Development of a Tissue-Mimicking Brain Phantom for Neurosurgical Pre-Operative Planning and Training

Direct physical intervention in the treatment of patients in the area of neurosurgery represents a high risk which can be minimized with the employment of 3D physical models. These models provide a thorough physical display in 3D with detailed information related to the morphology of internal structures and their spatial location with surrounding structures. The aim of this study was to develop a brain substitute material based on gelatin that simulates the mechanical properties of brain tissue. Tissue mimicking materials were developed by matching the mechanical properties of porcine brain tissue under compressive loading at strain rates typical of surgical procedures. A brain phantom was fabricated using the tissue mimicking material, the brain (cortex and internal structures) and skull were created in a 3-step process where molds were fabricated with a 3D modeling software, printed in Polylactic Acid (PLA) and finally cast with brain tissue-mimicking material. To further test the quality of the developed material, a haptic test was conducted at Clemson University. A total of 22 bioengineering students assessed the haptic sense of two different tissue-mimicking material brain phantoms comparing them with real brain tissue. It was possible to fabricate two brain substitute materials that resembled the mechanical properties of brain tissue which were used to recreate patient-specific brain replicas in the form of tissue mimicking phantoms. These brain phantoms provide a realistic haptic sense similar to brain tissue which realism has potential as an educational tool and preoperative planning device for neurosurgery procedures

Ceramic coatings for Cervical Total Disc Replacement

Surgical interventions for the treatment of chronic neck pain, which affects 330 million people globally, include fusion and cervical total disc replacement (CTDR). Most of the currently clinically available CTDRs designs include a metal-on-polymer (MoP) bearing. Numerous studies suggest that MoP CTDRs are associated with issues similar to those affecting other MoP joint replacement devices, including excessive wear and wear particle-related inflammation and osteolysis. The aim of this study was to investigate the biotribology of a novel metal-on-metal (MoM) design of cervical total disc replacement device in its pristine form and coated with chromium nitride or silicon nitride, in order to understand the influence of loading conditions upon the tribological performance of the implant, and to investigate biological effects of the wear debris produced by the implants. To achieve this, a series of studies were carried out. Chromium nitride and silicon nitride coatings have been characterised for their mechanical properties, chemical composition and surface finish. Whilst some of the experiments showed minor differences between the mechanical properties and adhesion of the coatings, there was no indication of significant differences between the chromium nitride and silicon nitride coated samples. Functional testing in the six-station spine wear simulator showed that MoM CTDRs produced wear volumes significantly lower than those of the commercially available MoP devices. The wear volumes were reduced further by three-fold, following testing under altered ISO-18192-1:2011 kinematics, whereby, reduced ranges of motions were applied. Whilst the silicon nitride coated CTDRs failed catastrophically early in the test, chromium nitride coated CTDRs produced an eight-fold reduction in wear volumes, when compared to the pristine devices tested under the same conditions. Investigation of potential biological effects of the particles generated in wear testing showed that that high concentrations (5-50µm3 per cell) of CoCrMo particles resulted in significant reduction of cell viability of the L929 fibroblast cells, but not the dural fibroblasts, which were used in this study. No ceramic coating particles, at any concentrations, caused significant reduction of cell viability. In summary, results presented in this thesis showed that whilst the MoM CTDR device exhibited significantly lower wear rates than those of the commercially available MoP devices, the cytotoxic wear particles could potentially lead to adverse biological reactions, particularly in patients with metal hypersensitivity, and lead to devastating consequences similar to those of failed MoM THRs. Currently, the consequences of similar failure, leading to metalosis or pseudotumour formation in the vicinity of the spinal cord are unknown. During the investigation of the ceramic coatings, it was also found that chromium nitride ceramic coating could not only lower wear rates further, but it also has the potential to reduce the cytotoxic potential of the wear particles

Design, Development, Testing at ISO standards and in-vivo feasibility study of a novel Polymeric Heart Valve Prosthesis

