Joanna Brunker

Pulsed photoacoustic Doppler flowmetry using time-domain cross-correlation: Accuracy, resolution and scalability

The feasibility of making spatially resolved measurements of blood velocity using a pulsed photoacoustic Doppler technique in acoustic resolution mode has been investigated. Doppler time shifts were quantified via cross-correlation of photoacoustic waveform pairs generated within a blood-simulating phantom using pairs of light pulses. The phantom comprised micron-scale absorbers imprinted on an acetate sheet and moved at known velocities. The photoacoustic waves were detected using PZT ultrasound transducers operating at center frequencies of 20 MHz, 5 MHz and 3.5 MHz; measurements of velocity and resolution were calculated from the mean cross-correlation function of 25 waveform pairs. Velocities in the range ±0.15 to ±1.5 ms(-1) were quantified with accuracies as low as 1%. The transducer focal beam width determines a maximum measurable velocity |V(max)| beyond which correlation is lost due to absorbers moving out of the focal beam between the two laser pulses. Below |V(max)| a measurement resolution of <4% of the measured velocity was achieved. Resolution and |V(max)| can be scaled to much lower velocities such as those encountered in microvasculature (< 50 mms(-1)). The advantage of pulsed rather than continuous-wave excitation is that spatially resolved velocity measurements can be made, offering the prospect of mapping flow within the microcirculation.

Pulsed photoacoustic Doppler flowmetry using a cross correlation method

The feasibility of making spatially resolved measurements of blood flow using pulsed photoacoustic Doppler techniques has been explored. Doppler time shifts were quantified via cross-correlation of pairs of photoacoustic waveforms generated within a blood-simulating phantom using pairs of laser light pulses. The photoacoustic waves were detected using a focussed or planar PZT ultrasound transducer. This approach was found to be effective for quantifying the linear motion of micron-scale absorbers imprinted on an acetate sheet moving with velocities in the range 0.15 to 1.50 ms-1. The effect of the acoustic spot diameter and the time separation between the laser pulses on measurement resolution and the maximum measurable velocity is discussed. The distinguishing advantage of pulsed rather than continuous-wave excitation is that spatially resolved velocity measurements can be made. This offers the prospect of mapping flow within the microcirculation and thus providing insights into the perfusion of tumours and other pathologies characterised by abnormalities in flow status.

A tissue equivalent phantom for simultaneous near-infrared optical tomography and EEG

We describe a phantom which enables EEG and near-infrared optical tomography to be performed simultaneously over the same volume. The phantom provides a surface electrical contact impedance comparable to that of the human scalp, whilst also possessing an optical scattering coefficient and electrical conductivity equivalent to that of brain tissue. The construction of the phantom is described, as is the resulting simultaneous EEG and near infrared optical tomography experiment, which, to our knowledge, is the first performed on a scale comparable to that of the infant human brain. This imaging experiment successfully shows the suitability of this phantom construction for the assessment of simultaneous EEG and near infrared optical tomography systems.

Pulsed photoacoustic Doppler flow measurements in blood-mimicking phantoms

The feasibility of making spatially resolved measurements of blood flow using pulsed photoacoustic Doppler techniques has been explored. Doppler time shifts were quantified via cross-correlation of pairs of photoacoustic waveforms generated within a blood-simulating phantom using pairs of laser light pulses. The photoacoustic waves were detected using a focussed or planar PZT ultrasound transducer. For each flow measurement, a series of 100 waveform pairs was collected. Previous data processing methods involved rejection of poorly correlated waveform pairs; the modal velocity value and standard deviation were then extracted from the selected distribution of velocity measurements. However, the data selection criteria used in this approach is to some extent arbitrary. A new data analysis protocol, which involves averaging the 100 cross-correlation functions and thus uses all of the measured data, has been designed in order to prevent exclusion of outliers. This more rigorous approach has proved effective for quantifying the linear motion of micron-scale absorbers imprinted on an acetate sheet moving with velocities in the range 0.14 to 1.25 ms-1. Experimental parameters, such as the time separation between the laser pulses and the transducer frequency response, were evaluated in terms of their effect on the accuracy, resolution and range of measurable velocities. The technique was subsequently applied to fluid phantoms flowing at rates less than 5 mms-1 along an optically transparent tube. Preliminary results are described for three different suspensions of phenolic resin microspheres, and also for whole blood. Velocity information was obtained even under non-optimal conditions using a low frequency transducer and a low pulse repetition frequency. The distinguishing advantage of pulsed rather than continuous-wave excitation is that spatially resolved velocity measurements can be made. This offers the prospect of mapping flow within the microcirculation and thus providing insights into the perfusion of tumours and other pathologies characterised by abnormalities in flow status.

