MEMS-based system and image processing strategy for epiretinal prosthesis.

Retinal prostheses have the potential to restore some level of visual function to the patients suffering from retinal degeneration. In this paper, an epiretinal approach with active stimulation devices is presented. The MEMS-based processing system consists of an external micro-camera, an information processor, an implanted electrical stimulator and a microelectrode array. The image processing strategy combining image clustering and enhancement techniques was proposed and evaluated by psychophysical experiments. The results indicated that the image processing strategy improved the visual performance compared with direct merging pixels to low resolution. The image processing methods assist epiretinal prosthesis for vision restoration.

A diagnostic algorithm to optimize data collection and interpretation of Ripple Maps in atrial tachycardias.

BACKGROUND: Ripple Mapping (RM) is designed to overcome the limitations of existing isochronal 3D mapping systems by representing the intracardiac electrogram as a dynamic bar on a surface bipolar voltage map that changes in height according to the electrogram voltage-time relationship, relative to a fiduciary point. OBJECTIVE: We tested the hypothesis that standard approaches to atrial tachycardia CARTO™ activation maps were inadequate for RM creation and interpretation. From the results, we aimed to develop an algorithm to optimize RMs for future prospective testing on a clinical RM platform. METHODS: CARTO-XP™ activation maps from atrial tachycardia ablations were reviewed by two blinded assessors on an off-line RM workstation. Ripple Maps were graded according to a diagnostic confidence scale (Grade I - high confidence with clear pattern of activation through to Grade IV - non-diagnostic). The RM-based diagnoses were corroborated against the clinical diagnoses. RESULTS: 43 RMs from 14 patients were classified as Grade I (5 [11.5%]); Grade II (17 [39.5%]); Grade III (9 [21%]) and Grade IV (12 [28%]). Causes of low gradings/errors included the following: insufficient chamber point density; window-of-interest<100% of cycle length (CL); <95% tachycardia CL mapped; variability of CL and/or unstable fiducial reference marker; and suboptimal bar height and scar settings. CONCLUSIONS: A data collection and map interpretation algorithm has been developed to optimize Ripple Maps in atrial tachycardias. This algorithm requires prospective testing on a real-time clinical platform.

Light-controlled biphasic current stimulator IC using CMOS image sensors for high-resolution retinal prosthesis and in vitro experimental results with rd1 mouse.

Retinal prosthetic devices stimulate retinal nerve cells with electrical signals proportional to the incident light intensities. For a high-resolution retinal prosthesis, it is necessary to reduce the size of the stimulator pixels as much as possible, because the retinal nerve cells are concentrated in a small area of approximately 5 mm × 5 mm. In this paper, a miniaturized biphasic current stimulator integrated circuit is developed for subretinal stimulation and tested in vitro. The stimulator pixel is miniaturized by using a complementary metal-oxide-semiconductor (CMOS) image sensor composed of three transistors. Compared to a pixel that uses a four-transistor CMOS image sensor, this new design reduces the pixel size by 8.3%. The pixel size is further reduced by simplifying the stimulation-current generating circuit, which provides a 43.9% size reduction when compared to the design reported to be the most advanced version to date for subretinal stimulation. The proposed design is fabricated using a 0.35 µm bipolar-CMOS-DMOS process. Each pixel is designed to fit in a 50 µ m × 55 µm area, which theoretically allows implementing more than 5000 pixels in the 5 mm × 5 mm area. Experimental results show that a biphasic current in the range of 0 to 300 µA at 12 V can be generated as a function of incident light intensities. Results from in vitro experiments with rd1 mice indicate that the proposed method can be effectively used for retinal prosthesis with a high resolution.

[Specifity of optic disc evaluation in healthy subjects with large optic discs and physiologic cupping using confocal scanning laser ophthalmoscopy]. / Spezifität der konfokalen Scanning Laser Ophthalmoskopie bei großen Sehnerven mit physiologischer Exkavation.

