Photoacoustic Imaging Research Articles

Optical tuning of copolymer-in-oil tissue-mimicking materials for multispectral photoacoustic imaging

Objective. The availability of tissue-mimicking materials (TMMs) for manufacturing high-quality phantoms is crucial for standardization, evaluating novel quantitative approaches, and clinically translating new imaging modalities, such as photoacoustic imaging (PAI). Recently, a gel comprising the copolymer styrene-ethylene/butylene-styrene (SEBS) in mineral oil has shown significant potential as TMM due to its optical and acoustic properties akin to soft tissue. We propose using artists’ oil-based inks dissolved and diluted in balsam turpentine to tune the optical properties. Approach. A TMM was fabricated by mixing a SEBS copolymer and mineral oil, supplemented with additives to tune its optical absorption and scattering properties independently. A systematic investigation of the tuning accuracies and relationships between concentrations of oil-based pigments and optical absorption properties of the TMM across visible and near-infrared wavelengths using collimated transmission spectroscopy was conducted. The photoacoustic spectrum of various oil-based inks was studied to analyze the effect of increasing concentration and depth. Main results. Artists’ oil-based inks dissolved in turpentine proved effective as additives to tune the optical absorption properties of mineral oil SEBS-gel with high accuracy. The TMMs demonstrated long-term stability and suitability for producing phantoms with desired optical absorption properties for PAI studies. Significance. The findings, including tuning of optical absorption and spectral shape, suggest that this TMM facilitates the development of more sophisticated phantoms of arbitrary shapes. This approach holds promise for advancing the development of PAI, including investigation of the spectral coloring effect. In addition, it can potentially aid in the development and clinical translation of ultrasound optical tomography.

Removing Artifacts in Transcranial Photoacoustic Imaging With Polarized Self-Attention Dense-UNet

ObjectivePhotoacoustic imaging (PAI) is a promising transcranial imaging technique. However, the distortion of photoacoustic signals induced by the skull significantly influences its imaging quality. We aimed to use deep learning for removing artifacts in PAI. MethodsIn this study, we propose a polarized self-attention dense U-Net, termed PSAD-UNet, to correct the distortion and accurately recover imaged objects beneath bone plates. To evaluate the performance of the proposed method, a series of experiments was performed using a custom-built PAI system. ResultsThe experimental results showed that the proposed PSAD-UNet method could effectively implement transcranial PAI through a one- or two-layer bone plate. Compared with the conventional delay-and-sum and classical U-Net methods, PSAD-UNet can diminish the influence of bone plates and provide high-quality PAI results in terms of structural similarity and peak signal-to-noise ratio. The 3-D experimental results further confirm the feasibility of PSAD-UNet in 3-D transcranial imaging. ConclusionPSAD-UNet paves the way for implementing transcranial PAI with high imaging accuracy, which reveals broad application prospects in preclinical and clinical fields.

Emerging Trends in Targeted Magnetic Nanoparticle Imaging for Precision Medicine in Oncology

In cancer care's dynamic landscape, targeted imaging is pivotal for advancing precision medicine. This review focuses on the role of magnetic nanoparticles (MNPs), particularly magnetic iron oxide nanoparticles (MIONPs) and superparamagnetic iron oxide nanoparticles (SPIONs), in personalized diagnostics and treatments for oncology. Current trends and future directions in MNP imaging, addressing challenges like biocompatibility, toxicity, and regulatory considerations, are discussed. The review explores MIONPs' theranostic potential, especially in brain drug delivery monitoring through magnetic resonance imaging (MRI) or magnetic particle imaging (MPI). Variousnanoparticle types, including SPIONs as MRI contrast agents, are highlighted. The article covers challenges in nanoparticle modification, including methoxy- polyethylene glycol (mPEG), and discusses gold nanoparticles (AuNPs) for photoacoustic imaging, as well as insights into fluorescent semiconductor quantum dots (QDs). The conclusion emphasizes rapid and accurate tumoridentification, introduces carbon nanotubes (CNTs) for cancer therapy and diagnosis, and underscores the transformative role of lipid-based nanocarriers incancer research. The multifaceted applications of nanotechnology in cancer diagnostics and treatment are discussed throughout, showcasing a paradigm shift.Crucial challenges in unlocking nanotechnology's full potential in cancer care, such as safety concerns, robust clinical trials, synthesis methods standardization, regulatory approval, biodegradability, tailoring nanotherapies, economic viability, ethical considerations, and interdisciplinary collaboration, are addressed. Addressing these challenges holds the promise of elevating nanotechnology into a potent force in the ongoing battle against cancer.

