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1.
Nat Biomed Eng ; 4(3): 286-297, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32165736

RESUMO

The monitoring of vascular-targeted therapies using magnetic resonance imaging, computed tomography or ultrasound is limited by their insufficient spatial resolution. Here, by taking advantage of the intrinsic optical properties of haemoglobin, we show that raster-scanning optoacoustic mesoscopy (RSOM) provides high-resolution images of the tumour vasculature and of the surrounding tissue, and that the detection of a wide range of ultrasound bandwidths enables the distinction of vessels of differing size, providing detailed insights into the vascular responses to vascular-targeted therapy. Using RSOM to examine the responses to vascular-targeted photodynamic therapy in mice with subcutaneous xenografts, we observed a substantial and immediate occlusion of the tumour vessels followed by haemorrhage within the tissue and the eventual collapse of the entire vasculature. Using dual-wavelength RSOM, which distinguishes oxyhaemoglobin from deoxyhaemoglobin, we observed an increase in oxygenation of the entire tumour volume immediately after the application of the therapy, and a second wave of oxygen reperfusion approximately 24 h thereafter. We also show that RSOM enables the quantification of differences in neoangiogenesis that predict treatment efficacy.


Assuntos
Diagnóstico por Imagem/métodos , Neovascularização Patológica/diagnóstico , Técnicas Fotoacústicas/métodos , Ultrassonografia/métodos , Neoplasias Vasculares/diagnóstico por imagem , Animais , Encéfalo/diagnóstico por imagem , Neoplasias do Ventrículo Cerebral/diagnóstico por imagem , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Craniotomia , Modelos Animais de Doenças , Endotelina-1 , Epinefrina , Feminino , Xenoenxertos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional , Lasers , Camundongos , Camundongos Endogâmicos BALB C , Oxigênio , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Neoplasias Vasculares/patologia , Vasoconstrição
3.
Chem Commun (Camb) ; 56(7): 1093-1096, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31894764

RESUMO

We prepared novel conjugated polymer based NIR-II nanoparticles, which display extremely high photothermal conversion efficiency (65%). Both in vitro and in vivo investigations revealed that the as-prepared nanoparticles exhibit excellent theranostic properties including an extremely high cancer cell killing ability, admirable tumor elimination efficiency (100%) and a remarkable photoacoustic imaging contrast enhancing ability.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Compostos de Organossilício/uso terapêutico , Polímeros/uso terapêutico , Tiadiazóis/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Células Hep G2 , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nanopartículas/química , Nanopartículas/efeitos da radiação , Compostos de Organossilício/química , Compostos de Organossilício/efeitos da radiação , Técnicas Fotoacústicas/métodos , Polímeros/química , Polímeros/efeitos da radiação , Nanomedicina Teranóstica/métodos , Tiadiazóis/química , Tiadiazóis/efeitos da radiação
4.
J Surg Oncol ; 121(1): 48-50, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31165483

RESUMO

BACKGROUND AND OBJECTIVES: Photoacoustic lymphangiography, which is based on photoacoustic technology, is an optical imaging that visualizes the distribution of light absorbing tissue components like hemoglobin or melanin, as well as optical absorption contrast imaging agents like indocyanine green (ICG) in the lymphatic channels, with high spatial resolution. In this report, we introduce the three-dimensional (3D) images of human lymphatic vessels obtained with photoacoustic lymphangiography. METHODS: We used the 3D photoacoustic visualization system (PAI-05). Some healthy subjects and lymphedema patients were recruited. To image the lymphatic structures of the limbs ICG was administered subcutaneously as in fluorescence lymphangiography. Photoacoustic images were acquired by irradiating the tissue using a laser at wavelengths of near-infrared region. On the same occasion, fluorescence images were also recorded. RESULTS: The lymphatic vessels up to the diameter of 0.2 mm could be observed three-dimensionally with the venules around them. In the patient-group, dermal backflow patterns were often observed as dense interconnecting 3D structures of lymphatic vessels. Collecting vessels passing below the dermis were also observed, which were not observed by fluorescence lymphography. CONCLUSIONS: Photoacoustic lymphangiography provided the detailed observation of each lymphatic vessel, leading to deeper understanding of 3D structures and physiological state of the vessel.


