Intravascular photoacoustic and optical coherence tomography imaging dual-mode system for detecting spontaneous coronary artery dissection: A feasibility study

In this work,we present an intravascular dual-mode endoscopic system capable of both intravascular photoacoustic imaging(IVPAI)and intravascular optical coherence tomography(IVOCT)for recognizing spontaneous coronary artery dissection(SCAD)phantoms.IVPAI provides high-resolution and high-penetration images of intramural hematoma(IMH)at different depths,so it is especially useful for imaging deep blood clots associated with imaging phantoms.IVOCT can readily visualize the double-lumen morphology of blood vessel walls to identify intimal tears.We also demonstrate the capability of this dual-mode endoscopic system using mimicking phantoms and biological samples of blood clots in ex vivo porcine arteries.The results of the experiments indicate that the combined IVPAI and IVOCT technique has the potential to provide a more accurate SCAD assessment method for clinical applications.

Triple-path feature transform network for ring-array photoacoustic tomography image reconstruction

Photoacoustic imaging(PAI)is a noninvasive emerging imaging method based on the photoacoustic effect,which provides necessary assistance for medical diagnosis.It has the characteristics of large imaging depth and high contrast.However,limited by the equipment cost and reconstruction time requirements,the existing PAI systems distributed with annular array transducers are difficult to take into account both the image quality and the imaging speed.In this paper,a triple-path feature transform network(TFT-Net)for ring-array photoacoustic tomography is proposed to enhance the imaging quality from limited-view and sparse measurement data.Specifically,the network combines the raw photoacoustic pressure signals and conventional linear reconstruction images as input data,and takes the photoacoustic physical model as a prior information to guide the reconstruction process.In addition,to enhance the ability of extracting signal features,the residual block and squeeze and excitation block are introduced into the TFT-Net.For further efficient reconstruction,the final output of photoacoustic signals uses‘filter-then-upsample’operation with a pixel-shuffle multiplexer and a max out module.Experiment results on simulated and in-vivo data demonstrate that the constructed TFT-Net can restore the target boundary clearly,reduce background noise,and realize fast and high-quality photoacoustic image reconstruction of limited view with sparse sampling.

Highly Sensitive MoS_2–Indocyanine Green Hybrid for Photoacoustic Imaging of Orthotopic Brain Glioma at Deep Site

Photoacoustic technology in combination with molecular imaging is a highly effective method for accurately diagnosing brain glioma. For glioma detection at a deeper site, contrast agents with higher photoacoustic imaging sensitivity are needed. Herein, we report a MoS_2–ICG hybrid with indocyanine green(ICG) conjugated to the surface of MoS_2 nanosheets. The hybrid significantly enhanced photoacoustic imaging sensitivity compared to MoS_2 nanosheets. This conjugation results in remarkably high optical absorbance across a broad near-infrared spectrum, redshifting of the ICG absorption peak and photothermal/photoacoustic conversion efficiency enhancement of ICG. A tumor mass of 3.5 mm beneath the mouse scalp was clearly visualized by using MoS_2–ICG as a contrast agent for the in vivo photoacoustic imaging of orthotopic glioma, which is nearly twofold deeper than the tumors imaged in our previous report using MoS_2 nanosheet. Thus, combined with its good stability and high biocompatibility, the MoS_2–ICG hybrid developed in this study has a great potential for high-efficiency tumor molecular imaging in translational medicine.

Stomach wall structure and vessels imaging by acoustic resolution photoacoustic microscopy

AIM To image stomach wall blood vessels and tissue, layerby-layer.METHODS We built up the acoustic resolution photoacoustic microscopy(AR-PAM) system for imaging layered tissues, such as the stomach wall. A tunable dye laser system was coupled to a fiber bundle. The fibers of the bundle were placed in nine directions with an incident angle of 45° around a high-frequency ultrasound transducer attached to the acoustic lens. This structure formed a dark field on the tissue surface under the acoustic lens and the nine light beams from the fibers to be combined near the focal point of the acoustic lens. The sample piece was cut from a part of the porcine stomach into a petri dish. In order to realize photoacoustic depth imaging of tumor, we designed a tumor model based on indocyanine green(ICG) dye. The ICG solution(concentration of 129 μM/m L)was mixed into molten gel, and then a gel mixture of ICG(concentration of 12.9 μM/mL) was injected into the stomach submucosa. The injection quantity was controlled by 0.1 mL to make a small tumor model. RESULTS An acoustic resolution photoacoustic microscopy based on fiber illumination was established and an axial resolution of 25 μm and a lateral resolution of 50 μm in its focal zone range of 500 μm has been accomplished. We tuned the laser wavelength to 600 nm. The photoacoustic probe was driven to do B-scan imaging in tissue thickness of 200 μm. The photoacoustic micro-image of mucosa and submucosa of the tissue have been obtained and compared with a pathological photograph of the tissue stained by hematoxylin-eosin staining. We have observed more detailed internal structure of the tissue. We also utilized this photoacoustic microscopy to image blood vessels inside the submucosa. High contrast imaging of the submucosa tumor model was obtained using ICG dye. CONCLUSION This AR-PAM is able to image layer-by-layer construction and some blood vessels under mucosa in the stomach wall without any contrast agents.

