<p>Uvod: Pacijenti na hemodijalizi (HD) imaju visoku stopu ukupnog i kardiovaskularnog morbiditeta i mortaliteta. Preko 80% bolesnika na HD ima neki tip kardiovaskularne bolesti. Hipervolemija značajno doprinosi njihovom nastanku, dovodeći do hipertenzije, hipertrofije miokarda leve komore, srčane insuficijencije i nastanka plućnog edema. Procena stanja volemije kod pacijenata na HD najče&scaron;će se vr&scaron;i kliničkim pregledom, uprkos nezadovoljavajućoj specifičnosti i senzitivnosti. Hipervolemija je prisutna kod određenog broja pacijenata, uprkos normotenziji, odsustvu edema i urednom auskultatornom nalazu na plućima. Različite metode se koriste za procenu stanja volemije, svaka sa određenim manama. Upotreba analize bioelektrične impedanse zahteva skupu opremu i potro&scaron;ni materijal, vrednosti B-tipa natriuretskog peptida (BNP) i njegovog N terminalnog propeptida (NT-proBNP) zavise i od stanja volemije i od srčane funkcije, kao i od tipa dijalizne membrane. Ehokardiografija (EHO) i ultrazvuk donje &scaron;uplje vene (UZ ICV) sa određivanjem dijametara u inspirijumu i ekspirijumu (IVCDi i IVCDe) zahteva posebno obučen kadar. Ultrazvuk pluća (UZ pluća) je jednostavna, brza i jeftina metoda za detekciju ekstravaskularne plućne tečnosti (EVLW). EVLW predstavlja onu količinu tečnosti koja se nalazi u plućnom intersticijumu. UZ pluća detektuje EVLW kao UZ artefakte zvane &bdquo;B linije&ldquo;. Količina EVLW zavisna je od pritiska punjenja leve komore i povećava se u stanjima hipervolemije, &scaron;to se na UZ pluća manifestuje kao veći broj detektovanih &bdquo;B linija&ldquo;. Zbir svih &bdquo;B linija&ldquo; detektovanih na definisanim mestima na grudnom ko&scaron;u naziva se &bdquo;skor B linija&ldquo; (BLS) i koristi se za kvantifikaciju EVLW pomoću UZ pluća. Cilj: Uporediti adekvatnost i efikasnost UZ pluća u proceni stanja volemije kod pacijenata na HD u odnosu na standardne tehnike UZ donje &scaron;uplje vene, EHO i BNP-a. Proceniti mogućnost pojednostavljenja protokola UZ pregleda pluća redukcijom broja analiziranih plućnih polja. Materijal i metode: Istraživanje je sprovedeno kao studija preseka od aprila 2016. do juna 2017. godine na 83 pacijenta koji su se nalazili na hroničnom programu HD u Službi za HD Odeljenja za internu medicinu Op&scaron;te bolnice Kikinda. Ispitanicima je prvog dana HD u nedelji neposredno pre HD urađen UZ pluća, UZ IVC, EHO, i uzorkovanje krvi za određivnje vrednosti BNP-a. Potom su pacijenti dijalizirani prema svojim utvrđenim HD protokolima. Neposredno nakon HD ponovljeni su UZ pluća, UZ IVC, EHO, a uzorkovanje krvi za BNP je ponovljeno pre započinjanja sledeće HD u nedelji, da bi se izbegao neposredni postdijalizni skok BNP-a. Za poređenje varijabli kori&scaron;ćeni su T test parova odnosno Vilkoksonov test, a za ispitivanje korelacije Pirsonov odnosno Spirmanov test, u zavisnosti od distribucije varijabli. Razlike između grupa ispitanika ispitivane su pomoću jednofaktorske analize varijanse (ANOVA) za kontinuirane varijable, a za kategorijske je kori&scaron;ćena analiza kontingencijskih tabela. Analiza glavnih komponenata (PCA) je kori&scaron;ćena za procenu mogućnosti redukcije broja ispitivanih plućnih polja. Rezultati: Utvrđena je signifikantna razlika između predijaliznih (pre HD) srednjih vrednosti BLS-a (18,85) i postdijaliznih (post HD) srednjih vrednosti BLS-a (7,30); između srednjih vrednosti BNP-a pre HD (894,89 pg/ml) i post HD (487,74 pg/ml); između srednjih vrednosti IVCDe pre HD (10,45 mm) i post HD (7,85 mm); između srednjih vrednosti IVCDi pre HD (7,20 mm) i post HD (4,41 mm); između srednjih vrednosti indeksa kolapsibilnosti IVC pre HD (32%) i post HD (45%). Utvrđene su i signifikantne razlike između srednjih vrednosti sledećih EHO parametara: dijametar leve pretkomore pre HD (3,78 cm) i post HD (3,53 cm), dijametra leve komore u dijastoli pre HD (5,21 cm) i post HD (4,96 cm), dijametra leve komore u sistoli pre HD (3,69 cm) i post HD (3,43 cm) i zapremine leve pretkomore u sistoli pre HD (60,54 ml) i post HD (52,36 ml). Sve razlike su bile signifikantne na nivou p&lt;0,0001. Dokazana je signifikantna pozitivna korelacija između BLS-a pre HD i BNP-a pre HD (&rho;=0,49, p&lt;0,01) i BNP-a post HD (0,43, p&lt;0,01); BLS-a pre HD i IVCDe pre HD (&rho;=0,29, p&lt;0,01), IVCDi pre HD (&rho;=0,30, p&lt;0,05) i IVCDi post HD (&rho;=0,23, p&lt;0,05) kao i između BLS-a post HD i BNP-a pre HD (&rho;=0,44, p&lt;0,01) i BNP-a post HD (&rho;=0,42, p&lt;0,01), između BLS-a post HD i IVCDe pre HD (&rho;=0,29, p&lt;0,05) IVCDi pre HD (&rho;=0,33, p&lt;0,05) i IVCDi post HD (&rho;=0,23, p&lt;0,05). Utvrđeno je da su bolesnici sa vi&scaron;im BLS-om imali niže vrednosti hemoglobina (p=0,006) i vi&scaron;e vrednosti visoko senzitivnog troponina T (p=0,02), kao i veće dijametre leve komore u sistoli (p=0,04). Pomoću PCA utvrđeno je da je moguća redukcija broja ispitivanih plućnih polja na 4 do 12 plućnih polja, koja bi bila odgovorna za 75,38% odnosno 84,51% varijabilnosti BLS-a. Zaključak: UZ pluća može adekvatno i efikasno da proceni stanje volemije i može se koristiti za ovu svrhu kod pacijenata na hroničnom programu HD. UZ pluća je brz, jednostavan i jeftin pregled koji se može izvoditi u bolesničkoj postelji i koji daje pouzdan podatak o bolesnikovom statusu volemije u realnom vremenu. UZ pluća bez većih te&scaron;koća mogao uključiti u kliničke protokole u svim centrima sa dostupnom opremom. Postoji mogućnost redukcije broja ispitivanih plućnih polja i time pojednostavljenja samog UZ pregleda pluća. UZ pluća može koristiti u proceni srčane funkcije kod pacijenata na HD. Pacijenti koji su procenjeni kao hipervolemični pomoću UZ pluća imaju povećan kardiovaskularni rizik, kao i pacijenti procenjeni kao hipervolemični pomoću vrednosti BNP-a i dijametra D&Scaron;V.