Assuntos
Vasos Linfáticos/diagnóstico por imagem , Linfedema/diagnóstico por imagem , Linfografia/métodos , Técnicas Fotoacústicas/métodos , Estudos de Casos e Controles , Feminino , Angiofluoresceinografia/métodos , Humanos , Imageamento Tridimensional/métodos , Pessoa de Meia-Idade
5.
Nat Biotechnol ; 38(3): 293-296, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31873214

RESUMO

We develop mid-infrared optoacoustic microscopy (MiROM) for label-free, bond-selective, live-cell metabolic imaging, enabling spatiotemporal monitoring of carbohydrates, lipids and proteins in cells and tissues. Using acoustic detection of optical absorption, MiROM converts mid-infrared sensing into a positive-contrast imaging modality with negligible photodamage and high sensitivity. We use MiROM to observe changes in intrinsic carbohydrate distribution from a diffusive spatial pattern to tight co-localization with lipid droplets during adipogenesis.


Assuntos
Aumento da Imagem/métodos , Gotículas Lipídicas/metabolismo , Técnicas Fotoacústicas/métodos , Células 3T3-L1 , Adipogenia , Animais , Metabolismo dos Carboidratos , Células HeLa , Humanos , Camundongos , Microscopia , Software , Espectroscopia de Infravermelho com Transformada de Fourier
6.
Int J Nanomedicine ; 14: 8647-8663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31806962

RESUMO

Background: Chemo-photothermal therapy has attracted intensive attention because of its low side effects and better therapeutic efficiency. Although many photothermal agents have been loaded with chemotherapeutic drugs for chemo-photothermal therapy, their applications are limited by complex synthetic protocols and long-term safety. Therefore, there is significant clinical value in the development of a simple system of biocompatible and biodegradable photothermal nanomaterials with high payloads of chemotherapeutic drugs for chemo-photothermal synergistic therapy. Materials and methods: In this study, PEG-modified polydopamine nanoparticles with mesoporous structure (MPDA-PEG) were successfully obtained by an emulsion-induced interface assembly strategy. Subsequently, paclitaxel (PTX) dissolved in acetone was loaded into the mesoporous channels of MPDA-PEG nanoparticles by solution absorption method. A PTX-loaded MPDA-PEG (MPDA-PEG-PTX) nanoplatform for combination of photothermal therapy (PTT) and chemotherapy was developed. Results: The synthesized MPDA-PEG nanoparticles had a great photothermal effect under near-infrared (NIR) laser irradiation and exhibited an enhanced photothermal effect with the increase of particle size. Meanwhile, MPDA-PEG nanoparticles also had a high payload of PTX, and the PTX release could be greatly accelerated by elevated temperature from photothermal effect. In MTT cytotoxicity assay, A549 cells incubated with MPDA-PEG-PTX under NIR laser irradiation (PTT + chemotherapy group) exhibited better therapeutic effect than single chemotherapy (MPDA-PEG-PTX group) and PTT (MPDA-PEG + Laser group). The synergistic therapeutic effect of MPDA-PEG-PTX with NIR laser irradiation in vivo was further investigated under the guidance of photoacoustic imaging (PAI), tumors of nude mice treated with MPDA-PEG-PTX with NIR laser irradiation were completely eliminated with minimal side effect. Conclusion: The MPDA-PEG-PTX nanoplatform is a simple and effective platform which can completely inhibit tumor growth with minimal side effects under NIR irradiation, and it exhibits better therapeutic effect than single chemotherapy and PTT.


Assuntos
Indóis/farmacologia , Nanopartículas/química , Paclitaxel/farmacologia , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Polímeros/farmacologia , Células A549 , Animais , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Indóis/administração & dosagem , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Tamanho da Partícula , Polímeros/administração & dosagem , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Int J Nanomedicine ; 14: 9809-9821, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849470

