Capillaroscopy is a non-invasive and safe tool which allows the evaluation of the morphology of the microcirculation. Since its recent incorporation in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis together with its assessed role to monitor disease progression, capillaroscopy became a ‘mainstream’ investigation for rheumatologists. Given its increasing use by a variety of physicians internationally both in daily practice to differentiate primary from secondary Raynaud's phenomenon, as well as in research context to predict disease progression and monitor treatment effects, standardisation in capillaroscopic image acquisition and analysis seems paramount. To step forward to this need, experts in the field of capillaroscopy/microcirculation provide in this very consensus paper their view on image acquisition and analysis, different capillaroscopic techniques, normal and abnormal capillaroscopic characteristics and their meaning, scoring systems and reliability of image acquisition and interpretation. / Revisión por pares

Nailfold capillaroscopy is a useful tool to diagnose endocrine, cardiovascular, neuropsychiatric, rheumatic and other diseases. Diagnoses are made on the presence or absence of certain types of capillary loops which are classified according to their shape. We have surveyed six clinicians, asking them to classify 217 capillary loops, in order to establish quantitative nailfold capillary loop classification criteria. The participating clinicians were not unanimous about the classification of any capillary, and there was no consensus about the class of 17% of the capillary loops. Some of the clinicians classified two occurrences of the same shape differently. This clearly demonstrates the need for well established classification criteria. Nailfold capillary loop classes can be divided into two major groups: Descriptive Classes (DC); "cuticulis", "open", "tortuous", "crossed", "bizarre" and "bushy", and Label Classes; "enlarged", "elongated" and "giant". Furthermore label classes can be divided into two groups, Width Anomaly Classes (WAC); "enlarged" and "giant", and Length Anomaly Class (LAC), "elongated". While descriptive classes give information about the shape of a loop, label classes emphasise dimensional anomalities of a loop. Assignment of a loop with one the descriptive or label classes causes information loss about the dimensions or shape, respectively. In order to preserve as much information as possible within a class, we propose a new class system that contains 17 classes which are the combination of WAC, LAC and DC. We propose quantitative classification criteria for commonly used classes: "cuticulis", "open", "tortuous", "elongated" and "giant". Although the class "enlarged" can be expressed quantitatively, inappropriate assignments of "enlarged" by the paricipating clinicians have not allowed us to set quantitative classification criteria. While definition of the class "crossed" is purely qualitative, a classification mechanism that is neither qualitative nor quantitative is proposed for "bizarre" and "bushy" loops. We propose the use of pattern recognition algorithms that are based on the evaluation of the capillary shape parameters such as loop length, loop width, limb width, the curvature, orientation, etc., to classify capillaries. By the use of mathematical morphology, skeletonization, topological relations, feature vectors, in an hierarchical structure, the software TANCCAS (The Automated Nailfold Capillary Classification and Analysis System) has been developed to calculate the shape parameters and to classify the capillary loops. These algorithms have been implemented on a Pentium PC and have resulted in an 88% accuracy level which is compared to participating clinicians' overall classifications of the test images.

