Breast cancer remains a clinical hurdle despite technoclinical advancements, primarily due to drug resistance mechanisms, from overexpression of drug efflux pumps. Modulating drug efflux/influx transporters like ABCG2 and HCP-1 can improve anticancer therapeutic approaches. Our study reports CuS-ALA metal-organic nanoprobes combining 5-aminolevulinic acid (5-ALA), a tumor targeting biomolecule, and near-infrared (NIR) light-absorbing copper sulfide (CuS) nanoparticles. These ALA-CuS nanoprobes (NPs) had excellent near-infrared (NIR) absorption properties along with high photothermal profile, stability, photoacoustic and fluorescence imaging properties. In vitro studies in breast cancer cell lines revealed uniform internalization and exhibited a synergistic cytotoxic effect in the case of ALA-CuS NPs when exposed to a NIR 808 nm light. Further mechanistic studies have revealed that these nanoprobes could target and modulate drug transporters, such as ABCG2 and HCP1, indicating their efficient role in targeted downregulation of resistance pathways and activating photodynamic and photothermal therapies-mediated intrinsic apoptotic cell death pathways in breast cancer. Furthermore, the ALA-CuS NPs were effective for the photoacoustic image-guided delivery when evaluated in a preclinical 4T1 syngeneic breast tumor model. The fluorescence biodistribution profile revealed that these nanoprobes were preferentially accumulated in the tumor, liver, and kidneys and revealed negligible toxic effects. However, following the NIR irradiation, the ALA-CuS NPs treated tumors were effectively ablated without obvious tumor recurrence within 21 days. Moreover, they reduced hypoxia, promoting tumor regression when combined with NIR light. Overall, the proposed ALA-CuS NPs could be a promising translational formulation for targeting drug resistance and aiding in synergizing multimodal theranostics-based breast cancer therapy.
Quantitative molecular imaging in photoacoustics is fundamentally limited by the ill-posed nature of spectral unmixing, where spectral overlap, noise, and unknown fluence introduce bias in conventional inversion-based methods. We introduce photoacoustic fingerprinting (PAF), a framework that reframes spectral unmixing as a fingerprint recognition problem. PAF interprets multispectral signals as high-dimensional fingerprints encoding both molecular composition and measurement distortions. Inspired by magnetic resonance fingerprinting, PAF uses a recurrent neural network trained on synthetic data spanning realistic mixtures, noise levels, and fluence variations to directly infer molecular concentrations from spectral shape. PAF enables accurate and robust quantification in regimes where conventional methods break down, including low signal-to-noise conditions, spectrally correlated mixtures, and unknown fluence distortions. In controlled simulations, PAF consistently outperformed non-negative least squares, with the largest gains observed for spectrally overlapping chromophores such as collagen. In phantom studies, PAF improved molecular specificity by correctly localizing collagen and recovering water contrast despite similar spectral reconstructions. In ex vivo mouse livers, PAF detected lipid accumulation associated with steatosis, and in human arteries, it identified molecular signatures consistent with thrombus and lipid-rich plaque. These results establish PAF as a generalizable framework for label-free molecular imaging and a promising step toward quantitative photoacoustic diagnostics.
Optoacoustic imaging (OAI) has emerged as a powerful modality for visualizing biological tissues with high spatial resolution and molecular specificity. When applied to skeletal muscle tissue, OAI provides unique opportunities to investigate muscle composition, function, and physiology beyond the capabilities of conventional imaging methods. Literature search was conducted in PubMed using ("Optoacoustic" OR "Photoacoustic") AND ("Muscle"), with relevant references additionally screened. Clinical studies include over 440 patients, mostly on skeletal muscle in neuromuscular disorders and peripheral artery disease. OAI detected structural changes such as fibrosis, and fatty infiltration, as well as functional impairments related to muscle perfusion and oxygenation. Preclinical studies demonstrate volumetric imaging of cardiac muscle, reflecting ongoing technological advances. This review summarizes the fundamental principles of optoacoustic muscle imaging, technical implementations, and translational applications. Furthermore, it discusses approaches to signal quantification, artifacts, as well as translation into clinical practice. Emphasis is placed on applications in the field of neuromuscular disease, where OAI holds promise as a non-invasive, radiation-free, and bedside imaging modality for characterizing and monitoring disease-specific muscle alterations. OAI represents a rapidly evolving field with significant potential for advancing both fundamental muscle physiology research and the diagnosis and monitoring of (neuro-)muscular disorders.