RESUMO

Introduction: Though widely studied for biomedical applications, the lack of current systemic studies on the in vivo fate of single-walled carbon nanohorns (SWCNHs) largely restricts their further applications, as real-time monitoring of their biodistribution remains a big challenge. Here, we aim to customize a label-free multispectral optoacoustic tomography (MSOT) method and systematically survey the fate of oxidized SWCNHs (SWCNHox) following different exposure routes by whole body imaging. Methods: Mice were given a suspension of SWCNHox with an average size of 136.4 nm via four different administration routes, and then imaged by MSOT. Results: After oral gavage, SWCNHox were mainly distributed in the gastrointestinal tract then excreted through the gut. Compared with the observation post first dosing, the accumulation of SWCNHox in the gastrointestinal tract was not obvious even after four-time oral gavage. Almost no SWCNHox were found at detectable levels in kidney, liver, blood and spleen. Following intravenous (iv) injection, SWCNHox were mainly presented and persisted in the spleen and liver, while very little in the kidney and almost none detectable in the intestine. SWCNHox accumulated significantly in the liver and spleen after four IV administrations. Following hypodermic and intramuscular injections, almost no SWCNHox could cross biological barriers and transport to the spleen, kidney or liver, likely due to their very low absorption rate. Almost all SWCNHox remained around the injection sites. For the first time, we have systematically investigated the in vivo fate of SWCNHs in a label-free and real-time manner. Conclusion: The findings of this study provide insights into the selection of appropriate exposure routes for potential biomedical applications of carbon nanomaterials.


Assuntos
Carbono/química , Nanoestruturas/administração & dosagem , Nanotubos de Carbono , Técnicas Fotoacústicas/métodos , Administração Oral , Animais , Injeções Intramusculares , Injeções Intravenosas , Injeções Subcutâneas , Camundongos Nus , Nanoestruturas/química , Distribuição Tecidual , Tomografia/métodos
8.
Nanoscale ; 11(47): 22788-22795, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31748768

RESUMO

Multifunctional theranostic nanoagents are attractive to realize comprehensive imaging and effective treatment of tumours. Herein, a novel strategy is developed to controllably guide the epitaxial growth of gold nanostructures onto MoS2 nanosheets. The as-prepared MoS2-Au nanostructures (MA) manifest an enhanced near-infrared (NIR) absorbance with strong photostability. After modification, the obtained MA-PEG shows strong X-ray attenuation and photothermal conversion ability, promising for CT and photoacoustic imaging with an enhanced intensity in tumours. Moreover, in vivo photothermal and radiation therapy with MA-PEG achieves synergistic tumour treatment efficiency through hyperthermia elevated oxygenation level and sensitized radiation therapy. This work illustrates the development of a unique MA nanostructure with enhanced NIR absorbance and strong photoelectric absorbance as a multifunctional theranostic agent with great potential for dual-modal imaging-guided photothermal-radiation therapy of cancer.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Molibdênio/química , Neoplasias/terapia , Técnicas Fotoacústicas/métodos , Nanomedicina Teranóstica/métodos , Animais , Linhagem Celular Tumoral , Eletroquímica , Feminino , Hipertermia Induzida/métodos , Luz , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas , Nanotecnologia/métodos , Transplante de Neoplasias , Oxigênio/química , Oxigênio/metabolismo , Fotoquímica , Fototerapia , Polímeros , Espectrofotometria Infravermelho , Propriedades de Superfície , Tomografia Computadorizada por Raios X , Raios X
9.
ACS Appl Mater Interfaces ; 11(49): 45467-45478, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31718131

RESUMO

Most of the existing single-component nanostructures cannot provide comprehensive diagnostic information, and their treatment strategies always have to combine other therapeutics as a complementary for effective biomedical application. Here, we adopted a facile approach to design a theranostic nanoflower (NF) with robust efficacy for comprehensive tumor diagnosis and quadruple synergistic cancer therapy. The NF is equipped with a metallic hybrid of several functional elements and flower-like superstructures and thus shows excellent in vitro and in vivo theranostic performance. It shows high X-ray attenuation coefficiency for the Bi element, strong near-infrared (NIR) plasmon absorbance and singlet oxygen (1O2) generation ability for the Mo element, and great photothermal conversion efficiency (54.7%) because of enhanced photoabsorption of the petal structure. Moreover, the NF realizes a very high doxorubicin-loading efficiency (90.0%) and bimodal pH/NIR-responsive drug release, posing a promise as a controlled drug carrier. The NF also shows excellent performance at trimodal magnetic resonance/X-ray computed tomography/photoacoustic imaging for comprehensive tumor diagnosis. To our best knowledge, it is the first time that integrating at least seven functions into one biomedical nanomaterial for well-rounded tumor theranostics has been reported. This "all-in-one" NF opens a new perspective in developing novel and efficient multifunctional nanotheranostics.


