Natriumpicosulfat-Tropfen erlauben eine sehr genaue Dosierung. Die randomisierte, plazebokontrollierte, doppelblinde cross-over Studie mit 20 gesunden Probanden wurde durchgeführt, um weitere Informationen sowohl über eine Dosis-Wirkungsbeziehung als auch über dosisabhängige pharmakokinetische Parameter und Verträglichkeit zu erhalten. Das Ziel war die Messung der Kolontransitzeit und der Zeit bis zum Wirkungseintritt und der Überprüfung, ob es eine Beziehung zwischen den kinetischen und dynamischen Parametern gibt. Die Probanden nahmen jeweils 5, 10 oder 15 mg Natriumpicosulfat-Tropfen oder Plazebo in einer oralen Einmaldosis. Die Kolontransitzeit, die Zeit bis zum Wirkungseintritt, die Urinausscheidung von BHPM (aktiver Metabolit von Natriumpicosulfat) und die Verträglichkeit wurden untersucht. Die mittlere Kolontransitzeit und die mittlere Zeit bis zum Wirkungseintritt waren nach Einnahme von 5, 10 und 15 mg Natriumpicosulfat-Tropfen im Vergleich zu Plazebo signifikant verkürzt. Es konnte jedoch keine eindeutige Dosis-Wirkungsbeziehung gefunden werden. Die Ausscheidung von BHPM sinkt mit Erhöhung der Natriumpicosulfatdosis und einer beschleunigten Kolontransitzeit. Die Verträglichkeit war gut. Die Nebenwirkungen (Magenkrämpfe, Blähungen) sind das Resultat der motilitätswirksamen Eigenschaften von Natriumpicosulfat. / Sodium picosulfate drops allow a very accurate dosage. The randomized, placebo-controlled, double blind cross-over study in 20 healthy volunteers was to provide further information about a dose-response ratio as well as dose-dependent pharmacokinetic parameters and tolerance. The aim was to measure transit time and time to onset of action and to check whether there was a correlation between kinetic and dynamic data. The volunteers received 5, 10 and 15 mg sodium picosulfate drops or placebo orally in a single dose. Colon transit time, time to onset of defecation, urinary excretion of BHPM (the active principle of sodium picosulfate) and tolerability were tested. Mean transit time and mean time to onset were significantly reduced by 5, 10 and 15 mg of sodium picosulfate, compared to placebo. No clear dose-response ratio could be found. The urinary excretion of BHPM dropped with increase of administered dose and accelerated transit velocity. The tolerance was good. The adverse events (stomach cramps, flatulence) are the result of motility stimulating effect of sodium picosulfate.

Arterial spin labeling is a completely non-invasive method for blood-flow measurement techniques. Alzheimer's disease pathology includes microvascular abnormalities in addition to practically all risk factors having a vascular component that reduces cerebral perfusion. Hemodynamic parameters of cerebral blood flow and arterial transit time were estimated via single-compartment modeling of pseudo continuous arterial spin labeling data and neurocognitive test scores (Alzheimer's disease assessment scale and mini-mental state examination) were compared between a group of healthy (N=20) and early Alzheimer's disease (N=25) subjects before and six months after the Alzheimer's subjects began treatment with cholinesterase inhibitors. The early Alzheimer's group showed improved CBF after 6 months' treatment in every Alzheimer's-prone region except the medial and lateral temporal lobes. No difference in arterial transit time was found between groups, indicating that the pathophysiological process causing hypoperfusion in Alzheimer's disease may differ from vascular dementia.

Arterial spin labeling is a completely non-invasive method for blood-flow measurement techniques. Alzheimer's disease pathology includes microvascular abnormalities in addition to practically all risk factors having a vascular component that reduces cerebral perfusion. Hemodynamic parameters of cerebral blood flow and arterial transit time were estimated via single-compartment modeling of pseudo continuous arterial spin labeling data and neurocognitive test scores (Alzheimer's disease assessment scale and mini-mental state examination) were compared between a group of healthy (N=20) and early Alzheimer's disease (N=25) subjects before and six months after the Alzheimer's subjects began treatment with cholinesterase inhibitors. The early Alzheimer's group showed improved CBF after 6 months' treatment in every Alzheimer's-prone region except the medial and lateral temporal lobes. No difference in arterial transit time was found between groups, indicating that the pathophysiological process causing hypoperfusion in Alzheimer's disease may differ from vascular dementia.

