Dissertationen zum Thema „Hemodynamické parametry“

Angina pectoris är bröstsmärta orsakat av myokardischemi, till följd av kranskärlsjukdom med eller utan stenoser eller icke kranskärlsjukdom. Arbetsprov är den vanligaste undersökningen för angina pectoris. Diffusa symtom och angina pectoris varianter utan stenoser med låg sensitivitet för elektrokardiografi (EKG) sänker den diagnostiska säkerheten i arbetsprov på kvinnor. Litteraturstudiens syfte var att utreda om hemodynamiska parametrar och riskbedömning med Pre-test sannolikhet (PTP) samt Dukes Löpbands Index (DTS, Dukes Treadmill Score) kan öka den diagnostiska säkerheten i arbetsprov på kvinnor. Inklusionskriterierna var vetenskapligt granskade kliniska studier på engelska, med information om etiskt godkännande eller samtycke. Snowballing metoden, PUBMED, MEDLINE och CINAHL användes. Studier som inkluderades i resultatet granskades återigen och jämfördes med varandra. Hemodynamiska parametrar, PTP och DTS ökar den diagnostiska säkerheten i arbetsprov på kvinnor. Denna diagnostiska säkerhet beror dock också på PTP metod, PTP riskgrupp, etnicitet och angina pectoris variant. Vidare forskning behövs om etnicitetspecifika PTP metoder, mekanismen bakom blodtrycksreaktionen, DTS på icke kranskärlsjukdomar samt metoder som kan skilja mellan olika icke kranskärlsjukdomar. Utan studier om Systematic COronary Risk Evaluation (SCORE) och Diamond Forrester Score (DFS) samt deras påverkan på arbetsprov, kan inte resultatet i litteraturstudien generaliseras till arbetsprov i Sverige.<br>Angina pectoris is chest pain and myocardial ischemia due to Coronary Artery Disease (CAD) or Non-Coronary Artery Disease (non-CAD). Exercise stress test (EST) is the most common diagnostic procedure for angina pectoris. Non-CAD, low sensitivity for exercise electrocardiography (ex-ECG) and diffuse symptoms lower the diagnostic accuracy for females. This review’s aim was to study whether haemodynamic parameters and risk stratifications with Pre-test probability (PTP) or Duke Treadmill Score (DTS) improves the diagnostic accuracy of EST for females. Inclusion criterions were English peer reviewed, clinical studies with mentioned ethical approval or consent. Snowballing, PUBMED, MEDLINE and CINAHL were used. Articles that were included in the results, were reviewed once again, and compared to one another. Hemodynamic parameters, PTP and DTS increase the diagnostic accuracy of EST in women. This diagnostic accuracy depends on PTP method, risk group, ethnicity, and angina pectoris variant. Further research regarding ethnic specific PTP methods, mechanism behind the blood pressure reaction, DTS for diagnosis of non-CAD and methods for differentiation of subtypes of non-CAD, would be valuable. Without studies about the Systematic Coronary Risk Evaluation (SCORE), Diamond Forrester Score (DFS), and their impact on ex-ECG, the result of this review cannot be generalized to ex-ECG in Sweden.

L’ablation partielle du foie est une chirurgie qui intervient dans le traitement des lésions du foie et lors d’une transplantation partielle de foie. Les relations entre l’hémodynamique du foie, son volume et ses fonctions restent à élucider pour mieux comprendre les causes des complications de ces chirurgies. Lors de la chirurgie, l’hémodynamique du foie est altérée suite à l’augmentation de la résistance au flux sanguin de l’organe. La régénération du foie semble dépendante des changements de débit et de pression dans la veine porte. D’autre part, comme le foie reçoit 25% du débit cardiaque, la chirurgie impacte la circulation sanguine globale. Dans ce contexte, le premier objectif est de mieux comprendre, grâce à des modèles mathématiques, l’influence de l’hépatectomie sur l’hémodynamique. Le second objectif est l’analyse de la perfusion et de la fonction du foie. Premièrement, la procédure chirurgicale, les conditions expérimentales ainsi que les mesures obtenues sont détaillées. Ensuite, les valeurs moyennes mesurées lors de douze chirurgies sont reproduites par un modèle de circulation entière, basé sur des équations différentielles ordinaires. Lors des différentes hépatectomies, des changements de forme de courbe sont observés. Un modèle de circulation entière, basée sur des équations 1D et 0D est proposé pour analyser ces changements. Ce travail pourrait permettre une meilleure compréhension des changements d’architecture du foie induits par l’hépatectomie. Puis, le transport dans le sang d’un composé ainsi que son traitement par le foie sont modélisés. Un modèle pharmacocinétique est développé et grâce aux mesures, les paramètres du modèle sont estimés<br>Major liver resection is being performed to treat liver lesions or for adult-to-adult living donor liver transplantation. Complications of these surgeries are related to a poor liver function. The links between liver hemodynamics, liver volume and liver function remain unclear and are important to better understand these complications. The surgery increases the resistance to blood flow in the organ, therefore it modifies liver hemodynamics. Large modifications of the portal vein hemodynamics have been associated with poor liver regeneration. Moreover the liver receives 25% of the cardiac outflow, therefore liver surgery may impact the whole blood circulation. In this context, the first goal is to investigate with mathematical models the impact of liver surgery on liver hemodynamics. The second goal is to study the liver perfusion and function with mathematical models. The first part describes the experimental conditions and reports the measurements recorded. Then, the second part focuses on the liver hemodynamics during partial hepatectomy. On one hand, the hemodynamics during several surgeries is quantitatively reproduced and explained by a closed-loop model based on ODE. On the other hand, the change of waveforms observed after different levels of liver resection is reproduced with a model of the global circulation, including 0D and 1D equations. This may contribute to a better understanding of the change of liver architecture induced by hepatectomy. Next, the transport in blood of a compound is studied. And a pharmacokinetics model and its parameter identification are developed to quantitatively analyze indocyanine green fluorescence dynamics in the liver tissue

The thesis includes a general introduction to monitoring and measurement of blood pressure of horses, the design of algorithms for pressure curve detection and the calculation of respiratory variabilities in mechanical ventilation under anaesthesia. The first two chapters focus on anatomy, on characteristics of blood flow and on vascular system. Then it deals with the measurement of blood pressure, monitoring of a horse under anaesthesia and it describes particular thermodynamic parameters. In the following part of the thesis, the methods of pressure curve detection are described. The last part contains the description of an algorithm designed for detection of pressure curve of horses in the environment of the program LabVIEW. The program calculates, displays and saves variabilities of systolic pressure, pulse volume, pressure amplitude, pulse frequency, peripheral resistance and vascular expansion from the detected values.

Thesis (M.A.)--West Virginia University, 1998.<br>Title from document title page. Document formatted into pages; contains viii, 101 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 53-60).

The goal of this study was to compare the morphological and hemodynamic characteristics of normal and remodeled vascular networks in the mouse gracilis muscle. To this end, previously developed models to assess flows and vascular branching were used to assess the normal and remodeled microcirculatory networks. The analysis revealed that the average individual vessel flow rates for vessels of similar caliber and total volumetric flow rates in the networks do not change for vessels of the same caliber after remodeling. Connectivity changes and average diameters primarily change in the larger arterioles after remodeling. A few correlations could be made between architectural and flow properties, however, further modifications in the analysis methods can make future correlations more effective. In order to improve the analysis a parameter sensitivity analysis tool (PSAT) was developed. The PSAT is helpful in teasing apart the individual effects of morphological parameters such as vessel connectivity, vessel diameters, and vessel lengths. In future, another important component that allows the investigator to exclusively alter vessel quantities for all the orders can be added to improve the PSAT.

The Banner University Medical Center's (BUMC) renal transplant program relies on the LifePort Kidney Transporter to optimize marginal kidney organs via hypothermic machine perfusion (HMP) prior to transplantation. Hemodynamic parameters produced by the device followed over the duration of support, combined with clinical experience, guide decisions in determining the acceptability of a donor kidney for implantation. Thus far, statistical evidence supporting ideal parameters remain undefined. The purpose of this study is to create a logistic model that will ascertain the post-implant sustainability of LifePort® supported kidneys and predict clinical outcomes. My hypothesis is that the statistical models constructed based on retrospective LifePort® parameters and clinical outcome data will successfully predict donor organ vascular health for transplantation and the optimal support duration. A successful model will contribute to increased efficiencies in the kidney transplant process as well as improved patient outcomes. An overview of the institution’s success was weighed using a survival analysis, with delayed graft function (DGF) as the endpoint. A logistic regression model and forecast model were built to predict the outcome for rejecting or accepting the organ for transplant, as well as to predict the hemodynamic parameters hours after the start of infusion. Results concluded a flow greater than 80 mL/min had a 90% probability of transplantation. The forecast model was capable of predicting flow for up to five hours. The calculated flow was in a 10 mL/min range of the actual flow, when up to one hour parameters were entered into the model. The study concluded practicality in the clinical setting, in kidney transplantation.

Cardiovascular disease is a large problem in the intensive care unit (ICU) due to its high prevalence in modern society. In the ICU, intensive monitoring is required to help diagnose cardiac and circulatory dysfunction. However, complex interactions between the patient, disease, and treatment can hide the underlying disorder. As a result, clinical staff must often rely on their skill, intuition, and experience to choose therapy, increasing variability in care and patient outcome. To simplify this clinical scenario, model-based methods have been created to track subject-specific disease and treatment dependent changes in patient condition, using only clinically available measurements. The approach has been tested in two pig studies on acute pulmonary embolism and septic shock and in a human study on surgical recovery from mitral valve replacement. The model-based method was able to track known pathophysiological changes in the subjects and identified key determinants of cardiovascular health such as cardiac preload, afterload, and contractility. These metrics, which can be otherwise difficult to determine clinically, can be used to help provide targets for goal-directed therapies to help provide deliver the optimal level of therapy to the patient. Hence, this model-based approach provides a feasible and potentially practical means of improving patient care in the ICU.

Laboratory tests are a primary resource for diagnosing patient diseases. However, physicians often make decisions based on a single laboratory result and have a limited perspective of the role of commonly-measured parameters in enhancing the diagnostic process. By providing a dynamic patient profile, the diagnosis could be more accurate and timely, allowing physicians to anticipate changes in the recovery trajectory and intervene more effectively. The assessment and monitoring of the circulatory system is essential for patients in intensive care units (ICU). One component of this system is the platelet count, which is used in assessing blood clotting. However, platelet counts represent a dynamic equilibrium of many simultaneous processes, including altered capillary permeability, inflammatory cascades (sepsis), and the coagulation process. To characterize the value of dynamic changes in platelet count, analytical methods are applied to datasets of critically-ill patients in (1) a homogeneous population of ICU cardiac surgery patients and (2) a heterogeneous group of ICU patients with different conditions and several hospital admissions. The objective of this study was to develop a methodology to anticipate adverse events using metrics that capture dynamic changes of platelet counts in a homogeneous population, then redefine the methodology for a more heterogeneous and complex dataset. The methodology was extended to analyze other important physiological parameters of the circulatory system (i.e., calcium, albumin, anion gap, and total carbon dioxide). Finally, the methodology was applied to simultaneously analyze some parameters enhancing the predictive power of various models. This methodology assesses dynamic changes of clinical parameters for a heterogeneous population of ICU patients, defining rates of change determined by multiple point regression and by the simpler fixed time parameter value ratios at specific time intervals. Both metrics provide prognostic information, differentiating survivors from non-survivors and have demonstrated being more predictive than complex metrics and risk assessment scores with greater dimensionality. The goal was to determine a minimal set of biomarkers that would better assist care providers in assessing the risk of complications, allowing them alterations in the management of patients. These metrics should be simple and their implementation would be feasible in any environment and under uncertain conditions of the specific diagnosis and the onset of an acute event that causes a patient's admission to the ICU. The results provide evidence of the different behaviors of physiologic parameters during the recovery processes for survivors and non-survivors. These differences were observed during the first 8 to 10 days after a patient's admission to the ICU. The application of the presented methodology could enhance physicians' ability to diagnose more accurately, anticipate changes in recovery trajectories, and prescribe effective treatment, leading to more personalized care and reduced mortality rates.

