Handbook of Tissue Optical Clearing: New Prospects in Optical Imaging

Cover
Half Title
Title Page
Copyright Page
Table of Contents
Preface
Acknowledgments
Editors
Contributors
Part I Basic principles of tissue optical clearing
	Chapter 1 Tissue optical clearing mechanisms
		Introduction
		Refractive index matching: Phantom study
		Optical clearing mechanisms as a result of water and agent fluxes
		Mechanism discrimination through the characterization of water and OCA fluxes
		Evaluation of the optical clearing mechanisms through the refractive index kinetics
		Dissociation of collagen
		Delipidation and decalcification
		Hyperhydration
		Decolorization
		Summary
		Acknowledgments
		References
	Chapter 2 Tissue optical clearing for Mueller matrix microscopy
		Introduction
		Mueller matrix imaging
			Tissue scattering matrix
			Mueller imaging device and principle
				Measurement of Mueller matrix
				Transmitted light Mueller matrix microscopes
				Backscattering Mueller matrix imaging and microscopes
			Matrix feature extraction
				Mueller matrix elements
				Characterization parameters derived from the Mueller matrix
		Polarization imaging and characterization applied in tissue OC
			Partial polarization measurements for OC
			Full polarization imaging at OC
				Variation characteristics of Mueller matrix with TOC
				Mueller matrix features for TOC by different agents
		Polarized light interactions with tissues
			Monte Carlo simulations of tissue scattering
				Introduction
				Anisotropic scatterers and optical effects
				Tissue models and phantoms
			Simulations of OC process
				Mechanisms and models
				Comparison between simulations and experiments
		Summary
		Acknowledgments
		References
	Chapter 3 Traditional and innovative optical clearing agents
		Introduction
		Classification of OCAs
		History of tissue optical clearing technique development
		One-component OCAs
		Multicomponent OCAs
		Innovative technologies for optical clearing
		Conclusion
		Acknowledgments
		References
	Chapter 4 Chemical enhancers for improving tissue optical clearing efficacy
		Introduction
		PG/Azone/Thiazone for improving in vitro skin optical clearing efficacy
			Chemical agents
			Different OCAs for optical clearing of skin
			Quantitative evaluation of enhancement of skin optical clearing efficacy
		Chemical penetration enhancers for improving in vivo skin optical clearing
			Accessing rat cutaneous vessels based on treatment with PEG400 and Thiazone
			Comparison of PG and Thiazone for enhancing in vivo skin optical clearing
		Liquid paraffin as a penetration enhancer for glycerol
			Effect of different concentrations based on skin by OCT imaging
			Evaluation of optical clearing based on diseased skin by OCT imaging
			Evaluation based on luminal organs by ultra-high resolution OCT imaging
			Evaluation of optical clearing based on skin reflection by spectroscopy
		Summary and prospect
		Acknowledgments
		References
	Chapter 5 Human skin autofluorescence and optical clearing
		Introduction
			Preamble
			Motivations: Issues and aims
		Skin intrinsic fluorophores, optical properties, and optical clearing
			Skin intrinsic fluorophores and in vivo tissue state optical biomarkers
			Optical clearing mechanisms and skin optical properties
				Skin optical clearing principle and agents
				Chemical and physical enhancers-based Skin OC approaches
		Skin AF and OC studies using spectro-imaging techniques and modelling tools
			Fluorescence confocal microscopy
			Multiphoton excitation autofluorescence microscopy
			Light sheet microscopy
			Light-induced AF spectroscopy
				OC-induced skin AF spectra modifications
				Numerical modelling: Skin AF spectra unmixing
				Experimental modeling: Three-layer fluorescent phantoms
		Conclusion and perspectives
		Acknowledgments
		References
	Chapter 6 Molecular modeling of post-diffusion phase of optical clearing of biological tissues
		Introduction
		Stages of molecular modeling
		Immersion agents (alcohols)
		Immersion agents (sugars)
		Assessment of OCA Concentration on spatial configuration of the collagen microfibril fragment
		Summary
		Acknowledgments
		References
	Chapter 7 Refractive index measurements of tissue and blood components and OCAs in a wide spectral range
		Introduction
		Optical coherence tomography
		Total internal reflection method and dispersion calculation
