Optical Monitoring of Living Brain Tissue (original) (raw)
Optical imaging as a link between cellular neurophysiology and circuit modeling
2009
Optical imaging most often refers to imaging modalities based on fl uorescent probes that transform network activity into optical signals. There are, however, approaches that use "intrinsic" optical signals that correlate with neuronal activity. These methods rely on changes in light absorption and scattering or tissue autofl uorescence, negating the need for exogenous application of chemical dyes (
Optical excitation and detection of neuronal activity
Journal of biophotonics, 2018
Optogenetics has emerged as an exciting tool for manipulating neural activity, which in turn, can modulate behavior in live organisms. However, detecting the response to the optical stimulation requires electrophysiology with physical contact or fluorescent imaging at target locations, which is often limited by photobleaching and phototoxicity. In this paper, we show that phase imaging can report the intracellular transport induced by optogenetic stimulation. We developed a multimodal instrument that can both stimulate cells with subcellular spatial resolution and detect optical pathlength changes with nanometer scale sensitivity. We found that optical pathlength fluctuations following stimulation are consistent with active organelle transport. Furthermore, the results indicate a broadening in the transport velocity distribution, which is significantly higher in stimulated cells compared to optogenetically inactive cells. It is likely that this label-free, contactless measurement of...
Non-invasive detection of fluorescence from exogenous chromophores in the adult human brain
NeuroImage, 2006
This is the first report on results proving that fluorescence of exogenous dyes inside the human brain can be excited and detected non-invasively at the surface of the adult head. Boli of indocyanine green (ICG) were intravenously applied to healthy volunteers, and the passage of the contrast agent in the brain was monitored by detecting the corresponding fluorescence signal following pulsed laser excitation at 780 nm. Our hypothesis that the observed fluorescence signal contains a considerable cortical fraction was corroborated by performing measurements with picosecond temporal resolution and analyzing distributions of times of arrival of photons, hence taking advantage of the well-known depth selectivity of that method. Our experimental findings are explained by Monte Carlo simulations modeling the head as a layered medium and taking into account realistic bolus kinetics within the extraand intracerebral compartment. Although a particular non-specific dye (ICG) was used, the results clearly demonstrate that fluorescencemediated imaging of the adult human brain is generally feasible. In particular, we will discuss how these results serve as proof of concept for non-invasive fluorescence brain imaging and may thus open the door towards optical molecular imaging of the human brain. D
Seeing right through you: applications of optical imaging to the study of the human brain
2003
A new set of techniques allows for the study of brain function by near-infrared light, exploiting two optical phenomena: Changes in light absorption are determined by changes in the concentration of substances like oxy-and deoxyhemoglobin, and changes in light scattering occur as a consequence of variations of properties of membranes and corpuscles in the neural tissue. Methods based on light absorption can be used to study hemodynamic changes in the brain, whereas those based on light scattering can be used to study neuronal activity and to provide anatomical information at a cellular and subcellular level. Three optical imaging approaches can be used to study living tissue: reflection, optical coherence tomography (OCT), and photon migration. These three approaches vary in their penetration (from less than a millimeter for reflection to up to 3-5 cm for photon migration) and spatial resolution (from a micron level for reflection and OCT to a millimeter and centimeter level for photon migration). This issue includes a collection of articles reviewing applications of these technologies to the study of brain and other bodily functions in humans.
CHAPTER 16. In vivo Brain Functional Imaging Using Oxygenation-related Optical Signal
Quenched-phosphorescence Detection of Molecular Oxygen, 2018
Over the last two decades brain optical imaging methods have yielded a number of revolutionary results when applied to the functional mapping of the cerebral cortex. The purpose of this review is to analyze research capabilities and limitations of the different optical imaging techniques based on the visualization of oxygenation and deoxygenation processes in the brain tissue, and the main capabilities and findings provided by these methods in experimental neuroscience. Starting with the general introduction of brain tissue physiology, we will describe the intrinsic optical imaging technique and several other optical oxygen imaging methods introduced during the last years, and then focusing on the phosphorescence quenching methods. So far, these methods, which operate in the different experimental settings and perform different analytical tasks, have been validated in the experiments with model animals, and some of them have potential for use under clinical settings with human patients.
