Type 1 Diabetes is a dangerous and life-long disease for which its prevalence is global. Research has shown that tight glycaemic control of this disease significantly reduces the risks of developing several life threatening diabetic complications. The Ets-Insulin-Bolus Calculator (EIBC), inspired by the Ets concept (Equivalent Teaspoon Sugar), was primarily designed to assist type I diabetics in improving their blood glucose control. The EIBC has shown to improve the average blood glucose level of type 1 diabetics. The need for this study however is to determine whether the ET!3C promotes tighter glycaemic control for type 1 diabetics based on a more-in-depth numerical analysis. With the use of the latest technology in blood glucose monitoring, the CGMS from Medtronic, mathematical models expressing and rating blood glucose control have been proposed and derived in this study. A clinical trial with type 1 diabetics has also been conducted. The use of the models together with the clinical trial results have shown that the EIBC does in fact promote tighter glycaemic control for type 1 diabetics. / Thesis (M.Ing. (Mechanical Engineering))--North-West University, Potchefstroom Campus, 2007.

In critically ill patients, the pathophysiology of sepsis can affect the interactions between the antibiotic, the bacteria and the patient, leading to potential therapeutic failure and the development of antibiotic resistance. It is well acknowledged that research that optimises antibiotic exposure will assist improvement of outcomes in this patient group. Although beta-lactam antibiotics, such as piperacillin and meropenem, are commonly selected for empiric therapy of sepsis, dosing is unlikely to be optimal. In patients without renal dysfunction, data suggests that disease-induced alterations to pharmacokinetic parameters result in low trough concentrations for significant periods within a dosing interval. Administration of these time-dependent antibiotics by continuous infusion has been suggested to improve the pharmacokinetic-pharmacodynamic profile. Knowledge of concentrations in the extracellular fluid of human tissue, which is the target site of most pathogens, is particularly instructive. Extracellular fluid concentrations can be determined using techniques such as microdialysis. Therefore, the principal aims of this Thesis were to determine the plasma and subcutaneous tissue pharmacokinetics of piperacillin and meropenem administered by bolus dosing and continuous infusion in critically ill patients with sepsis; and to use Monte Carlo simulations to compare the ability of different dosing strategies to achieve pharmacodynamic endpoints. This Thesis also sought to compare the clinical outcomes of bolus dosing and continuous infusion of a beta-lactam antibiotic, ceftriaxone, in a prospective randomised controlled trial and to perform a meta-analysis on clinical outcomes from other similar published studies. Finally, this Thesis aimed to systematically review the published literature to determine any correlation between antibiotic dosing and the development of antibiotic resistance. The results of the pharmacokinetic studies, using piperacillin and meropenem, indicate that beta-lactam distribution into subcutaneous tissue, in critically ill patients with sepsis, is less than that observed in previous studies in healthy volunteers yet superior to studies in patients with septic shock. This supports the notion that the peripheral concentration of drugs may be inversely related to the level of sickness severity. Administration by continuous infusion was found to maintain statistically significantly higher trough beta-lactam concentrations in both plasma and subcutaneous tissue. Further analysis of the plasma data using population pharmacokinetic modeling and Monte Carlo simulations described significant pharmacodynamic advantages for administering meropenem or piperacillin by continuous infusion to organisms with high minimum inhibitory concentrations. Given the documented pharmacodynamic advantages for administering beta-lactams by continuous infusion, a prospective randomized controlled clinical trial was conducted using the beta-lactam antibiotic ceftriaxone. In 57 critically ill patients, we found equivalence between continuous infusion and bolus dosing in the intention-to-treat analysis. However, our a priori analysis criteria, requiring patients receive at least 4-days antibiotic treatment, found significant clinical and bacteriological advantages for administration by continuous infusion. To further investigate any clinical differences between bolus dosing and continuous infusion of beta-lactam antibiotics, we performed a meta-analysis of all published studies. Our analysis of the 13 published prospective randomized controlled trials (846 hospitalised patients) showed equivalence of continuous infusion and bolus dosing. Possible confounders observed within, and between the studies, make interpretation of these results challenging. However, two large retrospective cohorts not included in the meta-analysis, found definitive clinical and bacteriological advantages suggesting further research may be appropriate. The possible relationship between antibiotic dosing, or exposures, on the development of resistance was investigated using a structured review of the published literature. Our analysis of relevant papers found a wealth of data describing increasing levels of resistance with sub-optimal antibiotic dosing, particularly for fluoroquinolone antibiotics, but also for other classes including beta-lactams. These results demonstrate the importance of optimizing antibiotic dosing to decrease the development of antibiotic susceptibility from sub-optimal dosing, particularly for critically ill patients who are likely to have low drug concentrations. The results of this Thesis, suggest that a large, prospective, multi-centre randomised controlled trial in critically ill patients with sepsis, is required to definitively determine the clinical utility of administration of beta-lactam antibiotics by continuous infusion.