Pour les mesures de débit et de volume d’hydrocarbures, les débitmètres à ultrasons se distinguent de par leur caractère non intrusif, ce qui réduit les pertes de charge. La plupart des débitmètres à temps de transit affichent des précisions influencées par les conditions d’écoulement. Pour utiliser ce principe en transactions commerciales, les recommandations stipulent : une linéarité < ± 0,20 %, une répétabilité < ± 0,02 % et une incertitude (coefficient d’étalonnage) < ± 0,027 %. Ce dispositif offre de réels avantages s’il permet de réduire le nombre de transducteurs ultrasonores et conserve son aspect non intrusif. Cela a amené à l’examen du projet sous ses angles hydrodynamique et acoustique. La thèse s’articule autour de deux axes liés. Le premier a comme objectif de déterminer les différentes méthodes de configuration de cordes et de reconstruction de profils de vitesse, pour déterminer une configuration optimale de l’instrument. À partir des résultats d’analyse de profils, un prototype de débitmètre a été développé et utilisé dans l’étude acoustique et expérimentale. Les signaux enregistrés en conditions réelles ont servi de base au développement d’une technique novatrice de mesure par temps de transit. / For measurements of flow and volume of liquid hydrocarbons, ultrasonic flowmeters distinguish themselves by their nonintrusive character, which reduces pressure losses. Most transit-time ultrasonic flowmeters have an accuracy which is influenced by the flow profile conditions. In order to be able to use this principle for custody transfer applications, the recommendations stipulate: a linearity < ± 0.20 %, a repeatability < ± 0.02 %, an uncertainty (calibration factor) < ± 0.027 %).This mechanism offers real advantages if it works with a reduced number of ultrasonic transducers and preserves its nonintrusive properties. These conditions have led to the examination of this project from the hydrodynamic and acoustic angles.This thesis is focuses on two linked areas. The first aims to identify the various configurations of paths and the reconstruction of the velocity profile, in order to determine an optimal configuration for the flowmeter. From the results of the profile analysis, a prototype of flowmeter was developed and used in the experimental phase. The recorded signals in real conditions were used as a basis for the development of an innovative method of transit-time measurement.

Smart phones today have become increasingly popular with the general public for its diverse abilities like navigation, social networking, and multimedia facilities to name a few. These phones are equipped with high end processors, high resolution cameras, built-in sensors like accelerometer, orientation-sensor, light-sensor, and much more. According to comScore survey, 25.3% of US adults use smart phones in their daily lives. Motivated by the capability of smart phones and their extensive usage, I focused on utilizing them for bio-medical applications. In this thesis, I present a new application for a smart phone to quantify the vital signs such as heart rate, respiratory rate and blood pressure with the help of its built-in sensors. Using the camera and a microphone, I have shown how the blood pressure and heart rate can be determined for a subject. People sometimes encounter minor situations like fainting or fatal accidents like car crash at unexpected times and places. It would be useful to have a device which can measure all vital signs in such an event. The second part of this thesis demonstrates a new mode of communication for next generation 9-1-1 calls. In this new architecture, the call-taker will be able to control the multimedia elements in the phone from a remote location. This would help the call-taker or first responder to have a better control over the situation. Transmission of the vital signs measured using the smart phone can be a life saver in critical situations. In today's voice oriented 9-1-1 calls, the dispatcher first collects critical information (e.g., location, call-back number) from caller, and assesses the situation. Meanwhile, the dispatchers constantly face a "60-second dilemma"; i.e., within 60 seconds, they need to make a complicated but important decision, whether to dispatch and, if so, what to dispatch. The dispatchers often feel that they lack sufficient information to make a confident dispatch decision. This remote-media-control described in this system will be able to facilitate information acquisition and decision-making in emergency situations within the 60-second response window in 9-1-1 calls using new multimedia technologies.

