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Tovar-Lopez F.J.,University of Vic | Rosengarten G.,University of Vic | Nasabi M.,University of Vic | Sivan V.,University of Vic | And 6 more authors.
PLoS ONE | Year: 2013

This paper reports on an investigation of mass transport of blood cells at micro-scale stenosis where local strain-rate micro-gradients trigger platelet aggregation. Using a microfluidic flow focusing platform we investigate the blood flow streams that principally contribute to platelet aggregation under shear micro-gradient conditions. We demonstrate that relatively thin surface streams located at the channel wall are the primary contributor of platelets to the developing aggregate under shear gradient conditions. Furthermore we delineate a role for red blood cell hydrodynamic lift forces in driving enhanced advection of platelets to the stenosis wall and surface of developing aggregates. We show that this novel microfluidic platform can be effectively used to study the role of mass transport phenomena driving platelet recruitment and aggregate formation and believe that this approach will lead to a greater understanding of the mechanisms underlying shear-gradient dependent discoid platelet aggregation in the context of cardiovascular diseases such as acute coronary syndromes and ischemic stroke. © 2013 Tovar-Lopez et al.

Aram P.,Institute Of Neurosciences Des Systemes | Aram P.,University of Sheffield | Freestone D.R.,University of Melbourne | Freestone D.R.,The Bionics Institute | And 6 more authors.
NeuroImage | Year: 2013

Neural fields are spatially continuous state variables described by integro-differential equations, which are well suited to describe the spatiotemporal evolution of cortical activations on multiple scales. Here we develop a multi-resolution approximation (MRA) framework for the integro-difference equation (IDE) neural field model based on semi-orthogonal cardinal B-spline wavelets. In this way, a flexible framework is created, whereby both macroscopic and microscopic behavior of the system can be represented simultaneously. State and parameter estimation is performed using the expectation maximization (EM) algorithm. A synthetic example is provided to demonstrate the framework. © 2012 Elsevier Inc.

Wise A.K.,The Bionics Institute | Wise A.K.,University of Melbourne | Fallon J.B.,The Bionics Institute | Fallon J.B.,University of Melbourne | And 6 more authors.
Neurotherapeutics | Year: 2011

Cochlear implants provide partial restoration of hearing for profoundly deaf patients by electrically stimulating spiral ganglion neurons (SGNs); however, these neurons gradually degenerate following the onset of deafness. Although the exogenous application of neurotrophins (NTs) can prevent SGN loss, current techniques to administer NTs for long periods of time have limited clinical applicability. We have used encapsulated choroid plexus cells (NTCells; Living Cell Technologies, Auckland, New Zealand) to provide NTs in a clinically viable manner that can be combined with a cochlear implant. Neonatal cats were deafened and unilaterally implanted with NTCells and a cochlear implant. Animals received chronic electrical stimulation (ES) alone, NTs alone, or combined NTs and ES (ES + NT) for a period of as much as 8 months. The opposite ear served as a deafened unimplanted control. Chronic ES alone did not result in increased survival of SGNs or their peripheral processes. NT treatment alone resulted in greater SGN survival restricted to the upper basal cochlear region and an increased density of SGN peripheral processes. Importantly, chronic ES in combination with NTs provided significant SGN survival throughout a wider extent of the cochlea, in addition to an increased peripheral process density. Re-sprouting peripheral processes were observed in the scala media and scala tympani, raising the possibility of direct contact between peripheral processes and a cochlear implant electrode array. We conclude that cell-based therapy is clinically viable and effective in promoting SGN survival for extended durations of cochlear implant use. These findings have important implications for the safe delivery of therapeutic drugs to the cochlea. © 2011 The American Society for Experimental NeuroTherapeutics, Inc.

PubMed | Royal Melbourne Hospital, University of Melbourne and The Bionics Institute
Type: Journal Article | Journal: Artificial organs | Year: 2016

Successful visual prostheses require stable, long-term attachment. Epiretinal prostheses, in particular, require attachment methods to fix the prosthesis onto the retina. The most common method is fixation with a retinal tack; however, tacks cause retinal trauma, and surgical proficiency is important to ensure optimal placement of the prosthesis near the macula. Accordingly, alternate attachment methods are required. In this study, we detail a novel method of magnetic attachment for an epiretinal prosthesis using two prostheses components positioned on opposing sides of the retina. The magnetic attachment technique was piloted in a feline animal model (chronic, nonrecovery implantation). We also detail a new method to reliably control the magnet coupling force using heat. It was found that the force exerted upon the tissue that separates the two components could be minimized as the measured force is proportionately smaller at the working distance. We thus detail, for the first time, a surgical method using customized magnets to position and affix an epiretinal prosthesis on the retina. The position of the epiretinal prosthesis is reliable, and its location on the retina is accurately controlled by the placement of a secondary magnet in the suprachoroidal location. The electrode position above the retina is less than 50 microns at the center of the device, although there were pressure points seen at the two edges due to curvature misalignment. The degree of retinal compression found in this study was unacceptably high; nevertheless, the normal structure of the retina remained intact under the electrodes.