Assuntos
Doxorrubicina/farmacologia , Portadores de Fármacos/farmacologia , Neoplasias/tratamento farmacológico , Nanomedicina Teranóstica , Animais , Bismuto/química , Calcogênios/química , Calcogênios/farmacologia , Terapia Combinada , Cobre/química , Doxorrubicina/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Células HeLa , Humanos , Camundongos , Nanoestruturas/química , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Técnicas Fotoacústicas/métodos , Fotoquimioterapia/métodos , Oxigênio Singlete/química , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Nat Commun ; 10(1): 5056, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699983

RESUMO

Macrophages are one of the most functionally-diverse cell types with roles in innate immunity, homeostasis and disease making them attractive targets for diagnostics and therapy. Photo- or optoacoustics could provide non-invasive, deep tissue imaging with high resolution and allow to visualize the spatiotemporal distribution of macrophages in vivo. However, present macrophage labels focus on synthetic nanomaterials, frequently limiting their ability to combine both host cell viability and functionality with strong signal generation. Here, we present a homogentisic acid-derived pigment (HDP) for biocompatible intracellular labeling of macrophages with strong optoacoustic contrast efficient enough to resolve single cells against a strong blood background. We study pigment formation during macrophage differentiation and activation, and utilize this labeling method to track migration of pro-inflammatory macrophages in vivo with whole-body imaging. We expand the sparse palette of macrophage labels for in vivo optoacoustic imaging and facilitate research on macrophage functionality and behavior.


Assuntos
Ácido Homogentísico/química , Microscopia Intravital/métodos , Ativação de Macrófagos , Macrófagos/citologia , Técnicas Fotoacústicas/métodos , Pigmentos Biológicos/química , Coloração e Rotulagem/métodos , Animais , Materiais Biocompatíveis , Diferenciação Celular , Citocinas/metabolismo , Ouro , Células HEK293 , Células HeLa , Humanos , L-Lactato Desidrogenase/metabolismo , Macrófagos/metabolismo , Melaninas , Camundongos , Nanopartículas , Nanotubos
11.
Nanoscale ; 11(43): 20630-20637, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31641722

RESUMO

Metal organic frameworks (MOFs) have attracted great interest as a smart drug delivery platform in the battle against cancer for their intriguing properties, such as high drug loading efficiency and microenvironment responsive degradation. Hence, the development of multifunctional MOFs integrating several theranostic elements is of crucial importance. In this work, we constructed a theranostic nanoplatform (DOX/Pd@ZIF-8) based on metal-organic frameworks encapsulating 2D Pd nanosheets and DOX using an all-in-one strategy, taking the advantages of the smart drug delivery function of MOFs and the excellent optical properties of Pd nanosheets. Polydopamine (PDA) was then introduced (DOX/Pd@ZIF-8@PDA) to improve the biocompatibility. DOX/Pd@ZIF-8@PDA exhibited excellent photothermal conversion effects and optoacoustic effects due to the strong NIR light absorption of Pd nanosheets. DOX was released in a pH-dependent manner and the release rates were accelerated in acidic solutions. However burst drug release in a relatively short period could be achieved upon 808 nm laser irradiation. Moreover, the potential of DOX/Pd@ZIF-8@PDA implemented as photoacoustic imaging contrast agents in vitro and in vivo was fully exploited and dual factor activated synergetic photo-chemo cancer therapy was successfully carried out.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Raios Infravermelhos , Estruturas Metalorgânicas/química , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Técnicas Fotoacústicas/métodos , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Meios de Contraste/química , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/uso terapêutico , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Indóis/química , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Nanoestruturas/toxicidade , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Paládio/química , Fotoquimioterapia , Polímeros/química
12.
Am Heart J ; 218: 20-31, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31655414

