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Author: Xiang Wu (Researcher in deep-tissue light delivery) Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
The application of light in biological research has significantly enhanced our understanding of the complex processes within living organisms, resulting in a multitude of breakthroughs and advancements in fields such as medicine and biotechnology. However, one significant challenge that limits the utility of light in vivo lies in the strong absorption and scattering of photons by the biological tissues, which prevent efficient and precise light delivery deep into the body. To address this challenge, we developed acoustic and optical bio-interfaces that can non-invasively deliver photons deep inside the tissue for various applications. First, we synthesized multi-color mechanoluminescent (ML) colloids as ultrasound-mediated nanoscopic light sources using a biomineral-inspired suppressed dissolution approach. This synthesis approach utilizes a unique phenomenon of suppressed dissolution observed in Nature, and can produce ML colloids down to 20 nm from their micro-sized precursors while preserving the optical properties. The produced ML colloids can be systemically delivered into the blood stream, and produce transient and localized light emission upon the stimulation of deep-penetrating focused ultrasound (FUS). We demonstrated that the ultrasound-mediated light emission can activate channelrhodopsin-2 (ChR2)-expressing neurons in the mouse brain, producing significant behavioral and histological changes. The use of an acoustic interface eliminates any brain implants or scalp incision, thus allowing non-invasive neuromodulation. Second, using a similar synthesis strategy, we produced multi-color persistent luminescence (PerL) colloids as circulation-delivered light sources. These PerL colloids can store photoexcitation energy in the lattice, and gradually release it as light in an extended period of time. We showed that these PerL colloids are among the brightest afterglow materials ever reported, with short emission wavelengths desired for activating light-sensitive proteins. We then demonstrated the utility of these PerL colloids in excitation-free imaging of brain vasculatures after systemic delivery, and used them as internal light sources to excite endogenously expressed fluorescent proteins in the mouse brain. Third, we developed an optical neuromodulation technique in the second near-infrared window (NIR-II, 1000−1700 nm) using semiconducting polymer nanotransducers with bandgap engineering. After local delivery into the brain, these nanotransducers strongly absorb brain-penetrant NIR-II light and efficiently convert it into heat, which can then activate ectopically expressed temperature sensitive ion channels for neuromodulation. We demonstrated the utility of this NIR-II neuromodulation technique in the motor cortex, hippocampus, and ventral tegmental area (VTA) of mice, producing significant behavioral, histological, and electrophysiological changes. The use of an NIR-II interface allows complete elimination of invasive brain implants and head tethering, which will be advantageous for the future study of social interactions in rodents.
Author: Fei Xia Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
Imaging with high spatial resolution and high specificity within intact tissues at depth has long been a critical research objective for implementation in biological studies. The development of imaging tools with the capability of deep imaging at cellular resolution would allow for more realistic and complicated biological hypotheses to be tested in their natural environment - intravitally. The most challenging aspects of such tool developments involve light scattering and aberration, which cause the light to distort along its propagation direction, limiting both its imaging depth and resolution. This thesis attempts to provide several solutions to overcomes these challenges. To overcome light scattering, imaging within the short-wave infrared region (SWIR, wavelength 1 - 2.5 micrometers) is explored in chapters 2-4. In chapter 2 and 3, reflectance confocal and fluorescence confocal microscopy are demonstrated providing 2-4 times deeper penetration than any previously reported work and preclude the possibility of using one-photon confocal microscopy for deep imaging, a method that has been rarely discussed. Furthermore, a study on the impact of staining inhomogeneity on the depth limit of fluorescence confocal microscopy also demonstrated the potential of confocal microscopy combined with SWIR and low staining inhomogeneity to achieve unprecedented imaging depth. After demonstrating the deep imaging capability of one-photon imaging at depth with a SWIR light source, a multimodal system combining three-photon, third-harmonic, and optical coherence microscopy (OCM) is demonstrated in chapter 4. This multimodal system was able to achieve simultaneous imaging depth comparable to imaging with multiple contrast mechanisms in terms of the fluorescence, the harmonic signal, and the backscattering. Furthermore, this multimodal system provided complementary information about the mouse in vivo and represented a powerful intravital biological imaging tool. To overcome