Biomedical subjects

Kenneth J Dormer

Publications and source records attributed to Kenneth J Dormer.

6 recordsLinked to original sources

PubMed2006

The permeability of SPION over an artificial three-layer membrane is enhanced by external magnetic field.

BACKGROUND: Sensorineural hearing loss, a subset of all clinical hearing loss, may be correctable through the use of gene therapy. We are testing a delivery system of therapeutics through a 3 cell-layer round window membrane model (RWM model) that may provide an entry of drugs or genes to the inner ear. We designed an in vitro RWM model similar to the RWM (will be referred to throughout the paper as RWM model) to determine the feasibility of using superparamagnetic iron oxide (Fe3O4) nanoparticles (SPION) for targeted delivery of therapeutics to the inner ear. The RWM model is a 3 cell-layer model with epithelial cells cultured on both sides of a small intestinal submucosal (SIS) matrix and fibroblasts seeded in between. Dextran encapsulated nanoparticle clusters 130 nm in diameter were pulled through the RWM model using permanent magnets with flux density 0.410 Tesla at the pole face. The SIS membranes were harvested at day 7 and then fixed in 4% paraformaldehyde. Transmission electron microscopy and fluorescence spectrophotometry were used to verify transepithelial transport of the SPION across the cell-culture model. Histological sections were examined for evidence of SPION toxicity, as well to generate a timeline of the position of the SPION at different times. SPION also were added to cells in culture to assess in vitro toxicity. RESULTS: Transepithelial electrical resistance measurements confirmed epithelial confluence, as SPION crossed a membrane consisting of three co-cultured layers of cells, under the influence of a magnetic field. Micrographs showed SPION distributed throughout the membrane model, in between cell layers, and sometimes on the surface of cells. TEM verified that the SPION were pulled through the membrane into the culture well below. Fluorescence spectrophotometry quantified the number of SPION that went through the SIS membrane. SPION showed no toxicity to cells in culture. CONCLUSION: A three-cell layer model of the human round window membrane has been constructed. SPION have been magnetically transported through this model, allowing quantitative evaluation of prospective targeted drug or gene delivery through the RWM. Putative in vivo carrier superparamagnetic nanoparticles may be evaluated using this model.

Journal Article↗

PubMed2006

Magnetic nanoparticles: inner ear targeted molecule delivery and middle ear implant.

Superparamagnetic iron oxide nanoparticles (SNP) composed of magnetite (Fe(3)O(4)) were studied preliminarily as vehicles for therapeutic molecule delivery to the inner ear and as a middle ear implant capable of producing biomechanically relevant forces for auditory function. Magnetite SNP were synthesized, then encapsulated in either silica or poly (D,L,-Lactide-co-glycolide) or obtained commercially with coatings of oleic acid or dextran. Permanent magnetic fields generated forces sufficient to pull them across tissue in several round window membrane models (in vitrocell culture, in vivo rat and guinea pig, and human temporal bone) or to embed them in middle ear epithelia. Biocompatibility was investigated by light and electron microscopy, cell culture kinetics, and hair cell survival in organotypic cell culture and no measurable toxicity was found. A sinusoidal magnetic field applied to guinea pigs with SNP implanted in the middle ear resulted in displacements of the middle ear comparable to 90 dB SPL.

Animals↗

PubMed2006

Magnetic resonance imaging compatibility and safety of the SOUNDTEC Direct System.

OBJECTIVE/HYPOTHESIS: The purpose of this study was to evaluate magnetic resonance imaging (MRI) compatibility and safety of an electromagnetic implanted hearing device (the SOUNDTEC Direct System; SOUNDTEC, Inc., Oklahoma City, OK) implant during a 0.3-Tesla open MRI imaging examination of the head and neck and to develop an MRI protocol that maximizes patient safety while minimizing the need for implant removal. The current literature regarding MRI compatibility of implantable hearing devices was reviewed. STUDY DESIGN: Linear and torsional forces, heating, and implant magnetization were evaluated in vitro. Implanted fresh-frozen human temporal bones were used to evaluate image distortion. A prospective study of 11 volunteers previously implanted with the SOUNDTEC Direct System was conducted to evaluate MRI compatibility and safety. A MEDLINE search of the literature between 1980 and July 2005 was reviewed to summarize MRI compatibility testing of implantable hearing devices. METHODS: Torsional and linear forces experienced by eight implant magnets were measured using calibrated neurologic Von Frey Hairs and compared with finite element analysis predictions as well as forces required to separate the incudostapedial joints of 12 fresh-frozen human temporal bones. Implant heating was determined by measuring the temperature change of eight implant vials compared with saline controls immediately after a head MRI scan. Implant magnetization was evaluated after repeated exposure to a 0.3-Tesla magnetic field. An 11-patient prospective study was performed to evaluate MRI compatibility in a 0.3-Tesla open MRI environment using adult volunteers previously implanted with the SOUNDTEC Direct System. A modified MRI protocol was developed to maximize patient safety. Each individual underwent an audiometric and otologic examination immediately before and after MRI. RESULTS: Peak linear force at the MRI entry measured 0.5 g +/- 0.2 standard deviation (SD). Maximum torque occurred at isocenter and measured 11.4 g-cm +/- 1.2 SD. The mean torque required to separate the incudostapedial joint was 33.8 g-cm +/- 20.4 SD. The average increase in temperature of the eight implant vials was 0.45 degrees C +/- 0.11 SD, whereas the increase in temperature of the three saline controls measured 0.47 degrees C +/- 0.11 SD. The average change in magnetic flux density of the 14 implant magnets tested was 22.0 gauss. Maximum image distortion occurred during the gradient echo sequence and measured 8.6 cm in diameter with a volume of 5,096 mm. Eleven patients completed a total of 12 head, one shoulder, and three lumbar 0.3-Tesla open MRI scans without patient- or device-related complications other than degradation of the MR image. There was no report of discomfort, tinnitus, dizziness, change in hearing, or change in device performance. All post-MRI changes in pure-tone thresholds, speech discrimination, soundfield thresholds, and aided soundfield thresholds were within the range of test-retest variability. CONCLUSION: When considering MRI of implantable ferromagnetic hearing devices, issues related to mechanical forces, implant heating, current induction, implant demagnetization, image degradation, and acoustic trauma must be considered. The SOUNDTEC Direct System is both MRI-compatible and safe in a 0.3-Tesla open MRI environment when a modified protocol is used. Degradation of the head MRI image may impair visualization of the ipsilateral temporal bone and adjacent structures within a 2.5- to 4.3-cm radius of the implant and is minimized by using a fast spin echo sequence.

