Photoacoustic Imaging Research Articles

Photoacoustic Imaging of Human Skin for Accurate Diagnosis and Treatment Guidance

Photoacoustic imaging (PAI) is a cutting-edge biomedical imaging modality, providing detailed anatomical and functional information about the area beneath the skin surface. Its light energy deposition is such that PAI typically provides clear images of the skin with high signal-to-noise ratios. Specifically, the rich optical contrast of PAI allows biological information related to lesion growth, malignancy, treatment response, and prognosis to be seen. Given its significant advantages and emerging role in imaging skin lesions, we summarize and comment on representative studies of skin PAI, such as the guidance of skin cancer biopsies and surgical excisions, and the accurate diagnosis of psoriasis. We conclude with our insights about the clinical significance of skin PAI, showing how its use to identify biological characteristics in lesion microenvironments allows early diagnosis and prognosis of disease.

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.

Cancer diagnosis and treatment platform based on manganese-based nanomaterials.

Cancer is a leading cause of death worldwide, and the development of new diagnostic and treatment methods is crucial. Manganese-based nanomaterials (MnNMs) have emerged as a focal point in the field of cancer diagnosis and treatment due to their multifunctional properties. These nanomaterials have been extensively explored as contrast agents for various imaging technologies such as magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and near-infrared fluorescence imaging (NIR-FL). The use of these nanomaterials has significantly enhanced the contrast for precise tumor detection and localization. Moreover, MnNMs have shown responsiveness to the tumor microenvironment (TME), enabling innovative approaches to cancer treatment. This review provides an overview of the latest developments of MnNMs and their potential applications in tumor diagnosis and therapy. Finally, potential challenges and prospects of MnNMs in clinical applications are discussed. We believe that this review would serve as a valuable resource for guiding further research on the application of manganese nanomaterials in cancer diagnosis and treatment, addressing the current limitations, and proposing future research directions.

Reconstruction methods for super-resolution imaging with PSF modulation

Recently, a super-resolution imaging method called the PSF (point spread function) modulation method was developed (Lu, IEEE TUFFC 2024). In this method, the amplitude, phase, or both of the PSF of a linear shift-invariant (LSI) imaging system is modulated so that the modulated PSF has a higher spatial frequency than that of the original PSF to reconstruct super-resolution images. The modulator can be produced and manipulated remotely by methods such as radiation force or it can be a physical particle such as micro- or nano-particle manipulated by an external force such as electrical and electromagnetic force. In principle, the super-resolution imaging method can be applied to any LSI imaging system, such as ultrasound, optical, photoacoustic, electromagnetic, underwater, nondestructive evaluation (NDE), and magnetic resonance imaging (MRI) system. These include pulse-echo ultrasound imaging, transmission imaging, wave source/field imaging, acoustical camera, and optical bright-field microscope. To optimize the quality of the images, methods for the reconstruction of pulse-echo and wave source/field super-resolution images are studied and the results will be presented. These methods include the uses of an analytic envelope of radio-frequency (RF) signals with and without windowing, “I” (in-phase) and “Q” (quadrature) signals, and the DC (direct current) component removal.

Deep-brain imaging with 3D integrated photoacoustic tomography and ultrasound localization microscopy

Photoacoustic computed tomography (PACT) is a proven technology for imaging hemodynamics in deep brain of small animal models. PACT is inherently compatible with ultrasound (US) imaging, providing complementary contrast mechanisms. While PACT can quantify the brain’s oxygen saturation of hemoglobin (sO2), US imaging can probe the blood flow based on the Doppler effect. Furthermore, by tracking gas-filled microbubbles, ultrasound localization microscopy (ULM) can map the blood flow velocity with sub-diffraction spatial resolution. In this work, we present a 3D deep-brain imaging system that seamlessly integrates PACT and ULM into a single device, 3D-PAULM. Using a low ultrasound frequency of 4 MHz, 3D-PAULM is capable of imaging the whole-brain hemodynamic functions with intact scalp and skull in a totally non-invasive manner. Using 3D-PAULM, we studied the mouse brain functions with ischemic stroke. Multi-spectral PACT, US B-mode imaging, microbubble-enhanced power Doppler (PD), and ULM were performed on the same mouse brain with intrinsic image co-registration. From the multi-modality measurements, we future quantified blood perfusion, sO2, vessel density, and flow velocity of the mouse brain, showing stroke-induced ischemia, hypoxia, and reduced blood flow. We expect that 3D-PAULM can find broad applications in studying deep brain functions on small animal models.

