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To understand complex biological process and disease progression, it is essential to comprehensively track biodynamics across entire organisms. The invaluable tracking tool, photoacoustic computed tomography (PACT), provides insights into structural, functional, and molecular aspects of living tissues. However, current small‐animal PACT systems suffer from low temporal/spatial resolution and a restricted field of view, and they are limited in the biological information they can provide, hindering research on whole‐body biodynamics. Here, it is demonstrated a continuous rotary‐scanning PACT system for rapid monitoring of various parameters within the relatively large torso of a small animal. In this PACT system, a hemispherical transducer array is continuously rotated at high speed, enabling a 3D scan of an entire mouse body in just 54 s, with a spatial resolution of 172–212 µm. The rapid rotary scanning allows us to not only image whole‐body structures but also to monitor pharmacokinetics and changes in hemoglobin oxygen saturation in living animals. This approach holds great promise for advancing the understanding of in vivo biological dynamics, opening up a new avenue of preclinical research in areas such as metabolic diseases and drug delivery. [ABSTRACT FROM AUTHOR]

Photoacoustic computed tomography (PACT) has centimeter‐level imaging ability and can be used to detect the human body. However, strong photoacoustic signals from skin cover deep tissue information, hindering the frontal display and analysis of photoacoustic images of deep regions of interest. Therefore, we propose a 2.5 D deep learning model based on feature pyramid structure and single‐type skin annotation to extract the skin region, and design a mask generation algorithm to remove skin automatically. PACT imaging experiments on the human periphery blood vessel verified the correctness our proposed skin‐removal method. Compared with previous studies, our method exhibits high robustness to the uneven illumination, irregular skin boundary, and reconstruction artifacts in the images, and the reconstruction errors of PACT images decreased by 20% ~ 90% with a 1.65 dB improvement in the signal‐to‐noise ratio at the same time. This study may provide a promising way for high‐definition PACT imaging of deep tissues. [ABSTRACT FROM AUTHOR]

This article reports the fine-tuning of the optical resonance wavelength (ORW) of surface-micromachined optical ultrasound transducer (SMOUT) arrays to enable ultrasound data readout with non-tunable interrogation light sources for photoacoustic computed tomography (PACT). Permanent ORW tuning is achieved by material deposition onto or subtraction from the top diaphragm of each element with sub-nanometer resolution. For demonstration, a SMOUT array is first fabricated, and its ORW is tuned for readout with an 808 nm laser diode (LD). Experiments are conducted to characterize the optical and acoustic performances of the elements within the center region of the SMOUT array. Two-dimensional and three-dimensional PACT (photoacoustic computed tomography) is also performed to evaluate the imaging performance of the ORW-tuned SMOUT array. The results show that the ORW tuning does not degrade the optical, acoustic, and overall imaging performances of the SMOUT elements. As a result, the fine-tuning method enables new SMOUT-based PACT systems that are low cost, compact, powerful, and even higher speed, with parallel readout capability. [ABSTRACT FROM AUTHOR]

Significance: Many techniques exist for screening retinal phenotypes in mouse models in vision research, but significant challenges remain for efficiently probing higher visual centers of the brain. Photoacoustic computed tomography (PACT), with optical sensitivity to hemodynamic response (HR) in brain and ultrasound resolution, provides unique advantages in comprehensively assessing higher visual function in the mouse brain. Aim: We aim to examine the reliability of PACT in the functional phenotyping of mouse models for vision research. Approach: A PACT-ultrasound (US) parallel imaging system was established with a one-dimensional (1D) US transducer array and a tunable laser. Imaging was performed at three coronal planes of the brain, covering the primary visual cortex and the four subcortical nuclei, including the superior colliculus, the dorsal lateral geniculate nucleus, the suprachiasmatic nucleus, and the olivary pretectal nucleus. The visual-evoked HR was isolated from background signals using an impulsebased data processing protocol. rd1 mice with rod/cone degeneration, melanopsinknockout (mel-KO) mice with photoreceptive ganglion cells that lack intrinsic photosensitivity, and wild-type mice as controls were imaged. The quantitative characteristics of the visual-evoked HR were compared. Results: Quantitative analysis of the HRs shows significant differences among the three mouse strains: (1) rd1 mice showed both smaller and slower responses compared with wild type (n = 10;10, p < 0.01) and (2) mel-KO mice had lower amplitude but not significantly delayed photoresponses than wild-type mice (n = 10;10, p < 0.01). These results agree with the known visual deficits of the mouse strains. Conclusions: PACT demonstrated sufficient sensitivity to detecting post-retinal functional deficits. [ABSTRACT FROM AUTHOR]

Significance: Photoacoustic computed tomography (PACT) is a promising noninvasive imaging technique for both life science and clinical implementations. To achieve fast imaging speed, modern PACT systems have equipped arrays that have hundreds to thousands of ultrasound transducer (UST) elements, and the element number continues to increase. However, large number of UST elements with parallel data acquisition could generate a massive data size, making it very challenging to realize fast image reconstruction. Although several research groups have developed GPU-accelerated method for PACT, there lacks an explicit and feasible step-by-step description of GPU-based algorithms for various hardware platforms. Aim: In this study, we propose a comprehensive framework for developing GPU-accelerated PACT image reconstruction (GPU-accelerated photoacoustic computed tomography), to help the research community to grasp this advanced image reconstruction method. Approach: We leverage widely accessible open-source parallel computing tools, including Python multiprocessing-based parallelism, Taichi Lang for Python, CUDA, and possible other backends. We demonstrate that our framework promotes significant performance of PACT reconstruction, enabling faster analysis and real-time applications. Besides, we also described how to realize parallel computing on various hardware configurations, including multicore CPU, single GPU, and multiple GPUs platform. Results: Notably, our framework can achieve an effective rate of ~871 times when reconstructing extremely large-scale three-dimensional PACT images on a dual-GPU platform compared to a 24-core workstation CPU. In this paper, we share example codes via GitHub. Conclusions: Our approach allows for easy adoption and adaptation by the research community, fostering implementations of PACT for both life science and medicine. [ABSTRACT FROM AUTHOR]