The retina is a highly metabolically active tissue with large demands on the supply of nutrients. Disorders affecting the retina often include some vasculopathy with an impact on retinal circulation. Studies of retinal haemodynamics could thus help to detect, differentiate and diagnose diseases, to monitor changes in disease as well as progression and efficiency of the therapy. The present studies were an attempt to validate and determine the clinical usefulness of a newly developed technique for studying the retinal circulation in human eyes. We used different techniques to evaluate different parameters of retinal circulation. We examined how leukocyte velocity determined with Blue Field Simulation and transit times, mean transite time (MTT) and arterio-venous passage (AVP), and vessel diameter, determined from fluorescein angiograms, together reflects the retinal circulation. MTT was determined with a method based on an Impulse-Response technique, MTTIR. In a study on monkeys we compared our method, together with two conventional methods, with an absolute measurement of retinal blood flow (RBF) determined with labelled microspheres. There was a weak, but not statistically significant, correlation between retinal blood flow and MTTIR (r2 = -0.60, p = 0.06), but no useful correlation between retinal blood flow and either of the other two measures of transit times. In a study on healthy eyes we determined the effect of a physiological provocation, changes in arterial blood gases, on retinal circulation. Breathing pure oxygen or increased level of carbon dioxide in inspired air had no effect on MTT, but oxygen reduced leukocyte velocity and vessel diameter and carbon dioxide increased leukocyte velocity significantly. We concluded that unchanged transit time trough the retinal tissue was not due to a lack of effect of the gas provocation but a result due to concomitant changes in volume and flow. In a study on eyes of patients with diabetic retinopathy we investigated the relation between the extent of retinal circulation changes and the severity of the diabetes retinopathy (DRP). Transit times were relatively unaffected until proliferative DRP (PDRP) developed. In eyes with PDRP both MTTIR and AVP were increased. After panretinal photocoagulation treatment MTTIR returned to normal levels and vessel diameters tended to decrease while leukocyte velocity and AVP remained unchanged. We concluded that the increase in MTTIR in eyes with PDRP is at least partly explained by vessel dilation, causing an increased volume of the retinal vascular bed.

Abstract Multimodal measurements are increasingly being employed in the study of human physiology. Brain studies in particular can draw advantage of simultaneous measurements using different modalities to analyse correlations, mechanisms and relationships of physiological signals and their dynamics in relation to brain functions. Moreover, multimodal measurements help to identify components of physiological dynamics generated specifically by the brain. This thesis summarizes the study, design and development of non-invasive medical instruments that can be utilized in conjunction with magnetic resonance imaging (MRI). A key challenge in the development of measurement methods is posed by the extraordinary requirements that the MRI environment poses - all materials need to be MR-compatible and the selected instruments and devices must not be affected by the strong magnetic field generated by the MRI scanner nor the MRI by the instruments placed within its scanning volume. The presented methods allow simultaneous continuous measurement of heart rate (HR) and metabolism from the brain cortex as well as pulse wave velocity (PWV) and blood pressure measurements in synchrony with electroencephalography (EEG) and MRI. Furthermore, the thesis explored the reliability and accuracy of the responses gathered by the developed instruments and, using new experimental methods, estimated the propagation of near-infrared light in the human brain. The goal of the novel multimodal measurement environment is to provide more extensive tools for medical researchers, neurologists in particular, to acquire accurate information on the function of the brain and the human body. Measurements have been performed on more than 70 persons using the presented multimodal setup to study such factors as the correlation between blood oxygen level-dependent (BOLD) data and low-frequency oscillations (LFOs) during the resting state. / Tiivistelmä Multimodaalisia kuvantamismenetelmiä käytetään enenevässä määrin ihmisen fysiologian ja elintoimintojen tutkimisessa. Erityisesti aivotutkimuksessa samanaikaisesti useammalla modaliteetilla mittaaminen mahdollistaa erilaisten fysiologisten mekanismien ja niiden korrelaatioiden tutkimisen kehon ja aivotoimintojen välillä. Lisäksi multimodaaliset mittaukset auttavat yksilöimään fysiologiset komponentit toisistaan ja identifioimaan aivojen tuottamia fysiologisia signaaleja. Tämä väitöskirja kokoaa tutkimustyön sekä laite- ja instrumentointisuunnittelun ja sen kehittämistyön ei-invasiivisesti toteutettujen lääketieteen mittausmenetelmien käyttämiseksi magneettikuvauksen aikana. Erityishaasteena työssä on ollut magneettikuvausympäristö, joka asettaa erityisvaatimuksia mm. mittalaitteissa käytettäville materiaaleille sekä laitteiden häiriönsiedolle magneettikuvauslaitteen aiheuttaman voimakkaan magneettikentän takia. Kehitettävät mittausmenetelmät eivät myöskään saa aiheuttaa häiriöitä magneettikuvauslaitteen tuottamalle kuvainformaatiolle. Väitöskirjassa esitettävät mittausmenetelmät tekevät mahdolliseksi mitata magneettikuvausympäristössä ihmisen sydämen sykettä, veren virtauksen kulkunopeutta ja verenpaineen vaihteluja sekä aivokuoren metaboliaa - kaikki synkronissa aivosähkökäyrän mittaamisen ja magneettikuvantamisen kanssa. Lisäksi väitöskirjassa tutkitaan kehitettyjen mittausmenetelmien antamaa mittaustarkkuutta sekä arvioidaan lähi-infrapunavalon etenemistä ihmisen aivoissa uudenlaisella menetelmällä. Kehitetyllä multimodaalisella mittausympäristöllä on tavoitteena antaa lääketieteen alan tutkijoille, erityisesti neurologeille, käyttöön mittausmenetelmiä, joiden avulla voidaan tutkia ihmisen aivojen ja kehon välisiä toimintoja aiempaa kattavammin. Laitekokonaisuudella on tutkittu jo yli 70:tä henkilöä. Näissä mittauksissa on tutkittu mm. veren happitasojen hitaita vaihteluja ihmisen aivojen ollessa lepotilassa, ns. resting state -tilassa.

