Modular discrete-wavelength light source synchronised with an intensity imaging camera for high-speed multispectral imaging

Lead Research Organisation: University of Birmingham
Department Name: School of Computer Science

Abstract

Colour plays an important role in the clinical diagnosis of many conditions. However, the receptors in the eye, as well as the sensors in a standard colour camera, provide only a limited representation of the visible spectrum in the form of three broad bands: red, green and blue. Multispectral images, where many narrow spectral bands are recorded, can yield information beyond what is possible by observation or conventional photography. In particular, advanced computational techniques can be used to derive biopsy-like quantitative maps characterising tissue composition in a totally non-invasive manner. Different sets of spectral bands can be selected, through optimisation techniques, to visualise different tissue components such as oxidised and non-oxidised blood, melanin, macular pigment, density of cells and organelles, etc. These techniques work well in situations where the tissue can be immobilised, but in some applications (e.g. retinal imaging, endoscopy), the tissue under examination is subject to involuntary movement and so can become displaced in a sequence of images. Whilst the displacement can be corrected using image processing techniques (image registration), the illumination of points also changes under movement, and this cannot be corrected by registration. It is thus necessary to obtain images at timescales faster than the natural movement of the tissue, at the same ensuring sufficiently long exposure times to maintain high image quality.A wide variety of commercial digital imaging systems are available based on broadband (e.g. white light) sources and digital video cameras. Where limited spectral bandwidth is required, narrow optical filters can be inserted. However, such systems may not allow a series of images at different spectral bands to be acquired with the speed sufficient for non-stationary objects. The principal objective of this project is to develop a modular imaging system which can be used in a range of imaging instruments to enable them to sequentially acquire digital images at an arbitrary number of wavelengths at video speed frame rates. The system will comprise a discrete multispectral light source synchronised with a scientific-grade monochrome imaging camera, connected via a computer controlled interface so that illumination and image capture are synchronised and the sequence and timing of the acquisition can be selected according to the needs of the application.The design will be exemplified by building and demonstrating a prototype system for use with a fundus camera for rapid multispectral imaging of the retina. Recent research has shown that quantitative maps of retinal blood derived from such image data may provide a substitute for invasive fluorescein angiography, commonly used to reveal retinal haemorrhages which are an early sign of diabetic retinopathy and may lead to blindness. Similar maps showing the quantity and distribution of Macular Pigment could be used to predict the risk of developing sight-threatening complications in age-related macular degeneration (ARMD).The proposed imager is a generic device with potentially broad applicability. As well as improving multispectral retinal imaging, the project will demonstrate the value of the imager as a flexible research device for exploratory studies in biosciences involving fluorescence microscopy studies of dynamic processes in living cells. Other applications envisaged include the use of the imager with diagnostic imaging systems such as endoscopes and optical tomography systems for non-invasive in-vivo diagnosis and monitoring of human tissues and organs.
 
Description In this project we have developed a flexible imaging system capable of sequentially acquiring digital images at arbitrary wavebands at video speed frame rates. The system comprises a multispectral light source which can accommodate a combination of up to 12 light-emitting diodes (LEDs) and laser-diodes. Light from the diodes is transmitted via an optical fibre cable which can be connected to a range of imaging instruments. The light source is synchronised with the highly sensitive CCD camera, and both are connected to a PC. The sequence and timing of the acquisition can be selected via a simple user interface according to the needs of the application.

The system has been validated for several biomedical imaging applications. For retinal imaging a commercial ocular microscope (a fundus camera) was modified by replacing its standard xenon flash lamp with the output from the optical fibre cable, and by adding a computer-controlled trigger. Tests on human volunteers showed practically no movement between 6 successive frames acquired at 20-50ms (displacement of up to 2 pixels was the same as for a stationary artificial eye); and minimal movement (maximum up to 6 pixels) between 36 frames. Images resolve details down to 50 microns and are thus capable of showing small retinal vessels and microaneurysms. Multispectral images of this quality provide an excellent input to the image analysis algorithms which generate quantitative maps of retinal blood and which may provide a substitute for invasive fluorescein angiography, used to reveal haemorrhages which are an early sign of diabetic retinopathy. Similar maps for Macular Pigment could be used to predict the risk of developing age-related macular degeneration.

In another application the imaging system was connected to a research microscope, replacing its Mercury light source and a set of optical filters with our system's optical fibre cable output. Fluorescent beads were crisply imaged at exposure times of 10ms, and cells containing fluorescent proteins (YFP and GFP) at exposure times of 100ms. The relatively low power of the new light source means that cells are not damaged during the imaging process, which could be the case when using a powerful Mercury lamp. The imager is thus highly suitable for studies of dynamic processes in living cells, important for understanding many diseases including cancers and autoimmune diseases.

In conclusion, we have demonstrated that the new imager potentially has a broad applicability in medicine and biosciences. It will continue to be evaluated in a variety of studies of the human retina, as well as for near-infrared spectroscopy applications of tissue oxygenation; and in biosciences, for tracking of fluorescent markers which precisely target and highlight abnormal sites in the body.
Exploitation Route -diagnosis of eye diseases (a non-invasive substitute for fluorescein angiography; evaluation of quantity and distribution of Macular Pigment which is believed to be a predictive factor in the risk of developing sight-threatening complications in agerelated

macular degeneration)


Ophalmic imaging - healthcare;

Ophthalmic imaging - industrial R&D
Sectors Healthcare

 
Description Multispectral Retinal Image Analysis (MRIA): A new technique for the assessment of age-related macular degeneration and its treatment
Amount £95,989 (GBP)
Funding ID R116/0509 
Organisation The Dunhill Medical Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2010 
End 06/2012
 
Description Collaboration with Aston University Ophthalmic Research Group and Aston Research Centre for Healthy Ageing 
Organisation Aston University
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration on the use of the multispectral retinal imager for quantification of macular pigment and prognosis for the Age Related Macular Degeneration. Research collaboration; setting up of a clinical evaluation.
Start Year 2009
 
Description Instrumentation for multispectral retinal imaging 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Development of the imaging protocol, wavelength selection, experimental validation
Collaborator Contribution Design and construction of a multispectral light source
Impact Several research publications (see publications listed under EPSRC grant EP/E0652361/1 Research grant from The Dunhill Medical Trust that used the device developed jointly with UCL
Start Year 2006
 
Title Multispectral retinal imaging system 
Description The system was used for retinal imaging associated with Age Related Macular Degeneration in a study funded by The Dunhill Medical Trust. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2012
Development Status On hold
Impact A small study carried out was insufficient for firm conclusions, but the device has a potential to improve diagnosis in AMD. 
 
Title Multispectral Retinal Image Analysis (MRIA) 
Description Novel image interpretation method for multispectral images of the retina. 
Type Of Technology Software 
Year Produced 2012 
Impact Successfully applied in the study of AMD funded by The Dunhill Medical Trust. 
 
Description Multispectral Retinal Image Analysis: a new technique for the assessment of macular pigment 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Disseminating information on a user-friendly imaging tool (multispectral retinal image analysis, MRIA) for quantification of macular pigment, so that low levels of this substancecan be flagged in individuals and appropriate dietary measures can be

taken either to reduce the potential risk of developing AMD or to slow/reduce its progression.

General knowledge dissemination.
Year(s) Of Engagement Activity 2011