</p> / <p>Introduction: Patients on hemodialysis (HD) have a high general morbidity and all-cause mortality, as well as high cardiovascular morbidity and mortality. More than 80% of patients on HD have some cardiovascular disease. Hypervolemia plays a significant role here, contributing to hypertension, left ventricular hypertrophy, heart failure and pulmonary edema. Fluid status assessment in HD is still mostly clinical, despite having low specificity and sensitivity. A number of patients remain hypervolume, despite being normotensive, without edema or bibasilar crackles on lung auscultation. Different methods are used for volume status assessment in HD setting, no method without its flaws. Bioelectric impedance analysis requires expensive equipment and supplies. B type natriuretic peptide (BNP) values, and those of its terminal propeptide (NT-proBNP) depend on volume status, cardiac function as well as type of dialysis membrane used. Echocardiography (ECHO) and ultrasonography of inferior vena cava (IVC US) with measurements of its diameters in inspirum and expirium (IVCDi and IVCDe) require trained medical personnel. Lung ultrasound (LUS) is a simple, fast and inexpensive method for detection of extravascular lung water (EVLW), which is the water contained in the lung interstitium. LUS detects EVLW as ultrasonographic artefacts called &bdquo;B lines&ldquo;. EVLW is dependent on left ventricular filling pressures and is increased in volume overload, manifesting as more &bdquo;B lines&ldquo; on LUS. The sum of all &bdquo;B lines&ldquo; detected on predetermined places on the chest is called &bdquo;B line score&ldquo; (BLS) and is used to quantify EVLW using LUS. Goal: Compare the adequacy and efficacy of LUS in assessment of volume status in patients on HD to other methods (IVC US, ECHO, BNP). Assess the possibility of simplifying LUS by reducing the number of examined lung fields. Materials and methods: A cross-section study was performed from April 2016 to June 2017. on 83 dialysis patients in Dialysis unit of Internal medicine department of General hospital Kikinda. LUS, ECHO, IVC US and blood sampling for BNP were performed on the first dialysis day of the week, just prior to HD. Patients were then dialyzed according to their dialysis protocols. After HD all tests were repeated, except blood sampling for BNP, which was sampled just prior to the next HD session in order to avoid elevated BNP values after HD. Variables were compared using double sample T test or Wilcoxon test. Correlation was assessed using Pearson&rsquo;s or Spearman&rsquo;s test, depending on variable distribution. Differences between groups were tested using one-way analysis of variance for continuous variables and contingency tables for categorical variables. Principal component analysis (PCA) was used to assess the possibility of lung field reduction. Results: There was a significant difference between BLS predialysis (pre HD) (mean 18,85) and BLS postdialysis (post HD) (mean 7,30); between IVCDe pre HD (mean 10,45 mm) and IVCDe post HD (mean 7,85 mm); between IVCDi pre HD (mean 7,20 mm) and IVCDi post HD (mean 4,41 mm); between CCI pre HD (mean 32%) and CCI post HD (mean 45%), between BNP pre HD (mean 894,89 pg/ml) and BNP post HD (mean 487,74 pg/ml). There was also a significant difference between the following ECHO parameters: left atrial diameter pre HD (mean 3,78 cm) and post HD (mean 3,53 cm), left ventricular internal diameter in diastole pre HD (mean 5,21 cm) and post HD (mean 4,96 cm) and left ventricular internal diameter in sistole pre HD (mean 3,69 cm) and post HD (mean 3,43 cm), left atrial volume in sistole pre HD (mean 60,54 ml) and post HD (mean 52,36 ml). All differences were significant at a level of p&lt;0,0001. There was a significant positive correlation between BLS pre HD and BNP pre HD (&rho;=0,49, p&lt;0,01) and BNP post HD (&rho;=0,43, p&lt;0,01); BLS pre HD and IVCDe pre HD (&rho;=0,29, p&lt;0,01) IVCDi pre HD (&rho;=0,30, p&lt;0,05) and IVCDi post HD (&rho;=0,23, p&lt;0,05); between BLS post HD and BNP pre HD (&rho;=0,44, p&lt;0,01) and BNP post HD (&rho;=0,42, p&lt;0,01); between BLS post HD and IVCDe pre HD (&rho;=0,29, p&lt;0,05), IVCDi pre HD (&rho;=0,33, p&lt;0,05) and IVCDi post HD (&rho;=0,23, p&lt;0,05). Subjects with higher BLS had lower hemoglobin levels (p=0,006), higher troponin T levels (p=0,02) and greater left ventricular internal dimensions in sistole (p=0,04). PCA showed that there is a possibility of lung field reduction to 12 lung fields and even down to 4 lung fields, which would account for 84,51% or 75,38% of BLS variability. Conclusion: LUS can be used to adequately and effectively assess volume status in patients on HD. LUS is simple, fast and inexpensive exam with bedside capability, which gives accurate volume status data in real time. The exam can be implemented into dialysis unit protocols without difficulty. There is a possibility of simplifying LUS by reducing the number of examined lung fields. LUS can be used in assessment of cardiac function in patients on HD. Patients rated as hypervolemic by LUS have increased cardiovascular risk, as well as patients rated as hypervolemic by BNP levels or IVC diameters.</p>

Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) contrast has become a universal methodology in functional neuroimaging. However, the BOLD signal consists of a mix of physiological parameters and has relatively poor reproducibility. As fMRI becomes a prominent research tool for rehabilitation studies involving repeated measures of the human brain, more quantitative and stable fMRI contrasts are needed. This dissertation enhances quantitative measures to complement BOLD fMRI. These additional markers, cerebral blood flow (CBF) and cerebral blood volume (CBV) (and hence cerebral metabolic rate of oxygen (CMRO₂) modeling) are more specific imaging markers of neuronal activity than BOLD. The first aim of this dissertation assesses feasibility of complementing BOLD with quantitative fMRI measures in subjects with central visual impairment. Second, image acquisition and analysis are developed to enhance quantitative fMRI by quantifying CBV while simultaneously acquiring CBF and BOLD images. This aim seeks to relax assumptions related to existing methods that are not suitable for patient populations. Finally, CBF acquisition using a low-cost local labeling coil, which improves image quality, is combined with simultaneous acquisition of two types of traditional BOLD contrast. The demonstrated enhancement of CBF, CBV and CMRO₂measures can lead to better characterization of pathophysiology and treatment effects.

Orientador: Francisco José Teixeira Neto / Resumo: Objetivo: Avaliar os efeitos da perda moderada de sangue seguida por reposição volêmica (RV) no índice de volume sanguíneo intratorácico (ITBVI), índice do volume global diastólico final (GEDVI), variação da pressão de pulso (VPP) e variação do volume sistólico (VVS).Delineamento experimental: Estudo prospectivo aleatorizado.Animais: Sete cães da raça Pointer Inglês (20 a 31,2 kg).Métodos: A anestesia foi mantida com sevofluorano sob ventilação mecânica no modo volume controlado com bloqueio neuromuscular induzido pelo atracúrio. A concentração expirada de sevofluorano (ETsevo), foi ajustada de forma a inibir alterações na frequência cardíaca e na pressão arterial média (PAM) em resposta à estimulação nociceptiva (< 20% mudança relativa). As variáveis estudadas foram registradas no momento basal, após retirada de 14 a 16 mL/kg da volemia e após a RV com sangue autólogo. Resultados: A anestesia foi mantida com 3,1 ± 0,3% de ETsevo. Um animal discrepante (“outlier”) não foi incluído da análise estatística. A hemorragia diminuiu significativamente (P < 0,05) o índice cardíaco (IC), índice sistólico (IS) e PAM em 20-25% dos valores basais (variações percentuais nos valores médios). A RV aumentou significativamente a PAM em relação aos valores registrados após hemorragia (31% de aumento); enquanto o IC e IS elevaram-se significativamente após a RV (29-30% acima dos valores basais). Após a hemorragia, o ITBVI e GEDVI se reduziram significativamente em 15% em relação aos val... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objective: To evaluate the effects moderate blood loss followed by volume replacement (VR) on intra-thoracic blood volume index (ITBVI), global end-diastolic volume index (GEDVI), pulse pressure variation (PPV), and stroke volume variation (SVV).Study design: Prospective, randomized study.Animals: Seven English Pointer dogs (20.0–31.2 kg).Methods: Anesthesia was maintained with sevoflurane under volume-controlled ventilation and atracurium induced neuromuscular blockade. End-expired sevoflurane (ETsevo) concentrations were adjusted to inhibit heart rate and mean arterial blood pressure (MAP) changes in response to nociceptive stimulation (< 20% relative change). Data recorded at baseline, after withdrawal of 14–16 mL kg-1 of blood volume and after VR with autologous blood.Results: Anesthesia was maintained with 3.1 ± 0.3 vol% of ETsevo concentrations. One outlier was excluded from the statistical analysis. Hemorrhage significantly (P < 0.05) decreased cardiac index (CI), stroke index (SI), and MAP by 20–25% from baseline (percent changes in mean values). Volume replacement significantly increased MAP in comparison to values recorded after hemorrhage (31% increase); while CI and SI were significantly increased after VR in comparison hemorrhage and to baseline (29–30% above baseline). The ITBVI and GEDVI were decreased by 15% from baseline after blood loss; while VR significantly increased ITBVI and GEDVI by 21% from values recorded after hemorrhage. Relat... (Complete abstract click electronic access below) / Mestre

This work deals with possibilities of ultrasound perfusion analysis for the absolute quantification of perfusion parameters. In the theoretical part of this work are discussed possibilities of using of the ultrasound contrast agents and approaches for the perfusion analysis. New methods for the perfusion analysis are suggested and tested in the practical part of this work. The methods are based on convolutional model in which the concentration of the contrast agent is modeled as aconvolution of the arterial input function and the tissue residual function. The feasibility of these methods for the absolute quantification of perfusion parameters is shown on data from phantom studies, simulations and also preclinical and clinical studies. The software for the whole process of the perfusion analysis was developed for using in hospitals.

