Decision-making process in radiology: the magnetic resonance example in the TA context

Based on the report for “Project IV” unit of the PhD programme on Technology Assessment (Doctoral Conference) at Universidade Nova de Lisboa (December 2011). This thesis research has the supervision of António Moniz (FCT-UNL and ITAS-KIT) and Michael Decker (Karlsruhe Institute of Technology-ITAS). Other members of the thesis committee are Carlos Alberto da Silva (University of Évora), José Maria de Albuquerque (Institute of Welding and Quality), Lotte Steuten (University of Twente), Mário Forjaz Secca (FCT-UNL) and Nelson Chibeles Martins (FCT-UNL).

Technology governance in radiology: the example of magnetic resonance imaging

Based on the report for the unit “Project III” of the PhD programme on Technology Assessment in 2011. The unit was supervised by Prof. António B. Moniz (FCT-UNL).

Electron transfer complex between nitrous oxide reductase and cytochrome c552 from Pseudomonas nautica: kinetic, nuclear magnetic resonance, and docking studies

Biochemistry. 2008 Oct 14;47(41):10852-62. doi: 10.1021/bi801375q

Psicopatologia obsessivo-compulsiva na distonia focal primária : aspectos neuropsiquiátricos de uma doença do movimento

RESUMO: pela contracção involuntária de grupos musculares de extensão variável, originando movimentos involuntários e posturas anómalas, por vezes dolorosas. O tratamento convencional consiste em injecções localizadas de toxina botulínica, podendo, em casos refractários, estar indicado o tratamento por estimulação cerebral profunda. A neurobiologia da distonia focal primária permanece incompletamente compreendida. Os estudos de neuro-imagem estrutural e funcional revelam alterações subtis da anatomia e funcionamento do estriado e das vias cortico-basais, com destaque para o aumento do volume, da actividade metabólica e da neuroplasticidade do putamen e de áreas corticais motoras, pré-motoras e sensitivas. O conjunto destas alterações aponta para uma disrupção da regulação inibitória de programas motores automáticos sustentados pelo estriado e pelas vias ortico-subcorticais. Nos últimos anos tem crescido o interesse pelas manifestações psiquiátricas e cognitivas da distonia (estas últimas muito pouco estudadas). Tem despertado particular interesse a possível associação entre distonia focal primária e perturbação obsessivo-compulsiva (POC), cuja neurobiologia parece notavelmente sobreponível à da distonia primária. Com efeito, os estudos de neuro-imagem estrutural e funcional na POC revelam consistentemente aumento do volume e actividade do estriado e do córtex órbito-frontal, apontando mais uma vez para uma disfunção do controlo inibitório, no estriado, de programas comportamentais e cognitivos automáticos. Objectivos: 1. Explorar a prevalência e intensidade de psicopatologia em geral, e de psicopatologia obsessivo-compulsiva em particular, numa amostra de indivíduos com distonia focal primária; 2. Explorar a ocorrência, natureza e intensidade de alterações do funcionamento cognitivo numa amostra de indivíduos com distonia focal primária; 3. Investigar a associação entre a gravidade da distonia focal, a intensidade da psicopatologia, e a intensidade das alterações cognitivas. Metodologia: Estudo de tipo transversal, caso-controlo, observacional e descritivo, com objectivos puramente exploratórios. Casos: 45 indivíduos com distonia focal primária (15 casos de blefaroespasmo, 15 de cãibra do escrivão, 15 de distonia cervical espasmódica), recrutados através da Associação Portuguesa de Distonia. Critérios de inclusão: idade = 18; distonia focal primária pura (excluindo casos de distonia psicogénica possível ou provável de acordo com os critérios de Fahn e Williams); Metabolismo do cobre e Ressonância Magnética Nuclear sem alterações. Controlos doentes: 46 casos consecutivos recrutados a partir da consulta externa do Hospital Egas Moniz: 15 doentes com espasmo hemifacial, 14 com espondilartropatia cervical, 17 com síndrome do canal cárpico. Controlos saudáveis: 30 voluntários. Critérios de exclusão para todos os grupos: Mini-Mental State Examination patológico, tratamento actual com anti-colinérgicos, antipsicóticos, inibidores selectivos da recaptação da serotonina, antidepressivos tri- ou tetracíclicos. Avaliação: Avaliação neurológica: história e exame médico e neurológico completos. Cotação da gravidade da distonia com a Unified Dystonia Rating Scale. Avaliação psicopatológica: Symptom Check-List-90-Revised; entrevista psiquiátrica de 60 minutos incluindo a Mini-International Neuropsychiatric Interview (MINI), versão 4.4 (validada em Português), complementada com os módulos da MINI Plus versão 5.0.0 para depressão ao longo da vida e dependência/ abuso do álcool e outras substâncias ao longo da vida; Yale-Brown Obsessive-Compulsive Symptom Checklist e a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Avaliação neuropsicológica: Wisconsin Card Sorting Test (WCST; flexibilidade cognitiva); Teste de Stroop (inibição de resposta); Block Assembly Test (capacidade visuo-construtiva); Teste de Retenção Visual de Benton (memória de trabalho visuo-espacial). Análise estatística:os dados foram analisados com a aplicação informática SPSS for Windows, versão 13. Para a comparação de proporções utilizaram-se o teste do Chi-quadrado e o teste de Fisher. Para a comparação de variáveis quantitativas entre dois grupos utilizou-se o teste t de Student ou o teste U de Mann-Whitney (teste de Wilcoxon no caso de amostras emparelhadas). Para comparações de médias entre três grupos recorreu-se à Análise de Variância a um factor (variáveis de intervalo e de rácio), ou ao teste de Kruskal-Wallis (variáveis ordinais). Para o estudo da associação entre variáveis foram utilizados os coeficientes de correlação de Pearson ou de Spearman, a análise de correlações canónicas, a análise de trajectórias e a regressão logística. Adoptou-se um Alpha de 0.05. Resultados: Os doentes com distonia focal primária apresentaram uma