Abstract Retrograde cerebral perfusion (RCP) techniques have been adopted in aortic arch surgery for clinical use. The clear benefits of RCP are that it reduces embolic injury and prolongs the permissible period of hypothermic circulatory arrest (HCA). At the same time, however, there is a great deal of evidence according to which RCP may be associated with an increased risk of fluid sequestration and cerebral edema. In the current study intermittent RCP was compared with continuous RCP and HCA alone to clarify if periodical RCP decreases fluid sequestration (I). HCA is an effective method of cerebral protection, but is associated with long cardiopulmonary bypass times, and coagulation disturbances. We tested the hypothesis that deep hypothermic RCP could improve cerebral outcome during moderate HCA (II and III). Glutamate excitotoxicity plays an important role in the development of ischemic brain injury. The purpose of the present study was to determine the efficacy of lamotrigine, a Na+ channel blocker, to mitigate cerebral injury after HCA (IV). A chronic porcine model was used in the present series of studies. Hemodynamic, electrophysiologic, and metabolic monitoring were performed until four hours after the instigation of rewarming. S-100β was measured up to 20 hours. Daily behavioral assessment performed until death or elective sacrifice on the seventh postoperative day. After continuous RCP the median fluid sequestration volume was 145 (0–250) ml compared with -50 (-100 - 0) ml after intermittent RCP (p = 0.04). In comparison of 15°C RCP to HCA alone during moderate 25°C hypothermia, 5/6 animals in the RCP group survived seven days compared with 2/6 in the HCA group (p = 0.04). The total histopathologic scores in the RCP(15°C) group were lower than those for the RCP(25°C) group during moderate 25°C hypothermia (p = 0.04). EEG bursts were recovered better in the RCP(15°C) group at 3 hours after the start of rewarming compared to HCA group (p = 0.05). The rate of EEG burst recovery was higher in lamotrigine treated animals compared to placebo treated animals after 4 hours during the rewarming (p = 0.02). Among the animals that survived for 7 days, the median behavioral score was higher in the lamotrigine group (8) compared with controls (7) (p = 0.02). The results indicate that intermittent RCP decreases the rate of fluid sequestration after continuous RCP. The cold RCP at moderate systemic hypothermia seems to provide a better neurological outcome than that with moderate temperature RCP, a finding suggesting that enhanced cranial hypothermia is the major beneficial factor of RCP. The Na+ channel blocker lamotrigine improves neurological outcome after a prolonged period of HCA. In conclusion, two refinements in the RCP concept are to administer it at low temperatures and if longer periods of perfusion are necessary, RCP should be applied intermittently.

La perfusion intraveineuse, continue ou intermittente, est un acte courant dans les services de soins bien que non dénué de risque. Différents dispositifs médicaux peuvent être employés pour permettre l’administration parfois simultanée de plusieurs substances actives. Ces dispositifs peuvent, de par leurs caractéristiques propres, générer des fluctuations plus ou moins importantes du débit massique de principe actif, c’est-à-dire la quantité de médicament administrée au patient par unité de temps. Le premier axe de travail concernant ces dispositifs médicaux est l’étude des prescriptions des normes, en particulier les définitions, les méthodes d’essai et les seuils de conformité attendus. Les principaux éléments de physiologie et de mécanique des fluides sont abordés afin d’appréhender la problématique. Cette étude est complétée par l’analyse des données de la littérature concernant l’impact des dispositifs médicaux sur le débit massique des principes actifs délivrés par voie intraveineuse. Une revue systématique de la littérature a été effectuée. Elle porte sur les travaux in vitro ou in vivo se rapportant au sujet et concernant tout élément susceptible de modifier le débit ou la concentration du médicament perfusé. Le premier travail expérimental réalisé in vitro concerne la perfusion simultanée de trois médicaments au moyen d’un dispositif unique de perfusion présentant plusieurs points d’accès. Les trois médicaments étaient perfusés par pousse-seringues et une solution d’hydratation par gravité. Le but de cette étude était d’évaluer l'impact des caractéristiques (volume résiduel et valve anti-retour) de deux dispositifs de perfusion, un premier présentant un très faible volume résiduel (0,046 ml) et une valve anti-retour et le second présentant un volume résiduel élevé (6,16 ml) et sans valve anti-retour) sur le débit massique de trois principes actifs. La quantification simultanée de trois principes actifs en solution (dinitrate d’isosorbide, midazolam et noradrénaline) a nécessité la mise au point d’une méthode multivariée sur spectre UV (régression partial least square (PLS)). Cette technique a permis de doser en continu (1 dosage par seconde) les trois principes actifs à la sortie de la ligne de perfusion. La méthode a été validée dans les échelles de concentrations respectives de 5-60, 10-80 et 2,5-20 µg.mL-1 pour le dinitrate d’isosorbide, le midazolam et la noradrénaline, dans des mélanges binaires et 6,67 à 30, 0,83 à 7,5 et 1,67 à 23,33 µg.ml−1 pour ces mêmes produits, dans des mélanges ternaires. La mise au point du modèle a permis de retenir la zone du spectre située entre 220 et 300 nm associée à un index Q2cum optimal. L’étude de recouvrement, employant le modèle pour prédire les compositions de 8 mélanges ternaires, retrouvait des valeurs de concentrations situées dans un intervalle de 99,5 à 101 % des valeurs théoriques. Les principaux paramètres dans cette étude étaient 1) l'évolution du débit massique des trois médicaments, 2) la valeur du plateau du débit massique à l'équilibre, et 3) l’efficience de perfusion (flow change efficiency (FCE)). Le FCE est obtenu en divisant l’aire sous la courbe du débit massique expérimental en fonction du temps par l’aire sous la courbe du débit massique attendu en fonction du temps. Ce paramètre est calculé pour chaque intervalle de 5 minutes après le début de la perfusion. Les systèmes de perfusion avec un volume résiduel réduit offrent de façon significative un meilleur FCE (53,0  15,4% avec un volume résiduel très faible après 5 minutes de perfusion comparativement à 5,6  8,2% avec un système de perfusion avec un volume résiduel élevé), quel que soient les conditions de changements de débit. Une relation non-linéaire a été établie entre le volume résiduel, le temps depuis le début de la perfusion et le FCE. [...] / Intravenous infusion, whether used continuously or intermittently, is a common feature in healthcare, although not without risk. Various medical devices can be used to administer the infusion, sometimes simultaneously, of several active substances . These devices, because of their characteristics, may generate more or less significant variations in drug mass flow rate, which is the amount of drug delivered per unit of time to the patient. The first part of this work on these medical devices focuses on studying standard requirements and norms, especially definitions, as well as trial methods and expected conformity thresholds. The main elements of physiology and fluid mechanics are also addressed to offer a better grasp of the problems involved. This study is complemented by analyses of published data on the impact of medical devices on drug mass flow rate when delivered intravenously. A systematic review of publications was made, covering in vitro or in vivo studies related to the topic, targeting more particularly any infusion device likely to alter the flow or concentration of the infused drug. The first experimental in vitro work involves the simultaneous infusion of three drugs using a single infusion device with several access points. The three drugs were infused by syringe pump and a hydration solution by gravity. The purpose of this study was to assess the impact of certain features (residual volume and check valve) of two infusion devices (the former with very low residual volume and a check valve and the latter with a high residual volume and no check valve) on the mass flow of three active ingredients. Simultaneous quantification of three active ingredients in solution (isosorbide dinitrate, midazolam and norepinephrine) made it necessary to develop a multivariate method on UV spectrum (partial least square regression (PLS)). This technique meant that the three drugs could be dosed continuously (1 dose per second) at the catheter egress. The method was validated for concentration scales of 5-60, 10-80 and from 2.5 to 20 µg/ml for isosorbide dinitrate, midazolam and noradrenaline in binary mixtures and 6.67 to 30, 0.83 to 7.5 and 1.67 to 23.33 µg/ml for the same products, in ternary mixtures. The perfecting of the model made it possible to maintain the spectral region between 220 and 300 nm with an optimal Q2cum index. The recovery study, performed on prediction sets containing eight different ternary mixtures of isosorbide dinitrate, midazolam and noradrenalin, yielded recovery values ranging from 99.5 to 101% of the theoretic values. The main parameters assessed in this study were 1) the evolution of mass flow rate for the three drugs, 2) the value of the plateau mass flow rate, and 3) flow change efficiency (FCE).. FCE is obtained by dividing the area under the curve of the experimental mass flow in relation to time by the area under the curve of the expected mass flow in relation to time. This parameter was calculated at each 5-minute interval after the start of infusion. Infusion systems with reduced residual volume provided significantly better FCE (53.0  15.4% with very low residual volume after 5 minutes’ infusion compared to 5.6  8.2% with high residual volume), regardless of any changes in flow conditions. A nonlinear relationship was established between residual volume, time since the onset of infusion and FCE. [...]