This master thesis deals with the contrast agents and their application in the ultrasound perfusion analysis. It is focused on Bolus & Burst method which, as a combination of two approaches that have been used so far, allows an absolute quantification of perfusion parameters in the region of interest. Contrast agent concentration time sequence is modeled as a convolution of the parametrically defined arterial input function and the tissue residual funkction. Thesis discusses different mathematical models of these functions as well as the methods of the parameters estimation. The methods functionality is validated on simulated and also preclinical data.

Kohlenmonoxid (CO) wird nach Einatmung weitgehend an Hämoglobin gebunden, eine minimale Bindung findet auch an Myoglobin statt. Die Kohlenmonoxid-Hämoglobinkonzentration (COHb) im Blut steigt nach Inhalation proportional zur inhalierten CO-Menge und zur Hämoglobinmasse an. Dieser Anstieg wird über die CO-Hämoxymetrie ermittelt und resultierend aus der CO-Verdünnung die Hämoglobinmenge berechnet. Über die Hämoglobinkonzentration und den Hämatokrit kann im Anschluss das Blutvolumen berechnet werden. Grundsätzlich ist dieses Verfahren seit über 100 Jahren bekannt und wird seit ca. 1995 als Routinemethode zur Blutvolumenbestimmung in der Sportmedizin verwendet. Es existieren darüber hinaus methodische Probleme durch die CO-Abatmung und die Evaluierung in großen Kollektiven. Die hier vorgestellte Methodik beinhaltet die Weiterentwicklung der CO-Methode zur Direktmessung im geschlossenen System. Die Probanden atmen dabei ein exakt definiertes Bolus-Volumen in einem geschlossenen Atmungssystem über 15 Minuten ein. Die maximale Arbeitsplatzkonzentration (MAK: COHb 5%), also die resultierende COHb-Konzentration im Blut bei einer CO-Langzeitexposition von 35 ppm, wird in der Regel nur leicht überschritten. Dazu wurden an 104 Probanden zwei Vergleichsmessungen in definiertem Abstand und an 20 Probanden Wiederholungsmessungen nach Blutspende zum Nachweis der Reliabilität und Validität durchgeführt. Zusätzlich ist die Abfallkinetik von COHb an 20 Probanden bestimmt worden. Im Ergebnis stellt sich methodenbedingt ein COHb-Steady-State nach 9 Minuten Rückatmung im geschlossenen System ein. Der Typical-Error der Messwiederholung der Methodik liegt bei 1,9% bzw. nach weiterer Modifizierung der Methodik bei 1,3%. Der Nachweis eines Blutverlustes von 490 ml im Rahmen einer Blutspende zeigt nur eine minimale Abweichung von 10 g Hämoglobinmasse zwischen gemessenem und kalkuliertem Verlust. Die Halbwertszeit von COHb wurde mit 135 min bestimmt. Die verwendete Methodik zeigt aufgrund der induzierten COHb-Steady-State-Kinetik Vorteile bei der Anwendung und Genauigkeit. Der Nachweis der Wiederholbarkeit und Messgenauigkeit konnte an einem hinreichend großen Kollektiv gezeigt werden. Bei Mehrfachanwendung bietet die Sensitivität der Methodik die Möglichkeit der Aufdeckung von Manipulationen des Blutes über Erythropoetin (EPO) oder Eigenbluttransfusion. Dabei bewegt sich die eingesetzte CO-Belastung während der Methode im Bereich des Konsums von wenigen Zigaretten.

