Os pacientes portadores de afecções ateroscleróticas das artérias coronárias, que necessitam tratamento odontológico sob anestesia local com vasoconstritor, constituem um grupo especial de manejo por múltiplos aspectos. Trata-se de doença que pode apresentar, nestas circunstâncias, complicações com potencial de gravidade como: arritmias, angina instável e até mesmo infarto agudo do miocárdio. O cirurgião-dentista diante destes riscos deve conhecer as soluções anestésicas, bem como as interações medicamentosas e eventuais repercussões cardiovasculares. Objetivos: avaliar a ocorrência das seguintes variáveis detectoras de isquemia miocárdica durante ou após o tratamento odontológico:1) alterações do segmento ST avaliadas pelo sistema Holter; hipocontratilidade do ventrículo esquerdo pela Doppler-ecocardiografia e elevação dos marcadores bioquímicos; 2) precordialgia, arritmias e insuficiência mitral. Métodos: Os pacientes coronariopatas eram submetidos à exodontia sob anestesia local com ou sem vasoconstritor, divididos em dois grupos (sorteio por envelope). Em todos praticava-se monitoração eletrocardiográfica com Holter por 24 horas; Doppler-ecocardiograma antes e após intervenção odontológica e dosavam-se os marcadores bioquímicos antes e 24 horas após a exodontia (CKMB massa, CKMB atividade e troponina T). Aferia-se, também, a freqüência cardíaca e a pressão arterial nas fases pré, pós-anestesia e pós-exodontia. A Doppler-ecocardiografia avaliava a contratilidade segmentar do ventrículo esquerdo e a eventual ocorrência de insuficiência mitral. Resultados: 54 pacientes com doença coronária comprovada por cinecoronariografia e com indicação de extração dentária foram incluídos no estudo, no período de maio de 2004 a maio de 2005. Os casos foram divididos em dois grupos: grupo I com 27 pacientes tratados sob anestesia local com vasoconstritor e grupo II, 27 casos sem vasoconstritor. A média das idades no grupo I foi 58 (DP 7,98) anos e no grupo II de 55 anos (DP 8,57); 59,3 por cento eram do sexo masculino no grupo I e 66,7 por cento no grupo II; 66,6 por cento apresentaram infarto do miocárdio prévio com ou sem supradesnivelamento do segmento ST no grupo I e 77,7 por cento no grupo II. No grupo I a média de dentes extraídos foi de 1,6 dentes por paciente (DP 0,96) e 1,8 dentes por paciente (DP 1,21) no grupo II e a média de tubetes anestésicos por paciente no grupo I foi 1,5 tubetes (DP 0,87) e 1,8 tubetes (DP 0,79) no grupo II. Três pacientes do grupo I apresentaram depressão do segmento ST (1,0 mm), durante a aplicação da anestesia, e em nenhum deles verificou-se presença de isquemia avaliada pelos outros métodos; dois outros pacientes do mesmo grupo I tiveram elevação da CKMB massa. No estudo não se observou ocorrência ou agravamento de hipocontratilidade segmentar do ventrículo esquerdo, precordialgia, arritmias ou insuficiência mitral. Conclusão: Exodontia praticada sob uso de anestesia com epinefrina 1:100.000 não implica em riscos isquêmicos adicionais, uma vez que realizada com boa técnica anestésica e manutenção do tratamento farmacológico prescrito pelo cardiologista / Background: Patients with coronary artery disease, needing odontological treatment under local anesthesia with vasoconstrictor agents, comprised a special group to manage because of multiple aspects. In this situation, cardiovascular disease can be presented with serious complications, such as: arrhythmias, unstable angina and even acute myocardial infarction. The dental practioner facing these controversies must know the anesthesical solutions, drug interactions and possible cardiovascular repercussions. Objectives: To evaluate the occurrence of myocardial ischemic parameters during or after the odontological treatment such as: 1) ST-segment changes evaluated by Holter system, left ventricular hypocontractility by Doppler-echocardiography and serium biomarkers elevation; 2) angina pectoris, arrhythmias and mitral insufficiency. Methods: The coronary patients were submitted to dental extractions under local anesthesia with or without vasoconstrictor and were divided into two groups according to randomization. All patients were monitor with Holter throughout 24 hours; Doppler-echocardiograms were done before and after odontological interventions and the biochemical markers were measured before and 24 