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 me...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.展开更多
We theoretically investigate the feasibility of reconstructing the transverse structures of femtosecond laser filaments in air by photoacoustic tomography.To simulate the emission and transmission of filament-induced ...We theoretically investigate the feasibility of reconstructing the transverse structures of femtosecond laser filaments in air by photoacoustic tomography.To simulate the emission and transmission of filament-induced ultrasonic signals more truly,a series of experimentally recorded cross-sectional images are used to simulate the initial pressure rise from multiple filaments(MFs).The aperture size and sensitivity of the detector was incorporated into the reconstruction algorithm.The results show that frequency of acoustic signals induced by MFs with maximum volumetric energy density~100 k J/m^(3)is about 2 MHz below.The initial spatial distribution of optical filaments can be clearly reconstructed with the back projection based algorithm.We recommend a PAT system with transducers of a lower central frequency and a stronger apodization working at a longer scanning radius can be used in photoacoustic image reconstruction of femtosecond laser multifilaments.This study demonstrates the feasibility of using photoacoustic tomography to reconstruct femtosecond multifilament images,which is helpful for studying the complex dynamic processes of multifilament and multifilament manipulation and is also valuable for the remote applications of laser filaments.展开更多
Spinal cord injury is a severe neurological disorder;however,current treatment methods often fail to restore nerve function effectively.Spinal cord stimulation via electrical signals is a promising therapeutic modalit...Spinal cord injury is a severe neurological disorder;however,current treatment methods often fail to restore nerve function effectively.Spinal cord stimulation via electrical signals is a promising therapeutic modality for spinal cord injury.Based on similar principles,this review aims to explore the potential of optical and acoustic neuromodulation techniques,emphasizing their benefits in the context of spinal cord injury.Photoacoustic imaging,renowned for its noninvasive nature,high-resolution capabilities,and cost-effectiveness,is well recognized for its role in early diagnosis,dynamic monitoring,and surgical guidance in stem cell therapies for spinal cord injury.Moreover,photoacoustodynamic therapy offers multiple pathways for tissue regeneration.Optogenetics and sonogenetics use genetic engineering to achieve precise neuronal activation,while photoacoustoelectric therapy leverages photovoltaic materials for electrical modulation of the nervous system,introducing an innovative paradigm for nerve system disorder management.Collectively,these advancements represent a transformative shift in the diagnosis and treatment of spinal cord injury,with the potential to significantly enhance nerve function remodeling and improve patient outcomes.展开更多
The temperature of an organism provides key insights into its physiological and pathological status.Temperature monitoring can effectively assess potential health issues and plays a critical role in thermal treatment....The temperature of an organism provides key insights into its physiological and pathological status.Temperature monitoring can effectively assess potential health issues and plays a critical role in thermal treatment.Photoacoustic imaging(PAI)has enabled multi-scale imaging,from cells to tissues and organs,where its high contrast,deep penetration,and high resolution make it an emerging tool in biomedical imaging field.Benefiting from the linear correlation between the Grüneisen parameter and temperature within the range of 10–55∘C,the PAI has been developed as novel noninvasive label-free tool for temperature monitoring especially for thermotherapy mediated by laser,ultrasound,and microwave.Additionally,by utilizing temperature-responsive photoacoustic nanoprobes,the temperature information of the targeted organism can also be extracted with enhanced imaging contrast and specificity.This review elucidates the basic principles of temperature monitoring technology implemented by PAI,further highlighting the limitations of traditional photoacoustic thermometry,and summarizes recent technological advancements in analog simulation,calibration method,measurement accuracy,nanoprobe design,and wearable improvement.Furthermore,we discuss the biomedical applications of PA temperature monitoring technology in photothermal therapy and ultrasound therapy,finally,anticipating future developments in the field.展开更多
Photoacoustic imaging(PAI)employs short laser pulses to excite absorbing materials,producing ultrasonic waves spanning a broad spectrum of frequencies.These ultrasonic waves are captured surrounding the sample and uti...Photoacoustic imaging(PAI)employs short laser pulses to excite absorbing materials,producing ultrasonic waves spanning a broad spectrum of frequencies.These ultrasonic waves are captured surrounding the sample and utilized to reconstruct the initial pressure distribution tomographically.Despite the wide spectral range of the laser-generated photoacoustic signal,an individual transducer can only capture a limited segment of the signal due to its constrained bandwidth.Herein,we have developed a multi-bandwidth ring array photoacoustic computed tomography(PACT)system,incorporating a probe with two semi-ring arrays:one for high frequency and the other for low frequency.Utilizing the two semi-ring array PAIs,we have devised a specialized deep learning model,comprising two serially connected U-net architectures,to autonomously generate multi-bandwidth full-view PAIs.Preliminary results from simulations and in vivo experiments illustrate the system's robust multi-bandwidth imaging capabilities,achieving an excellent PSNR of 34.78 dB and a structural similarity index measure(SSIM)of 0.94 in the high-frequency reconstruction of complex mouse abdominal structures.This innovative PACT system is notable for its capability to seamlessly acquire multi-bandwidth full-view PAIs,thereby advancing the application of PAI technology in the biomedical domain.展开更多
