Low-cost photoacoustic imaging systems based on laser diode and light-emitting diode excitation

Photoacoustic imaging,an emerging biomedical imaging modality,holds great promise for preclinical and clinical researches.It combines the high optical contrast and high ultrasound resolution by converting laser excitation into ultrasonic emission.In order to generate photoacoustic signal e±-ciently,bulky Q-switched solid-state laser systems are most commonly used as excitation sources and hence limit its commercialization.As an alternative,the miniaturized semiconductor laser system has the advantages of being inexpensive,compact,and robust,which makes a signi¯cant e®ect on production-forming design.It is also desirable to obtain a wavelength in a wide range from visible to nearinfrared spectrum for multispectral applications.Focussing on practical aspect,this paper reviews the state-of-the-art developments of low-cost photoacoustic system with laser diode and light-emitting diode excitation source and highlights a few representative installations in the past decade.

Fiber laser technologies for photoacoustic microscopy

Fiber laser technology has experienced a rapid growth over the past decade owing to increased applications in precision measurement and optical testing,medical care,and industrial applications,including laser welding,cleaning,and manufacturing.A fiber laser can output laser pulses with high energy,a high repetition rate,a controllable wavelength,low noise,and good beam quality,making it applicable in photoacoustic imaging.Herein,recent developments in fiber-laser-based photoacoustic microscopy(PAM)are reviewed.Multispectral PAM can be used to image oxygen saturation or lipid-rich biological tissues by applying a Q-switched fiber laser,a stimulated Raman scattering-based laser source,or a fiber-based supercontinuum source for photoacoustic excitation.PAM can also incorporate a single-mode fiber laser cavity as a high-sensitivity ultrasound sensor by measuring the acoustically induced lasing-frequency shift.Because of their small size and high flexibility,compact head-mounted,wearable,or hand-held imaging modalities and better photoacoustic endoscopes can be enabled using fiber-laser-based PAM.

Concurrent photoacoustic and ultrasound microscopy with a coaxial dual-element ultrasonic transducer

Simultaneous photoacoustic and ultrasound(PAUS)imaging has attracted increasing attention in biomedical research to probe the optical and mechanical properties of tissue.However,the resolution for majority of the existing PAUS systems is on the order of 1 mm as the majority are designed for clinical use with low-frequency US detection.Here we developed a concurrent PAUS microscopy that consists of optical-resolution photoacoustic microscopy(OR-PAM)and high-frequency US pulse-echo imaging.This dual-modality system utilizes a novel coaxial dual-element ultrasonic transducer(DE-UST)and provides anatomical and functional information with complementary contrast mechanisms,achieving a spatial resolution of 7μm for PA imaging and 106μm for US imaging.We performed phantom studies to validate the system’s performance.The vasculature of a mouse’s hind paw was imaged to demonstrate the potential of this hybrid system for biomedical applications.

Photoacoustic microscopy based on transparent piezoelectric ultrasound transducers

Photoacoustic microscopy(PAM),due to its deep penetration depth and high contrast,is playing an increasingly important role in biomedical imaging.PAM imaging systems equipped with conventional ultrasound transducers have demonstrated excellent imaging performance.However,these opaque ultrasonic transducers bring some constraints to the further development and application of PAM,such as complex optical path,bulky size,and difficult to integrate with other modalities.To overcome these problems,ultrasonic transducers with high optical transparency have appeared.At present,transparent ultrasonic transducers are divided into optical-based and acoustic-based sensors.In this paper,we mainly describe the acoustic-based piezoelectric transparent transducers in detail,of which the research advances in PAM applications are reviewed.In addition,the potential challenges and developments of transparent transducers in PAM are also demonstrated.