End-stage liver disease (ESLD) is one of the leading causes of death worldwide. Currently, the only curative option for patients with ESLD is liver transplantation. However, the demand for donor livers far exceeds the available supply, partly because many potentially viable livers are discarded following biopsy evaluation. While biopsy is the gold standard for assessing liver histological features related to graft quality and transplant suitability, it often leads to high discard rates due to its susceptibility to sampling errors and limited spatial coverage. Besides, biopsy is invasive, time-consuming, and unavailable in clinical facilities with limited resources. Here, we present an AI-assisted photoacoustic/ultrasound (PA/US) imaging framework for quantitative assessment of human donor liver graft quality and transplant suitablity at the whole-organ scale. With multimodal volumetric PA/US images as the input, our deep-learning (DL) model accurately predicted the risk level of fibrosis and steatosis, which indicate the graft quality and transplant suitability, when comparing with true pathological scores. DL also identified the imaging modes (PAI wavelength and B-mode USI) that correlated the most with prediction accuracy, without relying on ill-posed spectral unmixing. Our method was evaluated in six discarded human donor livers comprising sixty spatially matched regions of interest. Our study will pave the way for a new standard of care in organ graft quality and transplant suitability that is fast, noninvasive, and spatially thorough to prevent unnecessary organ discards in liver transplantation.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial infiltration of polarized M1 macrophages that secrete pro-inflammatory cytokines (TNF-α/IL-1/IL-6) and activate JAK-STAT/NF-κB pathways. These events disrupt the osteoblast-osteoclast balance to induce cartilage degradation and bone erosion. Current disease-modifying antirheumatic drugs (DMARDs), including tofacitinib, show limited efficacy due to systemic toxicity, poor bone-targeting capacity, and inability to restore bone homeostasis. To overcome these limitations, we developed a multifunctional nanoplatform (MBGN-Tofa@PDA-FA) based on magnesium-doped mesoporous bioactive glass nanoparticles (Mg-MBGNs) to codeliver the JAK inhibitor tofacitinib and osteoimmunomodulatory Mg2+/Ca2+ ions, aiming to overcome the severe systemic toxicity of free drugs. This system suppresses inflammation by polarizing macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype (M1-to-M2 repolarization), and synergistically promotes osteoblast differentiation. Polydopamine (PDA) coating improves colloidal stability and enables photoacoustic imaging (PAI), while folic acid (FA) modification ensures selective uptake by folate receptor-overexpressing macrophages. By integrating imaging with targeted therapeutic delivery, this platform provides both real-time monitoring and enhanced treatment efficacy. Collectively, our strategy establishes a promising precision theranostic approach for RA by uniting targeted immunomodulation, bone regeneration, and treatment evaluation. Furthermore, in vivo evaluations demonstrated the excellent biodistribution and biosafety profile of this nanoplatform, reinforcing its strong potential for clinical translation.
Oncolytic reovirus, particularly Pelareorep, is a promising cancer therapeutic due to selective replication in Ras-activated tumor cells and immunomodulatory effects. This review aims to critically evaluate current and emerging in vivo tracking strategies, emphasizing translational relevance and clinical implementation. We systematically analyzed preclinical and clinical studies employing optical imaging, nuclear imaging, magnetic resonance imaging, ultrasound/photoacoustic techniques, molecular reporters, and nanoparticle-based platforms. Special focus was placed on integrating functional imaging and molecular assays in Pelareorep trials to monitor viral distribution and therapeutic response. Optical imaging offers high sensitivity for preclinical investigations; however, it is limited by shallow tissue penetration. Nuclear imaging provides quantitative, whole-body monitoring that is suitable for clinical translation, whereas MRI and ultrasound/photoacoustic modalities enable real-time visualization of both structural and functional aspects. Nanotechnology-based platforms facilitate multimodal imaging and targeted delivery, while molecular tools such as reporter genes, CRISPR-driven circuits, and viral barcoding further enhance spatiotemporal resolution. Clinical trials with Pelareorep demonstrate the feasibility of integrating imaging with molecular assays to evaluate safety, delivery efficiency, and antitumor activity. Persisting challenges include limited genome capacity, immune-mediated clearance, and suboptimal signal penetration. Emerging strategies, including synthetic biology reporters, AI-driven image analysis, biosensors, and liquid biopsies, provide scalable, patient-specific tracking solutions. This integrative framework bridges preclinical insights with clinical translation, supporting optimized design, monitoring, and personalization of oncolytic reovirus therapy.