hours after the dental extractions (CKMB mass, CKMB activity and Troponin T). Besides that, cardiac rate and blood pressure were also measured pre and post-anesthesia and post-dental extractions. The Doppler-echocardiograms were done to evaluate the left ventricular contractility and possible mitral insufficiency. Results: Between May 2004 and May 2005, fifty-four patients with coronary artery disease and with indication for dental extraction were included in this study. Patients were equally divided into two groups: 27 patients treated with local anesthesia with vasoconstrictor (group I) and 27 patients without vasoconstrictor (group II). The mean age of group I was 58 years old (SD 7.98) and of group 2 was 55 years old (SD 8.57); male gender was 59.3 per cent in group I and 66.7 per cent in group II; 66.6 per cent had previous myocardial infarction with or without ST elevation in group I and 77.7 per cent in group II. In group I the mean dental extraction was 1.6 teeth per patient (SD 0.96) and 1.8 teeth per patient (SD 1.21) in group II. The mean number of anesthesic tubes per patient were 1.5 tubes (SD 0.87) and 1.8 tubes (SD 0.79) for groups I and II, respectively. Three patients from group I had ST-segment depression (1.0 mm) during the anesthesia application, and in none of these patients were observed any other ischemic method. Two other patients from group I had CKMB mass elevation. In none of the patients was observed left ventricular hypocontractility, angina pectoris, arrhythmias or mitral insufficiency. Conclusions: The dental extraction performed under the use of anesthesia with epinephrine 1:100,000 do not cause additional ischemical risks, since it is done with good anesthesical technique and maintenance of the pharmacological treatment prescribed by the cardiologist

A fluoxetina, fármaco inibidor seletivo da recaptação de serotonina (ISRS), tem sido amplamente utilizada no tratamento da depressão. Este antidepressivo possui diversos efeitos sobre o sistema cardiovascular podendo alterar a função cardíaca e a inibição da função de diversos receptores e canais iônicos diretamente envolvidos na regulação do tônus vasomotor. Crestani et al. (2011) demonstraram que ratos tratados cronicamente com fluoxetina exibem aumento da pressão arterial e redução do componente simpático do baroreflexo. Estes resultados sugerem aumento do tônus vasomotor e desequilíbrio de fatores responsáveis por sua regulação. A hipótese do trabalho é que o tratamento crônico com fluoxetina aumentará a reatividade vascular a estímulos contráteis e diminuirá para estímulos relaxantes. Portanto o objetivo do presente trabalho foi investigar se o tratamento crônico com fluoxetina promove alterações de reatividade no leito mesentérico arterial isolado de ratos e em artérias mesentéricas isoladas. Foram utilizados ratos Wistar (230-270 gr) divididos em 2 grupos: (I) veículo (água por 21 dias) e (II) fluoxetina crônico (fluoxetina 10 mg/kg/dia por 21 dias na água de beber). Protocolos de reatividade vascular da artéria mesentérica de resistência e do leito arterial mesentérico (LAM), de expressão gênica e proteica de componentes das vias de sinalização envolvidos nestas respostas foram realizados. O tratamento crônico com fluoxetina promoveu redução da resposta contrátil a fenilefrina. Este resultado foi associado a uma menor expressão de tirosina hidroxilase e recaptação de noradrenalina nas terminações simpáticas do LAM. A sinalização da ERK1/2 também foi diminuída. Em contraste, houve aumento da resposta contrátil ao cloreto de potássio, sem alteração da contração a estimulação elétrica periarterial. O tratamento com fluoxetina promoveu ainda aumento de óxido nítrico (NO), maior fosforilação do resíduo serina1177 da eNOS e sensibilidade dos canais para K+ ativados por ATP (KATP). Em conclusão, a fluoxetina promove redução da resposta contrátil no LAM devido ao aumento de NO e participação de canais para K+. Além disso, a regulação negativa da liberação de noradrenalina e da sinalização da ERK1/2 pode contribuir para a menor resposta contrátil no músculo liso vascular. O aumento da resposta relaxante na artéria mesentérica de resistência pode ser mediado pelo aumento de NO, maior fosforilação da eNOS e ativação de canais para KATP . / Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) drug, has