Biology subjects

Palanker, D.

Publications and source records attributed to Palanker, D..

27 records · Page 2Linked to original sources

bioRxiv2021

Interferometric imaging of thermal expansion for temperature control in retinal laser therapy

Precise control of the temperature rise is a prerequisite for proper photothermal therapy. In retinal laser therapy, the heat deposition is primarily governed by the melanin concentration, which can significantly vary across the retina and from patient to patient. In this work, we present a method for determining the optical and thermal properties of layered materials, directly applicable to the retina, using low-energy laser heating and phase-resolved optical coherence tomography (pOCT). The method is demonstrated on a polymer-based tissue phantom heated with a laser pulse focused onto an absorbing layer buried below the phantoms surface. Using a line-scan spectral-domain pOCT, optical path length changes induced by the thermal expansion were extracted from sequential B-scans. The material properties were then determined by matching the optical path length changes to a thermo-mechanical model developed for fast computation. This method determined the absorption coefficient with a precision of 2.5% and the temperature rise with a precision of about 0.2{degrees}C from a single laser exposure, while the peak did not exceed 8{degrees}C during 1 ms pulse, which is well within the tissue safety range and significantly more precise than other methods.

bioengineering↗

bioRxiv2021

Electronic "photoreceptors" enable prosthetic vision with acuity matching the natural resolution in rats

Localized stimulation of the inner retinal neurons for high-acuity prosthetic vision requires small pixels and minimal cross-talk from neighboring electrodes. Local return electrodes within each pixel limit crosstalk, but can over-constrain the electric field, thus precluding efficient stimulation with subretinal pixels smaller than 50 m. Here we demonstrate high-resolution prosthetic vision based on a novel design of a photovoltaic array, where field confinement is achieved dynamically, leveraging the adjustable conductivity of the diodes under forward bias to turn the designated pixels into transient returns. We validated computational modeling of the field confinement in such an optically-controlled circuit by ex-vivo and in-vivo measurements. Most importantly, using this strategy, we demonstrated that the grating acuity with 40 m pixels matches the pixel pitch, while with 20 m pixels, it reaches the 28 m limit of the natural visual resolution in rats. This method enables customized field shaping based on individual retinal thickness and distance from the implant, paving the way to prosthetic vision with acuity as high as 20/80 in atrophic macular degeneration.

bioengineering↗

bioRxiv2020

Vertical-junction Photodiodes for High-resolution Retinal Prostheses

ObjectiveTo restore central vision in patients with atrophic age-related macular degeneration, we replace the lost photoreceptors with photovoltaic pixels, which convert light into current and stimulate the secondary retinal neurons. Clinical trials demonstrated prosthetic acuity closely matching the sampling limit of the 100 m pixels, and hence smaller pixels are required for improving visual acuity. However, with smaller flat bipolar pixels, the electric field penetration depth and the photodiode responsivity significantly decrease, making the device inefficient. Smaller pixels may be enabled (1) by increasing the diode responsivity using vertical p-n junctions and (2) by directing the electric field vertically using 3-D electrodes. Here, we demonstrate such novel photodiodes and test the retinal stimulation in a vertical electric field. ApproachArrays of silicon photodiodes of 55, 40, 30, and 20 m in width, with vertical p-n junctions, were fabricated. The electric field in the retina was directed vertically by a common return electrode at the edge of the devices. Optical and electronic performance of the diodes was characterized in-vitro, and retinal stimulation threshold measured by recording the visually evoked potentials (VEPs) in rats with retinal degeneration. Main resultsThe photodiodes exhibited sufficiently low dark current (<10 pA) and responsivity at 880 nm wavelength as high as 0.51 A/W, with 85% internal quantum efficiency, independent of pixel size. Field mapping in saline demonstrated uniformity of the pixel performance in the array. The full-field stimulation threshold was as low as 0.057{+/-}0.029 mW/mm2 with 10 ms pulses, independent of pixel size. SignificancePhotodiodes with vertical p-n junctions demonstrated excellent charge collection efficiency independent of pixel size, down to 20 m. Vertically-oriented electric field provides a stimulation threshold that is independent of pixel size. These results are the first steps in validation of the feasibility of scaling down the photovoltaic pixels for subretinal stimulation.

bioengineering↗

bioRxiv2020

Decoding network-mediated retinal response to electrical stimulation: implications for fidelity of prosthetic vision

