Photoacoustic imaging (PAI) is an emerging hybrid imaging modality that combines high-contrast optical imaging with high-spatial-resolution ultrasound imaging. PAI can provide a high spatial resolution and significant imaging depth by utilizing the distinctive spectroscopic characteristics of tissue, which gives it a wide variety of applications in biomedicine and preclinical research. In addition, it is non-ionizing and non-invasive, and photoacoustic (PA) signals are generated by a short-pulse laser under thermal expansion. In this study, we describe the basic principles of PAI, recent advances in research in human and animal tissues, and future perspectives.

Atrial fibrillation (A-fib) is the most common type of heart arrhythmia, typically treated with radiofrequency catheter ablation to isolate the heart from abnormal electrical signals. Monitoring the formation of ablation-induced lesions is crucial for preventing recurrences and complications arising from excessive or insufficient ablation. Existing imaging modalities lack real-time feedback, and their intraoperative usage is in its early stages. A critical need exists for an imaging-based lesion indexing (LSI) method that directly reflects tissue necrosis formation. Previous studies have indicated that spectroscopic photoacoustic (sPA) imaging can differentiate ablated tissues from their non-ablated counterparts based on PA spectrum variation. In this paper, we introduce a method for detecting ablation lesion boundaries using sPA imaging. This approach utilizes ablation LSI, which quantifies the ratio between the signal from ablated tissue and the total tissue signal. We enhance boundary detection accuracy by adapting a regression model-based compensation. Additionally, the method was cross-validated with clinically used intraoperative monitoring parameters. The proposed method was validated with ex vivo porcine cardiac tissues with necrotic lesions created by different ablation durations. The PA-measured lesion size was compared with gross pathology. Statistical analysis demonstrates a strong correlation (R > 0.90) between the PA-detected lesion size and gross pathology. The PA-detected lesion size also exhibits a moderate to strong correlation (R > 0.75) with local impedance changes recorded during procedures. These results suggest that the introduced PA imaging-based LSI has great potential to be incorporated into the clinical workflow, guiding ablation procedures intraoperatively.

This paper presents a comprehensive overview of the potential applications for Photo-Acoustic (PA) imaging employing functional nanoparticles. The exploration begins with an introduction to nanotechnology and nanomaterials, highlighting the advancements in these fields and their crucial role in shaping the future. A detailed discussion of the various types of nanomaterials and their functional properties sets the stage for a thorough examination of the fundamentals of the PA effect. This includes a thorough chronological review of advancements, experimental methodologies, and the intricacies of the source and detection of PA signals. The utilization of amplitude and frequency modulation, design of PA cells, pressure sensor-based signal detection, and quantification methods are explored in-depth, along with additional mechanisms induced by PA signals. The paper then delves into the versatile applications of photoacoustic imaging facilitated by functional nanomaterials. It investigates the influence of nanomaterial shape, size variation, and the role of composition, alloys, and hybrid materials in harnessing the potential of PA imaging. The paper culminates with an insightful discussion on the future scope of this field, focusing specifically on the potential applications of photoacoustic (PA) effect in the domain of biomedical imaging and nanomedicine. Finally, by providing the comprehensive overview, the current work provides a valuable resource underscoring the transformative potential of PA imaging technique in biomedical research and clinical practice.

UNASSIGNED: Photoacoustic imaging (PAI) is an emerging technology that holds high promise in a wide range of clinical applications, but standardized methods for system testing are lacking, impeding objective device performance evaluation, calibration, and inter-device comparisons. To address this shortfall, this tutorial offers readers structured guidance in developing tissue-mimicking phantoms for photoacoustic applications with potential extensions to certain acoustic and optical imaging applications.
UNASSIGNED: The tutorial review aims to summarize recommendations on phantom development for PAI applications to harmonize efforts in standardization and system calibration in the field.
UNASSIGNED: The International Photoacoustic Standardization Consortium has conducted a consensus exercise to define recommendations for the development of tissue-mimicking phantoms in PAI.
UNASSIGNED: Recommendations on phantom development are summarized in seven defined steps, expanding from (1) general understanding of the imaging modality, definition of (2) relevant terminology and parameters and (3) phantom purposes, recommendation of (4) basic material properties, (5) material characterization methods, and (6) phantom design to (7) reproducibility efforts.
UNASSIGNED: The tutorial offers a comprehensive framework for the development of tissue-mimicking phantoms in PAI to streamline efforts in system testing and push forward the advancement and translation of the technology.

Spectral photoacoustic imaging in combination with unmixing techniques may be applied to retrieve information about high-risk features present in atherosclerotic plaques, possibly providing prognostic insights into future stroke events. We present the photoacoustic spectral contrast found in 12 systematically scanned advanced atherosclerotic plaques in the near-infrared wavelength range (850-1250 nm). The main absorbers are lipid, water, and hemoglobin, with the highest photoacoustic intensities at the lipid\'s second overtone at 1190 and 1210 nm. Linear unmixing resulted in visualizing regions with high lipid and hemoglobin absorption, corresponding to the histological presence of lipid and intraplaque hemorrhage. A non-negative matrix factorization approach reveals differences in lipid spectral contrast, providing potential insights into the vulnerability of atherosclerotic plaque. These results provide a reference for future, more complex, in vivo photoacoustic imaging of carotid artery atherosclerosis, potentially contributing to assessing the risk of future events and treatment decision.

