Photoacoustic Research Articles

NIR-II Fluorescence/Photoacoustic Dual Ratiometric Probes with Unique Recognition Site for Quantitatively Visualizing H2S2 in Vivo.

Hydrogen persulfide (H2S2) plays a significant role in redox biology and signal transduction; therefore, quantitative visualization of H2S2 in the deep tissue of living organisms is essential for obtaining reliable information about relevant pathophysiological processes directly. However, currently reported H2S2 probes are unsuitable for this purpose because of their poor selectivity for many polysulfide species or their short wavelength, which hinders precise imaging in deep tissues. Herein, for the first time, we report a unique H2S2-mediated dithiole formation reaction. Based on this reaction, we construct the first NIR-II fluorescence (FL) and photoacoustic (PA) dual-ratiometric probe (NIR-II-H2S2) for quantitatively visualizing H2S2 in vivo. This probe shows dual-ratiometric NIR-II fluorescence (I840/I1000, 107-fold) and photoacoustic (PA800/PA900, 6.5-fold) responses towards Na2S2 species with high specificity, excellent sensitivity (1.8nM), improved water solubility, and deep-tissue penetration. More importantly, using NIR-II dual-ratiometric FL/PA imaging, we successfully demonstrated that the probe could be used to accurately quantify the fluctuating H2S2 levels in the liver-injury mouse models induced by lipopolysaccharides or metformin drugs. Overall, this study not only presents a promising tool for H2S2-related pathological research, but also provides a unique recognition site that may be generalized for designing more useful H2S2 imaging agents in the future.

NIR‐II Fluorescence/Photoacoustic Dual Ratiometric Probes with Unique Recognition Site for Quantitatively Visualizing H2S2 in Vivo

Hydrogen persulfide (H2S2) plays a significant role in redox biology and signal transduction; therefore, quantitative visualization of H2S2 in the deep tissue of living organisms is essential for obtaining reliable information about relevant pathophysiological processes directly. However, currently reported H2S2 probes are unsuitable for this purpose because of their poor selectivity for many polysulfide species or their short wavelength, which hinders precise imaging in deep tissues. Herein, for the first time, we report a unique H2S2‐mediated dithiole formation reaction. Based on this reaction, we construct the first NIR‐II fluorescence (FL) and photoacoustic (PA) dual‐ratiometric probe (NIR‐II‐H2S2) for quantitatively visualizing H2S2 in vivo. This probe shows dual‐ratiometric NIR‐II fluorescence (I840/I1000, 107‐fold) and photoacoustic (PA800/PA900, 6.5‐fold) responses towards Na2S2 species with high specificity, excellent sensitivity (1.8 nM), improved water solubility, and deep‐tissue penetration. More importantly, using NIR‐II dual‐ratiometric FL/PA imaging, we successfully demonstrated that the probe could be used to accurately quantify the fluctuating H2S2 levels in the liver‐injury mouse models induced by lipopolysaccharides or metformin drugs. Overall, this study not only presents a promising tool for H2S2‐related pathological research, but also provides a unique recognition site that may be generalized for designing more useful H2S2 imaging agents in the future.

On the dual-phase-lag thermal response in the pulsed photoacoustic effect: A theoretical and experimental 1D-approach

In a recent work, assuming a Beer–Lambert optical absorption and a Gaussian laser time profile, it was shown that the exact solutions for a 1D photoacoustic (PA) boundary-value-problem predict a null pressure for optically strong absorbent materials. In order to overcome this inconsistency, a heuristic correction was introduced by assuming that heat flux travels a characteristic length during the duration of the laser pulse [M. Ruiz-Veloz et al., J. Appl. Phys. 130, 025104 (2021)] τp. In this work, we obtained exact analytical solutions in the frequency domain for a 1D boundary-value-problem for the Dual-Phase-Lag (DPL) heat equation coupled with a 1D PA-boundary-value-problem via the acoustic wave equation. Temperature and pressure solutions were studied by assuming that the sample and its surroundings have a similar characteristic thermal lag response time τT; therefore, the whole system is assumed to have a similar thermal relaxation. A second assumption for τT is that it is considered as a free parameter that can be adjusted to reproduce experimental results. Solutions for temperature and pressure were obtained for a one-layer 1D system. It was found that for τT<τp, the DPL temperature has a similar thermal profile of the Fourier heat equation; however, when τT≥τp, this profile is very different from the Fourier case. Additionally, via a numerical Fourier transform, the wave-like behavior of DPL temperature is explored, and it was found that as τT increases, thermal wave amplitude is increasingly attenuated. Exact solutions for pressure were compared with experimental PA signals, showing a close resemblance between both data sets, particularly in time domain, for an appropriated value of τT; the transference function was also calculated, which allowed us to find the maximum response in frequency for the considered experimental setup.