Objetivos. Analisar prospectivamente os dados de capilaroscopiaperiungueal (CPU) em pacientes com dermatomiosite recém-diagnosticada (DM) e correlacioná-los com citocinas angiogênicas séricas e características clínicas e laboratoriais. Métodos. Vinte e três pacientes com DM com < 12 meses de sintomas foram incluídos no estudo. Para avaliar os níveis de citocinas séricas, os pacientes foram pareados 23 voluntários saudáveis por idade, sexo e etnia. As características da CPU e os parâmetros da atividade da DM foram analisados. Resultados. Foram observados níveis aumentados de angiogenina (ANG) e de fator de crescimento de endotélio vascular-1 (VEGF1) séricos de forma significativa em pacientes com DM em comparação com os controles saudáveis. Os níveis de ANG sérica correlacionaram-se positiva e negativamente, respectivamente, com a densidade capilar e as áreas avasculares. Além disso, a densidade capilar correlacionou-se inversamente com o número de capilares ectasiados, capilares gigantes e áreas avasculares. O número de capilares ectasiados correlacionou-se positivamente com a Escala Visual Analógica (EVA) do paciente e do médico, a presença de eritema facial, capilares gigantes e micro-hemorragias. Os capilares gigantes apresentaram correlação positiva com EVA do médico e da atividade cutânea, capilares ectasiados, áreas avasculares, micro-hemorragias e capilares em forma de arbustos e correlação negativa com a densidade capilar. Micro-hemorragias correlacionaram-se positivamente com o sinal de \"V do decote\" e EVA do médico. O VEGF1 sérico não mostrou relação com os parâmetros da CPU ou com características clínicas e laboratoriais relacionadas a DM. Além disso, 15 dos 23 pacientes foram avaliados prospectivamente após 3,21 anos. Todos os pacientes tiveram resposta clínica com melhora significativa em todos os parâmetros da CPU, exceto em relação a capilares ectasiados e número de capilares em forma de arbustos. Conclusões. A CPU pode ser uma ferramenta útil para avaliar a atividade da doença em DM de início recente e a sua correlação com a ANG sérica sugere a participação desta citocina na neoangiogênese da doença / Objectives. To prospectively analyze nailfold capillaroscopy (NC) findings in new-onset dermatomyositis (DM) and to correlate NC findings with serum angiogenic cytokines and DM clinical and laboratory features. Methods. Twenty-three patients with DM who experienced < 12 months of symptoms were included in the study. To assess serum cytokine levels, 23 age-, sexand ethnicity-matched healthy volunteers were used. NC characteristics and DM activity parameters were analyzed. Results. Significantly higher serum angiogenin (ANG) and vascular endothelial growth factor-1 (VEGF1) levels were observed in DM patients than in controls. Capillary density and avascular areas correlated positively and negatively, respectively, with serum levels of ANG. Moreover, the capillary density correlated inversely with the number of enlarged and giant capillaries and avascular areas. The number of enlarged capillaries correlated positively with patient and physician VAS, the presence of a facial rash, giant capillaries and microhemorrhages. Giant capillaries had a positive correlation with physician and cutaneous VAS, enlarged capillaries, avascular areas, microhemorrhages and bushy capillaries and a negative correlation with capillary density. Microhemorrhages correlated positively with the \"V-neck\" sign and physician VAS. VEGF1 showed no relationship with the NC parameters with DMrelated clinical and laboratory features. Additionally, 15 out of 23 patients were assessed prospectively after 3.21 years. All patients had a major clinical response with significant improvement in all NC parameters, except for enlarged and bushy capillaries. Conclusions. The NC may be a useful tool to assess disease activity in recent-onset DM, and it can also reinforce the role of ANG in the angiogenesis of this myopathy

Introdução: A capilaroscopia periungueal (CPU) tem sido relacionada ao dano a órgãos-alvo na esclerose sistêmica (ES). No entanto, estudos relativos à gravidade das alterações da CPU com a mortalidade evidenciam resultados discrepantes. Este estudo tem como objetivo verificar associação da gravidade da microangiopatia periférica na CPU com o risco de morte na ES. Pacientes e métodos: Cento e setenta pacientes com ES foram prospectivamente avaliados e acompanhados em média de 9,3 anos. Além da avaliação clínica, os pacientes foram submetidos à sorologia, testes de função pulmonar, ecocardiograma e tomografia computadorizada pulmonar de alta resolução (TCAR). A perda capilar na CPU foi avaliada pelo escore avascular (EA), que varia de 0 a 3. O número médio de ectasias, megacapillaries e hemorragias por dedo também foi registrado. O modelo de Cox proporcional Uni e Multivariado foi