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.

RBC Membrane Camouflaged Semiconducting Polymer Nanoparticles for Near-Infrared Photoacoustic Imaging and Photothermal Therapy

Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated SPNs with sur-face cloaked by red blood cell membrane(RBCM)are developed for highly e ective photoacoustic imaging and photothermal therapy.The resulting RBCM-coated SPN(SPN@RBCM)displays remarkable near-infrared light absorption and good photosta-bility,as well as high photothermal conver-sion e ciency for photoacoustic imaging and photothermal therapy.Particularly,due to the small size(<5 nm),SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity.The RBCM endows the SPNs with prolonged systematic circulation time,less reticuloendothelial system uptake and reduced immune-recognition,hence improving tumor accumulation after intravenous injection,which provides strong photoacoustic signals and exerts excellent photothermal therapeutic e ects.Thus,this work provides a valuable paradigm for safe and highly e cient tumor pho-toacoustic imaging and photothermal therapy for further clinical translation.

Influence of limited-view scanning on depth imaging of photoacoustic tomography

We study the influence of limited-view scanning on the depth imaging of photoacoustic tomography. The situation, in which absorbers are located at different depths with respect to the limited-view scanning trajectory, is called depth imaging and is investigated in this paper. The results show that limited-view scanning causes the reconstructed intensity of deep absorbers to be weaker than that of shallow ones and that deep absorbers will be invisible if the scanning range is too small. The concept of effective scanning angle is proposed to analyse that phenomenon. We find that an effective scanning angle can well predict the relationship between scanning angle and the intensity ratio of absorbers. In addition, limited-view scanning is employed to improve image quality.

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.

Customized anterior segment photoacoustic imaging for ophthalmic burn evaluation in vivo

Photoacoustic imaging has many advantages in ophthalmic application including high-resolution,requirement of no exogenous contrast agent,and noninvasive acquisition of both morphologic and functional information.However,due to the limited depth of focus of the imaging method and large curvature of the eye,it remains a challenge to obtain high quality vascular image of entire anterior segment.Here,we proposed a new method to achieve high quality imaging of anterior segment.The new method applied a curvature imaging strategy based on only one time scanning,and hence is time efficient and more suitable for ophthalmic imaging compared to previously reported methods using similar strategy.A custom-built photoacoustic imaging system was adapted for ophthalmic application and a customized image processing method was developed to quantitatively analyze both morphologic and functional information in vasculature of the anterior segment.The results showed that the new method improved the image quality of anterior segment significantly compared to that of conventional high resolution photoacoustic imaging.More importantly,we applied the new method to study ophthalmic disease in an in vivo mouse model for the first time.The results verified the suitability and advantages of the new method for imaging the entire anterior segment and the numerous potentials of applying it in ophthalmic imaging in future.

Photoacoustic viscoelasticity imaging dedicated to mechanical characterization of biological tissues

Since changes in mechanical properties of biological tissues are often closely related to pathology,the viscoelastic properties are important physical parameters for medical diagnosis.A photoacoustic(PA)phase-resolved method for noninvasively characterizing the biological tissue viscoelasticity has been proposed by Gao et al.[G.Gao,S.Yang,D.Xing,\Viscoelasticity imaging of biological tissues with phase-resolved photoacoustic measurement,"Opt.Lett.36,3341–3343(2011)].The mathematical relationship between the PA phase delay and the viscosity–elasticity ratio has been theoretically deduced.Moreover,systems of PA viscoelasticity(PAVE)imaging including PAVE microscopy and PAVE endoscopy were developed,and high-PA-phase contrast images re°ecting the tissue viscoelasticity information have been successfully achieved.The PAVE method has been developed in tumor detection,atherosclerosis characterization and related vascular endoscopy.We reviewed the development of the PAVE technique and its applications in biomedical¯elds.It is believed that PAVE imaging is of great potential in both biomedical applications and clinical studies.