Responsive Theranostic Nanoprobe for Ratiometric Photoacoustic Monitoring of Hypochlorous Acid‐Mediated Inflammation in Cancer Photothermal Therapy

AbstractCancer detection and inflammation monitoring during photothermal therapy (PTT) enable timely cancer intervention and precise inflammation control, advancing to address inflammation‐related tumor recurrence and metastasis associated with PTT. This can be achieved through real‐time monitoring biomarker for cancer and inflammation, like hypochlorous acid (HOCl), a highly reactive oxygen species (hROS) in body with elevated levels in inflammation. Here, a HOCl‐responsive theranostic nanoprobe is introduced, AuNRs@SiO2‐CAA for ratiometric photoacoustic (PA) cancer detection and inflammation monitoring during PTT. AuNRs@SiO2‐CAA emits PA signals at 680 and 820 nm, with only PA680 undergoing changes in the presence of HOCl, enabling precise HOCl imaging via recording changes of ratiometric PA signals (PA680/PA820). AuNRs@SiO2‐CAA exhibits high selectivity and sensitivity, with a detection limit of 0.34 µM for ratiometric PA imaging of HOCl. In vivo, it effectively detects tumor, drives PTT, and monitors inflammation during PTT by sensing HOCl. The successful development of AuNRs@SiO2‐CAA offers a novel theranostic nanoprobe system for cancer diagnosis, poised to enhance PTT through precise inflammation control.

Tuning the Fe-Gd nanoparticles co-functionalized mesoporous carbon from sphere to nanobowl for advanced bioapplications

Studies on the function-integrated nanocomposites with well-tuned morphologies have received considerable interest. Here, we reported the preparation of mesoporous carbon nanobowl integrated with stoichiometric γ-Fe2O3 and GdPO4 nanoparticles (Fe-Gd/MCN-B) for morphological advantage exploration. Followed by (i) emulsion-induced interface anisotropic assembly of polydopamine, (ii) solvent evaporation-induced sorption of Wells-Dawson-like heterometallic cluster of {Fe6Gd6P6} and (iii) temperature-programmed carbonization, Fe-Gd/MCN-B with the size around 200 nm was isolated. Our in-vitro studies revealed that Fe-Gd/MCN-B showed a 63.0 % amplified photoacoustic (PA) signal intensity as compared with its nanospherical analogue of Fe-Gd/MCN-S owing to the enhanced light harvesting and photothermal conversion on the interface of its nanobowl morphology. Furthermore, the combined magnetic resonance (MR) imagining, drug delivery and photothermal treatment efficacy in Fe-Gd/MCN-B were also validated in-vitro. These results demonstrated that the delicate design of the morphology of function-integrated nanocomposites is an available way for enhanced imaging performance.

Dual Enzyme-Driven Cascade Reactions Modulate Immunosuppressive Tumor Microenvironment for Catalytic Therapy and Immune Activation.

Lactate-enriched tumor microenvironment (TME) fosters an immunosuppressive milieu to hamper the functionality of tumor-associated macrophages (TAMs). However, tackling the immunosuppressive effects wrought by lactate accumulation is still a big challenge. Herein, we construct a dual enzyme-driven cascade reaction platform (ILH) with immunosuppressive TME modulation for photoacoustic (PA) imaging-guided catalytic therapy and immune activation. The ILH is composed of iridium (Ir) metallene nanozyme, lactate oxidase (LOx), and hyaluronic acid (HA). The combination of Ir nanozyme and LOx can not only efficiently consume lactate to reverse the immunosuppressive TME into an immunoreactive one by promoting the polarization of TAMs from the M2 to M1 phenotype, thus enhancing antitumor defense, but also alleviate tumor hypoxia as well as induce strong oxidative stress, thus triggering immunogenic cell death (ICD) and activating antitumor immunity. Furthermore, the photothermal performance of Ir nanozyme can strengthen the cascade catalytic ability and endow ILH with a PA response. Based on the changes in PA signals from endogenous molecules, three-dimensional multispectral PA imaging was utilized to track the process of cascade catalytic therapy in vivo. This work provides a nanoplatform for dual enzyme-driven cascade catalytic therapy and immune activation by regulating the immunosuppressive TME.