utilizado para analisar a associação do escore avascular com o risco de morte através da associação Hazard ratio (HR). Resultados: Por análise de Cox univariada, o escore avascular associado à mortalidade foi estatisticamente significativo (HR = IC 1.54, 95%: 1.13-2.09, p = 0.006), mas outras variáveis capilaroscópicas (número de ectasias, megacapillaries e hemorragias por dedo) não foram (p> 0,40 para todos os testes). Após o ajuste para escore de pele, idade, sexo, origem étnica, e sinais de isquemia digital, a associação entre o escore avascular perdeu significância estatística (HR = 1.23, IC: 0.84-1.81, p = 0.276). Também não houve associação significativa do escore avascular quando ajustado para uma combinação de resultados de exames complementares. Conclusões: A gravidade da desvascularização na CPU está relacionada a um maior risco de mortalidade na ES; No entanto, a associação não é estatisticamente significativa após ajuste para outras variáveis clínicas e laboratoriais. Apesar do fato de não mostrar uma associação independente do EA com a mortalidade, consideramos que é útil na avaliação de pacientes com diagnóstico de esclerose sistêmica, uma vez que pode dar uma visão geral e confiável da gravidade da doença. / Introduction: The nailfold capillaroscopy (NCF) has been related to end-organ damage in Systemic sclerosis (SSc). However, studies relating the severity of NCF alterations with mortality have rendered mixed results. This study aims to verify the association of the severity of peripheral microangiopathy in the NFC with the risk of death in SSc. Patients and methods: One hundred and seventy SSc patients were prospectively evaluated and followed a mean of 9.3 years. Besides clinical evaluation, patients underwent serology, pulmonary function tests, Doppler echocardiography, and pulmonary high resolution computed tomography (HRCT). Capillary loss on NCF was evaluated using the avascular score (AS), ranging from 0 to 3. The mean number of ectasias, megacapillaries and hemorrhages per finger was also recorded; univariate and multivariate Cox proportional models were used to analyze the association of the AS with the risk of death using hazard ratios (HR). Results: By univariate Cox analysis, the AS was statistically significantly associated with mortality (HR = 1.54, 95% CI: 1.13 to 2.09, p = 0.006), but other capillaroscopic variables (number of ectasias, megacapillaries and hemorrhages per finger) were not (p> 0.40 for all tests). After adjustment for skin score, age, gender, ethnic background, and signs of digital ischemia, the association between the AS weakened and lost statistical significance (HR = 1.23, CI: 0.84 to 1.81, p=0.276). There was also no significant association of the avascular score when adjusted for a combination of results of complementary tests. Conclusions: The severity of devascularization on NCF is related to a higher risk of mortality in SSc; however, the association disappeared after adjustment for other clinical and laboratory variables. Despite the fact that we were not able to show an independent association of the AS with mortality, we consider it useful in the evaluation in patients diagnosed with systemic sclerosis, since it can give a general view and reliable view of the severity of the disease.

Introdução: A capilaroscopia periungueal (CPU) tem sido relacionada ao dano a órgãos-alvo na esclerose sistêmica (ES). No entanto, estudos relativos à gravidade das alterações da CPU com a mortalidade evidenciam resultados discrepantes. Este estudo tem como objetivo verificar associação da gravidade da microangiopatia periférica na CPU com o risco de morte na ES. Pacientes e métodos: Cento e setenta pacientes com ES foram prospectivamente avaliados e acompanhados em média de 9,3 anos. Além da avaliação clínica, os pacientes foram submetidos à sorologia, testes de função pulmonar, ecocardiograma e tomografia computadorizada pulmonar de alta resolução (TCAR). A perda capilar na CPU foi avaliada pelo escore avascular (EA), que varia de 0 a 3. O número médio de ectasias, megacapillaries e hemorragias por dedo também foi registrado. O modelo de Cox proporcional Uni e Multivariado foi utilizado para analisar a associação do escore avascular com o risco de morte através da associação Hazard ratio (HR). Resultados: Por análise de Cox univariada, o escore avascular associado à mortalidade foi estatisticamente significativo (HR = IC 1.54, 95%: 1.13-2.09, p = 0.006), mas outras variáveis capilaroscópicas (número de ectasias, megacapillaries e hemorragias por dedo) não foram (p> 0,40 para todos os testes). Após o ajuste para escore de pele, idade, sexo, origem étnica, e sinais de isquemia digital, a associação entre o escore avascular perdeu significância estatística (HR = 1.23, IC: 0.84-1.81, p = 0.276). Também não houve associação significativa do