Showing papers by "Mark S. Humayun published in 2010"

An Integrated 256-Channel Epiretinal Prosthesis

Abstract: This paper reports an integrated 256-channel epiretinal prosthesis integrated circuit (IC). This epiretinal prosthesis system consists of a power telemetry subsystem to deliver 100 mW power, a data telemetry subsystem to transfer 2 Mbps data, digital controllers to decode stimulation patterns, and a 256-channel stimulator to generate user programmable bi-phasic current stimuli. In this study, dual-band telemetry is adopted to achieve both high power efficiency and high data rate. Frequencies of 2 and 22 MHz are chosen for power and data carrier frequencies, respectively. A mixed-mode and multiple-voltage design is applied to the stimulator for withstanding a high-compliance voltage of ± 10 V at the output stage as well as for reducing the area of each pixel. To add flexibility to the stimulator, each pixel has a local digital controller, which enables the stimulator IC to generate 256 parallel stimulations with various pulse widths and amplitudes. The chip is fabricated in TSMC 0.18 μm 32 V CMOS process with 256 area pads constructed above the stimulus current drivers.

Wireless Intraocular Pressure Sensing Using Microfabricated Minimally Invasive Flexible-Coiled LC Sensor Implant

Abstract: This paper presents an implant-based wireless pressure sensing paradigm for long-range continuous intraocular pressure (IOP) monitoring of glaucoma patients. An implantable parylene-based pressure sensor has been developed, featuring an electrical LC-tank resonant circuit for passive wireless sensing without power consumption on the implanted site. The sensor is microfabricated with the use of parylene C (poly-chloro-p-xylylene) to create a flexible coil substrate that can be folded for smaller physical form factor so as to achieve minimally invasive implantation, while stretched back without damage for enhanced inductive sensor-reader coil coupling so as to achieve strong sensing signal. A data-processed external readout method has also been developed to support pressure measurements. By incorporating the LC sensor and the readout method, wireless pressure sensing with 1-mmHg resolution in longer than 2-cm distance is successfully demonstrated. Other than extensive on-bench characterization, device testing through six-month chronic in vivo and acute ex vivo animal studies has verified the feasibility and efficacy of the sensor implant in the surgical aspect, including robust fixation and long-term biocompatibility in the intraocular environment. With meeting specifications of practical wireless pressure sensing and further reader development, this sensing methodology is promising for continuous, convenient, direct, and faithful IOP monitoring.

Mini Drug Pump for Ophthalmic Use

Abstract: Purpose: To evaluate the feasibility of developing a novel mini drug pump for ophthalmic use.Methods: Using principles of microelectromechanical systems engineering, a mini drug pump was fabricated. The pumping mechanism is based on electrolysis and the pump includes a drug refill port as well as a check valve to control drug delivery. Drug pumps were tested first on the bench-top and then after implantation in rabbits. For the latter, we implanted 4 elliptical (9.9 × 7.7 × 1.8 mm) non-electrically active pumps into 4 rabbits. The procedure is similar to implantation of a glaucoma aqueous drainage device. To determine the ability to refill and also the patency of the cannula, at intervals of 4–6 weeks after implantation, we accessed the drug reservoir with a transconjunctival needle and delivered approximately as low as 1 µL of trypan blue solution (0.06%) into the anterior chamber. Animals were followed by slit lamp examination, photography, and fluorescein angiography.Results: Bench-top testing showed 2...

Wafer-Level Parylene Packaging With Integrated RF Electronics for Wireless Retinal Prostheses

Abstract: This paper presents an embedded chip integration technology that incorporates silicon housings and flexible Parylene-based microelectromechanical systems (MEMS) devices. Accelerated-lifetime soak testing is performed in saline at elevated temperatures to study the packaging performance of Parylene C thin films. Experimental results show that the silicon chip under test is well protected by Parylene, and the lifetime of Parylene-coated metal at body temperature (37°C) is more than 60 years, indicating that Parylene C is an excellent structural and packaging material for biomedical applications. To demonstrate the proposed packaging technology, a flexible MEMS radio-frequency (RF) coil has been integrated with an RF identification (RFID) circuit die. The coil has an inductance of 16 μH with two layers of metal completely encapsulated in Parylene C, which is microfabricated using a Parylene-metal-Parylene thin-film technology. The chip is a commercially available read-only RFID chip with a typical operating frequency of 125 kHz. The functionality of the embedded chip has been tested using an RFID reader module in both air and saline, demonstrating successful power and data transmission through the MEMS coil.

