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1.
Sci China Life Sci ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32399767

RESUMO

Photoacoustic imaging (PAI) is an emerging technology that has been dramatically developed in the last decade. PAI, a combination of optical illumination and ultrasound detection, allows us to achieve fine resolution and obtain fruitful information of endogenous and exogenous chromophores. Among PAI imaging techniques, photoacoustic computed tomography (PACT) has been extensively used in human studies due to its deep tissue penetration (several centimeters). Alternatively, photoacoustic microscopy (PAM) offers higher resolution at the expense of penetration depth, which can also be advantageous in clinics. Recently, there has been increasing attention and studies on PAM of human tissues. In this paper, we will review principles of PAM and its applications to human tissues, including the breast tissue, carotid atheroma tissue, eye, gastrointestinal tissue, ovarian tissue and tooth ex vivo as well as the oral cavity and dermatological tissue in vivo. The paper is closed with the outlook regarding the potential applications of PAM in clinics.

2.
J Biophotonics ; 13(4): e201960200, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31920005

RESUMO

In this study, a novel photoacoustic microscopy (PAM) probe integrating white-light microscopy (WLM) modality that provides guidance for PAM imaging and complementary information is implemented. One single core of an imaging fiber bundle is employed to deliver a pulsed laser for photoacoustic excitation for PAM mode, which provides high resolution with deep penetration. Meanwhile, for WLM mode, the imaging fiber bundle is used to transmit two-dimensional superficial images. Lateral resolution of 7.2 µm for PAM is achieved. Since miniature components are used, the probe diameter is only 1.7 mm. Imaging of phantom and animals in vivo is conducted to show the imaging capability of the probe. The probe has several advantages by introducing the WLM mode, such as being able to conveniently identify regions of interest and align the focus for PAM mode. The prototype of an endoscope shows potential to facilitate clinical photoacoustic endoscopic applications.

3.
Anal Chem ; 91(9): 5499-5503, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30986341

RESUMO

We demonstrate a novel optomechanical synchronization method to achieve ultrahigh-contrast time-gated fluorescence imaging using live zebrafish as models. Silicon quantum dot nanoparticles (SiQDNPs) with photoluminescence lifetime of about 16 µs were used as the long-lived probes to enable background autofluorescence removal and multiplexing through time-gating. A continuous-wave 405 nm laser as the excitation source was focused on a rotating optical chopper on which the emission light beam obtained from an inverted fluorescence microscope was also focused but with a phase difference such that in a short delay after the excitation laser is blocked, the emission light beam passes through the optical chopper, initiating the image acquisition by a conventional sensor. Both excitation and detection time windows were synchronized by one optical chopper, eliminating the need for pulsed light source and image intensifier which is often used as ultrafast optical shutter. Through use of the cost-effective time-gating method, nearly all background autofluorescence emitted from the yolk sac of a zebrafish embryo microinjected with the SiQDNPs was removed, leading to a 45-fold increase in signal-to-background ratio. Furthermore, two kinds of fluorescence signals emitted from the microinjected SiQDNPs and the intrinsic green fluorescent protein of transgenic zebrafish larvae can be clearly separated through time-gating.

4.
J Biophotonics ; 12(3): e201800251, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30515990

RESUMO

Photoacoustic microscopy (PAM) is a noninvasive imaging technique and is excellent to study structural and functional changes in the microcirculation. In this work, a lipopolysaccharide (LPS)-induced inflammation model in mice is noninvasively evaluated by PAM. PAM is used to image the microvascular structural changes in mice for 8 hours after the LPS with different concentrations is applied. Quantitative analysis of five vessel parameters is conducted, which shows that the rate of reduction in microvasculature is highly dependent on the applied LPS concentrations. For low-concentration LPS, changes in the microvasculature are not obvious over the observation period, whereas for high-concentration LPS, quick and marked reduction in the microvasculature is observed. In addition, changes in capillaries are more significant than those in relatively large vessels. The results show that PAM is able to evaluate the inflammation mouse model by studying structural (and potentially functional) changes in the microcirculation. Furthermore, PAM may have potential for early intervention and treatment plan optimization of sepsis by monitoring the microcirculation and inflammatory response.

