Multispectral Photoacoustic Imaging Research Articles

Dual Enzyme-Driven Cascade Reactions Modulate Immunosuppressive Tumor Microenvironment for Catalytic Therapy and Immune Activation.

Lactate-enriched tumor microenvironment (TME) fosters an immunosuppressive milieu to hamper the functionality of tumor-associated macrophages (TAMs). However, tackling the immunosuppressive effects wrought by lactate accumulation is still a big challenge. Herein, we construct a dual enzyme-driven cascade reaction platform (ILH) with immunosuppressive TME modulation for photoacoustic (PA) imaging-guided catalytic therapy and immune activation. The ILH is composed of iridium (Ir) metallene nanozyme, lactate oxidase (LOx), and hyaluronic acid (HA). The combination of Ir nanozyme and LOx can not only efficiently consume lactate to reverse the immunosuppressive TME into an immunoreactive one by promoting the polarization of TAMs from the M2 to M1 phenotype, thus enhancing antitumor defense, but also alleviate tumor hypoxia as well as induce strong oxidative stress, thus triggering immunogenic cell death (ICD) and activating antitumor immunity. Furthermore, the photothermal performance of Ir nanozyme can strengthen the cascade catalytic ability and endow ILH with a PA response. Based on the changes in PA signals from endogenous molecules, three-dimensional multispectral PA imaging was utilized to track the process of cascade catalytic therapy in vivo. This work provides a nanoplatform for dual enzyme-driven cascade catalytic therapy and immune activation by regulating the immunosuppressive TME.

Optical tuning of copolymer-in-oil tissue-mimicking materials for multispectral photoacoustic imaging

Objective. The availability of tissue-mimicking materials (TMMs) for manufacturing high-quality phantoms is crucial for standardization, evaluating novel quantitative approaches, and clinically translating new imaging modalities, such as photoacoustic imaging (PAI). Recently, a gel comprising the copolymer styrene-ethylene/butylene-styrene (SEBS) in mineral oil has shown significant potential as TMM due to its optical and acoustic properties akin to soft tissue. We propose using artists’ oil-based inks dissolved and diluted in balsam turpentine to tune the optical properties. Approach. A TMM was fabricated by mixing a SEBS copolymer and mineral oil, supplemented with additives to tune its optical absorption and scattering properties independently. A systematic investigation of the tuning accuracies and relationships between concentrations of oil-based pigments and optical absorption properties of the TMM across visible and near-infrared wavelengths using collimated transmission spectroscopy was conducted. The photoacoustic spectrum of various oil-based inks was studied to analyze the effect of increasing concentration and depth. Main results. Artists’ oil-based inks dissolved in turpentine proved effective as additives to tune the optical absorption properties of mineral oil SEBS-gel with high accuracy. The TMMs demonstrated long-term stability and suitability for producing phantoms with desired optical absorption properties for PAI studies. Significance. The findings, including tuning of optical absorption and spectral shape, suggest that this TMM facilitates the development of more sophisticated phantoms of arbitrary shapes. This approach holds promise for advancing the development of PAI, including investigation of the spectral coloring effect. In addition, it can potentially aid in the development and clinical translation of ultrasound optical tomography.

Multiparametric Brain Hemodynamics Imaging Using a Combined Ultrafast Ultrasound and Photoacoustic System.

Studying brain-wide hemodynamic responses to different stimuli at high spatiotemporal resolutions can help gain new insights into the mechanisms of neuro- diseases and -disorders. Nonetheless, this task is challenging, primarily due to the complexity of neurovascular coupling, which encompasses interdependent hemodynamic parameters including cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral oxygen saturation (SO2). The current brain imaging technologies exhibit inherent limitations in resolution, sensitivity, and imaging depth, restricting their capacity to comprehensively capture the intricacies of cerebral functions. To address this, a multimodal functional ultrasound and photoacoustic (fUSPA) imaging platform is reported, which integrates ultrafast ultrasound and multispectral photoacoustic imaging methods in a compact head-mountable device, to quantitatively map individual dynamics of CBV, CBF, and SO2 as well as contrast agent enhanced brain imaging at high spatiotemporal resolutions. Following systematic characterization, the fUSPA system is applied to study brain-wide cerebrovascular reactivity (CVR) at single-vessel resolution via relative changes in CBV, CBF, and SO2 in response to hypercapnia stimulation. These results show that cortical veins and arteries exhibit differences in CVR in the stimulated state and consistent anti-correlation in CBV oscillations during the resting state, demonstrating the multiparametric fUSPA system's unique capabilities in investigating complex mechanisms of brain functions.