Photoacoustic Imaging With Single-Element, Low-Frequency Thin-Film PMUT

Photoacoustic Imaging With Single-Element, Low-Frequency Thin-Film PMUT

Improving photoacoustic imaging through the skull using deep learning: a numerical study

Photoacoustic computed tomography (PACT) has recently emerged as an attractive imaging modality for functional brain imaging due to its rich optical absorption contrast, high spatial and temporal resolutions, and relatively deep penetration. However, a major hurdle in using PACT for the human brain is distortion of the signal due to the skull, which negatively affects the quality of the images. In this project, we aimed to improve transcranial PACT using a U-Net architecture that can minimize distortion from the skull. This numerical study utilized a large collection of blood vessel images obtained from an online database and a computed tomography (CT) scan of an ex vivo human skull. The synthetic photoacoustic radiofrequency data were generated using the open-source wave solver k-Wave. Comparing the images generated by deep learning with the ground truth images, we achieved an average structural similarity index of 0.874 and an average peak signal-to-noise ratio of 17.92 dB.

Photoacoustic Imaging Radiomics to Identify Breast Cancer in BI-RADS 4 or 5 Lesions

ObjectivesTo develop a nomogram based on photoacoustic imaging (PAI) radiomics and BI-RADs to identify breast cancer (BC) in BI-RADS 4 or 5 lesions detected by ultrasound (US). MethodsIn this retrospective study, 119 females with 119 breast lesions at US and PAI examination were included (January 2022 to December 2022). Patients were divided into the training set (n = 83) or testing set (n = 36) to develop a nomogram to identify BC in BI-RADS 4 or 5 lesions. Relevant factors at clinic, BI-RADS category, and PAI were reviewed. Univariate and multivariate regression was used to evaluate factors for associations with BC. To evaluate the diagnostic performance of nomogram, the area under the curve (AUC) of receiver operating characteristic curve, accuracy, specificity and sensitivity was employed. ResultsThe nomogram that included BI-RADS category and PAI radiomics score demonstrated a high AUC of 0.925 (95%CI: 0.8467-0.9712) in the training set and 0.926 (95%CI: 0.846-1.000) in the test set. The nomogram also showed significantly better discrimination than the radiomics score (P = .048) or BI-RADS category (P = .009) in the training set. These significant differences were demonstrated in the testing set, outperform the radiomics score (P = .038) and BI-RADS category (P = .013). ConclusionsThe nomogram developed with BI-RADS and PAI radiomics score can effectively identify BC in BI-RADS 4 or 5 lesions. This technique has the potential to further improve early diagnostic accuracy for BC.

Dynamic monitoring of oxygen partial pressure in photodynamic therapy using pump-probe-based photoacoustic tomography.

Pump-probe-based photoacoustic tomography (PP-PAT) is an innovative and promising molecular imaging technique. In this study, we utilized PP-PAT for the first time, to the best of our knowledge, to monitor the dynamics of oxygen partial pressure (pO2) within murine tumors during photodynamic therapy (PDT) with methylene blue (MB). We developed, to our knowledge, a novel two-step fitting method to simultaneously map both the pO2 and the MB concentrations and implemented it with mexCuda to accelerate the pixel-wise-based calculation. The results demonstrated a penetration depth of up to 5 mm and revealed a significant decrease in pO2 during the PDT process, consistent with existing research findings. This study suggests that PP-PAT has the potential to become a valuable tool for intraoperative monitoring of PDT, thereby enhancing therapeutic efficacy.

Advancing immunotherapy in triple negative breast Cancer: A novel multimodal theranostic nanoplatform integrating synergetic ferroptosis and photothermal therapy

