scholarly journals High fidelity estimates of spikes and subthreshold waveforms from 1-photon voltage imaging in vivo

2020 ◽  
Author(s):  
Michael E. Xie ◽  
Yoav Adam ◽  
Linlin Z. Fan ◽  
Urs L. Böhm ◽  
Ian Kinsella ◽  
...  
Keyword(s):  
Signal To Noise Ratio ◽  
Nonnegative Matrix ◽  
Matrix Decomposition ◽  
High Signal ◽  
High Fidelity ◽  
Correlated Noise ◽  
Promising Tool ◽  
Mouse Cortex ◽  
Recent Developments

AbstractThe ability to probe the membrane potential of multiple genetically defined neurons simultaneously would have a profound impact on neuroscience research. Genetically encoded voltage indicators are a promising tool for this purpose, and recent developments have achieved high signal to noise ratio in vivo with 1-photon fluorescence imaging. However, these recordings exhibit several sources of noise that present analysis challenges, namely light scattering, out-of-focus sources, motion, and blood flow. We present a novel signal extraction methodology, Spike-Guided Penalized Matrix Decomposition-Nonnegative Matrix Factorization (SGPMD-NMF), which resolves supra- and sub-threshold voltages with high fidelity, even in the presence of correlated noise. The method incorporates biophysical constraints (shared soma profiles for spiking and subthreshold dynamics) and optical constraints (smoother spatial profiles from defocused vs. in-focus sources) to cleave signal from background. We validated the pipeline using simulated and composite datasets with realistic noise properties. We demonstrate applications to mouse hippocampus expressing paQuasAr3-s or SomArchon, mouse cortex expressing SomArchon or Voltron, and zebrafish spine expressing zArchon1.

scholarly journals Double-Layer Flexible Neural Probe With Closely Spaced Electrodes for High-Density in vivo Brain Recordings

2021 ◽  
Vol 15 ◽  
Author(s):  
Sara Pimenta ◽  
José A. Rodrigues ◽  
Francisca Machado ◽  
João F. Ribeiro ◽  
Marino J. Maciel ◽  
...  
Keyword(s):  
Double Layer ◽  
Signal To Noise Ratio ◽  
Low Cost ◽  
High Signal ◽  
Composition Analysis ◽  
Assessment Tests ◽  
Flexible Polymer ◽  
Mouse Cortex ◽  
Neural Probe

Flexible polymer neural probes are an attractive emerging approach for invasive brain recordings, given that they can minimize the risks of brain damage or glial scaring. However, densely packed electrode sites, which can facilitate neuronal data analysis, are not widely available in flexible probes. Here, we present a new flexible polyimide neural probe, based on standard and low-cost lithography processes, which has 32 closely spaced 10 μm diameter gold electrode sites at two different depths from the probe surface arranged in a matrix, with inter-site distances of only 5 μm. The double-layer design and fabrication approach implemented also provides additional stiffening just sufficient to prevent probe buckling during brain insertion. This approach avoids typical laborious augmentation strategies used to increase flexible probes’ mechanical rigidity while allowing a small brain insertion footprint. Chemical composition analysis and metrology of structural, mechanical, and electrical properties demonstrated the viability of this fabrication approach. Finally, in vivo functional assessment tests in the mouse cortex were performed as well as histological assessment of the insertion footprint, validating the biological applicability of this flexible neural probe for acquiring high quality neuronal recordings with high signal to noise ratio (SNR) and reduced acute trauma.

scholarly journals Genetically Encoded Fluorescent Indicators for Imaging Brain Chemistry

Biosensors ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 116
Author(s):  
Xiaoke Bi ◽  
Connor Beck ◽  
Yiyang Gong
Keyword(s):  
Dynamic Range ◽  
Signal To Noise Ratio ◽  
Spatial Scales ◽  
High Signal ◽  
Spatiotemporal Resolution ◽  
Brain Chemistry ◽  
Fluorescent Indicators ◽  
Recent Developments

Genetically encoded fluorescent indicators, combined with optical imaging, enable the detection of physiologically or behaviorally relevant neural activity with high spatiotemporal resolution. Recent developments in protein engineering and screening strategies have improved the dynamic range, kinetics, and spectral properties of genetically encoded fluorescence indicators of brain chemistry. Such indicators have detected neurotransmitter and calcium dynamics with high signal-to-noise ratio at multiple temporal and spatial scales in vitro and in vivo. This review summarizes the current trends in these genetically encoded fluorescent indicators of neurotransmitters and calcium, focusing on their key metrics and in vivo applications.