This article reports the fine-tuning of the optical resonance wavelength (ORW) of surface-micromachined optical ultrasound transducer (SMOUT) arrays to enable ultrasound data readout with non-tunable interrogation light sources for photoacoustic computed tomography (PACT). Permanent ORW tuning is achieved by material deposition onto or subtraction from the top diaphragm of each element with sub-nanometer resolution. For demonstration, a SMOUT array is first fabricated, and its ORW is tuned for readout with an 808 nm laser diode (LD). Experiments are conducted to characterize the optical and acoustic performances of the elements within the center region of the SMOUT array. Two-dimensional and three-dimensional PACT (photoacoustic computed tomography) is also performed to evaluate the imaging performance of the ORW-tuned SMOUT array. The results show that the ORW tuning does not degrade the optical, acoustic, and overall imaging performances of the SMOUT elements. As a result, the fine-tuning method enables new SMOUT-based PACT systems that are low cost, compact, powerful, and even higher speed, with parallel readout capability.

Combining the diffusive laser excitation and the photoacoustic signals detection, photoacoustic computed tomography (PACT) is uniquely suited for deep tissue imaging. A diffraction-limited ultrasound point detector is highly desirable for maximizing the spatial resolution and the field-of-view of the reconstructed volumetric images. Among all the available ultrasound detectors, micro-ring resonator (MRR) based ultrasound detectors offer the lowest area-normalized limit of detection (nLOD) in a miniature form-factor, making it an ideal candidate as an ultrasound point detector. However, despite their wide adoption for photoacoustic imaging, the underlying signal transduction process has not been systematically studied yet. Here we report a comprehensive theoretical model capturing the transduction of incident acoustic signals into digital data, and the associated noise propagation process, using experimentally calibrated key process parameters. The theoretical model quantifies the signal-to-noise ratio (SNR) and the nLOD under the influence of the key process variables, including the quality factor (Q-factor) of the MRR and the driving wavelength. While asserting the need for higher Q-factors, the theoretical model further quantifies the optimal driving wavelength for optimizing the nLOD. Given the MRR with a Q-factor of 1 × 105, the theoretical model predicts an optimal SNR of 30.1 dB and a corresponding nLOD of 3.75 × 10−2 mPa mm2/Hz1/2, which are in good agreement with the experimental measurements of 31.0 dB and 3.39 × 10−2 mPa mm2/Hz1/2, respectively. The reported theoretical model can be used in guiding the optimization of MRR-based ultrasonic detectors and PA experimental conditions, in attaining higher imaging resolution and contrast. The optimized operating condition has been further validated by performing PACT imaging of a human hair phantom.

Photoacoustic computed tomography (PACT) is a hybrid imaging modality that combines optical excitation and acoustic detection techniques. It obtains high‐resolution deep‐tissue images based on the deep penetration of light, the anisotropy of light absorption in objects, and the photoacoustic effect. Hence, PACT shows great potential in biomedical sample imaging. Recently, due to its advantages of high sensitivity to optical absorption and wide scalability of spatial resolution with the desired imaging depth, PACT has received increasing attention in preclinical and clinical practice. To date, there has been a proliferation of PACT systems designed for specific biomedical imaging applications, from small animals to human organs, from ex vivo to in vivo real‐time imaging, and from simple structural imaging to functional and molecular imaging with external contrast agents. Therefore, it is of great importance to summarize the previous applications of PACT systems in biomedical imaging and clinical practice. In this review, we searched for studies related to PACT imaging of biomedical tissues and samples over the past two decades; divided the studies into two categories, PACT imaging of preclinical animals and PACT imaging of human organs and body parts; and discussed the significance of the studies. Finally, we pointed out the future directions of PACT in biomedical applications. With the development of exogenous contrast agents and advances of imaging technique, in the future, PACT will enable biomedical imaging from organs to whole bodies, from superficial vasculature to internal organs, from anatomy to functions, and will play an increasingly important role in biomedical research and clinical practice. [ABSTRACT FROM AUTHOR]

Most photoacoustic computed tomography (PACT) systems usually ignore the anisotropy of the tissue absorption coefficient, which will lead to the lack of information in reconstructed images. In this work, the effect is addressed of the possible optical absorption anisotropy of tissue on PACT images. The functional relationship is derived between the photoacoustic response and the polarization angle of the excitation light. An adaptive polarized light photoacoustic imaging (AP-PACT) approach is proposed and shown to make up for the lack of imaging information and achieve optimal image contrast when imaging samples with anisotropic optical absorption, by utilizing the standard deviation of photoacoustic response as the feedback signal in an adaptive data acquisition process. The method is implemented both on phantom and in vitro experiments, which show that AP-PACT can recover anisotropic absorption-related information from reconstructed images and thus significantly improve their quality.

Abstract Photoacoustic computed tomography (PACT) is a hybrid imaging modality that combines optical excitation and acoustic detection techniques. It obtains high‐resolution deep‐tissue images based on the deep penetration of light, the anisotropy of light absorption in objects, and the photoacoustic effect. Hence, PACT shows great potential in biomedical sample imaging. Recently, due to its advantages of high sensitivity to optical absorption and wide scalability of spatial resolution with the desired imaging depth, PACT has received increasing attention in preclinical and clinical practice. To date, there has been a proliferation of PACT systems designed for specific biomedical imaging applications, from small animals to human organs, from ex vivo to in vivo real‐time imaging, and from simple structural imaging to functional and molecular imaging with external contrast agents. Therefore, it is of great importance to summarize the previous applications of PACT systems in biomedical imaging and clinical practice. In this review, we searched for studies related to PACT imaging of biomedical tissues and samples over the past two decades; divided the studies into two categories, PACT imaging of preclinical animals and PACT imaging of human organs and body parts; and discussed the significance of the studies. Finally, we pointed out the future directions of PACT in biomedical applications. With the development of exogenous contrast agents and advances of imaging technique, in the future, PACT will enable biomedical imaging from organs to whole bodies, from superficial vasculature to internal organs, from anatomy to functions, and will play an increasingly important role in biomedical research and clinical practice.