Development of integrated semiconductor optical sensors for functional brain imaging
2008
Optical imaging of neural activity is a widely accepted technique for imaging brain function in the field of neuroscience research, and has been used to study the cerebral cortex in vivo for over two decades. Maps of brain activity are obtained by monitoring intensity changes in back-scattered light, called Intrinsic Optical Signals (IOS), that correspond to fluctuations in blood oxygenation and volume associated with neural activity. Current imaging systems typically employ bench-top equipment including lamps and CCD cameras to study animals using visible light. Such systems require the use of anesthetized or immobilized subjects with craniotomies, which imposes limitations on the behavioral range and duration of studies. The ultimate goal of this work is to overcome these limitations by developing a single-chip semiconductor sensor using arrays of sources and detectors operating at near-infrared (NIR) wavelengths. A single-chip implementation, combined with wireless telemetry, will eliminate the need for immobilization or anesthesia of subjects and allow in vivo studies of free behavior. NIR light offers additional advantages because it experiences less absorption in animal tissue than visible light, which allows for imaging through superficial tissues. This, in turn, reduces or eliminates the need for traumatic surgery and enables long-term brain-mapping studies in freely-behaving animals. This dissertation concentrates on key engineering challenges of implementing the sensor. This work shows the feasibility of using a GaAs-based array of vertical-cavity v surface emitting lasers (VCSELs) and PIN photodiodes for IOS imaging. I begin with in vivo studies of IOS imaging through the skull in mice, and use these results along with computer simulations to establish minimum performance requirements for light sources and detectors. I also evaluate the performance of a current commercial VCSEL for IOS imaging, and conclude with a proposed prototype sensor. vi A doctoral degree is one of the most challenging undertakings someone can pursue, in part because of the amount of time required, and also because of the uncertainty that comes with doing original research. It is not an accomplishment achieved alone. As with others before me, I owe many thanks to a great number of people, without whom the work contained in this dissertation would not have been possible. I owe perhaps the greatest thanks to my family, especially my parents. My father, Ching-li Lee, was a cancer immunologist who instilled in me a passion for learning in general and an interest in science in particular. He passed away in 1991, when I was fourteen years old, leaving my mother, Ming-lea Lee, to raise three children on her own. My mother was a tireless worker, and made countless sacrifices to ensure the success of her children. It is to them that this work is dedicated. I am also thankful for the love and support of my brother George, an ever-present character foil in my life, and my sister Jenny, who kept me clothed throughout graduate school through her job in the fashion industry. My girlfriend, Sumer Seiki, has been a tireless champion and cheerleader. Sumer's parents, Don and Marian Seiki, also deserve much thanks for their endless support, particularly for all the food that they cooked for me and the heaping leftovers they would give me each time I visited them. I also owe a large debt of gratitude to the many people who enabled me to complete this particular work. First is my Principal Adviser, Professor James S. Harris, vii affectionately known as "The Coach". I first met Coach when I was a Master's degree student working for him as a teaching assistant. At the time, interdisciplinary biomedical research was on the rise, and I was impressed with both the breath of his knowledge and his willingness to pursue interdisciplinary research. He has an amazing mind, and his ability to adapt his research focus and attract the best students is second-to-none. It has been the greatest honor to be part of his research group. I also owe significant thanks Professor Krishna V. Shenoy, for serving as my associate adviser, Professor Stephen Smith, for sitting on my reading committee, and Professor Dwight Nishimura for serving as the chairperson for my oral examination. Prof. Smith is a pioneer in developing tools to study neuroscience, and his experience and insight were invaluable. Prof. Shenoy's work in neural prosthetics first inspired me to consider research in a neuroscience-related field, and led me to this project. He was also instrumental in helping me to focus my research and organize my thoughts. He was a constant source of encouragement, and without him I probably would have quit my studies long ago. Successful interdisciplinary research requires many collaborators, and this work was no different. I would like to thank Breault Research Organization (BRO) for providing free licenses for their ASAP simulation package, and Paul Holcomb at BRO for writing much of the simulation code. Dr. Mary Hibbs-Brenner and Klein Johnson at Vixar, Inc. generously donated the VCSELs used in the noise characterization work, Mr. Keith Gaul with the EE Department loaned me critical equipment, and Dr. Darwin Serkland at Sandia National Laboratory provided helpful information on VCSEL RIN. Professor Michael Stryker at UCSF, graciously allowed us to use his IOS imaging setup, and Dr. Jianhua Cang (now a professor at Northwestern University), and Dr. Megumi Kaneko performed the mouse surgery and imaging setup for the initial IOS wavelength studies. Professors Bruce Tromberg and Anthony Durkin, as well as Drs. Carol Hyakawa, David Cuccia, David Abookasis and Ms. Jessie Weber viii at UC Irvine provided invaluable advice and technical insight into tissue optics. My colleagues in the Harris Group are among the best minds in the world, and have provided a rich intellectual and social environment. Gail Chun-Creech, Prof. Harris's Administrative Assistant, deserves special recognition for her daily Herculean efforts to keep the group running smoothly. Evan Thrush, Ofer Levi, and Meredith Lee introduced me to the project that eventually became this thesis, and helped me through my first few years. Lynford Goddard's input into laser characterization and Paul Lim's help with noise measurements were keys to completing the VCSEL noise characterization. Thomas O'Sullivan and Anjia Gu proved to be wonderful roommates and friends. Zhilong Rao and I shared many a struggle together as office mates, and many others, including Seth Bank,
Biomedical Optics Express, 2015
The application of the fluorescence imaging method to living animals, together with the use of genetically engineered animals and synthesized photo-responsive compounds, is a powerful method for investigating brain functions. Here, we report a fluorescence imaging method for the brain surface and deep brain tissue that uses compact and mass-producible semiconductor imaging devices based on complementary metal-oxide semiconductor (CMOS) technology. An image sensor chip was designed to be inserted into brain tissue, and its size was 1500 × 450 μm. Sample illumination is also a key issue for intravital fluorescence imaging. Hence, for the uniform illumination of the imaging area, we propose a new method involving the epi-illumination of living biological tissues, and we performed investigations using optical simulations and experimental evaluation.