scholarly journals High-speed high-resolution laser diode-based photoacoustic microscopy for in vivo microvasculature imaging

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Xiufeng Li ◽  
Victor T C Tsang ◽  
Lei Kang ◽  
Yan Zhang ◽  
Terence T W Wong
Keyword(s):  
High Resolution ◽  
High Speed ◽  
High Performance ◽  
Continuous Wave ◽  
Signal To Noise Ratio ◽  
Cost Effective ◽  
High Signal ◽  
Photoacoustic Microscopy ◽  
Mouse Ear

AbstractLaser diodes (LDs) have been considered as cost-effective and compact excitation sources to overcome the requirement of costly and bulky pulsed laser sources that are commonly used in photoacoustic microscopy (PAM). However, the spatial resolution and/or imaging speed of previously reported LD-based PAM systems have not been optimized simultaneously. In this paper, we developed a high-speed and high-resolution LD-based PAM system using a continuous wave LD, operating at a pulsed mode, with a repetition rate of 30 kHz, as an excitation source. A hybrid scanning mechanism that synchronizes a one-dimensional galvanometer mirror and a two-dimensional motorized stage is applied to achieve a fast imaging capability without signal averaging due to the high signal-to-noise ratio. By optimizing the optical system, a high lateral resolution of 4.8 μm has been achieved. In vivo microvasculature imaging of a mouse ear has been demonstrated to show the high performance of our LD-based PAM system.

scholarly journals Methods for Voltage-Sensitive Dye Imaging of Rat Cortical Activity With High Signal-to-Noise Ratio

2007 ◽  
Vol 98 (1) ◽  
pp. 502-512 ◽  
Author(s):  
Michael T. Lippert ◽  
Kentaroh Takagaki ◽  
Weifeng Xu ◽  
Xiaoying Huang ◽  
Jian-Young Wu
Keyword(s):  
Dynamic Range ◽  
Signal To Noise Ratio ◽  
Field Potential ◽  
High Sensitivity ◽  
High Dynamic Range ◽  
High Signal ◽  
Blue Dye ◽  
Voltage Sensitive Dye ◽  
Imaging Device

We describe methods to achieve high sensitivity in voltage-sensitive dye (VSD) imaging from rat barrel and visual cortices in vivo with the use of a blue dye RH1691 and a high dynamic range imaging device (photodiode array). With an improved staining protocol and an off-line procedure to remove pulsation artifact, the sensitivity of VSD recording is comparable with that of local field potential recording from the same location. With this sensitivity, one can record from ∼500 individual detectors, each covering an area of cortical tissue 160 μm in diameter (total imaging field ∼4 mm in diameter) and a temporal resolution of 1,600 frames/s, without multiple-trial averaging. We can record 80–100 trials of intermittent 10-s trials from each imaging field before the VSD signal reduces to one half of its initial amplitude because of bleaching and wash-out. Taken together, the methods described in this report provide a useful tool for visualizing evoked and spontaneous waves from rodent cortex.

scholarly journals Rationally Designing Simple Rod-Like Amphiphilic NIR-Emissive AIE Probes for Precise In-Vivo Detection of Aβ Fibrils/Plaques at A Super-Early Stage

2021 ◽  
Author(s):  
Yipu Wang ◽  
Dong Mei ◽  
Xinyi Zhang ◽  
Da-Hui Qu ◽  
Ju Mei ◽  
...  
Keyword(s):  
High Performance ◽  
Ex Vivo ◽  
Early Stage ◽  
Signal To Noise Ratio ◽  
High Signal ◽  
In Vivo Detection ◽  
Different Strains ◽  
Aβ Fibrils

