A Monte Carlo simulation of light propagation through the retina has been developed to understand the path-length distributions within the retinal vessel. For full-field illumination, the path-length distribution within the vessel comprises directly backscattered light and light that has passed once or twice through the vessel. The origins of these light path-length distributions can be better understood by investigating different combinations of single-point illumination and detection positions. Perhaps the most significant observation is that illumination at the edges of the vessel, rather than over the whole field of view, and detection directly above the vessel capture only the light that has taken a single pass through the vessel. This path-length distribution is tightly constrained around the diameter of the vessel and can potentially provide enhancements for oxygen saturation imaging. The method could be practically implemented using an offset-pinhole confocal imaging system or structured light illumination.
KEYWORDS: Signal detection, Modulation, Acoustics, Scattering, Signal to noise ratio, Reconstruction algorithms, Data modeling, Tissue optics, Ultrasonography, Transducers
In pulsed ultrasound modulated optical tomography (USMOT), an ultrasound (US) pulse performs as a scanning probe within the sample as it propagates, modulating the scattered light spatially distributed along its propagation axis. Detecting and processing the modulated signal can provide a 1-dimensional image along the US axis. A simple model is developed wherein the detected signal is modelled as a convolution of the US pulse and the properties (ultrasonic/optical) of the medium along the US axis. Based upon this model, a maximum likelihood (ML) method for image reconstruction is established. For the first time to our knowledge, the ML technique for an USMOT signal is investigated both theoretically and experimentally. The ML method inverts the data to retrieve the spatially varying properties of the sample along the US axis, and a signal proportional to the optical properties can be acquired. Simulated results show that the ML method can serve as a useful reconstruction tool for a pulsed USMOT signal even when the signal-to-noise ratio (SNR) is close to unity. Experimental data using 5 cm thick tissue phantoms (scattering coefficient μs = 6.5 cm−1, anisotropy factor g = 0.93) demonstrate that the axial resolution is 160 μm and the lateral resolution is 600 μm using a 10 MHz transducer.
KEYWORDS: Doppler effect, Sensors, Signal detection, Diffusers, Semiconductors, Signal processing, Calibration, Semiconductor lasers, Photodiodes, Digital signal processing
A 32×32 pixel array has been fabricated in a 0.35-μm complementary metal-oxide semiconductor process with the aim of producing two-dimensional laser Doppler blood-flow images. In the design, each pixel contains five basic elements: a photodiode, a front-end consisting of a current to voltage converter, voltage amplifier, antialiasing filter, and buffer. The analog design is optimized for the detection of laser Doppler blood-flow signals and thus offers advantages over conventional sensors. The analog outputs are passed through an on-chip multiplexer and digitized by an external analog-to-digital converter. The sensor has been fully characterized electrically and optically using modulated electrical and optical signals. A calibration process for fixed pattern noise reduces the standard deviation of the ac gain by a factor of 2. The imaging response is tested by imaging a vibrating test structure and a rotating diffuser. Blood-flow measurements on a finger before and after occlusion demonstrate that the sensor array is capable of detecting blood-flow signals from tissue. The knowledge gained from the characterization of the design can be used to develop a fully integrated laser Doppler blood-flow sensors with a higher number of pixels.
Full field laser Doppler perfusion imaging offers advantages over scanning laser Doppler imaging as the effects of
movement artifacts are reduced. The increased frame rate allows rapid changes in blood flow to be imaged.
A custom made CMOS sensor offers several advantages over commercial cameras as the design can be optimized to the
detected signals. For example, laser Doppler signals are known to have a bandwidth from DC up to ~20KHz and be of a
low modulation depth. Therefore a design that can amplify the AC component and have a sampling rate and an antialiasing
filter appropriate to the signal bandwidth would be beneficial. An additional advantage of custom made sensors
is that on-chip processing of blood flow allows the data bottleneck that exists between the photo-detector array and
processing electronics to be overcome, as the processed data can be read out from the image sensor to a PC or display at
a low data rate.
A fully integrated 64x64 pixel array for imaging blood flow is presented. On-chip analog signal processing is used to
amplify the AC component, normalize the AC signal by the DC light intensity and provide anti-aliasing. On-chip digital
signal processing is used to implement the filters required to calculate blood flow.
The imaging array has been incorporated into a device that has been used in a clinical setting. Results are presented
demonstrating changes in blood flow in occlusion and release tests.