Enhancing the tissue penetration to improve sonodynamic immunotherapy for pancreatic ductal adenocarcinoma using membrane-camouflaged nanoplatform.

Sonodynamic therapy (SDT) is a promising strategy as an "in situ vaccine" to enhance activation of antitumor immune responses in solid tumors. However, the dense extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDAC) lead to hypoxia and limited penetration of most drugs, aggravating the immunosuppressive tumor microenvironment and limiting the efficacy of synergistic sonodynamic immunotherapy. Therefore, it is essential to regulate ECM in order to alleviate tumor hypoxia and enhance the efficacy of sonodynamic immunotherapy for PDAC. The CPIM nanoplatform, consisting of a macrophage membrane-coated oxygen and drug delivery system (CM@PFOB-ICG-α-Mangostin), was synthesized using ultrasound and extrusion methods. The in vivo homologous targeting and hypoxia alleviation capabilities of CPIM were evaluated through near-infrared (NIR) imaging and photoacoustic (PA) imaging. The tumor growth inhibition potential and ability to reprogram the tumor microenvironment by the CPIM nanoplatform were also investigated. Co-delivery of α-Mangostin inhibits CAFs and enhances stromal depletion, thereby facilitating better infiltration of macromolecules. Additionally, the nanoemulsion containing perfluorocarbon (PFC) can target tumor cells and accumulate within them through homologous targeting. The US irradiation results in the rapid release of oxygen, serving as a potential source of sonodynamic therapy for hypoxic tumors. Moreover, CPIM reshapes the immunosuppressive microenvironment increasing the population of cytotoxic T lymphocytes (CTLs), and enhancing their anti-tumor immune response through the use of anti-PDL1 antibodies to block immune checkpoints. The present study offers a potential strategy for the co-delivery of oxygen and α-Mangostin, aiming to enhance the penetration of tumors to improve SDT. This approach effectively addresses the existing limitations of immune checkpoint blockade (ICB) treatment in solid tumors, while simultaneously boosting the immune response through synergistic sonodynamic immunotherapy.

Multimodal Photoacoustic/Elastography Imaging for the Detection of Acute Radiation Dermatitis in Breast Radiation Therapy

Purpose: This study evaluates whether photoacoustic (PA), sound touch elastography (STE), and viscoelasticity (VE) can distinguish between normal and abnormal post-radiotherapy breast skin and compare these methods with RTOG criteria at a 20 Gy threshold. Methods: Patients meeting inclusion and exclusion criteria underwent PA, STE, and VE on the same day. Collected data included radiation dose, molecular type, RTOG, Fitzpatrick skin type, pathology, neoadjuvant chemotherapy status, TNM classification, surgical procedures, primary breast cancer location, BMI, and age. A sample of 41 patients was determined using a two-sample t-test. Statistical tools like T-tests, variance analysis, rank sum tests, and chi-square tests, along with random forest analysis and ROC curves, were used to evaluate the radiation dose effects. Results: Data from 66 patients showed significant differences in parameters such as dermis and subcutaneous tissue oxygen saturation, dermal thickness, and skin elasticity (p-values < 0.05). However, minimum values of oxygen saturation and some photoacoustic measures were not significantly different. Notably, at a 20 Gy radiation threshold, significant variations in oxygen saturation, abnormal dermal thickness, and skin STE and VE were observed, proving more accurate than RTOG grading. Conclusion: The study confirms the effectiveness of PA and elastography imaging in differentiating normal from abnormal breast tissue and assessing radiation-induced changes, highlighting the potential of these imaging techniques.