		Tissue dispersion calculation from spectral measurements through the Kramers–Kronig relations
		Refractive properties of blood and its components
		Measurement of RIs of biological tissues prior OC
		RI kinetics during optical clearing treatments
		THz pulsed spectroscopy of OCAs
		Conclusion
		Acknowledgments
		References
	Chapter 8 Water migration at skin optical clearing
		Introduction
		Structure and optical properties of skin
		Methods of water content estimation
		Raman spectroscopy for skin water content assessment
		Measurement of collagen hydration affected by OC using Raman spectroscopy
		Assessment of OC influence on skin water content dependent on the bonding strength using Raman spectroscopy
		Other methods for assessment of OC influence on skin water content
		Summary
		Acknowledgments
		References
	Chapter 9 Optical and mechanical properties of cartilage during optical clearing
		Introduction
		Cartilage optics at optical clearing
			Basic concept
			Visible range
			NIR range
		Cartilage mechanics at optical clearing
			Osmotic stress
			Compression tests
			Phase-stabilized swept source OCE measurements
			Perspectives of noncontact strain mapping by phase-resolved OCE
				Basic principles of phase-resolved OCE
				Brief description of a typical experiment on OCA-induced strain mapping
				OCA-induced strain sign-changing and concentration dependence of strain
		Conclusion
		Acknowledgment
		References
	Chapter 10 Compression optical clearing
		Introduction
		The effect of external mechanical compression on the optical properties of biological tissues
		The effect of external mechanical compression on the physiological properties of biological tissue
		Water transport in biological tissues under external mechanical compression
		The effect of external mechanical compression of the skin on the spectrum of its diffuse reflectance (model)
			Skin tissue model
			The skin reflectance spectrum calculation algorithm
			Calculation results
		Effect of external mechanical compression on optical and physiological properties of the skin (experiment)
			Experimental setup and the object of study
			Experimental results
				Temporal kinetics of in vivo diffuse reflectance spectra of the skin in the visible spectrum
				Temporal kinetics of in vivo diffuse reflectance spectra of the skin in the spectral range 500–600 nm
				Kinetics of changes in blood content and the degree of oxygenation of hemoglobin in the skin tissue during compression
				Temporal kinetics of in vivo diffuse reflectance spectra of the skin in the spectral range 600–800 nm
				Temporal kinetics of in vivo diffuse reflectance spectra of the skin in the NIR
		Summary
		Acknowledgments
		References
Part II Tissue optical clearing method for biology (3D imaging)
	Chapter 11 Optical clearing for multiscale tissues and the quantitative evaluation of clearing methods in mouse organs
		Introduction
		A brief review of optical clearing methods for multiscale biological tissues
			Small sample/neonatal sample/embryo clearing
			Intact and adult organ clearing
			Whole-body clearing
			Combination of different methods
			Methods suitable for immunostaining and lipophilic dyes
		Quantitative assessment of optical clearing methods in various intact mouse organs
			Clearing time and transparency
			Morphological retention
			Fluorescence preservation
			Imaging depth
		Summary
		Acknowledgments
		References
	Chapter 12 Ultrafast aqueous clearing methods for 3D imaging
		Introduction
		Rapid and simple optical clearing methods for hundreds-micron-thick tissue sections
			Rapid optical clearing method for brain sections based on sugar/sugar-alcohol
				Sugar/sugar-alcohol solution renders brain sections transparent rapidly
				Fluorescence preservation and imaging depth improvement with sugar/sugar-alcohol solutions
				Size and morphology maintenance after clearing with sugar/sugar-alcohol solutions
			FOCM: Ultrafast optical clearing method for brain sections
				Ultrafast tissue clearing process of thin brain sections by FOCM
				FOCM enables negligible size change and morphology distortion
				FOCM improves fluorescence imaging quality
		Raid optical clearing methods for embryos and millimeter-thick adult tissue blocks
			A rapid clearing method based on formamide or formamide/polyethylene glycol
