Rui Vasco Simões | Hospital Sant Joan De Deu (original) (raw)

Papers by Rui Vasco Simões

Magnetic Resonance in Medicine

Life, 2022

Introduction: Preeclampsia is a multi-system disorder unique to pregnancy responsible for a great... more Introduction: Preeclampsia is a multi-system disorder unique to pregnancy responsible for a great part of maternal and perinatal morbidity and mortality. The precise pathogenesis of this complex disorder is still unrevealed. Methods: We examined the pathophysiological pathways involved in early-onset preeclampsia, a specific subgroup representing its most severe presentation, using LC-MS/MS metabolomic analysis based on multi-level extraction of lipids and small metabolites from maternal blood samples, collected at the time of diagnosis from 14 preeclamptic and six matched healthy pregnancies. Statistical analysis comprised multivariate and univariate approaches with the application of over representation analysis to identify differential pathways. Results: A clear difference between preeclamptic and control pregnancies was observed in principal component analysis. Supervised multivariate analysis using orthogonal partial least square discriminant analysis provided a robust model wi...

Purpose: Bowel motion is a source of artifacts in mouse abdominal MRI. The use of fasting and hyo... more Purpose: Bowel motion is a source of artifacts in mouse abdominal MRI. The use of fasting and hyoscine butylbromide (BUSC) for the purpose of bowel motion reduction has been inconsistently reported, without a thorough assessment of efficacy. This work aimed to better evaluate these methods in the mouse with high-field MRI. Methods: Thirty-two adult C57BL/6 mice were imaged in a pre-clinical 9.4T MR scanner. A FLASH sequence with 284 repetitions was used, lasting 90 minutes, with a ~19s temporal resolution. Eight mice were injected with a high-dose and eight mice with a low-dose bolus of BUSC. Eight mice were food deprived for 4.5-6.5 hours and another group of 8 mice were injected with saline. Two readers reviewed the images and classified the magnitude of bowel motion during each scan. Also, the sum of the absolute differences between consecutive images was calculated for 10-11 min intervals throughout the acquisition and mapped voxelwise for identification of moving regions. After...

Ultrasound in Obstetrics & Gynecology, 2019

Poster discussion Hub abstracts with adequate fetal growth who delivered normally grown neonates ... more Poster discussion Hub abstracts with adequate fetal growth who delivered normally grown neonates (n = 279). To explore the potential influence of medical information in maternal stress, cases were subdivided according to whether there was (n = 229) or not (n = 53) an antenatal diagnosis of FGR. Results: The median [interquartile range (IQR)] maternal perceived stress scale was significantly higher in cases than in controls [23 (17-28) vs. 19 (14-25); p < 0.001]. Importantly, women without antenatal diagnosis of FGR but that delivered a neonate with a birthweight < 10 th centile have significantly higher PSS than controls (p < 0.05). Similarly, median maternal state anxiety was significantly higher in cases compared to controls [1.95 (1.7-2.45) vs. 1.75 (1.5-2.1); p < 0.001]. Conclusions: Maternal stress is increased in IUGR regardless and correlates significantly with birthweight. Knowing the diagnosis of IUGR did not influence the association.

