Isoindigo nanoparticles for photoacoustic imaging-guided tumor photothermal therapy

The key factor in photothermal therapy lies in the selection of photothermal agents.Traditional photothermal agents generally have problems such as poor photothermal stability and low photothermal conversion efficiency.Herein,we have designed and synthesized an isoindigo(IID)dye.We used isoindigo as the molecular center and introduced common triphenylamine and methoxy groups as rotors.In order to improve the photothermal stability and tumor targeting ability,we encapsulated IID into nanoparticles.As a result,the nanoparticles exhibited high photothermal stability and photothermal conversion efficiency(67%)upon 635 nm laser irradiation.Thus,the nanoparticles demonstrated a significant inhibitory effect on live tumors in photothermal therapy guided by photoacoustic imaging and provided a viable strategy to overcome the treatment challenges.

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.

Characterization of cerebrovascular changes in Alzheimer's disease mice by photoacoustic imaging

The cerebral vasculature plays a significant role in the development of Alzheimer's disease(AD),however,the specific association between them remains unclear.In this paper,based on the benefits of photoacoustic imaging(PAI),including label-free,high-resolution,in vivo imaging of vessels,we investigated the structural changes of cerebral vascular in wild-type(WT)mice and AD mice at different ages,analyzed the characteristics of the vascular in different brain regions,and correlated vascular characteristics with cognitive behaviors.The results showed that vascular density and vascular branching index in the cortical and frontal regions of both WT and AD mice decreased with age.Meanwhile,vascular lacunarity increased with age,and the changes in vascular structure were more pronounced in AD mice.The trend of vascular dysfunction aligns with the worsening cognitive dysfunction as the disease progresses.Here,we utilized in vivo PAI to analyze the changes in vascular structure during the progression of AD,elucidating the spatial and temporal correlation with cognitive impairment,which will provide more intuitive data for the study of the correlation between cerebrovascular and the development of AD.

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.

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.

CONTRAST-ENHANCED PHOTOACOUSTIC IMAGING USING INDOCYANINE GREEN-CONTAINING NANOPARTICLES

Contrast agents are attracting a great deal of attention in photoacoustic inaging.Here weintroduce an exogenous contrast agent that provides high photoacoustic signal amplitude at thenear-infrared wavelength._Our_agents consist_of Indocyanine green(ICG)and phospholi-pid-polyethylene glycol(PL-PEG),entitled ICG-PL-PEG nanoparticles,These nanoparticleshave overcome numerous limitations of ICG,such as poor aqueous stability,concentration-dependent aggregation and lack of target specificity.ICG-PL-PEG nanoparticles are bio-compatible and relatively nontoxic.All the components of ICG-PL-PEG nanoparticles havebeen approved for human use.Upon pulsed laser irradiation,the nanoparticles are more eficient inproducing photoacoustic waves than ICG alone.The results showed that ICG-PL-PEG nano-particles act as good contrast agents for photoacoustic imaging.These unique ICG-PL-PEGnanoparticles have great potential in clinical applications.

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.

Photoacoustic molecular imaging with functional nanoparticles

Photoacoustic imaging(PAI)breaks through the optical di®usion limit by making use of the PA e®ect.By converting incident photons into ultrasonic waves,PAI combines high contrast of optical imaging and high spatial resolution in depth tissue of ultrasound imaging in a single imaging modality.This imaging modality has now shown potential for molecular imaging,which enables visualization of biological processes with systemically introduced functional nanoparticles.In the current review,the potentials of di®erent optical nanoprobes as PAI contrast agents were elucidated and discussed.

Multifunctional conjugated polymer nanoparticles for photoacoustic-based multimodal imaging and cancer photothermal therapy

Photoacoustic imaging(PAI)is a hybrid imaging method based on photoacoustic(PA)effects,which is able to capture the structure,function,and molecular information of biological tissues with high resolution.To date,therapeutic techniques under the guidance of PAI have provided new strategies for accurate diagnosis and precise treatment of tumors.In particular,conjugated polymer nanoparticles have been extensively inspected for PA-based cancer theranostics largely due to their superior optical properties such as tunable spectrum and large absorption coefficient and their good biocompatibility,and abundant functional groups.This mini-review mainly focuses on the recent advances toward the development of novel conjugated polymer nanoparticles for PA-based multimodal imaging and cancer photothermal therapy.

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.

A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

Optical molecular imaging in cancer research:current impact and future prospect

Cancer has long been amajor threat to human health.Recent advancements inmolecular imaging have revolutionized cancer research by enabling early and precise disease localization,essential for effective management.In particular,optical molecular imaging is an invaluable cancer detection tool in preoperative planning,intraoperative guidance,and postoperative monitoring owing to its noninvasive nature,rapid turnover,safety,and ease of use.The tumor microenvironment and cells within it express distinct biomarkers.Optical imaging technology leverages these markers to differentiate tumor tissues from surrounding tissues and capture real-time images with high resolution.Nevertheless,a robust understanding of these cancer-relatedmolecules and their dynamic changes is crucial for effectivelymanaging cancer.Recent advancements in opticalmolecular imaging technologies offer novel approaches for cancer investigation in research and practice.This review investigates themodern opticalmolecular imaging techniques employed in both preclinical and clinical research,including bioluminescence,fluorescence,chemiluminescence,photoacoustic imaging,and Raman spectroscopy.We explore the current paradigm of optical molecular imaging modalities,their current status in preclinical cancer research and clinical applications,and future perspectives in the fields of cancer research and treatment.

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.

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.

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.

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 OF BIOLOGICAL TISSUES WITH INTENSITY-MODULATED CONTINUOUS-WAVE LASER

In this paper,a novel photoacoustic viscoelasticity imaging(PAVEI)technique that provides viscoelastic infornation of biological tissues is presented.We deduced the proocess of photoacoustic(PA)ffct on the basis of thermal viscoelasticity theory and est ablished the relationship between the PA phase delay and the vicoelasticity for soft solids.By detecting the phase delay of PA signal,the viscoelasticity distribution of absorbers can be mapped.Gelatin phantoms with diferent densities and different absorption cofficients were used to verify the dependence of PA VEI measurements.Moreover,tissue mimicking phantoms mixed with fat and collagen at different concentrations were used to testify the feasibility of this technique with reli able contrast.Finally,the PAVEI was sucossfully applied to discrimination between biological tissue constituents.Our experimental results demonstrate that this novel technique has the potential for visualizing the anatomical and biomechanical properties of biological tissues.

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.