Quantitative evaluation of the impact of variation of optical parameters on the estimation of blood hematocrit and oxygen saturation for dual-wavelength photoacoustics.

Photoacoustic (PA) spectroscopy is considered to be one of the most effective ways to measure the levels of hematocrit (H) and oxygenation saturation (S O 2) of blood, which are essential for diagnosing blood-related illnesses. This simulation study aims to investigate the impact of individual optical parameters, i.e., optical absorption coefficient (µ a), scattering coefficient (µ s), and anisotropy factor (g), on the accuracy of this technique in estimating the blood properties. We first performed the Monte Carlo simulations, using realistic optical parameters, to obtain the fluence maps for various samples. The wavelengths of the incident light were chosen to be 532, 700, 1000, and 1064 nm. Thereafter, the k-Wave simulations were executed, incorporating those fluence maps to generate the PA signals. The blood properties were obtained using the PA signals. We introduced variations in µ a, µ s, and g ranging from -10% to +10%, -10% to +10%, and -5% to +1%, respectively, at 700 and 1000 nm wavelengths. One parameter, at both wavelengths, was changed at a time, keeping others fixed. Subsequently, we examined how accurately the blood parameters could be determined at physiological hematocrit levels. A 10% variation in µ a induces a 10% change in H estimation but no change in S O 2 determination. Almost no change has been seen for µ s variation. However, a 5% (-5% to 0%) variation in the g factor resulted in approximately 160% and 115% changes in the PA signal amplitudes at 700 and 1000 nm, respectively, leading to ≈125% error in hematocrit estimation and ≈14% deviation in S O 2 assessment when nominal S O 2=70%. It is clear from this study that the scattering anisotropy factor is a very sensitive parameter and a small change in its value can result in large errors in the PA estimation of blood properties. In the future, in vitro experiments with pathological blood (inducing variation in the g parameter) will be performed, and accordingly, the accuracy of the PA technique in quantifying blood H and S O 2 will be evaluated.

High-frequency photoacoustic and ultrasound imaging for skin evaluation: Pilot study for the assessment of a chemical burn.

Skin architecture and its underlying vascular structure could be used to assess the health status of skin. A non-invasive, high resolution and deep imaging modality able to visualize skin subcutaneous layers and vasculature structures could be useful for determining and characterizing skin disease and trauma. In this study, a multispectral high-frequency, linear array-based photoacoustic/ultrasound (PAUS) probe is developed and implemented for the imaging of rat skin in vivo. The study seeks to demonstrate the probe capabilities for visualizing the skin and its underlying structures, and for monitoring changes in skin structure and composition during a 5-day course of a chemical burn. We analayze composition of lipids, water, oxy-hemoglobin, and deoxy-hemoglobin (for determination of oxygen saturation) in the skin tissue. The study successfully demonstrated the high-frequency PAUS imaging probe was able to provide 3D images of the rat skin architecture, underlying vasculature structures, and oxygen saturation, water, lipids and total hemoglobin.

Label-free optical imaging for brain cancer assessment.

Advances in label-free optical imaging offer a promising avenue for brain cancer assessment, providing high-resolution, real-time insights without the need for radiation or exogeneous agents. These cost-effective and intricately detailed techniques overcome the limitations inherent in magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scans by offering superior resolution and more readily accessible imaging options. This comprehensive review explores a variety of such methods, including photoacoustic imaging (PAI), optical coherence tomography (OCT), Raman imaging, and IR microscopy. It focuses on their roles in the detection, diagnosis, and management of brain tumors. By highlighting recent advances in these imaging techniques, the review aims to underscore the importance of label-free optical imaging in enhancing early detection and refining therapeutic strategies for brain cancer.

Multispectral Optoacoustic Tomography Enables In Vivo Anatomical and Functional Assessment of Human Tendons.

