Translação de um sistema de óptica de difusão para monitoramento de pacientes neurocríticos

Orientador: Rickson Coelho MesquitaTese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb WataghinResumo: As doenças cerebrovasculares são uma das principais causas de morte e incapacidade em todo o mundo. Em 2015, mais de 590.000 pacientes foram hospitalizados por estas doenças no Brasil, com aproximadamente 100.000 óbitos. A prevenção de danos secundários é um dos principais objetivos no tratamento de doenças cerebrovasculares graves, como o acidente vascular cerebral (AVC). No entanto, atualmente há uma falta de métodos não invasivos para monitoramento contínuo da fisiologia cerebral. Neste contexto, a espectroscopia óptica de difusão (DOS) e a espectroscopia de correlação de difusão (DCS) foram recentemente propostas como potenciais monitores não invasivos e contínuos capazes de fornecer informações neurofisiológicas em pacientes neurocríticos. Ao incidir luz infravermelha no escalpo, DCS pode medir o fluxo sanguíneo cerebral (CBF) e DOS pode medir as concentrações de oxi e desoxi-hemoglobina. A combinação de DOS e DCS foi explorada anteriormente para monitorar pacientes em vários cenários clínicos, como monitoramento neonatal, durante intervenções cerebrovasculares e para monitoramento de pacientes neurocríticos. No entanto, a confiabilidade da técnica para fornecer informações precisas em tempo real durante medições longitudinais, bem como durante alguns tipos de intervenções clínicas, permanece em grande parte não estudada. O principal objetivo desta tese foi mostrar que as técnicas de óptica de difusão podem auxiliar de maneira confiável e no monitoramento em tempo real de doenças cerebrovasculares. Para isso, desenvolvemos sistemas baseados em óptica de difusão e testamos a viabilidade destes sistemas em diferentes ambientes clínicos, envolvendo o monitoramento de pacientes dentro de uma unidade de terapia intensiva (UTI), bem como durante o tratamento endovascular de AVC. Primeiro, relatamos a construção e a translação de um sistema híbrido de óptica de difusão, combinando DOS e DCS, para o monitoramento em tempo real da fisiologia cerebral de pacientes internados em uma UTI. Mais especificamente, apresentamos dois estudos de caso, onde mostramos que os parâmetros neurofisiológicos medidos pelas técnicas de óptica de difusão são consistentes com a evolução clínica destes pacientes. Em seguida, relatamos a translação das técnicas de óptica de difusão para monitorar a hemodinâmicas cerebral durante o tratamento endovascular de dois pacientes com oclusões na artéria carótida interna. Nossos resultados identificaram um aumento induzido pela recanalização no CBF ipsilateral, com pouca ou nenhuma alteração no CBF contralateral e no fluxo sanguíneo extracerebral. Nossos resultados mostraram que a óptica de difusão tem grande potencial para monitorar os danos secundários em pacientes neurocríticos, sem interferir com práticas clínicas. Além disso, nossos resultados sugerem que o monitoramento hemodinâmico cerebral com as técnicas ópticas tem potencial para guiar terapias baseadas na fisiologia individual de pacientes. Por fim, para melhorar a confiabilidade das técnicas de ópticas de difusão, também propusemos a implementação de algoritmos aprimorados para a análise de dados. Mostramos que, usando um modelo de duas camadas para DOS/DCS, podemos melhorar a precisão na recuperação das alterações hemodinâmicas cerebraisAbstract: Cerebrovascular diseases are one of the main causes of death and disability worldwide. In 2015, there were more than 590.000 patients hospitalized due to cerebrovascular diseases in Brazil, with approximately 100.000 deaths. Prevention of secondary damage is an important goal in the treatment of severe neurological conditions, such as head trauma and stroke. However, there is currently a lack of non-invasive methods for continuous monitoring of cerebral physiology in real-time. More recently, diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) have been proposed as noninvasive and continuous bedside monitors capable of providing neurophysiology information in neurocritical patients. By shining near-infrared light from the scalp, DCS can measure microvascular cerebral blood flow (CBF), and DOS can measure oxy- and deoxy-hemoglobin concentrations. The combination of DOS and DCS has been previously explored to monitor patients in several clinical scenarios, such as neonatal monitoring, during cerebrovascular interventions, and for monitoring of neurocritical patients. However, the reliability of the technique to provide accurate real-time information during longitudinal (i.e., across multiple days) measurement as well as during a few different clinical interventions remains largely unaddressed. The main goal of this thesis was to show that diffuse optics can reliably aid in monitoring cerebrovascular diseases, in real-time. To that end, we have translated a diffuse optical system to different clinic environments: during long-term monitoring of patients inside an intensive care unit, as well as during an endovascular treatment of stroke. First, we reported the construction and translation of a hybrid diffuse optical system combining DOS and DCS for real-time monitoring of cerebral physiology in a neuro intensive care unit. By presenting two representative case-studies, we show that the neurophysiological parameters measured by diffuse optics at the bedside are consistent with the clinical evolution of the patients. Then, we reported the translation of diffuse optics to monitor frontal-lobe cerebral hemodynamic changes during endovascular treatment of two patients with ischemic stroke due to internal carotid artery occlusions. The monitoring instrument identified a recanalization-induced increase in ipsilateral CBF with little or no concurrent change in contralateral CBF and extracerebral blood flow. Taken together, our results showed that diffuse optics holds promise for monitoring secondary damage in neurocritical patients, with minimal interference with current clinical practices. Additionally, our results suggest that cerebral hemodynamic monitoring with diffuse optics has the potential to guide therapy based on the individual physiology of neurocritical patients. Last, to improve the reliability of the diffuse optical techniques, we have also proposed the implementation of improved algorithms for data analysis. We showed that by using a two-layer model for DOS/DCS, we can improve the accuracy of diffuse optics in recovering the cerebral hemodynamic changesDoutoradoFísicaDoutor em Ciências2014/25486-61504865/2015FAPESPCAPE