Ultrasound in Obstetrics & Gynecology, 2019

Oral communication abstracts Objectives: Chronic hypoxia is a powerful stimulus for the synthesis... more Oral communication abstracts Objectives: Chronic hypoxia is a powerful stimulus for the synthesis of erythropoietin (EPO) in the fetus resulting in an increase in erythrocyte production and in an increase in the oxygen-carrying capacity. We sought to describe the association between fetoplacental Doppler with cord blood EPO in small for gestational age (SGA) fetuses. Methods: A nested case-control study within a prospective cohort study including 124 controls (birthweight> p10) and 209 SGA cases (BW< p10). Cases an controls were followed-up with fetal biometry and fetoplacental Doppler. Cord blood concentrations of EPO were determined at delivery as a surrogate of chronic intrauterine hypoxia. Logistic regression predictive models evaluating the performance of fetal biometry and fetoplacental Doppler for the identification of chronic hypoxia were appraised. Results: Cord blood plasmatic EPO concentrations were significantly higher in SGA fetuses compared to controls (29.8 [17.2-58.7] vs 22.4 pg/mL [14.3-52.4],p = 0.05). In 87 (41.6%) of SGA fetuses, EPO was above 90 th centile. Among SGA fetuses, those with cord blood EPO concentrations above > 90 th centile presented non-significant differences in EFW centile [3 (1-9) vs 3 (1-8), p = 0.6] and ductus venosus z-score [0.11 (-0.91-0.95) vs.-0.33 (-0.95-0.56),p = 0.3], but higher uterine artery (UtA) z-score [1.42 (-0.58-2.95) vs 0.30 (-0.64-1.25),p = 0.01] and lower cerebroplacental (CPR) ratio z-score [

American Journal of Obstetrics and Gynecology, 2019

Ultrasound in Obstetrics & Gynecology, 2017

On this limited data, either mechanical or chemical IOL in suspected IUGR/SGA is reasonable. Howe... more On this limited data, either mechanical or chemical IOL in suspected IUGR/SGA is reasonable. However, a sizeable RCT specifically to answer the question of chemical versus mechanical IOL in this group, ± pooling of SGA subgroup data from general IOL trials, is required to provide definitive data. OP13.

2011 IEEE 11th International Conference on Data Mining Workshops, 2011

Abstract Pattern Recognition and Data Mining can provide invaluable insights in the field of neur... more Abstract Pattern Recognition and Data Mining can provide invaluable insights in the field of neuro oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic resonance, in the modalities of imaging and spectroscopy, is one of these methods that has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by magnetic resonance remains a challenge in terms of pathological area delimitation. In this ...

Proceedings of the National Academy of Sciences, 2004

Prostate cancer is the most common solid tumor in men, and it shares with all cancers the hallmar... more Prostate cancer is the most common solid tumor in men, and it shares with all cancers the hallmark of elevated, nonhomeostatic cell proliferation. Here we have tested the hypothesis that the SONIC HEDGEHOG (SHH)–GLI signaling pathway is implicated in prostate cancer. We report expression of SHH–GLI pathway components in adult human prostate cancer, often with enhanced levels in tumors versus normal prostatic epithelia. Blocking the pathway with cyclopamine or anti-SHH antibodies inhibits the proliferation of GLI1 + / PSA + primary prostate tumor cultures. Inversely, SHH can potentiate tumor cell proliferation, suggesting that autocrine signaling may often sustain tumor growth. In addition, pathway blockade in three metastatic prostate cancer cell lines with cyclopamine or through GLI1 RNA interference leads to inhibition of cell proliferation, suggesting cell-autonomous pathway activation at different levels and showing an essential role for GLI1 in human cells. Our data demonstrate...

Neoplasia (New York, N.Y.), 2015

Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer c... more Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer cells lines (highly metastatic 4T1; nonmetastatic 67NR) to identify differences in their glucose and glutamine metabolism in response to metabolic and environmental stress. Dynamic magnetic resonance spectroscopy of (13)C-isotopomers showed that 4T1 cells have higher glycolytic and tricarboxylic acid (TCA) cycle flux than 67NR cells and readily switch between glycolysis and oxidative phosphorylation (OXPHOS) in response to different extracellular environments. OXPHOS activity increased with metastatic potential in isogenic cell lines derived from the same primary breast cancer: 4T1 > 4T07 and 168FARN (local micrometastasis only) > 67NR. We observed a restricted TCA cycle flux at the succinate dehydrogenase step in 67NR cells (but not in 4T1 cells), leading to succinate accumulation and hindering OXPHOS. In the four isogenic cell lines, environmental stresses modulated succinate dehy...