been widely used in the treatment of depression. This antidepressant has several effects on the cardiovascular system and may alter cardiac function and also inhibits the function of several receptors and ion channels directly involved in the regulation of vasomotor tone. Crestani et al. (2011) reported that rats chronically treated with fluoxetine exhibit increased blood pressure and reduced sympathetic component of the baroreflex. These results suggest increased vasomotor tone and imbalance of factors responsible for its regulation. We hypothesize that the chronic treatment with fluoxetine will increase vascular reactivity to contractile stimulus and will reduce to relaxant stimulus. Therefore the objective of this study was to investigate whether chronic treatment with fluoxetine promotes changes on the reactivity of isolated mesenteric arterial bed and resistance mesenteric arteries from rats. Wistar rats (230-270 g) were used and divided in two groups: (I) vehicle (water for 21 days) and (II) chronic fluoxetine (fluoxetine 10 mg/ kg/ day for 21 days in drinking water). Protocols of vascular reactivity were performed on resistance mesenteric arteries and mesenteric arterial bed (MAB). In addition, gene and protein expression of the signaling pathways involved in these responses was evaluated. Chronic treatment with fluoxetine decreased contractile response to phenylephrine. This result was associated with reduced tyrosine hydroxylase expression as well as noradrenaline (NA) reuptake in MAB sympathetic nerve endings. Similarly, ERK 1/2 signaling was decreased. In contrast, fluoxetine treatment increased contractile response to potassium chloride (KCl) without changing the electric field stimulation-(EFS)-induced contraction. Fluoxetine treatment also increased nitric oxide (NO), the phosphorylation levels of eNOS at serine1177 residue and KATP channels sensitivity. In conclusion, fluoxetine promotes reduction of the contractile response in MAB due to increase in NO and K+ channels contribution. In addition, negative regulation of NA release and ERK 1/2 signaling may contribute to decrease smooth muscle contractile response. Increased resistance mesenteric artery relaxant response may be mediated by increased NO, eNOS phosphorylation and KATP channels activation.

A proteína dissulfeto isomerase (PDI) foi identificada como uma possível reguladora da NADPH oxidase (Nox) vascular, principal enzima responsável pela produção de espécies reativas de oxigênio (EROs) na hipertensão arterial. Assim, o objetivo deste trabalho foi investigar o papel da PDI na geração de EROs em leitos vasculares de ratos espontaneamente hipertensos (SHR) durante o desenvolvimento da hipertensão arterial. Os resultados demonstraram um aumento na geração de EROs, expressão de Nox1 e PDI, em artérias mesentéricas, coronárias e pulmonares de animais SHR com 8 e 12 semanas. Os animais foram tratados com Losartan, que reduziu a pressão arterial, a geração de EROs e a expressão de PDI e Nox1 em artérias mesentéricas, coronárias e artérias pulmonares de animais SHR; e também com Nifedipino, que embora tenha reduzido a pressão arterial e a geração de EROs e a expressão de Nox4, não reduziu a expressão de PDI. Os dados obtidos sugerem que a PDI poderia contribuir para o estresse oxidativo e disfunção vascular durante o desenvolvimento da hipertensão arterial. / Protein disulfide isomerase (PDI) was identified as a possible regulator of NADPH oxidase (Nox) vascular, major enzyme responsible for the reactive oxygen species (ROS) production in hypertension. The aim of this study was to investigate the role of PDI in ROS generation in spontaneously hypertensive rats (SHR) vascular beds during hypertension development. The results showed an increase in ROS generation, Nox1 and PDI expression in mesenteric, coronary and pulmonary arteries from SHR with 8 and 12 weeks old. The animals were treated with Losartan, which reduced blood pressure, the generation of ROS and expression of PDI and Nox1 in mesenteric arteries, coronary and pulmonary arteries of SHR, and also with Nifedipine, that also reduce blood pressure and ROS generation and Nox4 expression but did not reduce PDI expression. The data suggest that PDI could contribute to oxidative stress and vascular dysfunction during the development of hypertension.