pontuação média na Y- -BOCS significativamente superior à dos dois grupos de controlo. Em 24.4% dos doentes com distonia a pontuação na Y-BOCS foi superior a 16. Estes doentes eram predominantemente mulheres, tinham uma maior duração média da doença e referiam predominantemente sintomas obsessivo-compulsivos (SOC) de contaminação e lavagem. Os dois grupos com doença crónica apresentaram pontuações médias superiores às dos indivíduos saudáveis nas escalas de ansiedade, somatização e psicopatologia geral. Os doentes com distonia tratados com toxina botulínica apresentaram pontuações inferiores às dos doentes não tratados nas escalas de ansiedade generalizada, fobia, somatização e depressão, mas não na Y-BOCS. Sessenta por cento dos doentes com distonia apresentavam pelo menos um diagnóstico psiquiátrico actual ou pregresso. O risco de apresentar um diagnóstico psiquiátrico actual era menor nos doentes tratados com toxina botulínica, aumentando com a gravidade da doença. A prevalência de POC foi 8,3% e a de depressão major 37,7%. No WCST e na Prova de Benton, os doentes com distonia focal primária demonstraram um desempenho inferior ao de ambos os grupos de controlo, cometendo sobretudo erros perseverativos. Os doentes com distonia e pontuação na Y-BOCS > 16 cometeram mais erros e respostas perseverativas no WCST do que os restantes doentes com distonia. As análises de correlações e de trajectórias revelaram que nos doentes com distonia a gravidade da distonia foi, juntamente com a idade e a escolaridade, o factor que mais interagiu com o desempenho cognitivo. Discussão: o nosso estudo é o primeiro a descrever, nos mesmos doentes com distonia focal primária, SOC significativos e alterações cognitivas. Os nossos resultados confirmam a hipótese de uma associação clínica específica entre distonia focal primária e psicopatologia obsessivo-compulsiva. Confirmam igualmente que a distonia focal primária está associada a um maior risco de desenvolver morbilidade psiquiátrica ansiosa e depressiva. O tratamento com toxina botulínica reduz este risco, mas não influencia os SOC. Entre os doentes com distonia, os que têm SOC significativos poderão diconstituir um grupo particular com maior duração da doença (mas não uma maior gravidade), predomínio do sexo feminino e predomínio de SOC de contaminação e limpeza. Em termos cognitivos, os indivíduos com distonia focal primária apresentam défices significativos de flexibilidade cognitiva (particularmente acentuados nos doentes com SOC significativos) e de memória de trabalho visuo-espacial. Estes últimos devem-se essencialmente a um défice executivo e não a uma incapacidade visuo-construtiva ou visuo-perceptiva. A disfunção cognitiva não é explicável pela psicopatologia depressiva nem pela incapacidade motora, já que os controlos com doença periférica crónica tiveram um desempenho superior ao dos doentes com distonia. No seu conjunto os nossos resultados sugerem que os SOC que ocorrem na distonia focal primária constituem uma das manifestações clínicas da neurobiologia desta doença do movimento. O predomínio de sintomas relacionados com higiene e o perfil disexecutivo de alterações cognitivas–perseveração e dificuldades executivas de memória de trabalho visuo-espacial – apontam para a via cortico-basal dorso-lateral e para as áreas corticais que lhe estão associadas como estando implicadas na tripla associação entre sintomas motores, obsessivo-compulsivos e cognitivos. Conclusões: A distonia focal primária é um síndrome neuropsiquiátrico complexo com importantes manifestações não motoras, nomeadamente compromisso cognitivo do tipo disexecutivo e sintomas obsessivo-compulsivos. Clinicamente estas manifestações representam necessidades de tratamento que vão muito para além da simples incapacidade motora, devendo ser activamente exploradas e tratadas.-------------- ABSTRACT: Introduction: primary focal dystonia is an idiopathic movement disorder that manifests as involuntary, sustained contraction of muscular groups, leading to abnormal and often painful postures of the affected body part. Treatment is symptomatic, usually with local intramuscular injections of botulinum toxin. The neurobiology of primary focal dystonia remains unclear. Structural and functional neuroimaging studies have revealed subtle changes in striatal and cortical-basal pathway anatomy and function. The most consistent findings involve increased volume and metabolic activity of the putamen and of motor, pre-motor and somato-sensitive cortical areas. As a whole, these changes have been interpreted as reflecting a failure of striatal inhibitory control over automatic motor programs sustained by cortical-basal pathways. The last years have witnessed an increasing interest for the possible non-motor – mainly psychiatric and cognitive – manifestations of primary focal dystonia. The possible association of primary focal dystonia with obsessive-compulsive disorder (OCD) has raised particular interest. The neurobiology of the two disorders has indeed remarkable similarities: structural and functional neuroimaging studies in OCD have revealed increased volume and metabolic activity of the striatum and orbital-frontal cortex, again pointing to a disruption of inhibitory control of automatic cognitive and behavioural programs by the striatum. Objectives: 1. To explore the prevalence and severity of psychopathology – with a special emphasis on obsessive-compulsive symptoms (OCS) – in a sample of patients with primary focal dystonia;2. To explore the nature and severity of possible cognitive dysfunction in a sample of patients with primary focal dystonia; 3. To explore the possible association between dystonia severity, psychiatric symptom severity, and cognitive performance, in a sample of patients with primary focal dystonia. Methods: cross-sectional, case-control, descriptive study. Cases: forty-five consecutive, primary pure focal dystonia patients recruited from the Portuguese Dystonia Association case register (fifteen