Supramolecular assembly of Polydopamine@Fe nanoparticles with near-infrared light-accelerated cascade catalysis applied for synergistic photothermal-enhanced chemodynamic therapy

Chemodynamic therapy (CDT) via Fenton-like reaction is greatly attractive owing to its capability to generate highly cytotoxic •OH radicals from tumoral hydrogen peroxide (H2O2). However, the antitumor efficacy of CDT is often challenged by the relatively low radical generation efficiency and the high levels of antioxidative glutathione (GSH) in tumor microenvironment. Herein, an innovative photothermal Fenton-like catalyst, Fe-chelated polydopamine (PDA@Fe) nanoparticle, with excellent GSH-depleting capability is constructed via one-step molecular assembly strategy for dual-modal imaging-guided synergetic photothermal-enhanced chemodynamic therapy. Fe(III) ions in PDA@Fe nanoparticles can consume the GSH overexpressed in tumor microenvironment to avoid the potential •OH consumption, while the as-produced Fe(II) ions subsequently convert tumoral H2O2 into cytotoxic •OH radicals through the Fenton reaction. Notably, PDA@Fe nanoparticles demonstrate excellent near-infrared light absorption that results in superior photothermal conversion ability, which further boosts above-mentioned cascade catalysis to yield more •OH radicals for enhanced CDT. Taken together with T1-weighted magnetic resonance imaging (MRI) contrast enhancement (r1 = 8.13 mM−1 s−1) and strong photoacoustic (PA) imaging signal of PDA@Fe nanoparticles, this design finally realizes the synergistic photothermal-chemodynamic therapy. Overall, this work offers a new promising paradigm to effectively accommodate both imaging and therapy functions in one well-defined framework for personalized precision disease treatment.

A practical solution to improve the field of view in circular scanning-based photoacoustic tomography.

One of the primary challenges in ring single-element photoacoustic tomography systems is the low image quality in areas away from the center of the ring. This is mainly due to the limited field of view (FOV) of each transducer, which in turn reduces the imaging FOV. To address this shortcoming, we have put forward a practical and straightforward solution to enhance the FOV of circular scanning-based photoacoustic tomography (CS-PAT). This is accomplished by placing transducers at different angles instead of using a single transducer placed at a normal angle to the imaging target. We also modified the ring scanner inner wall surface to significantly reduce photoacoustic reverberation. By imaging several phantoms, we show a significant improvement in the images generated by our system imaging from 4.1 to over 7 for the signal-to-noise ratio and structural similarity index increased from 41% to 70%.

Quantitative Optical Imaging of Oxygen in Brain Vasculature.

The intimate relationship between neuronal activity and cerebral oxygenation underpins fundamental brain functions like cognition, sensation, and motor control. Optical imaging offers a noninvasive approach to assess brain oxygenation and often serves as an indirect proxy for neuronal activity. However, deciphering neurovascular coupling─the intricate interplay between neuronal activity, blood flow, and oxygen delivery─necessitates independent, high spatial resolution, and high temporal resolution measurements of both microvasculature oxygenation and neuronal activation. This Perspective examines the established optical techniques employed for brain oxygen imaging, specifically functional near-infrared spectroscopy, photoacoustic imaging, optical coherence tomography, and two-photon phosphorescent lifetime microscopy, highlighting their fundamental principles, strengths, and limitations. Several other emerging optical techniques are also introduced. Finally, we discuss key technological challenges and future directions for quantitative optical oxygen imaging, paving the way for a deeper understanding of oxygen metabolism in the brain.

Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo.