Introdução. A elevação dos marcadores inflamatórios e de necrose miocárdica, após intervenção coronária percutânea, pode interferir nos resultados clínicos. No entanto, pouco se conhece sobre a terapia com estatinas pré-procedimento na redução destes marcadores em pacientes estáveis de baixo risco. Objetivo. Avaliar se o uso de estatina, antes do implante eletivo de stent coronário (ISC), reduz os níveis plasmáticos de marcadores inflamatórios e de necrose miocárdica, em pacientes com doença arterial coronária (DAC), estáveis e de baixo risco. Métodos. Neste estudo observacional prospectivo, 100 pacientes (n=50 em uso de estatina vs n=50 sem uso de estatina) com DAC estável foram submetidos à implante eletivo de stent coronário. Marcadores inflamatórios (proteína C reativa [PCR], interleucina[IL] -6, fator de necrose tumoral- e matrix metaloproteinase-9) e marcadores de necrose miocárdica (troponina I e CK-MB ) foram dosados antes e 24 horas após o implante eletivo de stent coronário. Resultados. Todos os pacientes apresentaram um aumento significativo de PCR e IL-6, após ISC. No entanto, esse aumento foi anulado em pacientes que faziam uso de estatina antes de ISC em relação àqueles que não tomavam estatina: 75% vs 150% (p <0,001) e 192% vs 300% (p <0,01) respectivamente. Os outros marcadores pró-inflamatórios foram semelhantes para os dois grupos de pacientes. Troponina I e CK-MB não se alterou, após ISC, independentemente, da terapia com estatina anterior ou não. Conclusão. O pré-tratamento com estatina reduz a magnitude da inflamação após ISC, demonstrada por aumentos significativamente menores de PCR e IL-6, em pacientes com DAC, estável e de baixo risco. Lesão miocárdica periprocedimento foi irrelevante e não foi afetada pela terapia com estatina pré-procedimento nesta população / Background. The elevation of markers of inflammatory and myocardial necrosis after percutaneous coronary intervention may interfere on clinical outcome. However, little is known concerning preprocedural statin therapy on the reduction of these markers in stable patients at low-risk. Objective. To evaluate if statin therapy prior to elective coronary stent implantation (CSI) reduces the plasma levels of markers inflammatory and myocardial necrosis in patients with low-risk stable coronary artery disease (CAD). Methods. In this prospective, observational study, 100 patients (n=50 on statin therapy vs n=50 not on statin) with stable CAD underwent elective CSI. Inflammatory (C-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor-a and matrix metalloproteinase-9) and myocardial necrosis markers (troponin I and CK-MB) were determined before and 24 hours after CSI. Results. All patients presented a significant increase of CRP and IL-6 after CSI. However, this increase was blunted in patients on statin therapy prior to CSI than those without statin therapy: 75% vs 150% (p<0.001), and 192% vs 300% (p<0.01), respectively for PCR and IL-6. The other pro-inflammatory markers were not affected in both sets of patients. Troponin I and CK-MB did not change after CSI regardless of previous statin therapy or not. Conclusions. Previous treatment with statins reduces the magnitude of procedural inflammation, denoted by markedly lower increases of CRP and IL-6 levels, in elective CSI on stable CAD patients. Periprocedural myocardial injury was not significant in this population

FINALIDADE: Defeitos na depuração plasmática de quilomícrons e seus remanescentes (QM) predispõem à doença arterial coronária (DAC). QM ligam-se a seus receptores hepáticos específicos (RLP) e aos receptores de LDL (LDL-r). As estatinas reduzem o LDL-colesterol (LDL-C) e melhoram a depuração plasmática de QM, aumentando a expressão hepática do LDL-r. A ezetimiba (EZE), um bloqueador da absorção do colesterol, também aumenta a expressão de LDL-r nos seres humanos. Este estudo avaliou os efeitos isolados da EZE na depuração plasmatica de QM artificial em pacientes DAC. Também foram testados os efeitos da associação da sinvastatina em dose baixa com EZE em comparação com a máxima dose de sinvastatina sobre depuração plasmática de QM. MÉTODOS: 25 pacientes com DAC estável (idade 61 ± 5 anos), após um período de seis semanas de washout de estatinas, foram randomizados para um ou outro tratamento com 10 mg EZE (grupo 1, n = 13) ou sinvastatina 20 mg (grupo 2, n = 12). Os pacientes evoluíram para 10mg + 20mg de sinvastatina com EZE ou sinvastatina 80 mg, respectivamente. Os estudos cinéticos foram realizados no início e após 6 e 12 semanas de cada braço do tratamento. A emulsão lipídica de QM marcada com 14C-CE (que mede a remoção QM e remanescente) e 3H-TG (que mede a lipólise de QM) foi injetada e amostras de sangue foram coletadas durante 60 minutos para