Photoacoustic (PA) sensing has garnered growing interest as a volumetric optical-acoustic transduction modality that mitigates optical scattering and enables sensitive detection in complex matrices. However, conventional PA assays rely on diffusion-dominated biochemical reaction kinetics and endpoint-based signal acquisition, which limit their capacity for rapid and real-time monitoring. Here, we report a magnetic-actuation-enhanced indirect PA sensing platform that integrates rotating magnetic fields (RMFs) with real-time PA detection to accelerate and continuously monitor operationally homogeneous immunoassays (without separation or washing steps). Functionalized magnetic nanoparticles (MNPs) were actuated by the RMF into dynamic chained or clustered structures, thereby enhancing collision frequency with target analytes and promoting target-induced aggregation. The resultant MNP aggregates caused interparticle light shielding, enhanced light scattering of the particle system, and underwent rapid sedimentation, thereby modulating the PA signal amplitude, which enabled continuous volumetric PA monitoring. Using cardiac troponin I as a clinical target, the platform achieved detection limits of 0.9 pM (22 pg/mL) in buffer and 2 pM (48 pg/mL) in 50% serum, outperforming conventional passive or endpoint assays. Clinical serum validation showed strong concordance with a clinical reference method, underscoring the platform's utility in point-of-care diagnostics.
X-ray acoustic computed tomography (XACT) suffers from low SNR and limited-view detection when only a limited number of detector channels are available. To address these limitations, we introduce a two-stage limited-view signal recovery framework that integrates frequency-aware denoising (FAD) diffusion with geometry-integrated masked autoencoders (GIMAE). FAD jointly models temporal and spectral noise characteristics to restore clean RF measurements, while GIMAE leverages detector-layout-guided masking to infer missing angular channels and reconstruct full-view RF sinograms from limited-view inputs. The recovered signals are subsequently used for XACT image reconstruction via time-reversal algorithm. Simulation and experimental evaluations using multiple X-ray irradiated patterns demonstrate substantial improvements in reconstruction fidelity, with the proposed method boosting SSIM by 31.1% in simulation and by 26.4% in experiments-closely matching full-view references and outperforming limited-view acquisitions. This framework provides an effective and practical solution for high-quality limited-view XACT imaging under realistic noise-dominated conditions.
Integrative multiscale imaging bridges the gap between macroscopic organ structures and microscopic cellular processes, enabling holistic visualization of anatomy and function across scales. Photoacoustic imaging (PAI) leverages melanin's potent contrast for label-free melanoma detection, yet its potential in lung imaging, challenged by air-tissue acoustic impedance mismatch, remains unexplored for melanoma lung metastases (MLMs). We used hierarchical multiscale PAI, transitioning from whole-body macroscale to localized mesoscale and single-cell-resolution microscale. PAI also guided photoablation interventions in the first and second near-infrared windows, requiring only 10.4 pg intracellular melanin/cell. Bioinformatic analysis of human MLM tissues revealed perturbed signaling pathways compared with normal skin and lung tissues, accounting for dysfunctional melanogenesis to enable label-free PAI with high sensitivity and specificity. Malignant MLM lesions in living mice, resected mouse lungs, and human lungs were delineated with margins closely conforming to histology. The high sensitivity allowed visualization of low-cellularity microsatellite foci down to a few tens of cell clusters, with sufficient penetration in the lungs of mice and Bama minipigs. The multiscale imaging methodology streamlines a theranostic workflow and specifically identifies MLM burden in a progressive, label-free manner, which may aid real-time tumor ablation in the future.
Continuous monitoring of arterial waveforms is critical for assessing cardiovascular status in intensive care and intraoperative settings. However, conventional modalities relying on electronics or metallic transducers are strictly incompatible with the strong electromagnetic perturbations in clinical settings, especially magnetic resonance imaging (MRI) suites, creating a blind spot in patient monitoring. Here, we present a fully metal-free, all-fiber optoacoustic system (FOAS) that bridges this gap by integrating focused optical ultrasound generation with ultrasensitive fiber-laser detection in a compact wearable platform. This architecture enables beat-to-beat reconstruction of blood pressure waveforms with high fidelity, preserving morphological features essential for vascular compliance analysis. In-vivo validations, including physiological perturbations (exercise, caffeine) and measurements across 10 healthy volunteers, demonstrated the system's robustness in tracking hemodynamic dynamics and resolving inter-subject waveform variability (e.g., systolic-to-dicrotic notch interval). Crucially, the artifact-free operation was demonstrated inside an active 3 T MRI scanner, confirming superior electromagnetic immunity. This work establishes fiber optoacoustics as a transformative platform for ambulatory hemodynamic monitoring, extending precise cardiovascular profiling into electromagnetically constrained clinical environments.