Scanning photoacoustic imaging of submucosal gastric tumor based on a long focused transducer in phantom and in vitro experiments

Photoacoustic imaging,which can provide the maximum intensity contrast in tissue depth imaging without ionizing radiation,will be a promising imaging trend for tumor detection.In this paper,a column diffusionfiber was employed to carry a pulsed laser for irradiating stomach directly through esophagus based on the characteristics of gastric tissue structure.A long focused ultrasonic transducer was placed outside the body to detect photoacoustic signals of gastric tissue.Phantom and in vitro experiments of submucosal gastric tumors were carried out to check the sensitivity of scanning photoacoustic tomography system,including the lateral and longitudinal resolution of the system,sensitivity of different absorption coefficient in imaging,capability of transversal detection,and probability of longitudinal detection.The results demonstrate that our innovative technique can improve the parameters of imaging.The lateral resolution reaches 2.09 mm.Then a depth of 5.5mm with a longitudinal accuracy of 0.36mm below gastric mucosa of early gastric cancer(EGC)has been achieved.In addition,the optimal absorption coefficient differences among absorbers of system are 3.3-3.9 times.Results indicate that our photoacoustic imaging(PAI)system,is based on a long focusing transducer,can provide a potential application for detecting submucosal EGC without obvious symptoms.

Design of NO2 photoacoustic sensor with high reflective mirror based on low power blue diode laser

An NO2 photoacoustic sensor system with a high reflective mirror based on a low power blue diode laser is developed in this work. The excitation power is enhanced by increasing the number of reflections. Comparing with a traditional photoacoustic system, the pool constant is improved from 300.24(Pa·cm)/W to 1450.64(Pa·cm)/W, and the signal sensitivity of the photoacoustic sensor is increased from 0.016 μV/ppb to 0.2562 μV/ppb. The characteristics of temperature and humidity of the new photoacoustic sensor are also obtained, and the algorithm is adjusted to provide a quantitative response and drift of the resonance frequency. The results of this research provide a new method and concept for further developing the NO2 photoacoustic sensors.

Effects of size and arrangement of virtual transducer on photoacoustic tomography

In this paper, we investigate the effects of the relative size and arrangement of a virtual transducer on the image quality in limited-view photoacoustic tomography. A virtual transducer refers to the acoustic scatterers used to reflect photoacoustic waves and improve the images reconstructed from incomplete PA signal. Size and spatial arrangement determine the performance of the virtual transducer. In this study, the scatterers utilized as virtual transducers are arranged in different manners, such as on a straight line or on an arc line. We find that virtual transducers with a big distributing angle can provide more significant image improvement than with a small distributing angle, which is similar to the true transducers. We also change the size of virtual transducer and study its influence on image quality. It is found that the bigger scatterers provide better images than the smaller ones. Especially, when the size of scatterers is reduced to the wavelength of photoacoustic wave, the image quality observably decreases, owing to the strong diffraction effect. Thus, it is suggested that the size of the acoustical scatterers should be much larger than the photoacoustic wavelength. The simulations are conducted, and the results could be helpful for the application and further study of virtual transducer theory in limited-view photoacoustic tomography.

Reflection-mode photoacoustic microscopy using a hollow focused ultrasound transducer for in vivo imaging of blood vessels

A reflection-mode photoacoustic microscope using a hollow focused ultrasound transducer is developed for highresolution in vivo imaging.A confocal structure of the laser and the ultrasound is used to improve the system resolution.The axial and lateral resolutions of the system are measured to be ～ 32 μm and ～ 58 μm,respectively.Ex vivo and in vivo modes are tested to validate the imaging capability of the photoacoustic microscope.The adjacent vein and artery can be seen clearly from the reconstructed photoacoustic images.The results demonstrate that the reflectionmode photoacoustic microscope can be used for high-resolution imaging of micro-blood vessels,which would be of great benefit for monitoring the neovascularization in tumor angiogenesis.

Development of a Compact Photoacoustic Tomography Imaging System with Dual Single-Element Transducers for Image Enhancement

Objective:This paper proposes a new photoacoustic computed tomography(PACT)imaging system employing dual ultrasonic transducers with different frequencies.When imaging complex biological tissues,photoacoustic(PA)signals with multiple frequencies are produced simultaneously;however,due to the limited bandwidth of a single-frequency transducer,the received PA signals with specific frequencies may be missing,leading to a low imaging quality.Methods:In contrast to our previous work,the proposed system has a compact volume as well as specific selection of the detection center frequency of the transducer,which can provide a comprehensive range for the detection of PA signals.In this study,a series of numerical simulation and phantom experiments were performed to validate the efficacy of the developed PACT system.Results:The images generated by our system combined the advantages of both high resolution and ideal brightness/contrast.Conclusion:The interchangeability of transducers with different frequencies provides potential for clinical deployment under the circumstance where a single frequency transducer cannot perform well.

