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The Moscone Center
San Francisco, California, United States
28 January - 2 February 2017
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Brain Presentations

Clinical and Translational Neurophotonics, Optogenetics, and Optical Manipulation
(ordered by conference and paper number)


Implantable lithographically defined photonic microprobe
Paper 10470-45

Author(s):  Mohammad Amin Tadayon, Columbia Univ. (United States), et al.
Conference 10470: Endoscopic Microscopy XIII
Session 9: New Endoscopic Technologies and Advances II

We demonstrate an implantable lithographically defined photonic microprobe. The probe consists of a high index polymer waveguide monolithically integrated with a microlens of NA = 0.56. Since these probes are lithographically defined, one can arbitrarily tune the FOV of the probe between 10 microns and up to 100’s of microns in diameter, tune the NA of the lens (between 0.25 and 0.7), as well as tune the length of the probe (between a few microns to several millimeters). We image via 500 μm long microprobe the cerebral cortex region of slices from ArcCreERT2 x ChR2-EYFP transgenic mice with high resolution.


Using a wearable near-infrared spectroscopy device in children with Tourette syndrome
Paper 10472-18

Author(s):  Pou-Leng Cheong, National Chiao Tung Univ. (Taiwan), et al.
Conference 10472: Diseases in the Breast and Reproductive System IV
Session 5: Developmental Biology and Pediatrics

Tourette syndrome (TS) is a neuropsychiatric disorder with motor or vocal tics which annoy patients and their families, leading to their low-esteem or secondary comorbidities. No other objective measures except for rating scales were available. NIRS is non-invasive, can be used repeatedly with low cost and is a promising tool for infants and children. However, most present NIRS studies use heavy commercial caps done in laboratory. Our work is to use a small device in a wearable NIRS device for studying brain activities in children with TS, and aim to further develop NIRS-based neurofeedback programs for TS children or ADHD.


Photobiomodulation for the brain: has the light dawned?
Paper 10477-1

Author(s):  Michael R. Hamblin, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States), et al.
Conference 10477: Mechanisms of Photobiomodulation Therapy XIII
Session 1: PBM therapy in Neuroregeneration and Neurorehabilitation

Photobiomodulation (PBM) describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is of most concern to humans in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: sudden events (stroke, traumatic brain injury, and global ischemia), degenerative diseases (dementia, Alzheimer’s and Parkinson’s), and psychiatric disorders (depression, anxiety, post traumatic stress disorder, autism). There is some evidence that all these seemingly diverse conditions can be beneficially affected by applying light to the head. There is even the possibility that PBM could be used for cognitive enhancement in normal healthy people. In this transcranial PBM (tPBM) application, near-infrared (NIR) light is often applied to the forehead because of the better penetration (no hair, longer wavelength). Some workers have used lasers, but recently the introduction of inexpensive light emitting diode (LED) arrays has allowed the development of light emitting helmets or “brain caps”. Transcranial LED light sources are ideally suited to be home use devices. This review will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the key pre-clinical studies and clinical trials that have been undertaken for diverse brain disorders.


Synapto-protective effect of low-level light emitting diode (LED) therapy in an in vitro model of status epilepticus
Paper 10477-4

Author(s):  Namgue Hong, Dankook Univ. (Korea, Republic of), et al.
Conference 10477: Mechanisms of Photobiomodulation Therapy XIII
Session 1: PBM therapy in Neuroregeneration and Neurorehabilitation

Low-level lighy therapy (LLLT) using LED on the status epilepticus has been unknown. Status epilepticus is the serious neurological diseases, leading to severe and widespread cell damage in the brain. This study suggests that photomodulation using LLLT at 660 nm can be useful for preventing neurodegenerative diseases, especially status epilepticus.


Non-invasive therapy for traumatic brain injury with NPLT
Paper 10477-7

Author(s):  Adelaide Micci, The Univ. of Texas Medical Branch (United States), et al.
Conference 10477: Mechanisms of Photobiomodulation Therapy XIII
Session 1: PBM therapy in Neuroregeneration and Neurorehabilitation

Traumatic brain injury (TBI) is a major cause of death and disability in the US. Recently we proposed Nano Pulse Laser Therapy (NPLT) for therapy of TBI and other disorders and developed and built a novel, medical grade NPLT system generating high-energy nanosecond NIR pulses. In this study we tested the ability of NPLT to reduce the activation of microglia (which plays a crucial role in systemic long term inflammation) in a rat model of TBI. Our results show that a 5-minute transcranial application of NPLT significantly reduces the activation of microglia and prevents brain volume loss after TBI.


Transcranial red and near-infrared lasers at fluency of 8 J/cm2 enhances brain mitochondrial function in aging model
Paper 10477-28

Author(s):  Farzad Salehpour, Tabriz Univ. of Medical Sciences (Iran, Islamic Republic of), et al.
Conference 10477: Mechanisms of Photobiomodulation Therapy XIII
Session 4: Mechanisms of PBM Therapy

Recently, transcranial photobiomodulation (PBM) is proposed as an innovative modality for neuroenhancement. Present work focused on the mitochondrial protection of red and near-infrared (NIR) PBM against d-galactose induced brain aging in mice. Red (660 nm) and NIR (810 nm) lasers (at 4 and 8 J/cm2 and 10-Hz pulsed wave) were applied transcranially there day/week in d-galactose-received (500 mg/kg/subcutaneous) mice for six weeks. Transcranial PBM with red and NIR at 8 J/cm2 results in improvement of vital mitochondria, and increase in the mitochondrial membrane potential, cytochrome c oxidase activity and ATP production in the brain.


Improved identification of cranial nerves using paired-agent imaging: topical staining protocol optimization through experimentation and simulation
Paper 10478-19

Author(s):  Veronica C. Torres, Illinois Institute of Technology (United States), et al.
Conference 10478: Molecular-Guided Surgery: Molecules, Devices, and Applications IV
Session 4: Contrast Agents

A novel approach for enhanced identification of cranial nerves through optimization of imaging methods is presented. Through animal and simulation studies, candidate imaging agents, and statin and rinse protocols were evaluated. Contrast achieved with nerve-specific fluorophores was improved with direct application and co-administration of a control agent, which corrects for non-specific uptake of the targeted agent. When coupled with optimal staining time and number of rinses, this paired-agent imaging approach lends a clinically relevant method to better delineate cranial nerves and avoid accidental nerve damage.


Low level light therapy on stroke with a portable and Illumination-parameter adjustable LED helmet
Paper 10480-2

Author(s):  Pengbo Wang, Univ. of Electronic Science and Technology of China (China), et al.
Conference 10480: Clinical and Translational Neurophotonics 2018
Session 1: Operative and Post Op. Therapy

In this study, we designed a portable multi-layered 3D printed helmet with water-cooling, inside of which had been evenly placed 33 LED sources of 810nm. LEDs are placed on the brain surface with haircut. Radiation duration, pulse width, and duty cycle of each LED source can remotely and independent controlled by a particularly developed software. Six chronic, mild or moderate stroke participants were treated for three courses and got neuropsychological testing, which showed obvious improvement in memory and executive functioning. This clinical trial highlighted the great potential of transcranial LLLT as a novel, effective, and non-invasive therapy for stroke treatment.


Optical mapping of prefrontal activity in pathological gamblers
Paper 10480-7

Author(s):  Zhen Yuan, Univ. of Macau (Macao, China), et al.
Conference 10480: Clinical and Translational Neurophotonics 2018
Session 2: Optical Spectroscopy: Clinical I

Functional near-infrared spectroscopy (fNIRS) has emerged as a highly promising brain mapping technique that enables continuously and noninvasively monitoring the hemodynamic responses in the human brain. In this study, fNIRS was utilized to identify the different brain activation patterns between pathological gamblers (PGs) and heathy controls (HCs). Specifically, we examined the hemodynamic changes in the prefrontal cortex using fNIRS recordings during the completion of executive function and decision making tasks for both PGs and HCs. Our mapping results revealed that PGs and HCs exhibited notable differences in the hemodynamic responses and brain activation patterns across the prefrontal region.


