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Journal ArticleDOI

Recent progress in tissue optical clearing

TL;DR: Using the tissue optical clearing technique with advanced microscopy image or labeling technique, applications for 3D microstructure of whole tissues such as brain and central nervous system with unprecedented resolution are demonstrated.
Abstract: Tissue optical clearing technique provides a prospective solution for the application of advanced optical methods in life sciences. This paper gives a review of recent developments in tissue optical clearing techniques. The physical, molecular and physiological mechanisms of tissue optical clearing are overviewed and discussed. Various methods for enhancing penetration of optical-clearing agents into tissue, such as physical methods, chemical-penetration enhancers and combination of physical and chemical methods are introduced. Combining the tissue optical clearing technique with advanced microscopy image or labeling technique, applications for 3D microstructure of whole tissues such as brain and central nervous system with unprecedented resolution are demonstrated. Moreover, the difference in diffusion and/or clearing ability of selected agents in healthy versus pathological tissues can provide a highly sensitive indicator of the tissue health/pathology condition. Finally, recent advances in optical clearing of soft or hard tissue for in vivo imaging and phototherapy are introduced.

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Citations
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Journal ArticleDOI
01 Apr 1988-Nature
TL;DR: In this paper, a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) is presented.
Abstract: Deposits of clastic carbonate-dominated (calciclastic) sedimentary slope systems in the rock record have been identified mostly as linearly-consistent carbonate apron deposits, even though most ancient clastic carbonate slope deposits fit the submarine fan systems better. Calciclastic submarine fans are consequently rarely described and are poorly understood. Subsequently, very little is known especially in mud-dominated calciclastic submarine fan systems. Presented in this study are a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) that reveals a >250 m thick calciturbidite complex deposited in a calciclastic submarine fan setting. Seven facies are recognised from core and thin section characterisation and are grouped into three carbonate turbidite sequences. They include: 1) Calciturbidites, comprising mostly of highto low-density, wavy-laminated bioclast-rich facies; 2) low-density densite mudstones which are characterised by planar laminated and unlaminated muddominated facies; and 3) Calcidebrites which are muddy or hyper-concentrated debrisflow deposits occurring as poorly-sorted, chaotic, mud-supported floatstones. These

9,929 citations

Journal ArticleDOI
01 Oct 2015-Nature
TL;DR: The distribution of α-catulin–GFP+c-kit+ cells indicated that HSCs were more common in central marrow than near bone surfaces, and in the diaphysis relative to the metaphysis, indicating that α- catulin−GFP−c-Kit+ cells are comparable in HSC purity to cells obtained using the best markers currently available.
Abstract: Haematopoietic stem cells (HSCs) reside in a perivascular niche but the specific location of this niche remains controversial. HSCs are rare and few can be found in thin tissue sections or upon live imaging, making it difficult to comprehensively localize dividing and non-dividing HSCs. Here, using a green fluorescent protein (GFP) knock-in for the gene Ctnnal1 in mice (hereafter denoted as α-catulin(GFP)), we discover that α-catulin(GFP) is expressed by only 0.02% of bone marrow haematopoietic cells, including almost all HSCs. We find that approximately 30% of α-catulin-GFP(+)c-kit(+) cells give long-term multilineage reconstitution of irradiated mice, indicating that α-catulin-GFP(+)c-kit(+) cells are comparable in HSC purity to cells obtained using the best markers currently available. We optically cleared the bone marrow to perform deep confocal imaging, allowing us to image thousands of α-catulin-GFP(+)c-kit(+) cells and to digitally reconstruct large segments of bone marrow. The distribution of α-catulin-GFP(+)c-kit(+) cells indicated that HSCs were more common in central marrow than near bone surfaces, and in the diaphysis relative to the metaphysis. Nearly all HSCs contacted leptin receptor positive (Lepr(+)) and Cxcl12(high) niche cells, and approximately 85% of HSCs were within 10 μm of a sinusoidal blood vessel. Most HSCs, both dividing (Ki-67(+)) and non-dividing (Ki-67(-)), were distant from arterioles, transition zone vessels, and bone surfaces. Dividing and non-dividing HSCs thus reside mainly in perisinusoidal niches with Lepr(+)Cxcl12(high) cells throughout the bone marrow.