With increase of social aging, Alzheimer's disease (AD) has been one of the serious diseases threatening human health. The occurrence of A<i>β </i>fibrils<i> </i>or plaques is recognized as the hallmark of AD.<i> </i>Currently, optical imaging has stood out to be a promising technique for the imaging of A<i>β</i> fibrils/plaques and the diagnosis of AD. However, restricted by their poor blood-brain barrier (BBB) penetrability, short-wavelength excitation and emission, and aggregation-caused quenching (ACQ) effect, the clinically used gold-standard optical probes such as <a>thioflavin</a> T (ThT) and thioflavin S (ThS), are not effective enough in the early diagnosis of AD <i>in vivo</i>. Herein, we put forward an “all-in-one” design principle and demonstrate its feasibility in developing high-performance fluorescent probes which are specific to A<i>β</i> fibrils/plaques and promising for super-early <i>in</i>-<i>vivo</i> diagnosis of AD. As a proof of concept, a simple rod-like amphiphilic NIR fluorescent AIEgen, i.e., AIE-CNPy-AD, is developed by taking the specificity, BBB penetration ability, deep-tissue penetration capacity, high signal-to-noise ratio (SNR) into consideration. AIE-CNPy-AD is constituted by connecting the electron-donating and accepting moieties through single bonds and tagging with a propanesulfonate tail, giving rise to the NIR fluorescence, aggregation-induced emission (AIE) effect, amphiphilicity, and rod-like structure, which in turn result in high binding-affinity and excellent specificity to A<i>β</i> fibrils/plaques, satisfactory ability to penetrate BBB and deep tissues, ultrahigh SNR and sensitivity, and high-fidelity imaging capability. <i>In-vitro, ex-vivo,</i> and <i>in-vivo</i> <a>identifying of A<i>β</i> fibrils/plaques</a> in different strains of mice indicate that AIE-CNPy-AD holds the universality to the detection of A<i>β</i> fibrils/plaques. It is noteworthy that AIE-CNPy-AD is even able to trace the small and sparsely distributed A<i>β</i> fibrils/plaques in very young AD model mice such as 4-month-old APP/PS1 mice which are reported to be the youngest mice to have A<i>β</i> deposits in brains, suggesting its great potential in diagnosis and intervention of AD at a super-early stage.

scholarly journals Sequential average segmented microscopy for high signal-to-noise ratio motion-artifact-free in vivo heart imaging

2013 ◽  
Vol 4 (10) ◽  
pp. 2095 ◽  
Author(s):  
Claudio Vinegoni ◽  
Sungon Lee ◽  
Paolo Fumene Feruglio ◽  
Pasquina Marzola ◽  
Matthias Nahrendorf ◽  
...  
Keyword(s):  
Signal To Noise Ratio ◽  
Motion Artifact ◽  
High Signal ◽  
Signal To Noise ◽  
Heart Imaging ◽  
Noise Ratio

scholarly journals All-optical electrophysiology reveals brain-state dependent changes in hippocampal subthreshold dynamics and excitability

2018 ◽  
Author(s):  
Yoav Adam ◽  
Jeong J. Kim ◽  
Shan Lou ◽  
Yongxin Zhao ◽  
Daan Brinks ◽  
...  
Keyword(s):  
High Speed ◽  
Near Infrared ◽  
Neuronal Excitability ◽  
Signal To Noise Ratio ◽  
Brain State ◽  
Promising Tool ◽  
State Dependent ◽  
Subthreshold Voltage ◽  
Targeted Gene Expression

AbstractA technology to record membrane potential from multiple neurons, simultaneously, in behaving animals will have a transformative impact on neuroscience research1. Parallel recordings could reveal the subthreshold potentials and intercellular correlations that underlie network behavior2. Paired stimulation and recording can further reveal the input-output properties of individual cells or networks in the context of different brain states3. Genetically encoded voltage indicators are a promising tool for these purposes, but were so far limited to single-cell recordings with marginal signal to noise ratio (SNR) in vivo4-6. We developed improved near infrared voltage indicators, high speed microscopes and targeted gene expression schemes which enabled recordings of supra- and subthreshold voltage dynamics from multiple neurons simultaneously in mouse hippocampus, in vivo. The reporters revealed sub-cellular details of back-propagating action potentials, correlations in sub-threshold voltage between multiple cells, and changes in dynamics associated with transitions from resting to locomotion. In combination with optogenetic stimulation, the reporters revealed brain state-dependent changes in neuronal excitability, reflecting the interplay of excitatory and inhibitory synaptic inputs. These tools open the possibility for detailed explorations of network dynamics in the context of behavior.

scholarly journals Upconversion Nanoparticles Decorated with Polysialic Acid for Solid Tumors Visualization In Vivo