Clinically available prosthetic heart valves are life-saving, but imperfect: mechanical valves requiring anticoagulation therapy, whilst bioprosthetic valves have limited durability. Polymer valves offer the prospect of good durability without the need for anticoagulation. We report the design and development of a polymeric heart valve, its bench-testing at ISO standards, and preliminary extravivo and in-vivo short-term feasibility. Prototypes were manufactured by injection moulding of styrenic block copolymers to achieve anisotropic mechanical properties. Design was by finite element stress-strain modelling, which has been reported previously, combined with feedback from bench and surgery-based testing using various combinations of materials, valve geometry and processing conditions. Bench testing was according to ISO 5840:2015 standards using an in-vitro cardiovascular hydrodynamic testing system and an accelerated fatigue tester. Bench comparisons were made with a best-in-class bio-prosthesis. Preliminary clinical feasibility evaluations included extra-vivo and short-term (1-24 hours) in-vivo testing in a sheep model. The optimised final prototype met the requirements of ISO standards with hydrodynamic performance equivalent to the best-in-class bioprosthesis. Bench durability of greater than 1.2 billion cycles (30 years equivalent) was achieved (still ongoing). Extra-vivo sequential testing (n=8) allowed refinement of external diameter, 3D shape, a low profile, flexibility, suturability, and testing of compatibility to magnetic resonance imaging and clinical sterilisation. In vivo short-term (1-24 hours) feasibility (n=3) confirmed good suturability, no mechanical failure, no trans-valvular regurgitation, competitive trans-valvular gradients, and good biocompatibility at histopathology. We have developed and tested at ISO standards a novel prosthetic heart valve featuring competitive bench-based hydrodynamics and durability, well beyond the ISO requirements and comparable to a best-in-class bioprosthesis. In-vivo short-term feasibility testing confirmed preliminary safety, functionality and biocompatibility, supporting progression to a long-term efficacy trial.King's College, Cambridg

Microscale Infrared Technologies for Spectral Filtering and Wireless Neural Dust

Pivotal technologies, such as optical computing, autonomous vehicles, and biomedical implantables, motivate microscale infrared (IR) components. Hyperspectral imagers (HSI), for example, require compact and narrowband filters to obtain high-spatial and -spectral resolution images. HSIs acquire continuous spectra at each pixel, enabling non-destructive analyses by resolving IR scattering/absorption signatures. Toward this end, dielectric subwavelength gratings (SWG) are intriguing filter candidates since they are low-loss, have no moving parts, and exhibit narrow spectral features. Wireless neural implantables are another apropos microscale IR technology. Wireless IR data and power transfer disposes of infection-prone percutaneous wires by leveraging the IR transparency window in biological tissue. This dissertation contains two related topics. The first details SWG IR filters, and the second studies progress toward wireless neural motes. This work extends the capabilities of SWG IR filters. Following a theoretical overview, mid-wave infrared (MWIR, 3-7 um) transmittance filters are experimentally demonstrated using the zero-contrast grating scheme. Via a facile silicon fabrication process, we realize narrowband polarization-dependent and polarization-independent MWIR transmittance filters with some of the highest Q observed in MWIR SWGs. An empirical study confirms the relationship between filter performance and grating size, an important trade-off for HSIs. We then demonstrate GaAs SWG filters for monolithic integration with active optoelectronic devices. The GaAs SWGs perform comparably to their silicon counterparts. To enable narrowband filtering at normal incidence, we investigate symmetry-breaking in geometrically asymmetric gratings. The presented SWG geometries access quasi-bound states in the continuum (BIC). Studies in Fano resonance and diffraction efficiency symmetry provide physical insight. Asymmetric 1D and 2D SWGs furnish polarization-dependent and -independent filtering, respectively. We experimentally demonstrate normal incidence long-wave IR (LWIR, 7-12 um) transmittance filtering in asymmetric SWGs and confirm symmetry-breaking implications. A reduced-symmetry hexagonal pattern presents an early design for truly polarization-independent quasi-BIC coupling in SWGs. Advancements in implantable neural devices promise great leaps in brain mapping and therapeutic intervention. To meet this challenge, we investigated a wireless neural mote system using near-infrared (NIR, 800 nm – 3 um) photovoltaics and LEDs to wirelessly harvest power and transmit data. The neural recorders consist of three subsystems: an epitaxial GaAs-based optoelectronic chip, a Si CMOS IC, and a carbon fiber probe. Though this work encompasses the efforts of many, this dissertation outlines contributions in a few critical areas. To overcome low-flux LED emission, we devise an optical setup with ≈0.1% photon detection efficiency. Monte Carlo techniques model NIR scattering in biological tissue. Another steep challenge is the heterogeneous integration of the three material systems in a compact (200x170x150 um^3) package. To relay data and power between the GaAs and CMOS chips, through-wafer vias are critical. Using a novel selective copper plating technique, we demonstrate through-wafer GaAs vias with <2 Ohm series resistance. Additionally, conductive blind vias are presented for carbon fiber probe insertion. A self-aligned parylene etch mask permits sub-kOhm connection to a buried metal contact while maintaining GOhm substrate isolation. Both via structures meet the requirements of being low-resistance, insulated from the substrate, and amendable to thinned wafer processing. Finally, we demonstrate extensive processing on thinned chips and advances toward full heterogeneous integration via flip-chip alignment and solder bump bonding.PHDElectrical and Computer EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169986/1/barrowm_1.pd

