The clinical management of glioma remains a challenge. The prognosis is poor—for glioblastoma multiforme, the most virulent of these brain cancers, survival is only ~1 year. Surgical resection of the tumor is the first line of defense. Several studies demonstrate a survival advantage in patients who undergo near-complete tumor resection; however, achieving complete resection is limited by the difficulty of visualizing residual tumor after de-bulking. Intraoperative fluorescence guidance is a promising candidate to better visualize residual tumor. The most clinically developed form uses protoporphyrin IX fluorescence, the precursor to heme in its biosynthesis which preferentially accumulates in tumor cells after the administration of 5-aminolevulinic acid. Challenges remain in quantitatively assessing the fluorescence to reduce variability of outcome and improve tumor detection specificity, and in observing sub-surface tumor fluorescence. To these ends, this work outlines the development of intraoperative techniques to 1) quantify tissue fluorescence using a handheld fiberoptic probe and 2) improve detection by reconstructing the depth-resolved fluorescence topography of sub-surface tumor. As a critical component to achieve these objectives, a technique to measure the tissue optical properties was developed. This technique used diffuse reflectance measurements mediated by a handheld fiberoptic probe to derive the tissue optical properties. The handheld fiberoptic probe was further developed to include fluorescence spectroscopy. A novel algorithm to combine the fluorescence measurement and the tissue optical properties was derived in order to extract the quantitative fluorescence spectrum, i.e. fluorescence without confounding effects of tissue optical properties. The concentration of fluorescent tumor biomarker can then be extracted. The quantitative fluorescence work culminated in deployment of the fiberoptic probe in clinical trials for the resection of intracranial tumors. The quantitative fluorescence probe out-performed a state-of-the-art fluorescence surgical microscope for a broad range of brain tumor pathologies. A novel technique for depth-resolved fluorescence detection was developed utilizing multi-excitation fluorescence imaging. An algorithm to extract depth information from the multi-excitation images was derived, with validation in phantoms and a rat brain tumor model. This demonstrates the potential for depth-resolved fluorescence imaging, which there is a clear need for in tumor resection guidance.

There have been many advances in surgical residency education and similar interest exists in fellowship education. This study evaluated perceptions among spine surgeons about the specific competencies required for successful spine surgical fellowship training, and then compared these perceptions to clinical practice. Firstly, a questionnaire was administered to spine fellow trainees and academic spine surgeons across Canada in order to identify the cognitive and technical skills required for successful spine fellowship training. Fellowship trainees and supervisors had similar perceptions on the relative importance of specific cognitive and technical competencies. Differences in perceptions were found when comparing surgeons based on background residency specialty training (orthopaedic surgical or neurosurgical). Secondly, using administrative data, a retrospective study assessed volumes, surgeon characteristics, and outcomes for surgery of the degenerative lumbar spine in Ontario between 1995 and 2001. Neurosurgeons were found to perform more decompressions, and more total procedures, than orthopaedic surgeons with similar outcomes.

There have been many advances in surgical residency education and similar interest exists in fellowship education. This study evaluated perceptions among spine surgeons about the specific competencies required for successful spine surgical fellowship training, and then compared these perceptions to clinical practice. Firstly, a questionnaire was administered to spine fellow trainees and academic spine surgeons across Canada in order to identify the cognitive and technical skills required for successful spine fellowship training. Fellowship trainees and supervisors had similar perceptions on the relative importance of specific cognitive and technical competencies. Differences in perceptions were found when comparing surgeons based on background residency specialty training (orthopaedic surgical or neurosurgical). Secondly, using administrative data, a retrospective study assessed volumes, surgeon characteristics, and outcomes for surgery of the degenerative lumbar spine in Ontario between 1995 and 2001. Neurosurgeons were found to perform more decompressions, and more total procedures, than orthopaedic surgeons with similar outcomes.

ABSTRACT Granite Butterfly is a novel about three women—grandmother, mother, and daughter—and the unusual attachments that break apart their family. Tuula Laine is a Rockport, Massachusetts, native of Finnish descent, whose parents moved to Cape Ann for work in the area’s granite quarries. Her life changes one afternoon when her son Henri, a brilliant surgeon who has never seriously dated anyone before, visits with his pregnant girlfriend, Coreen. Tuula immediately senses that Coreen not the right match for him in terms of age, education, or temperament, and as the couple separates and unites over the course of one summer, Tuula witnesses, for the first time, the pattern of desire and abandonment that will define their relationship. By the time Tuula’s granddaughter, Suvi, is fourteen years old, she, too, has established a destructive relationship pattern with Coreen: whenever Coreen and Henri separate, Suvi’s mother clings to her until they develop a bond closer to that of sisters than a mother and child. In the final movement of the novel, this bond, and the bond between Suvi’s parents, is finally put to the test. Granite is cut into precise blocks—dynamite is never used, lest it shatter the stone. In a few short weeks, the Laine family is pulled apart, but unlike with quarrying, there is no way to divide them in a careful manner, no way to detach them that isn’t violent and abrupt, no way to predict, or guide, where they will split.