				ClearT/T2: Detergent- and solvent-free rapid tissue clearing methods
			RTF: A rapid and versatile clearing method based on ClearT2
				Improved transparency of tissues by rapid RTF clearing
				RTF enables visualization of axons in intact embryos and neurons in embryonic brain
			ScaleSQ: Rapid clearing of thick brain blocks
				Rapid clearing process of ScaleSQ
				Preservation of fluorescence and ultrastructure
		Rapid clearing methods for 3D mapping of intact organs
			ACT: A rapid and scalable clearing method for large samples
				ACT clearing system
				Comparison of ACT with other methods
				Scalability of ACT for clearing of various whole organs and whole bodies
			Ultrafast aqueous clearing system for 3D mapping of intact organs
				Clearing protocol of MACS
				Comparison of MACS with other clearing protocols
				Applicability of MACS for various whole organs and whole bodies
				Application of MACS in 3D visualization of neuronal and vascular structures
		Summary
		Acknowledgments
		References
	Chapter 13 Challenges and opportunities in hydrophilic tissue clearing methods
		Introduction
		Brief history of the development of hydrophilic tissue clearing methods
		Chemistry of hydrophilic tissue clearing methods
			Delipidation
			Decolorization
			Decalcification
			Refractive index matching
		Features of modern hydrophilic tissue clearing methods
		Opportunities for hydrophilic tissue clearing methods in histological and pathological applications
			Human 3D histology and pathology
			Design of versatile and robust 3D staining methods
		Opportunities for hydrophilic tissue clearing methods in organ- and organism-wide whole-cell profiling
			Whole-organ atlas with single-cell resolution
			Whole-organ comparison analysis of multiple samples
		Conclusions and perspectives
		References
	Chapter 14 Combination of tissue optical clearing and 3D fluorescence microscopy for high-throughput imaging of entire organs and organisms
		Introduction
			Principle of traditional TPEM
		Limitations of traditional TPEM application by light scattering
			Tissue optical clearing with TPEM
		Tissue optical clearing with LSFM
		Principle of conventional LSFM
		Three challenges and corresponding methods for LSFM
		Conclusions and outlook
		Acknowledgments
		References
	Chapter 15 Endogenous fluorescence preservation from solvent-based optical clearing
		Introduction
		Introducing a resin for archiving of cleared samples
			Screening of the resin and resin embedding of the specimens
			Resin embedding enables fluorescence preservation with repetitive long-term illumination
			Resin embedding enables fluorescence preservation during long-term storage
		Screening fluorescence-friendly organic compounds
			FluoClearBABB improves endogenous fluorescence
				Hydrocarbon content of alcoholic component contributes to fluorescence preservation
				FluoClearBABB enables long-term preservation of GFP fluorescence
			uDISCO based on diphenyl ether preserves endogenous fluorescence for months
				uDISCO maintains endogenous GFP signal for months
				uDISCO shows better fluorescence signal quality after whole-body clearing than 3DISCO
			Propyl gallate in sDISCO stabilizes fluorescence of samples immersed in DBE or BABB
				Propyl gallate prevents generation of peroxides and aldehydes and stabilizes fluorescence
				sDISCO protects fluorescence better than uDISCO and FluoClearBABB
			PEG component in PEGASOS clearing agents efficiently protects endogenous fluorescence
				PEGASOS retains most of the GFP and tdTomato fluorescence
				PEGASOS clearing medium enables long-term fluorescence preservation
				PEG component in clearing medium contributes to fluorescence preservation
		Adjusting the conditions in the clearing and storage process
			Temperature and pH adjustments in FDISCO achieves a high level of fluorescence preservation
				Development of FDISCO by temperature and pH adjustments
				FDISCO preserves the fluorescence signals of different fluorescent proteins
				Temperature adjustment is applicable to other clearing protocols
			a-uDISCO based on pH adjustment for optimization of GFP fluorescence preservation
				Determination of optimal pH value for the optimization of clearing protocol
				a-uDISCO achieves improved fluorescence preservation
		Summary
		Acknowledgments
		References