The Fontan repair is a three-stage palliative surgical procedure for single ventricle congenital heart diseases, ultimately resulting in the right heart bypass. This is accomplished by routing the systemic venous return directly to the lungs. Although this procedure reduces the mortality rate, its long-term outcome is still considered far from optimal. Over the years several modifications have been suggested, ultimately leading to the total cavopulmonary connection (TCPC), which is the current procedure of choice. A better understanding of the hemodynamics in the TCPC is critical for further optimization of the TCPC design and surgical planning, which may lead to improved surgical outcome. Recent experimental and numerical studies have focused on characterizing the fluid dynamics of the TCPC but to date no study has attempted to relate the geometry of the TCPC anatomies with their hemodynamic parameters. The present study therefore proposes to quantify the complex geometrical characteristics of patient-specific TCPC anatomies and correlate these characteristics with their hemodynamic efficiency. A technique using skeletonization approach is thus developed to achieve this goal. The centerline approximation of the TCPC geometry is used to extract main geometric parameters such as vessel area, curvature and offset. The developed methodology is then applied to characterize the shape of various TCPC templates including extra-cardiac (EC) and intra-atrial (IA) TCPCs, TCPCs with bilateral Superior Vena Cavae and geometries before the third stage. The obtained geometric parameters are then related to the TCPC hemodynamics, particularly to the power loss.

Submitted by Mario BC (mario@bc.ufrpe.br) on 2016-06-13T13:47:43Z No. of bitstreams: 1 Maria Albeline Silva de Lacerda.pdf: 765473 bytes, checksum: c89c99400df21609a6c505748d7ff4d1 (MD5)<br>Made available in DSpace on 2016-06-13T13:47:43Z (GMT). No. of bitstreams: 1 Maria Albeline Silva de Lacerda.pdf: 765473 bytes, checksum: c89c99400df21609a6c505748d7ff4d1 (MD5) Previous issue date: 2015-02-26<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES<br>The hemodynamic of uterine arteries and the adequate blood supply are important to the uterine physiology. The aim of this study was to determine patterns of flowmetry of uterine arteries using Doppler ultrasonography, in physiologic conditions (estrous cycle) and pathologic (pyometra). The animals (n=56) were distributed in heterogenic samples of each phase of estrous cycle (proestrous – n=7, estrous – n=5, dietrous – n= 19 and anestrous – n=13) or pyometra (n=12). All studied animals were submitted to ultrasound mode B exam, and media uterine artery was identified using Doppler tools. The pulsativity (IP), resistivity (IR) and systole/diastole (S/D) indexes and diastolic end (ED), systolic pick (PS), TAMAX, and heart rhythm (HR) were automatically determined by the ultrasound machine. The results showed that there is no significant difference between analyzed parameters and estrous cycle phases. However, comparing healthy animals in diestrus with pyometra, higher averages (P <0.05) of IP (8.54 ± 5.92) and IR (1.00 ± 0.11) was observed in the healthy compared to those with pyometra (PI = 4.49 ± 2.51 and 0.89 ± IR = 0.13). It was also observed higher mean TAMAX in pyometra (6.09 ± 15.09 cm/s) compared to healthy animals (2.72 ± 1.94 cm/s). With respect to the PS, a tendency (P = 0.07) of higher mean value was observed in pyometra (29.8 ± 15.35 cm/s) compared to healthy animals in diestrus phase (23.08 ± 8.61 cm/s). The other parameters showed no difference between groups. It was concluded that the phases of the estrous cycle do not interfere with hemodynamic parameters. Furthermore, the uterine artery blood flow has increased speed and decreased vascular resistance associated with pyometra.<br>A hemodinâmica das artérias uterinas e o adequado suprimento sanguíneo são importantes para a fisiologia úterina. Assim, objetivou-se estabelecer relações da condição fisiológica (em diferentes fases do ciclo estral) e patológica (piometra) com os parâmetros hemodinâmicos obtidos pela ultrassonografia Doppler colorido e pulsado, em artérias uterinas médias de cadelas. Foram utilizadas 56 cadelas, divididas em fases do ciclo estral: proestro (n=7), estro (n=5), diestro (n=19) e anestro (n=13); e piometra (n=12). Para o exame ultrassonográfico foi utilizado equipamento portátil (M5, Mindray), com sonda convexa (4–8 MHz), para medir automaticamente os índices de pulsatilidade (IP), resistividade (IR), relação sístole/diástole (S/D), velocidades final diastólica (ED), do pico sistólico (PS) e Velocidade Máxima Média do Ciclo (TAMAX), além da frequência cardíaca (HR). O útero foi identificado na avaliação modo-B e, em seguida acionado o modo Doppler, com ângulo de insonação ≤60º. Os resultados fluxométricos não mostraram diferenças entre as fases do ciclo estral. Porém, quando comparados animais em diestro saudável com os apresentando piometra, maiores médias (P<0,05) de IP (8,54±5,92) e IR (1,00±0,11) ocorreram nos saudáveis comparados aos com piometra (IP = 4,49±2,51 e IR = 0,89±0,13). Também foi observada maior média de TAMAX nos com piometra (6,09±15,09 cm/s) comparada aos saudáveis (2,72±1,94 cm/s). Com relação ao PS, foi observada uma tendência (P=0,07) de maior média nos com piometra (29,8±15,35 cm/s) comparados aos saudáveis na fase de diestro (23,08±8,61 cm/s). Os outros parâmetros não mostraram diferença entre os grupos. Conclui-se que as fases do ciclo estral não interferem nos parâmetros hemodinâmicos estudados. Por outro lado, a artéria uterina média apresenta aumento da velocidade de fluxo sanguíneo e diminuição da resistência vascular associada à piometra.

Aims: (1) Explore the physiological effect of renal denervation (RDN) (2) Explore the efficacy of distal denervation on blood pressure (BP) reduction in patients undergoing directly observed anti-hypertensive therapy (DOT) to minimise measurement bias (3) Evaluate the 6-month safety of distal denervation Methods: Patients with resistant hypertension were recruited and underwent assessment of drug compliance by assaying urinary drug levels. All subsequent measurements were recorded under DOT. Pre-denervation, office and ambulatory BP were measured, and patients underwent bilateral renal angiography and invasive measurement of aortic and renal arterial pressure and blood flow velocity. RDN was performed using the Symplicity Spyral catheter, denervating in the main renal arteries and each distal branch >3mm diameter. Invasive and non-invasive measurements were repeated 6-months post denervation under DOT. Results: 16 patients underwent denervation (age 63±12 years) with referral office SBP 180±18 mmHg. In total each patient received 22.6±5.0 ablations, 9.3±2.9 ablations in the main trunk and 13.3±4.8 ablations distally. At 6-months follow-up, overall unblinded 24-hour SBP reduction was -5.1±7.5 mmHg (p=0.020), with DBP reduction -3.4±4.9 mmHg (p=0.018). At 6-months follow-up an overall increase in renal blood flow velocity occurred at rest (1.91±3.51cm/s, p=0.04) and under identical sedation states (1.81±3.44 cm/s, p=0.05). Patients with the largest reduction in ambulatory SBP at 6-months had the largest increase in renal blood flow acutely after RDN (R 2=0.60, p < 0.001) and the largest decrease in renal resistance (R2=0.56, p < 0.001). Quantitative vessel angiography showed no significant change in any main or distal renal artery dimensions at 6-months. Conclusion: This unblinded study of distal RDN showed a significant reduction in ambulatory systolic and diastolic BP with no safety concerns at 6-months. These exploratory results suggest that acute changes in renal hemodynamics may be predictive of blood pressure response at 6-months follow-up.

Introduction: Cardiovascular diseases are the leading causes of death in the world. Included in this group, ischemic heart disease (IHD) is more frequent and responsible for high morbidity and mortality rates. Last two decades, a significant progress had happened to the recognition, management and treatment in patients with IHD, which determined a meaningful reduction in death rates, infarctions and recurrent ischemias. Despite technological advancement is increasing and its use of contemporary techniques, pain and anxiety cause a series of physiological repercussions that may impair the quality of clinical outcomes. Objectives: This study focused on identify in literature the music effect to pain, anxiety and hemodynamic parameters before and after percutaneous cardiac procedures. Method: This is a systematic review with meta-analysis that followed all recommendations of the Cochrane Collaboration and the verification items recommended by the tool Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA), as well as based on the Assessing the tool Methodological Quality of Systematic Reviews (AMSTAR). Results: 40 papers were found on a initial research, and 11 of them filled the inclusion criteria. These papers showed music is effective to reduce anxiety and hemodynamic parameters, and it was also confirmed in the meta-analysis which identified a meta-analytic estimate of difference among the average rates of 4.02 (95% HF: 2.48 to 6.68), even though it was chosen by the researcher. However, its effects on pain were inconclusive, which was also shown in the meta-analysis that identified a non-significant meta-analytic estimate of -0.01 (95% HF: -0.36 to 0.32) when VAS was used, although there is still a necessity for forthcoming studies. Due to the variability of genres and time of musical exposure, it was not possible to determine which music or for how long are the ideal to achieve more positive results on the outcomes of interest, but, it may presume soft, slow beats and instrumental songs show better results. Regarding how to execute it, the use of headphones is recommended as it allows the patient to focus its attention on the musical stimulus. Most of the studies obtained good methodological quality and low risk of bias. Whereas meta-analysis identified risk of publication bias for studies about anxiety. Conclusion: That systematic review identified music is effective to reduce anxiety and hemodynamic parameters. Nonetheless the results were inconclusive in order to determine association in pain reduction. These results may be useful in the development of recommendations for use of music in interventional cardiology.<br>Introdução: As doenças cardiovasculares são as principais causas de morte no mundo. Dentro desse grupo, as doenças isquêmicas do coração (DIC) são as mais frequentes e responsáveis por altos números de morbimortalidade. Nas últimas duas décadas ocorreram grandes avanços no reconhecimento, manejo e tratamento de pacientes com DIC, o que determinou significativa redução das taxas de óbito, infartos e isquemia recorrente. Apesar do crescente avanço tecnológico e da utilização de técnicas contemporâneas, a dor e ansiedade ocasionam uma série de repercussões fisiológicas que podem prejudicar a qualidade dos desfechos clínicos. Objetivos: Este estudo tem como objetivo identificar na literatura o efeito da música sob a dor, ansiedade e parâmetros hemodinâmicos antes e após procedimentos cardíacos percutâneos. Método: Trata-se de uma revisão sistemática com metanálise que seguiu todas as recomendações da Colaboração Cochrane e seguindo os itens de verificação preconizados pela ferramenta Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), bem como se baseou na ferramenta Assessing the Methodological Quality of Systematic Reviews (AMSTAR). Resultados: Foram encontrados 40 artigos na busca inicial dos quais 11 preencheram os critérios de inclusão. Estes demonstraram que a música é efetiva na redução da ansiedade e dos parâmetros hemodinâmicos, sendo ainda confirmada na metanálise que identificou uma estimativa metanalítica de diferença nas médias padronizadas de 4.02 (IC 95%: 2.48 a 6.68), mesmo sendo escolhida pelo pesquisador. Contudo, seus efeitos sobre a dor foram inconclusivos, o que também foi mostrado na metanálise que identificou uma estimativa metanalítica não significativa de -0,01 (IC 95%: -0,36 a 0,32) quando se utilizou a EVA, sendo necessário a realização de estudos futuros. Devido a variabilidade dos estilos e tempo de exposição musical, não se pôde determinar qual a música e o tempo de exposição ideais para alcançar resultados mais positivos sobre os desfechos de interesse, mas infere-se que aquelas de batidas suaves, sem letras e lentas presentem melhores efeitos. Quanto à forma de aplicação, a utilização de fones de ouvido é recomendada, pois permite que o paciente foque sua atenção no estimulo musical. A maior parte dos estudos obteve boa qualidade metodológica com baixo risco de viés. Já a metanálise identificou risco de viés de publicação para os estudos que abordaram ansiedade. Conclusão: Esta revisão sistemática identificou que a música é efetiva na redução da ansiedade e dos parâmetros hemodinâmicos. Entretanto, os resultados foram inconclusivos para determinar associação na redução da dor. Estes resultados podem ser úteis no desenvolvimento de recomendações para utilização da música na cardiologia intervencionista.<br>Aracaju, SE

