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      Photoacoustic imaging in the second near-infrared window: a review

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          Abstract.

          Photoacoustic (PA) imaging is an emerging medical imaging modality that combines optical excitation and ultrasound detection. Because ultrasound scatters much less than light in biological tissues, PA generates high-resolution images at centimeters depth. In recent years, wavelengths in the second near-infrared (NIR-II) window (1000 to 1700 nm) have been increasingly explored due to its potential for preclinical and clinical applications. In contrast to the conventional PA imaging in the visible (400 to 700 nm) and the first NIR-I (700 to 1000 nm) window, PA imaging in the NIR-II window offers numerous advantages, including high spatial resolution, deeper penetration depth, reduced optical absorption, and tissue scattering. Moreover, the second window allows a fivefold higher light excitation energy density compared to the visible window for enhancing the imaging depth significantly. We highlight the importance of the second window for PA imaging and discuss the various NIR-II PA imaging systems and contrast agents with strong absorption in the NIR-II spectral region. Numerous applications of NIR-II PA imaging, including whole-body animal imaging and human imaging, are also discussed.

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          Most cited references174

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          Contrast agents for molecular photoacoustic imaging.

          Photoacoustic imaging (PAI) is an emerging tool that bridges the traditional depth limits of ballistic optical imaging and the resolution limits of diffuse optical imaging. Using the acoustic waves generated in response to the absorption of pulsed laser light, it provides noninvasive images of absorbed optical energy density at depths of several centimeters with a resolution of ∼100 μm. This versatile and scalable imaging modality has now shown potential for molecular imaging, which enables visualization of biological processes with systemically introduced contrast agents. Understanding the relative merits of the vast range of contrast agents available, from small-molecule dyes to gold and carbon nanostructures to liposome encapsulations, is a considerable challenge. Here we critically review the physical, chemical and biochemical characteristics of the existing photoacoustic contrast agents, highlighting key applications and present challenges for molecular PAI.
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            In vivo three-photon microscopy of subcortical structures within an intact mouse brain

            Two-photon fluorescence microscopy (2PM) 1 enables scientists in various fields including neuroscience 2,3 , embryology 4 , and oncology 5 to visualize in vivo and ex vivo tissue morphology and physiology at a cellular level deep within scattering tissue. However, tissue scattering limits the maximum imaging depth of 2PM within the mouse brain to the cortical layer, and imaging subcortical structures currently requires the removal of overlying brain tissue 3 or the insertion of optical probes 6,7 . Here we demonstrate non-invasive, high resolution, in vivo imaging of subcortical structures within an intact mouse brain using three-photon fluorescence microscopy (3PM) at a spectral excitation window of 1,700 nm. Vascular structures as well as red fluorescent protein (RFP)-labeled neurons within the mouse hippocampus are imaged. The combination of the long excitation wavelength and the higher order nonlinear excitation overcomes the limitations of 2PM, enabling biological investigations to take place at greater depth within tissue.
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              Crucial breakthrough of second near-infrared biological window fluorophores: design and synthesis toward multimodal imaging and theranostics.

              The development of fluorophores and molecular probes for the second near-infrared biological window (NIR-II, 1000-1700 nm) represents an important, newly emerging and dynamic field in molecular imaging, chemical biology and materials chemistry. Because of reduced scattering, minimal absorption and negligible autofluorescence, NIR-II imaging provides high resolution, a high signal-to-noise ratio, and deep tissue penetration capability. Among various state-of-the-art bioimaging modalities, one of the greatest challenges in developing novel probes is to achieve both high resolution and sensitivity. The chemical design and synthesis of NIR-II fluorophores suitable for multimodal imaging is thus emerging as a new and powerful strategy for obtaining high-definition images. NIR-II fluorophores may convert NIR-II photons into heat for photothermal therapy and be excited by NIR-II light to produce singlet oxygen for photodynamic therapy. The presence of simultaneous diagnostic and therapeutic capabilities in a single probe can be used for precise treatment. In this review, we have focused on recent advances in the chemical design and synthesis of NIR-II fluorophores from small organic molecules to organic and inorganic nanoparticles, and we have further discussed recent advances and key operational differences in reported NIR-II imaging systems and biomedical applications based on NIR-II imaging, such as multimodal imaging, photothermal and photodynamic therapy, guidance for intraoperative surgery, and drug delivery.
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                Author and article information

                Journal
                J Biomed Opt
                J Biomed Opt
                JBOPFO
                JBO
                Journal of Biomedical Optics
                Society of Photo-Optical Instrumentation Engineers
                1083-3668
                1560-2281
                9 April 2019
                April 2019
                9 April 2019
                : 24
                : 4
                : 040901
                Affiliations
                [1]Nanyang Technological University , School of Chemical and Biomedical Engineering, Singapore
                Author notes
                [* ]Address all correspondence to Manojit Pramanik, E-mail: manojit@ 123456ntu.edu.sg
                Author information
                https://orcid.org/0000-0003-3091-7023
                https://orcid.org/0000-0003-2865-5714
                Article
                JBO-180571VRR 180571VRR
                10.1117/1.JBO.24.4.040901
                6990072
                30968648
                fde4ff5b-a504-47d9-9e54-259a76f19dc3
                © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
                History
                : 2 October 2018
                : 18 March 2019
                Page count
                Figures: 13, Tables: 0, References: 195, Pages: 20
                Funding
                Funded by: Singapore Ministry of Health’s National Medical Research Council
                Award ID: NMRC/OFIRG/0005/2016: M4062012
                Categories
                Review Papers
                Paper
                Custom metadata
                Upputuri and Pramanik: Photoacoustic imaging in the second near-infrared window: a review

                Biomedical engineering
                photoacoustic imaging,second near-infrared window,deep-tissue imaging,small animal imaging,contrast agents

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