RESUMO

Intravascular imaging has enabled in vivo assessment of coronary artery pathology and detection of plaque characteristics that are associated with increased vulnerability. Prospective invasive imaging studies of coronary atherosclerosis have demonstrated that invasive imaging modalities can detect lesions that are likely to progress and cause cardiovascular events and provided unique insights about atherosclerotic evolution. However, despite the undoubted value of the existing imaging techniques in clinical and research arenas, all the available modalities have significant limitations in assessing plaque characteristics when compared with histology. Hybrid/multimodality intravascular imaging appears able to overcome some of the limitations of standalone imaging; however, there are only few histology studies that examined their performance in evaluating plaque pathobiology. In this article, we review the evidence about the efficacy of standalone and multi-modality/hybrid intravascular imaging in assessing plaque morphology against histology, highlight the advantages and limitations of the existing imaging techniques and discuss the future potential of emerging imaging modalities in the study of atherosclerosis.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Procedimentos Endovasculares/métodos , Imagem Multimodal/métodos , Placa Aterosclerótica/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Endossonografia , Previsões , Humanos , Técnicas Fotoacústicas/métodos , Placa Aterosclerótica/patologia , Ondas de Rádio , Espectrometria de Fluorescência , Espectroscopia de Luz Próxima ao Infravermelho , Tomografia de Coerência Óptica
13.
Biomater Sci ; 7(12): 5002-5015, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31617526

RESUMO

Photoacoustic (PA) imaging is gaining momentum due to its greater depth of field, low background, and 3D imaging capabilities. However, traditional PA imaging agents (e.g. dyes, quantum dots, etc.) are usually unstable in plasma and bind to serum proteins, and thus cleared rapidly. Because of this, the nanoparticle encapsulation of PA imaging agents is becoming increasingly popular. Therefore, the rational design of carrier nanoparticles for this purpose is necessary for strong imaging signal intensity, high biosafety, and precise targeting. Herein, we systematically evaluate the influence of the chemical and physical surface functionalization of mesoporous silica nanoparticles (MSNs) on the photo-stability, loading, release, and photoacoustic (PA) signal strength of the FDA approved small molecule contrast agent, indocyanine green (ICG). Chemical functionalization involved the modification of MSNs with silanes having amine (NH2) or phosphonate (PO3) terminal groups, whereas physical modifications were performed by capping the ICG loaded MSNs with lipid bilayer (LB) or layer-by-layer (LBL) polyelectrolyte coatings. The NH2-MSNs display the highest ICG mass loading capacity (16.5 wt%) with a limited release of ICG (5%) in PBS over 48 h, while PO3-MSNs only loaded ICG around 3.5 wt%. The physically modified MSNs (i.e. LBMSNs and LBLMSNs) were vacuum loaded resulting in approximately 9 wt% loading and less than 10% ICG release in 48 h. Pure ICG was highly photo-unstable and showed 20% reduction in photoluminescence (PL) within 3 h of exposure to 800 nm, while the ICG loaded onto functionalized MSNs did not photo-degrade. Among the tested formulations, NH2-MSNs and LBLMSNs presented 4-fold in vitro PA signal intensity enhancement at a 200 µg mL-1 equivalent ICG dose. Similar to the in vitro PA imaging, NH2-MSNs and LBLMSNs performed the best when subcutaneously injected into mouse cadavers with 1.29- and 1.43-fold PA signal enhancement in comparison to the pure ICG, respectively.


Assuntos
Verde de Indocianina/química , Nanopartículas/química , Técnicas Fotoacústicas/métodos , Dióxido de Silício/química , Animais , Camundongos , Porosidade
14.
J Clin Neurosci ; 70: 242-246, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31477467

