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Illustration of the effect of laminar flow and light attenuation, resulting in generation of the largest amplitude photoacoustic signals in slow-moving absorbers at the near edge of the tube.:
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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 demonst...
Similar publications
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...
Citations
... [9][10][11] Since then, several experimental studies using AR-PAM have been introduced, implemented, and evaluated. 12,13 A particularly interesting application is the time domain correlational shift Doppler proposed by Brunker et al. 14 In their work, they demonstrated the potential of calculating flow speed via A-line crosscorrelation in the time domain and performing fixed angle correction to estimate the actual speed with solid and linear flow phantoms. 12 Other methods of obtaining photoacoustic flowmetry information, such as the dual-pulse photoacoustic flowmetry, have also been implemented. ...
... 12,13 A particularly interesting application is the time domain correlational shift Doppler proposed by Brunker et al. 14 In their work, they demonstrated the potential of calculating flow speed via A-line crosscorrelation in the time domain and performing fixed angle correction to estimate the actual speed with solid and linear flow phantoms. 12 Other methods of obtaining photoacoustic flowmetry information, such as the dual-pulse photoacoustic flowmetry, have also been implemented. 15 However, the short delay required to take advantage of the Grueneisen relaxation effect renders it very challenging to adapt for AR-PAM application. ...
Significance
Photoacoustic Doppler flowmetry offers quantitative blood perfusion information in addition to photoacoustic vascular contrast for rectal cancer assessment.
Aim
We aim to develop and validate a correlational Doppler flowmetry utilizing an acoustic resolution photoacoustic microscopy (AR-PAM) system for blood perfusion analysis.
Approach
To extract blood perfusion information, we implemented AR-PAM Doppler flowmetry consisting of signal filtering and conditioning, A-line correlation, and angle compensation. We developed flow phantoms and contrast agent to systemically investigate the flowmetry’s efficacy in a series of phantom studies. The developed correlational Doppler flowmetry was applied to images collected during in vivo AR-PAM for post-treatment rectal cancer evaluation.
Results
The linearity and accuracy of the Doppler flow measurement system were validated in phantom studies. Imaging rectal cancer patients treated with chemoradiation demonstrated the feasibility of using correlational Doppler flowmetry to assess treatment response and distinguish residual cancer from cancer-free tumor bed tissue and normal rectal tissue.
Conclusions
A new correlational Doppler flowmetry was developed and validated through systematic phantom evaluations. The results of its application to in vivo patients suggest it could be a useful addition to photoacoustic endoscopy for post-treatment rectal cancer assessment.
... In such PA velocimetry, the cross-correlation (CC) of pairs of PA signals has been proposed [18][19][20][21]. PA signal pairs generated from clusters of RBCs irradiated with pulsed lasers are measured at the ultrasound transducer (UST). ...
... This is analogous to the classical equation of the Doppler frequency derived for a moving object, with the key distinction being that the velocity is now proportional to the time shift rather than the frequency shift [19,21]. The proposed method enables the estimation of both the object's moving velocity and direction of movement using the time shift t s obtained from the CC analysis of the PA signal pair. ...
Photoacoustic (PA) velocimetry holds the advantage of detecting ultrasound signals from selective targets sensitive to specific wavelengths of light irradiation. In particular, it is expected to be applied for measuring blood flow in microvasculature. However, PA velocimetry has not been sufficiently investigated for small velocity ranges down to several tens of millimeters per second. This study evaluates the performance and uncertainty of PA velocity measurements using a single graphite cylinder (GC) as a moving object. A pair of short laser pulses irradiated the object within a brief time interval. The velocity was measured based on the cross-correlation peak of successive PA signal pairs in the time domain. The limiting measurement uncertainty was 3.4 mm/s, determined by the sampling rate of the digitizer. The object motion was controlled in a sinusoidal linear motion, realized using a loudspeaker. With the PA measurement, the velocity of the object was obtained with a time resolution in milliseconds and with directional discrimination. Notably, the PA velocity measurements successfully provided the local velocities of the object across a wide range, with the reference velocity obtained as the time derivative of the displacement data acquired using a laser displacement sensor (LDS). The PA measurement exhibited uncertainties ranging from 0.86 to 2.1 mm/s for the maximum and minimum velocities during the experiment. The uncertainties are consistent with those in stationary cases, and nearly constant in the investigated velocity range. Furthermore, the PA measurements revealed local fine velocities of the object, which were not resolved by the reference velocities of the LDS measurements. The capability of the PA velocity measurement was found to be advantageous for measurements of objects with dynamic variations in magnitude and direction.