patients with blepharospasm, 15 with cervical dystonia and 15 with writer’s cramp). Inclusion criteria were: age = 18; primary pure focal, late-onset dystonia (excluding possible or probable psychogenic dystonia according to the Fahn & Williams criteria); normal copper metabolism and Magnetic Resonance Imaging. Diseased controls: forty-six consecutive subjects from our hospital case register (15 patients with hemi-facial spasm; 14 with cervical spondilarthropathy and cervical spinal root compression; 17 with carpal tunnel syndrome). Healthy controls were 30 volunteers.Exclusion criteria for all groups: Mini-Mental State Examination score below the validated cut-off for the Portuguese population (<23 for education between 1 and 11 years; <28 for education >11 years); use of anti-cholinergics, neuroleptics, selective serotonin reuptake inhibitors, triciclic or tetraciclic antidepressants. Assessment: neurological assessment: complete medical and neurological history and physical examination; dystonia severity scoring with the Unified Dystonia Rating Scale. Psychiatric assessment:Symptom Check-List-90-Revised; 60 minute-long psychiatric interview, including Mini-International Neuropsychiatric Interview (MINI), version 4.4 (validated Portuguese version), extended with the sections for life-time major depressive disorder and life-time alcohol and substance abuse disorder from MINI-Plus version 5.0.0; Yale-Brown Obsessive-Compulsive Symptom Checklist and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Cognitive assessment: Wisconsin Card Sorting Test (WCST; cognitive set-shifting ability); Stroop Test (response inhibition); Block Assembly Test(visual-constructive ability); Benton’s Visual Retention Test (visual-spatial working memory). Statistic analysis: Data were analyzed with SPSS for Windows version 13. Proportions were compared using Chi-Square test, or Fisher’s exact test when appropriate. Student’s t-test or Mann-Whitney’s U test (or Wilcoxon’s teste in the case of matched samples) were used for two-group comparisons. P-values were corrected for multiple comparisons. One-way ANOVA with Bonferroni post-hoc analysis (interval data), or the Kruskal-Wallis Test (ordinal data), were used for three-group comparisons. Associations were analysed with Pearson’s or Spearman’s correlation coefficients, canonical correlations, path analysis and logistic regression analysis. Alpha was set at 0.05. Results: Dystonia patients had higher Yale-Brown Obsessive-Compulsive Symptom scores than both control groups. 24.4% of primary dystonia patients had a Y-BOCS score > 16. These patients were predominantly women; they had longer disease duration, and showed a predominance of hygiene-related OCS. The two groups with chronic disease had higher anxiety, somatization and global psychopathology scores than healthy subjects. Primary dystonia patients undergoing treatment with botulinum toxin had lower anxiety, phobia, somatization and depression scores than their untreated counterparts, but similar Y-BOCS scores. Sixty percent of primary dystonia patients had at least one lifetime psychiatric diagnosis. The odds of having a currently active psychiatric diagnosis were lower in botulinum toxin treated patients, and increased with dystonia severity. The prevalence of OCD was 6.7%, and the lifetime prevalence of major depression was 37.7%. Primary dystonia patients had a lower performance than the two control groups in both the WCST and Benton’s Visual Retention Test, mainly due to an excess of perseveration errors. Primary dystonia patients with Y-BOCS score > 16 had much higher perseveration error and perseveration response scores than dystonia patients with Y-BOCS = 16. Correlation and path analysis showed that, in the primary dystonia group, dystonia severity, along with age and education, was the main factor influencing cognitive performance. Discussion: our study is the first description ever of concomitant significant OCS and cognitive impairment in primary dystonia patients. Our results confirm that primary dystonia is specifically associated with obsessive-compulsive psychopathology. They also confirm that primary focal dystonia patients are at a higher risk of developing anxious and depressive psychiatric morbidity. Treatment with botulinum toxin decreases this risk, but does not influence OCS. Primary focal dystonia patients with significant OCS may constitute a particular subgroup. They are predominantly women, with higher disease duration (but not severity) and a predominance of hygiene related OCS.In terms of cognitive performance, primary focal dystonia patients have significant deficits involving set-shifting ability and visual-spatial working memory. The latter result from an essentially executive deficit, rather than from a primary visual-constructive apraxia or perceptual deficit. Furthermore, cognitive flexibility difficulties were more prominent in the subset of primary dystonia patients with significant OCS. The cognitive dysfunction found in dystonia patients is not attributable to depressive psychopathology or motor disability, as their performance was significantly lower than that of similarly impaired diseased controls. Our results suggest that OCS in primary focal dystonia are a direct, primary manifestation of the motor disorder’s neurobiology. The predominance of hygiene-related symptoms and the disexecutive pattern of cognitive impairment – set-shifting and visual-spatial working memory deficits – suggest that the dorsal-lateral cortical-basal pathway may play a decisive role in the triple association of motor dysfunction, OCS and cognitive impairment. Conclusions: primary focal dystonia is a complex neuropsychiatric syndrome with significant non- -motor manifestations, namely cognitive executive deficits and obsessive-compulsive symptoms.Clinically, our results show that PFD patients may have needs for care that extend far beyond a merely motor disability and must be actively searched for and treated.