The Kahne rumen sensor (bolus) is a device developed to measure temperature, pressure and pH in non-fistulated animals. This bolus allows real-time monitoring of the rumen environment, which could help preventing health problems such as rumen acidosis in cows. It is less invasive to use boluses compared to other technologies that measure the ruminal pH (e.g. rumenocentesis). Kahne boluses and transceivers are commercially available in the market. Several studies on the relationships between data recorded by the bolus and actual data recorded by independent devices were conducted. The bolus temperature and pressure were compared with actual temperature and pressure under controlled conditions. The pH drift was studied by comparing the difference between bolus and direct measurement over time. The capture of the data was calculated for each bolus in various experiments to examine the factors affecting the data capture rate of the boluses. Animal to animal variation was studied using boluses in a group of cows fed and managed under uniform conditions. An animal experiment involving fistulated cows eating two different diets was performed using boluses to monitor the changes of ruminal pH. There was no apparent interruption to normal animal behaviour as a result of using boluses. Regression relationships between bolus measurements and actual data for both temperature and pressure were developed and used for calibration of bolus data. The pH drift was a problem, as the regression relation between the pH difference and the time for one bolus from one experiment could not represent this bolus on other experiment. The data capture rate on the hourly basis ranged from 0 to 100%, but was usually between 30 to 70%. The data capture rate was affected by many factors and further studies to identify these factors are needed. A study of animal to animal variation suggests that in a comparison of 2 treatments, a minimum 3 cows per group would be required to detect the standard deviation of 0.11 for a pH difference of 5% of the mean (approximately 0.35 pH units). Seventeen cows per group would be required to detect the standard deviation of 0.33 for the same difference. The boluses effectively monitored the ruminal pH change in cows easting two different diets and the profile of change of pH was successfully analysed. Feeding 7.6 kg baleage twice a day cause pH to decrease at 0.009 pH units per minute during feeding, while offering a similar quantity of grass and hay once a day resulted in a decrease of 0.0009 pH units per minute during feeding. The beginning of pH increase was about 1 hour following feeding and continuous during resting and rumination. The level of pH increase did not differ significantly for two diets.. The Kahne devices appear to have advantages compared to other technologies for the measurement of parameters of the rumen environment on a real-time basis. Boluses are especially good at intensively monitoring the temperature, pressure, and pH in the rumen. The major limitations of this technology to be used are the data capture rate and the pH drift. By improving the limitations found in the experiment, the Kahne rumen sensor could become very useful for both scientific research and under commercial conditions for monitoring animal health.

abstract: Type 1 diabetes (T1D) is a chronic disease that affects 1.25 million people in the United States. There is no known cure and patients must self-manage the disease to avoid complications resulting from blood glucose (BG) excursions. Patients are more likely to adhere to treatments when they incorporate lifestyle preferences. Current technologies that assist patients fail to consider two factors that are known to affect BG: exercise and alcohol. The hypothesis is postprandial blood glucose levels of adult patients with T1D can be improved by providing insulin bolus or carbohydrate recommendations that account for meal and alcohol carbohydrates, glycemic excursion, and planned exercise. I propose an evidence-based decision support tool, iDECIDE, to make recommendations to improve glucose control by taking into account meal and alcohol carbohydrates, glycemic excursion and planned exercise. iDECIDE is deployed as a low-cost and easy to disseminate smartphone application. A literature review was conducted on T1D and the state-of-the-art in diabetes technology. To better understand self-management behaviors and guide the development of iDECIDE, several data sources were collected and analyzed: surveys, insulin pump paired with glucose monitoring, and self-tracking of exercise and alcohol. The analysis showed variability in compensation techniques for exercise and alcohol and that patients made unaided decisions, suggesting a need for better decision support. The iDECIDE algorithm can make insulin and carbohydrate recommendations. Since there were no existing in-silico methods for assessing bolus calculators, like iDECIDE, I proposed a novel methodology to retrospectively compare insulin pump bolus calculators. Application of the methodology shows that iDECIDE outperformed the Medtronic insulin pump bolus calculator and could have improved glucose control. This work makes contributions to diabetes technology researchers, clinicians and patients. The iDECIDE app provides patients easy access to a decision support tool that can improve glucose control. The study of behaviors from diabetes technology and self-report patient data can inform clinicians and the design of future technologies and bedside tools that integrate patient’s behaviors and perceptions. The comparison methodology provides a means for clinical informatics researchers to identify and retrospectively test promising insulin blousing algorithms using real-life data. / Dissertation/Thesis / Doctoral Dissertation Biomedical Informatics 2017