Development of a hybrid photoacoustic and optical monitoring system for the study of laser ablation processes upon the removal of encrustation from stonework

In the context of this work,a prototype hybrid photoacoustic(PA)and optical system for the on-line monitoring of laser cleaning procedures is presented.The developed apparatus has enabled the detection of MHz frequency range acoustic waves generated during the laser ablation process.The intrinsically generated PA signals combined with high resolution optical images provide the opportunity to follow the cleaning process accurately and in real time.Technical mock-ups have been used to demonstrate the potential of this novel technique with emphasis given to applications that refer to the restoration of Cultural Heritage(CH)surfaces.Towards this purpose,the real time monitoring of the laser assisted removal of unwanted encrustation from stonework has been achieved using IR and UV wavelengths.This novel approach has allowed for the precise determination of the critical number of laser pulses required for the elimination of the encrustation layer,while highlighting the dominant ablation mechanisms according to the irradiation wavelength.The promising results obtained using the prototype hybrid PA and optical system can open up new perspectives in the monitoring of laser cleaning interventions,promoting an improved restoration outcome.

High-speed high-resolution laser diode-based photoacoustic microscopy for in vivo microvasculature imaging

Laser diodes(LDs)have been considered as cost-effective and compact excitation sources to overcome the requirement of costly and bulky pulsed laser sources that are commonly used in photoacoustic microscopy(PAM).However,the spatial resolution and/or imaging speed of previously reported LD-based PAM systems have not been optimized simultaneously.In this paper,we developed a high-speed and high-resolution LD-based PAM system using a continuous wave LD,operating at a pulsed mode,with a repetition rate of 30 kHz,as an excitation source.A hybrid scanning mechanism that synchronizes a one-dimensional galvanometer mirror and a two-dimensional motorized stage is applied to achieve a fast imaging capability without signal averaging due to the high signal-to-noise ratio.By optimizing the optical system,a high lateral resolution of 4.8μm has been achieved.In vivo microvasculature imaging of a mouse ear has been demonstrated to show the high performance of our LD-based PAM system.

Flexible fiber-laser ultrasound sensor for multiscale photoacoustic imaging

Photoacoustic imag ing(PAI)is a nonin vasive biomedical imag ing tech no logy capable of multiscale imag ing of biological samples from orga ns dow n to cells.Multiscale PAI requires differe nt ultraso und tra nsducers that are flat or focused because the current widely-used piezoelectric transducers are rigid and lack the flexibility to tune their spatial ultrasound responses.Inspired by the rapidly-developing flexible photonics,we exploited the inherent flexibility and low-loss features of optical fibers to develop a flexible fiber-laser ultrasound sensor(FUS)for multiscale PAI.By simply bending the fiber laser from straight to curved geometry,the spatial ultraso und resp onse of the FUS can be tuned for both wide-view optical-resolution photoacoustic microscopy at optical diffraction-limited depth(~1 mm)and photoacoustic computed tomography at optical dissipation-limited depth of several centimeters.A radio-frequency demodulation was employed to get the readout of the beat frequency variation of two orthogonal polarization modes in the FUS output,which ensures low-noise and stable ultrasound detection.Compared to traditional piezoelectrical transducers with fixed ultrasound responses once manufactured,the flexible FUS provides the freedom to design multiscale PAI modalities including wearable microscope,intravascular endoscopy,and portable tomography system,which is attractive to fundamental biologic-al/medical studies and clinical applications.

Improvement in resolution of fiber-laser photoacoustic tomography based on a virtual-point concept

In this study,a virtual-point concept was introduced into fiber-laser photoacoustic tomography to improve the elevational image resolution.The flexible fiber laser was bent into an arc shape to conform to the ultrasound wavefront,which formed an ultrasound focus at the center of the arc.The synthetic aperture focusing technique was utilized to reconstruct the images;as a result,the elevational resolution particularly within the out-of-focus region was considerably improved compared to the resolution of an image retrieved by multiplexing the PA time-resolved signals with sound velocity.The all-optical fiber-laser photoacoustic tomography system with a high spatial resolution has potential for various applications,including biomedical research and preclinical/clinical diagnosis.