Reshaping Immunosuppressive Tumor Microenvironment Using Ferroptosis/Cuproptosis Nanosensitizers for Enhanced Radioimmunotherapy

AbstractRadiotherapy, a traditional cancer treatment, not only controls local tumor growth but also potentially induces immunogenic cell death, initiating systemic immune responses. However, radiotherapy resistance and immunosuppressive tumor microenvironments often limit the potency of radiation‐induced anti‐tumor immune responses, rendering them insufficient for clinical applications. Consequently, trimetallic nanoparticles are constructed with dual enzymatic activity, AuBiCu‐distearoyl phosphoethanolamine‐PEG nanoparticles (AuBiCu‐PEG NPs), to synergistically improve radiotherapy resistance through X‐ray deposition, hypoxia alleviation, and ferroptosis and cuproptosis induction. This approach promotes radiotherapy‐induced immunogenic cell death and boosts anti‐tumor immune responses. Furthermore, AuBiCu‐PEG NPs effectively reversed radiation‐induced upregulation of programmed cell death 1 ligand 1 (PD‐L1), inhibit tumor immune evasion, and reshaped the immune microenvironment. Non‐invasive and real‐time longitudinal monitoring of nanoparticle accumulation in tumors can be achieved using spectral computed tomography (CT) and photoacoustic (PA) imaging. In summary, the designed AuBiCu‐PEG NPs serve as promising nanoplatforms for immune microenvironment remodeling and can be used in multimodal molecular imaging‐guided ferroptosis‐cuproptosis‐enhanced radiotherapy.

Clinical application of photoacoustic imaging for cervical precursor lesion detection.

Early diagnosis of a precursor lesion in the uterine cervix is an essential factor in uterine cervical cancer prevention. Although colposcopy is an established procedure for detecting high-risk patients, its accuracy and reproducibility are relatively low. Some supportive or alternative techniques to improve the early diagnosis of a precursor lesion have been studied, and correct diagnosis with high reliability using a minimally invasive, cost-effective technique has been pursued. This study aimed to examine the possibility of using photoacoustic (PA) imaging as a supportive technique to improve the accuracy of early diagnosis of cervical precursor lesions. A PA imaging system for microvessels was used to detect angiogenesis in severe lesions. A total of 21 patients who underwent surgical treatment and 114 outpatients who visited our colposcopy clinic were examined. A retrospective evaluation of PA images was performed as follows: (i) pathological assessment of the specific PA findings and (ii) retrospective evaluation of the severe lesion detection rate through PA. PA image evaluation and pathological findings showed dense angiogenesis in a severe precursor lesion appearing as a "hot spot" in the PA image. A comparison with colposcopy findings was performed for accuracy evaluation, and the detection rate of severe lesions using PA was relatively high (positive predictive value, 84.5%; negative predictive value, 82.1%). Our results indicate the possibility of using PA imaging for early diagnosis of severe cervical precursor lesions. With its ability to yield quantitative information, PA imaging can improve ultrasound diagnosis.

The use of gold and magnetite-gold composite nanoparticles for the enhanced detection of Salmonella LT2 cells under photoacoustic flow cytometry

Photoacoustic flow cytometry (PAFC) is an emerging technology that has generated significant interest in several research fields, particularly in bacteremia. The application of functionalised nanoparticles like gold and iron oxide-gold complex (Fe3O4-Au) has been realised to enhance the photoacoustic (PA) detection of bacteria cells under PAFC systems. Inclusively, the bacteria cell concentrations are statistically quantified through the number of time-signal detection counts. This study uses a similar technique by using gold (Au) and magnetite-gold complex (Fe3O4-Au) nanoparticles in the PAFC system to improve the detection of Salmonella LT2 (SLT2) cells under 532 nm laser irradiation, resulting in over a 200 % increase. However, this study’s contribution comes from the post-processing and analysis of PA time signals after exposing various concentrations of SLT2 cells. Upon fast Fourier transform (FFT) analysis of time signals, a distinct peak frequency at 2.75 MHz was significantly attributed to SLT2 as its likely acoustic frequency fingerprint, even at its lowest concentrations (10 CFU/ml). Furthermore, an electromagnetic wave simulation (optical scattering and heat transfer in fluids) was employed to distinguish the PA and Photothermal contributions of the nanoparticles in the system. The resulting data consolidates the continuous wave transform (CWT) of the time signal, where 22.5 – 30 µs was strongly affiliated with PA, and 32–40 µs was that of the photo-thermal-acoustic effect—indicating that both signals can be used to detect and potentially confirm the eradication of SLT2 cells. Overall, magnetised Fe3O4-Au nanoparticles yielded more efficiency through its reproducible PA time signals with 0.84 standard deviations, and its 2.75 MHz frequency peak area matches most accurately with the SLT2 cell concentration by 97.3 %.