Made available in DSpace on 2016-06-02T19:22:11Z (GMT). No. of bitstreams: 1 6251.pdf: 2137348 bytes, checksum: c2a00dd9baf672490949a036d79336a8 (MD5) Previous issue date: 2014-09-26<br>Universidade Federal de Minas Gerais<br>Literature reports that genetic polymorphisms may determine important modulations on athletes phenotypes, such as height, cardiovascular adaptations, use of energy substrates as well as electrolyte and hormonal balance. It is possible that individuals who express the alpha actinin 3 gene (ACTN3; ancestral homozygous RR or heterozygous RX) may offer advantages in movements that require strength and fast twitch compared with individuals with XX genotype. ACTN3 is a sarcomeric Z line component, which is important for the actin filaments anchorage and myofibrillar arrangement maintenance. Regarding AMP deaminase (AMPD1) polymorphism, it has been reported that athletes with the mutant allele (allele T) may present disadvantages in intense and repetitive physical activities, since the enzyme encoded by this gene is responsible for the ATP resynthesis after intense muscle contractions. Polymorphisms in the angiotensin converting enzyme gene (ACE; deletion allele D) and angiotensinogen (AGT; mutated allele T) may favor athletes in activities requiring strength, due to the fact of higher Angiotensin (Ang) II circulating levels. The present study investigated whether polymorphisms in ACTN3, AMPD1, ACE and AGT genes, alone or in combination, may influence the hemodynamic and cardiac parameters as well as soccer players performance during physical tests such as jump, speed and endurance. Saliva from 220 young professional soccer players (14-20 years) from São Paulo Futebol Clube (Brazil) was collected. Then, total DNA was extracted from saliva and polymerase chain reaction (PCR) was used for genotyping of athletes. To provide more reliability to the study, athletes were also separated according to their age. Before this separation, the athletes with the mutation in the ACTN3 gene jumped lower heights in Squat Jump test (SJ) (RR/RX = 33.64 ± 5.31 vs XX = 30.81 ± 4.51 cm, p = 0.007), as well as in the Under (U)-15 (RR/RX = 34.88 ± 5.39 vs XX = 30.59 ± 4.07 cm, p = 0.04) and U- 17 (RR/RX = 35.82 ± 4.35 vs XX = 30.24 ± 5.16 cm, p = 0.01) categories. In the Counter Movement Jump test (CMJ), RR/RX jumped 37.26 ± 5.72 cm and XX 34.12 ± 4.84 cm (p = 0.005). In the U-17 category, RR/RX jumped 38.56 ± 5.69 cm and XX 32.90 ± 6.06 cm (p = 0.02). In the Counter Movement Jump with arms (CMJb) test, with all athletes, RR/RX jumped 43.85 ± 6.38 cm and XX 40.61 ± 5.06 cm (p = 0.009). The speed test (30 m) showed in the U-17 category that RR/RX were faster than the XX athletes (RR/RX = 4.13 ± 0.13 vs XX = 4.27 ± 0 17 s, p = 0.04). Regarding AMPD1 gene, no significant difference was found in the jumps and endurance tests, but in the speed test (10 m), CC athletes were faster than those with CT/TT genotypes (CC = 1.53 ± 0.19 vs CT/TT = 1.62 ± 0.16 s, p = 0.04). Athletes with DD genotype (ACE) jumped significantly higher in CMJb test compared with ID/II (DD = 44.37 ± 6.22 vs ID/II = 42.35 ± 6.23 cm, p = 0.02). In the U-17 category, DD athletes jumped higher in SJ (DD = 38.04 ± 5.00 vs ID/II = 33.16 ± 4.11 cm, p = 0.01), CMJ (DD = 41.03 ± 5.64 vs ID/II = 35.76 ± 4.26 cm, p = 0.01) and CMJb (DD = 48.62 ± 5.98 vs ID/II = 42.42 ± 4.81 cm, p = 0.007). In the endurance test, athletes from U-16 category with genotypes ID/II, traveled greater distances compared with DD (ID/II = 1.467 ± 63.70 vs DD =1.244 ± 64.25 m, p = 0.04). The DD genotype also favored athletes in speed test (30 m), either for players from U-14 category (DD = 4.29 ± 0.19 vs ID/II = 4.40 ± 0.16 s, p = 0.02) or for the U- 17 category (DD = 4.07 ± 0.15 vs ID/II = 4.20 ± 0.13 s, p = 0.04). AGT gene polymorphism did not influence the performance in the tests, but athletes with the mutant genotype (TT) showed greater left ventricle (LV) hypertrophy (114.6 ± 105.2 g/m2 for TT, 92.16 ± 18.88 g/m2 for MT and 94.78 ± 21.08 g/m2 for MM, p = 0.04) without any change in cardiac and other hemodynamic parameters. Greater LV hypertrophy (DD = 96.95 ± 19.96, ID = 90.14 ± 21.58 and II = 91.67 ± 21.09 g/m2, p = 0.04) and higher ejection fraction (DD = 71.73 ± 7.71, ID = 69.48 ± 6.51 and II = 68.59 ± 5.72 %, p = 0.02) were also found in the athletes with the DD genotype. The analysis of genes combination on athletic performance, when characteristics of strength and muscle fast twitch in the ranking by score were taken into account, showed that athletes with the highest scores (5-8) jumped higher than those with lower scores (1-4) in SJ test (score 5 to 8 = 33.80 ± 5.16 vs score 1 to 4 = 31.60 ± 5.22 cm, p = 0.01) and CMJ test (score 5 to 8 = 43.90 ± 6.85 vs score 1 to 4 = 41.87 ± 5.98 cm, p = 0.04). The present results suggest that RR/RX (ACTN3), DD (ACE) and CC (AMPD1) genotypes may benefit soccer players in activities requiring strength and fast twitch. In addition, ID/II genotypes seem to provide more resistance to athletes in endurance activity. In the future, the organization, standardization and ethical responsibility will be required in the management of these genetic markers for use in athletes training process.<br>Há relatos na literatura de que os polimorfismos genéticos podem determinar importantes modulações nos fenótipos dos atletas, como por exemplo, estatura, adaptações cardiovasculares, utilização dos substratos energéticos bem como balanço eletrolítico e hormonal. É possível que indivíduos que expressem o gene alfa actinina 3 (ACTN3; genótipos RR para homozigotos ancestrais ou RX para heterozigotos) possam apresentar vantagens em movimentos que exijam força e rápida contração muscular quando comparados aos indivíduos com genótipo XX. Isto pelo fato de a ACTN3 ser um componente da linha Z sarcomérica, o qual é importante para o ancoramento dos miofilamentos de actina e manutenção do arranjo miofibrilar. Com relação ao polimorfismo no gene AMP deaminase (AMPD1), tem sido relatado que os atletas que apresentam o alelo mutado (alelo T) possam apresentar desvantagens em atividades físicas intensas e repetitivas, uma vez que a enzima codificada por este gene é responsável pela ressíntese de ATP muscular após intensas contrações. Os polimorfismos nos genes da enzima conversora de angiotensina (ECA; alelo de deleção D) e angiotensinogênio (AGT; alelo T mutado) podem favorecer os atletas em atividades que requeiram força, isto por conta dos maiores níveis circulantes de Angiotensina (Ang) II. Este estudo investigou se os polimorfismos nos genes ACTN3, AMPD1, ECA e AGT, combinados ou não, podem influenciar nos parâmetros hemodinâmicos, cardíacos e no desempenho de jogadores de futebol em testes físico-motores tais como saltos, velocidade e endurance. Foi coletada a saliva de 220 jogadores jovens (14 a 20 anos) das categorias de base profissional do São Paulo Futebol Clube, Brasil. Em seguida, o DNA total foi extraído a partir da saliva e ensaios de reação em cadeia da polimerase (PCR) foram utilizados para a genotipagem dos atletas. Para conferir mais fidedignidade ao estudo, os atletas foram também separados de acordo com a idade. Antes desta separação, os atletas com a mutação no gene ACTN3 saltaram menos no teste Squat Jump (SJ) (RR/RX = 33,64 ± 5,31 vs XX = 30,81 ± 4,51 cm, p = 0,007), assim como nas categorias Sub-15 (RR/RX = 34,88 ± 5,39 vs XX = 30,59 ± 4,07 cm, p = 0,04) e Sub-17 (RR/RX = 35,82 ± 4,35 vs XX = 30,24 ± 5,16 cm, p = 0,01). No teste Counter Movement Jump (CMJ) os RR/RX saltaram 37,26 ± 5,72 cm e os XX 34,12 ± 4,84 cm (p = 0,005). Na categoria Sub-17, detectou-se que os RR/RX saltaram 38,56 ± 5,69 cm e os XX 32,90 ± 6,06 cm (p = 0,02). No teste Counter Movement Jump com os braços (CMJb), com todos os atletas, os RR/RX saltaram 43,85 ± 6,38 cm e os XX 40,61 ± 5,06 cm (p = 0,009). O teste de velocidade de deslocamento (30 m) revelou, na categoria Sub-17, que os RR/RX foram mais velozes que os atletas XX (RR/RX = 4,13 ± 0,13 vs XX = 4,27 ± 0,17 s, p = 0,04). Com relação ao gene AMPD1, nenhuma diferença significativa foi encontrada nos testes de saltos e endurance, porém no teste de velocidade de deslocamento (10 m), os atletas CC foram mais velozes comparados àqueles com genótipos CT/TT (CC = 1,53 ± 0,19 vs CT/TT = 1,62 ± 0,16 s, p = 0,04). Atletas com o genótipo DD (ECA) saltaram significativamente mais alto no teste CMJb comparados aos ID/II (DD = 44,37 ± 6,22 vs ID/II 42,35 ± 6,23 cm, p = 0,02). Na categoria Sub-17, os atletas DD saltaram mais nos testes SJ (DD = 38,04 ± 5,00 vs ID/II = 33,16 ± 4,11 cm, p = 0,01), CMJ (DD = 41,03 ± 5,64 vs ID/II = 35,76 ± 4,26 cm, p = 0,01) e CMJb (DD = 48,62 ± 5,98 vs ID/II = 42,42 ± 4,81 cm, p = 0,007). No teste de endurance, atletas da categoria Sub-16 com os genótipos ID/II, percorreram maiores distâncias comparados aos DD (ID/II = 1.467 ± 63,70 vs DD = 1.244 ± 64,25 m, p = 0,04). O genótipo DD do gene da ECA também favoreceu os atletas no teste de velocidade (30 m), pois jogadores da categoria Sub-14 com o referido genótipo foram mais velozes comparados aos ID/II (DD = 4,29 ± 0,19 vs ID/II = 4,40 ± 0,16 s, p = 0,02). O mesmo pôde ser visto para a categoria Sub-17 (DD = 4,07 ± 0,15 vs ID/II = 4,20 ± 0,13 s, p = 0,04). O polimorfismo no gene AGT parece não influenciar o desempenho nos testes propostos, porém atletas com o genótipo mutado (TT) apresentaram maior hipertrofia do ventrículo esquerdo (VE; 114,6 ± 105,2 g/m2 para TT; 92,16 ± 18,88 g/m2 para MT e 94,78 ± 21,08 g/m2 para MM, p = 0,04), sem qualquer outra alteração nos outros parâmetros cardíacos e hemodinâmicos. Maior hipertrofia do VE (DD = 96,95 ± 19,96; ID = 90,14 ± 21,58 e II = 91,67 ± 21,09 g/m2, p = 0,04) e maior fração de ejeção (DD = 71,73 ± 7,71; ID = 69,48 ± 6,51 e II = 68,59 ± 5,72 %, p = 0,02) também foram encontradas nos atletas com o genótipo DD. A análise da combinação dos genes no desempenho dos atletas, quando se privilegiaram as características de força e explosão muscular no ranqueamento por escore, revelou que os atletas com os escores mais altos (5 a 8) saltaram mais comparados àqueles com escores mais baixos (1 a 4) no teste SJ (Escore 5 a 8 = 33,80 ± 5,16 vs Escore 1 a 4 = 31,60 ± 5,22 cm, p = 0,01) e no teste CMJ (Escore 5 a 8 = 43,90 ± 6,85 vs Escore 1 a 4 = 41,87 ± 5,98 cm, p = 0,04). Os resultados do presente estudo sugerem que os genótipos RR/RX (ACTN3), DD (ECA) e CC (AMPD1) podem beneficiar os jogadores de futebol em atividades que requeiram força e rápida contração muscular. Além disso, os genótipos ID/II parecem proporcionar mais resistência aos atletas em atividade de endurance. Para o futuro, serão necessárias organização, padronização e responsabilidade ética no manejo desses dados genéticos para a utilização no processo de formação de atletas.