Ablation therapy is a type of minimally invasive treatment, utilized for various organs including the brain, heart, and kidneys. The accuracy of the ablation process is critically important to avoid both insufficient and excessive ablation, which may result in compromised efficacy or complications. The thermal ablation is formulated by two theoretical models: the heat transfer (HT) and necrosis formation (NF) models. In modern medical practices, feed-forward (FF) and temperature feedback (TFB) controls are primarily used as ablation control methodologies. FF involves pre-therapy procedure planning based on previous experiences and theoretical knowledge without monitoring the intraoperative tissue response, hence, it can\'t compensate for discrepancies in the assumed HT or NF models. These discrepancies can arise due to individual patient\'s tissue characteristic differences and specific environmental conditions. Conversely, TFB control is based on the intraoperative temperature profile. It estimates the resulting heat damage based on the monitored temperature distribution and assumed NF model. Therefore, TFB can make necessary adjustments even if there is an error in the assumed HT model. TFB is thus seen as a more robust control method against modeling errors in the HT model. Still, TFB is limited as it assumes a fixed NF model, irrespective of the patient or the ablation technique used. An ideal solution to these limitations would be to actively monitor heat damage to the tissue during the operation and utilize this data to control ablation. This strategy is defined as necrosis feedback (NFB) in this study. Such real-time necrosis monitoring modalities making NFB possible are emerging, however, there is an absence of a generalized study that discusses the integration and quantifies the significance of the real-time necrosis monitor techniques for ablation therapy. Such an investigation is expected to clarify the universal principles of how these techniques would improve ablation therapy. In this study, we examine the potential of NFB in suppressing errors associated with the NF model as NFB is theoretically capable of monitoring and suppressing the errors associated with the NF models in its closed control loop. We simulate and compare the performances of TFB and NFB with artificially generated modeling errors using the finite element method (FEM). The results show that NFB provides more accurate ablation control than TFB when NF-oriented errors are applied, indicating NFB\'s potential to improve the ablation control accuracy and highlighting the value of the ongoing research to make real-time necrosis monitoring a clinically viable option.

Liposomal J-Aggregates of Indocyanine Green (L-JA) can serve as a biocompatible and biodegradable nanoparticle for photoacoustic imaging and photothermal therapy. When compared to monomeric IcG, L-JA are characterized by longer circulation, improved photostability, elevated absorption at longer wavelengths, and increased photoacoustic signal generation. However, the documented methods for production of L-JA vary widely. We developed an approach to efficiently form IcG J-aggregates (IcG-JA) directly in liposomes at elevated temperatures. Aggregating within fully formed liposomes ensures particle uniformity and allows for control of J-aggregate size. L-JA have unique properties compared to IcG. L-JA provide significant contrast enhancement in photoacoustic images for up to 24 hours after injection, while IcG and unencapsulated IcG-JA are cleared within an hour. L-JA allow for more accurate photoacoustic-based sO2 estimation and particle tracking compared to IcG. Furthermore, photothermal heating of L-JA with an 852nm laser is demonstrated to be more effective at lower laser powers than conventional 808nm lasers for the first time. The presented technique offers an avenue for formulating a multi-faceted contrast agent for photoacoustic imaging and photothermal therapy that offers significant advantages over other conventional agents.

Atherosclerosis is a primary global health concern due to its high morbidity and mortality. This disease is characterized by a complex interplay of chronic inflammation, oxidative stress, and proteolytic enzymes. Traditional imaging techniques struggle to capture the dynamic biochemical processes within atherosclerotic plaques. Herein, we have developed a novel unimolecular photoacoustic probe (UMAPP) that combines specific recognition sites for neutrophil elastase (NE) and the redox pair O2•‒/GSH into a cohesive molecular platform, allowing in vivo monitoring of oxidative stress and activated neutrophils within plaques. UMAPP features a boron-dipyrromethene (BODIPY) core linked to a hydrophilic NE-cleavable tetrapeptide, and dual oxidative stress-responsive catechol moieties, enabling NE-mediated modulation of photoinduced electron transfer, affecting the photoacoustic intensity at 685 nm (PA685), while oxidation and reduction of the catechol groups by O2•‒ and GSH lead to reversible, ratiometric changes in the photoacoustic spectrum. Preliminary applications of UMAPP have successfully differentiated between atherosclerotic and healthy mice, assessed the impact of pneumonia on plaque composition, and validated the probe\'s efficacy in drug-treatment studies, detecting molecular changes prior to observable histopathological alterations. UMAPP\'s integrated molecular imaging approach holds significant promise for advancing the diagnosis and management of atherosclerosis by enabling earlier and more precise detection of vulnerable plaques.

BACKGROUND: HER2 is a key biomarker for breast cancer treatment and prognosis. Traditional assessment methods like immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are effective but costly and time-consuming. Our model incorporates these methods alongside photoacoustic imaging to enhance diagnostic accuracy and provide more comprehensive clinical insights.
METHODS: A total of 301 breast tumors were included in this study, divided into HER2-positive (3+ or 2+ with gene amplification) and HER2-negative (below 3+ and 2+ without gene amplification) groups. Samples were split into training and validation sets in a 7:3 ratio. Statistical analyses involved t-tests, chi-square tests, and rank-sum tests. Predictive factors were identified using univariate and multivariate logistic regression, leading to the creation of three models: ModA (clinical factors only), ModB (clinical plus ultrasound factors), and ModC (clinical, ultrasound, and photoacoustic imaging-derived oxygen saturation (SO2)).
RESULTS: The area under the curve (AUC) for ModA was 0.756 (95 % CI: 0.69-0.82), ModB increased to 0.866 (95 % CI: 0.82-0.91), and ModC showed the highest performance with an AUC of 0.877 (95 % CI: 0.83-0.92). These results indicate that the comprehensive model combining clinical, ultrasound, and photoacoustic imaging data (ModC) performed best in predicting HER2 expression.
CONCLUSIONS: The findings suggest that integrating clinical, ultrasound, and photoacoustic imaging data significantly enhances the accuracy of predicting HER2 expression. For personalised breast cancer treatment, the integrated model could provide a comprehensive and reproducible decision support tool.

UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.