Non‐alcoholic fatty liver disease is the most common liver disorder worldwide, which strongly correlates to obesity, diabetes, and metabolic syndromes. Complementary to mainstream liver diagnostic modalities, photoacoustic tomography (PAT) can provide high‐speed images with functional optical contrast. However, PAT has not been demonstrated to study fatty liver anatomy with clear volumetric vasculatures. The livers of multiple rats are non‐invasively imaged in vivo using the recently developed 3D PAT platform. The system provides isotropically high spatial resolution in 3D space, presenting clear angiographic structures of rat livers without injecting contrast agents. Furthermore, to quantitatively analyze the difference between the livers of lean and obese rats, the authors measured several PAT features and statistical differences between the two groups are observed. In addition to the anatomy, a time‐gated strategy is applied to correct respiration‐induced motion artifacts and extracted the hemodynamics of major blood vessels during the breathing cycles. This study demonstrates the capabilities of 3D‐PAT to reveal both angiographic anatomy and function in rat livers, providing hematogenous information for fatty liver diagnosis. 3D‐PAT, as a new tool for preclinical research, warrants further improvements to be transferred to human pediatric liver imaging. [ABSTRACT FROM AUTHOR]

Intravenous injection is a rapid, low-cost, and direct method that is commonly used to deliver multifarious biotherapeutics and vaccines. However, intravenous injection often causes trauma or tissue injury that requires professional operation. Transdermal drug delivery overcomes the aforementioned defects, and the microneedles (MNs) array is one of the most promising transdermal drug delivery platforms. Timely, precise, and non-invasive monitoring and evaluation of the effects of MNs in transdermal administration is significant to the research of drug efficiency response to specific diseases. In this sense, photoacoustic computed tomography (PACT), which provides wavelength-selective and deep-penetrating optical contrast, could be a promising imaging tool for in situ evaluation of the treatment effects. In this work, we propose the use of PACT to non-invasively assess the effects of real-time drug delivery in glioma tumors through transdermal administration with degradable indocyanine green-loaded hyaluronic acid MNs (ICG-HA-MNs). The outcome is systematically and quantitatively compared with that via intravenous injection. It is found that the photoacoustic signals of ICG in the tumor site express a faster elevation and shorter duration time in the intravenous injection group; by contrast, the photoacoustic signals demonstrate a lower intensity but prolonged duration time in the MNs group. The observed phenomenon indicates faster response but shorter drug duration for intravenous injection, which is in contrast with the lower loading but prolonged performance for transdermal drug delivery with MNs. These results exhibit good consistency with the earlier, common-sense findings reported from other aspects, confirming that PACT can serve as a potential imaging tool to precisely, non-invasively, and quickly evaluate in situ drug delivery effects and provide constructive guidance for the design and fabrication of microneedles. [ABSTRACT FROM AUTHOR]

Acoustically detecting the optical absorption contrast, photoacoustic imaging (PAI) is a highly versatile imaging modality that can provide anatomical, functional, molecular, and metabolic information of biological tissues. PAI is highly scalable and can probe the same biological process at various length scales ranging from single cells (microscopic) to the whole organ (macroscopic). Using hemoglobin as the endogenous contrast, PAI is capable of label-free imaging of blood vessels in the brain and mapping hemodynamic functions such as blood oxygenation and blood flow. These imaging merits make PAI a great tool for studying ischemic stroke, particularly for probing into hemodynamic changes and impaired cerebral blood perfusion as a consequence of stroke. In this narrative review, we aim to summarize the scientific progresses in the past decade by using PAI to monitor cerebral blood vessel impairment and restoration after ischemic stroke, mostly in the preclinical setting. We also outline and discuss the major technological barriers and challenges that need to be overcome so that PAI can play a more significant role in preclinical stroke research, and more importantly, accelerate its translation to be a useful clinical diagnosis and management tool for human strokes. [ABSTRACT FROM AUTHOR]

Purpose: Noninvasive detection of high-risk plaques is still challenging. In this study, we aimed to noninvasively assess αvβ3-integrin expression using a customed photoacoustic (PA) computed tomography (PACT)/ultrasound (US) system in atherosclerotic lesions of varying degrees of severity and to explore its potential value for detecting high-risk plaques. Methods: We constructed αvβ3-integrin-targeted ultrasmall gold nanorods (AuNRs) with cyclo Arg-Gly-Asp (cRGD) and tested their properties. Employing C57BL/6 J (wild-type, WT) mice and apolipoprotein E gene knockout (ApoE−/−) mice fed either a chow diet or a high-fat/high-cholesterol diet (HFHCD), we established varying degrees of lesion severity. In vivo PACT/US imaging was performed to assess αvβ3-integrin expression in the 4 groups by cRGD-AuNRs. Further histopathologic examination was conducted to evaluate the plaque vulnerability indicators. Results: The data showed that cRGD-AuNRs exhibited excellent photothermal conversion capacity, stability, targeting ability, and biocompatibility. The immunohistochemical results indicated that αvβ3-integrin was upregulated with increasing aggravation of the lesions. In vivo PACT/US imaging showed good consistency with αvβ3-integrin expression. Notably, ApoE−/− mice fed a HFHCD showed an abrupt PA intensity increase compared with the other groups. The histopathologic examination verified that the atherosclerotic plaques of ApoE−/− mice fed the HFHCD developed unstable phenotypes. Correlation analysis showed that PA intensity was mainly related to inflammation and angiogenesis among all of the indicators. Conclusion: Our data indicated that αvβ3-integrin is an effective indicator of plaque instability, and noninvasive PACT/US molecular imaging assessment of αvβ3-integrin holds promise in detecting high-risk plaques. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging (PAI) has been developed, and photoacoustic computed tomography (PACT) is widely used for in vivo tissue and mouse imaging. Simulated annealing (SA) algorithm solves optimization problems, and compressed sensing (CS) recovers sparse signals from undersampled measurements. We aim to develop an advanced sparse imaging framework for PACT, which invloves the use of SA to find an optimal sparse array element distribution and CS to perform sparse imaging. PACT reconstructions were performed using a dummy and porcine liver phantoms. Compared to traditional sparse reconstruction algorithms, the proposed method recovers signals using few ultrasonic transducer elements, enabling high-speed, low-cost PACT for practical application. [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is characterized by the sudden interruption of blood supply to the brain, resulting in neurological impairments and even mortality. Photoacoustic computed tomography (PACT) integrates the high contrast of optical imaging and the penetration of ultrasound imaging, enabling non-invasive IS evaluation. However, the image reconstruction quality significantly affects the oxyhemoglobin saturation (sO 2 ) estimation. This study investigates a model-based with total variation minimized by augmented Lagrangian and alternating direction (MB-TVAL3) approach and compared it with the widely used back-projection (BP) and delay-and-sum (DAS) algorithms. Both simulations and in vivo experiments are conducted to validate the performance of the MB-TVAL3 algorithm, showing a higher sO 2 estimation accuracy and sensitivity in detecting infarct area compared to BP and DAS. The findings of this study emphasize the impact of acoustic inverse problem on the accuracy of sO 2 estimation and the proposed approach offers valuable support for IS evaluation and cerebrovascular diagnosis., (© 2024 Wiley‐VCH GmbH.)