Tissue scaffolds are an integral part of the tissue engineering process, assisting in the culturing of cells in three
dimensions. It is important to understand both the properties of the scaffold and the growth of cells within the scaffold.
This paper describes a system to characterise scaffolds using acoustic techniques alone and the development of an
ultrasound modulated optical tomography system to study the growth of cells within the scaffolds.
Our interest is in characterising the properties of gel-based and polymer foam-based scaffolds. Results from a purely
acoustic system have been used to investigate the properties of foam scaffolds manufactured from synthetic polyesters
poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) via a supercritical fluid process. As these are porous
materials, they are particularly challenging acoustically as the pores scatter sound significantly. However, it is
demonstrated that acoustic signals are detectable through a 6mm thick scaffold.
Although acoustics alone can be used to characterize many properties of the scaffolds, useful information can also be
obtained from optical techniques e.g. monitoring the growth of cells within the scaffold via optical absorption or
fluorescence techniques. Light scattering is of course a significant problem for relatively thick engineered tissue
(~5mm). The acoustic approach has been extended to include laser illumination and detection of the ultrasound
modulated optical pulse. Images of optically-absorbing materials embedded in gel-based tissue phantoms will be
presented demonstrating that a lateral resolution of 250μm and an axial resolution of ~90μm can be achieved in
scattering samples.
In pulsed ultrasound modulated optical tomography (USMOT), as an ultrasound (U/S) pulse propagates, it performs as a
scanning probe within the sample, and modulates the scattered light spatially distributed along the axis of propagation.
By detecting and processing the modulated signal, the information along the U/S axis of the sample (1D image) is
studied. The signal is modelled as a convolution of the U/S pulse and the ultrasonic and optical properties of the medium
along the U/S focus. Based upon this model, a Maximum Likelihood (ML) method for image reconstruction is
established. The ML data inversion technique for a pulsed USMOT signal is, for the first time to our knowledge,
investigated both theoretically and practically. The ML method inverts the pulsed USMOT signal to retrieve the spatially
varying properties of the sample along the U/S scanning column, and then the optical absorption property can be
acquired. The results show that the ML method can serve as a useful fitting tool for a pulsed USMOT signal even in the
presence of noise. The work illustrates the application of this iterative algorithm on simulated and experimental data.
Experimental results using 5cm thick animal tissue phantoms (scattering coefficient μs is 6.5cm-1) demonstrate that the
resolution is better than 100μm using a 10MHz transducer.
An evaluation of the optimum choice of wavelengths, when using the 'Modified Lambert-Beer law' to estimate blood
oxygen saturation, that minimises the mean error across a range of oxygen saturation values is presented. The stability of
this approach and its susceptibility to noise are also considered.
Rotating orthogonal polarization imaging is a new technique that provides quantitative measurements of the polarization properties of scattering media, such as tissue, which are free from surface reflections. The technique is investigated using both experiments and Monte Carlo simulations of a polarizing target embedded within a scattering medium. The technique is sensitive to the polarization properties of the target up to a depth of 17 mean free paths. Preliminary images of bovine tendon, lamb tendon, chicken breast, and human skin are also demonstrated.
To ensure the sustainability of tissue engineered products there is a need to consider the engineering and manufacturing
issues related to them particularly for the purposes of process optimization and product quality assurance. This work
describes the application of Raman spectroscopy for in process monitoring of a skin substitute and rotating orthogonal
polarization imaging to track collagen alignment in a tissue engineered tendon. The skin substitute studied is produced
from culturing fibroblasts in a fibrin matrix. Throughout the production process the fibroblasts secrete extracellular
matrix and in doing so deposit collagen in the matrix. Key to optimization of the skin substitute production process is
development of strategies to track the collagen and fibrin content. The work presented here discusses the feasibility of
Raman spectroscopy to resolve fibrin and collagen components in the skin substitutes. Collagen alignment is also
important in the engineering of many tissues, in particular tendons. Thus, this work will also investigate the ability of
rotating orthogonal polarization imaging to track collagen alignment in a tissue engineered tendon.