The Gastroesophageal Reflux Disease (GERD) and the symptoms of the Pharyngeal Bolus can make the subject show complaints of impairments of swallowing. The goal of this study was to analyze the dynamics of swallowing in subjects that showed GERD and/or Pharyngeal Bolus through videofluoroscopy in young adults and old people. The reports of 34 subjects between 18 and 85 years old from both genders from the Radiology and Image Service of the Gastroenterological Institute of São Paulo were analyzed and categorized in groups: G1 - with GERD; G2 - with Pharyngeal Bolus; G3 - with Pharyngeal Bolus and GERD; and in sub-groups GA - elderly and GB - adults, with an average age of 74.9 and 43.8 years respectively, in order to study if the effects of ageing would represent an impact on the swallowing physiology. The analyses of the characteristics of the oral an pharyngeal phases of swallowing were carried out in percentages through the spreadsheets and based on the Ott et al. scales, (1996) to the oropharyngeal swallowing dysphagia, in slight, moderate and severe dysphagia -, and based on the Martin-Harris et al. scale, (2007) to the pharyngeal swallowing. The analysis of the pharyngeal phase was realized on the percentages of the most evident characteristics and also with the examination of the statistics of dependant variables. The chi-square test was used, with the level of significance p < 0,05 among the groups, so as to analyze a possible association among the variables. The results showed delay in the control and transportation of the food bolus and intraoral stasis with higher percentage on G3 and in tongue base on G2. There was a predominance of early pharyngeal swallowing in vallecula and piriform recesses in all groups. The laryngeal penetration occurred in all groups, but the incidence was higher in G1 and 1 subject breathed. The cleaning maneuvers were performed in all of them, with the most evident DS in higher levels to the pudding consistency. The harshness degree ranged from normal swallowing to slight dysphagia for all. The study of the relations among the characteristics of the pharyngeal phase presented significant results (p < 0,05) to the relation of the variables beginning of pharyngeal swallowing with laryngeal penetration and the beginning place of the pharyngeal swallowing with the harshness degree of the oropharyngeal dysphagia in young adults. / A Doença do Refluxo Gastroesofageano (DRGE) e o sintoma do Glóbus Faríngeo podem levar o sujeito a apresentar queixas de distúrbios da deglutição. O objetivo do estudo foi analisar a dinâmica da deglutição em sujeitos que apresentaram DRGE e / ou Glóbus Faríngeo por meio da videofluoroscopia em adultos jovens e idosos. Foram interpretados laudos de 34 sujeitos com idade entre 18 e 85 anos, de ambos os sexos, do Serviço de Radiologia e Imagem do Instituto Gastroenterológico de São Paulo, caracterizados como: G1 - Grupo com DRGE; G2 - Grupo com Glóbus Faríngeo; G3 - Grupo com Glóbus Faríngeo e DRGE; e criados os subgrupos GA adultos idosos e GB - adultos jovens com média de idade de 74,9 e 43,8 anos respectivamente, para estudar se os efeitos da idade apresentariam impacto na fisiologia da deglutição. As análises das características das fases oral e faríngea da deglutição foram realizadas em percentuais através de planilhas e baseadas nas escalas de Ott et al. (1996) para disfagias orofaríngeas em disfagia leve, moderada e grave e na escala de Martin-Harris et al. (2007) para a deglutição faríngea. A análise da fase faríngea foi realizada diante dos percentuais das características de maior evidência e analisada a estatística de variáveis dependentes. Foi utilizado o teste Qui - quadrado, com nível de significância p < 0,05 nos grupos, para avaliar possível associação entre as variáveis. Os resultados mostraram atraso no controle e transporte do bolo alimentar e estase intraoral com maior percentual no G3 e em base de língua para o G2. Houve predomínio de início de deglutição faríngea em valécula e recessos piriformes para todos os grupos. A penetração laríngea ocorreu em todos grupos, mas a maior incidência foi em G1. Nas manobras de limpeza a deglutição seca apresentou maior evidência em níveis mais elevados para a consistência pudim. O grau de severidade variou entre deglutição normal e disfagia leve para todos os grupos estudados. O estudo da relação entre as características da fase faríngea apresentou resultados significativos (p < 0,05) para a relação das variáveis início de deglutição faríngea com penetração laríngea e com grau de severidade das disfagias orofaríngeas para todos os grupos.

