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.

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.

Photoacoustic image-guided corpus cavernosum intratunical injection of adipose stem cell-derived exosomes loaded polydopamine thermosensitive hydrogel for erectile dysfunction treatment

Stem cell-derived exosomes(SC-EXO)was an emerging therapeutic agent in regenerative medicine.Intratunical injection of SC-EXO is considered as a prospective approach for erectile dysfunction(ED)treatment.However,high vascularization of cavernous body makes effective retention a major challenge for SC-EXO intratunical injection.In this study,a Polydopamine nanoparticles(PDNPs)incorporated poly(ethylene glycol)-poly(ε-caprolactone-co-lactide)(PDNPs-PELA)thermosensitive hydrogels were fabricated by a facile in situ polymerization for intratunical administration of adipose stem cell-derived exosomes(EXO).The hydrogels exhibited sol-gel transition at body temperature.Moreover,the in-situ polymerization of PDNPs using poly(ethylene glycol)-poly(ε-caprolactone-co-lactide)(PELA)block copolymer as a template was found to be more stable dispersion in the gel system.After being encapsulated into the hydrogel,EXO shows sustained release behavior within two weeks.In vivo animal experiments revealed that exosomes released from hydrogel lead to the healing of endothelial cells and neurons,increase of the cavity’s pressure,thereby restoring the erectile function.In particular,since the PDNPs in thermosensitive gels have excellent photoacoustic performance,the hydrogel can be accurately delivered into the tunica albuginea by the guidance of real-time photoacoustic imaging.These results suggest that the as-prepared PDNPs-PELA has a promising future as an injectable exosome carrier for ED treatment.

A microvascular image analysis method for optical-resolution photoacoustic microscopy

Optical-resolution photoacoustic microscopy(OR-PAM)has been shown to be an excellent tool for high-resolution imaging of microvasculature,and quantitative analysis of the microvascula-ture can provide valuable information for the early diagnosis and treatment of various vascular-related diseases.In order to address the characteristics of weak signals,discontinuity and small diameters in photoacoustic microvascular images,we propose a method adaptive to the micro-vascular segmentation in photoacoustic images,including Hessian matrix enhancement and the morphological connection operators.The accuracy of our vascular segmentation method is quantitatively evaluated by the multiple criteria.To obtain more precise and continuous mi-crovascular skeletons,an improved skeleton extraction framework based on the multistencil fast marching(MSFM)method is developed.We carried out in vivo OR-PAM microvascular imaging in mouse ears and subcutaneous hepatoma tumor model to verify the correctness and superiority of our proposed method.Compared with the previous methods,our proposed method can extract the microvascular network more completely,continuously and accurately,and provide an ef-fective solution for the quantitative analysis of photoacoustic microvascular images with many small branches.

Photoacoustic imaging principle and analysis of the images by MSOT

Photoacoustic imaging, also called optoacoustic tomography, is a non-destructive biomedical imaging technique which employs acoustic detection to image optical absorption contrast with high-resolution deep into scattering tissue. Photoacoustic imaging overcomes the limit of high light scattering in the tissue and realized in vivo high-resolution and high-contrast imaging in the deep tissue. Photoacoustic imaging technology has been rapid development in recent years and make constantly breakthrough from a technical level to the application level. This paper describes the basic principles of photoacoustic imaging technology and make an example analysis by multispectral optoacoustic tomography （MSOT）.

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.

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.

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.

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 detection of follicular thyroid carcinoma using targeted Nano-Au-Tripods

Follicular thyroid carcinoma(FTC)is the second most common form of thyroid malignancy,and it is associated with more aggressive growth and worse long-term survival outcomes relative to papillary thyroid carcinoma(PTC).Reliable approaches to preoperative FTC detection,however,remain to be established.Herein,a targeted Affibody-Au-Tripod nanoprobe was developed and successfully utilized to facilitate the targeted photoacoustic imaging(PAI)of epidermal growth factor receptor(EGFR)-positive cells and tumors.These Affibody-Au-Tripods were found to be highly sensitive and specific for cells expressing EGFR when used as a PA contrast agent in vitro,and studies conducted in an FTC-133 subcutaneous tumor model system in mice further revealed that these Affibody-Au-Tripods were able to specifically target these EGFR-expressing tumors while providing a strong photoacoustic signal in vivo.Importantly,these nanoprobes exhibited negligible cytotoxicity and robust chemical and physical stability,making Affibody-Au-Tripods promising candidates for targeted PAI-based FTC diagnosis.In addition,these nanoprobes have the potential to facilitate the individualized treatment of patients harboring EGFRpositive tumors.

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.

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.

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.

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.

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.

PEGylated liposomal photosensitizers as theranostic agents for dual-modal photoacoustic andffuorescence imaging-guided photodynamic therapy

The photosensitizer(PS)as photodynamic therapy(PDT)agent,can also serve as the contrast agent for dual-modalffuorescence imaging(FLI)and photoacoustic imaging(PAI)for precise cancer theranostics.In this study,the PAI capability of commercial PS,benzoporphyrin derivative monoacid ring-A(BPD)were examined and compared with that from the other PSs and dyes such as TPPS_(4),Cy5 dye and ICG.We discovered that BPD exhibited its advantage as contrast agent for PAI.Meanwhile,BPD can also serve as the contrast agent for enhanced FLI.In particular,the PEGylated nanoliposome(PNL)encapsulated BPD(LBPD)was produced for contrast enhanced dual-modal FLI and PAI and imaging-guided high-efficiency PDT.Enhanced FLI and PAI results demonstrated the significant accumulation of LBPD both within and among individual tumor during 24 h monitoring for in vivo experiment tests.In-vitro and in-vivo PDT tests were also performed,which showed that LBPD have higher PDT efficiency and can easily break the blood vessel of tumor tissues as compared to that from BPD.It was discovered that LBPD has great potentials as a diagnosis and treatment agent for dual-modal FLI and PAI-guided PDT of cancer.

Chronic cranial window for photoacoustic imaging: a mini review

Photoacoustic(PA)microscopy is being increasingly used to visualize the microcirculation of the brain cortex at the micron level in living rodents.By combining it with long-term cranial window techniques,vasculature can be monitored over a period of days extending to months through a field of view.To fulfill the requirements of long-term in vivo PA imaging,the cranial window must involve a simple and rapid surgical procedure,biological compatibility,and sufficient optical-acoustic transparency,which are major challenges.Recently,several cranial window techniques have been reported for longitudinal PA imaging.Here,the development of chronic cranial windows for PA imaging is reviewed and its technical details are discussed,including window installation,imaging quality,and longitudinal stability.