Drug abusers have impaired cerebral oxygenation and cognition during exercise

Sem informaçãoBackground: Individuals with Substance Use Disorder (SUD) have lower baseline metabolic activity of the prefrontal cortex (PFC) associated with impairment of cognitive functions in decisionmaking and inhibitory control. Aerobic exercise has shown to improve PFC function and cognitive performance, however, its effects on SUD individuals remain unclear. Purpose: To verify the cognitive performance and oxygenation of the PFC during an incremental exercise in SUD individuals. Methods: Fourteen individuals under SUD treatment performed a maximum graded exercise test on a cycle ergometer with continuous measurements of oxygen consumption, PFC oxygenation, and inhibitory control (Stroop test) every two minutes of exercise at different intensities. Fifteen non-SUD individuals performed the same protocol and were used as control group. Results: Exercise increased oxyhemoglobin (O(2)Hb) and total hemoglobin (tHb) by 9% and 7%, respectively. However, when compared to a non-SUD group, this increase was lower at high intensities (p< 0.001), and the inhibitory cognitive control was lower at rest and during exercise (p< 0.007). In addition, PFC hemodynamics during exercise was inversely correlated with inhibitory cognitive performance (reaction time) (r = -0.62, p = 0.001), and a lower craving perception for the specific abused substance (p = 0.0189) was reported immediately after exercise. Conclusion: Despite SUD individuals having their PFC cerebral oxygenation increased during exercise, they presented lower cognition and oxygenation when compared to controls, especially at elevated intensities. These results may reinforce the role of exercise as an adjuvant treatment to improve PFC function and cognitive control in individuals with SUD.1211115Sem informaçãoSem informaçãoSem informaçã

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EU-GEI)