Foundation models(FMs)have rapidly evolved and have achieved signicant accomplishments in computer vision tasks.Specically,the prompt mechanism conveniently allows users to integrate image prior information into the m...Foundation models(FMs)have rapidly evolved and have achieved signicant accomplishments in computer vision tasks.Specically,the prompt mechanism conveniently allows users to integrate image prior information into the model,making it possible to apply models without any training.Therefore,we proposed a workflow based on foundation models and zero training to solve the tasks of photoacoustic(PA)image processing.We employed the Segment Anything Model(SAM)by setting simple prompts and integrating the model's outputs with prior knowledge of the imaged objects to accomplish various tasks,including:(1)removing the skin signal in three-dimensional PA image rendering;(2)dual speed-of-sound reconstruction,and(3)segmentation ofnger blood vessels.Through these demonstrations,we have concluded that FMs can be directly applied in PA imaging without the requirement for network design and training.This potentially allows for a hands-on,convenient approach to achieving efficient and accurate segmentation of PA images.This paper serves as a comprehensive tutorial,facilitating the mastery of the technique through the provision of code and sample datasets.展开更多
Acoustic-resolution photoacoustic microscopy(AR-PAM)suffers from degraded lateral resolution due to acoustic diffraction.Here,a resolution enhancement strategy for AR-PAM via a mean-reverting diffusion model was propo...Acoustic-resolution photoacoustic microscopy(AR-PAM)suffers from degraded lateral resolution due to acoustic diffraction.Here,a resolution enhancement strategy for AR-PAM via a mean-reverting diffusion model was proposed to achieve the transition from acoustic resolution to optical resolution.By modeling the degradation process from high-resolution image to low-resolution AR-PAM image with stable Gaussian noise(i.e.,mean state),a mean-reverting diffusion model is trained to learn prior information of the data distribution.Then the learned prior is employed to generate a high-resolution image from the AR-PAM image by iteratively sampling the noisy state.The performance of the proposed method was validated utilizing the simulated and in vivo experimental data under varying lateral resolutions and noise levels.The results show that an over 3.6-fold enhancement in lateral resolution was achieved.The image quality can be effectively improved,with a notable enhancement of∼66%in PSNR and∼480%in SSIM for in vivo data.展开更多
Deep learning(DL)is making significant inroads into biomedical imaging as it provides novel and powerful ways of accurately and efficiently improving the image quality of photoacoustic microscopy(PAM).Off-the-shelf DL...Deep learning(DL)is making significant inroads into biomedical imaging as it provides novel and powerful ways of accurately and efficiently improving the image quality of photoacoustic microscopy(PAM).Off-the-shelf DL models,however,do not necessarily obey the fundamental governing laws of PAM physical systems,nor do they generalize well to scenarios on which they have not been trained.In this work,a physics-embedded degeneration learning(PEDL)approach is proposed to enhance the image quality of PAM with a self-attention enhanced U-Net network,which obtains greater physical consistency,improves data efficiency,and higher adaptability.The proposed method is demonstrated on both synthetic and real datasets,including animal experiments in vivo(blood vessels of mouse's ear and brain).And the results show that compared with previous DL methods,the PEDL algorithm exhibits good performance in recovering PAM images qualitatively and quantitatively.It overcomes the challenges related to training data,accuracy,and robustness which a typical data-driven approach encounters,whose exemplary application envisions to provide a new perspective for existing DL tools of enhanced PAM.展开更多
The brain lymphatic system plays a crucial role in maintaining homeostasis,clearing metabolic waste,and regulating neuroinflammation.Its dysfunction is strongly linked to neurodegenerative diseases such as Alzheimer&#...The brain lymphatic system plays a crucial role in maintaining homeostasis,clearing metabolic waste,and regulating neuroinflammation.Its dysfunction is strongly linked to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.In this study,we employed dual-contrast functionalphotoacoustic microscopy to evaluate the impact of lipopolysaccharide-induced central nervous system inflammation on brain lymphatic function and to explore the protective effects of the P2X7 receptor(P2X7R)antagonist.Our findings demonstrated that lipopolysac-charide intervention led to impaired function of the meningeal lymphatic vessels,which was par-tially restored by the P2X7R antagonist,whereas its effects on the glymphatic system and cerebral vessels were minimal.This study further supports the feasibility of photoacoustic microscopy for assessing brain lymphatic function and highlights the therapeutic potential of P2X7R antagonism.These findings suggest that P2X7R may serve as a key target for modulating brain-lymphatic interactions,providing an experimental foundation for developing intervention strategies for neuroinflammatory and neurodegenerative diseases.展开更多