Multi-function optical probe system for medical and veterinary applications

Abstract: A device includes a handpiece having a probe tip disposed at an end thereof, and, connected to the handpiece such that, at the probe tip, a functionality of each is provided, a plurality of probes. The probes may include an optical coherence tomography (OCT) probe, an endoillumination probe, a laser therapy probe, an ultrasound imaging probe, an electrocautery probe, an RF ablation probe, a cryosurgical probe, an irrigator, and/or a mechanical probe.

Methods of determining motion and distance during medical and veterinary procedures

Abstract: A system, for use with a cannula insertable into human or animal tissue, for measuring relative motion during a surgical procedure includes a probe having a probe tip insertable into the cannula, and means for determining relative motion between the cannula and the probe tip.

Medical and veterinary imaging and diagnostic procedures utilizing optical probe systems

Abstract: An imaging method includes providing a handpiece having a probe tip insertable into human or animal tissue disposed at an end thereof, and, an optical coherence tomography (OCT) probe connected to the handpiece such that a functionality of the OCT probe is provided at the probe tip. The probe tip is disposed adjacent to or into human or animal tissue. Imaging of the tissue, measuring at least one of a feature size or a quantifiable characteristic of a structure in the tissue for biometry analysis, and/or performing a diagnostic procedure on the tissue or a device implanted in the tissue is performed with the OCT probe.

Brightness as a function of current amplitude in human retinal electrical stimulation

Abstract: Retinitis pigmentosa and age-related macular degeneration are two of the more frequent causes of blindness in the developed world.1-3 Both diseases are progressive and begin with the degeneration of photoreceptors. In later stages of these diseases, bipolar, amacrine, and ganglion cells are still present, though their numbers are significantly decreased4-6 and their spatial organization and circuitry are significantly disorganized.7,8 There are more than 180 different gene mutations that result in photoreceptor diseases for which there is currently no cure or treatment.1 Ideally, it would be possible to develop a treatment for these conditions that would not require targeting each genetic defect independently. Several groups are developing implantable microelectronic visual prostheses that produce percepts by electrically stimulating remaining retinal neurons. To date, several groups have succeeded in generating visual percepts via electrical stimulation with implanted acute, semi-acute, and long-term retinal prostheses in human patients.9-14 The ultimate goal of these projects is to generate useful vision in blind patients by transforming a video stream into a spatial and temporal sequence of electrical pulses that represents meaningful visual information. However, creating a perceptually meaningful pattern of stimulation is dependent on a detailed understanding of the perceived intensity of any given stimulation pattern; to date, the literature examining the perceptual consequences of electrical stimulation remains relatively sparse.10-12,15-20 A visual prosthesis should produce regions of constant brightness across a range of brightness levels, and ideally these brightness levels should be consistent with the apparent brightness of objects as they appear to those with normal vision. Our goal was to examine how apparent brightness changes as a function of stimulation intensity in two blind human subjects chronically implanted with a prototype epiretinal prosthesis consisting of a 4 × 4 array of 16 stimulating electrodes. In experiment 1, subjects rated the apparent brightness of pulse stimuli on individual electrodes using a reference pulse of fixed amplitude. We found that apparent brightness as a function of current amplitude can be described using a simple power function. In experiment 2, a brightness-matching technique was used to compare apparent brightness across pairs of electrodes. We found that the apparent brightness of a given electrode can be related to other electrodes on the array using the same simple power function model. The results from these two experiments suggest that a relatively simple model for scaling current across electrodes may, to a first approximation, be capable of producing equivalently bright phosphenes across an entire array.

In vivo snapshot hyperspectral image analysis of age-related macular degeneration

Abstract: Drusen, the hallmark lesions of age related macular degeneration (AMD), are biochemically heterogeneous and the identification of their biochemical distribution is key to the understanding of AMD. Yet the challenges are to develop imaging technology and analytics, which respect the physical generation of the hyperspectral signal in the presence of noise, artifacts, and multiple mixed sources while maximally exploiting the full data dimensionality to uncover clinically relevant spectral signatures. This paper reports on the statistical analysis of hyperspectral signatures of drusen and anatomical regions of interest using snapshot hyperspectral imaging and non-negative matrix factorization (NMF). We propose physical meaningful priors as initialization schemes to NMF for finding low-rank decompositions that capture the underlying physiology of drusen and the macular pigment. Preliminary results show that snapshot hyperspectral imaging in combination with NMF is able to detect biochemically meaningful components of drusen and the macular pigment. To our knowledge, this is the first reported demonstration in vivo of the separate absorbance peaks for lutein and zeaxanthin in macular pigment.