It is believed that with ageing comes a decline in many cognitive processes, ranging from memory, language and executive function to response inhibition and motor and visual processes. However, memory has attracted much attention and is of particular interest in ageing research. This is because it is a form of cognition that probably suffers the clearest decline with age, and can have a detrimental effect on day-to-day living. Additionally, as people are living longer these problems are affecting an increasing number of people and has therefore become an issue of concern. It is believed that these declines stem from neurophysiological changes that occur alongside ageing. It can be seen that research into this area is of particular importance to better understand the healthy ageing brain, and how illnesses such as Alzheimer's disease differ from this normal progression. The focus of this PhD project addresses this issue by exploring healthy age-related declines in recognition memory and their neural correlates, using brain imaging techniques to investigate underlying changes in brain structure. Novel recognition memory tasks were developed (Chapter 4) to tap underlying processes supporting scene recognition (recollection and familiarity), and were run alongside selected cognitive tasks taken from existing standardised batteries (Chapter 5). In addition to these behavioural measures, MR imaging datasets were collected relating to structural (Chapter 6), perfusion and functional (Chapter 7) as well as diffusion (Chapter 8) measures of the brain. The relationships between these imaging measures were investigated in Chapter 9, in addition to looking at how they related individually to a measure of recollection memory when accounting for the influence each imaging measure had on the others. Overall, age effects were found for the novel recognition memory tasks, in particular showing a significant decline in recollection performance with age. This was associated with a number of neurophysiological measures (functional, perfusion, diffusion and volume) which also showed age-related changes. After taking into account the relative contribution of these measures to task performance, no single imaging measure was found to be a significant predictor of recollection performance.

京都大学 / 新制・課程博士 / 博士(医科学) / 甲第23117号 / 医科博第128号 / 新制||医科||8(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 花川 隆, 教授 中本 裕士, 教授 溝脇 尚志 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The goal of this diploma thesis was to create a script in MATLAB, which is capable to load DICOM pictures, read the data in their headers and then select the right series for perfusion analysis. This analysis is based on detection of contrast fluid in bloodstream and tissue and right interpretation of concentration changes of this fluid in time. This work is trying to describe a way of building an ultimate system capable of autonomous tumor analysis and classification. In the end, there is an analysis of DICOM sample performed by created script.