determinar taxas de remoção fracionária de radioisótopos (TFR) por análise compartimental. As comparações foram feitas por analise de medidas repetidas (ANOVA). RESULTADOS: Não houve diferenças nas características clínicas e laboratoriais entre os grupos. As TFR de 14C-CE (1/min) no grupo 1 foram 0,005 ± 0,004, 0,011 ± 0,007 e 0,018 ± 0,004 e no grupo 2 foram 0,004 ± 0,002, 0,011 ± 0,008 e 0,019 ± 0,007, respectivamente, à admissão, 6 e 12 semanas ( p <0,05 e ns, respectivamente, para comparações de tempo e grupo). As TFR de 3H-TG (1/min) no grupo 1 foram de 0,017 ± 0,01, 0,024 ± 0,011 e 0,042 ± 0,013 e no grupo 2 foi de 0,01 ± 0,016, 0,022 ± 0,009 e 0,037 ± 0,011, respectivamente, no início do estudo, 6 e 12 semanas ( p <0,05 e ns, respectivamente, para comparações de tempo e grupo). Mudanças semelhantes também foram encontradas para o LDL-C (mg/dL): 142 ± 22,113 ± 19, 74 ± 17 para grupo1 e 119 ± 22, 92 ± 15 e 72 ± 15 para o grupo 2, respectivamente, na admissão, 6 e 12 semanas (p <0,05 para o tempo e ns para o grupo). CONCLUSÃO: EZE isolada aumentou a remoção do plasma de QM e remanescentes e a associação com a sinvastatina aumentou os seus efeitos. A sinvastatina em dose baixa associada à EZE apresentou efeitos favoráveis semelhantes tanto na depuração plasmática de QM quanto na redução de LDL-C em comparação com 80mg de sinvastatina / PURPOSE: Defects on plasma clearance of chylomicrons and their remnants (CM) predispose to coronary heart disease (CHD). CM bind both to their specific liver receptors (LRP) and to the LDL receptors (LDL-r). Statins reduce LDL-cholesterol (LDL-C) and improve the plasma clearance of CM by increasing the expression of hepatic LDL-r. Ezetimibe (EZE), a cholesterol absorption blocker, also increases LDL-r expression in humans. This study evaluated the isolated effects of EZE on the plasma clearance of artificial CM in CHD subjects. We also tested the effects of the association of low dose simvastatin with EZE in comparison with maximal simvastatin dose upon CM plasma clearance. METHODS: 25 stable CHD patients (age 61 ± 5 years, 98%men) after a 6 week statin washout period were randomized for either treatment with EZE 10 mg (group 1, n= 13) or simvastatin 20 mg (group 2 n=12). Patients were progressed to 10mg EZE+ simvastatin 20mg or simvastatin 80 mg, respectively. Kinetic studies were done at baseline and after 6 and 12 weeks of each treatment arm. The CM emulsion labelled with 14C-CE (that measures CM and remnant removal) and 3H-TG (that measures CM lipolysis) was injected and blood samples were collected during 60 minutes to determine radioisotopes fractional catabolic rates (FCR) by compartmental analysis. Comparisons were made repeated measurements ANOVA. RESULTS: There were no differences in clinical and laboratory characteristics between the groups. The 14C-CE FCR (1/min) in group 1 were 0.005±0.004, 0.011±0.007 and 0.018±0.004 and in group 2 were 0.004±0.002, 0.011±0.008 and 0.019±0.007 respectively at baseline, 6 and 12 weeks (p<0.05 and n.s respectively for time and group comparisons). The 3H-TG FCR (1/min) in group 1 were 0.017±0.01, 0.024±0.011 and 0.042±0.013 and in group 2 were 0.01± 0.016, 0.022±0.009 and 0.037±0.011 respectively at baseline, 6 and 12 weeks (p <0.05 and n.s respectively for time and group comparisons). Similar changes were also found for LDL-C (mg/dL):142 ± 22,113 ± 19, 74 ± 17 for group1 and 119 ± 22, 92 ± 15, and 72 ± 15 for group 2 respectively at baseline, 6 and 12 weeks (p<0.05 for time and n.s. for group). CONCLUSION: EZE alone increased the removal from plasma of CM and remnants, the association with simvastatin increased its effects. The low dose simvastatin associated with EZE showed similar favourable effects in both CM plasma clearance and LDL-C in comparison with 80 mg simvastatin

Depression is an independent risk factor for morbidity and mortality in patients with coronary artery disease (CAD). Altered autonomic nervous system (ANS) activity, a common feature of depression, is also a risk factor for cardiac events in patients with CAD. Heart rate variability (HRV) reflects ANS activity, and reduced HRV predicts morbidity in cardiac populations. The purpose of this study was to determine whether differences in HRV exist between depressed and nondepressed patients with CAD. Twenty-one depressed inpatients, with angiographically documented CAD were retrospectively matched to 21 nondepressed CAD patients by sex, age, and smoking status. Demographic, medical, psychological interview data, and 24-hour ECG recordings were obtained. Depressed subjects had significantly lower HRV, or trends toward lower HRV, than nondepressed subjects, even after controlling for severity of CAD. Subject groups did not differ on left ventricular ejection fraction, history of myocardial infarction, or any other relevant medical variable assessed. These results suggest that depression is associated with decreased HRV in patients with CAD, and may help to explain the increased rates of cardiac events observed in CAD patients with depression.