An electrically-activated dynamic tissue-equivalent phantom for assessment of diffuse optical imaging systems

A novel design of solid dynamic phantom with tissue-like optical properties is presented, which contains variable regions of contrast which are activated electrically. Reversible changes in absorption are produced by localized heating of targets impregnated with thermochromic pigment. A portable, battery-operated prototype has been constructed, and its optical and temporal characteristics have been investigated. The phantom has been developed as a means of assessing the performance of diffuse optical imaging systems, such as those used to monitor haemodynamic changes in the brain and other tissues. Images of the phantom have been reconstructed using data acquired with a continuous wave optical topography system.

Velocity measurements in whole blood using acoustic resolution photoacoustic Doppler

Acoustic resolution photoacoustic Doppler velocimetry promises to overcome the spatial resolution and depth penetration limitations of current blood flow measuring methods. Despite successful implementation using blood-mimicking fluids, measurements in blood have proved challenging, thus preventing in vivo application. A common explanation for this difficulty is that whole blood is insufficiently heterogeneous relative to detector frequencies of tens of MHz compatible with deep tissue photoacoustic measurements. Through rigorous experimental measurements we provide new insight that refutes this assertion. We show for the first time that, by careful choice of the detector frequency and field-of-view, and by employing novel signal processing methods, it is possible to make velocity measurements in whole blood using transducers with frequencies in the tens of MHz range. These findings have important implications for the prospects of making deep tissue measurements of blood flow relevant to the study of microcirculatory abnormalities associated with cancer, diabetes, atherosclerosis and other conditions.

Acoustic resolution photoacoustic Doppler velocimetry in blood-mimicking fluids

Photoacoustic Doppler velocimetry provides a major opportunity to overcome limitations of existing blood flow measuring methods. By enabling measurements with high spatial resolution several millimetres deep in tissue, it could probe microvascular blood flow abnormalities characteristic of many different diseases. Although previous work has demonstrated feasibility in solid phantoms, measurements in blood have proved significantly more challenging. This difficulty is commonly attributed to the requirement that the absorber spatial distribution is heterogeneous relative to the minimum detectable acoustic wavelength. By undertaking a rigorous study using blood-mimicking fluid suspensions of 3 μm absorbing microspheres, it was discovered that the perceived heterogeneity is not only limited by the intrinsic detector bandwidth; in addition, bandlimiting due to spatial averaging within the detector field-of-view also reduces perceived heterogeneity and compromises velocity measurement accuracy. These detrimental effects were found to be mitigated by high-pass filtering to select photoacoustic signal components associated with high heterogeneity. Measurement under-reading due to limited light penetration into the flow vessel was also observed. Accurate average velocity measurements were recovered using “range-gating”, which furthermore maps the cross-sectional velocity profile. These insights may help pave the way to deep-tissue non-invasive mapping of microvascular blood flow using photoacoustic methods.