RESUMO

Accurate margin delineation and safe maximal resection of glioma is one of the most challenging problems of neurosurgery, due to its close resemblance to normal brain parenchyma. However, different intraoperative visualization methods have been used for real-time intraoperative investigation of the borders of the resection cavity, each having advantages and limitations. This preliminary study was designed to simulate multi-wavelength photoacoustic imaging for brain tumor margin delineation for maximum safe resection of glioma. Since the photoacoustic signal is directly related to the amount of optical energy absorption by the endogenous tissue chromophores such as hemoglobin; it may be able to illustrate the critical structures such as tumor vessels during surgery. The simulation of the optical and acoustic part was done by using Monte-Carlo and k-wave toolbox, respectively. As our simulation results proved, at different wavelengths and depths, the amount of optical absorption for the blood layer is significantly different from others such as normal and tumoral tissues. Furthermore, experimental validation of our approach confirms that, by using multi-wavelengths proportional to the depth of the tumor margin during surgery, tumor margin can be differented using photoacoustic imaging at various depths. Photoacoustic imaging may be considered as a promising imaging modality which combines the spectral contrast of optical imaging as well as the spatial resolution of ultrasound imaging, and may be able to delineate the vascular-rich glioma margins at different depths of the resection cavity during surgery.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Neuroimagem/métodos , Técnicas Fotoacústicas/métodos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Glioma/patologia , Glioma/cirurgia , Humanos , Margens de Excisão , Método de Monte Carlo
15.
Opt Express ; 27(14): 19369-19381, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31503697

RESUMO

Photoacoustic endomicroscopy (PAEM) is capable of imaging fine structures in digestive tract. However, conventional PAEM employs a tightly focused laser beam to irradiate the object, which results in a limited depth-of-field (DOF). Here, we propose a scanning-domain synthesis of optical beams (SDSOB) to optimize both transverse resolution and the DOF by synthetic effective focused beams in scanning domain for the PAEM. By utilizing the SDSOB technique, multiple defocused and scattered beams are refocused to synthesize virtual focuses covering a large range of depth. A transverse point spread function that is 5.7-time sharper, and a transverse spatial bandwidth that is 8.5-time broader than those of the conventional PAEM were simulatively obtained through SDSOB-PAEM at the defocus distance of 2.4 mm. We validated the transverse resolution improvement at both in- and out-focus positions via phantom experiments of carbon fibers. In addition, in vivo rabbit experiments were conducted to acquire vascular images over radial depth range of 900 µm. And further morphological analysis revealed that the SDSOB images were acquired with abundant vascular branches and nodes, large total-length and small average-length of blood vessels, which indicated that the SDSOB-PAEM achieved high-resolution imaging in distinct rectal layers. All these results suggest that the SDSOB-PAEM possesses high transverse resolution and extended DOF, which demonstrates the SDSOB-PAEM can provide more accurate information for clinical assessment.


Assuntos
Microscopia , Fenômenos Ópticos , Técnicas Fotoacústicas/métodos , Animais , Simulação por Computador , Feminino , Análise Numérica Assistida por Computador , Imagens de Fantasmas , Coelhos
17.
Nat Commun ; 10(1): 4277, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537800

RESUMO

Chronic cranial window (CCW) is an essential tool in enabling longitudinal imaging and manipulation of various brain activities in live animals. However, an active CCW capable of sensing the concealed in vivo environment while simultaneously providing longitudinal optical access to the brain is not currently available. Here we report a disposable ultrasound-sensing CCW (usCCW) featuring an integrated transparent nanophotonic ultrasonic detector fabricated using soft nanoimprint lithography process. We optimize the sensor design and the associated fabrication process to significantly improve detection sensitivity and reliability, which are critical for the intend longitudinal in vivo investigations. Surgically implanting the usCCW on the skull creates a self-contained environment, maintaining optical access while eliminating the need for external ultrasound coupling medium for photoacoustic imaging. Using this usCCW, we demonstrate photoacoustic microscopy of cortical vascular network in live mice over 28 days. This work establishes the foundation for integrating photoacoustic imaging with modern brain research.


Assuntos
Encéfalo/diagnóstico por imagem , Técnicas Fotoacústicas/métodos , Crânio/cirurgia , Ultrassonografia/métodos , Animais , Camundongos , Camundongos Endogâmicos C57BL
18.
Adv Mater ; 31(40): e1902279, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31414515