	Chapter 16 Progress in ex situ tissue optical clearing – shifting immuno-oncology to the third dimension
		Introduction
		Overview of ex situ TOC methods
			Organic solvents
			Hyperhydrating solutions
			High-refractive index aqueous solutions
			Tissue transforming methods
		Application of TOC to immune organs
			Bone and bone marrow
			Spleen
			Lymph nodes
			TOC in cancer research
		Summary
		Acknowledgments
		References
Part III Towards in vivo tissue optical clearing
	Chapter 17 In vivo skin optical clearing methods for blood flow and cell imaging
		Introduction
		Enhancement method of skin optical clearing
			Physical enhancement methods
			Chemical enhancement methods
			Combinations of physical and chemical enhancement methods
		In vivo skin optical clearing windows for vascular and cellular imaging
			Dorsal skin optical clearing window
			Ear skin optical clearing window
			Footpad skin optical clearing window
		Summary
		Acknowledgments
		References
	Chapter 18 In vivo skull optical clearing for imaging cortical neuron and vascular structure and function
		Introduction
		SOCS: Providing a surgery-free skull window
		“Transparent skull”: For chronic imaging
		SOCW: Optical clearing skull window for synaptic imaging
			Methods
			In vivo two-photon microscopy through SOCW
			Dynamic synaptic monitoring
			Repeated observation through SOCW
		USOCA: Switchable optical clearing skull window for long-term cortical observation
			Methods
			Two-photon laser scanning microscopy enhancement using USOCA
			USOCA for different ages and long-term repeated observation
			USOCA for large-field visualization of middle cerebral artery occlusion
			USOCA for visualization of cortical vascular leakage
			Safety evaluation of USOCA
		Combination of SOCW and USCOA: Syncretic in vivo skull optical clearing method for deep-cortical imaging
		VNSOCA: Skull optical clearing window for the region of visible to NIR-II light
		Summary and prospect
		Acknowledgments
		References
	Chapter 19 In vivo skin optical clearing in humans
		Introduction
		Skin structure and optical properties
		Mechanisms of skin optical clearing
		Transepidermal delivery: Physical and chemical enhancers
		Examples of human skin optical clearing in vivo applications
			Optical coherence tomography
			Reflectance, transmittance, and fluorescence spectroscopy
			Raman spectroscopy
			Photoacoustic diagnostics
			Laser speckle contrast imaging
			Hyperspectral imaging
		Conclusion
		Acknowledgments
		References
	Chapter 20 Optical clearing of blood and tissues using blood components
		Introduction
		Optical properties of blood
		Optical clearing of blood by dextrans
		Optical clearing of blood by glucose and fructose
		Optical clearing of blood by hemoglobin solutions
		Optical clearing of blood by PEG, PPG, and PG
		Optical clearing of blood in blood vessels
		In vivo optical clearing of skin by blood and hemoglobin
		In vitro optical clearing of gastric wall mucosa by hemoglobin
		Conclusions
		Acknowledgments
		References
	Chapter 21 Blood and lymph flow imaging at optical clearing
		Introduction
		Methods of optical imaging
			Optical coherence tomography
			Time-domain optical coherence tomography (TD-OCT)
			Spectral domain optical coherence tomography (SD-OCT)
			Basic mathematical model of OCT signal formation in spectral domain
			Resolving power of the OCT
			Functional OCT
			Laser speckle contrast imaging
		Optical clearing for assessment of blood and lymph microcirculation
		Summary
		Acknowledgments
		References
Part IV Combination of tissue optical clearing and optical imaging/spectroscopy for diagnostics
	Chapter 22 Optical clearing aided photoacoustic imaging in vivo
		Introduction
		Optical clearing–aided optical resolution photoacoustic imaging
		Optical clearing–aided acoustic resolution photoacoustic imaging
		Conclusions
		Acknowledgments
		References
	Chapter 23 Enhancement of contrast in photoacoustic – fluorescence tomography and cytometry using optical clearing and contrast agents
		Introduction
		Contrast and contrast-enhancing methods
		Photoacoustic contrast agents
			Endogenous contrast agents
			Exogenous contrast agents
				Metallic nanoparticles
				Carbon materials
				Semiconducting structures
				Fluorescent dyes
			Contrast agents based on plasmonic–fluorophore interfaces