Multiwavelength laser diode based portable photoacoustic and ultrasound imaging system for point of care applications.

Vascular diseases are a leading cause of death and disability worldwide. Despite having precursor conditions like peripheral arterial disease (PAD), they are often only diagnosed after the onset of stroke or heart attack. Low-cost, portable, noninvasive, point-of-care (POC), label-free assessment of deep vascular function benefits PAD diagnosis, especially in resource poor settings of the world. Doppler ultrasound-based blood flow measurements can diagnose PAD, albeit with limited sensitivity and specificity. To overcome this, here, we propose the first-of-its-kind dual-modality photoacoustic-and-ultrasound (PAUS) imaging system that integrates a multiwavelength pulsed laser diode (PLD) with a compact ultrasound data acquisition unit. The mesoscopic imaging depth of the portable PLD-PAUS system was validated using tissue phantoms, and its multispectral photoacoustic imaging capabilities were validated using an atherosclerosis-mimicking phantom. Furthermore, we demonstrated high-contrast volumetric in vivo photoacoustic imaging of rodent abdominal vasculature and quantified vessel reactivity due to hypercapnia stimulation. The multiparametric functional and molecular imaging capabilities of the PLD-PAUS system holds promise for POC applications.

Depth-Specific Hypoxic Responses to Spreading Depolarizations in Gyrencephalic Swine Cortex Unveiled by Photoacoustic Imaging.

Spreading depolarizations (SDs) are a marker of brain injury and have a causative effect on ischemic lesion progression. The hemodynamic responses elicited by SDs are contingent upon the metabolic integrity of the affected tissue, with vasoconstrictive reactions leading to pronounced hypoxia often indicating poor outcomes. The stratification of hemodynamic responses within different cortical layers remains poorly characterized. This pilot study sought to elucidate the depth-specific hemodynamic changes in response to SDs within the gray matter of the gyrencephalic swine brain. Employing a potassium chloride-induced SD model, we utilized multispectral photoacoustic imaging (PAI) to estimate regional cerebral oxygen saturation (rcSO2%) changes consequent to potassium chloride-induced SDs. Regions of interest were demarcated at three cortical depths covering up to 4mm. Electrocorticography (ECoG) strips were placed to validate the presence of SDs. Through PAI, we detected 12 distinct rcSO2% responses, which corresponded with SDs detected in ECoG. Notably, a higher frequency of hypoxic responses was observed in the deeper cortical layers compared to superficial layers, where hyperoxic and mixed responses predominated (p < 0.001). This data provides novel insights into the differential oxygenation patterns across cortical layers in response to SDs, underlining the complexity of cerebral hemodynamics post-injury.

Video-rate endocavity photoacoustic/harmonic ultrasound imaging with miniaturized light delivery.

Endocavity ultrasound (US) imaging is a frequently employed diagnostic technique in gynecology and urology for the assessment of male and female genital diseases that present challenges for conventional transabdominal imaging. The integration of photoacoustic (PA) imaging with clinical US imaging has displayed promising outcomes in clinical research. Nonetheless, its application has been constrained due to size limitations, restricting it to spatially confined locations such as vaginal or rectal canals. This study presents the development of a video-rate (20Hz) endocavity PA/harmonic US imaging (EPAUSI) system. The approach incorporates a commercially available endocavity US probe with a miniaturized laser delivery unit, comprised of a single large-core fiber and a line beamshaping engineered diffuser. The system facilitates real-time image display and subsequent processing, including angular energy density correction and spectral unmixing, in offline mode. The spatial resolutions of the concurrently acquired PA and harmonic US images were measured at and in the radial direction, respectively, and 1.22deg and 1.50deg in the angular direction, respectively. Furthermore, the system demonstrated its capability in multispectral PA imaging by successfully distinguishing two clinical dyes in a tissue-mimicking phantom. Its rapid temporal resolution enabled the capture of kinetic dye perfusion into an ex vivo porcine ovary through the depth of porcine uterine tissue. EPAUSI proved its clinical viability by detecting pulsating hemodynamics in the male rat's prostate in vivo and accurately classifying human blood vessels into arteries and veins based on measurements. Our proposed EPAUSI system holds the potential to unveil previously overlooked indicators of vascular alterations in genital cancers or endometriosis, addressing pressing requirements in the fields of gynecology and urology.