543 citations

Journal ArticleDOI
TL;DR: How combining new clearing techniques with high-performing fluorescent proteins or small molecule tags, rapid volume imaging and efficient image informatics is resulting in comprehensive and quantitative organ-wide, single-cell resolution experimental data is discussed.

238 citations


Cites background from "Recent progress in tissue optical c..."

  • ...Dehydration that occurs during clearing also contributes to the efficiency of the clearing process, beyond the fluid volume replacement by RI-adjusting reagents (Jiang and Wang, 2004; Rylander et al., 2006; Yu et al., 2011; Zhu et al., 2013)....

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  • ...Although tissue clearing has a history that’s more than 100 years long (Spalteholz, 1914; Zhu et al., 2013), tissueclearing methods that can be implemented on practical timescales of days to weeks with a reasonable clearing efficiency for optic imaging are a much more recent development (Hama et…...

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  • ...Although tissue clearing has a history that’s more than 100 years long (Spalteholz, 1914; Zhu et al., 2013), tissueclearing methods that can be implemented on practical timescales of days to weeks with a reasonable clearing efficiency for optic imaging are a much more recent development (Hama et al....

    [...]

Journal ArticleDOI
TL;DR: The substantial reduction of light scattering multiplicity at tissue optical clearing that leads to a lesser influence of scattering on the measured intrinsic polarization properties of the tissue and allows for more precise quantification of these properties is demonstrated.
Abstract: This tutorial-review introduces the fundamentals of polarized light interaction with biological tissues and presents some of the recent key polarization optical methods that have made possible the quantitative studies essential for biomedical diagnostics. Tissue structures and the corresponding models showing linear and circular birefringence, dichroism, and chirality are analyzed. As the basis for a quantitative description of the interaction of polarized light with tissues, the theory of polarization transfer in a random medium is used. This theory employs the modified transfer equation for Stokes parameters to predict the polarization properties of single- and multiple-scattered optical fields. The near-order of scatterers in tissues is accounted for to provide an adequate description of tissue polarization properties. Biomedical diagnostic techniques based on polarized light detection, including polarization imaging and spectroscopy, amplitude and intensity light scattering matrix measurements, and polarization-sensitive optical coherence tomography are described. Examples of biomedical applications of these techniques for early diagnostics of cataracts, detection of precancer, and prediction of skin disease are presented. The substantial reduction of light scattering multiplicity at tissue optical clearing that leads to a lesser influence of scattering on the measured intrinsic polarization properties of the tissue and allows for more precise quantification of these properties is demonstrated.

231 citations

Journal ArticleDOI
TL;DR: FDISCO is an effective alternative to the three-dimensional mapping of whole organs and can be extensively used in biomedical studies and is compatible with labeling by multiple viruses and enables fine visualization of neurons with weak fluorescence labeling in the whole brain.
Abstract: Various optical clearing methods have emerged as powerful tools for deep biological imaging. Organic solvent–based clearing methods, such as three-dimensional imaging of solvent-cleared organs (3DISCO), present the advantages of high clearing efficiency and size reduction for panoptic imaging of large samples such as whole organs and even whole bodies. However, 3DISCO results in a rapid quenching of endogenous fluorescence, which has impeded its application. Here, we propose an advanced method named FDISCO to overcome this limitation. FDISCO can effectively preserve the fluorescence of various fluorescent probes and can achieve a long storage time of months while retaining potent clearing capability. We used FDISCO for high-resolution imaging and reconstruction of neuronal and vascular networks. Moreover, FDISCO is compatible with labeling by multiple viruses and enables fine visualization of neurons with weak fluorescence labeling in the whole brain. FDISCO represents an effective alternative to the three-dimensional mapping of whole organs and can be extensively used in biomedical studies.