A prospective, non-randomized observational study involving forty-nine patients undergoing coronary artery bypass surgery (CABG) with a unilateral harvesting of the internal thoracic artery (ITA) was carried out at the Department of Cardiac Surgery, Herzzentrum Dresden University hospital. Using a commercially available industrial-grade RGB camera and normal indoor lighting, the chest wall of the patients was scanned before surgery and in three follow-up measurements. The primary aim of this thesis was to show whether iPPG is sensitive enough to detect global signal changes after a major surgery – CABG in this case – and local signal changes due to the removal of the ITA, the main supply vessel of the chest wall. As a secondary aim, the thesis looked at subgroups of data to show if differences in signal existed between the colour channels of the RGB camera, subdivisions of the thorax and the surgical technique used as well as to show if demographic factors had an impact on signal strength. With mathematical programs developed by the Technical University Dresden, the scanned optical data was transformed into signal to noise ratios (SNR) used in imaging photoplethysmographic (iPPG) studies. The signal data was analysed in R and, based on a stepwise deletion, a multivariable mixed effects model was constructed. Adjusted versions of this model were used for the analysis of the subgroups of the data. Analysis of the data showed a significant decrease of iPPG signal strength after the CABG surgery with a steeper decrease and an attenuated recovery on the side of the ITA harvesting. Even though the signal variations were relatively small, using the models in this thesis, the differences were reliably detected by iPPG. The analysis of the data from the subdivisions of the chest and from patients’ groups determined by the surgical technique showed a caudo-cranial signal gradient on the ITA side twenty-four hours after the surgery and a stronger signal in the Pedicled group within twenty-four hours after the surgery. The latter calculations, however, were based on a possibly biased sample and should be verified using a controlled sample in prospective randomised study designs. Demographic factors showed no significant correlation with iPPG signal strength. iPPG was able to detect relatively small signal variations that could be associated with changes of cutaneous perfusion after major surgery. Future development could lead to non-invasive monitoring devices in the clinical practice of post-surgery care.:1. Introduction 1 1.1. Coronary Artery Bypass Grafting (CABG) 1 1.1.1. Historical Overview 1 1.1.2. Coronary Grafts 3 1.1.2.1. Pedicled vs. Skeletonised Grafts 4 1.2. Plethysmography 5 1.2.1. Air-Displacement Plethysmography (APG) 5 1.2.2. Strain Gauge Plethysmography (SGP) 6 1.2.3. Impedance Plethysmography (IPG) 6 1.2.4. Photoplethysmography (PPG) 7 1.2.5. Imaging Photoplethysmography (iPPG) 8 1.3. Hypothesis and Aim of the Thesis 11 2. Methods 13 2.1. Study Setting and Patients 13 2.2. Camera and Technical Setup 14 2.3. Recording Area and Regions of Interest 15 2.4. Signal Processing 16 2.5. Statistical Analysis 17 3. Results 19 3.1. Descriptive Properties of the Data 19 3.2. Signal Strength in the Three Colour Channels 20 3.3. Choosing a Multilevel Model 21 3.4. The Effect of the Major Surgery on the Signal Strength in the Three Colour Channels 22 3.5. The Effect of the Unilateral Resection of the Internal Thoracic Artery 25 3.6. Results from the Model Fitted to the Data 27 3.7. The Effect of Cofactors 28 3.8. Data from the Subdivisions of the Chest 29 3.9. The Effect of the Surgical Technique 31 4. Discussion 34 4.1. Signal Strength in the Red, Green and Blue Colour Channels 34 4.2. Signal from the Entire Chest Area 36 4.3. Signal from the Subdivisions of the Chest 37 4.4. The Influence of the Surgical Technique on Signal Strength 38 5. Conclusion 39 6. Abstract 41 7. Zusammenfassung 42 8. References 44 9. Appendix 60 10. Acknowledgements 82 11. Resume 83 Anlage 184 Anlage 2 85 / Eine prospektive, nicht randomisierte Studie mit neunundvierzig Patienten geplant für eine koronare Bypassoperation (CABG) mit einseitiger Präparation der Arteria thoracica interna (ITA) wurde im Herzzentrum Dresden, Universitätsklinikum durchgeführt. In einer präoperativen und in drei postoperativen Messungen wurde die Brustwand bei den untersuchten Patienten unter normaler Innenbeleuchtung mit Hilfe einer handelsüblichen, industriellen RGB Kamera untersucht. Das primäre Ziel der Arbeit war zu zeigen, ob iPPG als Messmethode genug Sensitivität besitzt um globale Signal-Veränderungen nach einem großen Eingriff – die CABG in diesem Fall – und lokale Signaländerung nach der Abnahme der ITA, die Hauptversorgungsarterie der Brustwand, zu erkennen. Als sekundäres Ziel der Arbeit war zu eruieren, ob iPPG Signaldifferenzen zwischen den Farbkanälen der RGB Kamera, den Brustwandaufteilungen und den Arten der ITA Präparation sowie nach den demographischen Faktoren detektieren konnte. Die gemessenen Daten wurden unter Verwendung von Eigentumsprogrammen der Technischen Universität Dresden in den, bei plethysmographischen Studien genutzten, Signal zu Geräusch Quotienten (SNR - signal to noise ratios) umgewandelt. Die gewonnenen Signaldaten wurden in R verarbeitet und durch Verwendung der Methode schrittweise Löschung wurde ein multivariables gemischte Effekte Modell erstellt. Angepasste Versionen dieses Modells wurden für die Analyse von Patientensubgruppen verwendet. Die Datenanalyse ergab eine signifikante Abschwächung des Signals nach der CABG, wobei die Thorax-Seite mit der ITA Präparation zeigte, im Vergleich mit der anderen Thorax-Seite, eine stärkere Abnahme und eine gedämpfte Rückbildung der Signalstärke. Obwohl die detektierte Signaländerungen relativ klein waren, sie konnten durch die entwickelten Modelle mittels iPPG zuverlässig detektiert werden. Die weitere Analyse der Daten aus den Brustwandaufteilungen und von Patientensubgruppen definiert nach Präparationsart der ITA zeigte auf der ITA Seite eine caudo-craniale Zunahme der Signalstärke ab vierundzwanzig Stunden und ein stärkeres Signal in der pedikulierten Präparationsgruppe bis vierundzwanzig Stunden nach der Operation. Allerdings, diese letztere Berechnungen wurden auf einem möglicherweise unausgewogenen Muster durchgeführt und sollten