BMC Pregnancy and Childbirth, 2014

Background: Preeclampsia is defined as new onset of hypertension and proteinuria at gestational w... more Background: Preeclampsia is defined as new onset of hypertension and proteinuria at gestational week 20 or after. However, use of these measures to predict preeclampsia before its clinical onset is unreliable, and evidence suggests that preeclampsia, eclampsia, or hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome may develop without hypertension or proteinuria being evident. Because of its unpredictability, varying clinical presentation and potential adverse outcomes, pregnant women with suspected preeclampsia require intensive monitoring or hospitalization. Beyond preeclampsia diagnosis, there is a high unmet medical need for more reliable predictive markers for preeclampsia to improve maternal and fetal outcomes and reduce unnecessary hospital admissions. An imbalance of circulating angiogenic and antiangiogenic factors, including raised soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF), has been found in women diagnosed with preeclampsia and before clinical onset of the disease. The PRediction of short-term Outcome in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) was designed to investigate the use of the sFlt-1/PlGF ratio in the short-term prediction of preeclampsia. Methods/Design: This global, multicenter, prospective, double-blind, non-interventional study aims to derive and validate cutoffs for the sFlt-1/PlGF ratio, to rule out (for 1 week) or rule in (within 4 weeks) the occurrence of preeclampsia/eclampsia/HELLP syndrome. Eligible participants are women presenting at 24 to <37 weeks' gestation with clinical suspicion of, but not manifest preeclampsia/eclampsia/HELLP syndrome. Clinical assessments, maternal serum sFlt-1/PlGF sampling and documentation of maternal/neonatal outcomes are performed at regular intervals, using strict diagnostic criteria for preeclampsia-related conditions and outcomes. Serum sFlt-1 and PlGF analysis will be performed using fully automated Elecsys® immunoassays. Investigators and participants will remain blinded to the results. Target recruitment is 1000 participants. Health economic analysis is also planned. Discussion: The results of PROGNOSIS will provide the most comprehensive evidence to date on the accuracy of the sFlt-1/PlGF ratio for short-term prediction of preeclampsia/eclampsia/HELLP syndrome. Adoption of the sFlt-1/PlGF test in clinical practice has the potential to reduce the frequency of adverse pregnancy outcomes for both mother and fetus, and decrease healthcare costs associated with unnecessary hospitalization of women with suspected preeclampsia.

Scientific Reports

Brain damage associated with Alzheimer's disease (AD) occurs even decades before the symptoma... more Brain damage associated with Alzheimer's disease (AD) occurs even decades before the symptomatic onset, raising the need to investigate its progression from prodromal stages. In this context, animal models that progressively display AD pathological hallmarks (e.g. TgF344-AD) become crucial. Translational technologies, such as magnetic resonance spectroscopy (MRS), enable the longitudinal metabolic characterization of this disease. However, an integrative approach is required to unravel the complex metabolic changes underlying AD progression, from early to advanced stages. TgF344-AD and wild-type (WT) rats were studied in vivo on a 7 Tesla MRI scanner, for longitudinal quantitative assessment of brain metabolic profile changes using MRS. Disease progression was investigated at 4 time points, from 9 to 18 months of age, and in 4 regions: cortex, hippocampus, striatum, and thalamus. Compared to WT, TgF344-AD rats replicated common findings in AD patients, including decreased N-acet...

Scientific Reports

Preeclampsia (PE) and fetal growth restriction (FGR) are both placenta-mediated disorders with un... more Preeclampsia (PE) and fetal growth restriction (FGR) are both placenta-mediated disorders with unclear pathogenesis. Metabolomics of maternal and fetal pairs might help in understanding these disorders. We recruited prospectively pregnancies with normotensive FGR, PE without FGR, PE + FGR and uncomplicated pregnancies as controls. Nuclear magnetic resonance metabolomics were applied on plasma samples collected at delivery. Advanced lipoprotein, glycoprotein and choline profiling was performed using the Liposcale test. The software package Dolphin was used to quantify 24 low-molecular-weight metabolites. Statistical analysis comprised the comparison between each group of complicated pregnancies versus controls, considering 5% false discovery rate correction. Lipid profiles were altered in accordance with the clinical presentation of these disorders. Specifically, PE mothers and FGR fetuses (with or without FGR or PE, respectively) exhibited a pro-atherogenic and pro-inflammatory prof...