5.
Opt Lett ; 43(20): 4875-4878, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30320772

RESUMO

Optical-resolution photoacoustic microscopy (OR-PAM) is an emerging imaging modality for studying biological tissues. However, in conventional single-view OR-PAM, the lateral and axial resolutions-determined optically and acoustically, respectively-are highly anisotropic. In this Letter, we introduce dual-view OR-PAM to improve axial resolution, achieving three-dimensional (3D) resolution isotropy. We first use 0.5 µm polystyrene beads and carbon fibers to validate the resolution isotropy improvement. Imaging of mouse brain slices further demonstrates the improved resolution isotropy, revealing the 3D structure of cell nuclei in detail, which facilitates quantitative cell nuclear analysis.


Assuntos
Microscopia/métodos , Técnicas Fotoacústicas/métodos , Carbono , Fibra de Carbono , Imageamento Tridimensional
6.
Opt Express ; 26(17): 21700-21711, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30130872

RESUMO

We present a miniature fiber-optic ultrasound transmitter for generating high-intensity focused ultrasound (HIFU) based on photoacoustic transduction. The HIFU device consists of a fiber and a photoacoustic lens. We develop a simple fabrication procedure for making the photoacoustic lens, which is coated with candle soot nanoparticles-polydimethylsiloxane composites. The fiber is used to deliver pulsed laser for photoacoustic excitation, which facilitates the use of the HIFU device by eliminating the need of free-space optical alignment. The HIFU device (6.5 mm in diameter) produces focused acoustic pressures up to >30 MPa in peak positive with a tight -6-dB focal volume of ~100 µm and ~500 µm in the lateral and axial directions, respectively. Acoustic cavitation induced by the HIFU device is demonstrated. The miniature HIFU device facilitates handheld operation. It holds promise for clinical applications in intraoperative high-precision HIFU therapy. It can even be used for intracavitary therapy with further miniaturization.

7.
J Biophotonics ; 11(12): e201800147, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30003707

RESUMO

A novel all-optical double gradient-index (GRIN) lens optical-resolution photoacoustic microscopy (OR-PAM), termed as DGL-PAM, is demonstrated. The miniature probe consists of a single-mode fiber and double GRIN lenses for optical focusing and a miniature fiber Fabry-Perot sensor for ultrasound detection. The new design is simple and realizes high resolution with long working distance (WD) by virtue of the double GRIN lenses. The overall size of the probe is 2.7 mm in diameter. High lateral resolution of 3.7 µm (at 532 nm laser wavelength) and long WD of 5.5 mm are achieved. In vivo OR-PAM of mouse ear demonstrates the imaging ability of DGL-PAM. Since precise alignment of optical and acoustic foci is not needed, the proposed DGL-PAM is relatively easy to implement. It has potential to be developed as a low-cost, disposable OR-PAM probe and for endoscopic applications. The proposed double GRIN lenses for making miniature endoscopic probes can also be applied to other modalities, such as optical coherence tomography and confocal fluorescence microscopy, to enable high resolution and long WD.


Assuntos
Lentes , Microscopia/instrumentação , Miniaturização/instrumentação , Técnicas Fotoacústicas/instrumentação , Animais , Orelha/diagnóstico por imagem , Desenho de Equipamento , Camundongos , Folhas de Planta
8.
Opt Lett ; 43(5): 1119-1122, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29489793

RESUMO

We present a miniature probe capable of both optical-resolution (OR) and acoustic-resolution (AR) photoacoustic microscopy. A gradient-index-lens fiber and a multimode fiber are used to deliver light for OR and AR illumination, respectively. The probe achieves lateral resolution of 3.1 µm for OR mode and 46-249 µm (at depth of 1.2-4.3 mm) for AR mode, respectively. The size of the probe attains 3.7 mm in diameter, which can be used for endoscopic applications. In vivo imaging of several different parts of a mouse demonstrates the excellent imaging ability of the probe.


Assuntos
Orelha Externa/irrigação sanguínea , Olho/irrigação sanguínea , Microscopia Acústica/instrumentação , Microvasos/diagnóstico por imagem , Técnicas Fotoacústicas/instrumentação , Animais , Desenho de Equipamento , Aumento da Imagem , Camundongos , Miniaturização , Imagens de Fantasmas
9.
Opt Lett ; 43(4): 775-778, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29443991

RESUMO

Ultrasound detection is performed by measuring laser reflection off a surface plasmon resonance cavity which is integrated at a single-mode fiber end facet. It shows a total noise (or laser RIN) equivalent pressure of 9.7 KPa (or 5.2 KPa) over 0-20 MHz, a 6-dB angular detection range as large as 70° near 10 MHz, a detection bandwidth larger than 125 MHz, and a stable performance for over 20 min without feedback in ambient conditions. Its small form factor, fiber-optic integration, almost omnidirectional responsivity and large bandwidth are favorable for in vivo applications and high resolution imaging.