Non-invasive and low-artifact in vivo brain imaging by using a scanning acoustic-photoacoustic dual mode microscopy

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 tissues with complex acoustic properties,such as brain imaging through scalp and skull.

Photoacoustic imaging of prostate cancer

Photoacoustic imaging(PAI),also known as optoacoustic imaging,is a rapidly growing imaging modality with potential in medical diagnosis and therapy monitoring.This paper focuses on the techniques of prostate PAI and its potential applications in prostate cancer detection.Transurethral light delivery combined with transrectal ultrasound detection overcomes light scattering in the surrounding tissue and provides optimal photoacoustic signals while minimizing invasiveness.While label-free PAI based on endogenous contrast has promising potential for prostate cancer detection,exogenous contrast agents can further enhance the sensitivity and speci¯city of prostate cancer PAI.Further in vivo studies are required in order to achieve the translation of prostate PAI to clinical implementation.The minimal invasiveness,relatively low cost,high speci¯city and sensitivity,and real-time imaging capability are valuable advantages of PAI that may improve the current prostate cancer management in clinic.

SIMULTANEOUS IMAGING OF A lacZ-MARKED TUMOR AND MICROVASCULATURE MORPHOLOGY IN VIVO BY DUAL-WAVELENGTH PHOTOACOUSTIC MICROSCOPY

Photoacoustic molecular imaging,combined with the reporter-gene technique,can provide a valuable tool for cancer research.The expression of the lacZ reporter gene can be imaged using photoacoustic imaging following the injection of X-gal,a colorimetric assay for the lacZ-encoded enzymeβ-galactosidase.Dual-wavelength photoacoustic microscopy was used to non-invasively image the detailed morphology of a lacZ-marked 9L gliosarcoma and its surrounding microvasculature simultaneously in vivo,with a superior resolution on the order of 10μm.Tumor-feeding vessels were found,and the expression level of lacZ in tumor was estimated.With future development of new absorption-enhancing reporter-gene systems,we anticipate this strategy can lead to a better understanding of the role of tumor metabolism in cancer initiation,progression,and metastasis,and in its response to therapy.

Closed/Open-Cell Photoacoustic Imaging for Spectroscopic Measurements

Photoacoustic imaging using a closed photoacoustic cell and an open photoacoustic cell with gas- microphone detection scheme was described. R/G/B LED light sources were used for the closed photoacoustic (PA) cell configuration. The colored specimen enclosed in a PA cell was imaged with R/G/B color light sources, and an image restored from the inverted PA images was compared with the original image. For open cell configuration, an open PA cell using a spheroidal acoustic resonator was applied to measure the amount of large-sized colored specimens. A calibration curve for a food red dye was obtained that apparently showed the ability of the present scheme to measure as a spectroscopic measurement tool.

Photoacoustic mesoscopy:pushing toward the depth limit in the high-resolution optical imaging for biomedical applications and clinical potentials

Photoacoustic mesoscopy(PAMe) offers high-sensitivity in vivo imaging based on the rich optical contrast in biological tissues,with sub-100-micron resolutions at a few millimeters depth. By benefiting from low ultrasonic scattering,this emerging technology has pushed the penetration depth beyond the optical diffuse limit unprecedented for high-resolution optical methods.Here,we review ed the state-of-art implementations of PAMe and their achievements in biological and primary clinical applications. With the high-frequency focused ultrasonic detector,the high-resolution optical visualization can be achieved by utilizing various PAMe systems. These capabilities of PAMe have made it well applicable for understanding the biological mechanisms,exploring the pathological features and analyzing the characteristics of human skin. Future improvements and prospects of PAMe are also mentioned,suggesting its great potential tow ards the corresponding emerging biomedical and clinical applications.