Nedsatt motilitet i esophagus kan vara en orsak till dysphagi. Högupplöst esophagusmanometri (HRM) är "golden standard" för att utvärdera esophagus motilitet. Defekter av motiliteten kan ses som avbrott i den isobariska konturen (IBC). Det finns ett samband mellan avbrott och inkomplett bolus clearance. Referensvärdena för HRM är utformade för att patienten ska ligga ner och svälja under undersökningen. Kroppens läge påverkar esophagus och värdena för HRM ändras signifikant beroende på om patienten ligger ned eller sitter upp. Det pågår diskussioner kring om undersökningen borde innefatta sväljningar i både liggande och sittande position för att öka den diagnostiska säkerheten. Denna studie innefattade 12 stycken patienter som frivilligt genomgick 10 extra sväljningar sittande utöver de i liggande position. En jämförelse i antalet avbrott i IBC gjordes mellan sväljningarna sittandes och liggandes. Resultatet visade att 24 av 118 sväljningar liggande hade avbrott i IBC och 94 var utan avbrott. När patienterna satt upp hade 68 av 120 sväljningar avbrott i IBC och 52 sväljningar utan avbrott. Hypotesen bekräftades då det föreligger en signifikant skillnad i antalet avbrott mellan sittande och liggande position. Det förekom fler avbrott i sittande position och avbrotten blev också längre i sittande position. Fortsatta studier med större urval erfordras. / Reduced motility in the esophagus can be a cause of dysphagia. High-resolution esophagus manometry (HRM) is the golden standard for evaluating esophageal motility. Defects of the motility can be seen as disruptions in the isobaric contour (IBC). There is a correlation between disruptions and incomplete bolus clearance. The references for HRM are made for the patient to lie down and swallow for the examination. The position of the body affects the esophagus and the values for HRM changes significantly depending on whether the patients is lying down or sitting up. There are discussions about whether the procedure should include both supine and sitting position to increase diagnostic reliability. This study included 12 patients who voluntarily underwent 10 additional swallows sitting up in addition to the supine position. A comparison of the disruptions in IBC was made between the swallows sitting and supine. The results showed that 24 out of 118 supine swallows had disruptions in IBC and 94 were without. When the patients sat up, 68 out of 120 swallows had disruptions in IBC and 52 were without. The hypothesis was confirmed as there were more disruptions in the sitting position and the disruptions were longer. Further studies are required.

No abstract available. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Clinical Epidemiology / unrestricted

Hintergrund: Im Rahmen intrakranieller Operationen kann die intraoperative Darstellung der Gehirndurchblutung die intraoperative Entscheidungsfindung unterstützen. Eine Alternative zu den etablierten Methoden der fluoreszenzgestützten Techniken und der Duplex-Sonographie stellt die intraoperative Perfusionsbildgebung auf Grundlage der Thermographie dar. Hiermit wird die temperaturabhängige, infrarote Strahlung des Gehirns gemessen, die annehmbar abhängig von der zerebralen Perfusion ist. Das Verfahren vereint die Vorteile des nebenwirkungsarmen, kontaktlosen, wiederholten und ökonomischen Einsatzes mit einem verhältnismäßig geringen apparativen Aufwand. Fragestellung/Hypothese: In der vorliegenden Arbeit sollen die intraoperativen Temperaturvariationen des Kortex thermographisch untersucht werden. Durch die intravenöse Applikation eines kalten Flüssigkeitsbolus kann ein systemischer Kältereiz erzeugt werden, der als thermographisches Kontrastmittel agiert. Die Untersuchung der Sensitivität der kortikalen Kältesignalerfassung in Abhängigkeit der Injektionsparameter des Flüssigkeitsbolus und anderer intraoperativer Variablen soll für die Etablierung eines robusten und klinisch nutzbaren Messaufbaus genutzt werden. Die gewonnenen Informationen sollen darüber hinaus zur Entwicklung eines Auswertungsalgorithmus für die automatisierte, thermographische Erfassung des kortikalen Kältesignals dienen. Abschließend werden potenzielle, klinische Anwendungsszenarien beschrieben. Material und Methoden: Die thermographischen Aufnahmen wurden mit ungekühlten Focal-Plane-Array-Kameras mit einer thermischen Auflösung von bis zu 20 mK durchgeführt. Es wurden 97 Patienten intraoperativ untersucht und insgesamt 210 Kältebolusinjektionen appliziert. Die zugrundeliegenden Pathologien waren größtenteils Glioblastome und zerebrale Metastasen sowie Gliome II°/III°, Hirninfarkte, arteriovenöse Malformationen und Aneurysmen. Nach chirurgischer Exposition des zerebralen Kortex wurde die thermographische Messung des Kortex gestartet. Es folgte die intravenöse Injektion der Kälteboli mit einer Temperatur von etwa 4°C aus physiologischer Kochsalzlösung und einem Volumen von 20 ml (59 % der Fälle) oder 50 ml (41 % der Fälle) über einen peripheren (76 % der Fälle) oder zentralen Venenkatheter (24 % der Fälle). Es wurden die Injektionsgeschwindigkeit und