Investigation of thermal diffusivity measurement technique based on photoacoustic signal response under the influence of three-dimesional heat transfer

In this study, we investigated the feasibility of measuring the thermal diffusivity of thermally thick solid material using the photoacoustic (PA) signal response in a three-dimensional heat diffusion state. For this purpose, we developed a heat conduction simulation model based on cylindrical coordinates to replicate the PA effect on three-dimensional heat diffusion. By numerical analysis, it was found that the phase of PA signal deviates from one-dimensional theory prediction when the lateral heat diffusion of the solid sample reaches the chamber wall of PA cell. Specifically, it was found that the phase lag inflects at the frequency where the sample’s thermal diffusion length μs is 0.91 mm at a chamber radius of 3 mm. By utilizing this correlation, the infection frequency can potentially provide the thermal diffusivity of the thermally thick sample. The experimental validation qualitatively confirmed that the phenomena observed in the numerical analysis occur in practice. However, quantitatively, the experimental results showed discrepancies from the numerical analysis, which is likely due to the influence of the radial distribution of laser intensity. Nonetheless, this issue can be resolved in practical applications through calibration using a reference sample. Numerical analysis suggested that for materials with thermal diffusivity lower than that of air, measuring thermal diffusivity could be seemingly impossible. However, the experimental results demonstrated that calibration with a reference sample having sufficiently lower thermal diffusivity than that of air effectively compensates for the influence of air’s thermal diffusion. The significant factor affecting the accuracy of thermal diffusivity determination with the proposed method is identifying the inflection frequency. It will be necessary to explore an appropriate method for determining the frequency by integrating multiple sources of information, such as simultaneously observing the amplitude of the PA signal.

In vivo imaging of alkaline phosphatase in lipid metabolic diseases with a photoacoustic probe

Lipid metabolic diseases have become an important challenge to global public health. Along with lifestyle changes, the incidence of obesity, diabetes and other metabolic syndromes is on the rise, and the number of patients with fatty liver disease is also increasing. Therefore, it is particularly important to develop effective lipid imaging strategies to monitor and manage fatty liver disease. Herein, based on the essential role of alkaline phosphatase (ALP) in both AS and OB, in vivo imaging of ALP was achieved in two lipid metabolic diseases models with a photoacoustic (PA) probe phosphorylated hemicyanine (P-Hcy). After being triggered by ALP, P-Hcy responded in different modalities including absorbance, fluorescence and, most significantly, PA-reporting. Notably, the PA signal showed the reliable linear correlation to the ALP level within the range of 0–800 U/L. The probe P-Hcy exhibited the advantages including high sensitivity, high selectivity, and steadiness in required biological conditions. The intracellular imaging results ensured that P-Hcy could visualize the ALP level in the foam cells induced from mouse mononuclear macrophages. In the healthy and lipid metabolic diseases models, P-Hcy was able to distinguish well between a lipid metabolic disease model and a healthy mouse model by photoacoustic imaging. By combining the ALP detection with P-Hcy in PA/fluorescence modality and traditional techniques such as blood biochemical testing and immunohistochemically staining, more potential strategy to accurately diagnose lipid metabolic diseases in the pre-clinical trials might be developed in future.