		Tissue optical clearing
			Tissue optical clearing method using immersion of tissues into optical-clearing agents
			Combination of optical clearing and contrast agents
			Ultrasound-based optical clearing
			Other optical clearing approaches
		Summary
		Acknowledgment
		References
	Chapter 24 Tissue optical clearing in the terahertz range
		Introduction
		THz dielectric permeability of water and biological tissues with and without application of hyperosmotic immersion agents
		Hyperosmotic agents for THz immersion optical clearing of tissue
		Other approaches to tissue dehydration
			Introduction
			Lyophilization
			THz optical properties of frozen tissues
			THz optical properties of dehydrated tissues
			THz optical properties of paraffin-embedded tissues
			THz optical properties of mechanically compressed tissues
		Discussion
		Conclusions
		Acknowledgment
		References
	Chapter 25 Magnetic resonance imaging study of diamagnetic and paramagnetic agents for optical clearing of tumor-specific fluorescent signal in vivo
		Introduction
		Materials and methods
			Optical clearing solutions
			Animal model
			Optical imaging
			Magnetic resonance imaging
			Statistical analysis
		Results and discussion
			Fluorescence and MRI measurements. Optical clearing of skin using a diamagnetic glycerol and DMSO containing mixture
			The use of MR contrast agents for OC
		Conclusions
		Acknowledgments
		References
	Chapter 26 Use of optical clearing and index matching agents to enhance the imaging of caries, lesions, and internal structures in teeth using optical coherence tomography and SWIR imaging
		Introduction
		Optical properties of dental hard tissues from 400 to 2300 nm
			Influence of hydration
			Refractive index (RI), polarized light, and imbibing agents
		Dental caries and demineralization and remineralization
		Caries detection and diagnostics
			Conventional methods of caries detection and diagnostics
			Optical transillumination
			Reflectance measurements
				Reflectance measurements for lesion activity assessment
		Optical coherence tomography
			Caries lesions and subsurface structures from tooth occlusal surfaces
			OCT Imaging of root surfaces
		Conclusions
		Acknowledgments
		References
	Chapter 27 Optical clearing of adipose tissue
		Introduction
			Structure of adipose tissue
			Optical properties of adipose tissue
			Different approaches to optical clearing of adipose tissue
			Histological investigation of adipose tissue changes after optical clearing
		Methods and materials
			OCAs
			Experimental setup
			OC protocols
				Ex vivo OC protocol
				In vivo OC protocol
			Histological analysis of samples
		Treatments of adipose tissue ex vivo and in vivo
			Fractional laser microablation (FLMA)
			US exposure in combination with application of OCA
			Combination of US and FLMA with OCA application
		Results
			Optical clearing of VAT
			Ex vivo optical clearing of adipose tissue (results of histology)
			In vivo measurements
		Conclusion
		Acknowledgments
		References
	Chapter 28 Diabetes mellitus-induced alterations of tissue optical properties, optical clearing efficiency, and molecular diffusivity
		Introduction
		Classification of DM
		Experimental models of DM
		Glycation of proteins
		Optical and structural properties of tissues at glycation and DM development
			Blood and cardiovascular system
		Diabetic abnormalities in the structure of various tissues
		Skin pathologies induced by DM
		Conclusion
		Acknowledgments
		References
	Chapter 29 Tissue optical clearing for in vivo detection and imaging diabetes induced changes in cells, vascular structure, and function
		Introduction
		Maladjustment of skin structure induced by diabetes
		Skin optical clearing for imaging diabetes-induced immune response dysfunction
			DTH mice model
			Cellular recruitment during DTH with the development of T1D
			Motility trajectory and displacement during DTH with the development of T1D
			The motility parameters of cells during DTH as progressive T1D develops
		Visualization of T1D-induced changes in skin microvascular function with the assistance of skin optical clearing technique
			T1D-induced enhancement of cutaneous vascular permeability
			T1D-mediated dysfunction of cutaneous vascular response to stimulations
		Comparison of diabetes-mediated cortical and cutaneous vascular response dysfunctions through in vivo optical clearing windows