Tendon injuries resulting from accidents and aging are increasing globally. However, key tendon functional parameters such as microvascularity and oxygen perfusion remain inaccessible via the currently available clinical diagnostic tools, resulting in disagreements on optimal treatment options. Here, a new noninvasive method for anatomical and functional characterization of human tendons based on multispectral optoacoustic tomography (MSOT) is reported. Healthy subjects are investigated using a hand-held scanner delivering real-time volumetric images. Tendons in the wrist, ankle, and lower leg are imaged in the near-infrared optical spectrum to utilize endogenous contrast from Type I collagen. Morphology of the flexor carpi ulnaris, carpi radialis, palmaris longus, and Achilles tendons are reconstructed in full. The functional roles of the flexor digitorium longus, hallicus longus, and the tibialis posterior tendons have been visualized by dynamic tracking during toe extension-flexion motion. Furthermore, major vessels and microvasculature near the Achilles tendon are localized, and the global increase in oxygen saturation in response to targeted exercise is confirmed by perfusion studies. MSOT is shown to be a versatile tool capable of anatomical and functional tendon assessments. Future studies including abnormal subjects can validate the method as a viable noninvasive clinical tool for tendinopathy management and healing monitoring.

Assessment of Oxygen Saturation in Breast Lesions Using Photoacoustic Imaging: Correlation With Benign and Malignant Disease.

BACKGROUND: Hypoxia is a hallmark of breast cancer (BC). Photoacoustic (PA) imaging, based on the use of laser-generated ultrasound (US), can detect oxygen saturation (So2) in the tissues of breast lesion patients. PURPOSE: To measure the oxygenation status of tissue in and on both sides of the lesion in breast lesion participants using a multimodal Photoacoustic/ultrasound (PA/US) imaging system and to determine the correlation between So2 measured by PA imaging and benign or malignant disease. MATERIALS AND METHODS: Multimodal PA/US imaging and gray-scale US (GSUS) of breast lesion was performed in consecutive breast lesion participants imaged in the US Outpatient Clinic between 2022 and 2023. Dual-wavelength PA imaging was used to measure the So2 value inside the lesion and on both sides of the tissue, and to distinguish benign from malignant lesions based on the So2 value. The ability of So2 to distinguish benign from malignant breast lesions was evaluated by the receiver operating characteristic curve (ROC) and the De-Long test. RESULTS: A total of 120 breast lesion participants (median age, 42.5 years) were included in the study. The malignant lesions exhibited lower So2 levels compared to benign lesions (malignant: 71.30%; benign: 83.81%; P < .01). Moreover, PA/US imaging demonstrates superior diagnostic results compared to GSUS, with an area under the curve (AUC) of 0.89 versus 0.70, sensitivity of 89.58% versus 85.42%, and specificity of 86.11% versus 55.56% at the So2 cut-off value of 78.85 (P < .001). The false positive rate in GSUS reduced by 30.75%, and the false negative rate diminished by 4.16% with PA /US diagnosis. Finally, the So2 on both sides tissues of malignant lesions are lower than that of benign lesions (P < .01). CONCLUSION: PA imaging allows for the assessment of So2 within the lesions of breast lesion patients, thereby facilitating a superior distinction between benign and malignant lesions.

Acoustic resolution photoacoustic Doppler flowmetry for assessment of patient rectal cancer blood perfusion.

Significance: Photoacoustic Doppler flowmetry offers quantitative blood perfusion information in addition to photoacoustic vascular contrast for rectal cancer assessment. Aim: We aim to develop and validate a correlational Doppler flowmetry utilizing an acoustic resolution photoacoustic microscopy (AR-PAM) system for blood perfusion analysis. Approach: To extract blood perfusion information, we implemented AR-PAM Doppler flowmetry consisting of signal filtering and conditioning, A-line correlation, and angle compensation. We developed flow phantoms and contrast agent to systemically investigate the flowmetry's efficacy in a series of phantom studies. The developed correlational Doppler flowmetry was applied to images collected during in vivo AR-PAM for post-treatment rectal cancer evaluation. Results: The linearity and accuracy of the Doppler flow measurement system were validated in phantom studies. Imaging rectal cancer patients treated with chemoradiation demonstrated the feasibility of using correlational Doppler flowmetry to assess treatment response and distinguish residual cancer from cancer-free tumor bed tissue and normal rectal tissue. Conclusions: A new correlational Doppler flowmetry was developed and validated through systematic phantom evaluations. The results of its application to in vivo patients suggest it could be a useful addition to photoacoustic endoscopy for post-treatment rectal cancer assessment.