Vitalparameter registriert. Nachfolgend wurden die thermographischen Sequenzen einer Datenvorverarbeitung unterzogen, um das Signal-Rausch-Verhältnis zu verbessern. Es folgte die Auswertung der resultierenden Temperatur-Zeit-Reihen zur Kältesignaldetektion mit der Hauptkomponentenanalyse nach Steiner et al., dem Bigauss-Algorithmus nach Hollmach und einer manuellen Analyse (Steiner et al., 2011; Hollmach, 2016). Die Qualität der Auswertungsalgorithmen wurden auf Basis von 10 parallelen Kältebolus-ICG-Injektionen überprüft. Die ICG-Signale wurden als Referenz für die Kältesignaldetektionen genutzt. Die Beschreibung der Kältesignale erfolgte anhand der Parameter twash-in, tmin(T), trise, ttransit und ΔT. Ergebnisse: Die Thermographie kann kleinste Temperaturvariation des Kortex von bis zu 20 mK aufzeichnen. Periodische Temperaturänderungen können zum Teil durch physiologische Prozesse wie Atmung und Herzaktion erklärt werden, während andere spontane Temperaturschwankungen bisher keinen pathophysiologischen Äquivalenten zugewiesen werden können. Das systemische Kältesignal in Form des intravenösen Kältebolus kann bei der kortikalen Passage thermographisch als Temperatursenke registriert werden. Die Sensitivität der Kältesignalerfassung wird wesentlich durch die Injektionsparameter Bolusvolumen, Applikationsort und -geschwindigkeit bestimmt und lässt sich durch eine periphervenöse, 50 ml umfassende Bolusinjektion mit einer Geschwindigkeit von ≥ 5,4 ml/s auf über 70 % steigern. Die Vitalparameter beeinflussen die Kältesignaldetektion nicht. Die Validierung der Kältesignaldetektionen mittels paralleler Kältebolus-ICG-Injektionen offenbarte, dass die präexistenten Auswertungsalgorithmen der Hauptkomponentenanalyse und des Bigauss-Algorithmus eine hohe Sensitivität von 90 % hinsichtlich anteilig richtig-positiver Kältesignaldetektionen erzielen. Jedoch wurden in 90 % der Referenzfälle falsch-positive Kältesignale erkannt, sodass eine geringe Spezifität und ein geringer positiv-prädiktiver Wert resultiert. Beide Algorithmen weisen eine hohe Fehleranfälligkeit auf und sind ungeeignet, um intraoperativ das systemische Kältesignal zuverlässig zu erfassen. Aus den gewonnenen Erkenntnissen der manuellen Analyse der ICG-Kältebolus-Referenzfälle konnte der optimierte AKE-Auswertungsalgorithmus (Automatisierte Kältesignaldetektion nach Empirischem Vorwissen) entwickelt werden. Der AKE-Algorithmus besitzt in den Referenzfällen eine Sensitivität von 100 % und eine qualitativ deutlich verbesserte Spezifität. Der AKE-Algorithmus ist in der Lage, im intraoperativen Einsatz die Kältesignale innerhalb weniger Minuten nach der Kältebolusinjektion zuverlässig in Form zweidimensionaler Parameterkarten zu visualisieren. Auf Basis des AKE-Algorithmus wurden die Kältesignalerfassungen in verschiedenen intrakraniellen Pathologien untersucht. Die Kältesignalparameter in Glioblastomen präsentieren neben einer großen Heterogenität eine durchschnittlich erhöhte Perfusion im Vergleich zum peritumoralen Gewebe in Form einer verminderten twash-in und einer erhöhten ttransit. Jedoch ist eine Identifizierung der Tumorgrenzen anhand der Kältesignaldetektionen nicht möglich, weil die Kältesignalparameter intra- und peritumoralen Gewebes nicht signifikant differieren. Bei der thermographischen Untersuchung maligner Hirninfarkte können die Infarktkerne bereits als hypotherme Kortexregionen und durch eine negative Kältesignaldetektion erfasst werden. Kollateralkreisläufe werden registriert und die Kältesignalparameter korrelieren mit dem postoperativen NIHSS. Die Kältesignalerfassung gelingt zunehmend im Übergang von CT-morphologisch demarkierten zu nicht-demarkierten Hirnarealen und zeigt begleitend eine kürzere twash-in. Damit besteht potenziell die Möglichkeit, in weiteren Untersuchungen die Penumbra zu untersuchen und prognostische Informationen zu gewinnen. Die Kältesignalerkennung bei AVMs konnte sicher erfolgen und die Perfusion der pathologischen Gefäßanteile nachweisen. Somit kann die Thermographie die vollständige Ausschaltung oberflächlicher AVMs unterstützen und ist des Weiteren in der Lage, die Perfusion des umgebenden Parenchyms zu beurteilen. Ebenso kann die Kältesignaldetektion bei der Operation von Aneurysmen zur Erfolgskontrolle und zur Erfassung Clip-bedingter kortikaler Minderperfusionen dienen. Schlussfolgerungen: Die thermographische Detektion eines systemischen Kältereizes ist möglich und kann intraoperativ zusätzliche Informationen generieren, die in operative Entscheidungen oder wissenschaftliche Untersuchungen einfließen können. Um einen robusten und zuverlässigen, intraoperativen Einsatz der thermographischen Kältesignaldetektion zu ermöglichen, sollten zukünftig ausschließlich 50 ml Boli, periphervenöse Injektionen und eine Injektionsgeschwindigkeit ≥ 5,4 ml/s verwendet werden. Für eine schnelle und zuverlässige, intraoperative Ergebnisgenerierung und -darstellung sollte der AKE-Algorithmus bevorzugt werden. Die thermographische Kältesignaldetektion eignet sich insbesondere für die Untersuchung primär vaskulärer Pathologien, wie