PURPOSE: Imaging methods of the optic nerve head appear to have an increasing impact in glaucoma diagnosis. The aim of this study is to evaluate the specifity of the Heidelberg Retina Tomograph (software version 1.7 and 3.0) in subjects with physiological cupping and large optic discs. PATIENTS AND METHODS: 27 eyes of 27 subjects (mean age 41.3 ± 15.8 years) with bilateral physiological cupping and large optic discs (vertical cup-to-disc-ratio > 0.3, optic disc area 2.48 ± 0.45 mm2, max. 3.54 mm2) were included in a clinical study. All subjects had an intraocular pressure < 22 mmHg, physiological cupping by funduscopy and no nerve fibre layer defects (Scanning Laser Ophthalmoscope, Rodenstock, Germany). Standard achromatic perimetry (Humphrey Field Analyzer, Humphrey-Zeiss, 24/2 SITA or full threshold), short-wavelength automated perimetry (Humphrey Field Analyzer, Humphrey-Zeiss), and frequency doubling technology (FDT, Humphrey-Zeiss) revealed no visual field defects. Optic disc imaging was performed in all subjects using the Heidelberg Retina Tomograph II (HRT). Optic disc images were transferred to the software-update of the HRT 3 (Version 3.0, Heidelberg Engineering). Specifity was calculated using the Moorfields regression analysis (MRA, software version 1.7 and 3.0) and the glaucoma probability score (GPS analysis) using all disc sectors and omitting the nasal and 3 nasal sectors. RESULTS: Specifity of the MRA (software version 1.7) was 66.6 % (most specific criteria), and 22.2 % (least specific criteria). Specifity of the MRA (software version 3.0) was 33.3 % (most specific criteria), and 14.8 % (least specific criteria), whereas specifity of the GPS analysis was 37.0 % (most specific criteria), and 11.1 % (least specific criteria). When the nasal sectors were omitted for analysis, specifity increased for the MRA analysis, but not for the GPS analysis. CONCLUSIONS: Specifity of the MRA was unsatisfactory using the software version 1.7 and 3.0 in subjects with large optic discs and physiological cupping when the nasal sectors were included in the analysis. The observer-independent GPS analysis did not improve the results in these subjects.

Label-free cytotoxicity screening assay by digital holographic microscopy.

We introduce a label-free technology based on digital holographic microscopy (DHM) with applicability for screening by imaging, and we demonstrate its capability for cytotoxicity assessment using mammalian living cells. For this first high content screening compatible application, we automatized a digital holographic microscope for image acquisition of cells using commercially available 96-well plates. Data generated through both label-free DHM imaging and fluorescence-based methods were in good agreement for cell viability identification and a Z'-factor close to 0.9 was determined, validating the robustness of DHM assay for phenotypic screening. Further, an excellent correlation was obtained between experimental cytotoxicity dose-response curves and known IC50 values for different toxic compounds. For comparable results, DHM has the major advantages of being label free and close to an order of magnitude faster than automated standard fluorescence microscopy.

Warning navigation system using real-time safe region monitoring for otologic surgery.

PURPOSE: We developed a surgical navigation system that warns the surgeon with auditory and visual feedback to protect the facial nerve with real-time monitoring of the safe region during drilling. METHODS: Warning navigation modules were developed and integrated into a free open source software platform. To obtain high registration accuracy, we used a high-precision laser-sintered template of the patient's bone surface to register the computed tomography (CT) images. We calculated the closest distance between the drill tip and the surface of the facial nerve during drilling. When the drill tip entered the safe regions, the navigation system provided an auditory and visual signal which differed in each safe region. To evaluate the effectiveness of the system, we performed phantom experiments for maintaining a given safe margin from the facial nerve when drilling bone models, with and without the navigation system. The error of the safe margin was measured on postoperative CT images. In real surgery, we evaluated the feasibility of the system in comparison with conventional facial nerve monitoring. RESULTS: The navigation accuracy was submillimeter for the target registration error. In the phantom study, the task with navigation ([Formula: see text] mm) was more successful with smaller error, than the task without navigation ([Formula: see text] mm, [Formula: see text]). The clinical feasibility of the system was confirmed in three real surgeries. CONCLUSIONS: This system could assist surgeons in preserving the facial nerve and potentially contribute to enhanced patient safety in the surgery.

A cost effective simulator for education of ultrasound image interpretation and probe manipulation.

Ultrasonography is the lowest cost no risk medical imaging technique. However, reading an ultrasonographic (US) image as well as performing a good US probe positioning remain difficult tasks. Education in this domain is today performed on patients, thus limiting it to the most common cases. In this paper, we present a cost effective simulator that allows US image practice and realistic probe manipulation from CT data. More precisely, we tackle the issue of providing a realistic interface for the probe manipulation with a basic haptic feedback.