			In vivo optical clearing window for dynamic monitoring of blood flow and blood oxygen
			Cerebral microvascular dysfunction as T1D develops
			Quantitative comparison of cerebral and cutaneous microvascular functional response during the development of T1D
			Insulin-mediated cerebral and cutaneous function improvement in T1D mice
			Summary
		Acknowledgments
		References
	Chapter 30 Light operation on cortex through optical clearing skull window
		Introduction
		Combination of skull optical clearing and PDT for blood–brain barrier opening
			Methods
			Ex vivo assessment of BBB opening induced by photodynamic effect through optical clearing skull window
			In vivo observation of BBB opening through optical clearing skull window
			BBB opening for GM1-liposomes
			Age differences in photodynamic effect–induced BBB opening through optical clearing skull window
		Laser ablation of neuronal dendrites
			Methods
			Monitoring dendrites after laser ablation through optical clearing skull window
			Observation of microglia response after laser ablation through optical clearing skull window
		Vis-NIR-II skull optical clearing window for NIR-II light manipulation
			Methods
			NIR-II Laser-induced single blood vessel injury in cortex
		Summary and prospect
		Acknowledgments
		References
	Chapter 31 The role of optical clearing to enhance the applications of in vivo OCT and photodynamic therapy: Towards PDT of pigmented melanomas and beyond
		Introduction
		Optical clearing for in vivo tumor spectroscopy/imaging
		Photodynamic therapy of tumors
		Optical clearing in PDT treatment of melanoma
		Conclusions
		Acknowledgments
		References
	Chapter 32 Combination of tissue optical clearing and OCT for tumor diagnosis via permeability coefficient measurements
		Quantifying optical clearing agent (OCAs) permeability and clearing on human tissue with optical coherence tomography (OCT)
			Permeability coefficient measurements (pcm) and OCT human tissue imaging in vivo and in vitro
		Combination of physical and nanoparticles strategy for enhancing optical imaging performance
			Evaluation of synergy efficacy with OCAs on tissue using OCT
			TOC technique for improvement of photoacoustic imaging quality
			Nanoparticles for OCT contrast enhancement imaging
		Challenges and perspectives
		Acknowledgments and funding
		References
	Chapter 33 Optical clearing for cancer diagnostics and monitoring
		Introduction
		Enhanced tumor imaging through optical clearing
		OC-induced ultraviolet tissue windows as a new means for potential cancer diagnosis and treatment
		Evaluation of the third OC mechanism as a cancer diagnostic and monitoring procedure
		Future perspectives
		Acknowledgments
		References
	Chapter 34 Contrast enhancement and tissue differentiation in optical coherence tomography with mechanical compression
		Introduction: Mechanisms of controlling tissue optical properties by mechanical compression
		A simple model of compression effect on sample scattering properties
		Compression as a tool for controlling biotissue optical properties: A review
		Compression as a tool in optical coherence tomography ex vivo
		Effect of mechanical compression on OCT images of skin in vivo
		Combined effect of mechanical compression and temperature on OCT images of human skin
		Conclusion
		Acknowledgments
		References
	Chapter 35 Measurement of the dermal beta-carotene in the context of multimodal optical clearing
		Introduction
		Optical properties of beta-carotene
		Detection of dermal beta-carotene using multimodal OC
			Compression OC
			Immersion OC
			Computational OC
		Summary
		Acknowledgments
		References
	Chapter 36 Optical clearing and molecular diffusivity of hard and soft oral tissues
		Introduction
		Materials and methods
		Optical properties of human gums and dentin in the spectral range 350–800 nm
		OC efficiency and kinetics of human gingival tissues
		Determination of the diffusion coefficient of dyes and OCAs in dentin of a human tooth in vitro
		Conclusions and perspectives
		Acknowledgments
		References
	Chapter 37 Optical clearing and Raman spectroscopy: In vivo applications
		Introduction
		Raman spectroscopy for in vivo studies: Advantages and disadvantages
		The portable Raman system
		Summary
		Acknowledgments
		References
Index