With the increasing number of patients suffering from some metabolic diseases leading to the development of atherosclerosis there is an urgent need for early diagnosis of the scale. If we think about disability sclerotic cerebral arteries, the optimal method of investigation is duplex ultrasonography, which is relatively inexpensive and friendly for the patient. To assess not only the structure and extent of atherosclerotic plaque, but also to assess the extent of any narrowing of the arteries and to evaluate the hemodynamic impact of structural changes present. It is an ideal candidate for screening in primary or secondary prevention of stroke, as well as for regular checks dispensarized patients. Knowledge of normal hemodynamic conditions in the cervical carotid stream is necessary in the assessment of various pathological conditions. This paper seeks to offer the most comprehensive view on the issue of carotid stenoses ultrasonografisty eyes. For practical reasons we focus on localized stenosis in the carotid bulb, the number is high above the stenosis in other locations.

Nos últimos anos, diversos estudos realizados apontam a rigidez arterial como a maior causa de risco cardiovascular. Este parâmetro hemodinâmico tem sido amplamente investigado, aparecendo normalmente associado ao aumento da pressão arterial e ao envelhecimento. A medição da velocidade da onda de pulso, VOP, é considerada o método padrão para avaliar a rigidez arterial. Actualmente, apesar de este ser bem aceite pela comunidade médica/científica, os equipamentos que se encontram disponíveis no mercado são bastante onerosos e difíceis de operar, mesmo por profissionais da área. Pelas razões apontadas, é difícil encontrar estes aparelhos em consultórios médicos e em unidades clínicas/hospitalares. Foi esta a problemática que motivou o estudo de novos métodos para a determinação da rigidez arterial, bem como de outros parâmetros hemodinâmicos associados a esta, como é o caso do índice de aumentação, AIx, índice braço-pé, IBP, entre outros. Este trabalho centrou-se no desenvolvimento de novas perspectivas de utilização para sensores piezoeléctricos, com circuitos de acondicionamento de sinal e testes relacionados, assim como no desenvolvimento de uma ferramenta informática de análise. Foram também realizados testes em humanos, apenas com o objectivo de demonstrar que os resultados são consistentes e reprodutíveis. Questões relacionadas com a aquisição e processamento de sinal, que futuramente serão descritas, foram igualmente levantadas e analisadas durante o trabalho. Em adiantamento, pode-se afirmar que, em primeiro, o módulo NI USB 6210© demonstrou ser uma boa opção e, por último, que o uso do programa MatLab® providenciou um ambiente de análise ideal, assim como as curtas rotinas desenvolvidas e requeridas para um ano de projecto.

No mundo actual, há uma enorme preocupação em desenvolver e explorar métodos capazes de detectar parâmetros fisiológicos que indiciem riscos ou problemas de saúde. No caso das doenças cardiovasculares, principal causa de morte nos países desenvolvidos, a rigidez arterial é o principal factor de risco. A velocidade de onda de pulso (VOP), ou seja, a velocidade com que a onda de pressão se propaga ao longo de uma artéria, é considerada o método padrão para avaliar a rigidez arterial. Os equipamentos que se encontram disponíveis no mercado são muito dispendiosos, difíceis de operar e com limitações. Este projecto de investigação centrouse no desenvolvimento de novas sondas, baseadas em sensores piezoeléctricos, capazes de permitir o acesso a diferentes parâmetros hemodinâmicos de forma simples e nãoinvasiva, em especial a sonda dupla, cujo grande potencial seria o cálculo da VOP. Foram construídas duas bancadas de teste que reproduzem as propriedades do sistema cardiovascular, e que permitiram a caracterização dos sensores e validação dos algoritmos desenvolvidos. As sondas criadas permitem obter a onda de pressão original através do algoritmo de Desconvolução. Para a sonda dupla, demonstrouse que esta tem resolução temporal para os estudos da VOP. O presente trabalho pretende descrever aspectos ligados à arquitectura das sondas, as diferentes versões exploradas, os algoritmos criados e os resultados obtidos.

A associação entre a rigidez arterial e as doenças cardiovasculares é um importante tópico de investigação com vista ao conhecimento da condição hemodinâmica dos pacientes. Vários índices podem ser um indicador da rigidez arterial, a velocidade da onda de pulso (VOP) e o índice de aumentação, são dois exemplos. Outros tópicos relacionados com as ondas reflectidas são um poderoso indicador neste contexto. Nesta tese são usados sensores piezoeléctricos para registar a forma da onda de pressão e algoritmos capazes de fornecer informação acerca de certos parâmetros hemodinâmicos, em alternativa aos dispositivos disponíveis no mercado. A principal motivação para procurar uma alternativa a estes dispositivos relaciona-se com o preço a que estes estão disponíveis. O desenvolvimento de uma bancada de teste capaz de simular as principais características da dinâmica do sistema arterial constitui uma poderosa ferramenta com vista ao desenvolvimento de sondas e validação dos algoritmos usados para a extracção de informação clinicamente relevante. O índice de aumentação foi o principal parâmetro estudado, este foi avaliado por um novo algoritmo baseado na transformada de wavelet, em comparação com outros referenciados na literatura. O seu desempenho foi testado em pulsos a partir de uma simulação realista baseadas em exponenciais, bem como em dados experimentais obtidos em testes “clínicos” com alguns voluntários.

Tese de doutoramento em Engenharia Biomédica, apresentada à Faculdade de Medicina da Universidade de Coimbra<br>A grande incidência das doenças cardiovasculares no mundo estimulou a procura de novas soluções que permitam a deteção precoce de processos patológicos associados a este tipo de doenças. Especial ênfase foi dada a métodos que permitem a monitorização da pressão arterial e da forma de onda de pressão arterial, que fornecem uma ferramenta precisa que complementa o diagnóstico baseado em múltiplos parâmetros. Da análise das características da forma de onda da pressão arterial, e da sua velocidade de propagação, podem ser extraídas importantes parâmetros clínicos de modo a avaliar o risco cardiovascular, a adaptação vascular e a eficácia terapêutica. O uso de múltiplos parâmetros permite minimizar erros na estimação de um dos parâmetros. As soluções emergentes para a monitorização cardiovascular têm-se afastado de tecnologias invasivas e caras para soluções não invasivas e sem contacto. Neste sentido, os sistemas ópticos apresentam uma grande vantagem devido ao grande progresso tecnológico sofrido nas últimas décadas. A natureza de não contacto desta tecnologia permite a medição sem distorção da forma da onda arterial ultrapassando as limitações dos aparelhos comerciais usados para este tipo de avaliação. O principal objetivo deste trabalho consistia em demonstrar que é possível adquirir através do uso de uma metodologia óptica, a forma da onda de pressão arterial sem contacto, com uma configuração que permite medir a velocidade onda de pulso (VOP) local e determinar os principais parâmetros usando algoritmos dedicados. Foram desenvolvidos quatro protótipos: três baseados em luz não-coerente e um em luz coerente. As sondas foram desenvolvidas usando uma configuração comum, composta por dois fotodetectores distanciados de 2 cm, o que garante a deteção da onda de pulso em dois pontos distintos e permite uma determinação rigorosa do tempo de trânsito. Nas sondas de luz não-coerente foram testados três fotodetectores: fotodíodos de avalanche, fotodíodos planares, e fotodíodos de efeito lateral (LEP). Os componentes do sistema óptico (protótipos das sondas e caixa de aquisição) foram desenhados com as características físicas que permitem o uso clínico, como a portabilidade, o tamanho compacto, leves, de baixo consumo e com materiais de baixo custo, ergonómicas para o operador e confortáveis para o paciente, de modo a serem consideradas uma solução interessante para a comercialização. Os testes in vivo permitiram a seleção da melhor combinação sonda/algoritmo para a determinação da PWV, usando o método da correlação e a sonda baseada em fotodíodos planares que demonstrou ser mais eficiente para a aquisição de sinais em humanos. O sistema óptico desenvolvido mostrou boa reprodutibilidade na avaliação inter e intra-operador. Um estudo alargado foi desenvolvido em 131 sujeitos jovens, com um valor médio PWV de 33.33±0.72 ms-1, confirmando o seu aumento com a idade. O teste comparativo entre a onda de distensão medida com o sistema óptico na carótida e o perfil da onda de pressão adquirida invasivamente por um cateter intra-arterial mostrou uma grande correlação entre as duas ondas (valor médio de 0.958), validando a capacidade das sondas ópticas para estimar a forma da onda de pulso de modo não-invasivo e sem contacto. A sonda óptica baseada em luz coerente foi testada em combinação com algoritmos de processamento de sinal baseados nos métodos short time Fourier transform e empirical mode decomposition, demonstrando ser capaz de determinar os pontos característicos da forma de onda com baixo erro (menor que 5ms). Uma configuração alternativa foi testada usando um fotodetector com uma maior área que permitiu obter o efeito de self-mixing fora da cavidade laser. Esta característica abriu a possibilidade de construir uma nova sonda adaptada a esta nova técnica de modo a melhorar a qualidade do sinal e permitir uma aplicação biomédica. Globalmente, os resultados obtidos para a metodologias desenvolvidas (protótipos e ferramentas de processamento de sinal associados) mostraram ser possível de medir a onda de pulso arterial na carótida, para determinar vários parâmetros clínicos e avaliar a condição cardiovascular.<br>The world wide incidence of cardiovascular diseases (CVDs), has spurred the research efforts targeting new solutions that may be able to perform an early detection of the pathological processes associated with these diseases. Special emphasis has been given to the methods that allow the monitoring of the blood pressure and the arterial pulse waveform, thus providing a more precise tool to complement the diagnosis process based on a multi-parameter assessment approach. From the analysis of arterial pulse pressure waveform features, and its propagation velocity, important clinical parameters can be extracted in order to evaluate the CVD risk, the vascular adaptation and the therapeutic efficacy. The use of multiple parameters allows to minimize the error when compared to the approach where a subject is classified solely based on a single parameter. Emerging trends in cardiovascular monitoring are moving away from invasive and costly technologies towards non-invasive and low-cost solutions. In this sense, optical solutions represent a great advantage due to the immense technological progresses observed in the recent decades. The truly non-contact nature of optical techniques allows measurements without distortion in the shape of the pulse curve, which is one of the main limitations of the current commercial devices used in hemodynamic parameters assessment. The main objective of this work consists in demonstrating that with an optical system it is possible to acquire the arterial pulse waveform with a configuration that allows the local pulse wave velocity (PWV) measurement and the determination of the most important clinical parameters using dedicated algorithms, without physical contact with the skin of the patient. Four prototypes were developed: three based in non-coherent light and one with coherent light. All the developed optical probes have a common design structure. They include two identical photodetectors placed 2 cm apart from each other to guarantee accurate determination of local pulse transit time. Relatively to the non-coherent light probes three different probes base on photodetectors were tested: an avalanche photodiode, a planar photodiode and a lateral effect photodiode (LEP). The optical system components (probe prototypes and acquisition box) were designed to meet specific requirements that allow the clinical use, such as portability, compact size and low weight, low cost, limited power consumption, ergonomics and easy user-interface in order to be considered as an interesting solution for commercial purposes. The in vivo tests allowed the selection of the best algorithm and probe combination to determine PWV: cross-correlation algorithm and the probe with planar photodiodes demonstrated to be the most efficient. This system showed good reproducibility, as evaluated by both inter-operator and intra-operator analysis. A large study was performed in 131 young subjects, obtaining a mean value for PWV of 3.33±0.72 ms-1, thus confirming its significant increase with age. A comparative test between the distension waveform measured with the optical probe at the carotid artery and the invasive profile of the pulse pressure acquired by an intra arterial catheter showed a strong correlation (mean value of 0.958), and validates the ability of this non-invasive device to estimate the arterial pulse waveform. Also a coherent light probe was developed and tested using several processing techniques based on the short time Fourier transform and empirical mode decomposition algorithm. This approach demonstrated the ability to determine the main feature points in the waveform with low error in the pulse transit time determination (less than 5ms). An alternative configuration for the Doppler effect-based probe was tested, using a photodetector with a larger area in order to obtain the self-mixing effect outside the laser cavity. This feature opened the possibility to improve the quality of the signal which may foresee potential future biomedical applications. Globally, the results obtained with the developed methodologies (prototypes and associated algorithmic tools) proved that it is possible to measure the arterial pulse waveform in the carotid artery, to determine several clinical parameters and assess the cardiovascular condition with optical technology.<br>Fundação para a Ciência e Tecnologia - SFRH / BD / 79334 / 2011