10.
Opt Express ; 25(21): 25023-25035, 2017 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-29041174

RESUMO

A miniature all-optical probe for high-resolution photoacoustic (PA)-ultrasound (US) imaging using a large synthetic aperture is developed. The probe consists of three optical fibers for PA excitation, US generation, and detection of acoustic waves, respectively. The fiber for PA excitation has a large numerical aperture (NA) for wide-angle laser illumination. On the other hand, the fiber with a carbon black-polydimethylsiloxane composite coated on the end face of the optical fiber is used for wide-angle US transmission through laser-US conversion. Both the excited PA and backscattered US signals are detected by a fiber-tip Fabry-Perot cavity for wide-angle acoustic detection. The probe outer diameter is only ~2 mm. The synergy of the three optical fibers makes a large-NA synthetic aperture focusing technique for high-resolution PA and US imaging possible. High PA lateral resolutions of 104-154 µm and high US lateral resolutions of 64-112 µm over a depth range of > 4 mm are obtained. Compared with other existing miniature PA-US probes, to our knowledge, our probe achieves by far the best performance in terms of lateral resolutions and imaging depth range. The constructed probe has potential for endoscopic and intravascular imaging applications that require PA and US contrasts with high resolutions over a large depth range.

11.
Opt Express ; 25(17): 20162-20171, 2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-29041700

RESUMO

Photoacoustic endoscopy (PAE) is a promising tool for the detection of atherosclerotic plaque. In this work, we propose a novel design of a side-viewing PAE probe based on a synthetic aperture focusing technique (SAFT) to enable high transverse resolution over large depth of focus (DOF) along the radial direction. A point-like ultrasonic detector is used to ensure a wide detection angle and thus a large synthetic aperture for SAFT. We first perform numerical simulation to optimize the PAE probe design, which involves the placement of the point-like detector and the diameter of a reflection rod mirror. Then, experiments are conducted based on the optimized probe design. High transverse resolution of 115-190 µm over large DOF of 3.5 mm along the radial direction is experimentally obtained. The SAFT-based PAE holds promise for endoscopic imaging with a high transverse resolution for both the surface and deep regions of tissue.


Assuntos
Técnicas Fotoacústicas/métodos , Análise Espectral , Endoscopia , Ultrassom
12.
Opt Express ; 25(2): 1421-1434, 2017 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-28158024

RESUMO

Acoustic-resolution photoacoustic microscopy (ARPAM) plays an important role in studying the microcirculation system of biological tissues with deep penetration. High lateral resolution of ARPAM is achieved by using a high numerical aperture acoustic transducer. The deteriorated lateral resolution in the out-of-focus region can be alleviated by synthetic aperture focusing technique (SAFT). Previously, we reported a three-dimensional (3D) deconvolution ARPAM to improve both lateral and axial resolutions in the focus region. In this study, we present our extension of resolution enhancement to the out-of-focus region based on two-dimensional SAFT combined with the 3D deconvolution (SAFT+Deconv). In both the focus and out-of-focus regions, depth-independent lateral resolution provided by SAFT, together with inherently depth-independent axial resolution, ensures a depth-independent point spread function for 3D deconvolution algorithm. Imaging of 10 µm polymer beads shows that SAFT+Deconv ARPAM improves the -6 dB lateral resolutions from 65-700 µm to 20-29 µm, and the -6 dB axial resolutions from 35-42 µm to 12-19 µm in an extended depth of focus (DOF) of ∼2 mm. The signal-to-noise ratio is also increased by 6-30 dB. The resolution enhancement in three dimensions is validated by in vivo imaging of a mouse's dorsal subcutaneous microvasculature. Our results suggest that SAFT+Deconv ARPAM may allow fine spatial resolution with deep penetration and extended DOF for biomedical photoacoustic applications.