Hirninfarkte, AVMs oder Aneurysmen.:Inhaltsverzeichnis A Abbildungsverzeichnis B Tabellenverzeichnis C Abkürzungsverzeichnis 1 Einleitung 2 Medizinische Grundlagen 2.1 Präoperative Bildgebung in der Neurochirurgie 2.1.1 Konventionelles MRT, CT und Angiographie 2.1.1 Dynamisch-funktionelle MRT-Sequenzen 2.1.2 Neuronavigation 2.2 Intraoperative Bildgebung zur zerebralen Perfusionsvisualisierung 2.2.1 Fluoreszenzgestützte Techniken 2.2.2 Ultraschall 3 Thermographie 3.1 Physikalische Grundlagen 3.2 Anwendung der Thermographie in der Medizin 4 Zielstellung 5 Material und Methoden 5.1 Thermographische Messung 5.1.1 Messaufbau 5.1.2 Messinstrumentarium 5.1.3 Ablauf der Kältebolus-Messung 5.1.4 Simultane Erfassung des Infrarot- und ICG-Signals 5.2 Methoden der Datenverarbeitung 5.2.1 Vorverarbeitung der Daten 5.2.2 Hauptkomponentenanalyse 5.2.3 Bigauss-Algorithmus 5.3 Auswahl des Patientenkollektivs 6 Ergebnisse 6.1 Patientenkollektiv 6.2 Ergebnisse der Hauptkomponentenanalyse 6.3 Ergebnisse des Bigauss-Algorithmus 6.4 Manuelle Analyse und ICG-Fälle 6.4.1 Schlussfolgerungen der manuell analysierten ICG-Kälteboli 6.4.2 Ergebnisse aller manuell analysierten Kälteboli 6.5 Entwicklung des AKE-Algorithmus 6.6 Ergebnisse des AKE-Algorithmus 6.6.1 Allgemeine Kälteboluscharakteristik 6.6.2 Kältesignalparameter in Abhängigkeit der Injektionsparameter 6.6.3 Kältesignaldetektion als interpathologischer Vergleich 6.6.4 Kältesignaldetektion als intrapathologische Analyse 7 Diskussion 7.1 Vergleich der Verfahren der Kältesignaldetektion 7.2 Einflussfaktoren 7.2.1 Vitalparameter 7.2.2 Injektionsparameter 7.3 Bedeutung der Kältesignalparameter 7.4 Potential der Kältebolusdetektion in Pathologien mittels AKE-Algorithmus 7.4.1 Glioblastom 7.4.2 Maligner Hirninfarkt 7.4.3 Neurovaskuläre Pathologien 7.5 Thesen 8 Zusammenfassung / Summary 9 Literaturverzeichnis 10 Danksagung 11 Anlage 1 12 Anlage 2 / Background: In intracranial surgery, intraoperative imaging of cerebral blood flow can support intraoperative decision making. An alternative to established methods of fluorescence-based techniques and duplex sonography is intraoperative perfusion imaging based on thermography. It receives temperature-dependent, infrared radiation, which depends on cerebral perfusion. Thermography combines the advantages of low-side-effects, contactless, repeated and economical use with a relatively low outlay on equipment. Objective/Hypothesis: In the present work the intraoperative temperature variations of the cortex are to be examined thermographically. The intravenous application of a cold fluid bolus creates a systemic cold stimulus that acts as a thermographic contrast agent. By examining the sensitivity of the cortical cold signal acquisition depending on the injection parameters of the fluid bolus and other intraoperative variables, a robust and clinically usable measurement setup is to be established. The information obtained should also be used to develop an evaluation algorithm for the automated, thermographic detection of the cortical cold signal. Finally, potential clinical application scenarios are described. Material and Methods: The thermographic recordings were made with uncooled focal plane array cameras with a thermal resolution of up to 20 mK. 97 patients were examined intraoperatively and a total of 210 cold bolus injections were administered. The underlying pathologies were mostly glioblastomas and cerebral metastases as well as gliomas II° / III°, brain infarctions, arteriovenous malformations and aneurysms. After surgical exposure of the cerebral cortex, the thermographic measurement of the cortex was started. This was followed by intravenous injection of the cold 0,9% saline boluses with a temperature of about 4 °C and a volume of 20 ml (59% of cases) or 50 ml (41% of cases) via a peripheral (76% of cases) or central venous line (24% of cases). The injection rate and vital parameters were registered. The thermographic sequences were subsequently subjected to data preprocessing in order to improve the signal-to-noise ratio. The resulting temperature-time series are evaluated to find cold signals using the principal component analysis according to Steiner et al., the Bigauss algorithm according to Hollmach and a manual analysis (Steiner et al., 2011; Hollmach, 2016). The results were checked based on 10 parallel cold bolus ICG injections. The ICG signals were used as a reference for the cold signal detection. The cold signals were described by the parameters twash-in, tmin(T), trise, ttransit and ΔT. Results: Thermography can record smallest temperature variations of the cortex up to 20 mK. Periodic changes in temperature can be explained in part by physiological processes such as breathing and heart rate, while other spontaneous temperature fluctuations cannot yet be assigned to any pathophysiological equivalents. The systemic cold signal in the form of the intravenous cold bolus can be thermographically registered as a temperature drop during the cortical passage. The sensitivity of the cold signal detection is essentially determined by the