2021 ◽  
Author(s):  
P. A. Demina ◽  
N. V. Sholina ◽  
R. A. Akasov ◽  
D. A. Khochenkov ◽  
A. V. Nechaev ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Near Infrared ◽  
Signal To Noise Ratio ◽  
Polysialic Acid ◽  
Lymphatic Drainage ◽  
Circulation Time ◽  
High Signal ◽  
Upconversion Nanoparticles ◽  
Nonspecific Protein Adsorption

Abstract Upconversion nanoparticles (UCNPs) are a promising nanoplatform for bioreagent formation for in vivo imaging, which emit UV and blue light under the action of near-infrared radiation, providing deep tissue penetration and maintaining a high signal-to-noise ratio. In the case of solid tumor visualization, the UCNP surface functionalization is required to ensure a long circulation time, biocompatibility, and non-toxicity. The effective UCNP accumulation in the solid tumors is determined by the disturbed architecture of the vascular network and lymphatic drainage. This work demonstrates an approach to the UCNP biofunctionalization with endogenous polysialic acid for in vivo bioreagent formation. Bioreagents possess a low level of nonspecific protein adsorption and macrophage uptake, which allow the prolongation of the circulation time in the bloodstream up to 3 h. This leads to an intense photoluminescent signal in the tumor.

scholarly journals High Fidelity Spatial Light Modulator Configuration for Photo-Stimulation

2021 ◽  
Vol 9 ◽  
Author(s):  
Samira Aghayee ◽  
Mitchell Weikert ◽  
Phillip Alvarez ◽  
Gabriel A. Frank ◽  
Wolfgang Losert
Keyword(s):  
Spatial Light Modulator ◽  
Signal To Noise Ratio ◽  
Spatial Light Modulators ◽  
High Signal ◽  
High Fidelity ◽  
Light Modulator ◽  
Fourier Plane ◽  
Two Photon ◽  
Light Modulators ◽  
The Brain

For their capacity to shape optical wavefronts in real time into any desired illumination pattern, phase-only Spatial Light Modulators (SLM) have proven to be powerful tools for optical trapping and micromanipulation applications. SLMs are also becoming increasingly utilized in selective photo-stimulation of groups of neurons in the brain. However, conventional SLM based wavefront modulation introduces artifacts that are particularly detrimental for photo-stimulation applications. The primary issue is the unmodulated light that travels along the 0th order of diffraction. This portion of light is commonly blocked at the center of the object plane, which prevents photo-stimulation in the blocked region. We demonstrate a virtual lens configuration that moves the 1st order diffraction with the desired illumination pattern into the Fourier plane of the 0th order light. This virtual lens setup makes the whole field of view accessible for photo-stimulation and eliminates the need for removing the 0th order light in two-photon applications. Furthermore, in an example application to reconstruct a pattern consisting of an array of points, the virtual lens configuration increases the uniformity of the intensities these points. Moreover, diffraction-induced artifacts are also significantly reduced within the target plane. Therefore, our proposed high fidelity configuration yields target points with high signal to noise ratio.

scholarly journals Self-Reset Image Sensor With a Signal-to-Noise Ratio Over 70 dB and Its Application to Brain Surface Imaging

2021 ◽  
Vol 15 ◽  
Author(s):  
Thanet Pakpuwadon ◽  
Kiyotaka Sasagawa ◽  
Mark Christian Guinto ◽  
Yasumi Ohta ◽  
Makito Haruta ◽  
...  
Keyword(s):  
Neural Activity ◽  
Signal To Noise Ratio ◽  
Image Sensor ◽  
Oxide Semiconductor ◽  
High Signal ◽  
Unstable State ◽  
Signal To Noise ◽  
Compact Size ◽  
Noise Ratio

In this study, we propose a complementary-metal-oxide-semiconductor (CMOS) image sensor with a self-resetting system demonstrating a high signal-to-noise ratio (SNR) to detect small intrinsic signals such as a hemodynamic reaction or neural activity in a mouse brain. The photodiode structure was modified from N-well/P-sub to P+/N-well/P-sub to increase the photodiode capacitance to reduce the number of self-resets required to decrease the unstable stage. Moreover, our new relay board was used for the first time. As a result, an effective SNR of over 70 dB was achieved within the same pixel size and fill factor. The unstable state was drastically reduced. Thus, we will be able to detect neural activity. With its compact size, this device has significant potential to become an intrinsic signal detector in freely moving animals. We also demonstrated in vivo imaging with image processing by removing additional noise from the self-reset operation.

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