Objective: To examine the association between subclinical atherosclerosis (ascertained as coronary artery calcium; CAC) in asymptomatic individuals in the Central Appalachian region of the United States and individual- and geographic-level factors. Methods: Data were obtained from participants in CAC screening during 2012 and 2016. CAC score was assessed as CAC=0 (no plaque), 1≤CAC≤99 (mild plaque), 100≤CAC≤399 (moderate plaque), and CAC≥400 (severe plaque). Additionally, data on demographics (age, sex, and race), medical conditions, lifestyle factors, and family history of coronary artery disease (CAD) were obtained. Further, zip codes of place of residence for participants were used to generate geographic-level data. Descriptive statistics were used to estimate the prevalence of CAC, and multinomial logistic regression models were used to delineate significant factors. Results: Of 1512 participants, 57.6% had CAC>0. The prevalence of mild, moderate, and severe plaques was 31.6%, 16.3%, and 9.7%, respectively. Demographic, medical conditions, lifestyle factors, and family history of CAD were associated with increased risk for subclinical atherosclerosis. Further, the proportion of minority residents significantly increased the risk for severe plaque [RRR=1.06; p-value=0.04] and the proportion of residents on government assistance significantly decreased the risk for mild plaque [RRR=0.93; p-value=0.03]. Conclusion: The results imply that the proportion of minority residents in a geographic area is associated with increased relative risk for subclinical atherosclerosis, while the proportion of residents on government assistance decreased such risk. However, future geographic or neighborhood-level studies with larger sample size are needed to delineate further the consistency of these results in the Central Appalachian population.

Abnormalities in the vascular pattern of a retina, such as morphologic changes in vessel shape, branching pattern, width, tortuosity, or the appearance of retinal lesions, may be associated with the occurrence of retinopathies or cardiovascular diseases. Thus, an automated quantitative analysis of changes in vessel morphology may help indicating the clinical signs of aforementioned retinopathies, describing their early occurrence or severity. The responses obtained from different types of retinal vessels, i.e., arteries and veins, may be variable to retinopathies and their measurement may lead to a more precise diagnosis compared to that by the average response accounted for the entire vessel network. I propose a set of automated methods in order to analyze the retinal vessel network and to quantify its morphologic properties with respect to arteries and veins, in two-dimensional color fundus images. The analytical methods include; 1) Forma- tion of a well connected vessel network, 2) Structural mapping of a vessel network, 3) Artery-venous classification, and 4) Blood vessel hemorrhage detection. The quan- tification methods include vessel morphology analysis based on the measurement of tortuosity, width, branching angle, branching coefficient, and fractal dimension. The aforementioned morphologic parameters are measured with respect to arteries and veins separately in a vessel network. The methods are validated with the manually annotated retinal fundus images as a ground truth. The major contribution of this thesis includes the development of automated methods for; 1) Identification and separation of retinal vessel trees for individual vessel analysis, 2) Automated quantification of morphologic characteristics of retinal vessels for quick and precise measurement, 3) Automated quantification of vessel morphology with respect to arteries and veins, and 4) Analysis of two datasets, a) malarial retinopathy subject dataset, b) longitudinal study dataset. The ability of the automated methods to quantify the retinal vessel specific properties may enable the individual vessel analysis as an alternative to a time- consuming and subjective clinical evaluation, or to a quantitative morphology char- acterization averaged over the entire vessel network. The objective evaluation may indicate the progression of retinopathies precisely and may help characterizing nor- mal and abnormal vascular patterns with respect to arteries and veins. This may enable a quick diagnosis, treatment availability, prognosis, and facilitation of clinical health-care procedures in remote areas.