Aging is a natural physiological process with various challenges, related to the loss of homeostasis within the organism, which is not a disease, but a significantly strong risk factor for multiple diseases, including...Aging is a natural physiological process with various challenges, related to the loss of homeostasis within the organism, which is not a disease, but a significantly strong risk factor for multiple diseases, including myocardial infarction, stroke, some age-related cancers, macular degeneration, osteoarthritis, neurodegeneration, and many others. In the body, the main manifestation of aging is cellular aging, which exists within tissues and has a local or global impact on tissue function. However, the lack of effective aging detection tools has always been an issue that cannot be ignored in the field of aging research. Therefore,it is necessary to construct a non-invasive tool for in vivo detection of aging. Here, we show that the photoacoustic probe(LGAL), which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast to the hallmark of aging, and allows for the microscopic imaging of aging through the intact mice. Firstly, this tool LGAL has been successfully applied to detect senescence in cells, displaying stronger photoacoustic signals than normal cells. Then, by using the photoacoustic probe, the blood vessels and tissues inside the mice can be visualized. Young and elderly mice exhibit varying intensities of photoacoustic signals, marking the first time a probe has been used to explore the aging of blood vessels and tissues inside the mice. Finally, we monitored the changes in the degree of aging during tumor treatment under photoacoustic(PA) imaging for the first time. As the treatment time increased, the degree of aging of the tumor gradually deepened. We expect the powerful tool could be a noninvasive and powerful tool for the study of aging biology.展开更多
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 ...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.展开更多
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...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.展开更多
Photothermal therapy(PTT)is a cutting-edge cancer treatment that can kill cancer cells in hypoxic environments without relying on oxygen.Seeking of the ideal photothermal agents with a high absorption coefficient in t...Photothermal therapy(PTT)is a cutting-edge cancer treatment that can kill cancer cells in hypoxic environments without relying on oxygen.Seeking of the ideal photothermal agents with a high absorption coefficient in the near-infrared region,and a high excellent photothermal conversion efficiency is of great significance.Sulfone-Rhodanmine dye has showed an impressive absorption wavelength over 700 nm,but suffered from a stability issue.In this study,we synthesized five sulfone rhodamines and investigated the substitution effects on stability.SO_(2)R2 showed high stability and strong absorbance at 714 nm with an excellent photothermal conversion efficiency of 53.06%,making it suitable for accurate photoacoustic imaging-guided photothermal therapy in vivo.展开更多
Traditional diagnostic techniques including visual examination,ultrasound(US),and magnetic resonance imaging(MRI)have limitations of in-depth information for the detection of nail disorders,resolution,and practicality...Traditional diagnostic techniques including visual examination,ultrasound(US),and magnetic resonance imaging(MRI)have limitations of in-depth information for the detection of nail disorders,resolution,and practicality.This pilot study,for thefirst time,evaluates a dualmodality imaging system that combines photoacoustic tomography(PAT)with the US for the multiparametric quantitative assessment of human nail.The study involved a small cohort offive healthy volunteers who underwent PAT/US imaging for acquiring the nail unit data.The PAT/US dual-modality imaging successfully revealed thefine anatomical structures and microvascular distribution within the nail and nail bed.Moreover,this system utilized multispectral PAT to analyze functional tissue parameters,including oxygenated hemoglobin,deoxyhemoglobin,oxygen saturation,and collagen under tourniquet and cold stimulus tests to evaluate changes in the microcirculation of the nail bed.The quantitative analysis of multispectral PAT reconstructed images demonstrated heightened sensitivity in detecting alterations in blood oxygenation levels and collagen content within the nail bed,under simulated different physiological conditions.This pilot study highlights the potential of PAT/US dual-modality imaging as a real-time,noninvasive diagnostic modality for evaluating human nail health and for early detection of nail bed pathologies.展开更多
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...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.展开更多
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 im...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.展开更多
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 efficienc...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.展开更多