Blood pressure is one of the basic indicators of the health state of the cardiovascular system. High blood pressure is the main risk factor of ischemic heart disease, atherosclerosis and stroke. Therefore, it is important to monitor long-term changes in blood pressure and respond in time to these changes. Blood pressure meters are not standard household equipment, while a well-equipped smartphone is. Smartphones contain a large number of sensors capable of measuring biomedical signals. This thesis focuses on creating an application capable of determining blood pressure using data obtained from these sensors.

The thesis analyzes the optical laser range finders in real propagation environments. Itdescribes the various parts of optical laser range finders their properties and principles in relation to their performance balance. The paper presents the basic optical properties of lenses used in the transmitter and receiver. A separate chapter is devoted to the transit time method and factors influencing the measurement. The proportional directional reflectance analysisis a part of the thesis. In conclusion, the thesis contains the practical laboratory measurements of the relative directional reflectance of different materials and colors, and verification of the power level diagram.

<p>    </p> <p>Cerebrovascular diseases, such as stroke, constitute the most common life-threatening neurological disease in the United States. To support normal brain function, maintaining adequate brain perfusion (i.e., cerebral blood flow (CBF)) is important. Therefore, it is crucial to assess the brain perfusion so that early intervention in cerebrovascular diseases can be applied if abnormal perfusion is observed. The goal of my study is to develop metrics to measure the brain perfusion through modeling brain physiology using resting-state and task-based blood-oxygenation-level- dependent (BOLD) functional MRI (fMRI). My first and second chapters focused on deriving the blood arrival time using the resting-state BOLD signal. In the first chapters, we extracted the systemic low-frequency oscillations (sLFOs) in the fMRI signal from the internal carotid arteries (ICA) and the superior sagittal sinus (SSS). Consistent and robust results were obtained across 400 scans showing the ICA signals leading the SSS signals by about 5 seconds. This delay time could be considered as an effective perfusion biomarker that is associate with the cerebral circulation time (CCT). To further explore sLFOs in assessing dynamic blood flow changes during the scan, in my second chapter, a “carpet plot” (a 2-dimensional plot time vs. voxel) of scaled fMRI signal intensity was reconstructed and paired with a developed slope-detection algorithm. Tilted vertical edges across which a sudden signal intensity change took place were successfully detected by the algorithm and the averaged propagation time derived from the carpet plot matches the cerebral circulation time. Given that CO₂ is a vasodilator, controlling of inhaled CO₂ is able to modulate the BOLD signal, therefore, as a follow-up study, we focused on investigating the feasibility of using a CO₂ modulated sLFO signal as a “natural” bolus to track CBF with the tool developed from the second chapter. Meaningful transit times were derived from the CO₂-MRI carpet plots. Not only the timing, the BOLD signal deformation (the waveform change) under CO₂ challenge also reveals very useful perfusion information, representing how the brain react to stimulus. Therefore, my fourth chapter focused on characterizing the brain reaction to the CO₂ stimulus to better measure the brain health using BOLD fMRI. Overall, these studies deepen our understanding of fMRI signal and the derived perfusion parameters can potentially be used to assess some cerebrovascular diseases, such as stroke, ischemic brain damage, and steno-occlusive arterial disease in addition to functional activations. </p>