Relief of tumor hypoxia using a nanoenzyme amplifies NIR-II photoacoustic-guided photothermal therapy.

Hypoxia is a critical tumor microenvironment (TME) component. It significantly impacts tumor growth and metastasis and is known to be a major obstacle for cancer therapy. Integrating hypoxia modulation with imaging-based monitoring represents a promising strategy that holds the potential for enhancing tumor theranostics. Herein, a kind of nanoenzyme Prussian blue (PB) is synthesized as a metal-organic framework (MOF) to load the second near-infrared (NIR-II) small molecule dye IR1061, which could catalyze hydrogen peroxide to produce oxygen and provide a photothermal conversion element for photoacoustic imaging (PAI) and photothermal therapy (PTT). To enhance stability and biocompatibility, silica was used as a coating for an integrated nanoplatform (SPI). SPI was found to relieve the hypoxic nature of the TME effectively, thus suppressing tumor cell migration and downregulating the expression of heat shock protein 70 (HSP70), both of which led to an amplified NIR-II PTT effect in vitro and in vivo, guided by the NIR-II PAI. Furthermore, label-free multi-spectral PAI permitted the real-time evaluation of SPI as a putative tumor treatment. A clinical histological analysis confirmed the amplified treatment effect. Hence, SPI combined with PAI could offer a new approach for tumor diagnosing, treating, and monitoring.

NIR-II Photoacoustic Imaging-Guided Oxygen Delivery and Controlled Release Improves Photodynamic Therapy for Hepatocellular Carcinoma.

Hypoxia, a prominent hallmark of hepatocellular carcinoma (HCC), undermines curative outcomes, elevates recurrence rates, and fosters metastasis, particularly during photodynamic therapy (PDT) in clinical settings. Studies indicate that alleviating tumor hypoxia enhances PDT efficacy. However, persistent challenges, including suboptimal oxygen delivery efficiency and absence of real-time feedback on blood oxygen fluctuations during PDT, considerably impede therapeutic efficacy in tumor treatment. This study addresses these issues using near-infrared-II (NIR-II) photoacoustic (PA) imaging for tumor-targeted oxygen delivery and controlled release. For this purpose, a biomimetic oxygen delivery system designated BLICP@O2 is developed, which utilizes hybrid tumor cell membranes and thermosensitive liposomes as oxygen carriers, incorporating the NIR-II dye IR1048, photosensitizer chlorin e6 (Ce6), and perfluorohexane. Upon sequential irradiation at 1064 and 690nm, BLICP@O2 exhibits significant photothermal and photodynamic effects. Photothermal heating triggers oxygen release, enhancing the photodynamic effect of Ce6. Blood oxygen changes during PDT are tracked by multispectral PA imaging. Enhanced PDT efficacy, mediated by hypoxia relief, is convincingly demonstrated both in vitro and in vivo. This work presents an imaging-guided, dual-wavelength programmed cascaded treatment strategy for tumor-targeted oxygen delivery and controlled release, with real-time efficacy monitoring using PA imaging, offering valuable insights for overcoming challenges in PDT-based cancer therapy.

Diagnosis of liver fibrosis and liver function reserve through non-invasive multispectral photoacoustic imaging

Liver function reserve (LFR) is the sum of remnant functional hepatic cells after liver injury. In the pathologic process of liver fibrosis (LF), LFR is impaired. LFR assessment can help determine the safe scope of liver resection or drug regimen and predict prognosis of patients with liver disease. Here, we used a photoacoustic imaging (PAI) system to assess LF and LFR in rabbit models. We performed PAI, ultrasound elastography and biopsy for 21 rabbits developing none (n = 6) and LF (n = 15). In vivo indocyanine green (ICG) measurements by PAI showed that LF group presented a significantly attenuated ICG clearance compared to control group, indicating LFR impairment of LF. Another finding was a significantly higher collagen photoacoustic signal intensity value was observed in LF both in vivo and in vitro. Our findings demonstrated that PAI was potentially effective to evaluate LFR and collagen accumulation of LF.

Optical absorption spectra and corresponding in vivo photoacoustic visualization of exposed peripheral nerves.