Triple negative breast cancer (TNBC) is a subtype of breast cancer with high invasiveness and the worst prognosis. Immunotherapy has demonstrated significant potential in its treatment. However, the response rate remains unsatisfactory. In this work, we prepared multifunctional theranostic nanoplatforms (P-R@P/U-V) with synergetic ferroptosis and photothermal therapy (PTT) in improving TNBC tumor microenvironment for improving local treatment in situ, and synergistic anti-programmed cell death-ligand 1 (PD-L1) immunotherapy to prevent distant metastasis. With P-R@P/U-V, real-time monitoring of the specific distribution in tumors is possible due to the greatly improved ultrasound imaging (US), photoacoustic imaging (PAI), and magnetic resonance imaging (MRI) capabilities. Moreover, P-R@P/U-V has excellent photothermal conversion ability. Whereas PTT killed TNBC cells after laser irradiation, the liquid–gas phase transition not only improved US but also triggered controllable release of RSL3 in situ, enhancing ferroptosis of TNBC cells. Besides, the release of tumor-associated antigens (TAAs) increased via PTT and ferroptosis, strongly stimulating T cell activation, dendritic cell maturation, and anti-tumor cytokine secretion. The lung metastases of TNBC were significantly inhibited following the combined use of P-R@P/U-V and PD-L1 inhibitors. The multimodal and multifunctional nanoplatforms demonstrated excellent effects in early diagnosis and synergistic treatment of TNBC. This represents a novel strategy based on local treatment for additional enhanced anti-PD-L1 immunotherapy, with high clinical application prospects.

Dual-modal Photoacoustic and Ultrasound Imaging: from preclinical to clinical applications.

Photoacoustic imaging is a novel biomedical imaging modality that has emerged over the recent decades. Due to the conversion of optical energy into the acoustic wave, photoacoustic imaging offers high-resolution imaging in depth beyond the optical diffusion limit. Photoacoustic imaging is frequently used in conjunction with ultrasound as a hybrid modality. The combination enables the acquisition of both optical and acoustic contrasts of tissue, providing functional, structural, molecular, and vascular information within the same field of view. In this review, we first described the principles of various photoacoustic and ultrasound imaging techniques and then classified the dual-modal imaging systems based on their preclinical and clinical imaging applications. The advantages of dual-modal imaging were thoroughly analyzed. Finally, the review ends with a critical discussion of existing developments and a look toward the future.

Deciphering Oxygen‐Independent Augmented Photodynamic Oncotherapy by Facilitating the Separation of Electron‐Hole Pairs

AbstractDeveloping Type‐I photosensitizers provides an attractive approach to solve the dilemma of inadequate efficacy of photodynamic therapy (PDT) caused by the inherent oxygen consumption of traditional Type‐II PDT and anoxic tumor microenvironment. The challenge for the exploration of Type‐I PSs is to facilitate the electron transfer ability of photosensitization molecules for transforming oxygen or H2O to reactive oxygen species (ROS). Herein, we propose an electronic acceptor‐triggered photoinduced electron transfer (a‐PET) strategy promoting the separation of electron‐hole pairs by marriage of two organic semiconducting molecules of a non‐fullerene scaffold‐based photosensitizer and a perylene diimide that significantly boost the Type‐I PDT pathway to produce plentiful ROS, especially, inducing 3.5‐fold and 2.5‐fold amplification of hydroxyl (OH⋅) and superoxide (O2−⋅) generation. Systematic mechanism exploration reveals that intermolecular electron transfer and intramolecular charge separation after photoirradiation generate a competent production of radical ion pairs that promote the Type‐I PDT process by theoretical calculation and ultrafast femtosecond transient absorption (fs‐TA) spectroscopy. By complementary tumor diagnosis with photoacoustic imaging and second near‐infrared fluorescence imaging, this as‐prepared nanoplatform exhibits fabulous photocytotoxicity in harsh hypoxic conditions and terrific cancer revoked abilities in living mice. We envision that this work will broaden the insight into high‐efficiency Type‐I PDT for cancer phototheranostics.

Deciphering Oxygen-Independent Augmented Photodynamic Oncotherapy by Facilitating the Separation of Electron-Hole Pairs.

Developing Type-I photosensitizers provides an attractive approach to solve the dilemma of inadequate efficacy of photodynamic therapy (PDT) caused by the inherent oxygen consumption of traditional Type-II PDT and anoxic tumor microenvironment. The challenge for the exploration of Type-I PSs is to facilitate the electron transfer ability of photosensitization molecules for transforming oxygen or H2O to reactive oxygen species (ROS). Herein, we propose an electronic acceptor-triggered photoinduced electron transfer (a-PET) strategy promoting the separation of electron-hole pairs by marriage of two organic semiconducting molecules of a non-fullerene scaffold-based photosensitizer and a perylene diimide that significantly boost the Type-I PDT pathway to produce plentiful ROS, especially, inducing 3.5-fold and 2.5-fold amplification of hydroxyl (OH⋅) and superoxide (O2 -⋅) generation. Systematic mechanism exploration reveals that intermolecular electron transfer and intramolecular charge separation after photoirradiation generate a competent production of radical ion pairs that promote the Type-I PDT process by theoretical calculation and ultrafast femtosecond transient absorption (fs-TA) spectroscopy. By complementary tumor diagnosis with photoacoustic imaging and second near-infrared fluorescence imaging, this as-prepared nanoplatform exhibits fabulous photocytotoxicity in harsh hypoxic conditions and terrific cancer revoked abilities in living mice. We envision that this work will broaden the insight into high-efficiency Type-I PDT for cancer phototheranostics.