ObjectivePatients with the photovoltaic subretinal implant PRIMA demonstrated letter acuity by ~0.1 logMAR worse than the sampling limit for 100m pixels (1.3 logMAR) and performed slower than healthy subjects, which exceeded the sampling limit at equivalently pixelated images by ~0.2 logMAR. To explore the underlying differences between the natural and prosthetic vision, we compare the fidelity of the retinal response to visual and subretinal electrical stimulation through single-cell modeling and ensemble decoding. ApproachResponses of the retinal ganglion cells (RGC) to optical or electrical (1mm diameter arrays, 75m pixels) white noise stimulation in healthy and degenerate rat retinas were recorded via MEA. Each RGC was fit with linear-non-linear (LN) and convolutional neural network (CNN) models. To characterize RGC noise level, we compared statistics of the spike-triggered average (STA) in RGCs responding to electrical or visual stimulation of healthy and degenerate retinas. At the population level, we constructed a linear decoder to determine the certainty with which the ensemble of RGCs can support the N-way discrimination tasks. Main resultsAlthough LN and CNN models can match the natural visual responses pretty well (correlation ~0.6), they fit significantly worse to spike timings elicited by electrical stimulation of the healthy retina (correlation ~0.15). In the degenerate retina, response to electrical stimulation is equally bad. The signal-to-noise ratio of electrical STAs in degenerate retinas matched that of the natural responses when 78{+/-}6.5% of the spikes were replaced with random timing. However, the noise in RGC responses contributed minimally to errors in the ensemble decoding. The determining factor in accuracy of decoding was the number of responding cells. To compensate for fewer responding cells under electrical stimulation than in natural vision, larger number of presentations of the same stimulus are required to deliver sufficient information for image decoding. SignificanceSlower than natural pattern identification by patients with the PRIMA implant may be explained by the lower number of electrically activated cells than in natural vision, which is compensated by a larger number of the stimulus presentations.

neuroscience↗

bioRxiv2020

Harmonic-Balance Circuit Analysis for Electro-Neural Interfaces

ObjectiveAvoidance of the adverse electrochemical reactions at the electrode-electrolyte interface defines the voltage safety window and limits the charge injection capacity (CIC) of an electrode material. For an electrode that is not ideally capacitive, the CIC depends on the waveform of the stimulus. We study the modeling of the charge injection dynamics to optimize the waveforms for efficient neural stimulation within the electrochemical safety limits. ApproachThe charge injection dynamics at the electrode-electrolyte interface is typically characterized by the electrochemical impedance spectrum, and is often approximated by discrete-element circuit models. We compare the modeling of the complete circuit, including a non-linear driver such as a photodiode, based on the harmonic-balance (HB) analysis with the analysis based on various discrete element approximations. To validate the modeling results, we performed experiments with iridium-oxide electrodes driven by a current source with diodes in parallel, which mimics a photovoltaic circuit. Main resultsApplication of HB analysis based on a full impedance spectrum in frequency domain eliminates the complication of finding the discrete-element circuit model in traditional approaches. HB-based results agree with the experimental data better than the discrete-element circuit analysis. HB technique can be applied not only to demonstrate the circuit response to periodic stimulation, but also to describe the initial transient behavior when a burst waveform is applied. SignificanceHB-based circuit analysis accurately describes the dynamics of electrode-electrolyte interfaces and driving circuits for all pulsing schemes. This allows optimizing the stimulus waveform to maximize the CIC, based on the impedance spectrum alone.

bioengineering↗

bioRxiv2020

The optoretinogram reveals how human photoreceptors deform in response to light

Limited accessibility of retinal neurons to electrophysiology on a cellular scale in-vivo has restricted studies of their signaling to in-vitro preparations and animal models. Physiological changes underlying neural activity are mediated by variations in electrical potential that alter the surface tension of the cell membrane. In addition, physiological processes affect concentration of the cells constituents that results in variation of osmotic pressure. Both these phenomena affect the neurons shape which can be detected using interferometric imaging, thereby enabling non-invasive label-free imaging of physiological activity in-vivo with cellular resolution. Here, we apply high-speed phase-resolved optical coherence tomography in line-field configuration to image the biophysical phenomena associated with phototransduction in human cone photoreceptors in vivo. We demonstrate that individual cones exhibit a biphasic response to light: an early ms-scale fast contraction of the outer segment immediately after the onset of the flash stimulus followed by a gradual (hundreds of ms) expansion. We demonstrate that the contraction can be explained by rapid charge movement accompanying the isomerization of cone opsins, consistent with the early receptor potential observed in the electroretinogram and classical electrophysiology in-vitro. We demonstrate the fidelity of such all-optical recording of light-induced activity in the human retina, namely the optoretinogram, across a range of spatiotemporal scales. This approach incorporates functional evaluation into a routine clinical examination of retinal structure and thus holds enormous potential to serve as a biomarker for early disease diagnosis and monitoring therapeutic efficacy.