Phycocyanin (PC), a bioactive phycobiliprotein from Arthrospira maxima, exhibits strong antioxidant and therapeutic potential; however, its spectroscopic characterization becomes challenging when PC is incorporated into complex biopolymeric matrices due to matrix-induced signal interference. In this study, photoacoustic spectroscopy (PAS) was evaluated as an alternative, matrix-tolerant technique for detecting PC encapsulated within polysaccharide-based polymeric matrices, including alginate, agavins, κ-carrageenan, and carboxymethyl cellulose. PC-loaded matrices were characterized by using PAS, UV-vis spectrophotometry, FTIR spectroscopy, and optical microscopy to assess optical absorption, structural features, and potential matrix-analyte interactions. PAS successfully reproduced the characteristic PC absorption band near 620 nm across all matrices and PC concentrations, even in optically dense or highly scattering samples, where UV-Vis transmission measurements are unreliable. FTIR spectra enabled differentiation among polymer matrices and revealed formulation-dependent variations attributable to physicochemical interactions with PC. Morphometric analysis showed substantial differences in encapsulate size and surface characteristics among formulations, although these differences did not affect PAS detection. Overall, the results demonstrate that PAS is a reliable, nondestructive method for identifying PC regardless of matrix composition, morphology, or optical heterogeneity, highlighting its potential as an analytical tool for nutraceutical characterization in biopolymeric delivery systems.
Vessel localization is a key component of ultrasound (US) -guided interventional procedures. However, US imaging faces challenges such as insufficient resolution and a low recognition rate in skin vessel detection. In this study, a photoacoustic (PA) -US multi-modal imaging enhancement framework is proposed. High-resolution vascular light absorption maps from photoacoustic microscopy (PAM) provide objective and accurate labels for US images. Accurate enhancement of blood vessels in skin US images is realized by neural networks driven by high-quality data sources. The results of our novel architecture (UIU-Net) on an ex vivo dataset of controllable vascular complexity show that UIU-Net outperforms existing methods in complex vascular morphology. Based on in vivo experiments, UIU-Net predicts vessels with substantial similarity to actual vessels with the best performance compared to conventional methods, with a 25.57% improvement in the similarity coefficient. Extended to the rabbit ear vein puncture scenario, UIU-Net consistently enhances US images of deep microvasculature. This method successfully guided puncture interventions, establishing a US vascular enhancement paradigm guided by PA imaging. It provides an intelligent solution that combines anatomical fidelity with the ability to avoid microvessels, thereby reducing complications in minimally invasive interventional US settings.
High-resolution visualization of the mouse brain microvasculature is essential for advancing neurovascular research and understanding neurological disorders. Recent advances in pulse-echo ultrasound (US) and optoacoustic (OA) imaging enable angiographic imaging beyond the acoustic diffraction limit through localization of microbubbles in ultrasound localization microscopy (ULM) and light-absorbing microparticles in localization optoacoustic tomography (LOT). Despite their distinct contrast mechanisms, a direct comparison has been lacking. Here, we evaluate three-dimensional motion-contrast US and OA imaging, including their super-resolved variants ULM and LOT, using the same ultrasound array, localization and tracking algorithms, and frame rates. Studies in mice of different ages reveal complementary strengths: OA/LOT offers higher-SNR for cortical imaging, especially in older animals with thicker skulls, while the lower attenuation of ultrasound enables US/ULM to achieve substantially greater penetration depth and whole-brain coverage. This comparison provides practical guidance for choosing optimal localization-based strategies for cerebrovascular studies.