碩士<br>國立臺灣大學<br>電機工程學研究所<br>89<br>In recent years, ultrasonic contrast agents have been widely used to enhance ultrasonic backscattered signals in various imaging modes. However, research on estimating hemodynamic parameters based on traditional indicator-dilution theory with ultrasonic contrast agents is still at an early stage, due to complications encountered in clinical situations. In this thesis, we experimentally investigate the validity of applying the dilution theory under various flow conditions. Both a spherical ball system and a perfusion phantom system are explored. Parameters derived from experimental data and deconvolution of input and output curves are compared to theory. Results show that experimental parameters are close to theoretical values only in some specific situations. Nonetheless, when the experimental system deviate from an ideal system, qualitative analysis is still possible but flow quantification requires further investigation.

Ao longo dos últimos anos, a rigidez arterial tem tido um papel importante na avaliação e prevenção de doenças cardiovasculares que, segundo a Organização Mundial de Saúde, representam 30% de todas as mortes globais. A rigidez arterial descreve as propriedades das artérias e pode ser avaliada através de alguns parâmetros hemodinâmicos como a velocidade de onda de pulso (VOP). No Grupo de Electrónica e Investigação, algumas tecnologias têm sido desenvolvidas de modo a avaliar esses parâmetros hemodinâmicos de forma não invasiva, robusta e barata. Estas tecnologias são baseadas em acelerómetros, sensores piezoelectricos (PZ), sensores ópticos e em sensores acústicos. Este trabalho pretende dar continuidade ao estudo da avaliação de parâmetros hemodinâmicos usando uma nova sonda baseada em sensores PZ e software adequado. Estes elementos permitem analisar o sinal PZ e visualizar a onda de pressão arterial. A nova sonda PZ foi caracterizada em dois modelos de bancada e a partir de sinais adquiridos na artéria carótida comum em humanos. De modo a avaliar a VOP local foram também desenvolvidos e implementados alguns algoritmos de processamento de sinal. Os modelos de bancada permitiram simular propriedades clínicas do sistema cardiovascular em laboratório. Estes foram uma poderosa ferramenta permitindo mostrar que: os sensores PZ não sofrem efeito de crosstalk, através da resposta a impulso de ambos é possível recuperar a onda original pelo método da desconvolução e a resolução temporal determinada pelo algoritmo de detecção de amplitude mínima é de 1.5 ms. Alguns ensaios clínicos têm sido realizados pelos nossos colaboradores, representando um passo importante na validação da sonda em um grande número de pacientes. A partir do ensaio clínico realizado num pequeno grupo de voluntários saudáveis, a VOP local foi determinada usando dois algoritmos. Os valores da VOP local variaram de 2.03 – 7.22 m/s e com desvio padrão a variar de 0.74 – 6.17 m/s. Palavras-chave: Doenças Cardiovasculares, Rigidez arterial, arteria carotida comum, Sonda dupla piezoelétrica, Velocidade de onda de pulso (VOP) local, teste de bancada, resolução temporal.

Tese de doutoramento em Física, na Especialidade de Física Tecnológica, apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra<br>As doenças cardiovasculares (DCV) são a principal causa de morte mundial, e a rigidez arterial, em particular, é considerada um importante factor de risco. Esta tese encontra a sua motivação no impacto previsível que um instrumento preciso, não invasivo e fácil de usar para avaliação da condição hemodinâmica poderá dar ao diagnóstico e acompanhamento das DCV. Tecnicamente, a abordagem a esta questão baseia-se na crença de que a onda de pressão arterial (OPA) transmite informações valiosas sobre a rigidez arterial, e que esta pode ser estudada com precisão por instrumentação de custo moderado. A inexistência de abordagens de análise da OPA eficientes, bem como o crescente interesse em sistemas de apoio à decisão clínica, deram motivação extra a este trabalho. O principal objectivo deste trabalho foi o desenvolvimento de uma plataforma electrónica dedicada à avaliação da rigidez arterial. A sua implementação incluiu quatro etapas fundamentais: (1) uma plataforma multi-modular concebida para incorporar vários módulos clínicos, nomeadamente o módulo OPA projectado para reprodução da morfologia de pulso; (2) uma ferramenta algorítmica capaz de identificar informação importante na OPA; (3) testes de validação usados na avaliação da repetibilidade e reprodutibilidade da sonda; e (4) algoritmos de aprendizagem implementados para lidar com características vectorizadas. Os primeiros ensaios do módulo OPA consistiram na avaliação do desempenho da sua sonda piezoeléctrica (interface entre o paciente e o próprio módulo) em uma bancada de teste concebida para este propósito, onde um erro quadrático médio (RMSE) de 1.8 ± 0.22% foi observado, usando ondas de pressão sintetizadas. A sonda foi incorporada em um colar, e testada usando um banco de dados especialmente desenvolvido, construído a partir de 217 sujeitos, organizados em grupos, com diferentes características. Foi demonstrado que a identificação de diferentes parametrizações temporais e de amplitude para cada um dos grupos é possível, bem como a identificação de alterações fisiológicas em um grupo de sujeitos, após a implantação de um ”stent”. Os testes de validação mostraram resultados reprodutíveis e repetíveis, quando os dados foram obtidos por operadores bem treinados. O uso de técnicas de mineração de dados demonstrou resultados confiáveis, em particular, para os algoritmos de classificação (p.ex., o algoritmo Random Forest alcançou uma precisão de 96.95%) e metodologias de agrupamento, para as quais foi obtida uma boa correlação entre as indicações de alto risco (obtidas usando a abordagem desenvolvida) e o Índice de Aumentação (AIx). Globalmente, os resultados dão bons indicadores, sobre o uso desta metodologia (protótipo e ferramentas algorítmicas associadas), em alternativa a técnicas dispendiosas, tais como técnicas de ultra-sons ou a tonometria de aplanação, em ambiente clínico e de investigação.<br>Cardiovascular diseases (CVD) are the leading cause of death worldwide and arterial stiffness, in particular, is considered a major determinant of risk. This thesis meets its motivation in the foreseeable impact that an accurate, non-invasive and easy-to-use instrument for hemodynamic condition assessment could impart to the diagnosis and follow-up of CVD. Technically, the approach to this question is based upon on the belief that the Arterial Pressure Waveform (APW) conveys invaluable information about the arterial stiffness which can be accurately evaluated by means of moderate-cost instrumentation. The lack of efficient APW analysis approaches, as well as the growing interest in clinical decision support systems, brought extra motivation to this work. The main goal along this work was the development of an electronic platform dedicated to arterial stiffness assessment. Its full implementation included four main steps: (1) a multi-modular platform designed to incorporate several clinical data modules, namely the APW module designed to accurately retrieve pulse morphology; (2) an algorithmic tool capable of extracting relevant information from the APW signal; (3) sets of validation tests used in the assessment of probe repeatability and reproducibility and; (4) machine learning algorithms capable of dealing with vectorized features. The first trials of the APW module consisted in the assessment of its piezoelectric front end performance (interface between the patient and the probe itself) in a special purpose test bench, where a root mean square error (RMSE) of 1.8 ± 0.22% was observed using artificial cardiac-like pressure waves. The probe was incorporated in a collar and tested using a specially developed database built from 217 subjects, organized in groups, with different characteristics. It has been demonstrated that the identification of different time and amplitude parameterizations for each group is possible, as well the identification of physiological changes in a group of subjects, after a ”stent” implementation. The validation tests showed reproducible and repeatable results whenever data were obtained by well-trained operators. The use of data mining techniques demonstrated reliable results, in particular, classification algorithms (e.g., the Random Forest algorithm achieved an accuracy of 96.95%) and clustering methodologies, for which a good correlation between the high risk labels (retrieved from the implemented approach) and the Augmentation Index (AIx) was observed. Globally, results give clear positive indications concerning the use of the developed methodology (prototype and associated algorithmic tools) as an alternative to costly techniques, such as ultrasound or applanation tonometry, in clinical and in research environments.<br>This work is funded by National funds through Fundação para a Ciência e a Tecnologia - FCT - through the scholarship SFRH/BD/61356/2009 and by FEDER, through the Programa Operacional Factores de Competitividade - COMPETE - in the scope of project PTDC/SAU-BEB/100650/2008

abstract: A cerebral aneurysm is an abnormal ballooning of the blood vessel wall in the brain that occurs in approximately 6% of the general population. When a cerebral aneurysm ruptures, the subsequent damage is lethal damage in nearly 50% of cases. Over the past decade, endovascular treatment has emerged as an effective treatment option for cerebral aneurysms that is far less invasive than conventional surgical options. Nonetheless, the rate of successful treatment is as low as 50% for certain types of aneurysms. Treatment success has been correlated with favorable post-treatment hemodynamics. However, current understanding of the effects of endovascular treatment parameters on post-treatment hemodynamics is limited. This limitation is due in part to current challenges in in vivo flow measurement techniques. Improved understanding of post-treatment hemodynamics can lead to more effective treatments. However, the effects of treatment on hemodynamics may be patient-specific and thus, accurate tools that can predict hemodynamics on a case by case basis are also required for improving outcomes.Accordingly, the main objectives of this work were 1) to develop computational tools for predicting post-treatment hemodynamics and 2) to build a foundation of understanding on the effects of controllable treatment parameters on cerebral aneurysm hemodynamics. Experimental flow measurement techniques, using particle image velocimetry, were first developed for acquiring flow data in cerebral aneurysm models treated with an endovascular device. The experimental data were then used to guide the development of novel computational tools, which consider the physical properties, design specifications, and deployment mechanics of endovascular devices to simulate post-treatment hemodynamics. The effects of different endovascular treatment parameters on cerebral aneurysm hemodynamics were then characterized under controlled conditions. Lastly, application of the computational tools for interventional planning was demonstrated through the evaluation of two patient cases.<br>Dissertation/Thesis<br>Ph.D. Bioengineering 2013

