Optical Tissue Clearing: Illuminating Brain Function and Dysfunction.

Tissue optical clearing technology has been developing rapidly in the past decade due to advances in microscopy equipment and various labeling techniques. Consistent modification of primary methods for optical tissue transparency has allowed observation of the whole mouse body at single-cell resolution or thick tissue slices at the nanoscale level, with the final aim to make intact primate and human brains or thick human brain tissues optically transparent. Optical clearance combined with flexible large-volume tissue labeling technology can not only preserve the anatomical structure but also visualize multiple molecular information from intact samples in situ. It also provides a new strategy for studying complex tissues, which is of great significance for deciphering the functional structure of healthy brains and the mechanisms of neurological pathologies. In this review, we briefly introduce the existing optical clearing technology and discuss its application in deciphering connection and structure, brain development, and brain diseases. Besides, we discuss the standard computational analysis tools for large-scale imaging dataset processing and information extraction. In general, we hope that this review will provide a valuable reference for researchers who intend to use optical clearing technology in studying the brain.

[Optical diagnostic methods for early tumour diagnosis in the upper aerodigestive tract: Quo vadis?]. / Optische Diagnoseverfahren zur Tumorfrühdiagnostik im oberen Luft-Speise-Weg: Quo vadis?

BACKGROUND: Optical diagnostic methods may simplify and improve the early diagnosis of tumours of the upper aerodigestive tract; however, these have not yet found their way into clinical routine. OBJECTIVE: This article aims to define the problems that have prevented routine use of optical diagnostic methods so far, as well as listing and also explaining potential trendsetting approaches to overcome these difficulties. MATERIALS AND METHODS: The study is based on a combined analysis of publically accessible databases (PubMed MEDLINE, Thompson Reuters Web of Science, SPIE. Digital Library; full time period available; search strings: "oral cavity", "pharynx", "larnyx", "optical diagnosis", "optical biopsy", "optical coherence tomography", "confocal endomicroscopy", "fluorescence endoscopy", "narrow band imaging", "non-linear imaging", "fluorescence lifetime imaging"), as well as personal experiences. RESULTS: Both conceptual and methodical problems were determined, and possible solutions based on current developments are discussed. CONCLUSION: Optical diagnostic methods have the potential to revolutionise early diagnosis of upper aerodigestive tract malignancies, providing the different hurdles listed in this review can be overcome.

Raman Imaging from Microscopy to Nanoscopy, and to Macroscopy.

Raman spectroscopy can not only provide intrinsic fingerprint information about a sample, but also utilize the merits of the narrow bandwidth and low background of Raman spectra, offering itself as a promising multiplex analytical technique. Raman microscopy has become particularly attractive recently because it has demonstrated itself as an important imaging technique for various samples, from biological samples and chemical systems to industrially important silicon-based wafers. In this Concept article, some of the most recent advances in Raman imaging techniques are critically reviewed, and the advantages and problems associated with the current techniques are discussed. Particular emphasis is placed on its future directions, from both the technical and application sides.

Image-guided intraoperative radiation therapy: current developments and future perspectives.

Intraoperative electron beam radiation therapy (IOERT) procedures involve the delivery of radiation to a target area during surgery by means of a specific applicator. This treatment is currently planned by means of specific systems that incorporate tools for both surgical simulation and radiation dose distribution estimation. Although the planning step improves treatment quality and facilitates follow-up, the actual position of the patient, the applicator and other tools during the surgical procedure is unknown. Image-guided navigation technologies could be introduced in IOERT treatments, but an innovative solution that overcomes the limitations of these systems in complex surgical scenarios is needed. A recent publication describes a multi-camera optical tracking system integrated in IOERT workflow. This technology has shown appropriate accuracy in phantom experiments, and could also be of interest in other surgical interventions, where the restrictions solved by this system are also present.

Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives.

To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue.

Optical molecular imaging in atherosclerosis.

Current imaging techniques focus on evaluating the anatomical structure of blood vessel wall and atherosclerotic plaque. These techniques fail to evaluate the biological processes which take place in the vessel wall and inside the plaque. Novel imaging techniques like optical imaging can evaluate the biological and cellular processes inside the plaque and provide information which can be vital for better patient risk stratification. This review highlights the various optical imaging techniques and their application in assessing biological processes in atherosclerosis.

