593 research outputs found

    High-resolution photoacoustic vascular imaging in vivo using a large-aperture acoustic lens

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    Reflection-mode photoacoustic microscopy with dark-field laser pulse illumination and high frequency ultrasonic detection is used to non-invasively image blood vessels in the skin in vivo. Dark-field illumination minimizes the interference caused by strong photoacoustic signals from superficial structures. A high numerical-aperture acoustic lens provides high lateral resolution, 45-120 micrometers in this system while a broadband ultrasonic detection system provides high axial resolution, estimated to be ~15-20 micrometers. The optical illumination and ultrasonic detection are in a coaxial confocal configuration for optimal image quality. The system is capable of imaging optical-absorption contrast at up to 3 mm depth in biological tissue

    Multiview optical resolution photoacoustic microscopy

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    Optical resolution photoacoustic microscopy (OR-PAM), while providing high lateral resolution, has been limited by its relatively poor acoustically determined axial resolution. Although this limitation has been tackled in recent works by using either broadband acoustic detection or nonlinear photoacoustic effects, a flexible solution with three-dimensional optical resolution in reflection mode remains desired. Herein we present a multiview OR-PAM technique. By imaging the sample from multiple view angles and reconstructing the data using a multiview deconvolution method, we have experimentally demonstrated an isotropic optical resolution in three dimensions

    Photoacoustic tomography and sensing in biomedicine

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    Photoacoustics has been broadly studied in biomedicine, for both human and small animal tissues. Photoacoustics uniquely combines the absorption contrast of light or radio frequency waves with ultrasound resolution. Moreover, it is non-ionizing and non-invasive, and is the fastest growing new biomedical method, with clinical applications on the way. This review provides a brief recap of recent developments in photoacoustics in biomedicine, from basic principles to applications. The emphasized areas include the new imaging modalities, hybrid detection methods, photoacoustic contrast agents and the photoacoustic Doppler effect, as well as translational research topics

    Submicron-resolution Photoacoustic Microscopy of Endogenous Light-absorbing Biomolecules

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    Photoacoustic imaging in biomedicine has the unique advantage of probing endogenous light absorbers at various length scales with a 100% relative sensitivity. Among the several modalities of photoacoustic imaging, optical-resolution photoacoustic microscopy (OR-PAM) can achieve high spatial resolution, on the order of optical wavelength, at \u3c1 mm depth in biological tissue (the optical ballistic regime). OR-PAM has been applied successfully to structural and functional imaging of blood vasculature and red blood cells in vivo. Any molecules which absorb sufficient light at certain wavelengths can potentially be imaged by PAM. Compared with pure optical imaging, which typically targets fluorescent markers, label-free PAM avoids the major concerns that the fluorescent labeling probes may disturb the function of biomolecules and may have an insufficient density. This dissertation aims to advance label-free OR-PAM to the subcellular scale. The first part of this dissertation describes the technological advancement of PAM yielding high spatial resolution in 3D. The lateral resolution was improved by using optical objectives with high numerical apertures for optical focusing. The axial resolution was improved by using broadband ultrasonic transducers for ultrasound detection. We achieved 220 nm lateral resolution in transmission mode, 0.43 µm lateral resolution in reflection mode, 7.6 µm axial resolution in normal tissue, and 5.8 µm axial resolution with silicone oil immersion/injection. The achieved lateral resolution and axial resolution were the finest reported at the time. With high-resolution in 3D, PAM was demonstrated to resolve cellular and subcellular structures in vivo, such as red blood cells and melanosomes in melanoma cells. Compared with previous PAM systems, our high-resolution PAM could resolve capillaries in mouse ears more clearly. As an example application, we demonstrated intracellular temperature imaging, assisted by fluorescence signal detection, with sub-degree temperature resolution and sub-micron lateral resolution. The second part of this dissertation describes the exploration of endogenous light-absorbing biomolecules for PAM. We demonstrated cytochromes and myoglobin as new absorption contrasts for PAM and identified the corresponding optimal wavelengths for imaging. Fixed fibroblasts on slides and mouse ear sections were imaged by PAM at 422 nm and 250 nm wavelengths to reveal cytoplasms and nuclei, respectively, as confirmed by standard hematoxylin and eosin (H&E) histology. By imaging a blood-perfused mouse heart at 532 nm down to 150 µm in depth, we derived the myocardial sheet thickness and the cleavage height from an undehydrated heart for the first time. The findings promote PAM at new wavelengths and open up new possibilities for characterizing biological tissue. Of particular interest, dual-wavelength PAM around 250 nm and 420 nm wavelengths is analogous to H&E histology. The last part of this dissertation describes the development of sectioning photoacoustic microscopy (SPAM), based on the advancement in spatial resolution and new contrasts for PAM, with applications in brain histology. Label-free SPAM, assisted by a microtome, acquires serial distortion-free images of a specimen on the surface. By exciting cell nuclei at 266 nm wavelength with high resolution, SPAM could pinpoint cell nuclei sensitively and specifically in the mouse brain section, as confirmed by H&E histology. SPAM was demonstrated to generate high-resolution 3D images, highlighting cell nuclei, of formalin-fixed paraffin-embedded mouse brains without tissue staining or clearing. SPAM can potentially serve as a high-throughput and minimal-artifact substitute for histology, probe many other biomolecules and cells, and become a universal tool for animal or human whole-organ microscopy, with diverse applications in life sciences