RESUMO

Surfactant-stripped micelles are formed from a commercially available cyanine fluoroalkylphosphate (CyFaP) salt dye and used for high contrast photoacoustic imaging (PAI) in the second near-infrared window (NIR-II). The co-loading of Coenzyme Q10 into surfactant-stripped CyFaP (ss-CyFaP) micelles improves yield, storage stability, and results in a peak absorption wavelength in the NIR-II window close to the 1064 nm output of Nd-YAG lasers used for PAI. Aqueous ss-CyFaP dispersions exhibit intense NIR-II optical absorption, calculated to be greater than 500 at 1064 nm. ss-CyFaP is detected through 12 cm of chicken breast tissue with PAI. In preclinical animal models, ss-CyFaP is visualized in draining lymph nodes of rats through 3.1 cm of overlaid chicken breast tissue. Following intravenous administration, ss-CyFaP accumulates in neoplastic tissues of mice and rats bearing orthotopic mammary tumors without observation of acute toxic side effects. ss-CyFaP is imaged through whole compressed human breasts in three female volunteers at depths of 2.6-5.1 cm. Taken together, these data show that ss-CyFaP is an accessible contrast agent for deep tissue PAI in the NIR-II window.


Assuntos
Mama/citologia , Mama/diagnóstico por imagem , Raios Infravermelhos , Micelas , Imagem Óptica/métodos , Técnicas Fotoacústicas/métodos , Tensoativos/química , Absorção Fisico-Química , Animais , Humanos , Camundongos , Fosfatos/química , Ratos , Ubiquinona/análogos & derivados , Ubiquinona/química
19.
Adv Mater ; 31(40): e1902885, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31423690

RESUMO

Activatable theranostic agents that can be activated by tumor microenvironment possess higher specificity and sensitivity. Here, activatable nanozyme-mediated 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) loaded ABTS@MIL-100/poly(vinylpyrrolidine) (AMP) nanoreactors (NRs) are developed for imaging-guided combined tumor therapy. The as-constructed AMP NRs can be specifically activated by the tumor microenvironment through a nanozyme-mediated "two-step rocket-launching-like" process to turn on its photoacoustic imaging signal and photothermal therapy (PTT) function. In addition, simultaneously producing hydroxyl radicals in response to the high H2 O2 level of the tumor microenvironment and disrupting intracellular glutathione (GSH) endows the AMP NRs with the ability of enhanced chemodynamic therapy (ECDT), thereby leading to more efficient therapeutic outcome in combination with tumor-triggered PTT. More importantly, the H2 O2 -activated and acid-enhanced properties enable the AMP NRs to be specific to tumors, leaving the normal tissues unharmed. These remarkable features of AMP NRs may open a new avenue to explore nanozyme-involved nanoreactors for intelligent, accurate, and noninvasive cancer theranostics.


Assuntos
Materiais Biomiméticos/química , Peroxidases/metabolismo , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Microambiente Tumoral , Animais , Benzotiazóis/química , Terapia Combinada , Camundongos , Compostos Organometálicos/química , Povidona/química , Ácidos Sulfônicos/química
20.
Opt Lett ; 44(15): 3773-3776, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31368965

RESUMO

Hypoxia, a low tissue oxygenation condition caused by insufficient oxygen supply, leads to potentially irreversible tissue damage, such as brain infarction during stroke. Intravascular oxygenation has long been used by photoacoustic imaging, among other imaging modalities, to study hypoxia. However, intravascular oxygenation describes only the oxygen supply via microcirculation, which does not directly reflect the amount of free oxygen available for metabolism in the interstitial fluid. Therefore, to fully understand hypoxia, it is highly desirable to monitor blood oxygenation as well as tissue oxygenation during the same biological process. In this work, by combining high-resolution photoacoustic microscopy (PAM) and a novel bioreducible N-oxide-based hypoxia-sensitive probe HyP-650, we have demonstrated simultaneous imaging of intravascular oxygenation and tissue hypoxia. We have established detailed chemical, optical, and photoacoustic properties of HyP-650 for hypoxic activation in vitro and in living cells. We have also performed PAM on hindlimb ischemia models and tumor-bearing mice to study the correlation between intravascular oxygenation and tissue oxygenation at various hypoxic levels. We expect that Hyp-650 enhanced photoacoustic imaging will find a variety of applications in brain and cancer research.


Assuntos
Vasos Sanguíneos/diagnóstico por imagem , Vasos Sanguíneos/metabolismo , Oxigênio/metabolismo , Técnicas Fotoacústicas/métodos , Animais , Membro Posterior/irrigação sanguínea , Isquemia/metabolismo , Isquemia/patologia , Camundongos , Microscopia , Hipóxia Tumoral
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