Background: Successful healing of chronic apical periodontitis after endodontic treatment requires a reduction in the size of the radiolucent area and the healing of the bone. This study aimed to compare the effects of different irrigation activation techniques on healing in single-rooted mandibular premolar teeth with periapical lesions of endodontic origin. Methods: A total of 132 systemically healthy patients with mandibular single-rooted premolar teeth and a periapical index (PAI) score ≥ 3 were assigned to five experimental groups (Sonic activation, Passive ultrasonic irrigation, Photon-Induced Photoacoustic Streaming, Shock Wave Enhanced Emission Photoacoustic Streaming and Manual dynamic activation) and a control group (Conventional Syringe Irrigation). After access cavity preparation, the canals were prepared up to three sizes larger than the initial apical diameter with 5 mL of 2.5% NaOCl used between each file. Final irrigation was performed via the assigned activation system. The root canals were obturated with gutta-percha in a single visit. The effects of the activation systems on healing were compared at 1-year follow-up. The primary outcome measure was the change in lesion diameter. PAI score and fractal dimension (FD) were evaluated as secondary outcomes. Results: At the 1-year follow-up, FD values significantly increased, PAI scores and lesion size decreased in all groups compared with baseline (p < 0.001). However, the increase in FD was comparable among the irrigation groups (p > 0.05). In contrast, lesion size reduction and PAI-based healing rates favored the laser-activated groups. The PAI scores and lesion size in the control group were significantly greater than that in the laser groups (p < 0.05). Conclusions: At the 1-year follow-up, all the groups presented similar FD increases, while the laser irrigation groups presented significantly greater reductions in lesion size than did the control group.
Accurate and timely assessment of burn depth is critical for determining effective treatment strategies and improving patient outcomes. However, traditional diagnostic methods, such as visual inspection and histological analysis, are constrained by subjectivity, invasiveness, and diagnostic delays. Photoacoustic imaging (PAI), a hybrid modality combining optical contrast with ultrasonic resolution, has emerged as a promising tool for biomedical applications due to its high sensitivity to endogenous chromophores and capability for depth-resolved functional imaging. Although various PAI configurations have been investigated for non-invasive burn assessment, a comprehensive synthesis of this specific application is currently lacking. To address this gap, this review provides a detailed overview of the fundamental principles of PAI, evaluates its distinct advantages in burn depth assessment, and discusses current technological advancements, translational challenges, and future perspectives.
Diagnostic integration technology represents a significant advancement in cancer diagnosis and treatment. The combination of fluorescence probe-based imaging methods with photodynamic therapy (PDT) offers distinct advantages due to its high sensitivity and minimally invasive nature. However, the effective detection depth and spatial resolution of fluorescence imaging are limited by light scattering effects in biological tissues. Additionally, high concentrations of GSH in the tumor microenvironment (TME) neutralize reactive oxygen species (ROS) generated by PDT, directly inhibiting therapeutic efficacy. Therefore, developing a highly sensitive, high-resolution fluorescent probe to achieve integrated tumor diagnosis and treatment is of great significance. This study developed an activatable diagnostic-therapeutic probe, MB-2O-MB. In MB-2O-MB, methylene blue (MB) served as both the photosensitizer and signal reporting moiety, while a thiols-sensitive disulfide bond was introduced as the linker and response unit. When the probe reacted with GSH in tumor regions, the disulfide bond broke, causing structural dissociation and releasing free MB molecules. Experiments demonstrated that the probe exhibited strong interference resistance, and high sensitivity (LOD = 57.99 nM) for this reaction. Furthermore, the photoacoustic (PA) signal generated upon probe activation compensated for the limited tissue penetration depth of fluorescence imaging, enabling more precise spatial localization of tumor regions. Therapeutically, upon irradiation with 660 nm near-infrared (NIR) laser light, the released MB efficiently generated singlet oxygen, effectively inducing 4T1 tumor cell death. In vivo data further validated the significant tumor suppression effect of MB-2O-MB via PDT. In summary, MB-2O-MB achieves precise tumor localization and complete eradication through the synergistic combination of NIR fluorescence/PA dual-modality imaging and PDT. This strategy simultaneously overcomes the drug resistance bottleneck and imaging limitations of conventional photodynamic therapy, paving a new pathway for constructing highly selective and potent smart diagnostic and therapeutic systems, and significantly advancing precision medicine.