    Photoacoustic imaging in biomedicine and life sciences

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    Photo-acoustic imaging, also known as opto-acoustic imaging, has become a widely popular modality for biomedical applications. This hybrid technique possesses the advantages of high optical contrast and high ultrasonic resolution. Due to the distinct optical absorption properties of tissue compartments and main chromophores, photo-acoustics is able to non-invasively observe structural and functional variations within biological tissues including oxygenation and deoxygenation, blood vessels and spatial melanin distribution. The detection of acoustic waves produced by a pulsed laser source yields a high scaling range, from organ level photo-acoustic tomography to sub-cellular or even molecular imaging. This review discusses significant novel technical solutions utilising photo-acoustics and their applications in the fields of biomedicine and life sciences

    Photoacoustic Tomography: Principles and Advances

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    Photoacoustic tomography (PAT) is an emerging imaging modality that shows great potential for preclinical research and clinical practice. As a hybrid technique, PAT is based on the acoustic detection of optical absorption from either endogenous chromophores, such as oxy-hemoglobin and deoxy-hemoglobin, or exogenous contrast agents, such as organic dyes and nanoparticles. Because ultrasound scatters much less than light in tissue, PAT generates high-resolution images in both the optical ballistic and diffusive regimes. Over the past decade, the photoacoustic technique has been evolving rapidly, leading to a variety of exciting discoveries and applications. This review covers the basic principles of PAT and its different implementations. Strengths of PAT are highlighted, along with the most recent imaging results

    All-optical photoacoustic microscopy

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    AbstractThree-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

    Developing Photoacoustic Tomography Devices for Translational Medicine and Basic Science Research

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    Photoacoustic (PA) tomography (PAT) provides volumetric images of biological tissue with scalable spatial resolutions and imaging depths, while preserving the same imaging contrast—optical absorption. Taking the advantage of its 100% sensitivity to optical absorption, PAT has been widely applied in structural, functional, and molecular imaging, with both endogenous and exogenous contrasts, at superior depths than pure optical methods. Intuitively, hemoglobin has been the most commonly studied biomolecule in PAT due to its strong absorption in the visible wavelength regime. One of the main focuses of this dissertation is to investigate an underexplored wavelength regime—ultraviolet (UV), which allows us to image cell nuclei without labels and generate histology-like images naturally from unprocessed biological tissue. These preparation-free and easy-to-interpret characteristics open up new possibilities for PAT to become readily applicable to other important biomedical problems (e.g., surgical margin analysis, Chapter 2) or basic science studies (e.g., whole-organ imaging, Chapter 3). For instance, we developed and optimized a PA microscopy system with UV laser illumination (UV-PAM) to achieve fast, label-free, multilayered, and histology-like imaging of human breast cancer in Chapter 2. These imaging abilities are essential to intraoperative surgical margin analysis, which enables promptly directed re-excision and reduces the number of repeat surgeries. We have incorporated the Grüneisen relaxation (GR) effect with UV-PAM to improve the performance of our UV-PAM system (e.g., the axial resolution), thus providing more accurate three-dimensional (3D) information (Chapter 4). The nonlinear PA signals caused by the GR effect enable optical sectioning capability, revealing important 3D cell nuclear distributions and internal structures for cancer diagnosis. In the final focus of this dissertation, we have implemented a low-cost PA computed tomography (PACT) system with a single xenon flash lamp as the illumination source (Chapter 5). Lasers have been commonly used as illumination light sources in PACT. However, lasers are usually expensive and bulky, limiting their applicability in many clinical usages. Therefore, the use of a single xenon flash lamp as an alternative light source was explored. We found that PACT images acquired with flash lamp illumination were comparable to those acquired with laser illumination. This low-cost and portable PACT system opens up new potentials, such as low-cost skin melanoma imaging in undeveloped countries
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