Photoacoustic imaging (PAI) has been developed, and photoacoustic computed tomography (PACT) is widely used for in vivo tissue and mouse imaging. Simulated annealing (SA) algorithm solves optimization problems, and compressed sensing (CS) recovers sparse signals from undersampled measurements. We aim to develop an advanced sparse imaging framework for PACT, which invloves the use of SA to find an optimal sparse array element distribution and CS to perform sparse imaging. PACT reconstructions were performed using a dummy and porcine liver phantoms. Compared to traditional sparse reconstruction algorithms, the proposed method recovers signals using few ultrasonic transducer elements, enabling high-speed, low-cost PACT for practical application.

Full-ring dual-modal ultrasound and photoacoustic computed tomography has unique advantages of nearly isotropic spatial resolution, complementary contrast, deep penetration, and full-view detection. However, the imaging quality may be deteriorated by the inaccurate sound speed estimation. Automatic determining and compensation for sound speed has been a long-standing problem in image reconstruction. Here, we present new adaptive dual-speed ultrasound and photoacoustic computed tomography (ADS-USPACT) to address this challenge. The system features full-view coverage (360°), high-speed dual-modal imaging (10-Hz), automated dual sound speed correction, and synergistic high imaging quality. To correct the sound speed, we develop a two-compartment method that can automatically segment the sample boundary and search for the optimal sound speed based on the rich ultrasonic pulse-echo signals. The method does not require the operator’s intervention. We validate this technique in numerical simulation, phantom study, and in vivo experiments. The ADS-USPACT represents significant progress in dual-modal imaging.

Recently, indocyanine green (ICG), as an FDA-approved dye, has been widely used for phototherapy. It is essential to obtain information on the migration and aggregation of ICG in deep tissues. However, existing fluorescence imaging platforms are not able to obtain the structural information of the tissues. Here, we prepared ICG liposomes (ICG-Lips) and built a dual-wavelength photoacoustic computed tomography (PACT) system with piezoelectric ring-array transducer to image the aggregation of ICG-Lips in tumors to guide phototherapy. Visible 780 nm light excited the photoacoustic (PA) effects of the ICG-Lips and near-infrared 1064 nm light provided the imaging of the surrounding tissues. The aggregation of ICG-Lips within the tumor and the surrounding tissues was visualized by PACT in real time. This work indicates that PACT with piezoelectric ring-array transducer has great potential in the real-time monitoring of in vivo drug distribution. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging (PAI) is a noninvasive biomedical imaging technology capable of multiscale imaging of biological samples from organs down to cells. Multiscale PAI requires different ultrasound transducers that are flat or focused because the current widely-used piezoelectric transducers are rigid and lack the flexibility to tune their spatial ultrasound responses. Inspired by the rapidly-developing flexible photonics, we exploited the inherent flexibility and low-loss features of optical fibers to develop a flexible fiber-laser ultrasound sensor (FUS) for multiscale PAI. By simply bending the fiber laser from straight to curved geometry, the spatial ultrasound response of the FUS can be tuned for both wide-view optical-resolution photoacoustic microscopy at optical diffraction-limited depth (~1 mm) and photoacoustic computed tomography at optical dissipation-limited depth of several centimeters. A radio-frequency demodulation was employed to get the readout of the beat frequency variation of two orthogonal polarization modes in the FUS output, which ensures low-noise and stable ultrasound detection. Compared to traditional piezoelectrical transducers with fixed ultrasound responses once manufactured, the flexible FUS provides the freedom to design multiscale PAI modalities including wearable microscope, intravascular endoscopy, and portable tomography system, which is attractive to fundamental biological/medical studies and clinical applications.

Multispectral photoacoustic (PA) imaging faces two major challenges: the spectral coloring effect, which has been studied extensively as an optical inversion problem, and the spectral crosstalk, which is basically a result of non-ideal acoustic inversion. So far, there is no systematic work to analyze the spectral crosstalk because acoustic inversion and spectroscopic measurement are always treated as decoupled. In this work, we theorize and demonstrate through a series of simulations and experiments how imperfect acoustic inversion induces inaccurate PA spectrum measurement. We provide detailed analysis to elucidate how different factors, including limited bandwidth, limited view, light attenuation, out-of-plane signal, and image reconstruction schemes, conspire to render the measured PA spectrum inaccurate. We found that the model-based reconstruction outperforms universal back-projection in suppressing the spectral crosstalk in some cases.