Tese de doutoramento em Bioquimica (Biofisica Molecular), apresentada a Fac. de Ciencias e Tecnol... more Tese de doutoramento em Bioquimica (Biofisica Molecular), apresentada a Fac. de Ciencias e Tecnologia da Universidade de Coimbra

BMC …, Jan 1, 2010

Classifiers based on pattern recognition analysis of MRS(I) data are becoming important tools for... more Classifiers based on pattern recognition analysis of MRS(I) data are becoming important tools for the noninvasive diagnosis of human brain tumors . Here we investigate the potential interest of perturbation-enhanced MRSI (PE-MRSI), in this case acute hyperglycemia, during moderate brain hypothermia , for improving the discrimination between mouse brain MRS patterns of glioblastoma multiforme (GBM), low grade oligodendroglioma (ODG2), and non-tumor brain parenchyma (NT). Six GBM-bearing mice and two ODG2-bearing mice were scanned at 7 Tesla by PRESS-MRSI with 12 and 136 ms echo-time, during euglycemia (Eug) and also during induced acute hyperglycemia (Hyp), generating altogether four datasets per animal (echo time + glycemic condition): 12Eug, 136Eug, 12Hyp, and 136Hyp. For classifier development, using in-house built software SpectraClassifier 2.0 [5,6], all spectral vectors (spv) selected were unit length normalized (UL2) and used either as training set (76 GBM spv, four mice; 70 ODG2 spv, 2 mice; 54 NT spv, 6 mice) or as independent test set (2 mice, 61 GBM spv and 17 NT spv). All Fisher's LDA classifiers obtained had very good descriptive performance when extracting at least 10 features from the training sets as evaluated by Bootstrapping: correctly classified cases ≥ 99 %. Evaluation of predictive performance with the independent test set clearly revealed that 12Hyp MRSI-based classifiers with at least 5 features provided the best robustness: balanced error rate (BER) for spv prediction < 0.9 %. This highlights the potential interest of perturbation-enhanced MRSI protocols for improving the non-invasive characterization of brain tumors at a preclinical level.

… (ICDMW), 2011 IEEE …, Jan 1, 2011

Abstract Pattern Recognition and Data Mining can provide invaluable insights in the field of neur... more Abstract Pattern Recognition and Data Mining can provide invaluable insights in the field of neuro oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic resonance, in the modalities of imaging and spectroscopy, is one of these methods that has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by magnetic resonance remains a challenge in terms of pathological area delimitation. In this ...

PLOS ONE, Jan 1, 2012

Background: Pattern Recognition techniques can provide invaluable insights in the field of neuro-... more Background: Pattern Recognition techniques can provide invaluable insights in the field of neuro-oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic Resonance (MR), in the modalities of spectroscopy (MRS) and spectroscopic imaging (MRSI), has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by MR remains a challenge in terms of pathological area delimitation.

Ultrasound in Obstetrics and Gynecology

American Journal of Obstetrics and Gynecology, 2015

Neuromethods, 2012

The applications of two magnetic resonance techniques to the study of brain tumours are discussed... more The applications of two magnetic resonance techniques to the study of brain tumours are discussed. MRSI can be performed in vivo in animal models and HRMAS is performed ex vivo. The first one is able to provide "molecular images" of tumours and the second one gives rich metabolomic information from excised biopsies. The application of both techniques yields a high amount of multidimensional data, which can be analysed with complex statistical methods, such as those provided by pattern recognition techniques.