Golden Plasmophores with Tunable Photoluminescence and Outstanding Thermal and Photothermal Stability

AbstractAmong various hybrid nanomaterials, the combination of plasmonic nanoparticles and fluorophores in a single multifunctional nanoplatform, so‐called plasmophores, has attracted significant attention in different fields such as dark field, fluorescence, and photoacoustic imaging, biosensing, photothermal, and photodynamic therapy. Herein, author report a facile and controlled synthesis route of hybrid nanoplatforms composed of fluorescent gold nanoclusters (GNCs) coupled to plasmonic gold nanorods (GNRs) using controlled silica (SiO2) dielectric spacers of different thicknesses from now on referred to as GNR@SiO2@GNC plasmophores. The results show different degrees of plasmon‐enhanced fluorescence of the GNCs in their plasmophore hybrid system when placed at different distances from the plasmonic cores of the GNRs. On the other hand, these plasmophores show enhanced thermal stability compared to GNRs@CTAB (CTAB, cetyl trimethyl ammonium bromide). This results also demonstrated that upon annealing at elevated temperatures (800–1000 °C), the GNRs in the plasmophores are more thermally stable and robust than the GNRs@CTAB. More surprisingly, despite the commonly reported very low melting temperature of smaller‐size nanocrystals, the GNCs in the plasmophores showed high thermal stability and do not exhibit significant structural changes at elevated temperatures (800–1000 °C).

Single-stage approach for estimating optical parameters in spectral quantitative photoacoustictomography.

In quantitative photoacoustic tomography, the optical parameters of a target, most importantly the concentrations of chromophores such as deoxygenated and oxygenated hemoglobin, are estimated from photoacoustic data measured on the boundary of the target. In this work, a numerical approximation of a forward model for spectral quantitative photoacoustic tomography is constructed by utilizing the diffusion approximation for light propagation, the acoustic wave equation for ultrasound propagation, and spectral models of optical absorption and scattering to describe the wavelength dependence of the optical parameters. The related inverse problem is approached in the framework of Bayesian inverse problems. Concentrations of four chromophores (deoxygenated and oxygenated hemoglobin, water, and lipid), two scattering parameters (reference scattering and scattering power), and the Grüneisen parameter are estimated in a single-stage from photoacoustic data. The methodology is evaluated using numerical simulations in different full-view and limited-view imaging settings. The results show that, utilizing spectral data and models, the spectral optical parameters and the Grüneisen parameter can be simultaneously estimated. Furthermore, the approach can also be utilized in limited-view imaging situations.

Beyond synthetic aperture focusing: deconvolution-based elevation resolution enhancement using simulated point spread function for linear array-based three-dimensional photoacoustic imaging.

This paper introduces a deconvolution-based method to enhance the elevation resolution of a linear array-based three-dimensional (3D) photoacoustic (PA) imaging system. PA imaging combines the high contrast of optical imaging with the deep, multi-centimeter spatial resolution of ultrasound (US) imaging, providing structural and functional information about biological tissues. Linear array-based 3D PA imaging is easily accessible and applicable for ex vivo studies, small animal research, and clinical applications in humans. However, its elevation resolution is limited by the acoustic lens geometry, which establishes a single elevation focus. Previous work used synthetic aperture focusing (SAF) to enhance elevation resolution, but the resolution achievable by SAF is constrained by the size of the elevation focus. Here, we introduce the application of Richardson-Lucy deconvolution, grounded in simulated point-spread-functions, to surpass the elevation resolution attainable with SAF alone. We validated this approach using both simulation and experimental data, demonstrating that the full-width-at-half-maximum of point targets on the elevation plane was reduced compared to using SAF only, suggesting resolution improvement. This method shows promise for improving 3D image quality of existing linear array-based PA imaging systems, offering potential benefits for disease diagnosis and monitoring.