Realization of a 15-channel, hermetically-encased wireless subretinal prosthesis for the blind.

A miniaturized, hermetically-encased, wirelessly-operated retinal prosthesis has been developed for implantation and pre-clinical studies in Yucatan mini-pig animal models. The prosthesis conforms to the eye and drives a microfabricated polyimide stimulating electrode array with sputtered iridium oxide electrodes. This array is implanted in the subretinal space using a specially-designed ab externo surgical technique that affixes the bulk of the prosthesis to the surface of the sclera. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip and discrete power supply components. Feedthroughs from the case connect to secondary power- and data-receiving coils. In addition, long-term in vitro pulse testing was performed on the electrodes to ensure their stability for the long lifetime of the hermetic case. The final assembly was tested in vitro to verify wireless operation of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation pulse strength, duration and frequency were programmed wirelessly using a custom graphical user interface. Operation of the retinal implant has been verified in vivo in one pig for more than three months by measuring stimulus artifacts on the eye surface using a contact lens electrode.

Light-controlled retinal stimulation on rabbit using CMOS-based flexible multi-chip stimulator.

We implemented a light-sensing function on CMOS-based multi-chip stimulator for retinal prosthesis. Using the light-sensing circuitry attached to each stimulation electrode, the flexible multi-chip stimulator is capable of image-based patterned stimulation. We verified the function of the light-controlled decision based on the light intensity measured just beside the stimulation site. We also experimentally demonstrated in vivo retinal stimulation on rabbit's retina with light-controlled decision. The result of the present work is a simplified demonstration for the concept of retinal prosthesis with on-site imaging.

Online real-time reconstruction of adaptive TSENSE with commodity CPU/GPU hardware.

Adaptive temporal sensitivity encoding (TSENSE) has been suggested as a robust parallel imaging method suitable for MR guidance of interventional procedures. However, in practice, the reconstruction of adaptive TSENSE images obtained with large coil arrays leads to long reconstruction times and latencies and thus hampers its use for applications such as MR-guided thermotherapy or cardiovascular catheterization. Here, we demonstrate a real-time reconstruction pipeline for adaptive TSENSE with low image latencies and high frame rates on affordable commodity personal computer hardware. For typical image sizes used in interventional imaging (128 x 96, 16 channels, sensitivity encoding (SENSE) factor 2-4), the pipeline is able to reconstruct adaptive TSENSE images with image latencies below 90 ms at frame rates of up to 40 images/s, rendering the MR performance in practice limited by the constraints of the MR acquisition. Its performance is demonstrated by the online reconstruction of in vivo MR images for rapid temperature mapping of the kidney and for cardiac catheterization.

Assessment of the mechanical properties of the musculoskeletal system using 2-D and 3-D very high frame rate ultrasound.

One of the great challenges for understanding muscular diseases is to assess noninvasively the active and passive mechanical properties of the musculoskeletal system. In this paper we report the use of ultrafast ultrasound imaging to explore with a submillimeter resolution the behavior of the contracting tissues in vivo (biceps brachii). To image the contraction, which is a very brief phenomenon (100 ms), a recently designed ultrasound scanner prototype able to take up to 6000 frames/s was used. A very high frame rate from 1000 to 2500 frames/s was used to image the cross section plane of the muscle (transverse to fibers) enabling us to catch in real time the muscle contraction during a transient electrostimulation. Tissue velocities were obtained from radiofrequency based speckle tracking techniques and their profiles are discussed with respect to electrostimulation intensities and pulse repetition frequencies for different volunteers. Three-dimensional (3-D) very high frame rate movies were also acquired by repeating the experiment for different acquisition planes while triggering the imaging system with the electrostimulation device. The reconstructed 3-D velocity field allows the full localization of the contracting fibers bundle. This ultrasound technique, referred to as echo mechanomyography, offers new perspectives for in vivo and in situ noninvasive muscle diagnosis of an active contractile tissue.

[A novel system for tongue inspection based on hyperspectral imaging system].