Development of a cost-effective compact diode-laser-based photoacoustic sensing instrument for breast tissue diagnosis.

Significance: The photoacoustic (PA) technique, a noninvasive pump-probe technique, has found interesting applications in biomedical tissue diagnosis over the last decade. To take it a step further to clinical applications, the PA technique needs to be designed as an instrument focusing on a compact design, reducing the cost, and quickly providing a quantitative diagnosis. Aim: This work presents a design and characterization of a cost-effective, compact PA sensing instrument for biomedical tissue diagnosis. Approach: A compact laser diode case design is developed to house several laser diodes for PA excitation, and a pulsed current supply unit is also developed in-house to power the laser diodes to generate a 25 ns current pulse at a frequency of 20 kHz. After PA experimental data acquisition, the signal's frequency spectra were calculated to characterize the tissue quantitatively and correlated with their mechanobiological properties. Results: The corresponding dominant frequency peak in the PA spectral response (PASR) study was low in the fibrofatty normal breast tissue 0.26±0.03 MHz, compared to the dominant frequency peak of 1.60±0.016 MHz in the fibrocystic disease tissue, which had increased glandular and stromal elements, thereby increased tissue density. The histopathological findings correlated with the PASR results, and the fibrocystic breast disease tissue exhibited a higher dominant frequency peak and energy compared to the normal breast tissue. Conclusions: We experimented with an in vitro PASR study of fibrocystic human breast tissues and successfully differentiated different tissue types using quantitative spectral parameters peak frequency, mean frequency, and spectral energy. This gives the potential to take this technique further for cost-effective and quick clinical applications.

Photoacoustic imaging for cutaneous melanoma assessment: a comprehensive review.

Significance: Cutaneous melanoma (CM) has a high morbidity and mortality rate, but it can be cured if the primary lesion is detected and treated at an early stage. Imaging techniques such as photoacoustic (PA) imaging (PAI) have been studied and implemented to aid in the detection and diagnosis of CM. Aim: Provide an overview of different PAI systems and applications for the study of CM, including the determination of tumor depth/thickness, cancer-related angiogenesis, metastases to lymph nodes, circulating tumor cells (CTCs), virtual histology, and studies using exogenous contrast agents. Approach: A systematic review and classification of different PAI configurations was conducted based on their specific applications for melanoma detection. This review encompasses animal and preclinical studies, offering insights into the future potential of PAI in melanoma diagnosis in the clinic. Results: PAI holds great clinical potential as a noninvasive technique for melanoma detection and disease management. PA microscopy has predominantly been used to image and study angiogenesis surrounding tumors and provide information on tumor characteristics. Additionally, PA tomography, with its increased penetration depth, has demonstrated its ability to assess melanoma thickness. Both modalities have shown promise in detecting metastases to lymph nodes and CTCs, and an all-optical implementation has been developed to perform virtual histology analyses. Animal and human studies have successfully shown the capability of PAI to detect, visualize, classify, and stage CM. Conclusions: PAI is a promising technique for assessing the status of the skin without a surgical procedure. The capability of the modality to image microvasculature, visualize tumor boundaries, detect metastases in lymph nodes, perform fast and label-free histology, and identify CTCs could aid in the early diagnosis and classification of CM, including determination of metastatic status. In addition, it could be useful for monitoring treatment efficacy noninvasively.

Moving Beyond Simulation: Data-Driven Quantitative Photoacoustic Imaging Using Tissue-Mimicking Phantoms.