Photoacoustic computed tomography (PACT), a hybrid imaging modality combining optical excitation with acoustic detection, has rapidly emerged as a prominent biomedical imaging technique. We review the challenges and advances of PACT, including (1) limited view, (2) anisotropy resolution, (3) spatial aliasing, (4) acoustic heterogeneity (speed of sound mismatch), and (5) fluence correction of spectral unmixing. We performed a comprehensive literature review to summarize the key challenges in PACT toward practical applications and discuss various solutions. There is a wide range of contributions from both industry and academic spaces. Various approaches, including emerging deep learning methods, are proposed to improve the performance of PACT further. We outline contemporary technologies aimed at tackling the challenges in PACT applications. [ABSTRACT FROM AUTHOR]

The investigation of neuronal activity in non-human primate models is of critical importance due to their genetic similarity to human brains. In this study, we tested the feasibility of using photoacoustic imaging for the detection of cortical and subcortical responses due to peripheral electrical stimulation in a squirrel monkey model. Photoacoustic computed tomography and photoacoustic microscopy were applied on squirrel monkeys for real-time deep subcortical imaging and optical-resolution cortical imaging, respectively. The electrically evoked hemodynamic changes in primary somatosensory cortex, premotor cortices, primary motor cortex, and underlying subcortical areas were measured. Hemodynamic responses were observed in both cortical and subcortical brain areas at the cortices during external stimulation, demonstrating the feasibility of photoacoustic technique for functional imaging of non-human primate brain.

Significance: Many techniques exist for screening retinal phenotypes in mouse models in vision research, but significant challenges remain for efficiently probing higher visual centers of the brain. Photoacoustic computed tomography (PACT), with optical sensitivity to hemodynamic response (HR) in brain and ultrasound resolution, provides unique advantages in comprehensively assessing higher visual function in the mouse brain., Aim: We aim to examine the reliability of PACT in the functional phenotyping of mouse models for vision research., Approach: A PACT-ultrasound (US) parallel imaging system was established with a one-dimensional (1D) US transducer array and a tunable laser. Imaging was performed at three coronal planes of the brain, covering the primary visual cortex and the four subcortical nuclei, including the superior colliculus, the dorsal lateral geniculate nucleus, the suprachiasmatic nucleus, and the olivary pretectal nucleus. The visual-evoked HR was isolated from background signals using an impulse-based data processing protocol. rd1 mice with rod/cone degeneration, melanopsin-knockout (mel-KO) mice with photoreceptive ganglion cells that lack intrinsic photosensitivity, and wild-type mice as controls were imaged. The quantitative characteristics of the visual-evoked HR were compared., Results: Quantitative analysis of the HRs shows significant differences among the three mouse strains: (1)  rd1 mice showed both smaller and slower responses compared with wild type ( n = 10,10 , p < 0.01 ) and (2) mel-KO mice had lower amplitude but not significantly delayed photoresponses than wild-type mice ( n = 10,10 , p < 0.01 ). These results agree with the known visual deficits of the mouse strains., Conclusions: PACT demonstrated sufficient sensitivity to detecting post-retinal functional deficits., (© 2024 The Authors.)

Intravenous injection is a rapid, low-cost, and direct method that is commonly used to deliver multifarious biotherapeutics and vaccines. However, intravenous injection often causes trauma or tissue injury that requires professional operation. Transdermal drug delivery overcomes the aforementioned defects, and the microneedles (MNs) array is one of the most promising transdermal drug delivery platforms. Timely, precise, and non-invasive monitoring and evaluation of the effects of MNs in transdermal administration is significant to the research of drug efficiency response to specific diseases. In this sense, photoacoustic computed tomography (PACT), which provides wavelength-selective and deep-penetrating optical contrast, could be a promising imaging tool for in situ evaluation of the treatment effects. In this work, we propose the use of PACT to non-invasively assess the effects of real-time drug delivery in glioma tumors through transdermal administration with degradable indocyanine green-loaded hyaluronic acid MNs (ICG-HA-MNs). The outcome is systematically and quantitatively compared with that via intravenous injection. It is found that the photoacoustic signals of ICG in the tumor site express a faster elevation and shorter duration time in the intravenous injection group; by contrast, the photoacoustic signals demonstrate a lower intensity but prolonged duration time in the MNs group. The observed phenomenon indicates faster response but shorter drug duration for intravenous injection, which is in contrast with the lower loading but prolonged performance for transdermal drug delivery with MNs. These results exhibit good consistency with the earlier, common-sense findings reported from other aspects, confirming that PACT can serve as a potential imaging tool to precisely, non-invasively, and quickly evaluate in situ drug delivery effects and provide constructive guidance for the design and fabrication of microneedles.

Significance: Photoacoustic computed tomography (PACT) is a promising non-invasive imaging technique for both life science and clinical implementations. To achieve fast imaging speed, modern PACT systems have equipped arrays that have hundreds to thousands of ultrasound transducer (UST) elements, and the element number continues to increase. However, large number of UST elements with parallel data acquisition could generate a massive data size, making it very challenging to realize fast image reconstruction. Although several research groups have developed GPU-accelerated method for PACT, there lacks an explicit and feasible step-by-step description of GPU-based algorithms for various hardware platforms., Aim: In this study, we propose a comprehensive framework for developing GPU-accelerated PACT image reconstruction (GPU-accelerated photoacoustic computed tomography), to help the research community to grasp this advanced image reconstruction method., Approach: We leverage widely accessible open-source parallel computing tools, including Python multiprocessing-based parallelism, Taichi Lang for Python, CUDA, and possible other backends. We demonstrate that our framework promotes significant performance of PACT reconstruction, enabling faster analysis and real-time applications. Besides, we also described how to realize parallel computing on various hardware configurations, including multicore CPU, single GPU, and multiple GPUs platform., Results: Notably, our framework can achieve an effective rate of ∼ 871 times when reconstructing extremely large-scale three-dimensional PACT images on a dual-GPU platform compared to a 24-core workstation CPU. In this paper, we share example codes via GitHub., Conclusions: Our approach allows for easy adoption and adaptation by the research community, fostering implementations of PACT for both life science and medicine., (© 2024 The Authors.)