Advances in Photoacoustic Imaging for Interventional Application

The incidence and mortality of cardiovascular diseases and gastrointestinal cancer have gradually increased in recent years,and these diseases have become major social and public-health concerns.New requirements have been proposed for the clinical diagnosis of these diseases in the hope that,by accessing accurate structural information,to further grasp the functional information which closely related to the development of the diseases.Photoacoustic imaging is a new imaging method in which ultrasonic signals are generated from biological samples by laser-pulse irradiation.It has the advantages of high optical contrast,large ultrasound penetration depth,and high resolution.Additionally,it can acquire spectral information.The integration of a photoacoustic imaging system into a tiny imaging catheter can realize interventional imaging based on photoacoustic principles.The combination of structural imaging of cardiovascular and gastrointestinal lesion regions with photoacoustic spectroscopy to identify and quantify tissue components can realize highly sensitive functional imaging.After surveying the recent progress in the development of the photoacoustic imaging method for interventional application,with a particular emphasis on intravascular photoacoustic imaging,photoacoustic endoscopy,and photoacoustic spectroscopy,we summarize and identify future research directions for interventional photoacoustic imaging.

High-contrast imaging based on wavefront shaping to improve low signal-to-noise ratio photoacoustic signals using superpixel method

Photoacoustic(PA) imaging has drawn tremendous research interest for various applications in biomedicine and experienced exponential growth over the past decade. Since the scattering effect of biological tissue on ultrasound is two-to three-orders magnitude weaker than that of light, photoacoustic imaging can effectively improve the imaging depth.However, as the depth of imaging further increases, the incident light is seriously affected by scattering that the generated photoacoustic signal is very weak and the signal-to-noise ratio(SNR) is quite low. Low SNR signals can reduce imaging quality and even cause imaging failure. In this paper, we proposed a new wavefront shaping and imaging method of low SNR photoacoustic signal using digital micromirror device(DMD) based superpixel method. We combined the superpixel method with DMD to modulate the phase and amplitude of the incident light, and the genetic algorithm(GA) was used as the wavefront shaping algorithm. The enhancement of the photoacoustic signal reached 10.46. Then we performed scanning imaging by moving the absorber with the translation stage. A clear image with contrast of 8.57 was obtained while imaging with original photoacoustic signals could not be achieved. The proposed method opens new perspectives for imaging with weak photoacoustic signals.

Near-infrared dye-loaded magnetic nanoparticles as photoacoustic contrast agent for enhanced tumor imaging

Objective: Photoacoustic(PA) tomography(PAT) has attracted extensive interest because of its optical absorption contrast and ultrasonic detection. This study aims to develop a biocompatible and biodegradable PA contrast agent particularly promising for clinical applications in human body.Methods: In this study, we presented a PA contrast agent: 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)](DSPE-PEG)-coated superparamagnetic iron oxide(SPIO) nanoparticles(NPs) loaded with indocyanine green(ICG). We used ICG and SPIO NPs because both drugs are approved by the U.S. Food and Drug Administration. Given the strong absorption of near-infrared laser pulses, SPIO@DSPE-PEG/ICG NPs with a uniform diameter of ~28 nm could significantly enhance PA signals.Results: We demonstrated the contrast enhancement of these NPs in phantom and animal experiments, in which the in vivo circulation time of SPIO@DSPE-PEG/ICG NPs was considerably longer than that of free ICG. These novel NPs also displayed a high efficiency of tumor targeting.Conclusions: SPIO@DSPE-PEG/ICG NPs are promising PAT contrast agents for clinical applications.

On the Pollen Detection with Photoacoustic Imaging

A photoacoustic (PA) imaging that utilizes acoustic detection of sound generated by a specimen due to the absorption of modulated light was applied to measure the amount of the pollen of the Cryptomeria japonica, Asian allergic plant. High-sensitivity PA imaging can measure pollen particles with a large dynamic range from single particle to several hundred micrograms. The PA signal dependence on the amount of the pollen showed good correlation with the amount of pollen.

Recent developments in photoacoustic imaging and sensing for nondestructive testing and evaluation

Photoacoustic(PA)imaging has been widely used in biomedical research and preclinical studies during the past two decades.It has also been explored for nondestructive testing and evaluation(NDT/E)and for industrial applications.This paper describes the basic principles of PA technology for NDT/E and its applications in recent years.PA technology for NDT/E includes the use of a modulated continuous-wave laser and a pulsed laser for PA wave excitation,PA-generated ultrasonic waves,and all-optical PA wave excitation and detection.PA technology for NDT/E has demonstrated broad applications,including the imaging of railway cracks and defects,the imaging of Li metal batteries,the measurements of the porosity and Young’s modulus,the detection of defects and damage in silicon wafers,and a visualization of underdrawings in paintings.