Accurate measurement of optical absorption coefficients from photoacoustic imaging (PAI) data would enable direct mapping of molecular concentrations, providing vital clinical insight. The ill-posed nature of the problem of absorption coefficient recovery has prohibited PAI from achieving this goal in living systems due to the domain gap between simulation and experiment. To bridge this gap, we introduce a collection of experimentally well-characterised imaging phantoms and their digital twins. This first-of-a-kind phantom data set enables supervised training of a U-Net on experimental data for pixel-wise estimation of absorption coefficients. We show that training on simulated data results in artefacts and biases in the estimates, reinforcing the existence of a domain gap between simulation and experiment. Training on experimentally acquired data, however, yielded more accurate and robust estimates of optical absorption coefficients. We compare the results to fluence correction with a Monte Carlo model from reference optical properties of the materials, which yields a quantification error of approximately 20%. Application of the trained U-Nets to a blood flow phantom demonstrated spectral biases when training on simulated data, while application to a mouse model highlighted the ability of both learning-based approaches to recover the depth-dependent loss of signal intensity. We demonstrate that training on experimental phantoms can restore the correlation of signal amplitudes measured in depth. While the absolute quantification error remains high and further improvements are needed, our results highlight the promise of deep learning to advance quantitative PAI.

Combined ultrasound and photoacoustic C-mode imaging system for skin lesion assessment.

Accurate assessment of the size and depth of infiltration is critical for effectively treating and removing skin cancer, especially melanoma. However, existing methods such as skin biopsy and histologic examination are invasive, time-consuming, and may not provide accurate depth results. We present a novel system for simultaneous and co-localized ultrasound and photoacoustic imaging, with the application for non-invasive skin lesion size and depth measurement. The developed system integrates an acoustical mirror that is placed on an ultrasound transducer, which can be translated within a flexible water tank. This allows for 3D (C-mode) imaging, which is useful for mapping the skin structure and determine the invasion size and depth of lesions including skin cancer. For efficient reconstruction of photoacoustic images, we applied the open-source MUST library. The acquisition time per 2D image is <1 s and the pulse energies are below the legal Maximum Permissible Exposure (MPE) on human skin. We present the depth and resolution capabilities of the setup on several self-designed agar phantoms and demonstrate in vivo imaging on human skin. The setup also features an unobstructed optical window from the top, allowing for simple integration with other optical modalities. The perspective towards clinical application is demonstrated.

Characterization of adnexal lesions using photoacoustic imaging to improve sonographic O-RADS risk assessment.

OBJECTIVE: To assess the impact of photoacoustic imaging (PAI) on the assessment of ovarian/adnexal lesion(s) of different risk categories using the sonographic ovarian-adnexal imaging-reporting-data system (O-RADS) in women undergoing planned oophorectomy. METHOD: This prospective study enrolled women with ovarian/adnexal lesion(s) suggestive of malignancy referred for oophorectomy. Participants underwent clinical ultrasound (US) examination followed by coregistered US and PAI prior to oophorectomy. Each ovarian/adnexal lesion was graded by two radiologists using the US O-RADS scale. PAI was used to compute relative total hemoglobin concentration (rHbT) and blood oxygenation saturation (%sO2 ) colormaps in the region of interest. Lesions were categorized by histopathology into malignant ovarian/adnexal lesion, malignant Fallopian tube only and several benign categories, in order to assess the impact of incorporating PAI in the assessment of risk of malignancy with O-RADS. Malignant and benign histologic groups were compared with respect to rHbT and %sO2 and logistic regression models were developed based on tumor marker CA125 alone, US-based O-RADS alone, PAI-based rHbT with %sO2 , and the combination of CA125, O-RADS, rHbT and %sO2. Areas under the receiver-operating-characteristics curve (AUC) were used to compare the diagnostic performance of the models. RESULTS: There were 93 lesions identified on imaging among 68 women (mean age, 52 (range, 21-79) years). Surgical pathology revealed 14 patients with malignant ovarian/adnexal lesion, two with malignant Fallopian tube only and 52 with benign findings. rHbT was significantly higher in malignant compared with benign lesions. %sO2 was lower in malignant lesions, but the difference was not statistically significant for all benign categories. Feature analysis revealed that rHbT, CA125, O-RADS and %sO2 were the most important predictors of malignancy. Logistic regression models revealed an AUC of 0.789 (95% CI, 0.626-0.953) for CA125 alone, AUC of 0.857 (95% CI, 0.733-0.981) for O-RADS only, AUC of 0.883 (95% CI, 0.760-1) for CA125 and O-RADS and an AUC of 0.900 (95% CI, 0.815-0.985) for rHbT and %sO2 in the prediction of malignancy. A model utilizing all four predictors (CA125, O-RADS, rHbT and %sO2 ) achieved superior performance, with an AUC of 0.970 (95% CI, 0.932-1), sensitivity of 100% and specificity of 82%. CONCLUSIONS: Incorporating the additional information provided by PAI-derived rHbT and %sO2 improves significantly the performance of US-based O-RADS in the diagnosis of adnexal lesions. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Photoacoustic imaging for investigating tumor hypoxia: a strategic assessment.