... The laser light source at a wavelength of 532 nm works near the absorption wavelength of hemoglobin, and thus a blood relationship study was conducted [8]. In general, this has been studied using the optical resolution photoacoustic microscopy (OR-PAM) method, which generates many photoacoustic signals of hemoglobin in blood vessels [22] but some studies using the acoustic resolution photoacoustic microscopy (AR-PAM) method have also been conducted for blood vessels in deeper regions [23]. In addition, two or more wavelengths near the hemoglobin absorption peak were used to map the concentration of total hemoglobin and oxygen saturation. ...
... In 2016, Brunker and Beard developed the acoustic-resolution photoacoustic Doppler velocimetry technique based on the photoacoustic effects [23]. By overcoming the limitations of conventional blood flow measurement methods and allowing them to be measured at a resolution of several millimeters, it is possible to examine blood flow abnormalities in microvascular vessels (arterial sclerosis, diabetes, cancer, etc.) [23]. ...
... In 2016, Brunker and Beard developed the acoustic-resolution photoacoustic Doppler velocimetry technique based on the photoacoustic effects [23]. By overcoming the limitations of conventional blood flow measurement methods and allowing them to be measured at a resolution of several millimeters, it is possible to examine blood flow abnormalities in microvascular vessels (arterial sclerosis, diabetes, cancer, etc.) [23]. The optical microscopy method has a depth limitation (within ~1 mm) for measuring blood flow, and Doppler ultrasound is not suitable for measuring micro blood flow [23]. ...
The photoacoustic (PA) effect occurs when sound waves are generated by light according to the thermodynamic and optical properties of the materials; they are absorption spectroscopic techniques that can be applied to characterize materials that absorb pulse or continuous wave (CW)-modulated electromagnetic radiation. In addition, the wavelengths and properties of the incident light significantly impact the signal-to-ratio and contrast with photoacoustic signals. In this paper, we reviewed how absorption spectroscopic research results have been used in applying actual photoacoustic effects, focusing on light sources of each wavelength. In addition, the characteristics and compositions of the light sources used for the applications were investigated and organized based on the absorption spectrum of the target materials. Therefore, we expect that this study will help researchers (who desire to study photoacoustic effects) to more efficiently approach the appropriate conditions or environments for selecting the target materials and light sources.
... This imaging modality is known as an acoustic-resolution PAM (AR-PAM). AR-PAM breaks the limitation of optical diffusion and provides acoustic-resolution (a few tens to hundreds of micrometers) in deep tissue, which promises it a very wide range of applications, such as cancer detection, [11,12] in vivo brain imaging of small animals, [13][14][15][16][17] flow velocity monitoring, [18][19][20] and so on. [21][22][23][24][25][26][27][28][29][30][31][32] However, AR-PAM still faces the challenges of imaging through inhomogeneous multilayered media. ...