A medição da Velocidade de Onda de Pulso (VOP) é considerada a metodologia mais eficaz no diagnóstico da Rigidez Arterial, o maior factor de risco de doenças Cardiovasculares. No entanto, os equipamentos disponíveis hoje em dia no mercado são muito dispendiosos e exigem a manipulação por operadores treinados. Neste sentido, este projecto de investigação centrou-se no desenvolvimento de uma nova sonda dupla, baseada em dois sensores acústicos e na sua caracterização. O principal objectivo da sonda proposta é a determinação da VOP. No entanto permite também a determinação do Tempo de Ejecção do Ventrículo Esquerdo, um parâmetro muito importante na avaliação da função do ventrículo esquerdo. Para a caracterização da sonda, foram realizados vários testes de modo a avaliar o desempenho do equipamento ao nível da existência de cross-talk entre os dois sensores, o estudo da sua repetibilidade, a análise das formas de onda obtidas e a determinação resposta a impulso dos sensores. Também foi determinada a sua resolução temporal através de alguns testes realizados numa bancada de testes. Foram também recolhidos dados ‘clínicos’ de um grupo de voluntários, para determinação da sua VOP e Tempo de Ejecção do Ventrículo Esquerdo, revelando resultados muito interessantes e promissores. De facto, os valores obtidos para as VOP e especialmente paras os tempos de ejecção foram, de forma geral, muito próximos do esperado para cada indivíduo. Palavras-chave Doenças Cardiovasculares, Rigidez Arterial, Velocidade de Onda de Pulso Local, Tempo de Ejecção do Ventrículo Esquerdo, Sensores Acústicos

Dissertação de Mestrado em Engenharia Biomédica apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra.<br>As doenças cardiovasculares (DCVs) causam milhões de mortes todos os anos, sendo a principal causa de morte no mundo inteiro. A hipertensão é um dos mais relevantes factores de risco das doenças cardiovasculares. Assim sendo, é muito importante o desenvolvimento de um método de diagnóstico que seja barato, fácil utilização, preciso e capaz de detectar alterações precoces da performance do sistema cardiovascular, permitindo, desta forma, aumentar a probabilidade de sobrevivência. A análise da forma de onda da pressão sanguínea central fornece informações clínicas relevantes uma vez que patologias cardiovasculares alteram a sua forma de onda. Este projecto de investigação foca-se no desenvolvimento de um novo sensor hemodinâmico não-invasivo que integra um sensor piezoeléctrico e um acelerómetro ligados a um circuito demodulador. O sensor acessa a forma de onda da pressão sanguínea, simulada através das bancadas de teste desenvolvidas ao longo deste projecto. Numa fase inicial, os sinais resultantes são adquiridos recorrendo á utilização dos módulos de aquisição USB NI-6008 ou USB NI-6210 associado a um gerador arbitrário de formas de onda (Agilent), a uma fonte de alimentação e a um computador. Numa fase posterior foi utilizado um dispositivo multifuncional capaz gerar, guardar, converter, medir e analisar sinais analógicos e digitais (Digilent) e um computador. Algoritmos capazes de processar os sinais foram desenvolvidos utilizando o Matlab. Os resultados das avaliações da performance do sistema são apresentados ao longo da dissertação, incluindo os testes de validação efectuados nas bancadas de teste e a descrição da metodologia aplicada à análise dos sinais recolhidos. Testes experimentais provaram a eficiência da caixa de aquisição e da última versão da bancada de teste, permitindo adquirir, com precisão, sinais referentes à pressão arterial e à sua forma de onda. Palavras-Chave Doenças Cardiovasculares, Hipertensão, Forma de onda da pressão sanguínea da Carótida, Sensor Piezoeléctrico, Acelerómetro, Modulação, Desmodulação.

碩士<br>國立臺灣大學<br>生化科技學系<br>107<br>This study intended to evaluate the short-term effect of magnesium supplement at a Daily Recommended Index (DRI) level on cognitive function and on certain hemodynamic parameters. This study aimed to recruit cognitively impaired participants aged 60 and over who determined cognitive scores ≤ 26 using Mini-Mental State Examination (MMSE). Using a double-blind randomized placebo-controlled intervention trial design, participants were divided into magnesium intervention group and placebo group. Both groups were evaluated by Montreal Cognitive Assessment (MoCA), working memory test, carotid artery flow velocity, urinary magnesium and food frequency questionnaire. We recruited 50 (21 men and 29 women) ≥60 years elderly (placebo group: 75.0± 7.4 years; intervention group: 75.3± 7.6 years) with MMSE and MoCA cognitive score ≤26. In body mass index(BMI), education level, medical history(Hypertension, Heart disease, Type 2 Diabetes Mellitus and Hyperlipidemia) and daily magnesium intake, there were not significant difference between both groups. At baseline, urinary magnesium (placebo group: 5.4 ± 2.4 mg/dL, intervention group: 6.5 ± 5.2 mg/dL), urinary creatinine (placebo group: 70.7 ± 40.2 mg/dL, intervention group: 88.7 ± 52.8 mg/dL) and urinary magnesium/creatinine (placebo group: 0.088 ± 0.032, intervention group: 0.076 ± 0.036) did not significant difference between groups. The score of MoCA in placebo group was higher than intervention group but the difference was not significant (placebo group: 20.6 ±4.0, intervention group: 18.0 ± 6.2, P-value=0.0896) in baseline. Post-test was conducted two hours after intervention group was consumed 300mg magnesium citrate. Results indicated that there were no significant differences for all post-test measures between groups after two-hour intervention except for their MoCA score (placebo group: 23.8 ± 4.0，intervention group: 20.1 ± 6.6 , P-value=0.0226) and mean velocity of common carotid artery in left (placebo group: -1.57 ± 6.40 cm/s, intervention group: -5.11 ± 5.35 cm/s，P-value=0.0381). The amounts of urinary magnesium (placebo group: 4.5 ± 2.3 mg/dL, intervention group: 6.6 ± 4.4 mg/dL) and creatinine (placebo group: 57.5 ±34.5 mg/dL, intervention group: 87.8 ±63.0 mg/dL) were found higher in the intervention group compared to placebo group, but the differences were not statistically significant. Two hours after consuming magnesium citrate, urinary magnesium/creatinine increases were observed in both groups(placebo group: 0.090 ±0.038, intervention group: 0.085 ± 0.035) even though the changes were not significant. The one-time intervention of magnesium could not improve blood flow of carotid and cognitive function in 3 hours in this study. Our finding suggested that long-term magnesium intervention has more health-improving effect. Key words：Magnesium, double-blind, elderly, cognitive function, one-time intervention

博士<br>國立成功大學<br>航空太空工程學系<br>102<br>A reliable, non-invasive diagnostic tool for assessing cardiovascular characteristics and/or the connected end organ health state is still lacking. The present work aims at developing an identification procedure for estimating individual hemodynamic parameters based on a one-dimensional (1-D) tree-like vascular flow model. With the use of clinically available measurements, the proposed identification methods solve the hemodynamic inverse problem associated with the modeled vascular system, yielding the estimates of the unknown model parameters that are of clinical interest. For the present vascular diagnostic method, the arterial stiffness and stress-free lumen radius as well as the terminal lumped resistances and compliance that reflect the health state of the connected end organs were estimated. The present parameter estimation procedure uses measurable clinic data as system input and observation functions. Sensor data errors and measurement uncertainties are not considered. The measurements obtained at sites of interest are assumed noise-free and mutually compatible. The present identification procedure consists of a 1-D flow state estimator and a genetic parameter search algorithm, and thus both physical parameters and state estimation are included simultaneously in the identification procedure. Differential evolution (DE), a global genetic search algorithm, has been employed as the parameter optimizer. Parallel computing was applied to accelerate the speed of DE optimization. To cope with different data measurements obtained in vivo, identification methods that use pressure-flow rate (pq), pressure-velocity (pU), and diameter-velocity (DU) waveforms as system input/measurement pair were proposed and constructed. The present model-based identification algorithm was constructed and validated using a numerical 1-D hemodynamic simulation code which simulates pulsatile blood flow circulating in human arterial system with high-fidelity. In this simulation code, a high-resolution Roe’s scheme augmented by characteristics-based boundary condition treatments were developed to solve the complex wave reflection and re-reflection phenomena prevailing in the tree-like vascular network. Validations were performed on estimating regional vascular and terminal end-organ parameters, respectively, using both numerical and clinical data pairs to assess the feasibility and accuracy of the proposed identifier. The results show that all the three pq, pU and DU identification methods are accurate and feasible. For point-wise vascular diagnosis, the DU method has been particularly accurate, which may potentially extend the current usability of vascular ultrasonography onto a new horizon of evaluating local arterial stiffness non-invasively. For identifying individual parameters pertaining to a segmental arterial network of an arm, agreed hemodynamic waveforms reconstructed by the pq method were compared favorably to the in vivo measurements. Furthermore, the feasibility of identifying end-organ hemodynamic parameters using brachial (peripheral) pressure/wall distension waveforms was demonstrated. These preliminary successes indicate that, with the aid of model-based identification, a non-invasive, individual-based diagnosis of the organ health states using measurable observations at peripheral arteries is theoretically possible.

碩士<br>國立陽明大學<br>放射醫學科學研究所<br>94<br>Hemodynamic parameters such as relative cerebral volume (rCBV), relative cerebral blood flow (rCBF), and mean transit time (MTT) are assessed using dynamic susceptibility contrast MRI (DSC-MRI). The rCBF and MTT can be determined by deconvolution with an arterial input function(AIF). However, the singular value decomposition (SVD) deconvolution method is sensitive to the tracer delay that it often occurs in patients with cerebrovascular disease. We investigated the effect of tracer delay on rCBF determined by SVD deconvolution. Simulation study showed that shorter MTT will cause larger underestimation of rCBF and overestimation of MTT in tracer delay. Delay correction methods were developed to find tracer arrival delay between the AIF and concentration time curve, and concentration time curve was shifted to coincide with that of the AIF. The simulations showed that the corrected rCBF was more accurate than uncorrected one. However, rCBF was depended on threshold by SVD, threshold was found by simulation. Since everyone had different physics condition, therefore simulation condition was not fit to everyone. However, rCBF inaccuracy will affect MTT indirectly. We proposed a method that did not depend on threshold, and rCBF and MTT can calculated directly. At first, we assumed residual function equaled exponential decay. A curve fitting technique was used to find tracer arrival delay between the AIF and concentration time curve, and concentration time curve was shifted to coincide with that of the AIF. Finally, rCBF and MTT were determined using curve fitting. The simulations showed that the rCBF and MTT obtained from curve fitting was more accurate than the two SVD methods. We applied three methods of calculating the rCBF, MTT, and rCBV images for one normal volunteer and two patients. Finally, we analysis the results of images by scatter plot.

This dissertation presents the development and use of a novel optical imaging system capable of monitoring changes in blood flow, oxygenated hemoglobin, deoxygenated hemoglobin, and absolute pO₂ in the brain. There are several imaging modalities capable of monitoring these parameters separately. Laser speckle contrast imaging (LSCI) and multi-spectral reflectance imaging (MSRI) have been used to monitor relative blood flow and hemoglobin changes respectively. Phosphorescence quenching, while not typically used for imaging, is capable of noninvasive measurements of pO₂. Combining these three techniques has led to the development of an imaging system that could ultimately lead to a better understanding of brain physiology. By combining techniques such as LSCI and MSRI, it becomes possible to estimate the cerebral metabolic rate of oxygen (CMRO₂), an important indicator of neuronal function. It is equally important to understand absolute pO₂ levels so that oxygen metabolism can be examined in context. Integrating phosphorescence quenching and a spatial light modulator into the imaging system allowed absolute pO₂ to be simultaneously measured in distinct regions. This new combined system was used to investigate pathophysiological conditions such as cortical spreading depression (CSD) and ischemia. The observed hemodynamic changes associated with these events were largely dictated by baseline oxygen levels and varied significantly in different regions. This finding highlighted the importance of having a system capable of monitoring hemodynamic changes and absolute pO₂ simultaneously while maintaining enough spatial resolution to distinguish the changes in different regions. It was found that animals with low baseline pO₂ were unable to deliver enough oxygen to the brain during events like CSD because of the high metabolic demand. In order for this technique to become more prevalent among researchers, it is essential to make it cost effective and simple to use. This was accomplished by replacing the expensive excitation sources with cheaper light emitting diodes (LEDs) and redesigning the software interface so that it was easier to control the entire device. The final system shows the potential to become a key tool for researchers studying the role of absolute pO₂ and other hemodynamic parameters during pathophysiological conditions such as CSD and ischemia.<br>text

