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.

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.

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.

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.

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.

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.

A photoacoustic imaging system with variable gain at different depths

We established a photoacoustic imaging(PAI)system that can provide variable gain at different depths.The PAI system consists of a pulsed laser with an optical parametric oscillator working at a 728 nmwavelength and an imaging-acquisition-and-processing unit with an ultrasound transducer.Avoltage-controlled attenuator was used to realize variable gain at different depths when acquiring PAI signals.The proof-of-concept imaging results for variable gain at different depths were achieved using specic phantoms.Both resolution and optical contrast obtained through the results of variable gain for a targeted depth range are better than those of constant gain for all depths.To further testify the function,we imaged the sagittal section of the body of in vivo nude mice.In addition,we imaged an absorption sample embedded in a chicken breast tissue,reaching a maximum imaging depth of
4.6 cm.The results obtained using the proposed method showed better resolution and contrast than when using 50 dB gain for all depths.The depth range resolution was
1 mm,and the maximum imaging depth of our system reached
4.6 cm.Furthermore,blood vessels can be revealed and targeted depth range can be selected in nude mice imaging.

Antimonene Nanosheets - mediated Photoacoustic Imaging for Tumor Detection in vivo

Photoacoustic imaging(PAI)is a new non-invasive and non-ionizing biomedical imaging method developed in recent years.PAI exhibits the high resolution of optical imaging and the deep tissue penetration of acoustic imaging,breaking through the soft limit of traditional biomedical imaging.However,most early tumors exhibit non-obvious photoacoustic imaging,so it is important to develop effective extrinsic photoacoustic imaging agents.On this basis,antimonene nanosheets(AMNSs)was designed.As a new two-dimensional(2D)material,AMNSs has good light absorption,excellent photothermal conversion efficiency and photoacoustic performance in the band range of 300-900 nm.So,the AMNSs are expected to be used as a contrast agent to achieve high quality photoacoustic imaging of ultra-small tumors in vivo.

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）.

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.

Recent advances in applications of multimodal ultrasound-guided photoacoustic imaging technology

Photoacoustic imaging(PAI)is often performed simultaneously with ultrasound imaging and can provide functional and cellular information regarding the tissues in the anatomical markers of the imaging.This paper describes in detail the basic principles of photoacoustic/ultrasound(PA/US)imaging and its application in recent years.It includes near-infrared-region PA,photothermal,photodynamic,and multimode imaging techniques.Particular attention is given to the relationship between PAI and ultrasonic imaging;the latest high-frequency PA/US imaging of small animals,which involves not only B-mode,but also color Doppler mode,power Doppler mode,and nonlinear imaging mode;the ultrasonic model combined with PAI,including the formation of multimodal imaging;the preclinical imaging methods;and the most effective detection methods for clinical research for the future.

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.

Heavy-atom engineered hypoxia-responsive probes for precisive photoacoustic imaging and cancer therapy

Photoacoustic agents combining photodynamic therapy(PDT) and photothermal therapy(PTT) functions have emerged as potent theranostic agents for combating cancer. The molecular approaches for enhancing the near-infrared(NIR)-absorption and maximizing non-radiative energy transfer are essential for effective photoacoustic imaging(PAI) and therapy applications. In addition, such molecules with high specificity and affinity to cancer cells are urgently needed, which would further decrease the side effect during treatments. In this study, we applied a heavy-atom engineering strategy and introduced p-aminophenol,-thio, and-seleno moieties into NIR heptamethine cyanine(Cy7) skeleton(Cy7-X-NH_(2), X = O, S, Se) to significantly increase photothermal conversion efficiency for PTT and promote intersystem crossing for PDT.Additionally, we designed a series of nitroreductase(NTR)-activated photoacoustic probes(Cy7-X-NO_(2),X = O, S, Se), and target hypoxic tumors with NTR overexpression. Our prostate cancer targeting probe,Cy7-Se-NO_(2)-KUE, exhibited specific tumor photoacoustic signals and effective tumor killing through outstanding synergistic PTT/PDT in vivo. These findings highlighted a versatile strategy for cancer photoacoustic diagnosis and enhanced phototherapy.

Utilizing dual-responsive iridium(Ⅲ) complex for hepatocellular carcinoma: Integrating photoacoustic imaging with chemotherapy and photodynamic therapy

Stimuli-triggered release and alleviating resistance of iridium(Ⅲ)-based drugs at tumor sites remains challengeable for clinical hepatoma therapy.Herein,a doxorubicin@iridium-transferrin(DOX@Ir-TF)nanovesicle was synthesized by carboxylated-transferrin(TF)and doxorubicin-loaded amphiphilic iridium-amino with quaternary ammonium(QA)groups and disulfide bonds.The QA groups enhanced photophysical properties and broadened production capacity of photoinduced-reactive oxygen species(ROS),while the disulfide-bridged bonds regulated oxidative stress levels through reacting with glutathione(GSH);simultaneously,modification of TF improved recognition and endocytosis of the nanovesicle for tumor cells.Based on in-vitro results,a controlled-release behavior of DOX upon a dualresponsiveness of GSH and near-infrared ray(NIR)irradiation was presented,along with high-efficiency generation of ROS.After an intravenous injection,the nanovesicle was targeted at tumor sites,realizing TF-navigated photoacoustic imaging guidance and synergistic chemotherapy-photodynamic therapy under NIR/GSH stimulations.Overall,newly-synthesized DOX@Ir-TF nanovesicle provided a potential in subcutaneous hepatocellular carcinoma therapy due to integrations of targeting delivery,dual-stimuli responsive release,synergistic therapy strategy,and real-time monitoring.

Tumor microenvironment-activated theranostic nanoreactor for NIR-II Photoacoustic imaging-guided tumor-specific photothermal therapy

Theranostic agents that can be sensitively and specifically activated by the tumor microenvironment(TME)have recently attracted considerable attention.In this study,TME-activatable 3,3′,5,5′-tetramethylbenzidine(TMB)-copper peroxide(CuO_(2))@poly(lactic-co-glycolic acid)(PLGA)@red blood cell membrane(RBCM)(TCPR)nanoparticles(NPs)for second near-infrared photoacoustic imaging-guided tumor-specific photothermal therapy were developed by co-loading CuO_(2)NPs and TMB into PLGA camouflaged by RBCMs.As an efficient H_(2)O_(2)supplier,once exposed to a proton-rich TME,CuO_(2)NPs can generate H_(2)O_(2)and Cu^(2+),which are further reduced to Cu^(+) by endogenous glutathione.Subsequently,the Cu^(+)-mediated Fenton-like reaction produces cytotoxic·OH to kill the cancer cells and induce TMB-mediated photoacoustic and photothermal effects.Combined with the RBCM modification-prolonged blood circulation,TCPR NPs display excellent specificity and efficiency in suppressing tumor growth,paving the way for more accurate,safe,and efficient cancer theranostics.