Elastography can be used as a diagnostic method for quantitative characterization of tissue hardness information and thus,differential changes in pathophysiological states of tissues.In this study,we propose a new met...Elastography can be used as a diagnostic method for quantitative characterization of tissue hardness information and thus,differential changes in pathophysiological states of tissues.In this study,we propose a new method for shear wave elastography(SWE)based on laser-excited shear wave,called photoacoustic shear wave elastography(PASWE),which combines photoacoustic(PA)technology with ultrafast ultrasound imaging.By using a focused laser to excite shear waves and ultrafast ultrasonic imaging for detection,high-frequency excitation of shear waves and noncontact elastic imaging can be realized.The laser can stimulate the tissue with the light absorption characteristic to produce the thermal expansion,thus producing the shear wave.The frequency of shear wave induced by laser is higher and the frequency band is wider.By tracking the propagation of shear wave,Young’s modulus of tissue is reconstructed in the whole shear wave propagation region to further evaluate the elastic information of tissue.The feasibility of the method is verified by experiments.Compared with the experimental results of supersonic shear imaging(SSI),it is proved that the method can be used for quantitative elastic imaging of the phantoms.In addition,compared with the SSI method,this method can realize the noncontact excitation of the shear wave,and the frequency of the shear wave excited by the laser is higher than that of the acoustic radiation force(ARF),so the spatial resolution is higher.Compared to the traditional PA elastic imaging method,this method can obtain a larger imaging depth under the premise of ensuring the imaging resolution,and it has potential application value in the clinical diagnosis of diseases requiring noncontact quantitative elasticity.展开更多
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 syn...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.展开更多
Water photoacoustic microscopy(PAM)enables water absorption contrast mapping in deep biological tissue,which further allows a more detailed architecture analysis and facilitates a better understanding of metabolic and...Water photoacoustic microscopy(PAM)enables water absorption contrast mapping in deep biological tissue,which further allows a more detailed architecture analysis and facilitates a better understanding of metabolic and pathophysiological pathways.The strongest absorption peak of water in the near-infrared region occurs at 1930 nm,where the first overtone of the O-H bond lies.However,general light sources operating in this band hitherto still suffer from low optical signal-to-noise ratio and suboptimal pulse widths for photoacoustic signal generation.These lead to not only PAM contrast deterioration but also a high risk of sample photodamage.Consequently,we developed a hybrid optical parametrically-oscillating emitter(HOPE)source for an improved water PAM image contrast,leading to noninvasive and safer bioimaging applications.Our proposed source generates 1930 nm laser pulses with high spectral purity at a repetition rate of 187.5 kHz.The pulse width is flexibly tunable from 4 to 15 ns,and the maximum pulse energy is 700 nJ with a power stability of 1.79%.Leveraging these advancements,we also demonstrated high-contrast water PAM in multifaceted application scenarios,including tracking the dynamic of water distribution in a zebrafish embryo,visualizing the water content of a murine tumor xenograft,and mapping the fluid distribution in an edema mouse ear model.Finally,we showcased 1750-nm/1930-nm dual-color PAM for quantitative imaging of lipid and water distributions with reduced cross talk and imaging artifacts.Given all these results,we believe that our HOPE source can heighten water PAM’s relevance in both biological research and clinical diagnostics.展开更多
基金supported by University of Macao,China,Nos.MYRG2022-00054-FHS and MYRG-GRG2023-00038-FHS-UMDF(to ZY)the Macao Science and Technology Development Fund,China,Nos.FDCT0048/2021/AGJ and FDCT0020/2019/AMJ and FDCT 0011/2018/A1(to ZY)Natural Science Foundation of Guangdong Province of China,No.EF017/FHS-YZ/2021/GDSTC(to ZY)。
文摘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.
基金Project supported by the National Natural Science Foundation of China(Grant No.42105176)the National University of Defense Technology Independent Research Project(Grant No.ZK21-40)。
文摘We theoretically investigate the feasibility of reconstructing the transverse structures of femtosecond laser filaments in air by photoacoustic tomography.To simulate the emission and transmission of filament-induced ultrasonic signals more truly,a series of experimentally recorded cross-sectional images are used to simulate the initial pressure rise from multiple filaments(MFs).The aperture size and sensitivity of the detector was incorporated into the reconstruction algorithm.The results show that frequency of acoustic signals induced by MFs with maximum volumetric energy density~100 k J/m^(3)is about 2 MHz below.The initial spatial distribution of optical filaments can be clearly reconstructed with the back projection based algorithm.We recommend a PAT system with transducers of a lower central frequency and a stronger apodization working at a longer scanning radius can be used in photoacoustic image reconstruction of femtosecond laser multifilaments.This study demonstrates the feasibility of using photoacoustic tomography to reconstruct femtosecond multifilament images,which is helpful for studying the complex dynamic processes of multifilament and multifilament manipulation and is also valuable for the remote applications of laser filaments.