escore avascular quando ajustado para uma combinação de resultados de exames complementares. Conclusões: A gravidade da desvascularização na CPU está relacionada a um maior risco de mortalidade na ES; No entanto, a associação não é estatisticamente significativa após ajuste para outras variáveis clínicas e laboratoriais. Apesar do fato de não mostrar uma associação independente do EA com a mortalidade, consideramos que é útil na avaliação de pacientes com diagnóstico de esclerose sistêmica, uma vez que pode dar uma visão geral e confiável da gravidade da doença. / Introduction: The nailfold capillaroscopy (NCF) has been related to end-organ damage in Systemic sclerosis (SSc). However, studies relating the severity of NCF alterations with mortality have rendered mixed results. This study aims to verify the association of the severity of peripheral microangiopathy in the NFC with the risk of death in SSc. Patients and methods: One hundred and seventy SSc patients were prospectively evaluated and followed a mean of 9.3 years. Besides clinical evaluation, patients underwent serology, pulmonary function tests, Doppler echocardiography, and pulmonary high resolution computed tomography (HRCT). Capillary loss on NCF was evaluated using the avascular score (AS), ranging from 0 to 3. The mean number of ectasias, megacapillaries and hemorrhages per finger was also recorded; univariate and multivariate Cox proportional models were used to analyze the association of the AS with the risk of death using hazard ratios (HR). Results: By univariate Cox analysis, the AS was statistically significantly associated with mortality (HR = 1.54, 95% CI: 1.13 to 2.09, p = 0.006), but other capillaroscopic variables (number of ectasias, megacapillaries and hemorrhages per finger) were not (p> 0.40 for all tests). After adjustment for skin score, age, gender, ethnic background, and signs of digital ischemia, the association between the AS weakened and lost statistical significance (HR = 1.23, CI: 0.84 to 1.81, p=0.276). There was also no significant association of the avascular score when adjusted for a combination of results of complementary tests. Conclusions: The severity of devascularization on NCF is related to a higher risk of mortality in SSc; however, the association disappeared after adjustment for other clinical and laboratory variables. Despite the fact that we were not able to show an independent association of the AS with mortality, we consider it useful in the evaluation in patients diagnosed with systemic sclerosis, since it can give a general view and reliable view of the severity of the disease.

Introdução: A capilaroscopia periungueal (CPU) tem sido relacionada ao dano a órgãos-alvo na esclerose sistêmica (ES). No entanto, estudos relativos à gravidade das alterações da CPU com a mortalidade evidenciam resultados discrepantes. Este estudo tem como objetivo verificar associação da gravidade da microangiopatia periférica na CPU com o risco de morte na ES. Pacientes e métodos: Cento e setenta pacientes com ES foram prospectivamente avaliados e acompanhados em média de 9,3 anos. Além da avaliação clínica, os pacientes foram submetidos à sorologia, testes de função pulmonar, ecocardiograma e tomografia computadorizada pulmonar de alta resolução (TCAR). A perda capilar na CPU foi avaliada pelo escore avascular (EA), que varia de 0 a 3. O número médio de ectasias, megacapillaries e hemorragias por dedo também foi registrado. O modelo de Cox proporcional Uni e Multivariado foi utilizado para analisar a associação do escore avascular com o risco de morte através da associação Hazard ratio (HR). Resultados: Por análise de Cox univariada, o escore avascular associado à mortalidade foi estatisticamente significativo (HR = IC 1.54, 95%: 1.13-2.09, p = 0.006), mas outras variáveis capilaroscópicas (número de ectasias, megacapillaries e hemorragias por dedo) não foram (p> 0,40 para todos os testes). Após o ajuste para escore de pele, idade, sexo, origem étnica, e sinais de isquemia digital, a associação entre o escore avascular perdeu significância estatística (HR = 1.23, IC: 0.84-1.81, p = 0.276). Também não houve associação significativa do escore avascular quando ajustado para uma combinação de resultados de exames complementares. Conclusões: A gravidade da desvascularização na CPU está relacionada a um maior risco de mortalidade na ES; No entanto, a associação não é estatisticamente significativa após ajuste para outras variáveis clínicas e laboratoriais. Apesar do fato de não mostrar uma associação independente do EA com a mortalidade, consideramos que é útil na avaliação de pacientes com diagnóstico de esclerose sistêmica, uma vez que pode dar uma visão geral e confiável da gravidade da doença. / Introduction: The nailfold capillaroscopy (NCF) has been related to end-organ damage in Systemic