Doctor of Philosophy

dissertationThis dissertation provides an in-depth evaluation of microstimulation of the primary visual cortex (V1) using chronically implanted Utah Electrode Arrays (UEAs) in macaque monkeys for use as a visual prosthesis. Within the scope of this dissertation are several significant contributions. First, a minimally invasive and robust device for head fixation was developed. In comparison to other available designs, this device improved long-term outcomes by providing a stronger, less invasive interface that reduced the risk of infection. This device made it possible to acquire chronic microstimulation data in macaque monkeys. It has been tested on three animals and has provided a stable interface for over two years. Second, this dissertation is the first to describe the factors influencing the performance and safety of microstimulation of V1 with the UEA. Two UEAs were implanted in V1 of two macaque monkeys, and experiments were performed several months following implantation. The electrical and recording properties of the electrodes and the high-resolution visuotopic organization of V1 were measured. In addition, threshold stimulation levels that evoked behavioural responses using single electrodes were determined. Periodic microstimulation at currents up to 96 pA did not impair the ability to record neural signals and did not affect the animal's vision where the UEAs were implanted. It was discovered, however, that microstimulation at these levels evoked behavioural responses on only 8 of 82 systematically stimulated electrodes. It was suggested that the ability to evoke behavioral responses may depend on the location of the electrode tips within the cortical layers of V1, the distance of the electrode tips to neuronal somata, and the inability of nonhuman primates to recognize and respond to a generalized set of evoked percepts. Finally, this dissertation is the first to describe the spatial and temporal characteristics of microstimulation of V1 with the UEA over chronic time periods. Two years after implantation, it was found that consistent behavioural responses could be evoked during simultaneous stimulation of multiple contiguous electrodes. Saccades to electrically-evoked targets using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with a resolution comparable to the current epiretinal prostheses. These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a UEA-based visual prosthesis for the blind

Communication and control system for a 15-channel hermetic retinal prosthesis

A small, hermetic, wirelessly-controlled retinal prosthesis has been developed for pre-clinical studies in Yucatan minipigs. The device was attached conformally to the outside of the eye in the socket and received both power and data wirelessly from external sources. Based on the received image data, the prosthesis drove a subretinal thin-film polyimide array of sputtered iridium oxide stimulating electrodes. The implanted device included a hermetic titanium case containing a 15-channel stimulator and receiver chip and discrete circuit components. Feedthroughs in the hermetic case connected the chip to secondary power- and data-receiving coils, which coupled to corresponding external power and data coils driven by power amplifiers. Power was delivered by a 125 kHz carrier, and data were delivered by amplitude shift keying of a 15.5 MHz carrier at 100 kbps. Stimulation pulse strength, duration and frequency were programmed wirelessly from an external computer system. The final assembly was tested in vitro in physiological saline and in vivo in two minipigs for up to five and a half months by measuring stimulus artifacts generated by the implant's current drivers.United States. Dept. of Veteran AffairsUnited states. Dept. of Veterans Affairs. Boston Healthcare SystemNational Institutes of Health (U.S.)United States. Dept. of DefenseMassachusetts Lions Foundatio

Central nervous system microstimulation: Towards selective micro-neuromodulation

Electrical stimulation technologies capable of modulating neural activity are well established for neuroscientific research and neurotherapeutics. Recent micro-neuromodulation experimental results continue to explain neural processing complexity and suggest the potential for assistive technologies capable of restoring or repairing of basic function. Nonetheless, performance is dependent upon the specificity of the stimulation. Increasingly specific stimulation is hypothesized to be achieved by progressively smaller interfaces. Miniaturization is a current focus of neural implants due to improvements in mitigation of the body's foreign body response. It is likely that these exciting technologies will offer the promise to provide large-scale micro-neuromodulation in the future. Here, we highlight recent successes of assistive technologies through bidirectional neuroprostheses currently being used to repair or restore basic brain functionality. Furthermore, we introduce recent neuromodulation technologies that might improve the effectiveness of these neuroprosthetic interfaces by increasing their chronic stability and microstimulation specificity. We suggest a vision where the natural progression of innovative technologies and scientific knowledge enables the ability to selectively micro-neuromodulate every neuron in the brain

Fiber bragg gratings for medical applications and future challenges: A review

In the last decades, fiber Bragg gratings (FBGs) have become increasingly attractive to medical applications due to their unique properties such as small size, biocompatibility, immunity to electromagnetic interferences, high sensitivity and multiplexing capability. FBGs have been employed in the development of surgical tools, assistive devices, wearables, and biosensors, showing great potentialities for medical uses. This paper reviews the FBG-based measuring systems, their principle of work, and their applications in medicine and healthcare. Particular attention is given to sensing solutions for biomechanics, minimally invasive surgery, physiological monitoring, and medical biosensing. Strengths, weaknesses, open challenges, and future trends are also discussed to highlight how FBGs can meet the demands of next-generation medical devices and healthcare system