基金supported by the National Key R&D Program of China,No.2023YFC2509700the Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund,No.L232141the Research and Application of Clinical Characteristic Diagnosis and Treatment Program,No.Z221100007422019(all to WD)。
文摘Spinal cord injury is a severe neurological disorder;however,current treatment methods often fail to restore nerve function effectively.Spinal cord stimulation via electrical signals is a promising therapeutic modality for spinal cord injury.Based on similar principles,this review aims to explore the potential of optical and acoustic neuromodulation techniques,emphasizing their benefits in the context of spinal cord injury.Photoacoustic imaging,renowned for its noninvasive nature,high-resolution capabilities,and cost-effectiveness,is well recognized for its role in early diagnosis,dynamic monitoring,and surgical guidance in stem cell therapies for spinal cord injury.Moreover,photoacoustodynamic therapy offers multiple pathways for tissue regeneration.Optogenetics and sonogenetics use genetic engineering to achieve precise neuronal activation,while photoacoustoelectric therapy leverages photovoltaic materials for electrical modulation of the nervous system,introducing an innovative paradigm for nerve system disorder management.Collectively,these advancements represent a transformative shift in the diagnosis and treatment of spinal cord injury,with the potential to significantly enhance nerve function remodeling and improve patient outcomes.
基金supported by the National Natural Science Foundation of China(No.12174125)Guangdong Basic and Applied Basic Research Foundation(Nos.2024A1515010522 and 2021A1515011874).
文摘The temperature of an organism provides key insights into its physiological and pathological status.Temperature monitoring can effectively assess potential health issues and plays a critical role in thermal treatment.Photoacoustic imaging(PAI)has enabled multi-scale imaging,from cells to tissues and organs,where its high contrast,deep penetration,and high resolution make it an emerging tool in biomedical imaging field.Benefiting from the linear correlation between the Grüneisen parameter and temperature within the range of 10–55∘C,the PAI has been developed as novel noninvasive label-free tool for temperature monitoring especially for thermotherapy mediated by laser,ultrasound,and microwave.Additionally,by utilizing temperature-responsive photoacoustic nanoprobes,the temperature information of the targeted organism can also be extracted with enhanced imaging contrast and specificity.This review elucidates the basic principles of temperature monitoring technology implemented by PAI,further highlighting the limitations of traditional photoacoustic thermometry,and summarizes recent technological advancements in analog simulation,calibration method,measurement accuracy,nanoprobe design,and wearable improvement.Furthermore,we discuss the biomedical applications of PA temperature monitoring technology in photothermal therapy and ultrasound therapy,finally,anticipating future developments in the field.
基金supported by the National Key R&D Program of China[Grant No.2023YFF0713600]the National Natural Science Foundation of China[Grant No.62275062]+2 种基金the Project of Shandong Innovation and Startup Community of High-end Medical Apparatus and Instruments[Grant No.2021-SGTTXM-005]the Shandong Province Technology Innovation Guidance Plan(Central Leading Local Science and Technology Development Fund)[Grant No.YDZX2023115]the Taishan Scholar Special Funding Project of Shandong Province,and the Shandong Laboratory of Advanced Biomaterials and Medical Devices in Weihai[Grant No.ZL202402].
文摘Photoacoustic imaging(PAI)employs short laser pulses to excite absorbing materials,producing ultrasonic waves spanning a broad spectrum of frequencies.These ultrasonic waves are captured surrounding the sample and utilized to reconstruct the initial pressure distribution tomographically.Despite the wide spectral range of the laser-generated photoacoustic signal,an individual transducer can only capture a limited segment of the signal due to its constrained bandwidth.Herein,we have developed a multi-bandwidth ring array photoacoustic computed tomography(PACT)system,incorporating a probe with two semi-ring arrays:one for high frequency and the other for low frequency.Utilizing the two semi-ring array PAIs,we have devised a specialized deep learning model,comprising two serially connected U-net architectures,to autonomously generate multi-bandwidth full-view PAIs.Preliminary results from simulations and in vivo experiments illustrate the system's robust multi-bandwidth imaging capabilities,achieving an excellent PSNR of 34.78 dB and a structural similarity index measure(SSIM)of 0.94 in the high-frequency reconstruction of complex mouse abdominal structures.This innovative PACT system is notable for its capability to seamlessly acquire multi-bandwidth full-view PAIs,thereby advancing the application of PAI technology in the biomedical domain.
基金support from Strategic Project of Precision Surgery,Tsinghua UniversityInitiative Scientific Research Program,Institute for Intelligent Healthcare,Tsinghua University+5 种基金Tsinghua-Foshan Institute of Advanced ManufacturingNational Natural Science Foundation of China(61735016)Beijing Nova Program(20230484308)Young Elite Scientists Sponsorship Program by CAST(2023QNRC001)Youth Elite Program of Beijing Friendship Hospital(YYQCJH2022-9)Science and Technology Program of Beijing Tongzhou District(KJ2023CX012).