sclerosis (SSc). However, studies relating the severity of NCF alterations with mortality have rendered mixed results. This study aims to verify the association of the severity of peripheral microangiopathy in the NFC with the risk of death in SSc. Patients and methods: One hundred and seventy SSc patients were prospectively evaluated and followed a mean of 9.3 years. Besides clinical evaluation, patients underwent serology, pulmonary function tests, Doppler echocardiography, and pulmonary high resolution computed tomography (HRCT). Capillary loss on NCF was evaluated using the avascular score (AS), ranging from 0 to 3. The mean number of ectasias, megacapillaries and hemorrhages per finger was also recorded; univariate and multivariate Cox proportional models were used to analyze the association of the AS with the risk of death using hazard ratios (HR). Results: By univariate Cox analysis, the AS was statistically significantly associated with mortality (HR = 1.54, 95% CI: 1.13 to 2.09, p = 0.006), but other capillaroscopic variables (number of ectasias, megacapillaries and hemorrhages per finger) were not (p> 0.40 for all tests). After adjustment for skin score, age, gender, ethnic background, and signs of digital ischemia, the association between the AS weakened and lost statistical significance (HR = 1.23, CI: 0.84 to 1.81, p=0.276). There was also no significant association of the avascular score when adjusted for a combination of results of complementary tests. Conclusions: The severity of devascularization on NCF is related to a higher risk of mortality in SSc; however, the association disappeared after adjustment for other clinical and laboratory variables. Despite the fact that we were not able to show an independent association of the AS with mortality, we consider it useful in the evaluation in patients diagnosed with systemic sclerosis, since it can give a general view and reliable view of the severity of the disease.

Detection of diseases in an early stage is very important since it can make the treatment of patients easier, safer and more ecient. For the detection of rheumatic diseases, and even prediction of tendencies towards such diseases, capillaroscopy is becoming an increasingly recognized method. Nail-fold capillaroscopy is a non-invasive imaging technique that is used for analysis of microcirculation abnormalities that may lead todisease like systematic sclerosis, Reynauds phenomenon and others. The main goal of this master thesis project is to provide new tools and techniques for the analysis of capillaroscopy images from the nail-fold area. Image processing and machine learning techniques are applied to images obtained by digital microscopes, like Mediscope as produced by Optilia Instruments AB, Sollentuna. This thesis oers a novel way for segmentation of capillaries from images as well as (semi)automatic capillary width calculation and automatic annotation of capillaries. These tools provide new insights into the structure of capillaries and also reduce the time required for measurement/annotation of capillaries.

In the field of dynamic capillaroscopy, measurements of the capillary blood cell velocity (CBV) give significant insight into the human body. For instance, diabetes, hypertension and peripheral arterial occlusive disease all affect CBV. However, the videos used to measure CBV – captured with a microscope – are often displaced in relation to the microscope by small motions of the finger or toe. Stabilisation algorithms are commonly used to reduce this problem, in order to carry out measurements such as CBV using the stabilised video. Artificial capillaroscopy videos were used to compare the stabilisation algorithms Mutual information, Single-step DFT, Block matching and Phase correlation in terms of computational time; RMSE, PSNR and MSE; and resistance to blurring effects. Single-step DFT was indicated to be the best suited algorithm in all aforementioned metrics. / Inom dynamisk kapilläroskopi ger mätningar av kapillär blod-cell hastighet (CBV) signifikanta insikter inom den mänskliga kroppen. Till exempel, diabetes, hypertoni och perifer arteriell ocklusiv sjukdom påverkar CBV. Däremot är videorna som används för att mäta CBV – tagna med ett mikroskop – ofta förskjutna i relation till mikroskopet på grund av små rörelser av ett finger eller en tå. Stabiliseringsalgoritmer används vanligen för att reducera detta problemet med avsikt att därefter använda den stabiliserade videon för att mäta viktiga egenskaper, som till exempel CBV. Artificiella kapilläroskopivideor användes för att jämföra stabiliseringsalgorithmerna Mutual information, Single-step DFT, Block matching and Phase correlation inom beräkningstid; RMSE, PSNR och MSE; och resistens mot suddighet. Single-step DFT indikerades som den bäst lämpade algoritmen inom de ovannämnda måtten.