Prostate Cancer: The Role of Multiparametric Magnetic Resonance Imaging

Multiparametric Magnetic Resonance Imaging has been increasingly used for detection, localization and staging of prostate cancer over the last years. It combines high-resolution T2 Weighted-Imaging and at least two functional techniques, which include Dynamic Contrast–Enhanced Magnetic Resonance Imaging, Diffusion-Weighted Imaging, and Magnetic Resonance Imaging Spectroscopy. Although the combined use of a pelvic phased-array and an Endorectal Coil is considered the state-of-the-art for Magnetic Resonance Imaging evaluation of prostate cancer, Endorectal Coil is only absolute mandatory for Magnetic Resonance Imaging Spectroscopy at 1.5 T. Sensitivity and specificity levels in cancer detection and localization have been improving with functional technique implementation, compared to T2 Weighted-Imaging alone. It has been particularly useful to evaluate patients with abnormal PSA and negative biopsy. Moreover, the information added by the functional techniques may correlate to cancer aggressiveness and therefore be useful to select patients for focal radiotherapy, prostate sparing surgery, focal ablative therapy and active surveillance. However, more studies are needed to compare the functional techniques and understand the advantages and disadvantages of each one. This article reviews the basic principles of prostatic mp-Magnetic Resonance Imaging, emphasizing its role on detection, staging and active surveillance of prostate cancer.