dementsprechend auf kontrollierten Mustern in prospektiven randomisierten Studien verifiziert werden. Die demographischen Faktoren hatten keiner signifikanten Korrelation mit der iPPG Signalstärke. Die iPPG war geeignet kleine Signaländerungen assoziiert mit den erwarteten Änderungen der dermalen Perfusion bei einem großen chirurgischen Eingriff zu detektieren. Weitere Entwicklung der Technologie kann die Anwendung dieses nicht-invasive Monitoringsverfahren in der klinischen postoperativen Patientenversorgung ermöglichen.:1. Introduction 1 1.1. Coronary Artery Bypass Grafting (CABG) 1 1.1.1. Historical Overview 1 1.1.2. Coronary Grafts 3 1.1.2.1. Pedicled vs. Skeletonised Grafts 4 1.2. Plethysmography 5 1.2.1. Air-Displacement Plethysmography (APG) 5 1.2.2. Strain Gauge Plethysmography (SGP) 6 1.2.3. Impedance Plethysmography (IPG) 6 1.2.4. Photoplethysmography (PPG) 7 1.2.5. Imaging Photoplethysmography (iPPG) 8 1.3. Hypothesis and Aim of the Thesis 11 2. Methods 13 2.1. Study Setting and Patients 13 2.2. Camera and Technical Setup 14 2.3. Recording Area and Regions of Interest 15 2.4. Signal Processing 16 2.5. Statistical Analysis 17 3. Results 19 3.1. Descriptive Properties of the Data 19 3.2. Signal Strength in the Three Colour Channels 20 3.3. Choosing a Multilevel Model 21 3.4. The Effect of the Major Surgery on the Signal Strength in the Three Colour Channels 22 3.5. The Effect of the Unilateral Resection of the Internal Thoracic Artery 25 3.6. Results from the Model Fitted to the Data 27 3.7. The Effect of Cofactors 28 3.8. Data from the Subdivisions of the Chest 29 3.9. The Effect of the Surgical Technique 31 4. Discussion 34 4.1. Signal Strength in the Red, Green and Blue Colour Channels 34 4.2. Signal from the Entire Chest Area 36 4.3. Signal from the Subdivisions of the Chest 37 4.4. The Influence of the Surgical Technique on Signal Strength 38 5. Conclusion 39 6. Abstract 41 7. Zusammenfassung 42 8. References 44 9. Appendix 60 10. Acknowledgements 82 11. Resume 83 Anlage 184 Anlage 2 85

Stroke is an enormous global burden, six and a half-million people die fromstroke annually [1]. Effectively monitoring blood hemodynamic parameters suchas blood velocity and volume flow permits to help and cure people. This projectaimed to calibrate a custom-made wearable system for measuring cerebral bloodflow (CBF) using a photoplethysmography (PPG) sensor. The measurementswere validated using Doppler ultrasound as a reference method. Five (N=5)subjects (age = 24±1.41 years) were selected for the project. The PPG and Dopplerultrasound probe were placed above the left and right common carotid arteries(CCA), respectively. Measurements were taken simultaneously for 12 secondseach, with six consecutive measurements per subject and 2 time-synchronizedECG recordings. Subsequently, using an extraction algorithm the velocityenvelope (TAMEAN) was extracted from the Doppler image to obtain the bloodvolume flow (ml/min). After synchronization, the PPG signal output expressedin volts was calibrated to the corresponding volume, and a calibration curve wascreated.The extraction algorithm achieved remarkable results, with almost perfectcorrelation with the Doppler image reference, rT AM EAN =0.951 and rvolume=0.975demonstrating its reliability. Challenges encountered during postprocessingand synchronization highlighted the need for careful refinement in the projectframework. Despite successful signal processing and alignment techniques,calibration results were suboptimal due to synchronization difficulties andmotion artifacts. Limitations included impractical measurement locations andsusceptibility to movement artifacts. The calibration process did not yield theexpected outcomes and the project aim was not achieved. All the linear regressionmodels for each subject failed to accurately predict the volume flow based on themeasured voltages. Future work could focus on refining calibration procedures,improving synchronization methods, and expanding studies to include largercohorts. Although the wearable device was tested, the project’s goal was onlypartially achieved, underscoring the complexity of accurately measuring cerebralblood flow using PPG sensors. / Stroke är en enorm global börda, sex och en halv miljon människor dör av strokeårligen [1]. Effektiv övervakning av hemodynamiska blodparametrar såsomblodflödeshastighet och volymflöde gör det möjligt att hjälpa och bota människor.Detta projekt syftade till att kalibrera ett specialtillverkat bärbart system föratt mäta cerebralt blodflöde (CBF) med hjälp av en fotopletysmografisensor(PPG). Mätningarna validerades med Doppler-ultraljud som referensmetod. Fem(N=5) försökspersoner (ålder = 24±1.41 år) valdes ut för projektet. PPG- ochDoppler-ultraljudssonden placerades över vänster respektive höger gemensamhalsartär (CCA). Mätningar togs samtidigt i 12 sekunder vardera, med sexpå varandra följande mätningar per försöksperson och 2 tids-synkroniseradeEKG-inspelningar. Därefter användes en extraktionsalgoritm för att extraherahastighetskuvertet (TAMEAN) från Doppler-bilden för att få blodvolymflödet(ml/min). Efter synkronisering kalibrerades PPG-signalens utgång uttryckt i volttill motsvarande volym, och en kalibreringskurva skapades.Extraktionsalgoritmen uppnådde anmärkningsvärda resultat, med nästan perfektkorrelation med Doppler-bildreferensen, rT AM EAN =0.951 och rvolume=0.975,vilket visar dess tillförlitlighet. Utmaningar som uppstod under efterbearbetningoch synkronisering betonade behovet av noggrann förfining av projektetsramverk. Trots framgångsrik signalbehandling och justeringstekniker varkalibreringsresultaten suboptimala på grund av synkroniseringssvårigheteroch rörelseartefakter. Begränsningar inkluderade opraktiska mätplatser ochkänslighet för rörelseartefakter. Kalibreringsprocessen gav inte de förväntaderesultaten och projektmålet uppnåddes inte. Alla linjära regressionsmodellerför varje försöksperson misslyckades med att noggrant förutsäga volymflödetbaserat på de uppmätta spänningarna. Framtida arbete kan fokusera på att förfinakalibreringsprocedurer, förbättra synkroniseringsmetoder och utöka studier tillatt omfatta större kohorter. Även om den bärbara enheten testades, uppnåddesprojektets mål endast delvis, vilket understryker komplexiteten i att noggrantmäta cerebralt blodflöde med hjälp av PPG-sensorer.