Hypoxia causes the expression of signaling molecules which regulate cell division, lead to angiogenesis, and further, in the tumor microenvironment, promote resistance to chemotherapy and radiotherapy, and induce metastasis. Photoacoustic imaging (PAI) takes advantage of unique absorption characteristics of chromophores in tissues and provides the opportunity to construct images with a high degree of spatial and temporal resolution. In this review, we discuss the physiologic characteristics of tumor hypoxia, and current applications of PAI using endogenous (label free imaging) and exogenous (organic and inorganic) contrast agents. Features of various methods in terms of their efficacy for determining physiologic and proteomic phenomena are analyzed. This review demonstrates that PAI has the potential to understand tumor growth and metastasis development through measurement of regulatory molecule concentrations, oxygen gradients, and vascular distribution.

Transrectal Absorber Guide Raster-Scanning Optoacoustic Mesoscopy for Label-Free In Vivo Assessment of Colitis.

Optoacoustic imaging (OAI) enables microscale imaging of endogenous chromophores such as hemoglobin at significantly higher penetration depths compared to other optical imaging technologies. Raster-scanning optoacoustic mesoscopy (RSOM) has recently been shown to identify superficial microvascular changes associated with human skin pathologies. In animal models, the imaging depth afforded by RSOM can enable entirely new capabilities for noninvasive imaging of vascular structures in the gastrointestinal tract, but exact localization of intra-abdominal organs is still elusive. Herein the development and application of a novel transrectal absorber guide for RSOM (TAG-RSOM) is presented to enable accurate transabdominal localization and assessment of colonic vascular networks in vivo. The potential of TAG-RSOM is demonstrated through application during mild and severe acute colitis in mice. TAG-RSOM enables visualization of transmural vascular networks, with changes in colon wall thickness, blood volume, and OAI signal intensities corresponding to colitis-associated inflammatory changes. These findings suggest TAG-RSOM can provide a novel monitoring tool in preclinical IBD models, refining animal procedures and underlines the capabilities of such technologies to address inflammatory bowel diseases in humans.

Quantitative photoacoustic tomography with light fluence compensation based on radiance Monte Carlo model.

Objective. Photoacoustic tomography (PAT) is a rapidly evolving imaging modality that provides images with high contrast and spatial resolution showing the optical properties of biological tissues. The photoacoustic pressure is proportional to the product of the optical absorption coefficient and the local light fluence. The essential challenge in reconstructing quantitative images representing spatially varying absorption coefficients is the unknown light fluence. In addition, optical attenuation induces spatial variations in the light fluence, and the heterogeneity of the fluence determines the limits of reconstruction quality and depth.Approach.In this work, a reconstruction enhancement scheme is proposed to compensate for the variation in the light fluence in the absorption coefficient recovery. The inverse problem of the radiance Monte Carlo model describing light transport through the tissue is solved by using an alternating optimization strategy. In the iteration, the absorption coefficients and photon weights are alternately updated.Main results.The method provides highly accurate quantitative images of absorption coefficients in simulations, phantoms, andin vivostudies. The results show that the method has great potential for improving the accuracy of absorption coefficient recovery compared to conventional reconstruction methods that ignore light fluence variations. Comparison with state-of-the-art fluence compensation methods shows significant improvements in root mean square error, normalized mean square absolute distance, and structural similarity metrics.Significance.This method achieves high precision quantitative imaging by compensating for nonuniform light fluence without increasing the complexity and operation of the imaging system.