Photoacoustic imaging (PAI), featuring rich contrast, high spatial/temporal resolution and deep penetration, is one of the fastest-growing biomedical imaging technology over the last decade. To date, numbers of handheld and semi-handheld photoacoustic imaging devices have been reported with corresponding potential clinical applications. Here, we summarize emerged handheld and semi-handheld systems in terms of photoacoustic computed tomography (PACT), optoacoustic mesoscopy (OAMes), and photoacoustic microscopy (PAM). We will discuss each modality in three aspects: laser delivery, scanning protocol, and acoustic detection. Besides new technical developments, we also review the associated clinical studies, and the advantages/disadvantages of these new techniques. In the end, we propose the challenges and perspectives of miniaturized PAI in the future.

Linear‐array photoacoustic computed tomography (LA‐PACT), for its flexibility and simplicity, has great potential in providing anatomical and functional information of tissues. However, the limited coverage view impedes the LA‐PACT obtaining high‐quality images. In this study, a photoacoustic tomographic system with a hyperbolic‐array transducer was developed for stereoscopic PA imaging of carotid artery. The hyperbolic‐array PACT increases the receiving sensitivity for PA signal detection due to its transducer's geometric structure matching with the spherical wave. The control phantom experiment shows that the proposed system can expand the angular coverage of ∼1/3 more than that of the LA‐PACT system, and the volumetric PA images of rat's carotid artery demonstrates the potential of the system for carotid artery imaging. Furthermore, volumetric imaging of the human forearm verifies that the system has significant capability in human imaging, which indicates that it has bright prospect for assisting diagnosis in the vascular disease. [ABSTRACT FROM AUTHOR]

Recently, indocyanine green (ICG), as an FDA-approved dye, has been widely used for phototherapy. It is essential to obtain information on the migration and aggregation of ICG in deep tissues. However, existing fluorescence imaging platforms are not able to obtain the structural information of the tissues. Here, we prepared ICG liposomes (ICG-Lips) and built a dual-wavelength photoacoustic computed tomography (PACT) system with piezoelectric ring-array transducer to image the aggregation of ICG-Lips in tumors to guide phototherapy. Visible 780 nm light excited the photoacoustic (PA) effects of the ICG-Lips and near-infrared 1064 nm light provided the imaging of the surrounding tissues. The aggregation of ICG-Lips within the tumor and the surrounding tissues was visualized by PACT in real time. This work indicates that PACT with piezoelectric ring-array transducer has great potential in the real-time monitoring of in vivo drug distribution.

Abstract Neoadjuvant chemotherapy (NAC) has contributed to improving breast cancer outcomes, and it would ideally reduce the need for definitive breast surgery in patients who have no residual cancer after NAC treatment. However, there is no reliable noninvasive imaging modality accepted as the routine method to assess response to NAC. Because of the inability to detect complete response, post‐NAC surgery remains the standard of care. To overcome this limitation, a single‐breath‐hold photoacoustic computed tomography (SBH‐PACT) system is developed to provide contrast similar to that of contrast‐enhanced magnetic resonance imaging, but with much higher spatial and temporal resolution and without injection of contrast chemicals. SBH‐PACT images breast cancer patients at three time points: before, during, and after NAC. The analysis of tumor size, blood vascular density, and irregularity in the distribution and morphology of the blood vessels on SBH‐PACT accurately identifies response to NAC as confirmed by the histopathological diagnosis. SBH‐PACT shows its near‐term potential as a diagnostic tool for assessing breast cancer response to systemic treatment by noninvasively measuring the changes in cancer‐associated angiogenesis. Further development of SBH‐PACT may also enable serial imaging, rather than the use of current invasive biopsies, to diagnose and follow indeterminate breast lesions.

By providing complementary functional information, photoacoustic (PA) breast imaging based on the handheld ultrasound (US) probe has demonstrated promising potential for breast cancer diagnosis. However, the quantitative PA imaging primarily relies on the knowledge of the optical fluence distribution in the three-dimensional (3D) heterogeneous breast tissue. Previous studies based on the handheld system generally provided two-dimensional (2D) B-scan results, which contains limited anatomical information of the tissue and the lesion. This study proposed a method to perform 3D modeling of the photon transportation for dual-modality PA/US system based on the local 3D breast anatomical information by scanning US probe. Then the calculated optical fluence distribution can be used for PA imaging. Our phantom and clinical pilot study results demonstrated that this method has potential to improve the accuracy of the quantitative PA breast imaging, and it can also be used in other clinical implementations.

For many optical imaging modalities, image qualities are inevitably degraded by wavefront distortions caused by varying light speed. In optical microscopy and astronomy, adaptive optics (AO) has long been applied to compensate for such unwanted aberrations. Photoacoustic computed tomography (PACT), despite relying on the ultrasonic wave for image formation, suffers from the acoustic version of the same problem. However, this problem has traditionally been regarded as an inverse problem of jointly reconstructing both the initial pressure and the sound speed distributions. In this work, we proposed a method similar to indirect wavefront sensing in AO. We argued that wavefront distortions can be extracted and corrected by a frequency domain analysis of local images. In addition to an adaptively reconstructed aberration-free image, the speed of sound map can be subsequently estimated. We demonstrated the method by in silico, phantom, and in vivo experiments.

Neoadjuvant chemotherapy (NAC) has contributed to improving breast cancer outcomes, and it would ideally reduce the need for definitive breast surgery in patients who have no residual cancer after NAC treatment. However, there is no reliable noninvasive imaging modality accepted as the routine method to assess response to NAC. Because of the inability to detect complete response, post‐NAC surgery remains the standard of care. To overcome this limitation, a single‐breath‐hold photoacoustic computed tomography (SBH‐PACT) system is developed to provide contrast similar to that of contrast‐enhanced magnetic resonance imaging, but with much higher spatial and temporal resolution and without injection of contrast chemicals. SBH‐PACT images breast cancer patients at three time points: before, during, and after NAC. The analysis of tumor size, blood vascular density, and irregularity in the distribution and morphology of the blood vessels on SBH‐PACT accurately identifies response to NAC as confirmed by the histopathological diagnosis. SBH‐PACT shows its near‐term potential as a diagnostic tool for assessing breast cancer response to systemic treatment by noninvasively measuring the changes in cancer‐associated angiogenesis. Further development of SBH‐PACT may also enable serial imaging, rather than the use of current invasive biopsies, to diagnose and follow indeterminate breast lesions. [ABSTRACT FROM AUTHOR]