Haemostasis in endoscopic skull base surgery

The endoscopic approach to the skull base has revolutionised surgery in this region. Neurosurgery involves working around anatomical structures that are uniquely sensitive to damage and manipulation and patients may be left with the potentially devastating consequences of violating these structures. The endoscope allows the surgeon to visualise and reach areas that were previously only accessible with large amounts of destructive dissection. Tumours are able to be removed and aneurysms clipped without the need for large craniotomies and bony drilling. There are, however, drawbacks. The midline endoscopic route takes the surgeon between the carotid arteries. It potentially violates the anterior communicating artery complex and the basilar artery region anterior to the brainstem. These are important arteries that supply critical structures. Damage to these, or diminution of blood flow through them, results in profound neurological dysfunction or death. The rate of damage to the carotid artery with these approaches ranges from 1.1-9% depending on the specific approach and pathology. The carotid artery in this region does not generally lend itself to suturing, clipping or direct closure methods. Currently, the gold standard for repair is the application of crushed muscle patch to stop the bleeding and seal the vessel. The drawbacks to this are that it takes time to harvest and control the bleed (generally requiring 2 surgeons), and that there is a risk of pseudoaneurysm formation post recovery. This thesis describes novel techniques that may replace the muscle patch in order that a single surgeon may have this technique available to them immediately. Aims: To demonstrate the use of fibrin/thrombin/gelatin patches, fibrin/thrombin glues, beta-chitosan patches and self-assembling peptides on a sheep model of carotid artery haemorrhage and quantify the rate of pseudoaneurysm formation. To show the percentage of platelets activated by crushed and uncrushed muscle, chitosan, and fibrin and thrombin patches and gels using flow cytometry to further delineate the mechanism of action of crushed muscle as a haemostatic agent. To quantify the stress response in surgeons training on this sheep vascular haemorrhage model de novo, to quantify its effect on surgeons’ teamwork and communication skills, and determine the effect and value of training on modulation of this stress response.Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, Adelaide Medical School, 201

11th Annual Focus on Creative Inquiry Poster Forum Program

The 2016 Focus on Creative Inquiry Poster Forum displays a selection of the projects accomplished by Clemson University students in their Creative Inquiry teams. What is Creative Inquiry? It is small-group learning for all students, in all disciplines. It is the imaginative combination of engaged learning and undergraduate research – and it is unique to Clemson University. In Creative Inquiry, small teams of undergraduate students work with faculty mentors to take on problems that spring from their own curiosity, a professor’s challenge, or the pressing needs of the world around them. Students take ownership of their projects. They ask questions, they take risks, and they get answers

Research and technology highlights, 1993

This report contains highlights of the major accomplishments and applications that have been made by Langley researchers and by our university and industry colleagues during the past year. The highlights illustrate both the broad range of the research and technology activities supported by NASA Langley Research Center and the contributions of this work toward maintaining United States leadership in aeronautics and space research. This report also describes some of the Center's most important research and testing facilities