light aberration, adaptive optical methods are demonstrated in chapters 5-7. In chapter 5, a sensorless, adaptive optics, and indirect wavefront sensing system is demonstrated to improve SWIR-excited three-photon imaging, achieving about 7x signal enhancement in the mouse hippocampus area. This method is based on using the nonlinear three-photon fluorescence signal as feedback and involves light exposure during the optimization process. To reduce light exposure, a more direct wavefront sensing method is explored using a SWIR OCM system to directly sense the complex field of a biological sample in chapter 6. The advantage of this system, including its potential high-speed wavefront sensing and offline wavefront estimation, and its limitations with respect to phase stability are discussed. Finally, in chapter 7, a direct wavefront sensing method based on a cheap silicon wavefront sensor is presented. This method provides a convenient approach for aberration measurement with any experiment that involves SWIR ultrafast laser. This thesis shows the great promise to achieve high-resolution deep tissue imaging at a larger depth by combining longer wavelength at short-wave infrared region and adaptive optics. It is anticipated that this thesis work will open doors to much more exciting biological research in the near future.
Author: Bingbing Cheng Publisher: ISBN: Category : Diagnostic imaging Languages : en Pages : 135
Book Description
Fluorescence microscopic imaging in centimeter-deep tissue has been highly sought-after for many years because much interesting in vivo micro-information--such as microcirculation, tumor angiogenesis, and cancer metastasis--may deeply locate in tissue. However, it is very challenging because of strong tissue light scattering. This includes: how to confine the fluorescence emission into a small volume to achieve high spatial resolution; how to increase fluorescence emission efficiency to compensate the signal attenuation caused by small emission volume and tissue scattering/absorption; and how to reduce background fluorescence noise and exclusively differentiate signal photons from background photons to increase signal-to-noise ratio (SNR) and sensitivity. Ultrasonic scattering is two to three orders of magnitude less than light scattering in opaque biological tissue. Therefore, light focusing has been replaced by ultrasonic focusing to achieve high spatial resolution in deep tissue. In addition, high intensity focused ultrasound (HIFU) can noninvasively heat a small region deep within the body (hundreds of microns in lateral). If one can develop a contrast agent whose fluorescence emission is sensitive to this HIFU-induced temperature change and a sensitive imaging system which can detect the ultrasound-controlled photons that have been scattered many times, centimeter-deep tissue fluorescence microscopic imaging can be achievable. This study is focused on developing a fundamentally different imaging technology: ultrasound-switchable fluorescence (USF), including the contrast agent development and the imaging system development. Basically, the USF contrast agent developed in this work is thermosensitive and its fluorescence emission has a switch-like relationship with temperature. Its fluorescence emission can be switched on or off by a focused ultrasound beam generated from a HIFU transducer within its focal volume. Then the diffused USF photons propagate out and are detected by a sensitive USF imaging system. First, the excellent USF imaging contrast agents were developed by using the environment-sensitive fluorophores and thermosensitive polymers. We started investigating environment-sensitive fluorophores from visible light range up to near infrared (NIR) range since only NIR light can penetrate centimeter-deep in opaque biological tissues. Two basic thermosensitive polymers and their co-polymers were used, including: poly (N-isopropylacrylamide) (PNIPAM) and pluronic. Both linear polymer and nanoparticle based USF contrast agents were explored. Second, a sensitive frequency domain (FD) USF imaging system and an effective signal identification algorithm were developed. The lock-in amplifier adopted in the FD-USF imaging system and the correlation algorithm significantly improved the SNR and detection sensitivity. Third, the feasibility of USF imaging in centimeter-deep tissue with high resolution was demonstrated in both tissue-mimicking phantoms and ex vivo biological tissues. Multi-color high-resolution USF imaging in centimeter-deep tissue with high SNR and picomole sensitivity were also achieved. Fourth, the feasibility of in vivo USF imaging was demonstrated in living mice by using different types of USF contrast agents via both intravenous and local injections. In summary, the results provided in this work demonstrated for the first time the feasibility of centimeter-deep tissue fluorescence microscopic imaging with high SNR and picomole sensitivity via USF in tissue-mimicking phantoms, porcine muscle tissues, ex vivo mouse organs (liver and spleen), and in vivo mice. Multiplex USF imaging was also achieved, which is useful to simultaneously image multiple targets and observe their interactions. This work opens the door for future studies of center-deep tissue fluorescence microscopic imaging.