A major challenge of transcranial human brain photoacoustic computed tomography (PACT) is correcting for the acoustic aberration induced by the skull. Here, we present a modified universal back-projection (UBP) method, termed layered UBP (L-UBP), that can de-aberrate the transcranial PA signals by accommodating the skull heterogeneity into conventional UBP. In L-UBP, the acoustic medium is divided into multiple layers: the acoustic coupling fluid layer between the skull and detectors, the skull layer, and the brain tissue layer, which are assigned different acoustic properties. The transmission coefficients and wave conversion are considered at the fluid–skull and skull–tissue interfaces. Simulations of transcranial PACT using L-UBP were conducted to validate the method. Ex vivo experiments with a newly developed three-dimensional PACT system with 1-MHz center frequency demonstrated that L-UBP can substantially improve the image quality compared to conventional UBP.

Based on the energy conversion of light into sound, photoacoustic computed tomography (PACT) is an emerging biomedical imaging modality and has unique applications in a range of biomedical fields. In PACT, image formation relies on a process called acoustic inversion from received photoacoustic signals. While most PACT systems perform this inversion with a basic assumption that biological tissues are acoustically homogeneous, the community gradually realizes that the intrinsic acoustic heterogeneity of tissues could pose distortions and artifacts to finally formed images. This paper surveys the most recent research progress on acoustic heterogeneity correction in PACT. Four major strategies are reviewed in detail, including half-time or partial-time reconstruction, autofocus reconstruction by optimizing sound speed maps, joint reconstruction of optical absorption and sound speed maps, and ultrasound computed tomography (USCT) enhanced reconstruction. The correction of acoustic heterogeneity helps improve the imaging performance of PACT.

Abstract Three-dimensional (3D) image reconstruction involves the computations of an extensive amount of data that leads to tremendous processing time. Therefore, optimization is crucially needed to improve the performance and efficiency. With the widespread use of graphics processing units (GPU), parallel computing is transforming this arduous reconstruction process for numerous imaging modalities, and photoacoustic computed tomography (PACT) is not an exception. Existing works have investigated GPU-based optimization on photoacoustic microscopy (PAM) and PACT reconstruction using compute unified device architecture (CUDA) on either C++ or MATLAB only. However, our study is the first that uses cross-platform GPU computation. It maintains the simplicity of MATLAB, while improves the speed through CUDA/C++ − based MATLAB converted functions called MEXCUDA. Compared to a purely MATLAB with GPU approach, our cross-platform method improves the speed five times. Because MATLAB is widely used in PAM and PACT, this study will open up new avenues for photoacoustic image reconstruction and relevant real-time imaging applications.

Photoacoustic computed tomography (PACT) based on a full-ring ultrasonic transducer array is widely used for small animal wholebody and human organ imaging, thanks to its high in-plane resolution and full-view fidelity. However, spatial aliasing in full-ring geometry PACT has not been studied in detail. If the spatial Nyquist criterion is not met, aliasing in spatial sampling causes artifacts in reconstructed images, even when the temporal Nyquist criterion has been satisfied. In this work, we clarified the source of spatial aliasing through spatiotemporal analysis. We demonstrated that the combination of spatial interpolation and temporal filtering can effectively mitigate artifacts caused by aliasing in either image reconstruction or spatial sampling, and we validated this method by both numerical simulations and in vivo experiments. [ABSTRACT FROM AUTHOR]

Based on the energy conversion of light into sound, photoacoustic computed tomography (PACT) is an emerging biomedical imaging modality and has unique applications in a range of biomedical fields. In PACT, image formation relies on a process called acoustic inversion from received photoacoustic signals. While most PACT systems perform this inversion with a basic assumption that biological tissues are acoustically homogeneous, the community gradually realizes that the intrinsic acoustic heterogeneity of tissues could pose distortions and artifacts to finally formed images. This paper surveys the most recent research progress on acoustic heterogeneity correction in PACT. Four major strategies are reviewed in detail, including half-time or partial-time reconstruction, autofocus reconstruction by optimizing sound speed maps, joint reconstruction of optical absorption and sound speed maps, and ultrasound computed tomography (USCT) enhanced reconstruction. The correction of acoustic heterogeneity helps improve the imaging performance of PACT. [ABSTRACT FROM AUTHOR]

Chicken embryos have been proven to be an attractive vertebrate model for biomedical research. They have helped in making significant contributions for advancements in various fields like developmental biology, cancer research and cardiovascular studies. However, a non‐invasive, label‐free method of imaging live chicken embryo at high resolution still needs to be developed and optimized. In this work, we have shown the potential of photoacoustic tomography (PAT) for imaging live chicken embryos cultured in bioengineered eggshells. Laser pulses at wavelengths of 532 and 740 nm were used for attaining cross‐sectional images of chicken embryos at different developmental stages. Cross‐sections along different depths were imaged to gain knowledge of the relative depth of different vessels and organs. Due to high optical absorption of vasculature and embryonic eye, images with good optical contrast could be acquired using this method. We have thus reported a label‐free method of performing cross‐sectional imaging of chicken embryos at high resolution demonstrating the capacity of PAT as a promising tool for avian embryo imaging. [ABSTRACT FROM AUTHOR]

Mice and rats are rodent specimens commonly used in multidisciplinary research. Specifically, vasculature imaging of rodents has been widely performed in preclinical studies using various techniques, such as computed tomography, magnetic resonance imaging, and ultrasound imaging. Photoacoustic CT (PACT) is a noninvasive, nonionizing optical imaging technique derived from photoacoustic tomography and benefits from using intrinsic endogenous contrast agents to produce three-dimensional volumetric data from images. In this study, a commercial PACT device was employed to assess the cervicothoracic vasculature of mouse and rat specimens, which has rarely been examined using PACT, under two conditions with depilation and skin incision. Various blood vessels, including the common carotid artery, internal/external jugular veins, cranial vena cava, internal thoracic vein, and mammary, were identified in the acquired PACT images. The difference between the depilated and skin-incised specimens also revealed the presence of branches from certain blood vessels and specific anatomical features such as the manubrium of the sternum. This study presents detailed PACT images observing the cervicothoracic vasculature of rodent specimens and is expected to be used as a reference for various preclinical experiments on mice and rats.