KEYWORDS: Doppler effect, Signal processing, Digital signal processing, CMOS sensors, Diffusers, Blood circulation, Image processing, Sensors, Linear filtering, Imaging systems
Three sensor designs for full field laser doppler blood flow imaging will be demonstrated(i) 16x1 pixel linear array with mixed analogue and digital signal processing (ii) 4x4 pixel array with all analogue processing (iii) hybrid system which combines 32x32 pixel array with part on-chip processing linked to a field programmable gate array. Results are demonstrated using modulated light, tissue phantoms and blood flow in tissue. The efficient use of silicon when implementing the signal processing on-chip is discussed.
A fully integrated complementary metal-oxide-semiconductor 16×1 linear photodetector array with on-chip signal processing for applications in laser Doppler blood flow imaging has been designed and tested. Analog circuitry is used to provide the transimpedance amplifier, amplification of the modulated (ac) component, and antialiasing filter at each pixel, and also multiplexing of the 16 pixels. Digital signal processing is used to implement the lowpass, bandpass, and frequency-weighted filters, along with the signal averaging conventionally implemented as discrete components in laser Doppler blood flow imaging. The sensor demonstrates good agreement with simulation at each design stage. The measured optical performance of the array is demonstrated using modulated light signals and a vibrating test structure. As the first iteration of the chip, this 16×1 linear array provides an opportunity to evaluate the feasibility of full-field laser Doppler blood flow imaging with on-chip processing, with a view to providing a design that is scalable to a larger linear array or 2-D imaging array.
Rotating orthogonal polarization imaging of tissue consists of illumination in a single polarization state and detection in
the orthogonal state. Synchronously rotating the illumination and orthogonal detection provides an image that is free
from surface reflections and is sensitive to the polarization properties of the underlying tissue. Tissue phantom results are
presented which demonstrate that a polarizing target can be detected at a depth of 17 mean free paths within a scattering
medium. The results have been validated using a polarization sensitive Monte Carlo simulation.
Extracting light that has maintained its original polarization state can be used to improve the image resolution in imaging
or localize the volume probed in spectroscopy. This paper describes polarization dependent instrumentation and
modelling methods used in the imaging and spectroscopy of scattering media. The use of integrated optical sensors in
imaging the polarization difference signal is also demonstrated.
Light scattering provides a problem in optical spectroscopy as the relationship between attenuation and absorption in the presence of scattering is non-linear. Three simple methods of reducing the effects of scattering are considered in this paper, namely; polarization subtraction, use of an added absorber and spatial filtering.
There is an inevitable trade-off between the accuracy of the measurement and the signal to noise ratio as scattered light is rejected from the detector. It is demonstrated that polarization subtraction provides the optimum performance as it enables the relationship between attenuation and absorption coefficient to become more linear at a higher signal to noise ratio than both use of an added absorber and spatial filtering over a range of scattering coefficients.
There are many situations in optics (such as heterodyne microscopy and some biomedical imaging applications [1]) where the required information is carried on a modulated component of the received image. When, as frequently is the case, the frequency of modulation exceeds the frame rate of conventional imagers (i.e. CCD or CMOS charge integrating active pixel sensor cameras) this modulated component must be detected by a single detector rather than imaged in parallel by and array or camera. It is for these reasons that there is a pressing need for the development of new imaging technologies. In this paper we present a lock-in pixel for a CMOS modulated light camera (MLC) capable of detecting modulated components in the incident light. The detected frequency is independent of, and is much higher than the frame rate of any conventional commercial camera. The pixel presented here is capable of narrow band lock-in detection of light modulated between 10MHz and 75MHz even when superimposed on a large ambient background. We present the design of this pixel and experimental results that optically image the ultrasound field using a pixel fabricated in a standard 0.35mm CMOS process. We also discuss the current work increasing the frequency response, providing phase sensitive (I and Q) detection and the development of an imaging array leading to a full field modulated light camera.
The design of a single integrated lock-in pixel with a logarithmic response for a modulated light camera is described. The sensor has been designed to detect low light levels and can detect modulated light with frequency well above 2 MHz. An n-well photodiode, amplifier, mixer and 150 Hz low-pass filter have been implemented to allow continuous processing of the incident light. The performance of the sensor is demonstrated using an optoacoustic imaging system and tissue phantoms. A 1 MHz ultrasound transducer is used to modulate light scattered through a tissue phantom. An absorbing sphere is scanned through the medium and the improvement in imaging performance provided by ultrasound modulation is demonstrated.