Magnetic Resonance in Medicine

Life, 2022

Introduction: Preeclampsia is a multi-system disorder unique to pregnancy responsible for a great... more Introduction: Preeclampsia is a multi-system disorder unique to pregnancy responsible for a great part of maternal and perinatal morbidity and mortality. The precise pathogenesis of this complex disorder is still unrevealed. Methods: We examined the pathophysiological pathways involved in early-onset preeclampsia, a specific subgroup representing its most severe presentation, using LC-MS/MS metabolomic analysis based on multi-level extraction of lipids and small metabolites from maternal blood samples, collected at the time of diagnosis from 14 preeclamptic and six matched healthy pregnancies. Statistical analysis comprised multivariate and univariate approaches with the application of over representation analysis to identify differential pathways. Results: A clear difference between preeclamptic and control pregnancies was observed in principal component analysis. Supervised multivariate analysis using orthogonal partial least square discriminant analysis provided a robust model wi...

Purpose: Bowel motion is a source of artifacts in mouse abdominal MRI. The use of fasting and hyo... more Purpose: Bowel motion is a source of artifacts in mouse abdominal MRI. The use of fasting and hyoscine butylbromide (BUSC) for the purpose of bowel motion reduction has been inconsistently reported, without a thorough assessment of efficacy. This work aimed to better evaluate these methods in the mouse with high-field MRI. Methods: Thirty-two adult C57BL/6 mice were imaged in a pre-clinical 9.4T MR scanner. A FLASH sequence with 284 repetitions was used, lasting 90 minutes, with a ~19s temporal resolution. Eight mice were injected with a high-dose and eight mice with a low-dose bolus of BUSC. Eight mice were food deprived for 4.5-6.5 hours and another group of 8 mice were injected with saline. Two readers reviewed the images and classified the magnitude of bowel motion during each scan. Also, the sum of the absolute differences between consecutive images was calculated for 10-11 min intervals throughout the acquisition and mapped voxelwise for identification of moving regions. After...

Ultrasound in Obstetrics & Gynecology, 2019

Poster discussion Hub abstracts with adequate fetal growth who delivered normally grown neonates ... more Poster discussion Hub abstracts with adequate fetal growth who delivered normally grown neonates (n = 279). To explore the potential influence of medical information in maternal stress, cases were subdivided according to whether there was (n = 229) or not (n = 53) an antenatal diagnosis of FGR. Results: The median [interquartile range (IQR)] maternal perceived stress scale was significantly higher in cases than in controls [23 (17-28) vs. 19 (14-25); p < 0.001]. Importantly, women without antenatal diagnosis of FGR but that delivered a neonate with a birthweight < 10 th centile have significantly higher PSS than controls (p < 0.05). Similarly, median maternal state anxiety was significantly higher in cases compared to controls [1.95 (1.7-2.45) vs. 1.75 (1.5-2.1); p < 0.001]. Conclusions: Maternal stress is increased in IUGR regardless and correlates significantly with birthweight. Knowing the diagnosis of IUGR did not influence the association.