文摘Foundation models(FMs)have rapidly evolved and have achieved signicant accomplishments in computer vision tasks.Specically,the prompt mechanism conveniently allows users to integrate image prior information into the model,making it possible to apply models without any training.Therefore,we proposed a workflow based on foundation models and zero training to solve the tasks of photoacoustic(PA)image processing.We employed the Segment Anything Model(SAM)by setting simple prompts and integrating the model's outputs with prior knowledge of the imaged objects to accomplish various tasks,including:(1)removing the skin signal in three-dimensional PA image rendering;(2)dual speed-of-sound reconstruction,and(3)segmentation ofnger blood vessels.Through these demonstrations,we have concluded that FMs can be directly applied in PA imaging without the requirement for network design and training.This potentially allows for a hands-on,convenient approach to achieving efficient and accurate segmentation of PA images.This paper serves as a comprehensive tutorial,facilitating the mastery of the technique through the provision of code and sample datasets.
基金pported by the National Natural Science Foundation of China(62265011 and 62122033)Jiangxi Provincial Natural Science Foundation(20224BAB212006 and 20232BAB 202038)National Key Research and Develop-ment Program of China(2023YFF1204302)。
文摘Acoustic-resolution photoacoustic microscopy(AR-PAM)suffers from degraded lateral resolution due to acoustic diffraction.Here,a resolution enhancement strategy for AR-PAM via a mean-reverting diffusion model was proposed to achieve the transition from acoustic resolution to optical resolution.By modeling the degradation process from high-resolution image to low-resolution AR-PAM image with stable Gaussian noise(i.e.,mean state),a mean-reverting diffusion model is trained to learn prior information of the data distribution.Then the learned prior is employed to generate a high-resolution image from the AR-PAM image by iteratively sampling the noisy state.The performance of the proposed method was validated utilizing the simulated and in vivo experimental data under varying lateral resolutions and noise levels.The results show that an over 3.6-fold enhancement in lateral resolution was achieved.The image quality can be effectively improved,with a notable enhancement of∼66%in PSNR and∼480%in SSIM for in vivo data.
基金supported by National Natural Science Foundation of China(62227818,12204239,62275121)Youth Foundation of Jiangsu Province(BK20220946)+1 种基金Fundamental Research Funds for the Central Universities(30923011024)Open Research Fund of Jiangsu Key Laboratory of Spectral Imaging&Intelligent Sense(JSGP202201).
文摘Deep learning(DL)is making significant inroads into biomedical imaging as it provides novel and powerful ways of accurately and efficiently improving the image quality of photoacoustic microscopy(PAM).Off-the-shelf DL models,however,do not necessarily obey the fundamental governing laws of PAM physical systems,nor do they generalize well to scenarios on which they have not been trained.In this work,a physics-embedded degeneration learning(PEDL)approach is proposed to enhance the image quality of PAM with a self-attention enhanced U-Net network,which obtains greater physical consistency,improves data efficiency,and higher adaptability.The proposed method is demonstrated on both synthetic and real datasets,including animal experiments in vivo(blood vessels of mouse's ear and brain).And the results show that compared with previous DL methods,the PEDL algorithm exhibits good performance in recovering PAM images qualitatively and quantitatively.It overcomes the challenges related to training data,accuracy,and robustness which a typical data-driven approach encounters,whose exemplary application envisions to provide a new perspective for existing DL tools of enhanced PAM.
基金supported by STI2030-Major Projects(No.2022ZD0212200)National Natural Science Foundation of China(No.62305118)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2025A1515010953)China Postdoctoral Science Foundation(No.2022M721223).
文摘The brain lymphatic system plays a crucial role in maintaining homeostasis,clearing metabolic waste,and regulating neuroinflammation.Its dysfunction is strongly linked to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.In this study,we employed dual-contrast functionalphotoacoustic microscopy to evaluate the impact of lipopolysaccharide-induced central nervous system inflammation on brain lymphatic function and to explore the protective effects of the P2X7 receptor(P2X7R)antagonist.Our findings demonstrated that lipopolysac-charide intervention led to impaired function of the meningeal lymphatic vessels,which was par-tially restored by the P2X7R antagonist,whereas its effects on the glymphatic system and cerebral vessels were minimal.This study further supports the feasibility of photoacoustic microscopy for assessing brain lymphatic function and highlights the therapeutic potential of P2X7R antagonism.These findings suggest that P2X7R may serve as a key target for modulating brain-lymphatic interactions,providing an experimental foundation for developing intervention strategies for neuroinflammatory and neurodegenerative diseases.