Optical mapping of the brain activity in children with Down's syndrome
Paper 10480-8

Author(s):  Zhen Yuan, Univ. of Macau (Macao, China), et al.
Conference 10480: Clinical and Translational Neurophotonics 2018
Session 2: Optical Spectroscopy: Clinical I

Down’s syndrome (DS) has been shown to be associated with many neurological complications, including cognitive deficits, seizures, early-onset dementia that resembles Alzheimer’s disease, and neurological complications of systemic disorders. DS patients show to have poor performance in executive functions (EF) and fine motor skills. In this study, we examined the brain hemodynamic responses and brain activation patterns of DS children during the completion of EF and motor tasks. Revealing its neural mechanism of DS is not only able to contribute to the early intervention of this children with DS, but also increase understanding of developmental cascades in childhood.


Model choice influence on calibration of brain health monitoring using combined frequency domain near infrared spectroscopy and diffuse correlation spectroscopy
Paper 10480-12

Author(s):  Stefan A. Carp, Athinoula A. Martinos Ctr. for Biomedical Imaging, Massachusetts General Hospital (United States), et al.
Conference 10480: Clinical and Translational Neurophotonics 2018
Session 3: Optical Spectroscopy: Clinical II

Simultaneous diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS) measurements are increasingly being utilized as non-invasive methods to monitor brain health. Recently, a subject-specific calibration method has been proposed that employs probe pressure modulation to select parameters for the light transport model that isolate the pressure induced changes to the superficial skin layer. Using simulations of combined frequency domain-NIRS and DCS measurements, and data acquired on healthy volunteers and cardiovascular surgery patients, we compare the use of a layered slab geometry, that can be modeled analytically, versus a Monte Carlo based realistic head light transport model in applying this technique.


Intraoperative hyperspectral imaging of brain hemodynamics during epileptiform activity
Paper 10480-13

Author(s):  Audrey Laurence, Ecole Polytechnique de Montréal (Canada), et al.
Conference 10480: Clinical and Translational Neurophotonics 2018
Session 3: Optical Spectroscopy: Clinical II

Despite the several available tests used during pre-operative planning of epilepsy surgery, good outcome remains modest (≤65%). Here we present results obtained with an intraoperative hyperspectral imaging system illustrating how statistical analyses based on the low-frequency hemodynamic response to spikes can possibly be used as a physiological surrogate to delineate the epileptic focus during surgery. The imaging system produces cerebral blood volume and hemoglobin concentrations (HbO and HbR) maps at 20 fps. Maps obtained in 8 patients showed good concordance with the concurrent electrocorticography recordings. The system shows great potential for mapping epileptic activity during surgery and possibly improving resection accuracy.


Optical intrinsic signal imaging for brain tumor surgery
Paper 10480-14

Author(s):  Tien-Yu Hsiao, National Chiao Tung Univ. (Taiwan), et al.
Conference 10480: Clinical and Translational Neurophotonics 2018
Session 3: Optical Spectroscopy: Clinical II

Brain tumor can destroy surrounding cells by means of mechanisms and eventually lead to mortality. An accurate surgery holds the key to a good prognosis of brain tumor surgery. Nowadays, a magnetic resonance image prior to the surgery is still insufficient for clinical practice. In this study, we present an intraoperative optical intrinsic signal imaging system for brain tumor surgery as well as the data processing procedure to localize the site of tumors. Finally, lesions were distinguished successfully by examining local hemodynamic performance. From this results, we suggest that vessels in tumor regions have poor ability to provide oxygen.


Intraoperative reflectance and fluorescence spatial frequency domain imaging to enhance guidance of glioma resection
Paper 10480-18

Author(s):  Dennis J. Wirth, Dartmouth Hitchcock Medical Ctr. (United States), et al.
Conference 10480: Clinical and Translational Neurophotonics 2018
Session 4: Fluorescence Resection and Spectroscopy

A custom built wide-field imaging system was used for reflectance and 635 nm excitation of PpIX fluorescence spatial frequency domain imaging to enhance the guidance of glioma resection. SFDI was used to measure diffuse reflectance signal to map optical properties over the range of 420 nm to 720 nm. In the fluorescence regime, the demodulated signal was used to estimate the concentration and depth of PpIX. Our results show that the combination of reflectance and red-light excitation of PpIX fluorescence SFDI can allow real-time intraoperative mapping of subsurface tumors.


In vivo imaging of cerebral hemodynamics and tissue scattering in rat brain using a surgical microscope camera system
Paper 10480-21

Author(s):  Izumi Nishidate, Tokyo Univ. of Agriculture and Technology (Japan), et al.
Conference 10480: Clinical and Translational Neurophotonics 2018
Session 5: Optical Spectroscopy: Pre-Clinical I

We investigated a rapid imaging method to monitor the spatial distribution of total hemoglobin concentration, the tissue oxygen saturation, and the scattering power b in the expression of musp=a(lambda)^-b of in vivo cerebral cortex of rats during normoxia, hypoxia, and anoxia, using a surgical microscope camera system. The time courses of CHbO, CHbR, CHbT, and StO2 indicated the well-known physiological responses in cerebral cortex. On the other hand, a fast decrease in the scattering power b was observed after the respiratory arrest, which is similar to the negative deflection of the extracellular DC potential so-called anoxic depolarization.


Monte Carlo look up table-based inverse algorithm to estimate cerebral optical properties in small animals using frequency-domain near infrared spectroscopy
Paper 10480-25

Author(s):  Seung Yup Lee, Emory Univ. (United States), et al.
Conference 10480: Clinical and Translational Neurophotonics 2018
Session 5: Optical Spectroscopy: Pre-Clinical I

Absolute estimation of cerebral optical properties is challenging in small animals, including adult mice and neonatal rat pups. Herein we present a Monte Carlo lookup table-based inverse algorithm to estimate these properties non-invasively, i.e. with intact scalp/skull, using a multi-distance and multi-wavelength frequency-domain near infrared spectroscopy (FD-NIRS). Phantom and in vivo validation experiments suggest that the developed method can non-invasively estimate cerebral optical properties. Unlike other techniques, our approach enables non-invasive characterization of resting state oxygenation, comparison between animals, longitudinal assessment within a given animal, and quantification of oxygen metabolism when combined with diffuse correlation spectroscopy measurements of blood flow.


Inverse Monte Carlo lookup table method to determine cerebral tissue properties in small animals using diffuse reflectance spectroscopy
Paper 10480-26

Author(s):  Corey Zheng, Emory Univ. (United States), et al.
Conference 10480: Clinical and Translational Neurophotonics 2018
Session 5: Optical Spectroscopy: Pre-Clinical I

It is difficult to non-invasively assess cerebral optical properties of small rodents. We use diffuse reflectance spectroscopy and an inverse Monte-Carlo lookup table algorithm to estimate tissue optical properties, allowing us to obtain information about tissue oxygenation and hemoglobin concentration. We utilize this technique in both tissue-mimicking blood phantoms and in-vivo mice and neonatal rats, and compare against a commercial dissolved oxygen sensor. Our findings suggest that this approach can non-invasively assess brain optical properties in small rodents; thus enabling continuous and/or longitudinal cerebral monitoring.