Abnormal alpha-synuclein (αSyn) and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim to visualize αSyn inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. The fluorescent pyrimidoindole derivative THK-565 probe was characterized by means of recombinant fibrils and brains from 10- to 11-month-old M83 mice. Concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging were subsequently performed in vivo. Structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 T as well as scanning transmission x-ray microscopy (STXM) were performed to characterize the iron deposits in the perfused brains. Immunofluorescence and Prussian blue staining were further performed on brain slices to validate the detection of αSyn inclusions and iron deposition. THK-565 showed increased fluorescence upon binding to recombinant αSyn fibrils and αSyn inclusions in post-mortem brain slices from patients with PD and M83 mice. Administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 min post-intravenous injection by wide-field fluorescence compared to nontransgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. In conclusion, we demonstrated in vivo mapping of αSyn by means of noninvasive epifluorescence and vMSOT imaging and validated the results by targeting the THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.

Pharmacologic ascorbate induces transient hypoxia sensitizing pancreatic ductal adenocarcinoma to a hypoxia activated prodrug

Hypoxic tumor microenvironments pose a significant challenge in cancer treatment. Hypoxia-activated prodrugs like evofosfamide aim to specifically target and eliminate these resistant cells. However, their effectiveness is often limited by reoxygenation after cell death. We hypothesized that ascorbate's pro-oxidant properties could be harnessed to induce transient hypoxia, enhancing the efficacy of evofosfamide by overcoming reoxygenation.To test this hypothesis, we investigated the sensitivity of MIA Paca-2 and A549 cancer cells to ascorbate in vitro and in vivo. Ascorbate induced a cytotoxic effect at 5 mM that could be alleviated by endogenous administration of catalase, suggesting a role for hydrogen peroxide in its cytotoxic mechanism. In vitro, Seahorse experiments indicated that the generation of hydrogen peroxide consumes oxygen, which is offset at later time points by a reduction in oxygen consumption due to hydrogen peroxide's cytotoxic effect.In vivo, photoacoustic imaging showed pharmacologic ascorbate treatment at sublethal levels triggered a complex, multi-phasic response in tumor oxygenation across both cell lines. Initially, ascorbate generated transient hypoxia within minutes through hydrogen peroxide production, via reactions that consume oxygen. This initial hypoxic phase peaked at around 150 s and then gradually subsided. However, at longer time scales (approximately 300 s) a vasodilation effect triggered by ascorbate resulted in increased blood flow and subsequent reoxygenation. Combining sublethal levels of i. p. Ascorbate with evofosfamide significantly prolonged tumor doubling time in MIA Paca-2 and A549 xenografts compared to either treatment alone. This improvement, however, was only observed in a subpopulation of tumors, highlighting the complexity of the oxygenation response.

Unveiling Metabolic Similarities of Entheses in Patients with Psoriasis and Psoriatic Arthritis Using Noninvasive In Vivo Molecular Imaging: Results From a Cross-sectional Exploratory Study.

We assessed and compared molecular tissue changes at the entheses in patients with psoriasis (PsO) and psoriatic arthritis (PsA) and in healthy controls (HCs) in vivo using multispectral optoacoustic tomography (MSOT) and described their relationship with clinical and ultrasound findings of enthesitis. A cross-sectional study (MSOT and Arthrosonography in PsA) in biologic disease-modifying antirheumatic drug-naïve patients with PsA and PsO and HCs was performed. Participants underwent clinical, ultrasonographic, and MSOT examination of six entheses (lateral humeral epicondyle, distal patellar tendon attachment, and Achilles tendon attachment). MSOT-measured hemoglobin (Hb), oxygen saturation (SO2), collagen, and lipid levels were quantified, and mean differences between groups were calculated using linear mixed effects models. MSOT-measured analytes were compared between entheses with and without clinical and ultrasound anomalies. Ninety participants were included (30 PsO, 30 PsA, and 30 HCs), 540 entheses were clinically assessed, and 540 ultrasound and 830 MSOT scans were obtained. Patients with PsA and PsO showed increased oxygenated Hb (PsA: P = 0.003; PsO: P = 0.054) and SO2 (PsA: P < 0.001; PsO: P = 0.001) levels and decreased collagen signals (PsA: P < 0.001; PsO: P < 0.001) compared with HCs, with more pronounced changes in PsA. Significantly lower collagen levels (P = 0.01) and increased lipids (P = 0.03) were recorded in tender entheses compared with nontender ones. Erosions and enthesophytes on ultrasound were associated with significant differences in SO2 (P = 0.014) and lipid signals (P = 0.020), respectively. Patients with PsA and PsO exhibit an analogous metabolic pattern at the entheses that is exacerbated in the presence of inflammation. These findings support the notion of a psoriatic disease spectrum characterized by common immunometabolic tissue changes.