injection parameters bolus volume, injection site and injection rate. It can be increased to more than 70% with a peripheral venous line, 50 ml bolus volume and an injection rate of ≥ 5.4 ml/s. The vital parameters do not influence the cold signal detection. The validation of the cold signal detection using parallel cold bolus and ICG injections revealed that the pre-existent evaluation algorithms of the principal component analysis and the Bigauss algorithm achieve a high sensitivity of 90 % with regard to proportionally correct-positive cold signal detection. However, false-positive cold signals were detected in 90% of the reference cases, resulting in low specificity and low positive-predictive value. Both algorithms are highly susceptible to errors and are unsuitable for reliably detection of the systemic cold signal intraoperatively. From the knowledge obtained from the manual analysis of the ICG - cold bolus reference cases, the optimized AKE evaluation algorithm (Automated Cold signal detection based on Empirical prior knowledge) was developed. In the reference cases, the AKE algorithm has a sensitivity of 100% and a qualitatively significantly improved specificity. The AKE algorithm is able to reliably visualize the cold signals in two-dimensional parameter maps within a few minutes after the cold bolus injection during intraoperative use. Based on the AKE algorithm, the cold signal recordings in various intracranial pathologies were examined. The cold signal parameters of glioblastomas showed a high degree of heterogeneity and on average an increased cerebral perfusion by reduced twash-in and increased ttransit compared to peritumoral tissue. However, an identification of the tumour borders based on the cold signal detection is not possible because the cold signal parameters of intra- and peritumoral tissue do not differ significantly. In the thermographic examination of malignant brain infarctions, the infarct cores can be detected as hypothermic cortex regions and by negative cold signal detection. Collateral circuits are registered thermographically and the cold signal parameters correlate with the postoperative NIHSS. The cold signal acquisition succeeds increasingly in the transition from CT-morphologically infarcted to non-infarcted brain areas and shows a smaller twash-in. Therefore, the cold bolus detection has the potential to investigate the penumbra and to obtain prognostic information. Cold signal detection in AVMs was carried out safely and the perfusion of the pathological vessels were demonstrated. Thus, thermography can support the complete elimination of superficial AVMs and is also able to assess the perfusion of the surrounding parenchyma. Cold signal detection can also be used in the operation of aneurysms to monitor complete elimination and clipping-related cerebral perfusion changes. Conclusions: The thermographic detection of the systemic cold stimulus is possible and can generate additional information intraoperatively, which can be incorporated into intraoperative decision making or scientific studies. In order to enable robust and reliable, intraoperative use of thermographic cold signal detection, further cold bolus examinations should be standardized with intravenous injection of 50 ml boluses via peripheral venous line and an injection rate ≥ 5.4 ml/s. The AKE algorithm should be preferred for fast and reliable, intraoperative result generation. Thermographic cold signal detection is particularly suitable for the investigation of primarily vascular pathologies such as brain infarctions, AVMs or aneurysms.:Inhaltsverzeichnis A Abbildungsverzeichnis B Tabellenverzeichnis C Abkürzungsverzeichnis 1 Einleitung 2 Medizinische Grundlagen 2.1 Präoperative Bildgebung in der Neurochirurgie 2.1.1 Konventionelles MRT, CT und Angiographie 2.1.1 Dynamisch-funktionelle MRT-Sequenzen 2.1.2 Neuronavigation 2.2 Intraoperative Bildgebung zur zerebralen Perfusionsvisualisierung 2.2.1 Fluoreszenzgestützte Techniken 2.2.2 Ultraschall 3 Thermographie 3.1 Physikalische Grundlagen 3.2 Anwendung der Thermographie in der Medizin 4 Zielstellung 5 Material und Methoden 5.1 Thermographische Messung 5.1.1 Messaufbau 5.1.2 Messinstrumentarium 5.1.3 Ablauf der Kältebolus-Messung 5.1.4 Simultane Erfassung des Infrarot- und ICG-Signals 5.2 Methoden der Datenverarbeitung 5.2.1 Vorverarbeitung der Daten 5.2.2 Hauptkomponentenanalyse 5.2.3 Bigauss-Algorithmus 5.3 Auswahl des Patientenkollektivs 6 Ergebnisse 6.1 Patientenkollektiv 6.2 Ergebnisse der Hauptkomponentenanalyse 6.3 Ergebnisse des Bigauss-Algorithmus 6.4 Manuelle Analyse und ICG-Fälle 6.4.1 Schlussfolgerungen der manuell analysierten ICG-Kälteboli 6.4.2 Ergebnisse aller manuell analysierten Kälteboli 6.5 Entwicklung des AKE-Algorithmus 6.6 Ergebnisse des AKE-Algorithmus 6.6.1 Allgemeine Kälteboluscharakteristik 6.6.2 Kältesignalparameter in Abhängigkeit der Injektionsparameter 6.6.3 Kältesignaldetektion als interpathologischer Vergleich 6.6.4 Kältesignaldetektion als intrapathologische Analyse 7 Diskussion 7.1 Vergleich der Verfahren der Kältesignaldetektion 7.2 Einflussfaktoren 7.2.1 Vitalparameter 7.2.2 Injektionsparameter 7.3 Bedeutung der Kältesignalparameter 7.4 Potential der Kältebolusdetektion in Pathologien mittels AKE-Algorithmus 7.4.1 Glioblastom 7.4.2 Maligner Hirninfarkt 7.4.3 Neurovaskuläre Pathologien 7.5 Thesen 8 Zusammenfassung / Summary 9 Literaturverzeichnis 10 Danksagung 11 Anlage 1 12 Anlage 2