The overall aim of my PhD research work is to design, develop, and evaluate a new practical environment to generate separated representations of arterial and venous trees in non-contrast pulmonary CT imaging of human subjects and to extract quantitative measures at different tree-levels. Artery/vein (A/V) separation is of substantial importance contributing to our understanding of pulmonary structure and function, and immediate clinical applications exist, e.g., for assessment of pulmonary emboli. Separated A/V trees may also significantly boost performance of airway segmentation methods for higher tree generations. Although, non-contrast pulmonary CT imaging successfully captures higher tree generations of vasculature, A/V are indistinguishable by their intensity values, and often, there is no trace of intensity variation at locations of fused arteries and veins. Patient-specific structural abnormalities of vascular trees further complicate the task. We developed a novel multi-scale topo-morphologic opening algorithm to separate A/V trees in non-contrast CT images. The algorithm combines fuzzy distance transform, a morphologic feature, with a topologic connectivity and a new morphological reconstruction step to iteratively open multi-scale fusions starting at large scales and progressing towards smaller scales. The algorithm has been successfully applied on fuzzy vessel segmentation results using interactive seed selection via an efficient graphical user interface developed as a part of my PhD project. Accuracy, reproducibility and efficiency of the system are quantitatively evaluated using computer-generated and physical phantoms along with in vivo animal and human data sets and the experimental results formed are quite encouraging. Also, we developed an arc-skeleton based volumetric tree generation algorithm to generate multi-level volumetric tree representation of isolated arterial/venous tree and to extract vascular measurements at different tree levels. The method has been applied on several computer generated phantoms and CT images of pulmonary vessel cast and in vivo pulmonary CT images of a pig at different airway pressure. Experimental results have shown that the method is quite accurate and reproducible. Finally, we developed a new pulmonary vessel segmentation algorithm, i.e., a new anisotropic constrained region growing method that encourages axial region growing while arresting cross-structure leaking. The region growing is locally controlled by tensor scale and structure scale and anisotropy. The method has been successfully applied on several non-contrast pulmonary CT images of human subjects. The accuracy of the new method has been evaluated using manually selection of vascular and non-vascular voxels and the results found are very promising.

Atherosclerosis is a term coined to describe a state in which arterial wall thickens due to the accumulation of fatty materials like cholesterol. Though not completely understood, it is believed to occur due to the accumulation of macrophage white blood cells and promoted by low density lipoprotein. Increase in accumulation of plaque leads to enlargement of arteries as arterial wall tries to remodel itself. But eventually the plaque ruptures, letting out its inner content to blood stream. The ruptured plaque clots and heals and shrinks down as well but leaves behind stenosis - narrowing of cross section. Depending on the degree of stenosis blood supply from the artery to its respective organ could decrease and even get blocked completely. Frequently, as the vulnerable plaques rupture, thrombus formed as such could flow through bloodstream towards smaller vessels and block them, leading to a sudden death of tissues fed by that vessel. If the plaques do not rupture and artery gets enlarged to a great extent then it results in an aneurysm. Such blockage of coronary arteries in heart can lead to myocardial infarction - heart attack, in carotid arteries in brain can lead to what is called a stroke, in peripheral arteries in legs can lead to ulcers, gangrene (death of tissue) and hence loss of leg, in renal arteries can lead to kidney malfunction. The most disturbing fact about atherosclerosis is the inability to detect the disease in preliminary stages. As stated by Miller (2001), most of the times coronary artery disease (CAD) gets diagnosed only after 50-75 percent occlusion of arteries.