Acoustic resolution photoacoustic Doppler flowmetry: practical considerations for obtaining accurate measurements of blood flow

An assessment has been made of various experimental factors affecting the accuracy of flow velocities measured using a pulsed time correlation photoacoustic Doppler technique. In this method, Doppler time shifts are quantified via crosscorrelation of pairs of photoacoustic waveforms generated in moving absorbers using pairs of laser light pulses, and the photoacoustic waves are detected using an ultrasound transducer. The acoustic resolution mode is employed by using the transducer focal width, rather than the large illuminated volume, to define the lateral spatial resolution. This enables penetration depths of several millimetres or centimetres, unlike methods using the optical resolution mode, which limits the maximum penetration depth to approximately 1 mm. In the acoustic resolution mode, it is difficult to detect time shifts in highly concentrated suspensions of flowing absorbers, such as red blood cell suspensions and whole blood, and this challenge supposedly arises because of the lack of spatial heterogeneity. However, by assessing the effect of different absorption coefficients and tube diameters, we offer an alternative explanation relating to light attenuation and parabolic flow. We also demonstrate a new signal processing method that surmounts the previous problem of measurement under-reading. This method is a form of signal range gating and enables mapping of the flow velocity profile across the tube as well as measurement of the average flow velocity. We show that, using our signal processing scheme, it is possible to measure the flow of whole blood using a relatively low frequency detector. This important finding paves the way for application of the technique to measurements of blood flow several centimetres deep in living tissue.

Acoustic resolution photoacoustic Doppler velocity measurements in fluids using time-domain cross-correlation

Blood flow measurements have been demonstrated using the acoustic resolution mode of photoacoustic sensing. This is unlike previous flowmetry methods using the optical resolution mode, which limits the maximum penetration depth to approximately 1mm. Here we describe a pulsed time correlation photoacoustic Doppler technique that is inherently flexible, lending itself to both resolution modes. Doppler time shifts are quantified via cross-correlation of pairs of photoacoustic waveforms generated in moving absorbers using pairs of laser light pulses, and the photoacoustic waves detected using an ultrasound transducer. The acoustic resolution mode is employed by using the transducer focal width, rather than the large illuminated volume, to define the lateral spatial resolution. The use of short laser pulses allows depth-resolved measurements to be obtained with high spatial resolution, offering the prospect of mapping flow within microcirculation. Whilst our previous work has been limited to a non-fluid phantom, we now demonstrate measurements in more realistic blood-mimicking phantoms incorporating fluid suspensions of microspheres flowing along an optically transparent tube. Velocities up to 110 mm/s were measured with accuracies approaching 1% of the known velocities, and resolutions of a few mm/s. The velocity range and resolution are scalable with excitation pulse separation, but the maximum measurable velocity was considerably smaller than the value expected from the detector focal beam width. Measurements were also made for blood flowing at velocities up to 13.5 mm/s. This was for a sample reduced to 5% of the normal haematocrit; increasing the red blood cell concentration limited the maximum measurable velocity so that no results were obtained for concentrations greater than 20% of a physiologically realistic haematocrit. There are several possible causes for this limitation; these include the detector bandwidth and irregularities in the flow pattern. Better results are obtained using a detector with a higher centre frequency and larger bandwidth and tubes with a narrower diameter.

Processing methods for photoacoustic Doppler flowmetry with a clinical ultrasound scanner

Abstract. Photoacoustic flowmetry (PAF) based on time-domain cross correlation of photoacoustic signals is a promising technique for deep tissue measurement of blood flow velocity. Signal processing has previously been developed for single element transducers. Here, the processing methods for acoustic resolution PAF using a clinical ultrasound transducer array are developed and validated using a 64-element transducer array with a −6 dB detection band of 11 to 17 MHz. Measurements were performed on a flow phantom consisting of a tube (580  μm inner diameter) perfused with human blood flowing at physiological speeds ranging from 3 to 25  mm  /  s. The processing pipeline comprised: image reconstruction, filtering, displacement detection, and masking. High-pass filtering and background subtraction were found to be key preprocessing steps to enable accurate flow velocity estimates, which were calculated using a cross-correlation based method. In addition, the regions of interest in the calculated velocity maps were defined using a masking approach based on the amplitude of the cross-correlation functions. These developments enabled blood flow measurements using a transducer array, bringing PAF one step closer to clinical applicability.