基金financially supported by National Natural Science Foundation of China (Nos.21877048, 22077048, and 22277014)Guangxi Natural Science Foundation (Nos.2021GXNSFDA075003,AD21220061)the startup fund of Guangxi University (No.A3040051003)。
文摘Aging is a natural physiological process with various challenges, related to the loss of homeostasis within the organism, which is not a disease, but a significantly strong risk factor for multiple diseases, including myocardial infarction, stroke, some age-related cancers, macular degeneration, osteoarthritis, neurodegeneration, and many others. In the body, the main manifestation of aging is cellular aging, which exists within tissues and has a local or global impact on tissue function. However, the lack of effective aging detection tools has always been an issue that cannot be ignored in the field of aging research. Therefore,it is necessary to construct a non-invasive tool for in vivo detection of aging. Here, we show that the photoacoustic probe(LGAL), which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast to the hallmark of aging, and allows for the microscopic imaging of aging through the intact mice. Firstly, this tool LGAL has been successfully applied to detect senescence in cells, displaying stronger photoacoustic signals than normal cells. Then, by using the photoacoustic probe, the blood vessels and tissues inside the mice can be visualized. Young and elderly mice exhibit varying intensities of photoacoustic signals, marking the first time a probe has been used to explore the aging of blood vessels and tissues inside the mice. Finally, we monitored the changes in the degree of aging during tumor treatment under photoacoustic(PA) imaging for the first time. As the treatment time increased, the degree of aging of the tumor gradually deepened. We expect the powerful tool could be a noninvasive and powerful tool for the study of aging biology.
基金funding from the National Natural Science Foundation of China(NSFC)under grants 61627827,61705068the Natural Science Foundation of Fujian Province 2021J01813the Fujian Medical University Research Foundation of Talented Scholars XRCZX2021004.
文摘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.
基金partially supported by the National Key R&D Program of China (No.2022YFE0199700)the National Natural Science Foundation of China (NSFC) projects (Nos.22077139and 22122705)CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2022-I2M-2–002)。
文摘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.
基金the National Natural Science Foundation of China(Nos.21762045,21911540466)Shandong Provincial Natural Science Foundation(No.ZR2019YQ12)+1 种基金China Postdoctoral Science Foundation(No.219M652306)Taishan Scholar Project(No.tsqn201812049)for supporting this work。
文摘Photothermal therapy(PTT)is a cutting-edge cancer treatment that can kill cancer cells in hypoxic environments without relying on oxygen.Seeking of the ideal photothermal agents with a high absorption coefficient in the near-infrared region,and a high excellent photothermal conversion efficiency is of great significance.Sulfone-Rhodanmine dye has showed an impressive absorption wavelength over 700 nm,but suffered from a stability issue.In this study,we synthesized five sulfone rhodamines and investigated the substitution effects on stability.SO_(2)R2 showed high stability and strong absorbance at 714 nm with an excellent photothermal conversion efficiency of 53.06%,making it suitable for accurate photoacoustic imaging-guided photothermal therapy in vivo.
基金supported by the program of Chengdu Fifth people's hospital Fund,No.KYJJ 2021-29the Xinglin Scholars research program,No.YYZX2021037+1 种基金the Chengdu Medical Research Project,Nos.2022055 and 2023022,Chongqing Education Commission,Youth Fund(No.KJQN202000607)Chongqing postdoctoral research project(special funding project,No.2021XM3040).
文摘Traditional diagnostic techniques including visual examination,ultrasound(US),and magnetic resonance imaging(MRI)have limitations of in-depth information for the detection of nail disorders,resolution,and practicality.This pilot study,for thefirst time,evaluates a dualmodality imaging system that combines photoacoustic tomography(PAT)with the US for the multiparametric quantitative assessment of human nail.The study involved a small cohort offive healthy volunteers who underwent PAT/US imaging for acquiring the nail unit data.The PAT/US dual-modality imaging successfully revealed thefine anatomical structures and microvascular distribution within the nail and nail bed.Moreover,this system utilized multispectral PAT to analyze functional tissue parameters,including oxygenated hemoglobin,deoxyhemoglobin,oxygen saturation,and collagen under tourniquet and cold stimulus tests to evaluate changes in the microcirculation of the nail bed.The quantitative analysis of multispectral PAT reconstructed images demonstrated heightened sensitivity in detecting alterations in blood oxygenation levels and collagen content within the nail bed,under simulated different physiological conditions.This pilot study highlights the potential of PAT/US dual-modality imaging as a real-time,noninvasive diagnostic modality for evaluating human nail health and for early detection of nail bed pathologies.