Multi-functional nanosonosensitizer-engineered bacteria to overcome tumor hypoxia for enhanced sonodynamic therapy

BackgroundUltrasound-triggered sonodynamic therapy (SDT), with high safety and acceptance, has become a promising tumor treatment. However, the dense stroma, hypoxic microenvironment of tumor, and the unpredictable treatment timing limit the effectiveness of sonosensitizers and the antitumor therapeutic effect. Thus, it is crucial to develop an imaging-guided sensitization strategy for hypoxic tumor sonosensitization to improve the efficacy of SDT. MethodsIn this study, we developed a biohybrid system CB@HPP, which genetically engineered bacteria to express catalase (CB) and modified nanosonosensitizers (HPP) to the surface of these bacteria. Tumor hypoxia relief, tumor targeting, biocompatibility, and antitumor efficacy were evaluated through in vitro and in vivo experiments. In addition, the photoacoustic (PA), ultrasound (US), and fluorescence (FL) imaging effects of CB@HPP were evaluated in vivo and in vitro. ResultsAfter intravenous injection, CB@HPP was able to target tumor tissue. CB@HPP possessed efficient catalase activity and successfully degraded hydrogen peroxide to produce oxygen. Increased oxygen levels relief intratumoral hypoxia, thereby enhancing CB@HPP-mediated. In addition, CB@HPP showed FL/PA/US multimodal imaging capabilities, which reflects the aggregation effect of CB@HPP in the tumor and suggest the timing of treatment. ConclusionThe biohybrid system CB@HPP significantly alleviates tumor hypoxia, and multimodal imaging-mediated oxygen-producing SDT effectively suppresses tumors. This integrated imaging and therapeutic biohybrid system provides a more efficient and attractive cancer treatment strategy for SDT. Statement of significanceThis study developed a sensitizing SDT strategy for imaging-guided drug-targeted delivery and in situ oxygen production. We designed a biohybrid system CB@HPP, which was hybridized by the engineered bacteria with catalytic oxygen production and nanosonosensitizer with multimodal imaging capability. CB@HPP significantly alleviates tumor hypoxia, and multimodal imaging-mediated oxygen-producing SDT effectively suppresses tumors. This integrated imaging and therapeutic biohybrid system provides a more efficient and attractive cancer treatment strategy for SDT.

All-fiber miniature non-contact photoacoustic probe based on photoacoustic remote sensing microscopy for vascular imaging in vivo.

Photoacoustic (PA) remote sensing (PARS) microscopy represents a significant advancement by eliminating the need for traditional acoustic coupling media in PA microscopy (PAM), thereby broadening its potential applications. However, current PARS microscopy setups predominantly rely on free-space optical components, which can be cumbersome to implement and limit the scope of imaging applications. In this study, we develop an all-fiber miniature non-contact PA probe based on PARS microscopy, utilizing a 532-nm excitation wavelength, and showcase its effectiveness in in vivo vascular imaging. Our approach integrates various fiber-optic components, including a wavelength division multiplexer, a mode field adaptor, a fiber lens, and an optical circulator, to streamline the implementation of the PARS microscopy system. Additionally, we have successfully developed a miniature PA probe with a diameter of 4 mm. The efficacy of our imaging setup is demonstrated through in vivo imaging of mouse brain vessels. By introducing this all-fiber miniature PA probe, our work may open up new opportunities for non-contact PAM applications.

Photoacoustic thermal-strain measurement towards noninvasive and accurate temperature mapping in photothermal therapy

Photothermal therapy is a promising tumor treatment approach that selectively eliminates cancer cells while assuring the survival of normal cells. It transforms light energy into thermal energy, making it gentle, targeted, and devoid of radiation. However, the efficacy of treatment is hampered by the absence of accurate and noninvasive temperature measurement method in the therapy. Therefore, there is a pressing demand for a noninvasive temperature measurement method that is real-time and accurate. This article presents one such attempt based on thermal strain photoacoustic (PA) temperature measurement. The method was first modelled, and a circular array-based photoacoustic photothermal system was developed. Experiments with Indian ink as tumor simulants suggest that the temperature monitoring in this work achieves a precision of down to 0.3 °C. Furthermore, it is possible to accomplish real-time temperature imaging, providing accurate two-dimensional temperature mapping for photothermal therapy. Experiments were also conducted on human fingers and nude mice, validating promising potentials of the proposed method for practical implementations.