Volume overload is a common feature in patients on haemodialysis (HD). This contributes significantly to the cardiovascular disease burden seen in these patients. Clinical assessments of the volume state are often inaccurate. Techniques such as interdialytic blood pressure, relative blood volume monitoring, bioimpedance are available to improve clinical effectives. However all these techniques exhibit significant shortcomings in their accuracy, reliability and applicability at the bed side. We evaluated the usefulness of a dual compartment monitoring technique using Continuous Segmental Bioimpedance Spectroscopy (CSBIS) and Relative Blood Volume (RBV) as a tool to assess hydration status and determine dry weight. We also sought to evaluate the role of Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP) as a volume marker in dialysis patients. The Retrospective analysis of a historical cohort (n = 376, 55 Diabetic) showed a significant reduction in post-dialysis weights in the first three months of dialysis (72.5 to 70kg, p<0.027) with a non-significant increase in weight between months 6-12. The use of anti-hypertensive agents reduced insignificantly in the first 3 months, increased marginally between months 3-6 and significantly increased over the subsequent 6 months. The residual urea clearance (KRU) fell and dialysis times increased. The cohort was very different to that dialysing at Tassin and showed a dissociation between weight reduction and BP control. This may relate to occult volume overload. CSBIS-RBV monitoring in 9 patients with pulse ultrafiltration (pulse UF) showed distinct reproducible patterns relating to extra cellular fluid (ECF) and RBV rebound. An empirical Refill Ratio was then used to define the patterns of change and this was related to the state of their hydration. A value closer to unity was consistent with the attainment of best achievable target weight. The refill ratio fell significantly between the first (earlier) and third (last) rebound phase (1.97 ± 0.92 vs 1.32 ± 0.2). CSBIS monitoring was then carried out in 31 subjects, whilst varying dialysate composition, temperature and patient posture to analyse the effects of these changes on the ECF trace and to ascertain whether any of these interventions can trigger a change in the slope of the ECF trace distinct to that caused by UF. Only, isovolemic HD caused a change in both RBV and ECF in some patients that was explained by volume re-distribution due to gravitational shifts, poor vascular reactivity, sodium gradient between plasma and dialysate and the use of vasodilating antihypertensive agents. This has not been described previously. These will need to be explored further. The study did demonstrate a significant lack of comparability of absolute values of RECF between dialysis sessions even in the same patient. This too has not been described previously. This is likely to be due to subtle changes in fluid distribution between compartments. Therefore a relative changes must be studied. This sensitivity to subtle changes may increase the usefulness of the technique for ECF tracking through dialysis. The potential of dual compartment monitoring to track volume changes in real time was further explored in 29 patients of whom 21 achieved weight reductions and were able to be restudied. The Refill Ratio decreased significantly in the 21 patients who had their dry weights reduced by 0.95 ± 1.13 kg (1.41 ± 0.25 vs 1.25 ± 0.31). Blood pressure changes did not reach statistical significance. The technique was then used to examine differences in vascular refill between a 36oC and isothermic dialysis session in 20 stable prevalent patients. Pulse UF was carried out in both these sessions. There were no significant differences in Refill Ratios, energy removed and blood pressure response between the two sessions. The core temperature (CT) of these patients was close to 36oC and administering isothermic HD did not confer any additional benefit. Mean BNP levels in 12 patients during isovolemic HD and HD with UF did not relate to volume changes. ANP concentrations fell during a dialysis session in 11 patients from a mean 249 ± 143 pg/ml (mean ± SD) at the start of dialysis to 77 ± 65 pg/ml at the end of the session (p<0.001). During isolated UF levels did not change but fell in the ensuing sham phase indicating a time lag between volume loss and decreased generation. (136±99 pg/ml to 101±77.2 pg/ml; p<0.02) In a subsequent study ANP concentrations were measured throughout dialysis and in the post-HD period for 2 hours. A rebound in ANP concentration was observed occurring at around 90 min post-HD. The degree of this rebound may reflect the prevailing fluid state and merit further study. We have shown the utility of dual compartment monitoring with CSBIS-RBV technique and its potential in assessing volume changes in real time in haemodialysis patients. We have also shown the potential of ANP as an independent marker of volume status in the same setting. Both these techniques merit further study.