What's new in neuroimaging methods?

The rapid advancement of neuroimaging methodology and its growing availability has transformed neuroscience research. The answers to many questions that we ask about how the brain is organized depend on the quality of data that we are able to obtain about the locations, dynamics, fluctuations, magnitudes, and types of brain activity and structural changes. In this review an attempt is made to take a snapshot of the cutting edge of a small component of the very rapidly evolving field of neuroimaging. For each area covered, a brief context is provided along with a summary of a few of the current developments and issues. Then, several outstanding papers, published in the past year or so, are described, providing an example of the directions in which each area is progressing. The areas covered include functional magnetic resonance imaging (fMRI), voxel-based morphometry (VBM), diffusion tensor imaging (DTI), electroencephalography (EEG), magnetoencephalography (MEG), optical imaging, and positron emission tomography (PET). More detail is included on fMRI; its subsections include fMRI interpretation, new fMRI contrasts, MRI technology, MRI paradigms and processing, and endogenous oscillations in fMRI.

Clinical multiphoton tomography.

Clinical multiphoton tomography and two-photon microendoscopy provide clinicians and researchers with high-resolution in vivo optical biopsies based on two-photon autofluorescence, second harmonic generation, and fluorescence lifetime imaging. This review reflects state of the art technology and reports on applications in the fields of early stage melanoma detection, skin aging, nanoparticle imaging, tissue engineering, and in situ screening of pharmaceutical and cosmetical products. So far, more than 500 patients and volunteers in Europe, Asia, and Australia have been investigated with these novel molecular imaging tools.

Optical brain imaging in vivo: techniques and applications from animal to man.

Optical brain imaging has seen 30 years of intense development, and has grown into a rich and diverse field. In-vivo imaging using light provides unprecedented sensitivity to functional changes through intrinsic contrast, and is rapidly exploiting the growing availability of exogenous optical contrast agents. Light can be used to image microscopic structure and function in vivo in exposed animal brain, while also allowing noninvasive imaging of hemodynamics and metabolism in a clinical setting. This work presents an overview of the wide range of approaches currently being applied to in-vivo optical brain imaging, from animal to man. Techniques include multispectral optical imaging, voltage sensitive dye imaging and speckle-flow imaging of exposed cortex, in-vivo two-photon microscopy of the living brain, and the broad range of noninvasive topography and tomography approaches to near-infrared imaging of the human brain. The basic principles of each technique are described, followed by examples of current applications to cutting-edge neuroscience research. In summary, it is shown that optical brain imaging continues to grow and evolve, embracing new technologies and advancing to address ever more complex and important neuroscience questions.

Looking and listening to light: the evolution of whole-body photonic imaging.

Optical imaging of live animals has grown into an important tool in biomedical research as advances in photonic technology and reporter strategies have led to widespread exploration of biological processes in vivo. Although much attention has been paid to microscopy, macroscopic imaging has allowed small-animal imaging with larger fields of view (from several millimeters to several centimeters depending on implementation). Photographic methods have been the mainstay for fluorescence and bioluminescence macroscopy in whole animals, but emphasis is shifting to photonic methods that use tomographic principles to noninvasively image optical contrast at depths of several millimeters to centimeters with high sensitivity and sub-millimeter to millimeter resolution. Recent theoretical and instrumentation advances allow the use of large data sets and multiple projections and offer practical systems for quantitative, three-dimensional whole-body images. For photonic imaging to fully realize its potential, however, further progress will be needed in refining optical inversion methods and data acquisition techniques.

Recent advances in diffuse optical imaging.

We review the current state-of-the-art of diffuse optical imaging, which is an emerging technique for functional imaging of biological tissue. It involves generating images using measurements of visible or near-infrared light scattered across large (greater than several centimetres) thicknesses of tissue. We discuss recent advances in experimental methods and instrumentation, and examine new theoretical techniques applied to modelling and image reconstruction. We review recent work on in vivo applications including imaging the breast and brain, and examine future challenges.