Optical topography guided diffuse optical tomography for imaging brain function: a methodological study on semi-3 dimensional reconstruction
Paper 10480-28

Author(s):  Bingyuan Wang, Tianjin Univ. (China), et al.
Conference 10480: Clinical and Translational Neurophotonics 2018
Session 6: Optical Spectroscopy: Pre-Clinical II

An optical topography (OT) guided diffuse optical tomography (DOT) scheme is developed for functional imaging of the occipital cortex. The method extends the previously proposed semi-three-dimensional DOT methodology to reconstruction of two-dimensional extracerebral and cerebral images using a visual cortex oriented five-layered slab geometry, and incorporate the OT localization regularization in the cerebral reconstruction to achieve enhanced quantitative accuracy and spatial resolution. We validate the methodology using simulated data and demonstrate its merits in comparison to the standalone OT and DOT.


GRIN lens based confocal system for deep brain calcium imaging
Paper 10481-1

Author(s):  Ling Fu, Britton Chance Ctr. for Biomedical Photonics (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 1: In Vivo Mouse Brain Imaging I


Stimulus-evoked functional and blood perfusion changes in the healthy and tumorous rat somatosensory cortex imaged with UHR-OCT
Paper 10481-2

Author(s):  Kostadinka Bizheva, Univ. of Waterloo (Canada), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 1: In Vivo Mouse Brain Imaging I

A functional ultra-high resolution optical coherence tomography (UHR-OCT) system and a custom built whisker stimulator were used to image in-vivo and simultaneously, stimulus evoked intrinsic optical signals (IOS) and blood perfusion changes in the rat somatosensory cortex. The UHR-OCT provided ~ 3 µm axial and ~ 5 µm lateral resolution in brain tissue at 92 kHz image acquisition rate. Both healthy rats and rats with tumours in the somatosensory cortex were imaged. Results from this study showed localized and time correlated, stimulus-evoked changes in the IOS and blood perfusion in the rat somatosensory cortex.


Deep brain two-photon NIR fluorescence imaging for study of Alzheimer's disease
Paper 10481-4

Author(s):  Congping Chen, Hong Kong Univ. of Science and Technology (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 1: In Vivo Mouse Brain Imaging I

In this study, we reported a near-infrared (NIR) probe of amyloid species for deep two-photon brain imaging in Alzheimer’s disease (AD) mouse. Compared with commonly used probes with short-wavelength emission, the NIR probe (CRANAD-3) largely improves the depth of amyloid-beta (Aβ) plaque imaging through both thinned skull and open skull cranial window. In addition, the intrinsic fluorescence of the “aging pigment” lipofuscin was characterized in vivo by using spectroscopic and lifetime imaging. This study demonstrated the potential of near-infrared probes for in vivo, high-resolution and deep imaging of brain amyloid in Alzheimer’s disease.


Voluntary exercise confers protection against age-related deficits in brain oxygenation in awake mice model of Alzheimer's disease
Paper 10481-50

Author(s):  Lingjie Kong, Tsinghua Univ. (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

High-speed volumetric imaging of biological dynamics in deep tissue in vivo is highly desired. Here we exploit wavefront engineering as the solution. To compensate the wavefront distortion in heterogeneous tissues, we have developed the Iterative MultiPhoton Adaptive Compensation Technique and Multi-Pupil Adaptive Optics for deep tissue imaging. On high-speed volumetric imaging, we developed an optical phase-locked ultrasound lens to achieve MHz axial scanning, which ensures volume rate up to hundreds of Hz. We also integrated these techniques and demonstrated functional imaging of neuron network in awake, behaving animals and dynamical imaging of cells trafficking in the circulation system in vivo.


Exploring with a reflectance fiber probe the biological mechanisms inducing light scattering and absorption changes during rat somatosensory cortex activation: relevance for the study of neurovascular and neurometabolic coupling mechanisms
Paper 10481-8

Author(s):  Paul Shin, KAIST (Korea, Republic of), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 2: In Vivo Mouse Brain Imaging II

Optical coherence tomography (OCT) was applied to image functional hyperemia in the rat cortex. High-speed OCT angiography imaging was performed to investigate hemodynamic stimulus response over a wide field of view. Temporal changes in vessel diameter in different vessel compartments measured from the OCT angiography images were used to monitor localized hemodynamic changes at different levels of the vessel compartments. Quantitative measurement of blood flow was also performed in arteries using the same system, but with the phase-stabilized Doppler imaging technique. Fine spatiotemporal characteristics of arterial flow as well as a stimulus-induced response of pial arteries were investigated. Our results confirm the potential of OCT for the study of neurovascular coupling in small animal models.


Optically-transparent micro-ring resonator enables longitudinal cortical imaging by photoacoustic microscopy
Paper 10481-9

Author(s):  Pierre P. Marquet, Institut Univ. en Santé Mentale de Québec, Univ. Laval (Canada), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 2: In Vivo Mouse Brain Imaging II

The intrinsic optical signal (IOS) has been widely used to study cortical activation particularly neurovascular coupling mechanisms. However the specific biological processes mediating scattering and absorption changes during cortical activation remains elusive. We have developed a reflectance fiber probe allowing to perform in vivo spectroscopic measurements. Based on a spatially resolved approach and Monte Carlo simulations, taking into account of the second moment of the phase function, due to the small S-D separation (


Infrared light alters cardiorespiratory activity in a dose and site dependent manner in the in situ arterially perfused brainstem preparation
Paper 10482-10

Author(s):  Hao Li, Northwestern Univ. (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 2: Control II

We developed a micro-ring resonator ultrasonic detector using a simple and cost-efficient soft nanoimprint lithography (NIL) technology. This new ultrasonic detector, mounted on an optically transparent substrate, can be used to create a cranial window directly in small animal brains to replace glass seals. Using this functionalized cranial window, we achieved in vivo longitudinal cortical imaging using photoacoustic microscopy.


Brainsmatics: bridging the brain science and brain-inspired artificial intelligence
Paper 10481-10

Author(s):  Qingming Luo, Suzhou Institute of Brainmatics, Huazhong Univ. of Science and Technology (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 3: Brain-Wide Imaging I

Brainsmatics refers to the integrated, systematic approach of tracing, measuring, analyzing, managing and displaying cross-level brain spatial data with multi-scale resolution. Taking the Micro-Optical Sectioning Tomography (MOST) serial techniques as the core, we have developed a multidisciplinary complete technical system for Visualizing Brain-wide Network (VBN). Based on big data of three-dimensional fine structural and functional imaging of neuron types, neural circuits and networks, vascular network et al, with definite temporal-spatial resolution and specific spatial locations, brainsmatics makes it possible to better decipher the brain function and disease and promote the brain-inspired artificial intelligence by extracting cross-level and multi-scale temporal-spatial characteristics of brain connectivity.


Mapping the quantitative cytoarchitecture of the whole mouse brain by light-sheet microscopy and digital brain atlasing
Paper 10481-11

Author(s):  Ludovico Silvestri, LENS - Lab. Europeo di Spettroscopie Non-Lineari (Italy), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 3: Brain-Wide Imaging I

Quantitative and scalable whole-brain neuroanatomical mapping, with cellular resolution and molecular specificity, poses significant technological challenges. Here, we present an experimental pipeline, involving tissue clearing, light-sheet microscopy, atlas registration and image analysis, allowing the reconstruction of 3D maps of selected cell types in the whole mouse brain. By applying our pipeline to transgenically-labeled samples, we can produce an atlas of spatial distribution of genetically-defined cell types. Besides being a valuable reference for neurobiologists, these datasets can be used to build realistic simulations of neuronal functioning, such as in the Human Brain Project.


Imaging whole mouse brains with a dual resolution serial swept-source OCT scanner
Paper 10481-12

Author(s):  Joél Lefebvre, Ecole Polytechnique de Montréal (Canada), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 3: Brain-Wide Imaging I

A dual resolution serial OCT scanner was developed. It consists in a two-arm swept-source OCT, each arm coupled with different microscope objectives (3X / 40X). Removable mirrors were used to switch between arms, thus allowing low and high-resolution acquisitions within the same sample. The low-resolution OCT volumes (3X) were stitched together to provide a 3D map of the whole mouse brain. The high-resolution volumes (40X) were stitched together to create local high-resolution 3D maps of the tissue microstructure. This setup can be used to validate diffusion MRI metrics measured at any location in ex vivo brains.