neuroscience↗

bioRxiv2020

On mechanisms of light-induced deformations in photoreceptors

Photoreceptors in the retina convert light into electrical signals through a phototransduction cycle that consists of multiple electrical and biochemical events. Phase-resolved optical coherence tomography (pOCT) measurements of the optical path length (OPL) change in the cone photoreceptor outer segments after a light stimulus (optoretinogram) reveal a fast, ms-scale contraction by tens of nm, followed by a slow (hundreds of ms) elongation reaching hundreds of nm. Ultrafast measurements with a line-scan pOCT system show that the contractile response amplitude increases logarithmically with the number of incident photons, and its peak shifts earlier at higher stimulus intensities. We present a model that accounts for these features of the contractile response. Conformational changes in opsins after photoisomerization result in the fractional shift of charge across the disk membrane, leading to a transmembrane voltage change, known as the early receptor potential (ERP). Lateral repulsion of the ions on both sides of the membrane affects its surface tension and leads to its lateral expansion. Since the volume of the disks does not change much on a ms time scale, their lateral expansion leads to an axial contraction of the outer segment. With increasing stimulus intensity and resulting tension, the area expansion coefficient of the disk membrane also increases as thermally-induced fluctuations are pulled flat, resisting further expansion. This results in a logarithmic saturation of the deformation and a peak shift to earlier with brighter stimuli. Slow expansion of the photoreceptors is explained by the influx of water due to osmotic changes during phototransduction. Both effects closely match measurements in healthy human volunteers.

biophysics↗

bioRxiv2019

How neurons move during action potentials

Neurons undergo nanometer-scale deformations during action potentials, and the underlying mechanism has been actively debated for decades. Previous observations were limited to a single spot or the cell boundary, while movement across the entire neuron during the action potential remained unclear.\n\nWe report full-field imaging of cellular deformations accompanying the action potential in mammalian neuron somas (-1.8nm~1.3nm) and neurites (-0.7nm~0.9nm), using fast quantitative phase imaging with a temporal resolution of 0.1ms and an optical pathlength sensitivity of <4pm per pixel. Spike-triggered average, synchronized to electrical recording, demonstrates that the time course of the optical phase changes matches the dynamics of the electrical signal, with the optical signal revealing the intracellular potential rather than its time derivative detected via extracellular electrodes. Using 3D cellular morphology extracted via confocal microscopy, we demonstrate that the voltage-dependent changes in the membrane tension induced by ionic repulsion can explain the magnitude, time course and spatial features of the phase imaging. Our full-field observations of the spike-induced deformations in mammalian neurons opens the door to non-invasive label-free imaging of neural signaling.

neuroscience↗

bioRxiv2019

Performance of Complex Visual Tasks using Simulated Prosthetic Vision via Augmented-Reality Glasses

PurposePhotovoltaic subretinal prosthesis is designed for restoration of central vision in patients with age-related macular degeneration (AMD). We investigated the utility of prosthetic central vision for complex visual tasks using augmented-reality (AR) glasses simulating reduced acuity, contrast and visual field.\n\nMethodsAR glasses with blocked central 20{degrees} of visual field included an integrated video camera and software which adjusts the image quality according to three user-defined parameters: resolution, corresponding to the equivalent pixel size of an implant, field of view, corresponding to the implant size, and number of contrast levels. The real-time processed video was streamed on a screen in front of the right eye. Nineteen healthy participants were recruited to complete visual tasks including vision charts, sentence reading, and face recognition.\n\nResultsWith vision charts, letter acuity exceeded the pixel-sampling limit by 0.2 logMAR. Reading speed decreased with increasing pixel size and with reduced field of view (7-12{degrees}). In the face recognition task (4-way forced choice, 5{degrees} angular size) participants identified faces at >75% accuracy, even with 100 m pixels and only 2 grey levels. With 60 m pixels and 8 grey levels, the accuracy exceeded 97%.\n\nConclusionsSubjects with simulated prosthetic vision performed slightly better than the sampling limit on the letter acuity tasks, and were highly accurate at recognizing faces, even with 100 m/pixel resolution. These results indicate feasibility of the reading and face recognition using prosthetic central vision even with 100 m pixels, and performance improves further with smaller pixels.

neuroscience↗