A Mitochondria-Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR-II Imaging/Photoacoustic Imaging-Guided Phototherapy.

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near-infrared-II (NIR-II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria-targeting abilities, and a large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type-I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs-mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT.

A Mitochondria‐Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR‐II Fluorescence/Photoacoustic Imaging‐Guided Phototherapy

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near‐infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep‐penetrating, organelle‐targeted pyroptosis‐mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near‐infrared‐II (NIR‐II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria‐targeting abilities, and a large Stokes shift. Through nano‐precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type‐I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor‐targeting ability via NIR‐II fluorescence imaging (NIR‐II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs‐mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT.

Photoacoustic Imaging Using Polysaccharide-Porphyrin Complexes by Photoirradiation at Long Wavelengths.

Photoacoustic (PA) imaging is a novel biological imaging technique with superior depth resolution compared to fluorescence imaging. The efficacy of PA imaging depends on contrast agents that possess considerable absorbance at longer wavelengths, coupled with high permeability in biological tissue and minimal fluorescence, achieved through mitigating aggregation-caused quenching (ACQ) that attenuates PA intensity. Despite the successful transfer of porphyrin 2 featuring amino moieties from polysaccharides to liposomes, most of 2 incorporated within λ-carrageenan (CGN-2 complex) remained in CGN under acidic lysosomal conditions (pH 5.0). Consequently, the CGN-2 complex exhibited a strong PA signal under 680 nm photoirradiation in Colon26 cells owing to the ACQ of 2. Moreover, the PA intensity of the CGN-2 complex was further enhanced under 780 nm photoirradiation owing to the increased absorbance at 780 nm facilitated by the redshift of the Q-band at pH 5.0.

P-260 In Vitro Fertilization (IVF) using magnetotactic sperm cells and their prospects for assisted in vivo reproduction

Abstract Study question Are bovine Magnetotactic Sperm Cells (MSC) able to fertilize an oocyte in-vitro and Which would be the main requirements for translating this technology to in-vivo? Summary answer IVF using highly purified MSC result in embryo development until blastocyst stage. We demonstrate different alternatives to control multiple MSC, individually and as a swarm. What is known already Medical microrobots have appeared as the new generation of drug delivery vehicles. They are tiny devices in the order of a few micrometers, able to move in biological environments by different means, physical, chemical, or biohybrid. They are functionalized to deliver targeted therapies for drugs, cells, or other payloads. In assisted reproduction, sperm-hybrid microcarriers have been pioneered by our group, and various in vitro demonstrations have been done to assist sperm cells with motion deficiencies or low count and to deliver anticancer drugs for treating, for example, cervical and ovarian cancer, but so far in-vitro fertilization has never been shown. Study design, size, duration Experimental quantitative study design. A total of 520 bovine cumulus-oocyte complexes were used for in vitro fertilization. The analyzed sample groups were using bovine frozen sperm cells, MSC, or by evaluating parthenogenetic activation. A power of 0.98 with an a-error of 0.05 was used for the IVF experiments. Sperm samples in the control as well as the micromotor groups have been analyzed for different sperm parameters. Participants/materials, setting, methods Bovine MSC are created by thawing frozen sperm cells and adding polystyrene microparticles. Different sperm parameters were evaluated to check the effects of the particles in the cells. After developing a purification method for the MSC, bovine ovaries were collected from a slaughterhouse nearby and, after in vitro maturation, were used for the IVF experiments. Ultrasound, and photoacoustic imaging setups with a set of electromagnets were employed for real-time manipulation and visualization of MSC. Main results and the role of chance Sperm viability was significantly higher in the MSC group compared to the control group 6h after formation (72.3 ± 5.0% vs 35.0 ± 4.1%), and after 24 hours, both viabilities decreased drastically to 16.6 ± 3.9% and 7.7 ± 1.7% respectively, probably a possible local antioxidant effect by the microparticles through the formation of a protein corona. In the case of motility, the MSC group presented significantly higher motility up to 6h (64.0 ± 1.5%), and in all the measured times, the motility of the MSC group was higher than the control group. Purification of the micromotor sample was performed, but an average of 63 free sperm was still on the MSC sample. IVF experiments were performed, and blastocyst development was observed in IVF control (2x106 sperm/ml), medium concentration (same concentration as MSC group), and the MSC groups (275.000 sperm/ml). No blastocyst formation was observed in the parthenogenetic, parthenogenetic + particles, and low-concentration groups (number of free sperm). The MSC group was significantly different in cleavage and blastocyst rates compared to the low concentration groups, with p-values of 0.04552 and 0.005865, respectively, which suggest that fertilization may have occurred by the micromotors instead by the free sperm in the sample. Limitations, reasons for caution More studies of these MSC in the different gynecological tissues and on embryo development are needed to ensure the safety of future human translation. In addition, developing a detection system for micromotors in deep tissue is needed to perform in vivo experiments. Wider implications of the findings MSC show an alternative to efficiently guide efficiently sperm cells in different biological environments and can be a promising alternative method for assisted fertilization, and the treatment of a variety of gynecological diseases. They can also be used as exploratory tools to learn more about sperm migration in-vivo, among others Trial registration number European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program No. 853609