Multispectral photoacoustic imaging has the potential to identify lipid-rich, myelinated nerve tissue in an interventional or surgical setting (e.g., to guide intraoperative decisions when exposing a nerve during reconstructive surgery by limiting operations to nerves needing repair, with no impact to healthy or regenerating nerves). Lipids have two optical absorption peaks within the NIR-II and NIR-III windows (i.e., 1000 to 1350nm and 1550 to 1870nm wavelength ranges, respectively) which can be exploited to obtain photoacoustic images. However, nerve visualization within the NIR-III window is more desirable due to higher lipid absorption peaks and a corresponding valley in the optical absorption of water. We present the first known optical absorption characterizations, photoacoustic spectral demonstrations, and histological validations to support in vivo photoacoustic nerve imaging in the NIR-III window. Four in vivo swine peripheral nerves were excised, and the optical absorption spectra of these fresh ex vivo nerves were characterized at wavelengths spanning 800 to 1880nm, to provide the first known nerve optical absorbance spectra and to enable photoacoustic amplitude spectra characterization with the most optimal wavelength range. Prior to excision, the latter two of the four nerves were surrounded by aqueous, lipid-free, agarose blocks (i.e., 3% w/v agarose) to enhance acoustic coupling during in vivo multispectral photoacoustic imaging using the optimal NIR-III wavelengths (i.e., 1630 to 1850nm) identified in the ex vivo studies. There was a verified characteristic lipid absorption peak at 1725nm for each ex vivo nerve. Results additionally suggest that the 1630 to 1850nm wavelength range can successfully visualize and differentiate lipid-rich nerves from surrounding water-containing and lipid-deficient tissues and materials. Photoacoustic imaging using the optimal wavelengths identified and demonstrated for nerves holds promise for detection of myelination in exposed and isolated nerve tissue during a nerve repair surgery, with possible future implications for other surgeries and other optics-based technologies.

Integrated Photoacoustic, Ultrasound, and Angiographic Tomography (PAUSAT) for NonInvasive Whole-Brain Imaging of Ischemic Stroke.

Presented here is an experimental ischemic stroke study using our newly developed noninvasive imaging system that integrates three acoustic-based imaging technologies: photoacoustic, ultrasound, and angiographic tomography (PAUSAT). Combining these three modalities helps acquire multi-spectral photoacoustic tomography (PAT) of the brain blood oxygenation, high-frequency ultrasound imaging of the brain tissue, and acoustic angiography of the cerebral blood perfusion. The multi-modal imaging platform allows the study of cerebral perfusion and oxygenation changes in the whole mouse brain after stroke. Two commonly used ischemic stroke models were evaluated: the permanent middle cerebral artery occlusion (pMCAO) model and the photothrombotic (PT) model. PAUSAT was used to image the same mouse brains before and after a stroke and quantitatively analyze both stroke models. This imaging system was able to clearly show the brain vascular changes after ischemic stroke, including significantly reduced blood perfusion and oxygenation in the stroke infarct region (ipsilateral) compared to the uninjured tissue (contralateral). The results were confirmed by both laser speckle contrast imaging and triphenyltetrazolium chloride (TTC) staining. Furthermore, stroke infarct volume in both stroke models was measured and validated by TTC staining as the ground truth. Through this study, we have demonstrated that PAUSAT can be a powerful tool in noninvasive and longitudinal preclinical studies of ischemic stroke.

HSC-targeted delivery of shRNA-TGFβ1 by vitamin A-functionalized polyaminoglycoside for hepatic fibrosis therapy

Liver fibrosis is a scar repair response to liver injury and is a key aspect of liver disease. Transforming growth factor (TGFβ1), one of the most potent pro-fibrotic cytokines known, is involved in almost all critical dimensions of liver fibrosis development. Currently, attenuating the pro-fibrotic effect of TGFβ1 is a promising treatment for liver fibrosis. However, the key to applying this approach is to find a more reliable and effective targeting regulation. In this work, a targeting degradable nucleic acid delivery carrier (SS-HPVA) was constructed based on branched polyaminoglycoside (SS-HPT) modified by hepatic stellate cells (HSCs) targeting molecule vitamin A (VA) for the delivery of the TGFβ1 gene silencing plasmid pshRNA-TGFβ1. The reductive responsiveness and VA modification conferred SS-HPVA with high gene transfection ability and specific targeting properties to HSCs. Multispectral photoacoustic tomography and in vivo fluorescence imaging verified that the SS-HPVA/pshRNA-TGFβ1 system showed superior liver targeting ability, especially in the hepatic fibrosis model.On this basis, it was demonstrated that this system could exhibit good therapeutic effects on liver fibrosis by down-regulating TGFβ1 expression through non-invasive assays and histopathological analysis. Therefore, this gene silencing targeting delivery nanosystem is expected to provide a new strategy for the clinical treatment of liver fibrosis.