Application of Micro Electro Mechanical System(MEMS)Technology in Photoacoustic Imaging

Photoacoustic imaging(PAI)is a new biomedical imaging technology that provides a mixed contrast mechanism and excellent spatial resolution in biological tissues.It is a non-invasive technology that can provide in vivo anatomical and functional information.This technology has great application potential in microscopic imaging and endoscope system.In recent years,the devel-opment of micro electro mechanical system(MEMS)technology has promoted the improvement and miniaturization of the photoacoustic imaging system,as well as its preclinical and clinical appli-cations.This paper introduces the research progress of MEMS technology in photoacoustic micro-scope systems and the miniaturization of photoacoustic endoscope ultrasonic transducers,and points out the shortcomings of existing technology and the direction of future development.

Gastroscopy-conjugated photoacoustic and ultrasonic dual-mode imaging for detection of submucosal gastric cancer:in vitro study

This paper presents photoacoustic and ultrasonic dual-mode imaging for real-time detection of submucosal gastric cancer with a combination of gastroscopy.The diagnostic capacity was directly addressed via several phantoms and ex vivo experiments.Results demonstrated that superficial and submucosal gastric cancer can be diagnosed with a perceptible depth of 6.33 mm,a lateral accuracy of 2.23 mm,and a longitudinal accuracy of 0.17 mm though capturing the morphology of angiogenesis,which is a main character of the therioma-related change.The capability of gastroscopy-conjugated photoacoustic and ultrasonic dual-mode imaging system will own great potential in improving the clinical diagnostic rate of submucosal gastric cancer.

A quartz-enhanced photoacoustic spectroscopy sensor for measurement of water vapor concentration in the air

A compact and highly linear quartz-enhanced photoacoustic spectroscopy（QEPAS） sensor for the measurement of water vapor concentration in the air is demonstrated. A cost-effective quartz tuning fork（QTF） is used as the sharp transducer to convert light energy into an electrical signal based on the piezoelectric effect, thereby removing the need for a photodetector. The short optical path featured by the proposed sensing system leads to a decreased size. Furthermore, a pair of microresonators is applied in the absorbance detection module（ADM） for QTF signal enhancement. Compared with the system without microresonators, the detected QTF signal is increased to approximately 7-fold. Using this optimized QEPAS sensor with the proper modulation frequency and depth, we measure the water vapor concentration in the air at atmospheric pressure and room temperature. The experimental result shows that the sensor has a high sensitivity of 1.058parts-per-million.

Review of methods to improve the performance of linear array-based photoacoustic tomography

As a hybrid imaging modality that combines optical excitation with acoustic detection,photoacoustic tomography(PAT)has become one of the fastest growing biomedical imaging modalities.Among various types of transducer arrays used in a PAT system conguration,the linear array is the most commonly utilized due to its convenience and low-cost.Although linear array-based PAT has been quickly developed within the recent decade,there are still two major challenges that impair the overall performance of the PAT imaging system.Therst challenge is that the three-dimensional(3D)imaging capability of a linear array is limited due to its poor elevational resolution.The other challenge is that the geometrical shape of the linear array constrains light illumination.To date,substantial e®orts have been made to address the aforementioned challenges.This review will present current technologies for improving the elevation resolution and light delivery of linear array-based PAT systems.

The application of laser reflective tomography in near-field measurements of ultrasonic transducers

With Laser Reflective Tomography（LRT）,the near fields of ultrasonic transducers were measured and analyzed.The principle of LRT measurement of ultrasonic field distribution was introduced and an experimental system was set up.Acoustic pressure of a multiple element piston transducer was measured by using of a laser vibrometer.Its distribution in amplitude and phase was obtained.The acoustic pressure in the same region was measured with a needle hydrophone to validate the LRT method.Furthermore,through reconstruction of acoustic fields,it indicated that LRT method is suitable for predicting the distribution on transducers＇surface and conditions of active elements.

Compressed sensing in synthetic aperture photoacoustic tomography based on a linear-array ultrasound transducer

Photoacoustic tomography（PAT） has the unique capability of visualizing optical absorption inside several centimeters-deep biological tissue with a high spatial resolution. However, single linear-array transducer-based PAT suffers from the limited-view challenge, and thus the synthetic aperture configuration is designed that still requires multichannel data acquisition hardware. Herein, a feasible synthetic aperture PAT based on compressed sensing reconstruction is proposed. Both the simulation and experimental results tested the theoretical model and validated that this approach can improve the image resolution and address the limited-view problem while preserving the target information with a fewer number of measurements.