Unsupervised denoising of photoacoustic images based on the Noise2Noise network.

In this study, we implemented an unsupervised deep learning method, the Noise2Noise network, for the improvement of linear-array-based photoacoustic (PA) imaging. Unlike supervised learning, which requires a noise-free ground truth, the Noise2Noise network can learn noise patterns from a pair of noisy images. This is particularly important for in vivo PA imaging, where the ground truth is not available. In this study, we developed a method to generate noise pairs from a single set of PA images and verified our approach through simulation and experimental studies. Our results reveal that the method can effectively remove noise, improve signal-to-noise ratio, and enhance vascular structures at deeper depths. The denoised images show clear and detailed vascular structure at different depths, providing valuable insights for preclinical research and potential clinical applications.

Sparse sampling photoacoustic reconstruction with a graph regularization group sparse dictionary

Photoacoustic tomography (PAT) has emerged as a promising biomedical imaging technique. The combination of optical contrast and ultrasound spatial resolution in photoacoustic tomography overcomes the limitations of optical scattering, enabling clear imaging of tissue structures. However, achieving high-resolution photoacoustic images typically requires a large number of sensor detection elements for sufficient angular coverage. This demand for extensive data acquisition and processing raises concerns about efficiency and system complexity. While sparse sampling strategies can improve efficiency, preserving detailed structural information becomes challenging with a minimal number of detectors. To address the challenges of sparse sampling, compressed sensing (CS) techniques have been successfully applied for image reconstructions in 2D and 3D photoacoustic embodiments. In this context, we propose a joint graph regularization group sparse dictionary and total variational regularization (GRGS-TV) algorithm based on our previous work of a group sparse dictionary. It preserves structured information and geometric relationships among dictionary atoms. Moreover, TV regularization effectively preserves edge structures while exhibiting a certain degree of robustness and flexibility. Numerical simulations and in vivo experiments on mice validate the effectiveness of this method in improving photoacoustic image quality and suppressing artifacts. Comparative evaluations against other algorithms show enhanced performance in terms of image reconstruction evaluation indices. This innovative approach holds promise for advancing photoacoustic imaging in biomedical research and clinical diagnostics.

Enhancing vascular network visualization in 3D photoacoustic imaging: in vivo experiments with a vasculature filter

Filter-based vessel enhancement algorithms facilitate the extraction of vascular networks from medical images. Traditional filter-based algorithms struggle with high noise levels in images with false vessel extraction, and a low standard deviation (σ) value may introduce gaps at the centers of wide vessels. In this paper, a robust technique with less sensitivity to parameter tuning and better noise suppression than other filter-based methods for two-dimensional and three-dimensional images is implemented. In this study, we propose a filter that employs non-local means (NLM) for denoising, applying the vesselness function to suppress blob-like structures and filling the gaps in wide vessels without compromising edge quality or details. Acoustic resolution photoacoustic microscopy (AR-PAM) systems generate high-resolution volumetric photoacoustic images, but their vascular structure imaging suffers from out-of-focal signal-to-noise ratio (SNR) and lateral resolution loss. Implementing a synthetic aperture focusing technique (SAFT) based on a virtual detector (VD) improves out-of-focal region resolution and SNR. Combining the proposed filter with the SAFT algorithm enhances vascular structural imaging in AR-PAM systems. The proposed method is robust and applicable for animal tissues with less error of vasculature structure extraction in comparison to traditional fliter-based methods like Frangi and Sato filter. Also, the method is faster in terms of processing speed and less tuning parameters. We applied the method to a digital phantom to validate our approach and conducted in vivo experiments to demonstrate its superiority for real volumetric tissue imaging.