Une exploration multimodale permettrait d'identifier les biomarqueurs précoces du CNV permettrait de déterminer leur caractère prédictif. Chapitre (3): Dans ce chapitre, les résultats présentés montrent que l'augmentation maximale de la température était plus élevée dans le cerveau néonatal que dans le cerveau adulte. Chapitres (4 et 5): Le but principal de cette thèse était de fournir une approche multimodale du CNV et de la régulation neurovasculaire dans le cerveau du nouveau-né prématuré. Chapitre (4): Les résultats montrent que le volume sanguin cérébral régional (rCBV) et le rCMRO2 (Cerebral metabolic rate of oxygen) exercent une influence prédominante sur le débit sanguin cérébral régional (rCBF) à l'état de repos chez le prématuré. Chapitre (5): Les bouffées d'activité électroencéphalographique caractéristiques chez les nouveau-nés au repos se sont révélés couplées à une réponse hémodynamique transitoire complexes avec différents types de réponses incluant: (a) des réponses hémodynamiques stéréotypées positives (augmentations de HbO, CBF et CMRO2, diminution de HbR), (b )des réponses hémodynamiques négatives (augmentations de HbR, diminutions de HbO avec des diminutions de CBF et CMRO2), (c) des augmentations et des diminutions à la fois de HbO -HbR et de CMRO2 sans modification du CBF. Malgré des profils de réponse hémodynamique différents qui reflètent l'immaturité et la complexité des systèmes vasculaires et des réseaux neuronaux, l'établissement d'un couplage neurovasculaire a été caractérisé avec une évolution en fonction de l'âge / Neurovascular coupling (NVC) has become the key aspect for understanding brain function. A multimodal exploration would aim to identify the early NVC biomarkers and determine their predictive character. Paper (1): In this chapter, the photothermal interaction of NIR laser on human tissues were modelled in silico. The results demonstrated the safety of the noninvasive optical evaluation of the brain function and the maximum temperature increase was higher in the neonatal brain than in the adult brain. Paper (2 & 3): The main purpose of this thesis was to provide a multimodal view of the NVC and cerebrovascular regulation in the neonatal premature brain. Paper (2): Key findings included that rCBV and rCMRO2 have a predominant driving influence on rCBF at the resting-state in the preterm neonatal brain. Paper (3): The bursts of electroencephalographic activity in neonates in resting state were found to be coupled to a transient hemodynamic response involving different types of hemodynamic response including: (a) positive stereotyped hemodynamic responses (increases in HbO, decreases in HbR together with increases in CBF and CMRO2), (b) negative hemodynamic responses (increases in HbR, decreases in HbO together with decreases in CBF and CMRO2), (c) Increases and decreases in both HbO-HbR and CMRO2 together with no changes in CBF. The establishment of neurovascular coupling system was observed as a function of age. High coherence was observed between the cerebral hemodynamic (vascular) and electrical (neuronal) oscillations which was less in the non-encephalopathic newborns than in the two pathological groups

No description available.

Fescue toxicosis is a common problem in beef cattle grazing endophyte-infected (E+) tall fescue. Symptoms include decreases in feed intake, weight gain, and reproductive efficiency along with vasoconstriction. The mechanisms by which fescue toxicosis affects the bovine reproductive tract have yet to be discovered. The objective of this study was to determine if the onset of fescue toxicosis conditions would alter the blood perfusion observed in the CL and peripheral concentrations of progesterone in cattle. We hypothesized that during fescue toxicosis, the vasoconstrictive symptoms would lead to a reduction in CL blood perfusion thus decreasing peripheral concentrations of progesterone. Overall, fescue toxicosis was induced as cows fed an E+ treatment diet had greater rectal temperatures and reduced pulse pressure and mean arterial pressure measurements; however, total blood perfusion of the CL and peripheral concentrations of progesterone did not differ in cattle under fescue toxicosis compared to those without.