Nakagami statistics-based photoacoustic spectroscopy used for label-free assessment of bone tissue.

Quick identification of abnormal molecular metabolism of bone tissues is challenging. Photoacoustic (PA) spectroscopy techniques have great potential in molecular imaging. However, most of them are amplitude-dependent and easily affected by the light deposition, especially for bone tissues with high optical scattering. In this Letter, we propose a Nakagami statistics-based PA spectroscopy (NSPS) method for characterizing molecules in bone tissues. We indicate that the NSPS curve can intelligently identify changes in the content of molecules in bone tissues, with a high disturbance-resisting ability. The NSPS has remarkable potential for use in the early and rapid detection of bone diseases.

Burn depth assessment by dual-wavelength light emitting diodes-excited photoacoustic imaging in rats.

Accurate burn depth assessment is crucial to determine treatment plans for burn patients. We have previously proposed a method for performing burn depth assessments based on photoacoustic (PA) imaging, and we have demonstrated the validity of this method, which allows the successful detection of PA signals originating from the blood under the bloodless burned tissue, using rat burn models. Based on these findings, we started a clinical study in which we faced two technical issues: (1) When the burn depth was shallow, PA signals due to skin contamination and/or melanin in the epidermis (surface signals) could not be distinguished from PA signals originating from the blood in the dermis; (2) the size of the system was too large. To solve these issues, we propose a burn depth diagnosis based on dual-wavelength light emitting diodes (LEDs)-excited PA imaging. The use of LEDs rendered the system compact compared to the previous one that used a conventional solid-state laser. We replicated human burned skin by applying a titrated synthetic melanin solution onto the wound surface in albino rat burn models and measured their burn depths by PA excitation at 690 and 850 nm, where melanin and haemoglobin show greatly different absorption coefficients. As a result, the surface signals were eliminated by subtracting the PA signals at 690 nm from those at 850 nm. The resultant estimated burn depths were strongly correlated with the histological assessment results. The validity of the proposed method was also examined using a burn model of rats with real melanin.

Photoacoustic imaging provides an in vivo assessment of the preeclamptic placenta remodeling and function in response to therapy.

INTRODUCTION: There is a lack of effective therapeutic interventions for preeclampsia. A central factor in the etiology of the disease is the development of placental hypoxia due to abnormal vascular remodeling. However, methods to assess the impact of potential therapies on placental growth and remodeling are currently lacking. Here, we develop and validate ultrasound-guided photoacoustic imaging methods to monitor the placental response to therapeutic intervention. Establishing non-invasive tools to image placental function opens up previously unachievable understandings of placental therapeutic response. METHODS: Studies were performed in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. Preclinical research has identified tempol, a superoxide dismutase mimetic, and the phosphodiesterase inhibitor sildenafil as potential therapeutics for preeclampsia, as both improve in vivo maternal outcomes. PA images of the placental environment were acquired in RUPP rats receiving tempol (n = 8) or sildenafil (n = 8) to assess the longitudinal effects of treatment on placental oxygenation and vascular remodeling. Imaging measurements were validated with ex vivo histological analysis. RESULTS: Spectral photoacoustic imaging non-invasively measured placental hypoxia and impaired vascular growth two days after the RUPP procedure was implemented. Sildenafil significantly improved (p < 0.05) placental oxygenation and promoted vascular remodeling in RUPP animals, while RUPP animals treated with tempol had a diminished placental therapeutic response. DISCUSSION: We demonstrate that photoacoustic imaging provides in vivo measures of placental oxygenation and vascular remodeling, a previously unobtainable assessment of preeclamptic therapeutic response. These imaging tools have tremendous potential to accelerate the search for effective therapies for preeclampsia.