Line-illumination modulation for high-throughput optical-sectioning imaging
Paper 10481-14

Author(s):  Rui Jin, Wuhan National Lab. for Optoelectronics, Huazhong Univ. of Science and Technology (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 3: Brain-Wide Imaging I

Visualizing large-size biological samples in three dimensions with high throughput and resolution is crucial but challenging. Here, we proposed a Line-illumination Modulation (LiMo) method to achieve optical-sectioning imaging with high throughput by employing the Gaussian modulation of the line illumination in single strip scanning. We imaged an entire mouse hippocampal coronal plane of 10.4 × 6.5 mm at a voxel resolution of 0.16 × 0.16 × 1 μm in 160 s, demonstrating the improvement of imaging throughput compared with wide-field structured illumination microscopy. It provided a potential to develop whole-brain optical imaging with high throughput and resolution.


Photoacoustic tomography: Deep functional imaging at high spatiotemporal resolution
Paper 10481-15

Author(s):  Lihong V. Wang, California Institute of Technology (United States), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 4: Brain-Wide Imaging II

Photoacoustic tomography (PAT), combining optical and ultrasonic waves via the photoacoustic effect, provides in vivo functional, metabolic, molecular, and histologic imaging. PAT has the unique strength of high-resolution imaging across the length scales of organelles, cells, tissues, and organs with consistent contrast. PAT has the potential to empower multiscale biology research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT can image the entire brain of a rat or mouse with optical contrast in vivo. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in both humans and animals.


Volumetric optoacoustic mapping of fast neuronal activity in an isolated mouse brain model expressing genetically encoded calcium indicator
Paper 10481-16

Author(s):  Sven Gottschalk, Institute of Biological and Medical Imaging, Helmholtz Zentrum München GmbH (Germany), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 4: Brain-Wide Imaging II

Despite its apparent advantages for monitoring of fast neural activity, optoacoustic imaging of calcium activity deep in mammalian brain is hampered by strong blood absorption in the visible light spectrum as well as lack of activity labels excitable in the near-infrared window. Here we demonstrate real-time optoacoustic monitoring of calcium dynamics in an isolated whole mouse brain preparation labelled with genetically encoded calcium indicator GCaMP6f. The new technique captures calcium fluxes as true 3D information across the entire brain, thus enabling large-scale neural recording at penetration depths and spatio-temporal resolution scales not covered with the existing neuroimaging techniques.


Hybrid averaging optical coherence tomography angiography and applications in brain
Paper 10481-20

Author(s):  Peng Li, Zhejiang Univ. (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 5: Novel Technologies I

The current temporal, wavelength, angular and spatial averaging approaches trade imaging time and resolution for multiple independent measurements which improve flow contrast in optical coherence tomography angiography (OCTA). These averaging approaches are proved equivalent in principle, offering almost the same flow contrast enhancement as the number of averages increases and a hybrid averaging strategy is proposed for contrast enhancement by cost apportionment. It is demonstrated that, compared with any individual approach, hybrid averaging is able to offer a desired flow contrast without severe degradation of imaging time and resolution. Making use of the extended range of a VCSEL based swept source OCT, an angular averaging approach by path length encoding is also demonstrated for flow contrast enhancement.


Structure illuminated two-photon microscopy for high resolution imaging deep into the brain
Paper 10481-23

Author(s):  Yao Zheng, Zhejiang Univ. (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 5: Novel Technologies I

Two-photon microscopy has been widely used in neuroscience due to its deeper penetration depth compared with confocal microscopy. However, as imaging depth increases, its imaging quality will also degrade dramatically because of the accumulated aberration and scattered light. Here we report a high-resolution two-photon microscopy deep into the scattering medium, by structure illuminating the sample in the focal volume and demodulating the fluorescent signal thereafter. Our results show that compared with conventional two-photon microscopy the maximum imaging depth increases by hundreds micron in the mouse brain, and even in the surficial layer the imaging resolution is improved by around 15%.


High-speed, high-resolution in vivo brain imaging with wavefront shaping
Paper 10481-25

Author(s):  Na Ji, Univ. of California, Berkeley (United States), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 6: Novel Technologies II

With advances in optical imaging technology, the structure and function of the brain can now be interrogated at increasingly high spatial and temporal resolution. In this talk, I will describe our recent work combining wavefront shaping with optical microscopy to achieve high-speed, high-resolution (including super-resolution) imaging of the brain in vivo. Applying these techniques to a wide variety of model system, including fly, zebrafish, mouse, and ferret, we demonstrate how the improved speed and resolution benefit the investigation of the brain.


Generation of extremely thin light sheets allows fast isotropic imaging of whole mouse brains by ultramicroscopy
Paper 10481-26

Author(s):  Hans-Ulrich Dodt, Technische Univ. Wien (Austria), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 6: Novel Technologies II

By producing special light sheets of low numerical aperture (NA) we were able to generate extremely long thin sheets of light with a thickness in the one micron range and a vastly increased Rayleigh range. By using these light sheets in our ultramicroscope fast isotropic 3D imaging of whole mouse brains with objectives with a large field of view was possible.


Super-resolution localization microscopy with large field-of-view for mapping synaptic connectivity at multiple scales
Paper 10481-27

Author(s):  Zhenli Huang, Wuhan National Lab. for Optoelectronics, Huazhong Univ. of Science and Technology (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 6: Novel Technologies II

Super-resolution localization microscopy (SRLM) has the advantage of increasing field-of-view (FOV) without sacrificing either imaging speed or spatial resolution. However, the maximum FOV of popular SRLM is approximately 50 um x 50 um at the sample plane, which is insufficient for mapping of synaptic connectivity at multiple scales. Here we report our recent progresses in the technology development and applications of large-FOV SRLM, including the imaging performance of a back-illuminated sCMOS cameras with 95% QE, a high-power homogeneous illumination system for large-FOV SRLM, and some preliminary results of using large-FOV SRLM in mapping synaptic connectivity at multiple scales.


Simultaneous two-photon microscopy and magnetic resonance imaging at ultrahigh field of 16.4 Tesla
Paper 10481-28

Author(s):  Meng Cui, Purdue Univ. (United States), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 6: Novel Technologies II

fMRI based on the BOLD contrast has gained a prominent position in neuroscience for imaging brain activation. However, how the BOLD signal is linked to the neuronal activity and the glial cell dynamics is poorly understood. To elucidate the connection, we developed a dual-modality system for performing simultaneous fMRI and laser scanning two-photon microscopy.


UbasM: a simple, rapid, efficient balanced optical clearing method for brain imaging
Paper 10481-29

Author(s):  Lingling Chen, Shenzhen Univ. (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 6: Novel Technologies II

Optical clearing methods are highly in demand in organism-level biomedical system research since they can facilitate deep optical imaging by reducing light scattering in tissue and then enable three-dimensional signal visualization and quantification of tissues. While the previously reported optical clearing methods have addressed some of six key issues (transparency, preservation of membrane integrity, preservation of emission from fluorescence proteins, efficiency, reproducibility and convenience), none has yet addressed all of them. Here, we present a new, convenient, inexpensive and reproducible approach to optical clearing, termed UbasM, that successfully addresses all these criteria for the first time.


Interferometric near-infrared spectroscopy (iNIRS) at short source-detector separations
Paper 10481-30

Author(s):  Oybek Kholiqov, Univ. of California, Davis (United States), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 7: Human Brain Imaging

Interferometric near-infrared spectroscopy (iNIRS) is a time-of-flight- (TOF-) resolved sensing method for monitoring optical properties and dynamics of turbid media. To improve light collection efficiency and probe longer photon path lengths in vivo, we implement a short to null source-detector geometry setup and present methods to isolate the desired diffuse signal from large specular and non-diffuse signals. Furthermore, we present improved TOF resolution, dynamic range, and speed, and combine forward and backward sweeps to double the sampling rate for optical field autocorrelations. Collectively, these advances pave the way for the translation of iNIRS towards human cerebral cortex measurements.