Novel method to quantify traction in a vitrectomy procedure

Abstract: Aim To report a novel method to quantify traction applied to the retina using vitreous cutters during pars plana vitrectomy. Methods Fresh porcine eyes were positioned in a specially developed holder and transfixed to the retinal layers with a wire and the other end fixed to the load cell of a strain gauge. Five separate 20-gauge electrical drive mechanism vitrectors were introduced into the eye at a 45° angle and positioned at a distance of either 3 or 5 mm from the retina. Data from the strain gauge were acquired and the traction force computed. Results The analysis revealed that the vitreoretinal traction increased by 7.90 dynes for each 100 mm Hg increase in vacuum (p Conclusion The traction was directly proportional to the aspiration vacuum and inversely proportional to the cut rate. The cutter traction force increased with proximity to the retina.

Interim Performance Results from the Second Sight® ArgusTM II Retinal Prosthesis Study

Abstract: Subjects with retinal degeneration have been implanted with a 60+ electrode prosthesis in an FDA-approved clinical trial. The subjects had bare light perception or worse due to Retinitis Pigmentosa. They were evaluated using a number of tests such as grating visual acuity, object and letter recognition and orientation/ mobility. As of March 2010, over 30 subjects have been implanted with excellent safety. Subjects have been implanted an average of 18 months (range 6.7-33) and are tested with the Argus II system turned ON vs. OFF. All subjects now perceive light and can complete tasks significantly better (p< 0.05) with the system ON vs. OFF. Five subjects have regained measurable visual acuity (2.9 logMAR) with the system ON. Of 24 implanted subjects, 95% were able to correctly identify test letters with the system ON compared to 8% with the system OFF. With up to 3.2 total years of follow-up on the 32 subjects, this now constitutes the largest study of a visual prosthesis to date. The results confirm previous reports using the Argus I device as to the ability of this system to restore functional vision over the long-term. Higher resolution devices are in development. For more information, please contact Cathy Naples at (216) 707-6490. Mark S. Humayun, MD, PhD

Blood velocity measurement in the posterior segment of the rabbit eye using combined spectral Doppler and power Doppler ultrasound.

Abstract: Background It is challenging for the current Doppler imaging to detect blood flow in small retinal vessels. Power Doppler, with its high sensitivity to detect minimal blood flow, can be used with spectral Doppler to measure blood velocity in small vessels of the eye and orbit.

An experimental protocol of the model to quantify traction applied to the retina by vitreous cutters.

Abstract: PURPOSE The purpose of this study was to use a novel method to quantify the traction applied to the retina during vitrectomy. METHODS Five 20-gauge electric cutters were used. Fresh porcine eyes were positioned in a specially developed holder and transfixed to the retinal layers with a microwire, and the other end was fixed to the load cell of a strain gauge. The cutter to be assessed was introduced into the eye by a micromanipulator at a 45 degrees angle adjacent to the retina. The traction force was evaluated when the cutter was at 3 and 5 mm from the retina. As control, the experiment was repeated in eyes filled with water, and the results were compared to those when the eyes had vitreous gel. RESULTS Results from the eyes with vitreous gel indicate that retinal traction increased with increasing aspiration vacuum (7.90 dyn for each 100 mm Hg increased; P < 0.05) and proximity to the retina (2.17 dyn; P < 0.05) and decreased with increasing cut rate (2.51 dyn for each 500 cuts per minute increased; P < 0.05). In all eyes filled with water, traction was not observed. CONCLUSIONS The present study establishes a new reproducible technique to quantify vitreoretinal traction during vitrectomy and demonstrates that the effects of aspiration, distance from the retina, and cut rate are crucial factors in the amount of retinal traction created by vitreous cutters.

A new dual port cutter system for vitrectomy surgery.