148 citations

References
More filters
Journal ArticleDOI
01 Apr 1988-Nature
TL;DR: In this paper, a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) is presented.
Abstract: Deposits of clastic carbonate-dominated (calciclastic) sedimentary slope systems in the rock record have been identified mostly as linearly-consistent carbonate apron deposits, even though most ancient clastic carbonate slope deposits fit the submarine fan systems better. Calciclastic submarine fans are consequently rarely described and are poorly understood. Subsequently, very little is known especially in mud-dominated calciclastic submarine fan systems. Presented in this study are a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) that reveals a >250 m thick calciturbidite complex deposited in a calciclastic submarine fan setting. Seven facies are recognised from core and thin section characterisation and are grouped into three carbonate turbidite sequences. They include: 1) Calciturbidites, comprising mostly of highto low-density, wavy-laminated bioclast-rich facies; 2) low-density densite mudstones which are characterised by planar laminated and unlaminated muddominated facies; and 3) Calcidebrites which are muddy or hyper-concentrated debrisflow deposits occurring as poorly-sorted, chaotic, mud-supported floatstones. These

9,929 citations

Journal ArticleDOI
06 Apr 1990-Science
TL;DR: The fluorescence emission increased quadratically with the excitation intensity so that fluorescence and photo-bleaching were confined to the vicinity of the focal plane as expected for cooperative two-photon excitation.
Abstract: Molecular excitation by the simultaneous absorption of two photons provides intrinsic three-dimensional resolution in laser scanning fluorescence microscopy. The excitation of fluorophores having single-photon absorption in the ultraviolet with a stream of strongly focused subpicosecond pulses of red laser light has made possible fluorescence images of living cells and other microscopic objects. The fluorescence emission increased quadratically with the excitation intensity so that fluorescence and photo-bleaching were confined to the vicinity of the focal plane as expected for cooperative two-photon excitation. This technique also provides unprecedented capabilities for three-dimensional, spatially resolved photochemistry, particularly photolytic release of caged effector molecules.

8,905 citations

Journal ArticleDOI
23 Mar 2012-Science
TL;DR: A review of the state of the art of photoacoustic tomography for both biological and clinical studies can be found in this paper, where the authors discuss the current state-of-the-art and discuss future prospects.
Abstract: Photoacoustic tomography (PAT) can create multiscale multicontrast images of living biological structures ranging from organelles to organs. This emerging technology overcomes the high degree of scattering of optical photons in biological tissue by making use of the photoacoustic effect. Light absorption by molecules creates a thermally induced pressure jump that launches ultrasonic waves, which are received by acoustic detectors to form images. Different implementations of PAT allow the spatial resolution to be scaled with the desired imaging depth in tissue while a high depth-to-resolution ratio is maintained. As a rule of thumb, the achievable spatial resolution is on the order of 1/200 of the desired imaging depth, which can reach up to 7 centimeters. PAT provides anatomical, functional, metabolic, molecular, and genetic contrasts of vasculature, hemodynamics, oxygen metabolism, biomarkers, and gene expression. We review the state of the art of PAT for both biological and clinical studies and discuss future prospects.

3,518 citations

01 May 2010

1,984 citations


"Recent progress in tissue optical c..." refers background in this paper

  • ...Thus, better contrasting of these layers in OCT images was demonstrated for human rectum ex vivo [98] and human skin in vivo [99]....

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  • ...The temporal dependences of OCT image contrast for the epidermis–dermis junction measured at low and high pressures for volunteers of different ages were associated with different dynamics of water inflow, in particular connected with the different balance of free and bonded water for the young and aged skin and different elasticity of the skin of the various age groups [99]....

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Book
01 Jan 2000
TL;DR: The third edition of the biomedical optics classic Tissue Optics covers the continued intensive growth in tissue optics, in particular, the field of tissue diagnostics and imaging, that has occurred since 2007 as mentioned in this paper.
Abstract: This third edition of the biomedical optics classic Tissue Optics covers the continued intensive growth in tissue optics-in particular, the field of tissue diagnostics and imaging-that has occurred since 2007. As in the first two editions, Part I describes fundamentals and basic research, and Part II presents instrumentation and medical applications. However, for the reader's convenience, this third edition has been reorganized into 14 chapters instead of 9. The chapters covering optical coherence tomography, digital holography and interferometry, controlling optical properties of tissues, nonlinear spectroscopy, and imaging have all been substantially updated. The book is intended for researchers, teachers, and graduate and undergraduate students specializing in the physics of living systems, biomedical optics and biophotonics, laser biophysics, and applications of lasers in biomedicine. It can also be used as a textbook for courses in medical physics, medical engineering, and medical biology.

1,542 citations