Adult↗

PubMed2004

Human middle ear transfer function measured by double laser interferometry system.

HYPOTHESIS: Simultaneous measurements of vibrations on the stapes footplate, incudostapedial (IS) joint, and tympanic membrane (TM) can be made in both normal and drained cochleae, and the stapes displacement transfer function (S-DTF) and TM displacement transfer function (TM-DTF) are derived. BACKGROUND: A single laser Doppler interferometer previously has been used for measuring movement of the stapes or TM in temporal bones. However, there may be a limitation to optimally describing acoustic-mechanical transmission when the interferometer and temporal bone are moved frequently during experimental recordings. Simultaneous measurements of vibrations of the TM and stapes footplate, or TM and IS joint may reveal different acoustic-mechanical characteristics of the middle ear. METHODS: Dual laser interferometers simultaneously measured vibrations of the TM, IS joint, and stapes in 10 temporal bones with both intact and drained cochleae. From these measurements, the middle ear transfer function was expressed as the S-DTF, TM-DTF, and displacement transmission ratio (DTR). RESULTS: Simultaneous displacements of the TM, IS joint, and stapes footplate induced by sound pressure in the ear canal were recorded in both amplitude and phase. The middle ear transfer functions in terms of displacement ratio confirmed published single interferometer data but provided new information from drained cochlea. CONCLUSION: Stapes and TM displacement transfer functions were determined using dual interferometry, provided accurate amplitude and phase relationships from stapes footplate, IS joint, and TM, with new data from drained and normal cochlea.

Acoustic Stimulation↗

PubMed2002

An advanced computer-aided geometric modeling and fabrication method for human middle ear.

This paper presents a practical and systematic method for reconstructing accurate computer and physical models of the entire human middle ear. The proposed method starts with the histological section preparation of human temporal bone. Through tracing outlines of the middle ear components on the sections, a set of discrete points is obtained and employed to construct B-spline curves that represent the exterior contours of the components using a curve-fitting technique. The surface-skinning technique is then employed to quilt the B-spline curves for smooth boundary surfaces of the middle ear components using B-spline surfaces. The solid models of the middle ear components are constructed using these surfaces and then assembled to create the entire middle ear in a computer-aided design environment. This method not only provides an effective way to visualize and measure the three-dimensional structure of the middle ear, but also provides a detailed knowledge of middle ear geometry that is required for finite element analysis or multibody dynamic analysis of the human middle ear. In addition, the geometric model constructed using the proposed method is smooth and can be fabricated in various scales using solid freeform fabrication technology. The physical model of the human middle ear is extremely effective in realizing the middle ear anatomy and enhancing discussion and collaboration among researchers and physicians.

Anatomy, Cross-Sectional↗

PubMed2002

Three-dimensional modeling of middle ear biomechanics and its applications.

HYPOTHESIS: This study investigated whether combined technologies of finite element (FE) analysis and three-dimensional reconstruction of human temporal bones could be used to construct a computational model, useful in describing normal and pathologic middle ear sound conduction. BACKGROUND: FE models for biologic systems have been used in ear biomechanics. Three-dimensional reconstructions have also been made, but not in combination with FE modeling and laser interferometry measuring of human temporal bones. Furthermore, an FE model for the human middle ear with its ossicular attachments has not been reported on the basis of temporal bone histologic sections and morphometric reconstruction, to the authors' best knowledge. Because of the size, variability, and complexity of the middle ear, accurate morphologic data and boundary conditions are necessary for accurate FE modeling. METHODS: A fresh temporal bone was decalcified, embedded in celloidin, sectioned and stained, scanned, and digitized, and the normal middle ear was reconstructed. The histologic sections were used to construct a computer-aided design model with ligaments, muscles, and tendons as boundary conditions. The data thus obtained were converted into an FE mechanical model that was validated by comparison with displacements obtained by laser Doppler interferometry on 17 fresh human temporal bones. RESULTS: An FE model was generated, demonstrating dynamic behavior that moderately approximated the laser interferometric data from human temporal bones receiving 90-dB sound pressure level auditory frequencies at the tympanic membrane. CONCLUSION: Accurate FE modeling, incorporating both morphometric and interferometric performance data, predicted both normal and pathologic mechanical performance of the human ossicular chain.

Biomechanical Phenomena↗