基金supported by National Key R&D Program of China[2022YFC2402400]the National Natural Science Foundation of China[Grant No.62275062]Guangdong Provincial Key Laboratory of Biomedical Optical Imaging Technology[Grant No.2020B121201010-4].
文摘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.
基金supported by STI2030-Major Projects 2022ZD0212200,Hainan Province Key Area R&D Program(KJRC2023C30,ZDYF2021SHFZ094)Project of Collaborative Innovation Center of One Health(XTCX2022JKB02).
文摘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.
基金financially supported by the National Natural Science Foundation of China(22078046)Fundamental Research Fundamental Funds for the Central Universities(DUT22LAB601)+1 种基金Liaoning Binhai Laboratory(LBLB-2023-03)China Postdoctoral Science Foundation(2023M740487)。
文摘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.
基金supported by the National Key R&D Program of China(Grant No.2022YFC2402400)the National Natural Science Foundation of China(Grant No.62275062)and Guangdong Provincial Key Laboratory of Biomedical Optical Imaging Technology(Grant No.2020B121201010-4).
文摘Elastography can be used as a diagnostic method for quantitative characterization of tissue hardness information and thus,differential changes in pathophysiological states of tissues.In this study,we propose a new method for shear wave elastography(SWE)based on laser-excited shear wave,called photoacoustic shear wave elastography(PASWE),which combines photoacoustic(PA)technology with ultrafast ultrasound imaging.By using a focused laser to excite shear waves and ultrafast ultrasonic imaging for detection,high-frequency excitation of shear waves and noncontact elastic imaging can be realized.The laser can stimulate the tissue with the light absorption characteristic to produce the thermal expansion,thus producing the shear wave.The frequency of shear wave induced by laser is higher and the frequency band is wider.By tracking the propagation of shear wave,Young’s modulus of tissue is reconstructed in the whole shear wave propagation region to further evaluate the elastic information of tissue.The feasibility of the method is verified by experiments.Compared with the experimental results of supersonic shear imaging(SSI),it is proved that the method can be used for quantitative elastic imaging of the phantoms.In addition,compared with the SSI method,this method can realize the noncontact excitation of the shear wave,and the frequency of the shear wave excited by the laser is higher than that of the acoustic radiation force(ARF),so the spatial resolution is higher.Compared to the traditional PA elastic imaging method,this method can obtain a larger imaging depth under the premise of ensuring the imaging resolution,and it has potential application value in the clinical diagnosis of diseases requiring noncontact quantitative elasticity.
基金supported by the National Key R&D Program of China(Nos.2022YFB3808000,2022YFB3808001)the Project for High-Level Talent Innovation and Entrepreneurship of Quanzhou(No.2022C016R)+1 种基金the Medical Innovation Project of Science and Technology Program of Fujian Provincial Health Commission(No.2021CXA006)the Key Program of Qingyuan Innovation Laboratory(No.00221002).
文摘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.
基金supported by the Research Grants Council of the Hong Kong Special Administrative Region(SAR)of China(Grant Nos.HKU 17210522,HKU C7074-21G,HKU 17205321,and HKU 17200219)ITF MHKJFS Projects(Grant Nos.MHP/073/20 and MHP/057/21)the Health@InnoHK Program of the Innovation and Technology Commission of the Hong Kong SAR Government.
文摘Water photoacoustic microscopy(PAM)enables water absorption contrast mapping in deep biological tissue,which further allows a more detailed architecture analysis and facilitates a better understanding of metabolic and pathophysiological pathways.The strongest absorption peak of water in the near-infrared region occurs at 1930 nm,where the first overtone of the O-H bond lies.However,general light sources operating in this band hitherto still suffer from low optical signal-to-noise ratio and suboptimal pulse widths for photoacoustic signal generation.These lead to not only PAM contrast deterioration but also a high risk of sample photodamage.Consequently,we developed a hybrid optical parametrically-oscillating emitter(HOPE)source for an improved water PAM image contrast,leading to noninvasive and safer bioimaging applications.Our proposed source generates 1930 nm laser pulses with high spectral purity at a repetition rate of 187.5 kHz.The pulse width is flexibly tunable from 4 to 15 ns,and the maximum pulse energy is 700 nJ with a power stability of 1.79%.Leveraging these advancements,we also demonstrated high-contrast water PAM in multifaceted application scenarios,including tracking the dynamic of water distribution in a zebrafish embryo,visualizing the water content of a murine tumor xenograft,and mapping the fluid distribution in an edema mouse ear model.Finally,we showcased 1750-nm/1930-nm dual-color PAM for quantitative imaging of lipid and water distributions with reduced cross talk and imaging artifacts.Given all these results,we believe that our HOPE source can heighten water PAM’s relevance in both biological research and clinical diagnostics.