Ultrasound in Obstetrics & Gynecology, 2019

Oral communication abstracts Objectives: Chronic hypoxia is a powerful stimulus for the synthesis... more Oral communication abstracts Objectives: Chronic hypoxia is a powerful stimulus for the synthesis of erythropoietin (EPO) in the fetus resulting in an increase in erythrocyte production and in an increase in the oxygen-carrying capacity. We sought to describe the association between fetoplacental Doppler with cord blood EPO in small for gestational age (SGA) fetuses. Methods: A nested case-control study within a prospective cohort study including 124 controls (birthweight> p10) and 209 SGA cases (BW< p10). Cases an controls were followed-up with fetal biometry and fetoplacental Doppler. Cord blood concentrations of EPO were determined at delivery as a surrogate of chronic intrauterine hypoxia. Logistic regression predictive models evaluating the performance of fetal biometry and fetoplacental Doppler for the identification of chronic hypoxia were appraised. Results: Cord blood plasmatic EPO concentrations were significantly higher in SGA fetuses compared to controls (29.8 [17.2-58.7] vs 22.4 pg/mL [14.3-52.4],p = 0.05). In 87 (41.6%) of SGA fetuses, EPO was above 90 th centile. Among SGA fetuses, those with cord blood EPO concentrations above > 90 th centile presented non-significant differences in EFW centile [3 (1-9) vs 3 (1-8), p = 0.6] and ductus venosus z-score [0.11 (-0.91-0.95) vs.-0.33 (-0.95-0.56),p = 0.3], but higher uterine artery (UtA) z-score [1.42 (-0.58-2.95) vs 0.30 (-0.64-1.25),p = 0.01] and lower cerebroplacental (CPR) ratio z-score [

American Journal of Obstetrics and Gynecology, 2019

Ultrasound in Obstetrics & Gynecology, 2017

On this limited data, either mechanical or chemical IOL in suspected IUGR/SGA is reasonable. Howe... more On this limited data, either mechanical or chemical IOL in suspected IUGR/SGA is reasonable. However, a sizeable RCT specifically to answer the question of chemical versus mechanical IOL in this group, ± pooling of SGA subgroup data from general IOL trials, is required to provide definitive data. OP13.

2011 IEEE 11th International Conference on Data Mining Workshops, 2011

Abstract Pattern Recognition and Data Mining can provide invaluable insights in the field of neur... more Abstract Pattern Recognition and Data Mining can provide invaluable insights in the field of neuro oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic resonance, in the modalities of imaging and spectroscopy, is one of these methods that has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by magnetic resonance remains a challenge in terms of pathological area delimitation. In this ...

Proceedings of the National Academy of Sciences, 2004

Prostate cancer is the most common solid tumor in men, and it shares with all cancers the hallmar... more Prostate cancer is the most common solid tumor in men, and it shares with all cancers the hallmark of elevated, nonhomeostatic cell proliferation. Here we have tested the hypothesis that the SONIC HEDGEHOG (SHH)–GLI signaling pathway is implicated in prostate cancer. We report expression of SHH–GLI pathway components in adult human prostate cancer, often with enhanced levels in tumors versus normal prostatic epithelia. Blocking the pathway with cyclopamine or anti-SHH antibodies inhibits the proliferation of GLI1 + / PSA + primary prostate tumor cultures. Inversely, SHH can potentiate tumor cell proliferation, suggesting that autocrine signaling may often sustain tumor growth. In addition, pathway blockade in three metastatic prostate cancer cell lines with cyclopamine or through GLI1 RNA interference leads to inhibition of cell proliferation, suggesting cell-autonomous pathway activation at different levels and showing an essential role for GLI1 in human cells. Our data demonstrate...

Neoplasia (New York, N.Y.), 2015

Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer c... more Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer cells lines (highly metastatic 4T1; nonmetastatic 67NR) to identify differences in their glucose and glutamine metabolism in response to metabolic and environmental stress. Dynamic magnetic resonance spectroscopy of (13)C-isotopomers showed that 4T1 cells have higher glycolytic and tricarboxylic acid (TCA) cycle flux than 67NR cells and readily switch between glycolysis and oxidative phosphorylation (OXPHOS) in response to different extracellular environments. OXPHOS activity increased with metastatic potential in isogenic cell lines derived from the same primary breast cancer: 4T1 > 4T07 and 168FARN (local micrometastasis only) > 67NR. We observed a restricted TCA cycle flux at the succinate dehydrogenase step in 67NR cells (but not in 4T1 cells), leading to succinate accumulation and hindering OXPHOS. In the four isogenic cell lines, environmental stresses modulated succinate dehy...