A multi-aperture encoding scheme for increased SNR in photoacoustic Imaging

Photoacoustic imaging creates light-induced ultrasonic signals to provide valuable information on internal body structures and tissue morphology non-invasively. A multi-aperture photoacoustic imaging (MP-PAI) system is an improvement over conventional photoacoustic imaging (PAI) systems in terms of resolution, contrast, and field of view. Previously, a prototype MP-PAI system was introduced based on multiple capacitive micromachined ultrasound transducers (CMUTs) with shared channels, such that each element in a CMUT shares its channel with its counterpart in other CMUTs. The system uses the biasing voltages of the CMUTs to switch between them and multiplex the received signals in time. Notwithstanding all the enhancements, the signal-to-noise ratio (SNR) remains limited in PAI. To address this issue, we are proposing a multi-aperture encoding scheme (MAES) to further increase the SNR in a multi-aperture PAI system. The proposed method involves receiving signals with multiple CMUTs simultaneously based on an encoding matrix, instead of switching between individual CMUTs. As a result, shared channels contain a superposition of signals, which are later recovered by applying a decoding matrix. Here, an analytical model for computing SNR with an arbitrary encoding sequence is presented, and the method is validated through numerical simulations and in an experimental study. Bipolar and unipolar encoding sequences were considered for the experiments. The numerical results show, in comparison to conventional MP-PAI, that MAES will obtain an SNR gain of 5.8 and 8.8 dB for S-sequence and truncated Hadamard encodings, respectively, when using 15 transducers. In experiments, three transducers are encoded by S-sequences and show 1.5 dB improvement in SNR over conventional MP-PAI method, which aligns well with the analytical model.

A Bayesian approach for consistent reconstruction of inclusions

This paper considers a Bayesian approach for inclusion detection in nonlinear inverse problems using two known and popular push-forward prior distributions: the star-shaped and level set prior distributions. We analyze the convergence of the corresponding posterior distributions in a small measurement noise limit. The methodology is general; it works for priors arising from any Hölder continuous transformation of Gaussian random fields and is applicable to a range of inverse problems. The level set and star-shaped prior distributions are examples of push-forward priors under Hölder continuous transformations that take advantage of the structure of inclusion detection problems. We show that the corresponding posterior mean converges to the ground truth in a proper probabilistic sense. Numerical tests on a two-dimensional quantitative photoacoustic tomography problem showcase the approach. The results highlight the convergence properties of the posterior distributions and the ability of the methodology to detect inclusions with sufficiently regular boundaries.

Synchronously manipulating absorption and nonradiative transition of croconaine via donor engineering for efficient NIR-II photothermal theranostics

Organic molecules with strong absorption in the near-infrared (NIR)-II region are highly desired for cancer photothermal theranostics. However, it remains challenges to construct NIR-II photothermal agents with desired optical properties. This study reports a donor engineering approach to simultaneously manipulate the absorption and nonradiative transitions of croconaine dyes. By introducing different donor units with increasing electron donating ability to the backbone, the absorption of the synthesized croconaines were gradually red-shifted to NIR-II region, especially the benzo[c,d]indolium conjugated croconaine (CR1045). The extensive conjugation of CR1045 had a narrower HOMO-LUMO energy gap and strong NIR-II light responsiveness. Importantly, the steric repulsion between this large planar donor and croconate acceptor of CR1045 promotes the formation of a twisted intramolecular charge transfer (TICT) state, making it more prone to direct the absorbed energy towards heat-producing non-radiative decay rather than other dissipative pathways. And the nanoformulated CR1045 exhibits excellent optoacoustic generation capability and ultrahigh photothermal conversion efficiency (∼84%). In vitro and in vivo investigations confirm good optoacoustic imaging and effective photothermal treatment of tumors. Therefore, this work offers insights into donor regulation for the future development of efficient NIR-II photothermal agents.

Imaging in reconstructive microsurgery- current standards and latest trends.

In microsurgery, many different imaging techniques are available in both flap and lymphatic surgery that all come with their own advantages and disadvantages. In flap surgery, CT angiography is considered as the gold standard. Among others, Doppler ultrasound, color Doppler ultrasound, ICG, and smartphone-based thermal cameras are valuable imaging techniques. In lymphatic surgery, photoacoustic imaging, laser tomography, contrast-enhanced magnetic resonance imaging, and high frequency ultrasound stand available to surgeons next to the current standard of lymphoscintigraphy. It is crucial to know the advantages and disadvantages to various techniques and highly adviced to microsurgeons be capable of using a variety of them.