L’appréciation du pain par le consommateur est largement impactée par ses propriétés sensorielles, notamment les perceptions d’arômes et de texture en bouche. Ces perceptions ne peuvent pas être uniquement expliquées par la composition aromatique du pain ou par sa structure. Elles dépendent également de phénomènes dynamiques, résultant de la déstructuration du pain en bouche, très dépendante de chaque individu. L’objectif de ce projet de thèse est donc de mieux comprendre les déterminants liés au produit et à l’individu à l’origine des dynamiques de perceptions d’arômes et de texture du pain. Une stratégie multidisciplinaire, basée sur l’étude du processus oral en conditions réelles de mastication, a été mise en place pour répondre à cet objectif. Les résultats de cette étude montrent d’une part que la capacité d’hydratation et la rigidité de la mie jouent un rôle majeur dans l’évolution des propriétés des bols et des perceptions de texture et d’arômes au cours de la consommation. Ainsi, plus un pain a une capacité d’hydratation élevée, plus il sera facilement déstructuré et hydraté. De plus, un pain avec une mie rigide provoquerait une plus grande libération des composés d’arômes susceptibles d’interagir avec les récepteurs olfactifs sensoriels. D’autre part, deux types de comportements masticatoires, basés sur la durée de mastication, ont été identifiés entre les individus participant à l’étude. Ces comportements conduisent à des bols aux propriétés différentes au moment de la déglutition et à des dynamiques différentes de perception de texture et d’arôme. / The liking of the bread by the consumers is largely impacted by its sensory properties, and notably the aroma and texture perceived during inmouth consumption. These perceptions cannot be only explained by the volatile composition of the bread or by its structure. In fact, they also depend on dynamic phenomena, resulting from the breakdown of the bread in mouth, which depends on each individual. This PhD project aims thus to better understand the determinants linked to the product and to the individual at the origin of the dynamics of aroma and texture perceptions of bread. A multidisciplinary strategy, based on the study of the oral processing in real conditions of mastication was set up to fulfill this objective. The results show firstly that the hydration capacity and the rigidity of the crumb have a main impact on the evolution of bolus properties and texture and aroma perceptions during consumption. In this way, the higher the hydration capacity of the bread is, the more easily broken and hydrated it will be. Moreover, a bread with a rigid crumb could cause a higher release of volatile compounds susceptible to interact with the sensory olfactive receptors. In addition, two types of masticatory behavior, based on masticatory duration, were highlighted between the individuals of the study. These behaviors lead to bolus with different properties at swallowing time and at different dynamics of aroma and texture perceptions.

The Arterial Spin Labelling (ASL) method is a Magnetic Resonance technique used toquantify the cerebral perfusion. It has the big advantage to be non-invasive so doesn’tneed the injection of any contrast agent. But due to a relatively low Signal-to-NoiseRatio (SNR) of the signal acquired (only approximately 1% of the image intensity), ithas been hampered to be widely used in a clinical setting so far.The primary objective of this project is to make the method more robust by improvingthe quality of the images, the SNR, and by reducing the acquisition time. DifferentASL protocols with different sets of parameters have been investigated. The modificationsperformed on the protocol have been investigated by analyzing images acquired onhealthy volunteers. An optimized protocol leading to a good trade-off between the differentaspects of the method, has been suggested. It is characterized by a 3:43:44:0mm3with a two-segment acquisition.A more advanced ASL method implies the acquisition of images at different inversiontimes (TI), which is called the mutli-TI method. The influence of the range of TI used inthe method has been explored. An optimized TI range (from 410ms to 3860ms, sampledevery 150ms) has been suggested to make the ASL method as performant as possible.A numerical model and a fitting algorithm have been used to extract the informationon the perfusion from the images acquired. Different models have been investigated aswell as their influence on the reliability of the results.Finally, a criterion has been implemented to evaluate the reliability of the results sothat the clinician or the user of the method can figure out how much he can count onthe results provided by the method.