The clinical management of glioma remains a challenge. The prognosis is poor—for glioblastoma multiforme, the most virulent of these brain cancers, survival is only ~1 year. Surgical resection of the tumor is the first line of defense. Several studies demonstrate a survival advantage in patients who undergo near-complete tumor resection; however, achieving complete resection is limited by the difficulty of visualizing residual tumor after de-bulking. Intraoperative fluorescence guidance is a promising candidate to better visualize residual tumor. The most clinically developed form uses protoporphyrin IX fluorescence, the precursor to heme in its biosynthesis which preferentially accumulates in tumor cells after the administration of 5-aminolevulinic acid. Challenges remain in quantitatively assessing the fluorescence to reduce variability of outcome and improve tumor detection specificity, and in observing sub-surface tumor fluorescence. To these ends, this work outlines the development of intraoperative techniques to 1) quantify tissue fluorescence using a handheld fiberoptic probe and 2) improve detection by reconstructing the depth-resolved fluorescence topography of sub-surface tumor. As a critical component to achieve these objectives, a technique to measure the tissue optical properties was developed. This technique used diffuse reflectance measurements mediated by a handheld fiberoptic probe to derive the tissue optical properties. The handheld fiberoptic probe was further developed to include fluorescence spectroscopy. A novel algorithm to combine the fluorescence measurement and the tissue optical properties was derived in order to extract the quantitative fluorescence spectrum, i.e. fluorescence without confounding effects of tissue optical properties. The concentration of fluorescent tumor biomarker can then be extracted. The quantitative fluorescence work culminated in deployment of the fiberoptic probe in clinical trials for the resection of intracranial tumors. The quantitative fluorescence probe out-performed a state-of-the-art fluorescence surgical microscope for a broad range of brain tumor pathologies. A novel technique for depth-resolved fluorescence detection was developed utilizing multi-excitation fluorescence imaging. An algorithm to extract depth information from the multi-excitation images was derived, with validation in phantoms and a rat brain tumor model. This demonstrates the potential for depth-resolved fluorescence imaging, which there is a clear need for in tumor resection guidance.

No description available.

Bakgrund: Många av patienterna på en neurointensivvårdsavdelning (NIVA) vårdas med respirator under en längre eller kortare period av vårdtiden. Neurointensivvårdspatienterna bedöms ibland utifrån de kriterier för urträning och extubering som används på allmänna intensivvårdspatienter. Detta kan leda till för tidig extubation med reintubation som följd. Syfte: Redogöra för vilka kriterier som ska bedömas hos neurointensivvårdspatienter inför en extubering. Metod: Litteraturstudie. Resultat och slutsats: Neurointensivvårdspatienter behöver uppfylla en kombination av kriterier inför extubation. Hänsyn ska tas till de generella extubationskriterierna avseende andning och cirkulation. Dessutom ska patienten ha en tillräckligt hög medvetandegrad för att kunna följa någon form av uppmaning. Till sist ska patientens förmåga att hålla fri luftväg bedömas genom observation av hostkraft, sekretmängd/konsistens och svalgfunktion. Det behövs ytterligare forskning för att utröna i hur hög grad neurointensivvårdspatienterna behöver vara medvetna inför extubering och på vilket sätt detta bäst bedöms. Forskning behövs kring ett enhetligt tillvägagångssätt för bedömning av hostkraft, sekretmängd/konsistens och svalgfunktion. / Background: Many of the patients cared for in a neurocritical unit are treated with mechanical ventilation for a longer or shorter period of time during their stay in the unit. When weaning or extubating neurocritical patients, they are sometimes assessed according to the criteria for weaning and extubation used in general intensive care patients. This can cause premature extubation, resulting in re-intubation. Aim: Describe the criteria to be assessed in neurocritical patients prior to extubation. Method: Literature review. Results and conclusion: Neurocritical patients need to fulfil a combination of criteria prior to extubation. The general criteria in terms of respiration and circulation must be taken in to consideration, as well as the patient’s level of consciousness. The patient has to be conscious enough to be able to take directions. Lastly the patient’s ability to protect the airway must be assessed by observation of cough strength, the quantities and viscosity of the secretions and the patient’s swallowing function. Further research is required to ascertain the level of consciousness required in the neurocritical patients prior to extubation and in which way the assessment is best carried out. There is also need for further research considering a standardized measurement for assessing cough strength, the quantities and viscosity of secretions and swallowing function in these patients.

Traumatic Brain Injury (TBI) mainly affects young persons in traffic accidents and the elderly in fall accidents. Improvements in the clinical management have significantly improved the outcome following TBI but survivors still suffer from depression, memory problems, personality changes, epilepsy and fatigue. The initial injury starts a series of events that give rise to a secondary injury process and despite several clinical trials there is no drug available for clinical use that targets secondary brain injury mechanisms. Some recovery of function is seen during the first months following injury but is usually limited and there are no drugs that stimulate the recovery of lost function. Some of the recovery is attributed to plasticity, the brains ability to adapt to new circumstances, and enhancing plasticity via increased axonal growth has the potential to partly restore lost function. In this thesis mice were subjected to the controlled cortical impact model of TBI and functional outcome was evaluated using Morris water maze, the cylinder test and the rotarod. Brain tissue loss was measured in all Papers but the additional histological analyses differ among the Papers. Attempts to increase axonal growth were made by interfering with Nogo receptor function in Paper I and by conditional knockout of ephA4 in Paper II. Contrary to the hypothesis cognition was impaired in Paper I but otherwise no effects of treatment were detected in Paper I and II. Much is still unknown about plasticity and despite the discouraging results of Papers I and II this treatment approach is still worth further exploration. It is firmly established that TBI results in an inflammatory response and some aspects of it may damage brain tissue. In Papers III and IV the inflammatory response was attenuated using an IL-1β directed antibody which resulted in reduced tissue loss and edema while improving cognitive function. The results from Papers III and IV are encouraging and the possibility to find a treatment based on IL-1β inhibition appears promising.

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