Multimodal phototheranostics combines multi-dimensional optical imaging with light-activated therapy, offering a promising approach for precise cancer treatment. A major hurdle is creating long-wavelength organic molecules that can concurrently support multiple second near-infrared window (NIR-II) imaging modalities and synergistic phototherapy. Herein, we report a novel donor-acceptor-donor (D-A-D) structured squaraine dye (SQ8), rationally designed and selected via preliminary DFT calculations owing to its narrow bandgap and red-shifted optical properties. Notably, SQ8 spontaneously self-assembles into ordered J-aggregates in aqueous media, yielding an exceptionally red-shifted emission at 1281 nm. This ultra-long NIR-II fluorescence enables high-contrast deep-tissue imaging with superior signal-to-background ratio and spatial resolution. After co-assembly with DSPE-PEG2000, the formed nanoparticles (SQ8@NPs) display excellent water stability, a high photoluminescence quantum yield (PLQY = 0.842%), and a remarkable photothermal conversion efficiency (PCE = 43.3%) under 1064 nm laser irradiation. Leveraging these synergistic properties, SQ8@NPs achieve dual-modal NIR-II fluorescence and photoacoustic imaging (FLI/PAI) and effective light-triggered tumor ablation both in vitro and in vivo. This work not only expands the family of ultra-long wavelength organic fluorophores but also provides a robust paradigm for developing image-guided photothermal therapy (PTT) platforms for deep-seated tumors.
Rational design of nanocarriers as specific multidrug co-delivery systems to overcome the complex disease microenvironment still remains a critical challenge in precision nanomedicine. In this study, using dicarboxyl-functionalized indocyanine green (Bis-COOH-ICG) as an auxiliary ligand coordinated with Zr6 clusters, a defect-engineered and functionalized metal-organic framework (Fun-MOF) with hierarchically micro/mesoporous architectures was successfully developed for tumor photothermal/photodynamic combination therapy (PTT/PDT) as well as photoacoustic/fluorescence dual-modal imaging (PAI/FI). And, the hierarchical Fun-MOF enables efficient co-encapsulation of HSP90 inhibitor 17-AAG and catalase (CAT), thus receiving potent antitumor therapy by inhibiting HSP90 overexpression and scavenging hydrogen peroxide to remodel the hypoxic tumor microenvironment. Additionally, owing to the robust coordination chemistry between Zr6 clusters and carboxyl groups, the defective Fun-MOF also can incorporate other carboxyl-containing small-molecule therapeutics during MOF preparation, making it a universal platform for diverse theranostic applications.
The effectiveness of immunotherapy for hepatocellular carcinoma (HCC) is severely compromised by an immunosuppressive tumor microenvironment (TME) dominated by M2-polarized tumor-associated macrophages (TAMs), coupled with a lack of reliable strategies for real-time treatment monitoring. To address this, we developed a pH-responsive nanoimmunomodulator derived from macrophage exosomes for spatiotemporal TAM reprogramming combined with second near-infrared (NIR-II) theranostics. Our nanoplatform (anti-CD47 conjugated Croc@DMPC/Ag2Te/exosome, termed aCD47-CATE) is functionalized with anti-CD47 antibodies to block the CD47-"don't eat me" signal. For precise theranostics, it co-encapsulates silver telluride quantum dots for high-contrast NIR-II fluorescence imaging and croconaine J-aggregates that serve as efficient photothermal converters (emission >1100 nm) and acid-activated photoacoustic probes. The aCD47-CATE platform integrates acid-activated ratiometric photoacoustic imaging with NIR-II fluorescence for accurate tumor targeting and delineation. It effectively blocks CD47 to promote macrophage phagocytosis while exerting mild photothermal effects under NIR-II irradiation to induce immunogenic cell death. This combined action potently remodels the immunosuppressive TME, achieving significant antitumor efficacy. Transcriptomic profiling validated this mechanism, showing enhanced T-cell and macrophage activation alongside suppressed immunosuppressive signals. Collectively, aCD47-CATE represents a robust and multifaceted theranostic platform for image-guided photothermal immunotherapy in HCC.
Photoacoustic computed tomography (PACT) combines the high optical absorption contrast of optical excitation with the deep tissue penetration enabled by ultrasonic detection, making it a promising imaging modality. However, constraints on transducer density and angular coverage often result in sparse-view acquisitions that cause severe artifacts. In this work, we propose ND-net, a progressive dual-branch adversarial diffusion framework for efficient and high-quality sparse-view PACT reconstruction. The framework uses two stages where a residual artifact-reconstruction branch estimates structured sparse-view artifacts, followed by an adversarially guided full-view diffusion branch that refines structural information. By enabling flexible reverse transitions, ND-net supports large-step diffusion sampling with only four reverse iterations, improving inference efficiency. Experiments on simulated vessel data, circular phantom measurements, and in vivo mouse abdomen imaging demonstrate improved reconstruction quality over representative analytical and learning-based methods under highly sparse acquisition conditions. These results indicate that ND-net improves sparse-view PACT reconstruction while enabling efficient inference.