碩士<br>國立陽明大學<br>生物醫學影像暨放射科學系暨研究所<br>99<br>Purpose：A thresholding technique was applied to the relative cerebral blood volume (CBV) and relative cerebral blood flow (CBF) images for removing voxels either containing vessels or near vessels. Scaling factors were calculated for converting relative CBV and relative CBF values to absolute values. Quantitative measurements of CBV and CBF on brain parenchyma were improved. Material and methods：The independent component analysis technique was utilized to segment the arterial region on brain perfusion MRI for normal subjects and patients with stenosis, and found the arterial input function (AIF) for following calculation. Because voxels containing or near vessels had much higher relative CBV and relative CBF values than voxels containing only brain parenchyma, a thresholding technique can be applied to relative CBV and relative CBF images for segmenting vessel voxels. The relative CBV and relative CBF histograms were plotted for voxels included in the brain mask with CSF voxels removed. The median values of the two histograms were calculated. The thresholds were set at twice of the median values of the relative CBV and relative CBF histograms. Voxels with relative CBV or relative CBF values higher than the thresholds were classified as vessel voxels. These vessel voxels were removed from the brain mask. The thresholding technique was also applied to TTP images for finding normal brain parenchyma. The averaged relative CBV and relative CBF for the voxels segmented as normal brain parenchyma voxels were calculated for finding scaling factors to convert the relative CBV and relative CBF images into absolute CBV and CBF image, and correct the partial volume effect. Results：This method can solve the defects of absolute quantification caused by its poor resolving power in magnetic resonance imaging; moreover, CBV and CBF of white matter or gray matter were measured without magnetic susceptibility effect of the blood vessels. Conclusion：A post-processing technique was proposed for removing voxels either containing vessels or affected by vessels. And the proposed partial volume estimation technique provides a possible alternative for achieving quantitative measurements without using venous output function correction. Key words：brain perfusion MRI；arterial input function；vessel removal；cerebral blood volume；cerebral blood flow.

Tese de doutoramento em cotutela, na área de Engenharia Biomédica, apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra e à Université Angers - França<br>Laser speckle is an interference effect that has been considered as a main drawback in the use of coherent light sources. However, for a specific set of applications, this effect is used as source of information. Among these applications we can find the biomedical ones. Laser speckle has been used for decades for microvascular blood flow monitoring but only now starts to be considered as a method that can also be used for macrocirculation parameters extraction. This work aims at demonstrating that the laser speckle can be used for macrocirculation assessment with good reliability, using the same technique as the ones used in microcirculation assessment. The use of the same methods could lead to a rapid inclusion of this new evaluation in the existing devices. One of the most important laser speckle issues, that prevents a fully quantitative analysis, is the effect of static scatterers. This type of scatterers strongly influences the measurement of speckle contrast, leading to a wrong interpretation of the data. The other objective of this work is to study the effect of static scatterers on the laser speckle correlation and contrast which are used to quantify the blood flow. This thesis presents the studies conducted to explore the possibility of using the speckle effect for hemodynamic parameters measurement in macrocirculation and the experimental work performed on the effect of static scatterers in microcirculation. Before the experimental work, the thesis begins by an introduction to the basic laser speckle theory. A critical analysis of the available literature is performed in addition to the identification of the future laser speckle challenges. Several ideas are also proposed to deal with the most common issues. The work developed in the macrocirculation field shows that the laser speckle effect can be used to reliably extract the pulse pressure waveform. A multi-wavelength study was also conducted to determine which light wavelength is better for laser speckle macrocirculation analysis. Shorter wavelengths achieved the best results in identifying the heart rate. In a second test, using the same processing methods as the ones that are used in the current devices, speckle effect was able to reconstruct the pulse pressure waveform and identify feature points like the systolic peak and dicrotic notch. Moreover, the same system has been used to perform a two-dimensional segmentation of targets with longitudinal movements. An entropy-based algorithm was applied to the laser speckle data in order to discern between two identical targets where only one is moving. This method was able to perform a two-dimensional segmentation without any a priori knowledge on the scene or the target movement. Regarding the microcirculation field, an experimental test was performed to study the effect of static scatterers on the laser speckle signal. The experimental test consisted of a micro-channel device, used to simulate the blood flow inside small blood vessels, coupled with a set of different static scatterers layers. The recorded laser speckle data were analyzed in terms of correlation and contrast. The results show that the correlation between two consecutive images can identify the proportion of statics/dynamic scatterers and should be used in order to achieve a quantitative laser speckle technique. The speckle correlation also proved to be independent from the dynamic scatterers velocity. Regarding the laser speckle contrast, the temporal algorithm presents a good independence on the variation of static scatterers concentration. The spatio-temporal algorithm should be used because it presents a better concordance with laser speckle theory. To conclude, laser speckle is a highly versatile tool and proved to be able to extract hemodynamic parameters in macrocirculation. This work also demonstrates that the laser speckle correlation is able to estimate the ratio between static/dynamic scatterers with good reliability. Moreover, the temporal speckle contrast achieved a very good performance in discerning dynamic scatterers with different velocities. RESUMO: O laser speckle corresponde a um efeito de interferometria que foi muitas vezes considerado como uma grande limita c~ao do uso de fontes de luz coerente. No entanto, para um conjunto espec co de aplica c~oes, este efeito pode ser usado como fonte de informa c~ao. Entre estas aplica c~oes podemos encontrar v arias no ^ambito da biomedicina. Esta t ecnica tem vindo a ser utilizada durante d ecadas para avaliar a perfus~ao sangu nea mas, apenas agora, come ca a despertar interesse como meio de avaliar tamb em a macrocircula c~ao. Este trabalho pretende demonstrar que o efeito de laser speckle pode ser usado, tamb em, para extrair informa c~ao importante relativa a condi c~ao cardiovascular, nomeadamente da macrocircula c~ao, com boa abilidade e usando m etodos semelhantes aos j a aplicados na avalia c~ao da microcircula c~ao. O facto de serem usados os mesmo m etodos poder a levar a uma r apida inclus~ao deste tipo de an alise nos dispositivos j a existentes. No campo do uso de laser speckle para avalia c~ao da microcircula c~ao, uma das quest~oes mais importantes est a relacionada com o efeito dos dispersores est aticos. A quantidade de dispersores est aticos in uencia fortemente o sinal de laser speckle, levando a interpreta c~oes incorretas dos dados. Este e um dos fatores que impede a exist^encia de dispositivos laser speckle com capacidade de quanti car o uxo sangu neo. Devido a isto, o estudo do efeito de diferentes concentra c~oes de dispersores est aticos nos sinais de contraste e correla c~ao speckle e tamb em um dos objetivos deste trabalho. Esta tese apresenta os estudos realizados com o objetivo de testar a possibilidade de usar o efeito de laser speckle para avalia c~ao de par^ametros hemodin^amicos da microcircula c~ao e o trabalho experimental realizado no ^ambito do efeito dos dispersores est aticos. Antes do trabalho experimental, esta tese come ca por descrever os princ pios b asicos da teoria de laser speckle. Nesta sec c~ao e realizada uma an alise cr tica da literatura dispon vel e s~ao identi cados os desa os futuros desta t ecnica. Algumas ideias inovadoras s~ao tamb em propostas como m etodos para lidar com alguns dos problemas atuais da t ecnica de laser speckle. Os trabalhos desenvolvidos na area da macrocircula c~ao demonstraram que o efeito de laser speckle pode ser usado para extrair a forma de onda de pulso. Um estudo com fontes de luz de diferentes comprimentos de onda foi efetuado para determinar qual destes comprimentos de onda apresenta melhores resultados. Os comprimentos de onda mais curtos (luz verde) conseguiram atingir os melhores resultados na identi ca c~ao do ritmo card aco. Num segundo teste, usando os mesmo m etodos j a usados para a avalia c~ao da microcircula c~ao, o efeito de laser speckle foi capaz de reconstruir a onda de pulso e identi car pontos caracter sticos como o pico sist olico e o n o dicr otico. Para alem disto, este mesmo sistema foi usado num teste piloto para segmentar alvos bidimensionais com movimentos longitudinais. Um algoritmo baseado no c alculo da entropia foi usado com sucesso para distinguir dois alvos id^enticos, onde apenas um apresentava movimento. Para al em disto, este m etodo permitiu segmentar o alvo em movimento sem nenhuma informa c~ao antecipada sobre a movimenta c~ao dos alvos ou a disposi c~ao da cena. Relativamente ao campo da microcircula c~ao, um teste experimental foi desenvolvido para estudar o efeito dos dispersores est aticos no sinal de laser speckle. Este teste consistiu na avalia c~ao de um fantoma constitu do por um micro-canal e diferentes camadas de dispersores. Este fantoma foi usado para simular a perfus~ao sangu nea em vasos de pequeno calibre. Os dados recolhidos foram processados em termos de contraste e correla c~ao. Os resultados indicaram que a correla c~ao entre duas imagens consecutivas e capaz de identi- car a quantidade relativa de dispersores est aticos/din^amicos e deve ser usada como meio para atingir uma t ecnica completamente quantitativa. A correla c~ao de speckle demonstrou tamb em ser independente da velocidade dos dispersores din^amicos. Em rela c~ao ao contraste de speckle, o algoritmo temporal apresentou uma boa independ^encia em termos de concentra c~ao de dispersores est aticos. O algoritmo espa co-temporal demonstrou ser aquele que apresenta uma melhor coer^encia com a teoria do efeito laser speckle. Concluindo, o efeito de laser speckle e uma ferramenta altamente vers atil e provou ser capaz de extrair par^ametros hemodin^amicos relacionados com a macrocircula c~ao. Este trabalho tamb em demonstrou que a correla c~ao de laser speckle permite estimar o r acio entre a quantidade de dispersores est aticos/din^amicos com boa abilidade.<br>O laser speckle corresponde a um efeito de interferometria que foi muitas vezes considerado como uma grande limita¸c˜ao do uso de fontes de luz coerente. No entanto, para um conjunto espec´ıfico de aplica¸c˜oes, este efeito pode ser usado como fonte de informa¸c˜ao. Entre estas aplica¸c˜oes podemos encontrar v´arias no ˆambito da biomedicina. Esta t´ecnica tem vindo a ser utilizada durante d´ecadas para avaliar a perfus˜ao sangu´ınea mas, apenas agora, come¸ca a despertar interesse como meio de avaliar tamb´em a macrocircula¸c˜ao. Este trabalho pretende demonstrar que o efeito de laser speckle pode ser usado, tamb´em, para extrair informa¸c˜ao importante relativa `a condi¸c˜ao cardiovascular, nomeadamente da macrocircula¸c˜ao, com boa fiabilidade e usando m´etodos semelhantes aos j´a aplicados na avalia¸c˜ao da microcircula¸c˜ao. O facto de serem usados os mesmo m´etodos poder´a levar a uma r´apida inclus˜ao deste tipo de an´alise nos dispositivos j´a existentes. No campo do uso de laser speckle para avalia¸c˜ao da microcircula¸c˜ao, uma das quest˜oes mais importantes est´a relacionada com o efeito dos dispersores est´aticos. A quantidade de dispersores est´aticos influencia fortemente o sinal de laser speckle, levando a interpreta¸c˜oes incorretas dos dados. Este ´e um dos fatores que impede a existˆencia de dispositivos laser speckle com capacidade de quantificar o fluxo sangu´ıneo. Devido a isto, o estudo do efeito de diferentes concentra¸c˜oes de dispersores est´aticos nos sinais de contraste e correla¸c˜ao speckle ´e tamb´em um dos objetivos deste trabalho. Esta tese apresenta os estudos realizados com o objetivo de testar a possibilidade de usar o efeito de laser speckle para avalia¸c˜ao de parˆametros hemodinˆamicos da microcircula¸c˜ao e o trabalho experimental realizado no ˆambito do efeito dos dispersores est´aticos. Antes do trabalho experimental, esta tese come¸ca por descrever os princ´ıpios b´asicos da teoria de laser speckle. Nesta sec¸c˜ao ´e realizada uma an´alise cr´ıtica da literatura dispon´ıvel e s˜ao identificados os desafios futuros desta t´ecnica. Algumas ideias inovadoras s˜ao tamb´em propostas como m´etodos para lidar com alguns dos problemas atuais da t´ecnica de laser speckle. Os trabalhos desenvolvidos na ´area da macrocircula¸c˜ao demonstraram que o efeito de laser speckle pode ser usado para extrair a forma de onda de pulso. Um estudo com fontes de luz de diferentes comprimentos de onda foi efetuado para determinar qual destes comprimentos de onda apresenta melhores resultados. Os comprimentos de onda mais curtos (luz verde) conseguiram atingir os melhores resultados na identifica¸c˜ao do ritmo card´ıaco. Num segundo teste, usando os mesmo m´etodos j´a usados para a avalia¸c˜ao da microcircula¸c˜ao, o efeito de laser speckle foi capaz de reconstruir a onda de pulso e identificar pontos caracter´ısticos como o pico sist´olico e o n´o dicr´otico. Para alem disto, este mesmo sistema foi usado num teste piloto para segmentar alvos bidimensionais com movimentos longitudinais. Um algoritmo baseado no c´alculo da entropia foi usado com sucesso para distinguir dois alvos idˆenticos, onde apenas um apresentava movimento. Para al´em disto, este m´etodo permitiu segmentar o alvo em movimento sem nenhuma informa¸c˜ao antecipada sobre a movimenta¸c˜ao dos alvos ou a disposi¸c˜ao da cena. Relativamente ao campo da microcircula¸c˜ao, um teste experimental foi desenvolvido para estudar o efeito dos dispersores est´aticos no sinal de laser speckle. Este teste consistiu na avalia¸c˜ao de um fantoma constitu´ıdo por um micro-canal e diferentes camadas de dispersores. Este fantoma foi usado para simular a perfus˜ao sangu´ınea em vasos de pequeno calibre. Os dados recolhidos foram processados em termos de contraste e correla¸c˜ao. Os resultados indicaram que a correla¸c˜ao entre duas imagens consecutivas ´e capaz de identi- ficar a quantidade relativa de dispersores est´aticos/dinˆamicos e deve ser usada como meio para atingir uma t´ecnica completamente quantitativa. A correla¸c˜ao de speckle demonstrou tamb´em ser independente da velocidade dos dispersores dinˆamicos. Em rela¸c˜ao ao contraste de speckle, o algoritmo temporal apresentou uma boa independˆencia em termos de concentra¸c˜ao de dispersores est´aticos. O algoritmo espa¸co-temporal demonstrou ser aquele que apresenta uma melhor coerˆencia com a teoria do efeito laser speckle. Concluindo, o efeito de laser speckle ´e uma ferramenta altamente vers´atil e provou ser capaz de extrair parˆametros hemodinˆamicos relacionados com a macrocircula¸c˜ao. Este trabalho tamb´em demonstrou que a correla¸c˜ao de laser speckle permite estimar o r´acio entre a quantidade de dispersores est´aticos/dinˆamicos com boa fiabilidade.<br>FCT - PESSOA/Hubert Curien travelling program<br>Ações integradas Luso Francesas/PAUILF - CRUP e CPU