Non-Invasive Functional Optical Brain Imaging Methods: A Review
https://www.ijrrjournal.com/IJRR\_Vol.7\_Issue.5\_May2020/Abstract\_IJRR0020.html, 2020
Optical Brain Imaging is basically an imaging technique which uses light for understanding structures of our brain for various medical applications. Optical brain imaging methods within the last few years have showed tremendous revolutionary development. The current review is mainly focused on principles of novel brain imaging techniques. The methods included in this review are Intrinsic optical imaging, Diffuse Optical Tomography, Photoacoustic Microscopy, Diffuse Optical Tomography, Terahertz radiation, Near infrared microscopy, Voltage-sensitive dyes imaging, Ca 2+ and other ion sensitive dye Imaging, Auto fluorescence and Metabolic related optical imaging and Optical coherence tomography. Some of these methods find their applications in clinical research and others in experimental neuroscience.
NeuroImage, 2011
Cortical spreading depression (CSD) plays an important role in trauma, migraine and ischemia. CSD could induce pronounced hemodynamic changes and the disturbance of pH homeostasis which has been postulated to contribute to cell death following ischemia. In this study, we described a fluorescence-corrected multimodal optical imaging system to simultaneously monitor CSD associated intracellular pH (pH i) changes and hemodynamic response including hemoglobin concentrations and cerebral blood flow (CBF). CSD was elicited by application of KCl on rat cortex and direct current (DC) potential was recorded as a typical characteristic of CSD. The pH i shift was mapped by neutral red (NR) fluorescence which was excited at 516-556 nm and emitted at 625 nm. The changes in hemoglobin concentrations were determined by dualwavelength optical intrinsic signal imaging (OISI) at 550 nm and 625 nm. Integration of fluorescence imaging and dual-wavelength OISI was achieved by a time-sharing camera equipped with a liquid crystal tunable filter (LCTF). CBF was visualized by laser speckle contrast imaging (LSCI) through a separate camera. Besides, based on the dual-wavelength optical intrinsic signals (OISs) obtained from our system, NR fluorescence was corrected according to our method of fluorescence correction. We found that a transient intracellular acidification followed by a small alkalization occurred during CSD. After CSD, there was a prolonged intracellular acidification and the recovery of pH i from CSD took much longer time than those of hemodynamic response. Our results suggested that the new multimodal optical imaging system had the potential to advance our knowledge of CSD and might work as a useful tool to exploit neurovascular coupling under physiological and pathological conditions.
Use of voltage-sensitive dyes and optical recordings in the central nervous system
Progress in Neurobiology, 1995
Understanding the spatio-temporal features of the information processing occurring in any complex neural structure requires the monitoring and analysis of the activity in populations of neurons. Electrophysiological and other mapping techniques have provided important insights into the function of neural circuits and neural populations in many systems. However, there remain limitations with these approaches. Therefore, complementary techniques which permit the monitoring of the spatio-temporal activity in neuronal populations are of continued interest. One promising approach to monitor the electrical activity in potmlations of neurons or on multiple sites of a single neuron is with voltage-sensitive dyes coupled with optical r~cording techniques. This review concentrates on the use of voltage-sensitive dyes and optical imaging as tools to study the activity in neuronal populations in the central nervous system. Focusing on 'fast' voltage.sensitive dyes first, several technical issues and developments in optical imaging will be reviewed. These will include more recent developments in voltage-sensitive dyes as well as newer developments in optical recording technology. Second, studies using voltage-sensitive dyes to investigate information processing questions in the central nervous system and in the invertebrate nervous system will be reviewed. Some emphasis will be placed on the cerebellum, but the major goal is to survey how voltage-sensitive dyes and optical recordings have been utilized in the central nervous system. The review will include optical studies on the visual, auditory, olfactory, somatosensory, auditory, hippocampal and brainstem systems, as well as single cell studies addressing information processing questions. Discussion of the intrinsic optical signals is also included. The review attempts to show how voltage-sensitive dyes and optical recordings can be used to obtain high spatial and temporal resolution monitoring of neuronal activity.