Detection of cortical oxygen for clinical analysis and trends research of olfactory memory by using functional optical topography
Paper 10481-32

Author(s):  Yen Ting Chen, National Chiao Tung Univ. (Taiwan), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 7: Human Brain Imaging

Olfactory dysfunction is one of the earliest clinical features in cerebral diseases. Thus, the pathway for the olfactory response may be used as a potential biomarker in early stage of diseases. Near-infrared spectroscopy (NIRS) and also called diffuse optical imaging (DOI) technique is a noninvasive neuroimaging tool used to measure activation induced changes in cerebral hemoglobin concentration. In the results, the hemoglobin responses of orbitofrontal cortices are increased significantly during olfactory stimulation; nevertheless, the increasing amplitude would get smaller in every test later when olfactory memory has already been built. Our study shows that the multi-channel DOI system can provide high potential to apply to clinical neuroscience for diagnosis of olfactory disorders.


Advances of deep imaging in brain within optical tissue windows
Paper 10481-35

Author(s):  Lingyan Shi, Columbia Univ. (United States), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 8: Optical Sensing and Imaging for Brain Diseases

This talk will discuss the advantages of selecting the laser wavelengths for deep brain imaging. The near-infrared (NIR) radiation has been employed at wavelengths from 650 to 950 nm (optical tissue window I) for deep tissue imaging; however, the longer wavelengths in NIR have been overlooked due to a lack of suitable NIR imaging detectors. Three new optical windows in the NIR and demonstrates their potential for deep imaging. Golden window III from 1600 nm to 1870 nm in the NIR has a potential for longer penetration depth in brain or other tissues.


Long term imaging of living brain glial cancer cells
Paper 10481-36

Author(s):  Patricia M. A. Farias, Phornano Holding GmbH (Austria), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 8: Optical Sensing and Imaging for Brain Diseases

QDs synthesized in aqueous medium and functionalized with polyethylene glycol were used as fluorescent probes. They label and monitor living healthy and cancer brain glial cells in culture. Physical-chemical characterization was performed. Toxicological studies were performed by in vivo short and long term inhalation in animal models. Healthy and cancer glial living cells were incubated in culture media with highly controlled QDs. Specific features of glial cancer cells were enhanced by QD labelling. Cytoplasmic labelling pattern was clearly distinct for healthy and cancer cells. Labelled cells kept their normal activity for same period as non-labelled control samples.


Cerebral penetrating arteriole dynamics has important implication to the exacerbated ischemic injury in type 2 diabetes
Paper 10481-37

Author(s):  Yuandong Li, Univ. of Washington (United States), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 8: Optical Sensing and Imaging for Brain Diseases

Doppler optical microangiography elicits cerebral penetrating arterioles being an important indicator of the exacerbated ischemic brain damage in mice with type 2 diabetes.


White matter atrophy in spinocerebellar ataxia type 1 moue models revealed by serial optical coherence scanner
Paper 10481-39

Author(s):  Chao J. Liu, Univ. of Minnesota, Twin Cities (United States), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 8: Optical Sensing and Imaging for Brain Diseases

Spinocerebellar ataxia type 1 (SCA1) is a fatal inherited neurodegenerative disease. The mechanism of SCA1 progression remains unclear. In this study, we define quantitative assessments from intrinsic optical properties provided by a serial optical coherence scanner (SOCS). The local and global characteristics of nerve fiber organization are investigated as well. This study provides evidence of white matter atrophy in SCA1[82Q] mouse models. The findings have potential to serve as novel biomarkers that can facilitate the understanding of the pathological progression in the broader content of cerebellar circuitry in SCA1 and evaluate the efforts for potential treatments.


Photodynamic opening of blood-brain barrier
Paper 10481-40

Author(s):  Oxana V. Semyachkina-Glushkovskaya, Saratov State Univ. (Russian Federation), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 8: Optical Sensing and Imaging for Brain Diseases

In this study we clearly show the effectiveness of PD (635 nm, 15-20 J/cm2, 375 and 333 sec, respectively, 5-aminole-vulinic acid, 20 mg/kg, i.v.) for the temporal BBB opening for high weight molecular substances such as EBd (68 kDa) and dextran (70 kDa). For these irradiation doses the BBB was found disrupted 90 min after PD and restoring its integrity 4h later. The increase in concentration of photosensitizer was accomplished with severe disruption of the BBB resulting in perivascular edema, i.e. accumulation of extensive volumes of the solutes in perivascular space. We believe that these results are of high importance for the deeper understanding of PD effects on the cerebral vasculature and further for applications in biomedicine.


Investigating amyloid-beta plaques in whole brain sections of a mouse model of Alzheimer's disease with a visible light optical coherence microscope
Paper 10481-41

Author(s):  Antonia Lichtenegger, Medizinische Univ. Wien (Austria), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

A custom developed visible light spectral domain optical coherence microscope was utilized to investigate ex vivo brain tissue. The system operated in the visible wavelength range (λ=555 nm and Δλ=156 nm) resulting in an axial resolution of 0.82 μm in brain tissue. The combination of an automated x-y-z stage and microscope objectives with various magnifications facilitated the acquisition of rapid large-scale images from which regions of interest could be chosen for high resolution imaging. Whole cerebral brain sections from Alzheimer’s disease mice were imaged to investigate the accumulation of amyloid-beta plaques. The results were compared to healthy controls and histology.


Simultaneous OCT imaging and temperature sensing with a miniaturized fiber-optic probe
Paper 10481-42

Author(s):  Jiawen Li, The Univ. of Adelaide (Australia), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

Probes for temperature measurement deep within tissue, such as brain, are subject to a range of errors due to inappropriate placement. We present a miniaturized dual-function fiber-optic probe, with an outer diameter less than 260 μm, capable of optical coherence tomography (OCT) imaging and temperature sensing. An OCT microlens is fabricated on the end of a double clad fiber (DCF), and coated with a thin, transparent layer of rare-earth doped tellurite glass, to provide temperature-sensing capabilities. A DCF coupler is used to separate the OCT signal and the temperature-related fluorescence, enabling simultaneous image-guidance with temperature measurement.


A novel neurophotonics approach to study neural networks in vitro
Paper 10481-43

Author(s):  Erik P. Schartner, The Univ. of Adelaide (Australia), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

Probes for temperature measurement deep within tissue, such as brain, are subject to a range of errors due to inappropriate placement. We present a miniaturized dual-function fiber-optic probe, with an outer diameter less than 260 μm, capable of optical coherence tomography (OCT) imaging and temperature sensing. An OCT microlens is fabricated on the end of a double clad fiber (DCF), and coated with a thin, transparent layer of rare-earth doped tellurite glass, to provide temperature-sensing capabilities. A DCF coupler is used to separate the OCT signal and the temperature-related fluorescence, enabling simultaneous image-guidance with temperature measurement.


Three-dimensional reconstruction of the human brain cortex by means of a SWITCH/TDE-combined clearing method
Paper 10481-44

Author(s):  Wardiya Afshar Saber, School of Medicine, Univ. of St. Andrews (United Kingdom), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

Optogenetics is an emerging field that benefits from the synergy of optical and genetic technique. It allows non-invasive activation or inhibition of specific neurons using only light and enables repetitive interrogations of the same cells. We have recently combined it with purely optical readout of neural activity using a genetically encoded calcium reporter. We have also developed spatial and temporal protocols to quantify network dynamics in vitro. This is a novel quantitative use of neurophotonics to potentially understand human cognition, investigate how diseased neurons communicate thus enabling functional in vitro high-throughput screening and testing of dementia drug candidates.