Optimization on artifacts in photoacoustic images based on spectrum analyses and signal extraction.

Photoacoustic (PA) imaging is a promising technology for functional imaging of biological tissues, offering optical contrast and acoustic penetration depth. However, the presence of signal aliasing from multiple PA sources within the same imaging object can introduce artifacts and significantly impact the quality of the PA tomographic images. In this study, an optimized method is proposed to suppress these artifacts and enhance image quality effectively. By leveraging signal time-frequency spectrum, signals from each PA source can be extracted. Subsequently, the images are reconstructed using these extracted signals and fused together to obtain an optimized image. To verify this proposed method, PA imaging experiments were conducted on two phantoms and two in vitro samples and the distribution relative error and root mean square error of the images obtained through conventional and optimized methods were calculated. The results demonstrate that the proposed method successfully suppresses the artifacts and substantially improves the image quality.

Noninvasive Photothermal Therapy of Nasopharyngeal Cancer Guided by High Efficiency Optical-Absorption Nanomaterial Enhanced by NIR-II Photoacoustic Imaging.

Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC). The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC. Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT. The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.

Hypoxia-Specific Metal-Organic Frameworks Augment Cancer Immunotherapy of High-Intensity Focused Ultrasound.

As a noninvasive treatment modality, high-intensity focused ultrasound (HIFU)-induced antitumor immune responses play a vital role in surgery prognosis. However, limited response intensity largely hinders postoperative immunotherapy. Herein, a hypoxia-specific metal-organic framework (MOF) nanosystem, coordinated by Fe3+, hypoxic-activated prodrug AQ4N, and IDO-1 signaling pathway inhibitor NLG919, is developed for the potentiating immunotherapy of HIFU surgery. The loaded AQ4N enhances the photoacoustic imaging effects to achieve accurate intraoperative navigation. Within the HIFU-established severe hypoxic environment, AQ4N is activated sequentially, following which it cooperates with Fe3+ to effectively provoke immunogenic cell death. In addition, potent NLG919 suppresses IDO-1 activity and degrades the immunosuppressive tumor microenvironment aggravated by postoperative hypoxia. In vivo studies demonstrate that the MOF-mediated immunotherapy greatly inhibits the growth of primary/distant tumors and eliminates lung metastasis. This work establishes a robust delivery platform to improve immunotherapy and the overall prognosis of HIFU surgery with high specificity and potency.

Masked cross-domain self-supervised deep learning framework for photoacoustic computed tomography reconstruction

Accurate image reconstruction is crucial for photoacoustic (PA) computed tomography (PACT). Recently, deep learning has been used to reconstruct PA images with a supervised scheme, which requires high-quality images as ground truth labels. However, practical implementations encounter inevitable trade-offs between cost and performance due to the expensive nature of employing additional channels for accessing more measurements. Here, we propose a masked cross-domain self-supervised (CDSS) reconstruction strategy to overcome the lack of ground truth labels from limited PA measurements. We implement the self-supervised reconstruction in a model-based form. Simultaneously, we take advantage of self-supervision to enforce the consistency of measurements and images across three partitions of the measured PA data, achieved by randomly masking different channels. Our findings indicate that dynamically masking a substantial proportion of channels, such as 80%, yields meaningful self-supervisors in both the image and signal domains. Consequently, this approach reduces the multiplicity of pseudo solutions and enables efficient image reconstruction using fewer PA measurements, ultimately minimizing reconstruction error. Experimental results on in-vivo PACT dataset of mice demonstrate the potential of our self-supervised framework. Moreover, our method exhibits impressive performance, achieving a structural similarity index (SSIM) of 0.87 in an extreme sparse case utilizing only 13 channels, which outperforms the performance of the supervised scheme with 16 channels (0.77 SSIM). Adding to its advantages, our method can be deployed on different trainable models in an end-to-end manner, further enhancing its versatility and applicability.