Zielsetzung In den Industrieländern stellt der Schlaganfall nach kardiovaskulären und Krebs – erkrankungen die dritthäufigste Krankheitsgruppe dar. Im Hinblick auf die Therapie des akuten Schlaganfalls muss die bildgebende Diagnostik schnell und einfach das Ausmaß der zerebralen Ischämie beschreiben können. Ziel dieser Studie war die Einführung und die Validierung eines CT – Protokolls, welches die Diagnostik des akuten Schlaganfalls verbessern soll. Zu diesem CT – Protokoll gehören ein Nativ – CT des Schädels, eine CT – Perfusionsuntersuchung und eine CT – Angiographie. Zusätzlich wollte diese Arbeit herausfinden, ob es physiologische Unterschiede zwischen der grauen Substanz und der weißen Substanz gibt, deren Kenntnis entscheidend für die Auswertung von computertomographischen Perfusionsuntersuchungen sind. Material und Methoden Insgesamt wurden 101 Patienten (Alter von 14 – 94 Jahre, mittleres Alter 69 Jahre) mit einem 8 – bzw. 16 – Zeilen – MSCT (Light Speed Ultra oder Light Speed pro 16, GE Healthcare), die zur Abklärung einer zerebralen Ischämie zum CT vorgestellt wurden, untersucht. Zuerst wurde eine native CT – Serie akquiriert. In der Untersuchung der zerebralen Perfusion wurde eine 2 cm breite Schicht über 60 sec mit 20 intermittierenden Aufnahmen während einer Injektion von 40 ml Kontrastmittel (Iopromid, Jodgehalt von 370 mg) aufgezeichnet. Daran an schloss sich eine CT – Angiographie Untersuchung. Zur Bestimmung des regionalen zerebralen Blutflusses, des regionalen zerebralen Blutvolumens und der mittleren Verweildauer wurden definierte Messfelder (Regions of Interests, ROIs) bestimmt und mit der kontralateralen Hemisphäre verglichen. Ergebnisse Es konnte gezeigt werden, dass der regionale zerebrale Blutfluss und das Blutvolumen im Bereich der Hirnrinde höher sind als im Hirnmark. Insgesamt wurden 66 Patienten mit einer zerebralen Ischämie wurden gefunden. Bei 22 dieser Patienten konnte ein Infarktgeschehen in der Nativ – CT diagnostiziert werden. Diese Ischämien ließen sich auch in der CT – Perfusion mit reduziertem regionalem zerebralem Blutfluss und verlängerter mittlerer Verweildauer nachweisen. Zusätzlich fanden sich 44 Patienten von 101 Untersuchten, die in der CT – Perfusion ein Perfusionsdefizit aufwiesen. Bei diesen Patienten ließ sich kein entsprechendes Korrelat in der Nativ – CT nachweisen. Für 38 dieser 44 Patienten konnte eine CTA durchgeführt werden, wovon für 35 Patienten ein Korrelat zwischen der CT – Perfusion und der CTA gefunden werden konnte. Schlussfolgerung Die Ergebnisse dieser Arbeit zeigen, dass es physiologische Unterschiede zwischen der Hirnrinde und dem Hirnmark gibt, deren Kenntnis für die Bewertung computertomographischer Perfusionsuntersuchungen eine wesentliche Interpretationshilfe darstellt. In Bezug auf die Diagnostik des akuten Schlaganfalls mit der Nativ – CT konnte diese Arbeit zeigen, dass der Nachweis von Infarktfrühzeichen eingeschränkt ist. Mit Hilfe der CT – Perfusion ist es möglich, anhand von zerebralen Perfusionswerten den Schweregrad und die Ausdehnung der zerebralen Ischämie zu bestimmen. Die CT – Angiographie zeigt eine gute Korrelation zur CT – Perfusion, es lassen sich zuverlässig Gefäßverschlüsse darstellen. Im Hinblick auf das weitere Therapievorgehen geben diese Methoden eine wichtige Hilfestellung, etwa zur Überlegung, ob man eine Lysetherapie durchführen sollte oder nicht. / Purpose Stroke is the third – leading cause of death in developed countries, following cardiovascular disease and cancer. There is a need for an easily and rapidly performed technique to detect cerebral ischemia in the first hours after its occurrence. The purpose of this study was the introduction and validation of a Stroke protocol which includes an unenhanced CT scan, a CT Perfusion and a CT Angiography. Furthermore, the purpose of this study was to determine if there is a difference between Perfusion parameters in gray and white matter, which are necessary to know while performing perfusion maps. Data and Methodology A total of 101 patients (age range 14 – 94, average age 69 years) were examined using multiple row CT (8 / 16 row multiple detector, light ultra speed or light speed 16, GE medical systems) for diagnosing cerebral ischemia. First a series of native images was acquired. During the examination of cerebral perfusion a 2 cm wide slab was recorded for 60 sec with 20 intermittent scans following injection of 40 ml of contrast medium with an iodine content of 370 mg / ml. By defining Regions of Interests (ROIs) regional cerebral blood flow (CBF), regional cerebral blood volume (CBV) and mean transit time (MTT) were calculated. Results Physiological regional cerebral blood flow and cerebral blood volume in gray matter were higher than in white matter. In total 66 patients with a cerebral ischemia were found. The unenhanced CT detected 22 patients with cerebral ischemia, which were confirmed by CT Perfusion in all cases. These ischemic areas revealed reduced regional CBF and extended MTT. Furthermore an ischemia correlative was discovered by perfusion analysis for 44 patients (out of 101 investigated) where the extent of the cerebral ischemia had not been visible by unenhanced CT. For 38 out of 44 patients with cerebral ischemia we were able to perform a CTA. For 35 out of these 38 patients, we found a sizable correlation between perfusion maps and CTA. Conclusion There are physiological differences for CT Perfusion parameters between gray and white matter, which are necessary to know for the interpretation of perfusion maps. However, this examination was able to show that unenhanced CT is not always capable of showing early CT signs. With the help of CT perfusion it is possible to detect the extent of acute cerebral ischemia. Furthermore, CT Angiography shows a sizable correlation compared to CT Perfusion. In conjunction, these methods give important Information for the early diagnosis and the therapeutic strategy of ischemic brain injury.