Abstract: Purpose: To evaluate and compare the performance of several designs of 20-gauge dual port (DP) vitreous cutter tips with a standard 20-gauge single port tip. Methods: Custom 20-gauge pneumatic vitreous DP cutter tips with different sizes and port positions were evaluated through porcine vitreous and water flow rates. Five designed and fabricated DP cutter tips were compared with a normal single port control tip and evaluated by the measurement of water and porcine vitreous flow rates, and surgical examination in enucleated porcine eyes. Results: Some DP tips approached a maximum vitreous and water flow rates, removing water and vitreous faster than the normal control tip. With reference to surgical evaluation, some DP tips performed better than the single port tip for bulk vitrectomy, but none shaved the vitreous base more effectively. Conclusion: The DP cutter system has the potential to increase the flow rates depending on the size and position of the extra port. In the future, the DP cutter may allow the surgeon to perform bulk vitrectomy more efficiently.

Adjustable cannula systems and devices

Abstract: Various adjustable cannula systems are provided. The systems can include an adjustable cannula capable of expansion and/or contraction having an elongate body with a distal end and a proximal end. The adjustable cannula can be coupled to an upper housing and a lower housing such that rotation of the upper housing results in expansion or contraction of the adjustable cannula. The adjustable cannula can also have a proximal end having a lumen larger than a distal end lumen. A plurality of flanges can be formed in the elongate body by a plurality of slits that span a majority of a length of the cannula, including along or proximate to its proximal end and distal end.

Effect of multiple injections of small divided doses vs single injection of intravitreal bevacizumab on retinal neovascular model in rabbits.

Abstract: Background To compare effects of multiple injections of small divided doses of intravitreal bevacizumab vs a single injection using a retinal neovascular model in rabbits.

Systems for controlling optical probe functions during medical and veterinary procedures

Abstract: A device includes a handpiece having a probe tip disposed at an end thereof, and, an optical coherence tomography (OCT) probe connected to the handpiece such that, at the probe tip, a functionality of the OCT probe is provided. A sensor responsive to movement and/or handling of the handpiece for controlling the functionality of the OCT probe is disposed within or on the handpiece.

Image processing algorithm for cueing salient regions

Abstract: A method for cueing salient regions of an image in an image processing device is provided and includes the steps of extracting three information streams from the image. A set of Gaussian pyramids are formed from the three information streams by performing eight levels of decimation by a factor two. A set of feature maps are formed from a portion of the set of Gaussian pyramids. The set of feature maps are resized and summed to form a set of conspicuity maps. The set of conspicuity maps are normalized, weighted and summed to form the saliency map.

Ultrasonic Doppler measurements of blood flow velocity of rabbit retinal vessels using a 45-MHz needle transducer.

Abstract: Background The purpose of this study is to measure blood flow velocity of rabbit retinal vessels using a 45-MHz ultrasonic Doppler system with a needle transducer.

Ex Vivo implantation study of minimally invasive glaucoma drainage device

Abstract: We present in this paper the first ex vivo implantation results of our minimally invasive glaucoma drainage device (GDD.) The GDD is designed to treat glaucoma patients by draining out their extraneous aqueous humor out of the anterior chamber utilizing a MEMS micro-fluidic normally closed (NC) check valve. The NC check valve is encapsulated in protective tubing made from parylene C, which has been proved to be biocompatible in implantation. A new packaging and a bench-top testing procedure is established to characterize the integrated GDD prior to its implantation into enucleated porcine eyes. Pre-implanted characterization curve demonstrates a cracking pressure of 10–20 mmHg of the NC check valve, which agrees with our theoretical design. Ex vivo implantation results show that cracking pressure is measured as 24 mmHg by unloading the eye pressure. The little offset of the cracking pressure comes from the differences between the in vitro and ex vivo testing environments. The hysteresis behavior of the NC check valve is also examined during implantation and is presented here.

Injury and Repair: Prostheses

Abstract: Sight restoration in the event of retinal degenerative diseases or even loss of the eyes has been an aim of researchers for over 50 years Cortical prostheses, where visual signals are transmitted directly from a camera to the visual cortex, were the first to be studied, although technical difficulties and tissue complexities have slowed progress in this area Research on retinal electronic prosthetic devices has been more successful, with many groups around the world working on a technology that effectively replaces retinal photoreceptor cells Proof of principle has been established in that initial results from prosthesis clinical trials have demonstrated restoration of light perception and some form of vision in subjects originally having no or bare light perception