Indiana University-Purdue University Indianapolis (IUPUI)<br>While computed tomographic angiography (CTA) has emerged as a powerful noninvasive option that allows for direct visualization of arterial stenosis(AS), it cant assess the hemodynamic abnormality caused by an AS. Alternatively, trans-stenotic pressure gradient (TSPG) and fractional flow reserve (FFR) are well-validated hemodynamic indices to assess the ischemic severity of an AS. However, they have significant restriction in practice due to invasiveness and high cost. To fill the gap, a new computational modality, called InVascular has been developed for non-invasive quantification TSPG and/or FFR based on patient's CTA, aiming to quantify the hemodynamic abnormality of the stenosis and help to assess the therapeutic/surgical benefits of treatment for the patient. Such a new capability gives rise to a potential of computation aided diagnostics and therapeutics in a patient-specific environment for ASs, which is expected to contribute to precision planning for cardiovascular disease treatment. InVascular integrates a computational modeling of diseases arteries based on CTA and Doppler ultrasonography data, with cutting-edge Graphic Processing Unit (GPU) parallel-computing technology. Revolutionary fast computing speed enables noninvasive quantification of TSPG and/or FFR for an AS within a clinic permissible time frame. In this work, we focus on the implementation of inlet and outlet boundary condition (BC) based on physiological image date and and 3-element Windkessel model as well as lumped parameter network in volumetric lattice Boltzmann method. The application study in real human coronary and renal arterial system demonstrates the reliability of the in vivo pressure quantification through the comparisons of pressure waves between noninvasive computational and invasive measurement. In addition, parametrization of worsening renal arterial stenosis (RAS) and coronary arterial stenosis (CAS) characterized by volumetric lumen reduction (S) enables establishing the correlation between TSPG/FFR and S, from which the ischemic severity of the AS (mild, moderate, or severe) can be identified. In this study, we quantify TSPG and/or FFR for five patient cases with visualized stenosis in coronary and renal arteries and compare the non-invasive computational results with invasive measurement through catheterization. The ischemic severity of each AS is predicted. The results of this study demonstrate the reliability and clinical applicability of InVascular.

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2015<br>Introduction: Blood pressure, cardiac output, heart rate and stroke volume are influenced by the sleep-wake cycle. Healthy subjects have a decrease in blood pressure associated with sleep onset (SO). Patients with Obstructive Sleep Apnea (OSA) often lack this reduction. Obesity is a major risk factor for OSA, and it is not clear if obese patients without OSA demonstrate this dipping. The aim of this study is to investigate the hemodynamic changes during SO in an obese population with and without OSA. Methods: Hemodynamic parameters were recorded in 40 obese patients via Nexfin-HD® device. We divided the patients into obese without OSA (group A) and with OSA (group B) and the study period in two phases: (0) 5 min before SO and (1) 20 min after SO. A p<0.05 was considered statistically significant. Results: In both groups, SO wasn’t associated with a significant decrease in any variable. Group B had a significant higher variability in all variables in phase 1 than group A. SO was also associated with higher variability than in group A, however this result only reach statistical significance in systolic and mean arterial pressure. Discussion: The non-dipping pattern noticed in all variables in both groups indicates that obesity might be an independent risk factor for OSA related changes in physiological hemodynamic response to SO. Apneic and hypopneic episodes seem to play a major role in the oscillating hemodynamic parameters and higher variability seen in OSA. In conclusion, obesity and OSA might act as additive factors for hemodynamic instability during sleep.<br>Introdução: A pressão arterial, o output cardíaco, a frequência cardíaca e o volume sistólico são influenciados pelo ciclo sono/vigília. Nos indivíduos saudáveis, com o início do sono (IS), verifica-se um decréscimo da pressão arterial. No entanto, frequentemente, este decréscimo não se verifica em doentes com apneia obstrutiva do sono (AOS). A obesidade é um fator de risco major para a AOS e, não é claro, se os obesos sem AOS têm este decréscimo fisiológico. O objetivo deste estudo é investigar as alterações hemodinâmicas associadas ao início do sono em doentes obesos com e sem AOS.

Infinite-Dimensional Systems (IDSs) which have been made possible by recent advances in mathematical and computational tools can be used to model complex real phenomena. However, due to physical, economic, or stringent non-invasive constraints on real systems, the underlying characteristics for mathematical models in general (and IDSs in particular) are often missing or subject to uncertainty. Therefore, developing efficient estimation techniques to extract missing pieces of information from available measurements is essential. The human brain is an example of IDSs with severe constraints on information collection from controlled experiments and invasive sensors. Investigating the intriguing modeling potential of the brain is, in fact, the main motivation for this work. Here, we will characterize the hemodynamic behavior of the brain using functional magnetic resonance imaging data. In this regard, we propose efficient estimation methods for two classes of IDSs, namely Partial Differential Equations (PDEs) and Fractional Differential Equations (FDEs). This work is divided into two parts. The first part addresses the joint estimation problem of the state, parameters, and input for a coupled second-order hyperbolic PDE and an infinite-dimensional ordinary differential equation using sampled-in-space measurements. Two estimation techniques are proposed: a Kalman-based algorithm that relies on a reduced finite-dimensional model of the IDS, and an infinite-dimensional adaptive estimator whose convergence proof is based on the Lyapunov approach. We study and discuss the identifiability of the unknown variables for both cases. The second part contributes to the development of estimation methods for FDEs where major challenges arise in estimating fractional differentiation orders and non-smooth pointwise inputs. First, we propose a fractional high-order sliding mode observer to jointly estimate the pseudo-state and input of commensurate FDEs. Second, we propose a modulating function-based algorithm for the joint estimation of the parameters and fractional differentiation orders of non-commensurate FDEs. Sufficient conditions ensuring the local convergence of the proposed algorithm are provided. Subsequently, we extend the latter technique to estimate smooth and non-smooth pointwise inputs. The performance of the proposed estimation techniques is illustrated on a neurovascular-hemodynamic response model. However, the formulations are efficiently generic to be applied to a wide set of additional applications.

博士<br>國立陽明大學<br>腦科學研究所<br>106<br>Background: The impact of migraine on patient health is complicated by cerebro- and cardio-vascular risk factors and comorbidity. The role of central pulsatile hemodynamics in the pathogenesis of white matter hyperintensities (WMHs) in migraine patients has not been clarified. MicroRNAs (miRs) have emerged as important regulators of vascular endothelial functions. Yet, whether levels of miRs associated with endothelial dysfunction are altered in migraine patients remains unknown. Aims: Our study aims were (1) to shed light on possible mechanism of increased risk of vascular events and WMHs formation in migraine patients, (2) to investigate whether potential vascular parameters correlate with WMHs presence or clinical profiles in migraine patients, and (3) to explore the relationship between circulating endothelial-specific miRs and migraine. Methods: Patients with migraine without overt vascular risk factors and demographically-matched healthy controls were recruited prospectively. Cerebral WMHs volume was determined by T1-weighted magnetic resonance imaging with CUBE-fluid-attenuated-inversion-recovery sequences. Central systolic blood pressure (cSBP), carotid-femoral pulse wave velocity (cf-PWV), and carotid augmentation index (AI) were measured by applanation tonometry. Carotid pulsatility index (CPI) was derived from Doppler ultrasound carotid artery flow analysis. The levels of four endothelial-specific miRs (miR-155, miR-126, miR-21, and Let-7g) were quantified and expressed in terms of fold changes (2-ΔΔct) relative to mean levels in the control group. Associations of miRs levels with headache features and syncope comorbidity were explored. Results: Compared to the controls, the migraine patients had a higher WMHs frequency [odds ratio (OR), 2.75; P = 0.04) and greater mean WMHs volume (0.174 vs. 0.049, cm3, P = 0.04). Multivariable regression analysis showed that WMHs volume in migraine patients was positively associated with cSBP (P = 0.04) and cf-PWV (P < 0.001), but negatively associated with CPI (P = 0.04) after controlling for potential confounding factors. The interaction effects observed indicated that the influence of cf-PWV (P = 0.004) and cSBP (P = 0.03) on WMHs formation was greater for the lower-CPI subgroup of migraine patients. Compared to controls, migraine patients had upregulated expression of miR-155 (6.17-fold, P = 0.018), miR-126 (6.17-fold, P = 0.013), and let-7g (7.37-fold, P = 0.005). Levels of miR-155 (r = 0.375, P = 0.041) and miR-126 (r = 0.375, P = 0.041) were associated with the syncope frequency in the past year in migraine patients. Conclusions: Increased aortic stiffness or CBP in the presence of low intracranial artery resistance may predispose migraine patients to WMHs formation; this suggested pathophysiology differs from that observed in non-migraine elderly subjects. Circulating levels of endothelial-specific miRs were elevated and associated with syncope comorbidity in migraine patients. Our findings may shed light on understanding the mechanism mediating altered vascular dysfunctions in migraine and suggest that quantification of targeted vascular parameters and miRs, could be used for stratification of vascular risks in migraine patients.