In the application of photoacoustic human infant brain imaging, debubbled ultrasound gel or water is commonly used as a couplant for ultrasonic transducers due to their acoustic properties. The main challenge in using such a couplant is its discomfort for the patient. In this study, we explore the feasibility of a semi-dry coupling configuration to be used in photoacoustic computed tomography (PACT) systems. The coupling system includes an inflatable container consisting of a thin layer of Aqualene with ultrasound gel or water inside of it. Finite element method (FEM) is used for static and dynamic structural analysis of the proposed configuration to be used in PACT for infant brain imaging. The outcome of the analysis is an optimum thickness of Aqualene in order to meet the weight tolerance requirement with the least attenuation and best impedance match to recommend for an experimental setting.

Significance: Dynamic photoacoustic computed tomography (PACT) is a valuable imaging technique for monitoring physiological processes. However, current dynamic PACT imaging techniques are often limited to two-dimensional spatial imaging. Although volumetric PACT imagers are commercially available, these systems typically employ a rotating measurement gantry in which the tomographic data are sequentially acquired as opposed to being acquired simultaneously at all views. Because the dynamic object varies during the data-acquisition process, the sequential data-acquisition process poses substantial challenges to image reconstruction associated with data incompleteness. The proposed image reconstruction method is highly significant in that it will address these challenges and enable volumetric dynamic PACT imaging with existing preclinical imagers., Aim: The aim of this study is to develop a spatiotemporal image reconstruction (STIR) method for dynamic PACT that can be applied to commercially available volumetric PACT imagers that employ a sequential scanning strategy. The proposed reconstruction method aims to overcome the challenges caused by the limited number of tomographic measurements acquired per frame., Approach: A low-rank matrix estimation-based STIR (LRME-STIR) method is proposed to enable dynamic volumetric PACT. The LRME-STIR method leverages the spatiotemporal redundancies in the dynamic object to accurately reconstruct a four-dimensional (4D) spatiotemporal image., Results: The conducted numerical studies substantiate the LRME-STIR method's efficacy in reconstructing 4D dynamic images from tomographic measurements acquired with a rotating measurement gantry. The experimental study demonstrates the method's ability to faithfully recover the flow of a contrast agent with a frame rate of 10 frames per second, even when only a single tomographic measurement per frame is available., Conclusions: The proposed LRME-STIR method offers a promising solution to the challenges faced by enabling 4D dynamic imaging using commercially available volumetric PACT imagers. By enabling accurate STIRs, this method has the potential to significantly advance preclinical research and facilitate the monitoring of critical physiological biomarkers., (© 2024 The Authors.)

We present a method of imaging angiographic structures in human extremities, including hands, arms, legs, and feet, using a newly developed photoacoustic computed tomography (PACT) system. The system features deep penetration (1.8 cm in muscular tissues) with high spatial and temporal resolutions. A volumetric image is acquired within 5 to 15 s while each cross sectional image is acquired within 100 µs. Therefore, we see no blurring from motion in the imaging plane. Longitudinal and latitudinal cross-sectional images of a healthy volunteer clearly show the vascular network of each appendage and highlight the system's ability to image major and minor vasculatures, without the use of an external contrast or ionizing radiation. We also track heartbeatinduced arterial movement at a two-dimensional frame rate of 10 Hz. This work substantiates the idea that PACT could be used as a noninvasive method for imaging human vasculatures. [ABSTRACT FROM AUTHOR]

The optimal photoacoustic probe design is the key to obtain highest imaging sensitivity in photoacoustic computed tomography. Two commonly used probe design types are dark- and bright-field designs. We proposed a design for photoacoustic probe called quasibright-field illumination and compared the performance of all three kinds of probes theoretically and experimentally. Our conclusion is that the proposed quasibright-field illumination photoacoustic probe is superior compared to the existing probe designs as demonstrated. However, each type of illumination should still have its own advantages under certain circumstances. The dark-field illumination is capable of minimizing surface interference signals and reducing their contributions to the background of deeper signals. Hence, it should perform better when imaging samples with high optical absorbance at the surface layer. The bright field may perform better under circumstance when phase distortion is less. We also designed and fabricated three kinds of probes using a single multimode optical fiber for laser energy delivery instead of fiber bundle. Single fiber probes are low cost, transmit laser energy efficiently, and are compact for easy handling. Thus, our study not only provides a method for probe design but also a guidance for cost-effective transducer array-based photoacoustic probe design and manufacturing in the future. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging is a hybrid imaging modality that offers the advantages of optical (spectroscopic contrast) and ultrasound imaging (scalable spatial resolution and imaging depth). This promising modality has shown excellent potential in a wide range of preclinical and clinical imaging and sensing applications. Even though photoacoustic imaging technology has matured in research settings, its clinical translation is not happening at the expected pace. One of the main reasons for this is the requirement of bulky and expensive pulsed lasers for excitation. To accelerate the clinical translation of photoacoustic imaging and explore its potential in resource-limited settings, it is of paramount importance to develop portable and affordable light sources that can be used as the excitation light source. In this review, we focus on the following aspects: (1) the basic theory of photoacoustic imaging; (2) inexpensive light sources and different implementations; and (3) important preclinical and clinical applications, demonstrated using affordable light source-based photoacoustics. The main focus will be on laser diodes and light-emitting diodes as they have demonstrated promise in photoacoustic tomography—the key technological developments in these areas will be thoroughly reviewed. We believe that this review will be a useful opus for both the beginners and experts in the field of biomedical photoacoustic imaging.