13.
Biomed Opt Express ; 7(2): 369-80, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26977346

RESUMO

Acoustic-resolution photoacoustic microscopy (ARPAM) provides a spatial resolution on the order of tens of micrometers, and is becoming an essential tool for imaging fine structures, such as the subcutaneous microvasculature. High lateral resolution of ARPAM is achieved using high numerical aperture (NA) of acoustic transducer; however, the depth of focus and working distance will be deteriorated correspondingly, thus sacrificing the imaging range and accessible depth. The axial resolution of ARPAM is limited by the transducer's bandwidth. In this work, we develop deconvolution ARPAM (D-ARPAM) in three dimensions that can improve the lateral resolution by 1.8 and 3.7 times and the axial resolution by 1.7 and 2.7 times, depending on the adopted criteria, using a 20-MHz focused transducer without physically increasing its NA and bandwidth. The resolution enhancement in three dimensions by D-ARPAM is also demonstrated by in vivo imaging of the microvasculature of a chick embryo. The proposed D-ARPAM has potential for biomedical imaging that simultaneously requires high spatial resolution, extended imaging range, and long accessible depth.

14.
Photoacoustics ; 3(4): 143-150, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31467845

RESUMO

Three-dimensional photoacoustic microscopy (PAM) has gained considerable attention within the biomedical imaging community during the past decade. Detecting laser-induced photoacoustic waves by optical sensing techniques facilitates the idea of all-optical PAM (AOPAM), which is of particular interest as it provides unique advantages for achieving high spatial resolution using miniaturized embodiments of the imaging system. The review presents the technology aspects of optical-sensing techniques for ultrasound detection, such as those based on optical resonators, as well as system developments of all-optical photoacoustic systems including PAM, photoacoustic endoscopy, and multi-modality microscopy. The progress of different AOPAM systems and their representative applications are summarized.

15.
Photoacoustics ; 2(1): 39-46, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25302154

RESUMO

Ultrasound (US) and photoacoustic (PA) multimodality imaging has the advantage of combining good acoustic resolution with high optical contrast. The use of an all-optical scanhead for both imaging modalities can simplify integration of the two systems and miniaturize the imaging scanhead. Herein we propose and demonstrate an all-optical US/PA scanhead using a thin plate for optoacoustic generation in US imaging, a polymer microring resonator for acoustic detection, and a dichroic filter to switch between the two imaging modes by changing the laser wavelength. A synthetic-aperture focusing technique is used to improve the resolution and contrast. Phantom images demonstrate the feasibility of this design, and show that axial and lateral resolutions of 125 µm and 2.52°, respectively, are possible.

16.
Biomed Opt Express ; 4(11): 2657-66, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24298423

RESUMO

The feasibility of photoacoustic microscopy (PAM) for evaluation of angiogenesis inhibitor was investigated on a chick embryo model in vivo. Different concentrations of the angiogenesis inhibitor, Sunitinib, were applied to the chorioallantoic membrane (CAM) of the chick embryos. Imaging of microvasculature in embryo CAMs was acquired using a laser-scanning PAM system; while the optical microscopy (OM) capturing the microvascular images of the same set of CAMs for comparison served as a gold standard for validating the results from PAM. The microvascular density as a function of applied Sunitinib concentration has been quantified in both PAM and OM images. The results from these two modalities have a good agreement, suggesting that PAM could provide an unbiased quantification of microvascular density for objective evaluation of anti-angiogenesis medication. In comparison with conventional OM which enables only two-dimensional enface imaging, PAM is capable of three-dimensional analysis of microvessels, including not only morphology but also functions, as demonstrated in part by the imaging result on a canine bladder model. The emerging PAM technique shows promise to be used in clinical and preclinical settings for comprehensive and objective evaluation of anti-angiogenesis medications.

17.
Mol Imaging ; 12(8)2013.
Artigo em Inglês | MEDLINE | ID: mdl-24447615

RESUMO

Viewing individual cells and ambient microvasculature simultaneously is crucial for understanding tumor angiogenesis and microenvironments. We developed a confocal fluorescence microscopy (CFM) and photoacoustic microscopy (PAM) dual-modality imaging system that can assess fluorescent contrast and optical absorption contrast in biologic samples simultaneously. After staining tissues with fluorescent dye at an appropriate concentration, each laser pulse can generate not only sufficient fluorescent signals from cells for CFM but also sufficient photoacoustic signals from microvessels for PAM. To explore the potential of this system for diagnosis of bladder cancer, experiments were conducted on a rat bladder model. The CFM image depicts the morphology of individual cells, showing not only large polygonal umbrella cells but also intracellular components. The PAM image acquired at the same time provides complementary information on the microvascular distribution in the bladder wall, ranging from large vessels to capillaries. This device provides an opportunity to realize both histologic assay and microvascular characterization simultaneously. The combination of the information of individual cells and local microvasculature in the bladder offers the capability of envisioning the viability and activeness of these cells and holds promise for more comprehensive study of bladder cancer in vivo.