Change in cognitive process during dance video game play with different appendages for motor output
Paper 10481-45

Author(s):  Irene Costantini, LENS - Lab. Europeo di Spettroscopie Non-Lineari (Italy), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

The three-dimensional reconstruction of the human neural networks at cellular resolution still remains a big challenge. To analyze the architectural abnormalities in the cortical layering of the human brain cortex in three dimensions we exploited the possibility of combining high-resolution 3D imaging techniques with clearing methodologies. We successfully integrate the SWITCH immunohistochemistry technique with the TDE clearing method to image pediatric as well as adult human brain tissue with light sheet as well as two-photon fluorescence microscope. This new approach enables to characterize large human brain specimens with high-resolution optical techniques, giving the possibility to expand the histopathological studies to the third dimension.


Analysis of prefrontal cortex function in TD patient during working memory task and olfactory task by using fNIRS measurements
Paper 10481-46

Author(s):  Kota Suzuki, Meiji Univ. (Japan), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

We investigated the cortical hemodynamic activity patterns when a dance video game (DVG) was played either with the hand or the foot. Playing DVG induced comparable prefrontal activity regardless of the appendages, suggesting the equal employment of motor preparatory function in the prefrontal area. However the hemodynamic responses in the superior/middle temporal gyrus were smaller in hand-played DVG related to foot-played DVG, suggesting more demand for multi-sensory integration in the temporal cortices. Hand-played DVG may partially substitute foot-played DVG in the sense of cognitive training for the elderly people who have difficulty to play DVG in a standing position.


Diffusion quantification of IR-780 dye delivered using Lexiscan through the blood brain barrier
Paper 10481-47

Author(s):  WeiShan Hsiao, Institute of Biomedical Engineering, National Chiao Tung Univ. (Taiwan), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

The purpose of this study is to assess the hemodynamic changes of the prefrontal cortex (PFC) between TD patients and health controls during working memory task and olfactory task by using a 24-channels fNIRS device. In the working memory task, the results showed that the healthy group had larger activation in the PFC than the TD group, especially in the left dorsolateral prefrontal cortex. In the olfactory task, the TD group showed weaker task performance and lower activation in the orbitofrontal cortex than the healthy group. Our findings suggest that the fNIRS method can provide a high potential to apply to clinical neuroscience for TD diagnosis.


A software pipeline for high-throughput stitching and processing of teravoxel-sized 3D images of brain samples
Paper 10481-49

Author(s):  Rebecca W. Pak, Johns Hopkins Univ. (United States), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

Using fluorescence imaging, we have demonstrated the feasibility of delivering NIR dyes IR-780 and PY6133 (voltage-sensitive), to the brain tissue through non-invasive pharmacological techniques, via an adenosine agonist (Lexiscan). We compared two different injections of dye with and without Lexiscan. With Lexiscan, we observed significantly increased lifetime of the fluorescence signal. Images from the two injections at the same time points were registered and subtracted. Differences in the fluorescence signal, that can be attributed to the dye diffusion into the tissue, were localized and quantified. With this analysis, the dye appears to diffuse relatively locally to the blood vessels.


In vivo volumetric imaging of fast biological dynamics in deep tissue via wavefront engineering
Paper 10481-5

Author(s):  Giacomo Mazzamuto, LENS - Lab. Europeo di Spettroscopie Non-Lineari (Italy), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 1: In Vivo Mouse Brain Imaging I

Imaging whole mouse brain specimens through advanced high-resolution microscopy techniques produces big amounts of volumetric data that needs to be processed in an automatic fashion in order to extract valuable quantitative information. We are developing a software pipeline that allows us to perform different levels of processing including: stitching of overlapping 3D tiles, cell counting, cell segmentation, vascular segmentation. Given the extent of our datasets (several TB of data) and the need for high-throughput processing, we first developed a dedicated stitching tool aiming at speed and efficiency. Stitched images are then processed for automatic localization of soma allowing us to investigate cell distribution in different areas of the brain.


Hemodynamic monitoring in different cortical layers with a single fiber optical system
Paper 10481-51

Author(s):  Xuecong Lu, Ecole Polytechnique de Montréal (Canada), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

This paper seeks to study the effects of voluntary exercise on the change in oxygen delivery in an awake mice model of Alzheimer’s disease (AD). Experiments were performed on young, old and old with exercise transgenic APPPS1 mice and their WT controls. Brain tissue oxygenation was measured by two photon phosphorescence lifetime microscopy on the left sensory motor cortex. Cerebral blood flow was measured with OCT in a separate session. We found that the average tissue PO2 decreased with age but were regulated by exercise. The results suggest a potential for exercise to improve brain function with age and AD


Single camera hemodynamic imaging of mouse brain with intact skull
Paper 10481-53

Author(s):  Linhui Yu, Univ. of Calgary (Canada), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

Functional monitoring of highly-localized deep brain structures is of great interest. However, optical methods have limited depth penetration or sample large volumes due to tissue scattering. We demonstrate continuous measurement of localized hemodynamics in different cortical layers in response to thalamic deep brain stimulation (DBS) using a stereotaxically implanted single fiber optical system. Preliminary results revealed that the trend of the hemodynamic response differs in cortical layers, and the amplitude of the hemodynamic response varies with DBS amplitudes. The single fiber system can be a useful tool to study the effect of DBS and the mechanism of neurovascular coupling.


Long fiber based multi-channel NIRS system for freely moving mice
Paper 10481-54

Author(s):  Seung-Ho Paik, Korea Univ. (Korea, Republic of), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

We developed a single camera two channel hemodynamic imaging system that uses near-infrared light to monitor a mouse brain in vivo with an exposed, unthinned, and intact skull to explore the effect of Parkinson’s Disease on the functional connectivity of the brain during resting state. A unilaterally lesioned 6-hydroxydopamine (hemi-parkinsonian) mouse model was developed and was monitored for a 7 minute resting state. A clustering algorithm was applied to the recorded NIRS signal. The normal mice were able to be segmented according to functional brain region, however hemi-parkinsonian mice showed a loss of functional organization.


Understanding neurovascular mechanisms during cortical spreading depression in ischemic stroke rats using novel ECoG-LSCI technology
Paper 10481-55

Author(s):  Young Kyu Kim, Korea Univ. (Korea, Republic of), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

A multi-channel NIRS system was built to record the whole brain hemodynamics for freely moving mice. The mice were fitted with a 3D-printed skull probe to ensure proper contact to the scale. The probe consisted of optical fibers arranged across the brain. A tomographic image of the hemodynamic changes were reconstructed in real time. The tomographic images showed activation in the corresponding hemisphere during visual and tactile tasks for mice fixed to a stereotaxic frame and freely moving mice. This system will be useful for observing the transient hemodynamic changes according to various stimuli in a freely moving mouse.


Optical clearing method for skull tissue for in-vivo morphological imaging of the rat brain with UHR-OCT
Paper 10481-56

Author(s):  Han-Chi Pan, National Health Research Institutes (Taiwan), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

The authors developed a reliable multimodality imaging system for simultaneously recording of the electrocorticographic (ECoG) signals for brain activities and hemodynamics responses by laser speckle contrast imaging (LSCI), so-called ECoG-LSCI system, to real-time collecting the crucial information of neurovascular functions of the brain. The ECoG-LSCI system can be used to monitoring the neurovascular functions changes, such as somatosensory evoked potential (SSEP) attenuation of the somatosensory cortex forelimb (S1FL), resting-state evoked potential (RS-EP) decline of M1 and S1FL and induction of the cortical spreading depression (CSD)-like surges, known as peri-infarct depolarization (PID), in the focal photothrombotic ischemia (PTI) stroke rat model.