Post-Treated Prostate Cancer: Normal Findings and Signs of Local Relapse on Multiparametric Magnetic Resonance Imaging

The use of multiparametric magnetic resonance imaging (mp-MRI) for prostate cancer has increased over recent years, mainly for detection, staging, and active surveillance. However, suspicion of recurrence in the set of biochemical failure is becoming a significant reason for clinicians to request mp-MRI. Radiologists should be able to recognize the normal post-treatment MRI findings. Fibrosis and atrophic remnant seminal vesicles after prostatectomy are often found and must be differentiated from local relapse. Moreover, brachytherapy, external beam radiotherapy, cryosurgery, and hormonal therapy tend to diffusely decrease the signal intensity of the peripheral zone on T2-weighted images (T2WI) due to the loss of water content, consequently mimicking tumor and hemorrhage. The combination of T2WI and functional studies like diffusion-weighted imaging and dynamic contrast-enhanced improves the identification of local relapse. Tumor recurrence tends to restrict on diffusion images and avidly enhances after contrast administration either within or outside the gland. The authors provide a pictorial review of the normal findings and the signs of local tumor relapse after radical prostatectomy, external beam radiotherapy, brachytherapy, cryosurgery, and hormonal therapy.

Magnetic resonance imaging and ultrasound in hepatosplenic schistosomiasis mansoni

We report the findings of abdominal ultrasound and magnetic resonance imaging observed in a patient with advanced schistosomiasis mansoni. A 25-year-old man with hepatosplenic schistosomiasis and variceal bleeding confirmed by upper endoscopy was submitted to abdominal ultrasound and magnetic resonance imaging. During surgery for portal hypertension, a liver biopsy was taken and the diagnosis of Symmers' fibrosis was confirmed. magnetic resonance imaging scans gave more precise information about the gallbladder, periportal thickening and abdominal venous system than did the ultrasound.

A method to correct the flow distortion of offshore wind data using CFD simulation and experimental wind tunnel tests

The assessment of wind energy resource for the development of deep offshore wind plants requires the use of every possible source of data and, in many cases, includes data gathered at meteorological stations installed at islands, islets or even oil platforms—all structures that interfere with, and change, the flow characteristics. This work aims to contribute to the evaluation of such changes in the flow by developing a correction methodology and applying it to the case of Berlenga island, Portugal. The study is performed using computational fluid dynamic simulations (CFD) validated by wind tunnel tests. In order to simulate the incoming offshore flow with CFD models a wind profile, unknown a priori, was established using observations from two coastal wind stations and a power law wind profile was fitted to the existing data (a=0.165). The results show that the resulting horizontal wind speed at 80 m above sea level is 16% lower than the wind speed at 80 m above the island for the dominant wind direction sector.

Ultrasound and magnetic resonance imaging findings in Schistosomiasis mansoni: expanded gallbladder fossa and fatty hilum signs

INTRODUCTION: There is no study relating magnetic resonance imaging (MRI) to ultrasound (US) findings in patients with Schistosomiasis mansoni. Our aim was to describe MRI findings inpatients with schistosomal liver disease identified by US. METHODS: Fifty-four patients (mean age 41.6±13.5years) from an area endemic for Schistosomiasis mansoni were selected for this study.All had US indicating liver schistosomal fibrosis and were evaluated with MRI performed witha 1.5-T superconducting magnet unit (Sigma). RESULTS: Forty-seven (87%) of the 54 patientsshowing signs of periportal fibrosis identified through US investigation had confirmed diagnosesby MRI. In the seven discordant cases (13%), MRI revealed fat tissue filling in the hilar periportalspace where US indicated isolated thickening around the main portal vein at its point of entryto the liver. We named this the fatty hilum sign. One of the 47 patients with MRI evidence ofperiportal fibrosis had had his gallbladder removed previously. Thirty-five (76.1%) of the other46 patients had an expanded gallbladder fossa filled with fat tissue, whereas MRI of the remainingeleven showed pericholecystic signs of fibrosis. CONCLUSIONS: Echogenic thickening of thegallbladder wall and of the main portal vein wall heretofore attributed to fibrosis were frequentlyidentified as fat tissue in MRI. However, the gallbladder wall thickening shown in US (expandedgallbladder fossa in MRI) is probably secondary to combined hepatic morphologic changes inschistosomiasis, representing severe liver involvement.