Tongue inspection is an important diagnostic method in traditional Chinese medicine (TCM). However, due to its qualitative, subjective and experience-based nature, traditional tongue inspection has found very limited application in modem clinical medicine. In this paper, a novel system for tongue inspection based on hyperspectral imaging system is developed. The system includes image acquisition, feature extraction and classification functions. In this system, two kinds of quantitative features, spatial and spectral, are extracted from hyperspectral tongue images by using popular digital image processing techniques. Then, Bayesian networks are employed to model the relationship between these quantitative features and diseases. The preliminary results show that the system is sensitive to the abnormal tongues.

Image analysis for microelectronic retinal prosthesis.

By way of extracellular, stimulating electrodes, a microelectronic retinal prosthesis aims to render discrete, luminous spots-so-called phosphenes-in the visual field, thereby providing a phosphene image (PI) as a rudimentary remediation of profound blindness. As part thereof, a digital camera, or some other photosensitive array, captures frames, frames are analyzed, and phosphenes are actuated accordingly by way of modulated charge injections. Here, we present a method that allows the assessment of image analysis schemes for integration with a prosthetic device, that is, the means of converting the captured image (high resolution) to modulated charge injections (low resolution). We use the mutual-information function to quantify the amount of information conveyed to the PI observer (device implantee), while accounting for the statistics of visual stimuli. We demonstrate an effective scheme involving overlapping, Gaussian kernels, and discuss extensions of the method to account for shortterm visual memory in observers, and their perceptual errors of omission and commission.

Forward-looking intracardiac ultrasound imaging using a 1-D CMUT array integrated with custom front-end electronics.

Minimally invasive catheter-based electrophysiological (EP) interventions are becoming a standard procedure in diagnosis and treatment of cardiac arrhythmias. As a result of technological advances that enable small feature sizes and a high level of integration, nonfluoroscopic intracardiac echocardiography (ICE) imaging catheters are attracting increasing attention. ICE catheters improve EP procedural guidance while reducing the undesirable use of fluoroscopy, which is currently the common catheter guidance method. Phased-array ICE catheters have been in use for several years now, although only for side-looking imaging. We are developing a forward-looking ICE catheter for improved visualization. In this effort, we fabricate a 24-element, fine-pitch 1-D array of capacitive micromachined ultrasonic transducers (CMUT), with a total footprint of 1.73 mm x 1.27 mm. We also design a custom integrated circuit (IC) composed of 24 identical blocks of transmit/ receive circuitry, measuring 2.1 mm x 2.1 mm. The transmit circuitry is capable of delivering 25-V unipolar pulses, and the receive circuitry includes a transimpedance preamplifier followed by an output buffer. The CMUT array and the custom IC are designed to be mounted at the tip of a 10-Fr catheter for high-frame-rate forward-looking intracardiac imaging. Through-wafer vias incorporated in the CMUT array provide access to individual array elements from the back side of the array. We successfully flip-chip bond a CMUT array to the custom IC with 100% yield. We coat the device with a layer of polydimethylsiloxane (PDMS) to electrically isolate the device for imaging in water and tissue. The pulse-echo in water from a total plane reflector has a center frequency of 9.2 MHz with a 96% fractional bandwidth. Finally, we demonstrate the imaging capability of the integrated device on commercial phantoms and on a beating ex vivo rabbit heart (Langendorff model) using a commercial ultrasound imaging system.

An implantable microsystem as a vision prosthesis.

Blindness is often the result of degeneration of the light sensitive rods and cones of the retina in conditions such as retinitis pigmentosa and macula degeneration. An implantable vision prosthesis has been developed that electrically stimulates the retinal ganglion cells in such a way that action potentials in retinal ganglion cells are evoked, causing a visual sensation in the visual cortex. Clinical trials are about to be conducted.

Image processing for a high-resolution optoelectronic retinal prosthesis.