A single channel laser Doppler blood flowmetry device has been implemented using a photodetector linked to a field programmable gate array. Filters (low pass, band pass and frequency weighted) have been developed for processing Doppler signals to obtain flow and concentration measurements. The responses of these filters are demonstrated using measurements from modulated light signals, a rotating diffusing disc and in vivo measurements of blood flow.
An instrument for imaging skin lesions in four different polarization states and at four wavelengths is described. The instrument is based upon a polarization subtraction method that can be used to extract weakly scattered light and remove surface reflections, without the need to resort to matching fluid and glass plates. Monte Carlo simulations of a layered medium are used to demonstrate the sensitivity of the measurements to the underlying medium. Ideally one would like to extract the absorption, scattering and layer thickness of the medium. However, the problem is ill-conditioned and some prior knowledge of the lesion properties will be necessary for successful implementation.
KEYWORDS: Receivers, Temperature metrology, Transmitters, Microcontrollers, Binary data, Silicon, Control systems, Signal processing, Error control coding, Computer programming
Electronic hardware has been developed to telemetrically transmit temperature and strain measurements from within a public highway in the UK. These measurements provide an important health check for monitoring fatigue damage in pavements. Previous attempts at measuring strain and temperature have required lengths of cable to be installed in the highway. The installation of these cables is both expensive and damaging to the pavement and provides potentially unreliable electrical connections. The new systems consist of a retrofitted instrumented asphalt core which is bonded into the pavement structure. The core contains all the electronics necessary to record two temperatures and two strains. An analogue front end provides signal conditioning which is digitized and passed to microcontroller for endcoding. From there the data is transmitted via a low power radio link to a receiver and data logger positioned by the side of the road. The system has an in-situ operating life of 6 months on AA alkaline batteries. Results are presented of power management and fault tolerant radio protocol techniques, long term temperature variations, dynamic strain measurements within the highway, and RF transmission capabilities through a layer of asphalt.
KEYWORDS: Absorption, Scattering, Monte Carlo methods, Tissues, Sensors, Diffuse reflectance spectroscopy, Optical properties, Error analysis, In vivo imaging, Picosecond phenomena
A means of determining the concentration of hemoglobin in- vivo using diffuse reflectance is proposed which could be applied to the quantification of laser Doppler flowmetry data. Monte Carlo simulations were used to generate intensity vs. source-detector separation plots for optical fibers of 200 micrometers diameter, with separations up to 6 mm on the skin surface. The plots were then fitted to the equation; I(x) equals a0.exp(-a1x + a2x2) and a polynomial function derived for a1 that is dependent upon the reduced scattering, microsecond(s) ', and absorption, (mu) a, coefficients. Experimentally two wavelengths with a known difference in the absorption coefficient of hemoglobin, but sharing the same microsecond(s) ', are used to solve simultaneously the derived function for (mu) a, and give the hemoglobin concentration.
The paper investigates the imaging response of cw coherent systems for imaging through scattering media. Particular attention is paid to the confocal optical technique, and experimental results are presented that show the effect on the imaging spatial resolution as the optical configuration is altered. It is seen that if the scattering concentration is increased, there is a sudden reduction in spatial resolution. This point defines a so called transition region. We show how this transition region can be moved by altering the optical configuration. We also see that when heavily scattering media is being examined, it is possible to vary the optical configuration, what is in effect changing the optical response to various scattered components of light. This procedure can be likened to adjusting the time window in the pulsed time of flight technique, and is further investigated in the companion paper.
A novel coherent optical processor for discriminating between similar patterns is described. A multiplexed hologram of two complex spatial filters (CSF) synthesized with a common reference beam provides the correlation. The two halves of the template pattern are encoded in the two CSFs. The response of the system consists of two sets of reconstructed waves that interfere at the output plane. One set of the waves is made to phase shift with respect to the other. A phase shifting interferometric technique extracts the product of the two correlation signals. Results are shown to demonstrate improved discrimination over a traditional optical correlator.
A new coherent optical correlator system has been developed for intended application to breast cancer screening. Such a system must have an inherent capability to deal with patterns that have high degrees of similarity between the desired and rejected classes, due to the overall similarity between benign and malignant cells. Consequently, effort has been directed toward achieving this goal. This paper presents an optical configuration that contains two coherent optical processors (COPs) working in parallel and utilizes phase-stepping detection at the output to multiply the two correlation signals. It is shown how this scheme offers an excellent compromise between good discrimination and immunity from noise added in the input plane
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