Rickard N.A.,University of Canterbury | Rickard N.A.,The Bionics Institute | Smales C.J.,University of Canterbury | Rickard K.L.,University of Canterbury
International Journal of Pediatric Otorhinolaryngology | Year: 2013

Objective: One type of test commonly used to assess auditory processing disorders (APD) is the Frequency Pattern Test, in which triads of pure tones of two different frequencies are presented, and participants are required to accurately report the sequence of tones, typically using a verbal response. The test is widely used clinically, but in its current format, is an under-exploited means of addressing some candidate processes, such as temporal ordering and frequency discrimination, which might be affected in APD. Here we describe a computer-based version of an auditory pattern perception test, the BirdSong Game, which was designed to be an engaging research tool for use with school-aged children. Methods: In this study, 128 children aged 6-10 with normal peripheral hearing were tested. The BirdSong Game application was used to administer auditory sequential pattern tests, via a touch-screen presentation and response interface. A conditioning step was included prior to testing, in order to ensure that participants were able to adequately discriminate between the test tones, and reliably describe the difference using their own vocabulary. Responses were collected either verbally or manually, by having participants press cartoon images on the touch-screen in the appropriate sequence. The data was examined for age, gender and response mode differences. Results: Findings on the auditory tests indicated a significant maturational effect across the age range studied, with no difference between response modes or gender. Conclusions: The BirdSong Game is sensitive to maturational changes in auditory sequencing ability, and the computer-based design of the test has several advantages which make it a potentially useful clinical and research tool. © 2013 Elsevier Ireland Ltd.

O'Beirne G.A.,University of Canterbury | McGaffin A.J.,University of Canterbury | Rickard N.A.,University of Canterbury | Rickard N.A.,The Bionics Institute
International Journal of Pediatric Otorhinolaryngology | Year: 2012

Objective: One type of test commonly used to examine auditory processing disorders (APD) is the low-pass filtered speech test (LPFST), of which there are various versions. In LPFSTs, a monaural, low-redundancy speech sample is distorted by using filtering to modify its frequency content. Due to the richness of the neural pathways in the auditory system and the redundancy of acoustic information in spoken language, a normal listener is able to recognize speech even when parts of the signal are missing, whereas this ability is often impaired in listeners with APD. One limitation of the various versions of the LPFST is that they are carried out using a constant level of low-pass filtering (e.g. a fixed 1. kHz corner frequency) which makes them prone to ceiling and floor effects. The purpose of this study was to counter these effects by modifying the LPFST using a computer-based adaptive procedure, and to evaluate the performance of normal-hearing participants of varying ages on the test. Methods: In this preliminary study, 33 adults and 30 children (aged 8-11 years) with no known history of listening difficulties were tested. The University of Canterbury Adaptive Speech Test (UCAST) platform was used to administer a four-alternative forced-choice adaptive test that altered a low-pass filter (LPF) to track the corner frequency at which participants correctly identified a certain percentage of the word stimuli. Results: Findings on the University of Canterbury Adaptive Speech Test-Filtered Words (UCAST-FW) indicated a significant maturational effect. Adult participants performed significantly better on the UCAST-FW in comparison to the child participants. The UCAST-FW test was reliable over repeated administrations. Conclusions: An adaptive low-pass filtered speech test such as the UCAST-FW is sensitive to maturational changes in auditory processing ability. © 2012 Elsevier Ireland Ltd.

Francart T.,Catholic University of Leuven | Francart T.,The Bionics Institute | McDermott H.,The Bionics Institute | McDermott H.,University of Melbourne
PLoS ONE | Year: 2012

A significant fraction of newly implanted cochlear implant recipients use a hearing aid in their non-implanted ear. SCORE bimodal is a sound processing strategy developed for this configuration, aimed at normalising loudness perception and improving binaural loudness balance. Speech perception performance in quiet and noise and sound localisation ability of six bimodal listeners were measured with and without application of SCORE. Speech perception in quiet was measured either with only acoustic, only electric, or bimodal stimulation, at soft and normal conversational levels. For speech in quiet there was a significant improvement with application of SCORE. Speech perception in noise was measured for either steady-state noise, fluctuating noise, or a competing talker, at conversational levels with bimodal stimulation. For speech in noise there was no significant effect of application of SCORE. Modelling of interaural loudness differences in a long-term-average-speech-spectrum-weighted click train indicated that left-right discrimination of sound sources can improve with application of SCORE. As SCORE was found to leave speech perception unaffected or to improve it, it seems suitable for implementation in clinical devices. © 2012 Francart, McDermott.