BMC Pregnancy and Childbirth, 2014

Background: Preeclampsia is defined as new onset of hypertension and proteinuria at gestational w... more Background: Preeclampsia is defined as new onset of hypertension and proteinuria at gestational week 20 or after. However, use of these measures to predict preeclampsia before its clinical onset is unreliable, and evidence suggests that preeclampsia, eclampsia, or hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome may develop without hypertension or proteinuria being evident. Because of its unpredictability, varying clinical presentation and potential adverse outcomes, pregnant women with suspected preeclampsia require intensive monitoring or hospitalization. Beyond preeclampsia diagnosis, there is a high unmet medical need for more reliable predictive markers for preeclampsia to improve maternal and fetal outcomes and reduce unnecessary hospital admissions. An imbalance of circulating angiogenic and antiangiogenic factors, including raised soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF), has been found in women diagnosed with preeclampsia and before clinical onset of the disease. The PRediction of short-term Outcome in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) was designed to investigate the use of the sFlt-1/PlGF ratio in the short-term prediction of preeclampsia. Methods/Design: This global, multicenter, prospective, double-blind, non-interventional study aims to derive and validate cutoffs for the sFlt-1/PlGF ratio, to rule out (for 1 week) or rule in (within 4 weeks) the occurrence of preeclampsia/eclampsia/HELLP syndrome. Eligible participants are women presenting at 24 to <37 weeks' gestation with clinical suspicion of, but not manifest preeclampsia/eclampsia/HELLP syndrome. Clinical assessments, maternal serum sFlt-1/PlGF sampling and documentation of maternal/neonatal outcomes are performed at regular intervals, using strict diagnostic criteria for preeclampsia-related conditions and outcomes. Serum sFlt-1 and PlGF analysis will be performed using fully automated Elecsys® immunoassays. Investigators and participants will remain blinded to the results. Target recruitment is 1000 participants. Health economic analysis is also planned. Discussion: The results of PROGNOSIS will provide the most comprehensive evidence to date on the accuracy of the sFlt-1/PlGF ratio for short-term prediction of preeclampsia/eclampsia/HELLP syndrome. Adoption of the sFlt-1/PlGF test in clinical practice has the potential to reduce the frequency of adverse pregnancy outcomes for both mother and fetus, and decrease healthcare costs associated with unnecessary hospitalization of women with suspected preeclampsia.

Scientific Reports

Brain damage associated with Alzheimer's disease (AD) occurs even decades before the symptoma... more Brain damage associated with Alzheimer's disease (AD) occurs even decades before the symptomatic onset, raising the need to investigate its progression from prodromal stages. In this context, animal models that progressively display AD pathological hallmarks (e.g. TgF344-AD) become crucial. Translational technologies, such as magnetic resonance spectroscopy (MRS), enable the longitudinal metabolic characterization of this disease. However, an integrative approach is required to unravel the complex metabolic changes underlying AD progression, from early to advanced stages. TgF344-AD and wild-type (WT) rats were studied in vivo on a 7 Tesla MRI scanner, for longitudinal quantitative assessment of brain metabolic profile changes using MRS. Disease progression was investigated at 4 time points, from 9 to 18 months of age, and in 4 regions: cortex, hippocampus, striatum, and thalamus. Compared to WT, TgF344-AD rats replicated common findings in AD patients, including decreased N-acet...

Scientific Reports

Preeclampsia (PE) and fetal growth restriction (FGR) are both placenta-mediated disorders with un... more Preeclampsia (PE) and fetal growth restriction (FGR) are both placenta-mediated disorders with unclear pathogenesis. Metabolomics of maternal and fetal pairs might help in understanding these disorders. We recruited prospectively pregnancies with normotensive FGR, PE without FGR, PE + FGR and uncomplicated pregnancies as controls. Nuclear magnetic resonance metabolomics were applied on plasma samples collected at delivery. Advanced lipoprotein, glycoprotein and choline profiling was performed using the Liposcale test. The software package Dolphin was used to quantify 24 low-molecular-weight metabolites. Statistical analysis comprised the comparison between each group of complicated pregnancies versus controls, considering 5% false discovery rate correction. Lipid profiles were altered in accordance with the clinical presentation of these disorders. Specifically, PE mothers and FGR fetuses (with or without FGR or PE, respectively) exhibited a pro-atherogenic and pro-inflammatory prof...