Photoacoustic imaging is a potential candidate for in-vivo brain imaging, whereas, its imaging performance could be degraded by inhomogeneous multi-layered media, consisted of scalp and skull. In this work, we propose a low-artifact photoacoustic microscopy (LAPAM) scheme, which combines conventional acoustic-resolution photoacoustic microscopy with scanning acoustic microscopy to suppress the reflection artifacts induced by multi-layers. Based on similar propagation characteristics of photoacoustic signals and ultrasonic echoes, the ultrasonic echoes can be employed as the filters to suppress the reflection artifacts to obtain low-artifact photoacoustic images. Phantom experiment is used to validate the effectiveness of this method. Furthermore, LAPAM is applied for in-vivo imaging mouse brain without removing the scalp and the skull. Experimental results show that the proposed method successfully achieves the low-artifact brain image, which demonstrates the practical applicability of LAPAM. This work might improve the photoacoustic imaging quality in many biomedical applications, which involve tissue with complex acoustic properties, such as brain imaging through scalp and skull.
... Alternatively, a deconvolution algorithm can be applied to enhance lateral resolution of AR-PAM while circumventing the above-mentioned issues. Enhanced lateral resolution in AR-PAM would benefit applications such as PA velocimetry [6] and disease characterization [7]. ...
Acoustic-resolution photoacoustic microscopy (AR-PAM) image resolution is determined by the point spread function (PSF) of the imaging system. Previous algorithms, including Richardson–Lucy (R-L) deconvolution and model-based (MB) deconvolution, improve spatial resolution by taking advantage of the PSF as prior knowledge. However, these methods encounter the problems of inaccurate deconvolution, meaning the deconvolved feature size and the original one are not consistent (e.g., the former can be smaller than the latter). We present a novel deep convolution neural network (CNN)-based algorithm featuring high-fidelity recovery of multiscale feature size to improve lateral resolution of AR-PAM. The CNN is trained with simulated image pairs of line patterns, which is to mimic blood vessels. To investigate the suitable CNN model structure and elaborate on the effectiveness of CNN methods compared with non-learning methods, we select five different CNN models, while R-L and directional MB methods are also applied for comparison. Besides simulated data, experimental data including tungsten wires, leaf veins, and in vivo blood vessels are also evaluated. A custom-defined metric of relative size error (RSE) is used to quantify the multiscale feature recovery ability of different methods. Compared to other methods, enhanced deep super resolution (EDSR) network and residual in residual dense block network (RRDBNet) model show better recovery in terms of RSE for tungsten wires with diameters ranging from 30 μm to 120 μm. Moreover, AR-PAM images of leaf veins are tested to demonstrate the effectiveness of the optimized CNN methods (by EDSR and RRDBNet) for complex patterns. Finally, in vivo images of mouse ear blood vessels and rat ear blood vessels are acquired and then deconvolved, and the results show that the proposed CNN method (notably RRDBNet) enables accurate deconvolution of multiscale feature size and thus good fidelity.
... A p-value 0.05 was considered to indicate statistical significance. Introducing MBs in blood to produce incoherence in the PA signals can also be beneficial to improve the accuracy of Doppler based flow velocimetry techniques, for example, 39,40 since these techniques rely on high spatiotemporal incoherence for accuracy. However, some of the limitations in combining MBs with photoacoustics are that MBs will inherently exacerbate light scattering through the volume as well as scatter the PA waves propagating towards the detector. ...
A photoacoustic contrast mechanism is presented based on the photoacoustic fluctuations induced by microbubbles flowing inside a micro-vessel filled with a continuous absorber. It is demonstrated that the standard deviation of a homogeneous absorber mixed with microbubbles increases non-linearly as the microbubble concentration and microbubble size is increased. This effect is then utilized to perform photoacoustic fluctuation imaging with increased visibility and contrast of a blood flow phantom.
... Introducing MBs in blood to produce incoherence in the PA signals can also be beneficial to improve the accuracy of Doppler based flow velocimetry techniques, for example [38,39], since these techniques rely on high spatiotemporal incoherence for accuracy. However, some of the limitations in combining MBs with photoacoustics is that MBs will inherently exacerbate light scattering through the volume as well as scatter the PA waves propagating towards the detector. ...
