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Transorbital surgery has gained recent notoriety due to its incorporation into endoscopic skull base surgery. The body of published literature on the field is cadaveric and observation. The pre-clinical studies are focused on the use of the endoscope only. Furthermore the methodology utilised in the published literature is inconsistent and

Transorbital surgery has gained recent notoriety due to its incorporation into endoscopic skull base surgery. The body of published literature on the field is cadaveric and observation. The pre-clinical studies are focused on the use of the endoscope only. Furthermore the methodology utilised in the published literature is inconsistent and does not embody the optimal principles of scientific experimentation. This body of work evaluates a minimally invasive novel surgical corridor - the transorbital approach - its validity in neurosurgical practice, as well as both qualitatively and quantitatively assessing available technological advances in a robust experimental fashion. While the endoscope is an established means of visualisation used in clinical transorbital surgery, the microscope has never been assessed with respect to the transorbital approach. This question is investigated here and the anatomical and surgical benefits and limitations of microscopic visualisation demonstrated. The comparative studies provide increased knowledge on specifics pertinent to neurosurgeons and other skull base specialists when planning pre-operatively, such as pathology location, involved anatomical structures, instrument maneuvrability and the advantages and disadvantages of the distinct visualisation technologies. This is all with the intention of selecting the most suitable surgical approach and technology, specific to the patient, pathology and anatomy, so as to perform the best surgical procedure. The research findings illustrated in this body of work are diverse, reproducible and applicable. The transorbital surgical corridor has substantive potential for access to the anterior cranial fossa and specific surgical target structures. The neuroquantitative metrics investigated confirm the utility and benefits specific to the respective visualisation technologies i.e. the endoscope and microscope. The most appropriate setting wherein the approach should be used is also discussed. The transorbital corridor has impressive potential, can utilise all available technological advances, promotes multi-disciplinary co-operation and learning amongst clinicians and ultimately, is a means of improving operative patient care.
ContributorsHoulihan, Lena Mary (Author) / Preul, Mark C. (Thesis advisor) / Vernon, Brent (Thesis advisor) / O' Sullivan, Michael G.J. (Committee member) / Lawton, Michael T. (Committee member) / Santarelli, Griffin (Committee member) / Smith, Brian (Committee member) / Arizona State University (Publisher)
Created2021
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Description
A description of numerical and analytical work pertaining to models that describe the growth and progression of glioblastoma multiforme (GBM), an aggressive form of primary brain cancer. Two reaction-diffusion models are used: the Fisher-Kolmogorov-Petrovsky-Piskunov equation and a 2-population model that divides the tumor into actively proliferating and quiescent (or necrotic)

A description of numerical and analytical work pertaining to models that describe the growth and progression of glioblastoma multiforme (GBM), an aggressive form of primary brain cancer. Two reaction-diffusion models are used: the Fisher-Kolmogorov-Petrovsky-Piskunov equation and a 2-population model that divides the tumor into actively proliferating and quiescent (or necrotic) cells. The numerical portion of this work (chapter 2) focuses on simulating GBM expansion in patients undergoing treatment for recurrence of tumor following initial surgery. The models are simulated on 3-dimensional brain geometries derived from magnetic resonance imaging (MRI) scans provided by the Barrow Neurological Institute. The study consists of 17 clinical time intervals across 10 patients that have been followed in detail, each of whom shows significant progression of tumor over a period of 1 to 3 months on sequential follow up scans. A Taguchi sampling design is implemented to estimate the variability of the predicted tumors to using 144 different choices of model parameters. In 9 cases, model parameters can be identified such that the simulated tumor contains at least 40 percent of the volume of the observed tumor. In the analytical portion of the paper (chapters 3 and 4), a positively invariant region for our 2-population model is identified. Then, a rigorous derivation of the critical patch size associated with the model is performed. The critical patch (KISS) size is the minimum habitat size needed for a population to survive in a region. Habitats larger than the critical patch size allow a population to persist, while smaller habitats lead to extinction. The critical patch size of the 2-population model is consistent with that of the Fisher-Kolmogorov-Petrovsky-Piskunov equation, one of the first reaction-diffusion models proposed for GBM. The critical patch size may indicate that GBM tumors have a minimum size depending on the location in the brain. A theoretical relationship between the size of a GBM tumor at steady-state and its maximum cell density is also derived, which has potential applications for patient-specific parameter estimation based on magnetic resonance imaging data.
ContributorsHarris, Duane C. (Author) / Kuang, Yang (Thesis advisor) / Kostelich, Eric J. (Thesis advisor) / Preul, Mark C. (Committee member) / Crook, Sharon (Committee member) / Gardner, Carl (Committee member) / Arizona State University (Publisher)
Created2023
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Description
The emergence of invasive non-Typhoidal Salmonella (iNTS) infections belonging to sequence type (ST) 313 are associated with severe bacteremia and high mortality in sub-Saharan Africa. Distinct features of ST313 strains include resistance to multiple antibiotics, extensive genomic degradation, and atypical clinical diagnosis including bloodstream infections, respiratory symptoms, and fever. Herein,

The emergence of invasive non-Typhoidal Salmonella (iNTS) infections belonging to sequence type (ST) 313 are associated with severe bacteremia and high mortality in sub-Saharan Africa. Distinct features of ST313 strains include resistance to multiple antibiotics, extensive genomic degradation, and atypical clinical diagnosis including bloodstream infections, respiratory symptoms, and fever. Herein, I report the use of dynamic bioreactor technology to profile the impact of physiological fluid shear levels on the pathogenesis-related responses of ST313 pathovar, 5579. I show that culture of 5579 under these conditions induces profoundly different pathogenesis-related phenotypes than those normally observed when cultures are grown conventionally. Surprisingly, in response to physiological fluid shear, 5579 exhibited positive swimming motility, which was unexpected, since this strain was initially thought to be non-motile. Moreover, fluid shear altered the resistance of 5579 to acid, oxidative and bile stress, as well as its ability to colonize human colonic epithelial cells. This work leverages from and advances studies over the past 16 years in the Nickerson lab, which are at the forefront of bacterial mechanosensation and further demonstrates that bacterial pathogens are “hardwired” to respond to the force of fluid shear in ways that are not observed during conventional culture, and stresses the importance of mimicking the dynamic physical force microenvironment when studying host-pathogen interactions. The results from this study lay the foundation for future work to determine the underlying mechanisms operative in 5579 that are responsible for these phenotypic observations.
ContributorsCastro, Christian (Author) / Nickerson, Cheryl A. (Thesis advisor) / Ott, C. Mark (Committee member) / Roland, Kenneth (Committee member) / Barrila, Jennifer (Committee member) / Arizona State University (Publisher)
Created2016