Innes-Brown H.,The Bionics Institute | Marozeau J.,The Bionics Institute | Blamey P.,The Bionics Institute | Blamey P.,University of Melbourne
PLoS ONE | Year: 2011

Background: Enjoyment of music is an important part of life that may be degraded for people with hearing impairments, especially those using cochlear implants. The ability to follow separate lines of melody is an important factor in music appreciation. This ability relies on effective auditory streaming, which is much reduced in people with hearing impairment, contributing to difficulties in music appreciation. The aim of this study was to assess whether visual cues could reduce the subjective difficulty of segregating a melody from interleaved background notes in normally hearing listeners, those using hearing aids, and those using cochlear implants. Methodology/Principal Findings: Normally hearing listeners (N = 20), hearing aid users (N = 10), and cochlear implant users (N = 11) were asked to rate the difficulty of segregating a repeating four-note melody from random interleaved distracter notes. The pitch of the background notes was gradually increased or decreased throughout blocks, providing a range of difficulty from easy (with a large pitch separation between melody and distracter) to impossible (with the melody and distracter completely overlapping). Visual cues were provided on half the blocks, and difficulty ratings for blocks with and without visual cues were compared between groups. Visual cues reduced the subjective difficulty of extracting the melody from the distracter notes for normally hearing listeners and cochlear implant users, but not hearing aid users. Conclusion/Significance: Simple visual cues may improve the ability of cochlear implant users to segregate lines of music, thus potentially increasing their enjoyment of music. More research is needed to determine what type of acoustic cues to encode visually in order to optimise the benefits they may provide. © 2011 Innes-Brown et al.

Ganesan K.,University of Melbourne | Garrett D.J.,University of Melbourne | Ahnood A.,University of Melbourne | Shivdasani M.N.,The Bionics Institute | And 5 more authors.
Biomaterials | Year: 2014

The interface between medical implants and the human nervous system is rapidly becoming more and more complex. This rise in complexity is driving the need for increasing numbers of densely packed electrical feedthroughto carry signals to and from implanted devices. This is particularly crucial in the field of neural prosthesis where high resolution stimulating or recording arrays near peripheral nerves or in the brain could dramatically improve the performance of these devices. Here we describe a flexible strategy for implementing high density, high count arrays of hermetic electrical feedthroughs by forming conducting nitrogen doped nanocrystalline diamond channels within an insulating polycrystalline diamond substrate. A unique feature of these arrays is that the feedthroughs can themselves be used as stimulating electrodes for neural tissue. Our particular application is such a feedthrough, designed as a component of a retinal implant to restore vision to the blind. The hermeticity of the feedthroughs means that the array can also form part of an implantable capsule which can interface directly with internal electronic chips. The hermeticity of the array is demonstrated by helium leak tests and electrical and electrochemical characterisation of the feedthroughs is described. The nitrogen doped nanocrystalline diamond forming the electrical feedthroughs is shown to be non-cyctotoxic. New fabrication strategies, such as the one described here, combined with the exceptional biostability of diamond can be exploited to generate a range of biomedical implants that last for the lifetime of the user without fear of degradation. © 2013 Elsevier Ltd.

PubMed | University of Melbourne and The Bionics Institute
Type: Journal Article | Journal: PloS one | Year: 2016

Cochlear implants electrically stimulate spiral ganglion neurons (SGNs) in order to provide speech cues to severe-profoundly deaf patients. In normal hearing cochleae the SGNs depend on endogenous neurotrophins secreted by sensory cells in the organ of Corti for survival. SGNs gradually degenerate following deafness and consequently there is considerable interest in developing clinically relevant strategies to provide exogenous neurotrophins to preserve SGN survival. The present study investigated the safety and efficacy of a drug delivery system for the cochlea using nanoengineered silica supraparticles. In the present study we delivered Brain-derived neurotrophic factor (BDNF) over a period of four weeks and evaluated SGN survival as a measure of efficacy. Supraparticles were bilaterally implanted into the basal turn of cochleae in profoundly deafened guinea pigs. One ear received BDNF-loaded supraparticles and the other ear control (unloaded) supraparticles. After one month of treatment the cochleae were examined histologically. There was significantly greater survival of SGNs in cochleae that received BDNF supraparticles compared to the contralateral control cochleae (repeated measures ANOVA, p = 0.009). SGN survival was observed over a wide extent of the cochlea. The supraparticles were well tolerated within the cochlea with a tissue response that was localised to the site of implantation in the cochlear base. Although mild, the tissue response was significantly greater in cochleae treated with BDNF supraparticles compared to the controls (repeated measures ANOVA, p = 0.003). These data support the clinical potential of this technology particularly as the supraparticles can be loaded with a variety of therapeutic drugs.

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