A photoacoustic contrast mechanism is presented based on the photoacoustic fluctuations induced by microbubbles flowing inside a micro vessel filled with a continuous absorber. It is demonstrated that the standard deviation of a homogeneous absorber mixed with microbubbles increases non-linearly as the microbubble concentration and microbubble size is increased. This effect is then utilized to perform photoacoustic fluctuation imaging with increased visibility and contrast of a blood flow phantom.
... In addition, all the developed methods in ultra sound flow imaging can be adapted in PA imaging. Doppler imaging [78][79][80] and quantitative methods like crosscorrelation [77,81] and differential phase analysis [82] are among the robust methods that measure the flow. Most of the PA systems are based on Qswitch lasers with relatively low Pulse Repetition Frequency (PRF). ...
Pushing the ultrasound technology for better diagnosis, image resolution and cost
reduction is the core of this work. In this thesis, we explored several innovative
solutions for ultrasound imaging. We devised techniques and developed ultrasound
systems to address the challenges that are associated with vascular ultrasound
which can be subsumed into two main categories: a.) novel transducer architecture
and b.) novel imaging techniques.
The first approach consists of ultrasound system engineering for the realization
of the first multielement
Capacitive Micromachined Ultrasound Transducer (CMUT)
phased array for sidelooking
Intravascular Ultrasound (IVUS) imaging. The second
approach involves a system development for photoacoustic (PA) imaging in which
a specific dualfrequency
probe is designed and a novel quantitative ultrasound
approach for photoacoustic flow velocimetry imaging is devised.
An introduction to IVUS, PA imaging, and probe designing is provided in chapter
1. The technology of ultrasound imaging is described and the clinical demands
for improving the current technologies are provided.
In chapter 2 the crosscoupling
of transducer elements through the medium and
its effect on the frequency response of the CMUT array was discussed. Finite Element
Analysis (FEA) was carried out using the radiation impedance method for
analyzing this effect on the CMUT array which has wrapped around a catheter tip
with a cylindrical configuration. The crosstalk
between planar CMUT elements was
linked with dips in the frequency spectrum from experimental data and was shown
that the element crosstalks
don’t have detrimental effects on the array bandwidth.
In chapter 3 the first 96 elements CMUT phased array placed at the circumference
of a catheter tip with 1.2 mm diameter for the sidelooking
IVUS imaging was
described. A system for utilizing Coded Excitation (CE) to improve the penetration
depth and image signaltonoise
ratio (SNR) was developed. First, the CMUT array
was characterized showing that the 6dB
device bandwidth at 30 V DC biasing is 25
MHz with 20 MHz center frequency and has transmitted sensitivity of 37 kPa/V at
that frequency. A realtime
system and software tools in MATLAB were developed
for signal acquisitions and processing, beamforming, image optimization, and data
analysis for Bmode
IVUS.
A linear Frequency Modulation (FM) coded waveform was designed based on
the CMUT array characteristics and a wire phantom and a human coronary artery
plaque were imaged. By assessing the image quality of the reconstructed wire
phantom image, 60 𝜇m and 70 𝜇m axial resolution were achieved using the short
pulse and coded signal, respectively. Furthermore, an 8 dB gain in the SNR using
the FM signal was achieved.
PA signals can have a very large bandwidth and large dynamic range. In chapter
4 a broadband PA receiver was introduced which was incorporated in chapter 5
ffor the realization of a dualfrequency
probe for PA imaging of the human carotid
arteries.
First, it was demonstrated that with an appropriate electrical impedance matching,
offresonance
Polyvinylidene Difluoride (PVDF) transducers offer the bandwidth
and sensitivity to fully capture the PA signals. Using the FEA in COMSOL
and validating it with the experiment, it was shown that the elements crosstalk in a
28 𝜇m thick, kerfless PVDF arrays, where the electrodes were patterned onto the
piezoelectric material, were negligible. Second, by utilizing this approach in chapter
5, a dualfrequency
probe was proposed using a duallayer
piezoelectric material
consisting of lead zirconium titanate (PZT) for ultrasound stack and a kerfless PVDF
array for PA signal reception, which was placed on top of the PZT stack.