Fiber Bragg Gratings for Medical Applications and Future Challenges: A Review

[EN] In the last decades, fiber Bragg gratings (FBGs) have become increasingly attractive to medical applications due to their unique properties such as small size, biocompatibility, immunity to electromagnetic interferences, high sensitivity and multiplexing capability. FBGs have been employed in the development of surgical tools, assistive devices, wearables, and biosensors, showing great potentialities for medical uses. This paper reviews the FBG-based measuring systems, their principle of work, and their applications in medicine and healthcare. Particular attention is given to sensing solutions for biomechanics, minimally invasive surgery, physiological monitoring, and medical biosensing. Strengths, weaknesses, open challenges, and future trends are also discussed to highlight how FBGs can meet the demands of next-generation medical devices and healthcare system.This work was supported in part by INAIL (the Italian National Institute for Insurance against Accident at Work), through the BRIC (Bando ricerche in collaborazione) 2018 SENSE-RISC (Sviluppo di abiti intelligENti Sensorizzati per prevenzione e mitigazione di Rischi per la SiCurezza dei lavoratori) Project under Grant ID10/2018, in part by the UCBM (Universita Campus Bio-Medico di Roma) under the University Strategic HOPE (HOspital to the PatiEnt) Project, in part by the EU Framework Program H2020-FETPROACT-2018-01 NeuHeart Project under Grant GA 824071, by FCT/MEC (Fundacao para a Ciencia e Tecnologia) under the Projects UIDB/50008/2020 - UIDP/50008/2020, and by REACT (Development of optical fiber solutions for Rehabilitation and e-Health applications) FCT-IT-LA scientific action.Lo Presti, D.; Massaroni, C.; Leitao, CSJ.; Domingues, MDF.; Sypabekova, M.; Barrera, D.; Floris, I.... (2020). Fiber Bragg Gratings for Medical Applications and Future Challenges: A Review. IEEE Access. 8:156863-156888. https://doi.org/10.1109/ACCESS.2020.3019138S156863156888

Extraocular Surgical Approach for Placement of Subretinal Implants in Blind Patients: Lessons from Cochlear-Implants

In hereditary retinal diseases photoreceptors progressively degenerate, often causing blindness without therapy being available. Newly developed subretinal implants can substitute functions of photoreceptors. Retina implant extraocular surgical technique relies strongly on cochlear-implant know-how. However, a completely new surgical approach providing safe handling of the photosensor array had to be developed. The Retina Implant Alpha IMS consisting of a subretinal microphotodiode array and cable linked to a cochlear-implant-like ceramic housing was introduced via a retroauricular incision through a subperiosteal tunnel above the zygoma into the orbit using a specially designed trocar. Implant housing was fixed in a bony bed within a tight subperiosteal pocket in all patients. Primary outcomes were patient short term safety as well as effectiveness. Nine patients participated in the first part of the multicenter trial and received the subretinal visual implant in one eye. In all cases microphotodiode array pull-through procedure and stable positioning were possible without affecting the device function. No intraoperative complications were encountered. The minimally invasive suprazygomatic tunneling technique for the sensor unit as well as a subperiosteal pocket fixation of the implant housing provides a safe extraocular implantation approach of a subretinal device with a transcutaneous extracorporeal power supply

Are nanotechnology and robotics alternatives for therapeutic and theragnostic ophthalmic applications technologies for eye care services?

Objective: To identify new technological advances in biotechnology, nanotechnology and robotics and their application in diagnosis and therapeutics for visual health

Visual BOLD Response in Late Blind Subjects with Argus II Retinal Prosthesis

Retinal prosthesis technologies require that the visual system downstream of the retinal circuitry be capable of transmitting and elaborating visual signals. We studied the capability of plastic remodeling in late blind subjects implanted with the Argus II Retinal Prosthesis with psychophysics and functional MRI (fMRI). After surgery, six out of seven retinitis pigmentosa (RP) blind subjects were able to detect high-contrast stimuli using the prosthetic implant. However, direction discrimination to contrast modulated stimuli remained at chance level in all of them. No subject showed any improvement of contrast sensitivity in either eye when not using the Argus II. Before the implant, the Blood Oxygenation Level Dependent (BOLD) activity in V1 and the lateral geniculate nucleus (LGN) was very weak or absent. Surprisingly, after prolonged use of Argus II, BOLD responses to visual input were enhanced. This is, to our knowledge, the first study tracking the neural changes of visual areas in patients after retinal implant, revealing a capacity to respond to restored visual input even after years of deprivation