PD31-04 FIRST-IN-HUMAN CLINICAL TRIAL FOR THE ASSESSMENT OF KIDNEY TRANSPLANT QUALITY USING COMBINED QUANTITATIVE ULTRASOUND AND PHOTOACOUSTIC IMAGING

You have accessJournal of UrologyCME1 Apr 2023PD31-04 FIRST-IN-HUMAN CLINICAL TRIAL FOR THE ASSESSMENT OF KIDNEY TRANSPLANT QUALITY USING COMBINED QUANTITATIVE ULTRASOUND AND PHOTOACOUSTIC IMAGING Alexander Koven, Eno Hysi, Jihye Baek, Monica Farcas, Robert Stewart, Michael Ordon, Kenneth Pace, Adriana Krizova, Xiaolin He, Kevin Parker, Michael Kolios, and Darren Yuen Alexander KovenAlexander Koven More articles by this author , Eno HysiEno Hysi More articles by this author , Jihye BaekJihye Baek More articles by this author , Monica FarcasMonica Farcas More articles by this author , Robert StewartRobert Stewart More articles by this author , Michael OrdonMichael Ordon More articles by this author , Kenneth PaceKenneth Pace More articles by this author , Adriana KrizovaAdriana Krizova More articles by this author , Xiaolin HeXiaolin He More articles by this author , Kevin ParkerKevin Parker More articles by this author , Michael KoliosMichael Kolios More articles by this author , and Darren YuenDarren Yuen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003324.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While kidney transplantation has revolutionized the treatment of kidney failure, donor kidneys are in short supply. This leads physicians to accept kidneys from older and sicker donors. Many of these have pre-existing fibrosis and microvascular disease, which can cause damage and kidney function loss after transplantation. Unfortunately, current clinical tools for predicting graft outcomes fail to capture whole organ fibrosis and microvascular disease burden. Our group has developed quantitative ultrasound (US) and photoacoustic (PA) imaging to measure both collagen (the main component of fibrosis) and perfusion parameters. In this work, we investigate the use of US/PA imaging to noninvasively measure fibrosis and perfusion in human kidneys at the time of transplantation. METHODS: A VevoLAZR-X US/PA imaging system operating at 15 MHz was utilized for imaging. An algorithm using US frequency information (H-scan) was developed to estimate whole kidney fibrotic burden. Oxygen saturation (sO2) and total hemoglobin (HbT) were estimated using multispectral PA imaging. Donor kidneys were imaged in the operating room before transplantation during cold storage to measure H-scan fibrosis and then after vascular anastomosis to measure PA perfusion. For the primary outcome, H-scan fibrosis scores were correlated with fibrosis determined by HPS-stained biopsies. Clinical outcomes are also being collected for up to 5 years post-transplant. RESULTS: 46 patients have been imaged to date. These patients received either a living or deceased donor kidney transplant (LD n=23; DD n=23). As shown in Fig. 1a, the H-scan captures the increasing fibrotic burden with increasing %red pixels. Comparison with HPS-stained biopsies confirmed the accuracy of H-scan in assessing fibrosis (r=0.83, Fig. 1b). Post-perfusion, sO2 and HbT estimates were acquired (Fig. 1c), with the average sO2 increasing by approximately 20%. CONCLUSIONS: This is the first in-human study applying US/PA imaging to non-invasively and accurately measure kidney fibrovascular disease burden at the time of transplantation. Next steps will be to correlate imaging scores with clinical outcomes. Once complete, we expect our results will help optimize donor kidney selection and matching to the most appropriate recipients. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e901 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander Koven More articles by this author Eno Hysi More articles by this author Jihye Baek More articles by this author Monica Farcas More articles by this author Robert Stewart More articles by this author Michael Ordon More articles by this author Kenneth Pace More articles by this author Adriana Krizova More articles by this author Xiaolin He More articles by this author Kevin Parker More articles by this author Michael Kolios More articles by this author Darren Yuen More articles by this author Expand All Advertisement PDF downloadLoading ...