Fast raster-scan optoacoustic mesoscopy enables assessment of human melanoma microvasculature in vivo.

Melanoma is associated with angiogenesis and vascular changes that may extend through the entire skin depth. Three-dimensional imaging of vascular characteristics in skin lesions could therefore allow diagnostic insights not available by conventional visual inspection. Raster-scan optoacoustic mesoscopy (RSOM) images microvasculature through the entire skin depth with resolutions of tens of micrometers; however, current RSOM implementations are too slow to overcome the strong breathing motions on the upper torso where melanoma lesions commonly occur. To enable high-resolution imaging of melanoma vasculature in humans, we accelerate RSOM scanning using an illumination scheme that is coaxial with a high-sensitivity ultrasound detector path, yielding 15 s single-breath-hold scans that minimize motion artifacts. We apply this Fast RSOM to image 10 melanomas and 10 benign nevi in vivo, showing marked differences between malignant and benign lesions, supporting the possibility to use biomarkers extracted from RSOM imaging of vasculature for lesion characterization to improve diagnostics.

Assessment of Nanoparticle-Mediated Tumor Oxygen Modulation by Photoacoustic Imaging.

Photoacoustic imaging (PAI) is an invaluable tool in biomedical imaging, as it provides anatomical and functional information in real time. Its ability to image at clinically relevant depths with high spatial resolution using endogenous tissues as contrast agents constitutes its major advantage. One of the most important applications of PAI is to quantify tissue oxygen saturation by measuring the differential absorption characteristics of oxy and deoxy Hb. Consequently, PAI can be utilized to monitor tumor-related hypoxia, which is a crucial factor in tumor microenvironments that has a strong influence on tumor invasiveness. Reactive oxygen species (ROS)-based therapies, such as photodynamic therapy, radiotherapy, and sonodynamic therapy, are oxygen-consuming, and tumor hypoxia is detrimental to their efficacy. Therefore, a persistent demand exists for agents that can supply oxygen to tumors for better ROS-based therapeutic outcomes. Among the various strategies, NP-mediated supplemental tumor oxygenation is especially encouraging due to its physio-chemical, tumor targeting, and theranostic properties. Here, we focus on NP-based tumor oxygenation, which includes NP as oxygen carriers and oxygen-generating strategies to alleviate hypoxia monitored by PAI. The information obtained from quantitative tumor oxygenation by PAI not only supports optimal therapeutic design but also serves as a highly effective tool to predict therapeutic outcomes.

Programmable Acoustic Delay-Line Enabled Low-Cost Photoacoustic Tomography System.

Photoacoustic tomography (PAT) is an emerging technology for biomedical imaging that combines the superiorities of high optical contrast and acoustic penetration. In the PAT system, more PA signals are preferred to be detected from full field of view to reconstruct the PA images with higher fidelity. However, the requirement for more PA signals' detection leads to more time consumption for single-channel scanning-based PAT system or higher cost of data acquisition (DAQ) module for an array-based PAT system. To address this issue, we proposed a programmable acoustic delay-line (PADL) module to reduce DAQ cost and accelerate imaging speed for PAT system. The module is based on bidirectional conversion between acoustic signals and electrical signals, including ultrasound transmission in between to provide sufficient time delay. The acoustic delay-line module achieves tens or hundreds of microseconds' delay for each channel and is controlled by a programmable control unit. In this work, it achieves to merge four inputs of PA signals into one output signal, which can be recovered into original four PA signals in the digital domain after DAQ. The imaging experiments of pencil leads embedded in agar phantom are conducted by the PAT system equipped with the proposed PADL module, which demonstrated its feasibility to reduce the cost of the PAT system. An in vivo study of human finger PAT imaging with delay-line module verified its feasibility for biomedical imaging applications.