Author: National Research Council Publisher: National Academies Press ISBN: 030916463X Category : Science Languages : en Pages : 222
Book Description
Scientists and engineers have long relied on the power of imaging techniques to help see objects invisible to the naked eye, and thus, to advance scientific knowledge. These experts are constantly pushing the limits of technology in pursuit of chemical imagingâ€"the ability to visualize molecular structures and chemical composition in time and space as actual events unfoldâ€"from the smallest dimension of a biological system to the widest expanse of a distant galaxy. Chemical imaging has a variety of applications for almost every facet of our daily lives, ranging from medical diagnosis and treatment to the study and design of material properties in new products. In addition to highlighting advances in chemical imaging that could have the greatest impact on critical problems in science and technology, Visualizing Chemistry reviews the current state of chemical imaging technology, identifies promising future developments and their applications, and suggests a research and educational agenda to enable breakthrough improvements.
Author: Roberta Brayner Publisher: Springer Science & Business Media ISBN: 1447142136 Category : Technology & Engineering Languages : en Pages : 398
Book Description
With the increased presence of nanomaterials in commercial products such as cosmetics and sunscreens, fillers in dental fillings, water filtration process, catalysis, photovoltaic cells, bio-detection, a growing public debate is emerging on toxicological and environmental effects of direct and indirect exposure to these materials. Nanomaterials: A Danger or a Promise? forms a balanced overview of the health and environmental issues of nanoscale materials. By considering both the benefits and risks associated with nanomaterials, Nanomaterials: A Danger or a Promise? compiles a complete and detailed image of the many aspects of the interface between nanomaterials and their real-life application. The full cycle of nanomaterials life will be presented and critically assessed to consider and answer questions such as: How are nanomaterials made? What they are used for? What is their environmental fate? Can we make them better? Including coverage of relevant aspects about the toxicity of manufactured nanomaterials, nanomaterials life cycle, exposure issues, Nanomaterials: A Danger or a Promise? provides a comprehensive overview of the actual knowledge in these fields but also presents perspectives for the future development of a safer nanoscience. This comprehensive resource is a key reference for students, researcher, manufacturers and industry professionals alike.
Author: Surya N. Thakur Publisher: Elsevier ISBN: 0323972012 Category : Science Languages : en Pages : 692
Book Description
Photoacoustic and Photothermal Spectroscopy: Principles and Applications introduces the basic principles, instrumentation and major developments in the many applications of Photoacoustic and Photothermal Spectroscopy over the last three decades. The book explains the processes of sound generation by periodic optical excitation and ultrasonic generation by pulsed laser excitation and describes the workings of photoacoustic cells equipped with microphones and piezoelectric transducers. Photoacoustic imaging (PAI) is one of the fastest-growing imaging modalities of recent times. It combines the advantages of ultrasound and optical imaging techniques. These non-invasive and non-destructive techniques offer many benefits to users by enabling spectroscopy of opaque and inhomogeneous materials, (solid, liquid, powder, gel, gases) without any sample preparation, and more. Written in a non-mathematical, simple-to-read manner Presents recent developments in the field, along with the scope of future progress, including up-to-date references Includes detailed illustrations, such as equipment layout, spectra, experimental setups, tables, photographs, and more