Blind spectral unmixing for characterization of plaque composition based on multispectral photoacoustic imaging

To improve the assessment of carotid plaque vulnerability, a comprehensive characterization of their composition is paramount. Multispectral photoacoustic imaging (MSPAI) can provide plaque composition based on their absorption spectra. However, although various spectral unmixing methods have been developed to characterize different tissue constituents, plaque analysis remains a challenge since its composition is highly complex and diverse. In this study, we employed an adapted piecewise convex multiple-model endmember detection method to identify carotid plaque constituents. Additionally, we explore the selection of the imaging wavelengths in linear models by conditioning the coefficient matrix and its synergy with our unmixing approach. We verified our method using plaque mimicking phantoms and performed ex-vivo MSPAI on carotid endarterectomy samples in a spectral range from 500 to 1300 nm to identify the main spectral features of plaque materials for vulnerability assessment. After imaging, the samples were processed for histological analysis to validate the photoacoustic decomposition. Results show that our approach can perform spectral unmixing and classification of highly heterogeneous biological samples without requiring an extensive fluence correction, enabling the identification of relevant components to assess plaque vulnerability.

Full-visibility 3D imaging of oxygenation and blood flow by simultaneous multispectral photoacoustic fluctuation imaging (MS-PAFI) and ultrasound Doppler

We present a method and setup that provide complementary three-dimensional (3D) images of blood oxygenation (via quantitative photoacoustic imaging) and blood flow dynamics (via ultrasound Doppler). The proposed approach is label-free and exploits blood-induced fluctuations, and is implemented on a sparse array with only 256 elements, driven with a commercially available ultrasound electronics. We first implement 3D photoacoustic fluctuation imaging (PAFI) to image chicken embryo, and obtain full-visibility images of the vascular morphology. We obtain simultaneously 3D ultrasound power Doppler with a comparable image quality. We then introduce multispectral photoacoustic fluctuation imaging (MS-PAFI), and demonstrate that it can provide quantitative measurements of the absorbed optical energy density with full visibility and enhanced contrast, as compared to conventional delay-and-sum multispectral photoacoustic imaging. We finally showcase the synergy and complementarity between MS-PAFI, which provides 3D quantitative oxygenation (SO_2) imaging, and 3D ultrasound Doppler, which provides quantitative information on blood flow dynamics. MS-PAFI represents a promising alternative to model-based inversions with the advantage of resolving all the visibility artefacts without prior and regularization, by use of a straightforward processing scheme.

Assessment of nonalcoholic fatty liver function by photoacoustic imaging

SignificanceThe assessment of liver function plays an important role in the diagnosis of nonalcoholic fatty liver disease (NAFLD). Current noninvasive imaging methods have limited applicability in this regard.AimWe report an application of multispectral photoacoustic imaging (PAI), an emerging modality, to visualize lipid accumulation and liver function in NAFLD.ApproachWe first demonstrated the liver function reserve with indocyanine green (ICG) to verify the organ’s dysfunction due to NAFLD in a rabbit model. We then noninvasively quantified lipid content in the liver using multispectral PAI. The in vivo PAI results were compared and verified with photoacoustic ex vivo images and liver biopsy.ResultsA significant difference in the lipidmean value was observed [lipidmean = 0.081 ± 0.0161 arbitrary units (a.u.) control versus NAFLD 0.198 ± 0.048 a.u., P = 0.003]. Similar to in vivo analysis, a significant difference in lipidmean was observed (lipidmean = 0.0673 ± 0.0165 versus 0.486 ± 0.073 a.u., P < 0.0001) between control and NAFLD group ex vivo. For liver function, the control group showed a rapid decrease after the peak point, whereas the elimination of ICG for the NAFLD group was slower.ConclusionsOur study shows that PAI has the potential to provide a noninvasive biomarker for the assessment of liver function and lipid accumulation for NAFLD diagnosis and treatment.

Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression.

Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. However, the anti-inflammatory/immunosuppressive potential of platelets has been poorly explored. Here, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both platelet-associated and -independent antigen challenges. Utilizing multispectral photoacoustic tomography, we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in the liver, a process that we identified to be synergistically dependent on platelet glycoprotein Ibα and hepatic Ashwell-Morell receptor. Mechanistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with increased anti-inflammatory cytokines and circulating CD4+ regulatory T cells, abolishable by Kupffer cell depletion. Last, in a clinically relevant model of hemophilia A, presensitization with dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, these findings open new avenues toward understanding immune homeostasis and potentiate the therapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.