Deep brain imaging using an ultra-thin OCT endoscopy probe
Paper 10481-59

Author(s):  Nadine Haymour, Univ. of Waterloo (Canada), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

Optical clearing of skull tissue would allow for minimally invasive longitudinal brain imaging studies with optical imaging methods such as optical coherence tomography (OCT). In this study, an optical clearing solution and a protocol for its application were developed and tested on ex-vivo and in-vivo rat skulls. The treated rat skulls and brain tissue underneath were imaged with a research-grade OCT system operating at 1020 nm that provided 3.5 µm axial resolution in brain tissue. Results from this study demonstrated optical clearing of the skull tissue resulting in high resolution, high contrast OCT brain images.


Improved near infrared spectroscopy patch with conformal contact elastomeric substrate
Paper 10481-60

Author(s):  Woo June Choi, Univ. of Washington (United States), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

We develop an ultra-thin endoscopic probe for optical coherence tomography (OCT) imaging of deep brain tissue. The endoscopy probe is made of spliced and specialized fibers with stepwise transitional cores that functions as beam optics to deliver the probe beam onto sample with a 20 µm spatial resolution. The miniaturized imaging probe is mounted on motorized actuators, allowing for a combined rotation and pullback of the probe. We show that the integration of the probe device into a high-speed OCT system permits the sampling of tissue volume at greater depths below brain surface through inserting the probe into the deep brain.


Bio-signal impact of cybersickness caused by virtual reality
Paper 10481-61

Author(s):  Chang Hyun Park, Pusan National Univ. (Korea, Republic of), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

The conventional continuous wave (CW) type NIRS system have replied on the LEDs with sequential lightening of long sampling time. To solve this problem, we propose a frequency domain (FD) method to include a simultaneous LED lighting. In this presentation, we will present an improvement in sampling time and closely contact structure of NIRS patch system.


DeepBouton: automated identification of single-neuron axonal boutons at the brain-wide scale
Paper 10481-64

Author(s):  Yi Tien Lin, National Chiao Tung Univ. (Taiwan), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

Cybersickness is one of the most important problems of virtual reality (VR). To improve the user experience, this study investigated the bio-signal changes including the electroencephalography (EEG) and the heart rate when users suffered from the cybersickness. The results showed that a higher level of cybersickness feeling accompanied with the increased amplitude of mid- and high-frequency EEG signals. The P300 signals appeared with more latency, and their amplitudes decreased for people with cybersickness. In addition, the cybersickness caused the heart rate increase. In the future, it is promising to develop a VR safety indicator by monitoring the bio-signals.


Simultaneous two-layer two photon imaging with frequency multiplexing
Paper 10481-65

Author(s):  Shaoqun Zeng, Britton Chance Ctr. for Biomedical Photonics (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session

Abstract: Fine reconstructions of neuronal morphology are needed for mapping neural circuits. Inference of presynaptic axonal boutons, as a key part of single-neuron fine reconstructions, is critical for interpreting the patterns of neural circuit wiring schemes. However, automated bouton identification remains challenging for current neuron reconstruction tools, as they are being focused mainly on neurite skeleton drawing and have difficulties to quantify bouton morphology. Here, we developed an automatic method for recognizing single-neuron axonal boutons in whole-brain fluorescence microscopy datasets. The method is based on deep convolutional neural networks and density-peak clustering. Adaptive feature representations of bouton morphology can be learned through the convolutional networks and used for the bouton recognition. We demonstrated that the approach is effective in detecting single-neuron boutons at the brain-wide scale for both long-range projection pyramidal neurons and local interneurons.


Whole-brain imaging using multi-view sub-voxel-resolving light-sheet microscopy
Paper 10481-67

Author(s):  Yiming Guo, Britton Chance Ctr. for Biomedical Photonics (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session


Three-channel whole-brain optical imaging for visualizing dual-labeled input and output of neural circuit with co-located anatomical reference
Paper 10481-68

Author(s):  Jun Nie, Huazhong Univ. of Science and Technology (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session Mon: Poster Session


Imaging of stimulus-induced hemodynamic response in the rat cortex using phase-stabilized swept-source OCT
Paper 10481-7

Author(s):  Zhangheng Ding, Wuhan National Lab. for Optoelectronics, Huazhong Univ. of Science and Technology (China), et al.
Conference 10481: Neural Imaging and Sensing 2018
Session 2: In Vivo Mouse Brain Imaging II

We developed a three-channel wide-field large-volume tomography (WVT) system to achieve high-throughput acquisition blue, green and red fluorescence of a whole mouse brain. The measured lateral and axial resolutions were 0.47 and 2.94 μm in blue channel, 0.52 and 2.20 μm in green channel, and 0.56 and 2.35 μm in red channel. By this system, we imaged the input and output of Vgat neurons in M1 in a whole mouse brain at a voxel size of 0.32 × 0.32 × 2 μm. The results indicate that the three-channel WVT system will facilitate the study of the brain-wide neural circuit.


Computational algorithm for assessing inter-neuronal connectivity to optimize optogenetic stimulation and neural circuit activity
Paper 10482-30

Author(s):  Jeremy B. Ford, Vanderbilt Univ. (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 6: Mechanism

Infrared neural inhibition (INI) is a spatially precise method of applying neural heat block to suppress the propagation of neural activity. Reported INI temperature rises are viable for acute studies, but may be problematic for sustained clinical implementation. Our mathematical and computational models suggest that heating greater lengths along the axon (increasing block width) reduces the threshold inhibition temperature. Experimental validation in Aplysia demonstrates a reduction in the maximum INI-generated temperature rise by using two adjacent optical fibers (λ=1875nm) to increase block width. This suggests that INI temperature can be minimized by optimizing the block width.


Excitability of astrocyte in vitro with infrared neural stimulation
Paper 10482-6

Author(s):  Akhil Bandi, Rutgers, The State Univ. of New Jersey (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 1: Control I

We used non-invasive optogenetic stimulation of either the facial motor nerve or the muscles that control whisker movements in mice. We tracked changes in nerve and muscle function for up to 14 days after facial nerve transection. Stimulation of the cut nerve revealed nerve degeneration over 24 hours. Muscle stimulation could be used to evoke movements after denervation, but the movements were altered, including reduced retractions (backward movements), increased large-amplitude, non-adapting protractions (forward movements), and increased sensitivity to low intensity stimuli. Our results imply that peripheral optogenetics can probe neuromuscular functional adaptations, and help restore movement after nerve damage.


Measuring 3D temperature profiles using phase-decorrelation OCT
Paper 10483-50

Author(s):  Wilson R. Adams, Vanderbilt Univ. (United States), et al.
Conference 10483: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXII
Session 8: OCT New Technology II

Astrocytes have been implicated to play a key role in infrared neural stimulation (INS) of the brain. Prior in vivo observations in the brain show that astrocytes may be actively involved in INS with similar astrocytic involvement observed with nanoplasmonic photothermal stimulation, but astrocyte contributions to observed signals have yet to be independently validated. Using real-time calcium fluorescence microscopy, we found that astrocytes are independently affected by infrared light. Here, we present characterization of astrocyte responses in vitro to the INS physical parameter space with fluorescence and non-linear imaging.


In-vivo label-free optical detection of neural activities in retina
Paper 10482-12

Author(s):  Gjinovefa Kola, Case Western Reserve Univ. (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 3: Detection

Infrared light is a novel modality to alter neural activity. We hypothesized that its effect would be dose and site specific and tested this on cardiorespiratory activity generated by a complex neural circuit. We applied pulsed IR light to the dorsomedial medullary surface above the caudal Nucleus of the Solitary Tract (cNTS). At threshold radiant exposures, IR stimuli increased respiratory and heart rates similar to those evoked by glutamate microinjection into the cNTS. Suprathreshold stimuli differentially affected respiratory and heart rates. While its mechanism of action remains unclear, IR stimuli are focal, dose dependent and reversible.