This thesis provides insight into methods for estimating blood perfusion, emphasizing the need for accurate modeling in dynamic physiological environments. The thesis critically examines conventional error function solutions used in steady state or gradually changing blood flow scenarios, revealing their shortcomings in accurately reflecting more rapid changes in blood perfusion. To address this limitation, this study introduces a novel prediction model based on the finite-difference method (FDM) specifically designed to produce accurate results under different blood flow perfusion conditions. A comparative analysis concludes that the FDM-based model is consistent with traditional error function methods under constant blood perfusion conditions, thus establishing its validity under dynamic and steady blood flow conditions. In addition, the study attempts to determine whether analytical solutions exist that are suitable for changing perfusion conditions. Three alternative analytical estimation methods were explored, each exposing the common thread of inadequate responsiveness to sudden changes in blood perfusion. Based on the advantages and disadvantages of the error function and FDM estimation, a combination of these two methods was developed. Utilizing the simplicity and efficiency of the error function, the prediction of contact resistance and core temperature along with the initial blood perfusion was first made at the beginning of the data. Then the subsequent blood perfusion values were predicted using the FDM, as the FDM can effectively respond to changing blood perfusion values. / Master of Science / Blood perfusion, the process of blood flowing through our body's tissues, is crucial for our health. It's like monitoring traffic flow on roads, which is especially important during rapid changes, such as during exercise or medical treatments. Traditional methods for estimating blood perfusion, akin to older traffic monitoring techniques, struggle to keep up with these rapid changes. This research introduces a new approach, using a method often found in engineering and physics, called the finite-difference method (FDM), to create more accurate models of blood flow in various conditions. This study puts this new method to the test against the old standards. We discover that while both are effective under steady conditions, the FDM shines when blood flow changes quickly. We also examined three other methods, but they, too, fell short in these fast-changing scenarios. This work is more than just numbers and models; it's about potentially transforming how we understand and manage health. By combining the simplicity of traditional methods for initial blood flow estimates with the dynamic capabilities of the FDM, we're paving the way for more precise medical diagnostics and treatments.

Background Guidelines recommend the use of perfusion computed tomography (CT) to identify emergent large vessel ischemic stroke (ELVIS) patients who are likely to benefit from endovascular thrombectomy (EVT) if they present within 6-24 hour (late window) of stroke onset. We aim to determine if the interrater and intrarater reliability among physicians when recommending EVT is significantly different when perfusion CT or non-perfusion CT is reviewed. Methods A total of 30 non-consecutive patients were selected from our institutional database comprising 3144 cranial CT scans (January 2018-August 2022) performed for acute stroke symptoms. The clinical and radiologic data of the 30 patients were presented in random order to a group of 29 physicians in two separate sessions at least three weeks apart. In each session, the physicians evaluated each patient once with automated perfusion images and once without. We used non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG). Results Twenty-nine raters successfully completed the first round of surveys, with all but one of them also completing the second. The interrater (κG) agreement amonth 29 raters is similar with non-perfusion CT neuroimaging compared to perfusion CT neuroimaging (κG = 0.487; 95% CI 0.327,0.647 and κG =0.552; 95% CI 0.430,0.675). The 95% confidence intervals overlapped and both κG signify moderate agreement. The intrarater agreement κG had overlapping 95% confidence intervals for all 28 raters. κG was either substantial or excellent (0.81-1) for 71.4% (20/28) of patients in both groups. Conclusions Our findings suggest that automated perfusion images and quantitative values that are present in the perfusion CT neuroimaging but not in non-perfusion CT neuroimaging do not significantly affect the reliability of the decisions made by physicians on EVT for late window ELVIS patients. / Thesis / Master of Science (MSc) / Background and Methods Strokes that are associated with a blood clot in the brain may be treated by endovascular thrombectomy (EVT), a procedure that involves pulling the occlusion out. In this study we wanted to know whether a particular type of way to image the brain, perfusion computed tomography (CT) compared to plain CT makes a difference in how doctors decide on whether to treat these patients or not. Perfusion imaging comes at a cost and may not be available in all centers. Both imaging techniques are used to determine which patients would benefit from EVT (Endovascular Treatment). The goal of imaging is to confirm a stroke and assess whether a significant portion of the brain is still salvageable, as performing the procedure may not be beneficial otherwise. Results and Conclusions Our study suggests that the decisions made by physicians when reviewing patients with either imaging are comparable.