Motion Compensation for 3D Multispectral Handheld Photoacoustic Imaging.

Three-dimensional (3D) handheld photoacoustic (PA) and ultrasound (US) imaging performed using mechanical scanning are more useful than conventional 2D PA/US imaging for obtaining local volumetric information and reducing operator dependence. In particular, 3D multispectral PA imaging can capture vital functional information, such as hemoglobin concentrations and hemoglobin oxygen saturation (sO2), of epidermal, hemorrhagic, ischemic, and cancerous diseases. However, the accuracy of PA morphology and physiological parameters is hampered by motion artifacts during image acquisition. The aim of this paper is to apply appropriate correction to remove the effect of such motion artifacts. We propose a new motion compensation method that corrects PA images in both axial and lateral directions based on structural US information. 3D PA/US imaging experiments are performed on a tissue-mimicking phantom and a human wrist to verify the effects of the proposed motion compensation mechanism and the consequent spectral unmixing results. The structural motions and sO2 values are confirmed to be successfully corrected by comparing the motion-compensated images with the original images. The proposed method is expected to be useful in various clinical PA imaging applications (e.g., breast cancer, thyroid cancer, and carotid artery disease) that are susceptible to motion contamination during multispectral PA image analysis.

Recent advances in photoacoustic blind source spectral unmixing approaches and the enhanced detection of endogenous tissue chromophores

Recently, the development of learning-based algorithms has shown a crucial role to extract features of vital importance from multi-spectral photoacoustic imaging. In particular, advances in spectral photoacoustic unmixing algorithms can identify tissue biomarkers without a priori information. This has the potential to enhance the diagnosis and treatment of a large number of diseases. Here, we investigated the latest progress within spectral photoacoustic unmixing approaches. We evaluated the sensitivity of different unsupervised Blind Source Separation (BSS) techniques such as Principal Component Analysis (PCA), Independent Component Analysis (ICA), and Non-negative Matrix Factorization (NNMF) to distinguish absorbers from spectral photoacoustic imaging. Besides, the performance of a recently developed superpixel photoacoustic unmixing (SPAX) framework has been also examined in detail. Near-infrared spectroscopy (NIRS) has been used to validate the performance of the different unmixing algorithms. Although the NNMF has shown superior unmixing performance than PCA and ICA in terms of correlation and processing time, this is still prone to unmixing misinterpretation due to spectral coloring artifact. Thus, the SPAX framework, which also compensates for the spectral coloring effect, has shown improved sensitivity and specificity of the unmixed components. In addition, the SPAX also reveals the most and less prominent tissue components from sPAI at a volumetric scale in a data-driven way. Phantom experimental measurements and in vivo studies have been conducted to benchmark the performance of the BSS algorithms and the SPAX framework.

Photoacoustic image-guided biomimetic nanoparticles targeting rheumatoid arthritis

The high level of reactive oxygen species (ROS) in the rheumatoid arthritis (RA) microenvironment (RAM) and its persistent inflammatory nature can promote damage to joints, bones, and the synovium. Targeting strategies that integrate effective RAM regulation with imaging-based monitoring could lead to improvements in the diagnosis and treatment of RA. Here, we report the combined use of small interfering RNAs (siRNAsT/I) and Prussian blue nanoparticles (PBNPs) to silence the expression of proinflammatory cytokines TNF-α/IL-6 and scavenge the ROS associated with RAM. To enhance the invitro and invivo biological stability, biocompatibility, and targeting capability of the siRNAsT/I and PBNPs, macrophage membrane vesicles were used to prepare biomimetic nanoparticles, M@P-siRNAsT/I. The resulting constructs were found to suppress tumor necrosis factor-α/interleukin-6 expression and overcome the hypoxic nature of RAM, thus alleviating RA-induced joint damage in a mouse model. The M@P-siRNAsT/I of this study could be monitored via near-infrared photoacoustic (PA) imaging. Moreover, multispectral PA imaging without the need for labeling permitted the real-time evaluation of M@P-siRNAsT/I as a putative RA treatment. Clinical microcomputed tomography and histological analysis confirmed the effectiveness of the treatment. We thus suggest that macrophage-biomimetic M@P-siRNAsT/I and their analogs assisted by PA imaging could provide a new strategy for RA diagnosis, treatment, and monitoring.