acousto-optic signals using short bursts of high energy ultrasound and microbubbles (an ultrasound contrast agent often used in modern ultrasound scan to improve image quality). The investigation will be conducted by both laboratory based and human experiments. For a thorough understanding, computer models will also be developed to explain the different mechanisms that generate the acousto-optic signals. These investigations will allow the design of a reliable hybrid monitor optimized for clinical use in a range of different settings.
 
Description This grant has enabled our team to investigate the hybrid use of sound, light and microwaves, with potential applications in clinical monitoring:
(1) Acousto-optic (AO) imaging: We have successfully demonstrated an AO technique to image a colour picture hidden behind a 5 mm thick, highly scattering layer, using a CCD camera and an acoustic source. This technique can potentially be further developed to map colour features behind the human skull, e.g., mapping oxygenation changes over the brain cortex during functional task experiments, and mapping the location and size of subdural hematomas in head injured patients. In another study, we have shown for the first time the experimentally obtained spatial sensitivity maps of AO measurements. By incorporating focused ultrasound, the AO measurements become more sensitive to the region of interest deep inside the turbid medium. This work provides useful fundamental information for measuring localised oxygenation and designing AO sensing and tomography algorithms.
(2) Computational models: We have developed the first graphics processing unit accelerated computational Monte Carlo model for AO which is much faster than previous implementations. Based on this model, a more advanced one has been developed which can handle heterogeneous acoustic and optical media. This code is the fastest and most flexible one on AO to date. It is a powerful tool for the design of AO imaging/sensing systems. We have also developed the first quantitative reconstruction method for AO imaging which can recover both the optical absorption and scattering coefficients simultaneously. This reconstruction method not only allows optical scattering coefficient to be recovered for the first time alongside absorption, but also reduces the artefacts often found in an AO image caused by the "shadowing effect".
(3) Microbubble enhanced acousto-optic sensing: We have demonstrated the enhancement of AO signals in blood by using microbubbles with experiments and computer simulations. We have also published the first computational study showing how the microbubble-enhanced AO signals can be used to measure oxygen saturation in a large blood vessel. These studies will allow us to optimise a clinical diagnostic system based on AO.
(4) Hybrid microwave-optical monitor: We have developed the first-of-its-kind hybrid monitor to measure microvascular oxygenation changes in response to thermal provocation in muscle, and tested it in 4 human subjects. The hybrid probe is capable of inducing deep heat from the skin surface using mild microwaves (1-3W) and raises the deep tissue temperature by a few degrees Celsius. This causes vasodilation and the subsequent increase in blood volume is detected by the hybrid probe using near infrared spectroscopy. Based on the vasculature's response to external heat, this hybrid monitor can potentially be used to assess the obstruction of vasculature and disruption of sympathetic pathways in patients.
Exploitation Route One important progress we have made is the development of computational models and 3D reconstruction algorithms which we have described in details in a series of journal papers. These models and algorithms have also been implemented as a software package which can be used by various research groups worldwide to reconstruct 3D images of optical absorption and scattering coefficients using acousto-optic measurements acquired from their own imaging systems. For instance, we worked with a world renowned acousto-optics group in Paris (led by Dr Francois Ramaz at ESPCI) to adapt our codes to reconstruct optical images using measurements obtained from their acousto-optic photorefractive system. We continued this collaboration through a joint PhD studentship awarded by a French funding agency, Direction générale de l'armement. Biomedical acousto-optics research tend to focus on the detection system and the hardware involved. Our software package fulfils the need to exploit the acquired acousto-optic measurements in a more effective, accurate manner with a tractable, sound theoretical foundation. This work will eventually help bringing acousto-optic technology to the hospital.
Sectors Healthcare
 
Description The publications produced from this research have been cited in studies which aim to improve the diagnosis of patients through tissue, breast and brain imaging.
First Year Of Impact 2014
Sector Healthcare
Impact Types Societal
 
Description Thèses en coopération franco britannique (France and UK joint PhD studentship)
Amount € 129,000 (EUR)
Funding ID 2014385 
Organisation General Directorate for Armament 
Sector Academic/University
Country France
Start 10/2014 
End 09/2017
 
Title QUMOT 
Description We have developed the first graphics processing unit accelerated computational Monte Carlo model for acousto-optics (AO) which is much faster than previous implementations. Based on this model, a more advanced one has been developed which can handle heterogeneous acoustic and optical media. This code is the fastest and most flexible one on AO to date. It is a powerful tool for the design of AO imaging/sensing systems. We have also developed the first quantitative reconstruction method for AO imaging which can recover both the optical absorption and scattering coefficients simultaneously. This reconstruction method not only allows optical scattering coefficient to be recovered for the first time alongside absorption, but also reduces the artefacts often found in an AO image caused by the "shadowing effect". (DOI: 10.1117/1.JBO.18.12.126020 & 10.1117/1.JBO.17.4.045002 ) 
Type Of Material Computer model/algorithm 
Year Produced 2013 
Provided To Others? Yes  
Impact These models and algorithms have also been implemented as a software package which can be used by various research groups worldwide to reconstruct 3D images of optical absorption and scattering coefficients using acousto-optic measurements acquired from their own imaging systems. For instance, for the past year, we have been working with a world renowned acousto-optics group in Paris (led by Dr Francois Ramaz at ESPCI) to adapt our codes to reconstruct optical images using measurements obtained from their acousto-optic photorefractive system. We will continue this collaboration through a joint PhD studentship recently awarded by a French funding agency, Direction générale de l'armement. Currently, biomedical acousto-optics research mainly focuses on the detection system and the hardware involved. Our software package fulfils the need to exploit the acquired acousto-optic measurements in a more effective, accurate manner with a tractable, sound theoretical foundation. This work will eventually help bringing acousto-optic technology to the hospital. 
 
Description Acousto-Optic Imaging and Modelling 
Organisation ESPCI ParisTech
Country France 
Sector Academic/University 
PI Contribution We have developed a software package to analyse the measured data acquired by our collaborator using their acousto-optic imaging system. Based on these data, we can reconstruct 3D images of optical absorption and scattering.
Collaborator Contribution Our collaborator in Paris performed imaging experiments using their state-of-the-art acousto-optic photorefractive system to generate data which will then be analysed by our software.
Impact The collaboration is still in early stage. We have recently secured a joint France-UK PhD studentship funded by the Direction générale de l'armement to pursue this collaboration further (129K EUR). This will allow the PhD student to spend at least one year at UCL to further develop the acousto-optic technique. First publications from this collaboration are expected in early 2015.
Start Year 2013