Tese de doutoramento em Bioquimica (Biofisica Molecular), apresentada a Fac. de Ciencias e Tecnol... more Tese de doutoramento em Bioquimica (Biofisica Molecular), apresentada a Fac. de Ciencias e Tecnologia da Universidade de Coimbra

BMC …, Jan 1, 2010

Classifiers based on pattern recognition analysis of MRS(I) data are becoming important tools for... more Classifiers based on pattern recognition analysis of MRS(I) data are becoming important tools for the noninvasive diagnosis of human brain tumors . Here we investigate the potential interest of perturbation-enhanced MRSI (PE-MRSI), in this case acute hyperglycemia, during moderate brain hypothermia , for improving the discrimination between mouse brain MRS patterns of glioblastoma multiforme (GBM), low grade oligodendroglioma (ODG2), and non-tumor brain parenchyma (NT). Six GBM-bearing mice and two ODG2-bearing mice were scanned at 7 Tesla by PRESS-MRSI with 12 and 136 ms echo-time, during euglycemia (Eug) and also during induced acute hyperglycemia (Hyp), generating altogether four datasets per animal (echo time + glycemic condition): 12Eug, 136Eug, 12Hyp, and 136Hyp. For classifier development, using in-house built software SpectraClassifier 2.0 [5,6], all spectral vectors (spv) selected were unit length normalized (UL2) and used either as training set (76 GBM spv, four mice; 70 ODG2 spv, 2 mice; 54 NT spv, 6 mice) or as independent test set (2 mice, 61 GBM spv and 17 NT spv). All Fisher's LDA classifiers obtained had very good descriptive performance when extracting at least 10 features from the training sets as evaluated by Bootstrapping: correctly classified cases ≥ 99 %. Evaluation of predictive performance with the independent test set clearly revealed that 12Hyp MRSI-based classifiers with at least 5 features provided the best robustness: balanced error rate (BER) for spv prediction < 0.9 %. This highlights the potential interest of perturbation-enhanced MRSI protocols for improving the non-invasive characterization of brain tumors at a preclinical level.

… (ICDMW), 2011 IEEE …, Jan 1, 2011

Abstract Pattern Recognition and Data Mining can provide invaluable insights in the field of neur... more Abstract Pattern Recognition and Data Mining can provide invaluable insights in the field of neuro oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic resonance, in the modalities of imaging and spectroscopy, is one of these methods that has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by magnetic resonance remains a challenge in terms of pathological area delimitation. In this ...

PLOS ONE, Jan 1, 2012

Background: Pattern Recognition techniques can provide invaluable insights in the field of neuro-... more Background: Pattern Recognition techniques can provide invaluable insights in the field of neuro-oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic Resonance (MR), in the modalities of spectroscopy (MRS) and spectroscopic imaging (MRSI), has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by MR remains a challenge in terms of pathological area delimitation.

Ultrasound in Obstetrics and Gynecology

American Journal of Obstetrics and Gynecology, 2015

Neuromethods, 2012

The applications of two magnetic resonance techniques to the study of brain tumours are discussed... more The applications of two magnetic resonance techniques to the study of brain tumours are discussed. MRSI can be performed in vivo in animal models and HRMAS is performed ex vivo. The first one is able to provide "molecular images" of tumours and the second one gives rich metabolomic information from excised biopsies. The application of both techniques yields a high amount of multidimensional data, which can be analysed with complex statistical methods, such as those provided by pattern recognition techniques.