Chronic lower back pain is a major public health problem, with direct and indirect economic costs comparable to those of heart disease, depression and diabetes. In many cases this pain derives from degeneration of the intervertebral disc (IVD), a fibrous, avascular tissue that sits between the vertebrae in the spinal column. A novel treatment approach for this ‘discogenic’ pain is the injection of a hydrogel that hybridises in situ and restores the normal biomechanical function of the disc. While a number of promising materials are currently under development, existing approaches to removing degenerate material from the disc prior to injection are invasive and compromise the structural integrity of the disc. Mechanical fractionation of the tissue using acoustic cavitation generated by high intensity focussed ultrasound (HIFU) has the potential to be non-invasive, and to enhance the effectiveness of the procedure by preserving the outer regions of the disc. The primary goal of this thesis is to investigate the feasibility of this approach. The acoustic properties of the disc were first measured using a modified scanning acoustic microscope. The outer region of the disc, the annulus fibrosus (AF) was found to be highly attenuative compared to the central nucleus pulposus (NP). These measured properties were then used in a simplified two-dimensional model to simulate the shape of the acoustic pressure field within the disc. A configuration using two confocal spherically focussed 0.5 MHz single-element transducers was able to produce a tightly focused field suitable for use in the IVD. As preliminary experiments suggested that high pressure amplitudes were required to initiate cavitation inside the disc, the use of exogenous nuclei to lower this threshold was investigated. A novel class of solid sonosensitive nanoparticles (SNPs) suitable for use in the IVD were developed and characterised. These SNPs comprise a layer of hydrophobic silica particles deposited onto a polystyrene core, and are thought to trap small gas pockets in surface crevices. Coated particles were found to reduce the cavitation threshold significantly in both water and blood, from some 2.0 - 2.5 MPa at 1.067 MHz to below 1.0 MPa. The particles were also found to provide repeatable initiation of cavitation activity during prolonged or repeated exposures, and to exhibit good storage stability, suggesting that they they may be appropriate for use within the IVD. Finally, a combined therapy and monitoring system was designed, built and validated. The system comprised two confocal 0.5 MHz spherically focussed HIFU transducers with central openings, each co-axially aligned with either a single element passive cavitation detector or a 64-element array that could be used for both active and passive imaging. The system was found to be capable of initiating inertial cavitation in the disc at pressures as low as 2.5MPa in the presence of sonosensitive nanoparticles. Use of the array in active mode enables creation of a B-mode image that provides anatomical information on the boundaries of the IVD, whist the same array could be used for passive mapping of acoustic emissions arising fromthe HIFU focus during therapy. Two different exposure regimes were found to be capable of producing sizeable perforations within the NP without significantly damaging the AF, and preliminary investigations were carried out into themechanism of damage. The location and extent of cavitation as seen on passive maps acquired during treatment was found to coincide with the regions of NP fractionation. This confirms that passive acoustic mapping can provide the real-time treatment monitoring necessary to ensure both safety and efficacy of ultrasonic IVD fractionation. Prior to clinical application, a significant amount of further development is required to further validate non-invasive disc fractionation by HIFU and the subsequent steps for minimally invasive disc replacement using injectable hydrogels. The present work has nonetheless demonstrated for the first time that minimally invasive removal of degenerate disc tissue is feasible trough the combined use of sonosensitive nanoparticles and a relatively low-cost therapeutic ultrasound system that provides simultaneous anatomical imaging and real-time treatment monitoring by passive acoustic mapping.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:600738 |
| Date | January 2012 |
| Creators | Molinari, Michael B. |
| Contributors | Coussios, Constantin-C. ; Urban, Jill |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:7385c54f-a3d0-4467-aca4-c7a9b8686982 |
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