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Brazilian cave heritage under siege

info:eu-repo/semantics/publishe

Determinação das propriedades dinâmicas em meios turvos usando espectroscopia de correlação de difusão : aplicações ao tecido biológico

Orientador: Rickson Coelho MesquitaDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Física Gleb WataghinResumo: Técnicas de espectroscopia baseadas em óptica de difusão são essenciais para a obtenção das propriedades ópticas e dinâmicas em meios turvos, caracterizados pela predominância dos efeitos de espalhamento sobre a absorção. Nestas condições, a luz se propaga esfericamente no meio, num regime aproximadamente difusivo. A luz espalhada pode então ser detectada no mesmo plano de incidência, e sua detecção fornece informação das propriedades ópticas e dinâmicas das moléculas que compõem o meio. Em particular, a técnica encontra uma vasta aplicação no estudo das propriedades do tecido biológico, uma vez que este se comporta como um meio turvo na região do infravermelho próximo. Por se tratar de uma técnica experimental relativamente recente, pouco é conhecido em relação à propagação da luz em meios com diferentes geometrias, principalmente em relação às propriedades dinâmicas do meio. Este projeto propôs um estudo teórico-experimental detalhado da propagação da luz em meios turvos semi-infinitos e de duas camadas, com foco na obtenção das propriedades dinâmicas do meio, através de uma técnica óptica de difusão conhecida como espectroscopia de correlação de difusão (DCS). Mais especificamente, esse projeto testou as geometrias de um meio semi-infinito e de duas camadas, com o uso de simulações de Monte Carlo e experimentos em ambientes controlados. Foi mostrado que o uso da geometria de duas camadas, ao invés da de um meio semi-infinito, como é usualmente feito na literatura, traz melhoras significativas para a recuperação das propriedades de fluxo do meio. As geometrias usadas neste trabalho representam aproximações mais precisas das estruturas muscular e cerebral, por exemplo, e retratam diferentes situações encontradas em Biologia e Medicina. Por fim, o sistema também foi testado em voluntários sadios. Os resultados obtidos neste projeto tem aplicação direta nas áreas citadas, e podem contribuir significativamente para o desenvolvimento de técnicas físicas para o monitoramento cerebral e muscular na clínica médicaAbstract: Spectroscopic techniques based on diffuse optics are essential for determination of the optical and dynamical properties of turbid media, in which scattering predominates over absorption. Under these conditions, light propagates spherically in the medium, in an approximate diffusive regimen. Scattered light can thus be detected at the same plane of incidence, and its detection can provide information both on the optical and dynamical properties of the medium. Diffuse optical techniques are particularly useful to study the properties of biological tissue, since it behaves like a turbid medium in the near infrared region. Because diffuse optics is a relatively novel experimental technique, not much is known regarding the propagation of light in media with different geometries, particularly with relation to the dynamical properties of the medium. This project proposes a combined theoretical and experimental study of light propagation in semi-infinite and two-layered turbid media, focusing on the dynamical properties of the medium with a diffuse optical technique called diffuse correlation spectroscopy (DCS). More specifically, this project employed the semi-infinite and the two-layer geometries, testing them using Monte Carlo simulations and controlled enviroments. It was shown that by using a two-layer geometry, instead of the semi-infinite geometry, as routinely done in the literature, it is possible to significantly improve the accuracy of the recovered dynamical properties. The geometries tested in this work represent more accurate approximations for muscle and brain structures, for example, and therefore could depict different situations encountered in problems in the fields of Biology and Medicine. Last, the system was also tested in healthy subjects. The results obtained in this project have direct application in the above-cited fields, and may significantly contribute to the development of experimental techniques for diagnosis and/or monitoring of the brain and muscle in the clinicMestradoFísicaMestre em Físic

Affect during incremental exercise: The role of inhibitory cognition, autonomic cardiac function, and cerebral oxygenation