In an effort to restore visual perception in retinal diseases such as age-related macular degeneration or retinitis pigmentosa, a design was recently presented for a high-resolution optoelectronic retinal prosthesis having thousands of electrodes. This system requires real-time image processing fast enough to convert a video stream of images into electrical stimulus patterns that can be properly interpreted by the brain. Here, we present image-processing and tracking algorithms for a subretinal implant designed to stimulate the second neuron in the visual pathway, bypassing the degenerated first synaptic layer. For this task, we have developed and implemented: 1) A tracking algorithm that determines the implant's position in each frame. 2) Image cropping outside of the implant boundaries. 3) A geometrical transformation that distorts the image appropriate to the geometry of the fovea. 4) Spatio-temporal image filtering to reproduce the visual processing normally occurring in photoceptors and at the photoreceptor-bipolar cell synapse. 5) Conversion of the filtered visual information into a pattern of electrical current. Methods to accelerate real-time transformations include the exploitation of data redundancy in the time domain, and the use of precomputed lookup tables that are adjustable to retinal physiology and allow flexible control of stimulation parameters. A software implementation of these algorithms processes natural visual scenes with sufficient speed for real-time operation. This computationally efficient algorithm resembles, in some aspects, biological strategies of efficient coding in the retina and could provide a refresh rate higher than fifty frames per second on our system.

Recording invertebrate nerve activation with modulated light changes.

Optical scattering techniques have the potential to provide noninvasive measurements of neural activity with good spatial and temporal resolution. We used the lobster nerve as a model system to investigate and record event-related optical signals with a modulated light source and heterodyne detection system. We observed changes in the transmitted birefringent light intensity, corresponding with electrophysiological measurements of the action potential. The photon delay was below the detection threshold, in part due to the small size of the nerve bundle. Our system allowed us to place an upper bound on the magnitude of the phase change of 0.01 degrees. The physiological stability of the preparation allows comprehensive characterization of biological and instrumentation noise sources for testing optical measurement systems.

Optoelectronic retinal prosthesis: system design and performance.

The design of high-resolution retinal prostheses presents many unique engineering and biological challenges. Ever smaller electrodes must inject enough charge to stimulate nerve cells, within electrochemically safe voltage limits. Stimulation sites should be placed within an electrode diameter from the target cells to prevent 'blurring' and minimize current. Signals must be delivered wirelessly from an external source to a large number of electrodes, and visual information should, ideally, maintain its natural link to eye movements. Finally, a good system must have a wide range of stimulation currents, external control of image processing and the option of either anodic-first or cathodic-first pulses. This paper discusses these challenges and presents solutions to them for a system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a head-mounted near-to-eye projection system operating at near-infrared wavelengths. Photodiodes convert light into pulsed electric current, with charge injection maximized by applying a common biphasic bias waveform. The resulting prosthesis will provide stimulation with a frame rate of up to 50 Hz in a central 10 degrees visual field, with a full 30 degrees field accessible via eye movements. Pixel sizes are scalable from 100 to 25 microm, corresponding to 640-10,000 pixels on an implant 3 mm in diameter.

CAVE and fishtank virtual-reality displays: a qualitative and quantitative comparison.

We present the results from a qualitative and quantitative user study comparing fishtank virtual-reality (VR) and CAVE displays. The results of the qualitative study show that users preferred the fishtank VR display to the CAVE system for our scientific visualization application because of perceived higher resolution, brightness and crispness of imagery, and comfort of use. The results of the quantitative study show that users performed an abstract visual search task significantly more quickly and more accurately on the fishtank VR display system than in the CAVE. The same study also showed that visual context had no significant effect on task performance for either of the platforms. We suggest that fishtank VR displays are more effective than CAVEs for applications in which the task occurs outside the user's reference frame, the user views and manipulates the virtual world from the outside in, and the size of the virtual object that the user interacts with is smaller than the user's body and fits into the fishtank VR display. The results of both studies support this proposition.

Measurement of the amount and number of pollen particles of Cryptomeria japonica (taxodiaceae) by imaging with a photoacoustic microscope.

A photoacoustic microscope (PAM), which includes a condenser microphone and a pair of linear-motor-driven pulse stages, was specially designed for spectroscopic applications. The PAM was applied to measure the amount and number of pollen particles of Cryptomeria japonica (CJ), which is known for its allergic function against eyes and nose. The advantage of photoacoustic (PA) imaging is both its high sensitivity and its counting ability up to high concentrations of the specimen. The CJ pollen particles were fixed on a piece of adhesive tape or on albumen (egg white) on a glass slide set in a PA cell. The PA image showed the ability of this method to count CJ pollen from the several-hundred-milligram region to even a single particle. The PA signal obtained was integrated over the specimen surface. The dependence of the PA signal on the amount or number of the pollen particles was measured. The resulting coefficients of correlation of the calibration curves for the amount and the number of pollen particles were 0.94 and 0.97, respectively.