Nanocrystallized copper phosphate endowed with photothermal conversion and photoacoustic imaging capabilities

Copper-based nanomaterials have garnered significant attention for their potential applications in photothermal (PT) conversion and photoacoustic (PA) imaging due to their unique optical properties. However, current strategies often involve complex synthesis processes and the incorporation of additional materials, which limit their practical applicability. Here, we employed a straightforward nanocrystallization method to synthesize copper phosphate nanoparticles (Cu3(PO4)2 NPs), converting free copper ions into solid-phase nano-sized particles. This approach not only simplifies the synthesis process but also enhances the optical and thermal properties of the resulting Cu3(PO4)2 NPs. The Cu3(PO4)2 NPs achieved a temperature increase of over 20∘C and a PT conversion efficiency of 10.5% under 808 nm laser irradiation. Furthermore, Cu3(PO4)2 NPs exhibited strong, concentration-dependent PA signals, which enabled effective deep tissue imaging in vivo. The enhanced properties of Cu3(PO4)2 NPs can be attributed to the nanocrystallization of the particles, which alters the local environment of copper ions and enhances d−d transitions through specific ligand field effects. These effects increase light absorption, particularly in the NIR region, by facilitating better overlap of electronic states and enabling more efficient non-radiative relaxation processes. This highlights the significance of nano-structuring in developing advanced nanomaterials with tailored functionalities for biomedical applications.

Joint segmentation and image reconstruction with error prediction in photoacoustic imaging using deep learning

Deep learning has been used to improve photoacoustic (PA) image reconstruction. One major challenge is that errors cannot be quantified to validate predictions when ground truth is unknown. Validation is key to quantitative applications, especially using limited-bandwidth ultrasonic linear detector arrays. Here, we propose a hybrid Bayesian convolutional neural network (Hybrid-BCNN) to jointly predict PA image and segmentation with error (uncertainty) predictions. Each output pixel represents a probability distribution where error can be quantified. The Hybrid-BCNN was trained with simulated PA data and applied to both simulations and experiments. Due to the sparsity of PA images, segmentation focuses Hybrid-BCNN on minimizing the loss function in regions with PA signals for better predictions. The results show that accurate PA segmentations and images are obtained, and error predictions are highly statistically correlated to actual errors. To leverage error predictions, confidence processing created PA images above a specific confidence level.

Photoacoustic differential attenuation spectrum for bone assessment

Abstract Photoacoustic (PA) technology shows great potential in bone microstructure assessment. Due to the solid-liquid two-phase characteristics of cancellous bone, the PA signal received by transducers is aliasing of distributed PA source characteristics and acoustic propagation characteristics of cancellous bone. The contribution of various multi-scale distributed PA sources to the PA signal complexity leads to difficulty in identifying the sound propagation characteristics, making it difficult for quantitative assessment of bone microstructure. To eliminate the spectrum contribution of the PA source to the PA signal, we proposed an eccentric excitation-differential detection system and the acoustic propagation characteristics of cancellous bone can be obtained by calculating the PA differential attenuation spectrum (PA-DAS). The PA-DAS quantization parameter-slope is further extracted to quantify the attenuation of different frequency components. Simulation results show that slope strongly correlates to the porosity of cancellous bone, demonstrating the eccentric excitation-differential detection system combined with the PA-DAS method can realize the quantitative bone assessment.

Photoacoustic Signal Propagation Modes in Bone Tissue: a Simulation Study

Abstract Photoacoustic (PA) imaging has great potential in brain imaging. However, the strong acoustic attenuation and reverberation caused by the skull bone layers present challenges for PA brain imaging. In this work, we developed a three-dimensional (3D) photoacoustic numerical simulation platform using the finite difference time domain (FDTD) method to study PA signal generation and propagation in the human brain. This platform can simulate not only the propagation of longitudinal waves in soft tissues but also shear and longitudinal waves in hard tissues. Using this numerical simulation platform, we extensively simulated the propagation of PA waves in skull models with varying porosities, The results demonstrate that our 3D PA simulation platform accurately captures the propagation details of PA signals in the skull, including the refraction, reflection, and mode conversion of photoacoustic waves at tissue boundaries. Furthermore, an increase in skull porosity prolongs the duration of the photoacoustic signals and leads to high attenuation of PA signals for high frequency components. We expect that this study will contribute to the understanding of the impact on acoustic propagation of photoacoustic signals in cranial bone photoacoustic imaging.