<div><p>Background</p><p>Pleasure is a key factor for physical activity behavior in sedentary individuals. Inhibitory cognitive control may play an important role in pleasure perception while exercising, especially at high intensities. In addition, separate work suggests that autonomic regulation and cerebral hemodynamics influence the affective and cognitive responses during exercise.</p><p>Purpose</p><p>We investigated the effects of exercise intensity on affect, inhibitory control, cardiac autonomic function, and prefrontal cortex (PFC) oxygenation.</p><p>Methods</p><p>Thirty-seven sedentary young adults performed two experimental conditions (exercise and control) in separate sessions in a repeated-measures design. In the exercise condition, participants performed a maximum graded exercise test on a cycle ergometer as we continuously measured oxygen consumption, heart rate variability (HRV), and PFC oxygenation. At each of 8 intensity levels we also measured inhibitory control (Stroop test), associative and dissociative thoughts (ADT), and affective/pleasure ratings. In the control condition, participants sat motionless on a cycle ergometer without active pedaling, and we collected the same measures at the same points in time as the exercise condition. We evaluated the main effects and interactions of exercise condition and intensity level for each measure using two-way repeated measures ANOVAs. Additionally, we evaluated the relationship between affect and inhibitory control, ADT, HRV, and PFC oxygenation using Pearson’s correlation coefficients.</p><p>Results</p><p>For exercise intensities below and at the ventilatory threshold (VT), participants reported feeling neutral, with preservation of inhibitory control, while intensities above the VT were associated with displeasure (<i>p</i><0.001), decreased inhibitory control and HRV (<i>p</i><0.001), and increased PFC oxygenation (<i>p</i><0.001). At the highest exercise intensity, pleasure was correlated with the low-frequency index of HRV (r = -0.34; p<0.05) and the low-frequency/high-frequency HRV ratio (r = -0.33; p<0.05). PFC deoxyhemoglobin was correlated with pleasure two stages above the VT (r = -0.37; p<0.05).</p><p>Conclusion</p><p>Our results support the notion that exercise at high intensities influences inhibitory control and one’s perception of pleasure, which are linked to changes in cardiac autonomic control and cerebral hemodynamics. These findings strengthen the existence of an integrated brain-heart-body system and highlight the importance of exercise intensity in exercise-related behavior in sedentary individuals.</p></div

Drug abusers have impaired cerebral oxygenation and cognition during exercise

<div><p>Background</p><p>Individuals with Substance Use Disorder (SUD) have lower baseline metabolic activity of the prefrontal cortex (PFC) associated with impairment of cognitive functions in decision-making and inhibitory control. Aerobic exercise has shown to improve PFC function and cognitive performance, however, its effects on SUD individuals remain unclear.</p><p>Purpose</p><p>To verify the cognitive performance and oxygenation of the PFC during an incremental exercise in SUD individuals.</p><p>Methods</p><p>Fourteen individuals under SUD treatment performed a maximum graded exercise test on a cycle ergometer with continuous measurements of oxygen consumption, PFC oxygenation, and inhibitory control (Stroop test) every two minutes of exercise at different intensities. Fifteen non-SUD individuals performed the same protocol and were used as control group.</p><p>Results</p><p>Exercise increased oxyhemoglobin (O₂Hb) and total hemoglobin (tHb) by 9% and 7%, respectively. However, when compared to a non-SUD group, this increase was lower at high intensities (p<0.001), and the inhibitory cognitive control was lower at rest and during exercise (p<0.007). In addition, PFC hemodynamics during exercise was inversely correlated with inhibitory cognitive performance (reaction time) (r = -0.62, p = 0.001), and a lower craving perception for the specific abused substance (p = 0.0189) was reported immediately after exercise.</p><p>Conclusion</p><p>Despite SUD individuals having their PFC cerebral oxygenation increased during exercise, they presented lower cognition and oxygenation when compared to controls, especially at elevated intensities. These results may reinforce the role of exercise as an adjuvant treatment to improve PFC function and cognitive control in individuals with SUD.</p></div