Assuntos
Diagnóstico por Imagem/instrumentação , Microvasos/citologia , Bexiga Urinária/irrigação sanguínea , Bexiga Urinária/citologia , Animais , Corantes Fluorescentes , Humanos , Processamento de Imagem Assistida por Computador , Microscopia Confocal , Microscopia de Fluorescência , Microvasos/ultraestrutura , Técnicas Fotoacústicas , Ratos , Reprodutibilidade dos Testes , Bexiga Urinária/ultraestrutura
18.
Photoacoustics ; 1(2): 30-35, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-24466507

RESUMO

Imaging of the cells and microvasculature simultaneously is beneficial to the study of tumor angiogenesis and microenvironments. We designed and built a fiber-optic based photoacoustic microscopy (PAM) and confocal fluorescence microscopy (CFM) dual-modality imaging system. To explore the feasibility of this all-optical device for future endoscopic applications, a microelectromechanical systems (MEMS) scanner, a miniature objective lens, and a small size optical microring resonator as an acoustic detector were employed trying to meet the requirements of miniaturization. Both the lateral resolutions of PAM and CFM were quantified to be 8.8 µm. Axial resolutions of PAM and CFM were experimentally measured to be 19 µm and 53 µm, respectively. The experiments on ex vivo animal bladder tissues demonstrate the good performance of this system in imaging not only microvasculature but also cellular structure, suggesting that this novel imaging technique holds potential for improved diagnosis and guided treatment of bladder cancer.

19.
Opt Lett ; 37(20): 4263-5, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23073431

RESUMO

Achieving photoacoustic microscopic imaging through a miniaturized scanning head is a crucial step toward high-resolution photoacoustic endoscopy. In this work, we have developed a miniaturized probe head using a microelectromechanical systems (MEMS) based mirror for raster scan of the laser beam and our newly developed super broad bandwidth microring resonator based ultrasound detector for photoacoustic signal detection. Through this all-optical design, which offers unique advantages for endoscopic applications, this system is capable of three-dimensional (3D) imaging with high resolution of 17.5 µm in lateral direction and 20 µm in axial direction at a distance of 3.7 mm. After the performance of this system was validated through the experiments on printed grids and a resolution test target, microscopic imaging of the 3D microvasculatures in canine bladders was also conducted successfully, demonstrating the potential of novel photoacoustic endoscopic in future clinical management of bladder cancer.


Assuntos
Eletricidade , Fenômenos Mecânicos , Microscopia/métodos , Miniaturização/métodos , Técnicas Fotoacústicas/métodos , Animais , Cães , Imagens de Fantasmas , Bexiga Urinária/citologia
20.
Opt Express ; 20(2): 1588-96, 2012 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-22274501

RESUMO

We propose a new scanhead design for combined ultrasound (US)/photoacoustic (PA) imaging that can be applied to dual-modality microscopy and biomedical imaging. Both imaging modalities employ the optical generation and detection of acoustic waves. The scanhead consists of an optical fiber with an axicon tip for excitation, and a microring for acoustic detection. No conventional piezoelectric device is needed, and the cost of the design makes it suitable for one-time, disposable use. Furthermore, a single laser pulse is employed to generate both US and PA signals. A subband imaging method can be applied to the receiver to enhance the contrast between the US and PA signals. Phantom data demonstrate the feasibility of this approach.


Assuntos
Tecnologia de Fibra Óptica/métodos , Microscopia/métodos , Imagens de Fantasmas , Técnicas Fotoacústicas/métodos , Ultrassonografia/métodos , Desenho de Equipamento , Estudos de Viabilidade , Tecnologia de Fibra Óptica/instrumentação , Microscopia/instrumentação , Técnicas Fotoacústicas/instrumentação , Ultrassonografia/instrumentação
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