It has been discussed that the loading effect of the PVDF array narrows the
ultrasound bandwidth; however, the loading effect was minimized by considering
the PVDF array as the second matching layer of the ultrasound stack. Using 3D
FEA, a design with and without subdicing was modeled, and the results showed
that the 3dB
bandwidth of the ultrasound stacks were 87% and 75% relative to the
center frequencies. A transmit sensitivity of 17 kPa/V and 21 kPa/V were found for
those two realizations, respectively.
In chapter 6 a photoacoustic imaging system using a fast pulsed laser diode
and a novel quantitative ultrasound method based on normalized firstorder
field
autocorrelation function was developed to estimate flow velocities. It was demonstrated
how the decorrelation time of signals acquired over frames are related to
the flow speed and was shown that the PA flow analysis based on this approach is
an angle independent flow velocity imaging method. We baptized this method vPA:
Photoacoustic flow velocimetry imaging. Directional velocimetry imaging up to 20
mm/s in a phantom study was demonstrated, and vPA was applied to imaging flow
speed in the microvasculature of the chorioallantoic membrane (CAM) of a 6day
old chicken embryo where pulsatile flow in the arterial layer of the CAM was shown.
This chapter also showed that vPA has the potential to simultaneously image the
blood flow speed and extract the functional information like oxygen saturation of the
blood.
In chapter 7 the achievements were summarized and the limitations of our studies
were discussed with some recommendations for future work.
... To address this problem, researchers have explored various fast mechanical scanners, such as voice-coil scanner, water-immersible Galvo mirror, water-immersible MEMS scanner, polygon scanner, et al. Because these scanners can maintain the confocal alignment of the optical and acoustic foci, they can offer excellent sensitivity, large field of view, and fast scanning speed [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. The fastest mechanical scanning speed is limited by physical parameters, such as inertia force, vibration, and air bubbles. ...
We report fiber-based dual-foci fast-scanning OR-PAM that can double the scanning rate without compromising the imaging resolution, the field of view, and the detection sensitivity. To achieve fast scanning speed, the OR-PAM system uses a single-axis water-immersible resonant scanning mirror that can confocally scan the optical and acoustic beams at 1018 Hz with a 3-mm range. Pulse energies of 45˜100-nJ are sufficient for acquiring vascular and oxygen-saturation images. The dual-foci method can double the B-scan rate to 2036 Hz. Using two lasers and stimulated Raman scattering, we achieve dual-wavelength excitation on both foci, and the total A-line rate is 3.2-MHz. In in vivo experiments, we inject epinephrine and monitor the hemodynamic and oxygen saturation response in the peripheral vessels at 1.7 Hz over 2.5 × 6.7 mm². Dual-foci OR-PAM offers a new imaging tool for the study of fast physiological and pathological changes.
... In this Letter, we are concerned with only AR-PAM, which we refer to as PAM for simplicity. It has wide applications [3][4][5][6][7][8], particularly in in vivo brain imaging [9], microcirculation monitoring [10], cancer detection [11] and flow velocity measurement [12]. ...
Synthetic aperture imaging and virtual point detection have been exploited to extend the depth of view of photoacoustic microscopy. The approach is commonly based on a constant assumed sound speed, which reduces image quality. We propose a new, to the best of our knowledge, self-adaptive technique to estimate the speed of sound when integrated with this hybrid strategy. It is accomplished through linear regression between the square of time of flight detected at individual virtual detectors and the square of their horizontal distances on the focal plane. The imaging results show our proposed method can significantly improve the lateral resolution, imaging intensity, and spatial precision for inhomogeneous tissue.