Measuring IR-induced 3D temperature profiles using phase decorrelation OCT
Paper 10482-13

Author(s):  Subrata Batabyal, Nanoscope Technologies, LLC (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 3: Detection

Here, we report use of near-infrared low-coherent light for non-contact, label-free in-vivo detection of retinal activities in response to visual stimulation. We utilized phase sensitive optical coherence tomography for measuring fluctuations of light reflected from retina of wild type and retinal degenerated mice. With visual stimulation, fluctuations in optical path length difference were found to be higher than that without visual stimulation in wild type mice. However, no such changes observed in mice with photoreceptor degeneration. Our findings open up possibility for clinical use of this method for non-contact label free characterization of retinal functioning and identification of dystrophies.


Optical stimulation and monitoring of the visual system using bioluminescent opsin
Paper 10482-14

Author(s):  Junqi Zhuo, Case Western Reserve Univ. (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 3: Detection

Modulating peripheral nerve activity with IR light is being actively studied. Reducing the thermal load and increasing safety are major focuses. Unfortunately, accurately measuring 3D temperature profiles inside tissue can be challenging. We developed a method to measure IR-induced 3D temperature profiles using phase decorrelation OCT. As the temperature increases, the phase will decorrelate more rapidly due to increased Brownian motion. We measured the IR-induced temperature profile in a glycerol-water solution phantom with polystyrene beads. The resulting cross-sectional temperature profile image matched our predictions. In addition, the temperature in the region of interest increased with increasing the laser power.


A compact integrated device for spatially-selective optogenetic neural stimulation based on the Utah Optrode Array
Paper 10482-15

Author(s):  Samarendra K. Mohanty, Nanoscope Technologies, LLC (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 3: Detection

Here, we report development and characterization of bioluminescent opsin for simultaneous optical modulation and imaging of retinal and cortical activities using spectrally separated activation and detection channels. This new bioluminescent technique does not require an additional phototoxic external excitation source (as used for fluorescence). We quantified changes in bioluminescence activities in visual cortex of mice upon visual stimulation of the retina. The observed increased neural activities were found to correlate with the visual stimulation patterns. This method will be useful for monitoring changes in visual cortical activities during progression and repair of retinal degenerative diseases.


Single source for simultaneous two-photon stimulation and imaging based on spectral-temporal modulation of supercontinuum generation
Paper 10482-16

Author(s):  Robert Scharf, The Univ. of Utah (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 4: Delivery

We have developed an optrode array for optogenetic stimulation of the deep layers of the cortex. The device consists of a 10 × 10 array of optical waveguides made from BOROFLOAT® glass. We used wafer dicing, followed by etching and annealing, to create waveguide structures from the bulk material. Coupling the optrode array to a separately-fabricated µLED array allows us to deliver light through individual shanks in a controlled fashion. Crosstalk between adjacent optrodes has been mitigated by reducing the thickness of the glass backplane and the use of a silicon interposer layer with optical vias.


Modeling of cerebral blood flow in reaction to neural stimulation
Paper 10482-18

Author(s):  Yuan-Zhi Liu, Univ. of Illinois (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 4: Delivery

Optogenetics has become a very important tool in neuroscience research for manipulating neuron activities by flexible optical illumination. Photonic-crystal-fiber-based supercontinuum generation is proposed as a broadband coherent light source for both two-photon optogenetic stimulation and calcium imaging. Programmable pulse shaping is utilized to modulate the phases of specific wavelengths to tailor the temporal shapes of femtosecond pulses, which improves the SNR of high-speed calcium imaging and manipulates the absorption of optogenetic probes controllable optogenetic excitation. Video-rate calcium imaging results suggest that spectral-temporal programmable supercontinuum pulses provides a powerful tool for neural network activity research.


Light propagation analysis in neural tissue for wireless optogenetic nanonetworks
Paper 10482-21

Author(s):  Rex Chin-Hao Chen, Univ. of Wisconsin-Milwaukee (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 4: Delivery

Distributed blood flow control in the tissue has many potential applications such as drug delivery and developing new treatments. We previously achieved Single-Input-Single-Output (SISO) closed-loop blood flow control in cerebral vasculature with model free Proportional-Integral-Derivative (PID) controller. However, due to the increasing complexity of the online tuning process, using Model-free PID controller is not feasible for MIMO system. To provide a design platform for MIMO control system, we propose a two-dimensional MIMO time-series model of blood flow response evoked by an optical stimulus in the somatosensory cortex of ChR2 mice. The model emulates the flow increase in vessels’ cross-sections under different stimulation locations.


Targeted nano-enhanced Optical delivery of opsin for dry-AMD therapy
Paper 10482-23

Author(s):  Pedram Johari, Univ. at Buffalo (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 5: Manipulation

In this paper, analytical models of wireless optogenetic nanonetwork devices are analyzed to design miniature devices that are able to emit light to stimulate neurons at the micro-scale. The paper analyzes the energy harvesting from Zinc oxide nanowires, which in turn determines the quantity of light intensity emitted from the μ-LED. The paper first analyzes the light propagation behavior using the modified Beer-Lambert law to determine the its effect based on the neural cell’s chromophores. Secondly, the paper analyzes the light behavior for different layers of the cortex, to determine the path loss for different cell physiological properties.


An all-optical system for rapid and deep interrogation of behaviorally relevant activity patterns
Paper 10482-24

Author(s):  Sivakumar Gajjeraman, Nanoscope Technologies, LLC (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 5: Manipulation

Here, we report near-infrared laser based Nano-enhanced Optical Delivery (NOD) of opsin-encoding genes into retina of mouse models of retina degeneration in-vivo. In this method, the field enhancement by gold nanorods is utilized to transiently perforate retinal cell membrane to deliver exogenous molecules into cells in the targeted area of retina. SDOCT was used to monitor if there is any damage to retina and other ocular structures. The expression and functioning of opsin in targeted retina after in-vivo NOD opens new clinical approach for improving vision of patients with dry-age related macular degeneration.


Validating the temperature rise during infrared neural inhibition with increased block width
Paper 10482-3

Author(s):  Gilad Lerman, NYU School of Medicine (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 1: Control I

We have developed an all-optical, rapid two-photon optogenetic stimulation and imaging system with cellular resolution and 5 ms temporal precision. Using an amplified laser, together with wavefront shaping methods using a fast spatial light modulator, we were able to stimulate dozens of neurons deep in the olfactory bulb at a high rate (>100 Hz) with cellular resolution. We optimized the system parameters to enable the simultaneous stimulation of many cells (~60). We then demonstrated stimulation of mitral and tufted cells, at a high rate, generating artificial odor-evoked responses. We will present the system characteristics and discuss its potential applications.


Optogenetic probing of muscle function, active sensation, and recovery from nerve damage in the mouse whisker system
Paper 10482-5

Author(s):  Carlos Renteria, Univ. of Illinois (United States), et al.
Conference 10482: Optogenetics and Optical Manipulation 2018
Session 1: Control I

All-optical imaging systems have been developed that allow for the acquisition and stimulation of neuronal activity. Optogenetic experiments, however, typically undergo local stimulation based on brain region rather than inter-neural connectivity. We have thus developed an algorithm that assesses this connectivity based on the signaling dynamics of the cells. Through genetic learning, the algorithm learns which cells are connected based on action potential rise time, decay time, inter-neural timing, and the time of peaks. This algorithm provides a powerful tool for optogenetic researchers that allows for more directed and less arbitrary stimulation to elucidate the underlying neuronal circuitry.


Important Dates

Abstracts Due
17 July 2017

Author Notification
25 September 2017

Manuscripts Due
See Individual Conferences


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Journal of Biomedical Optics

Journal of Biomedical OpticsPublishes peer-reviewed papers that utilize modern optical technology for improved health care and biomedical research.