737 research outputs found

    Hemoglobins of the Cutthroat Trout Salmo clarki

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    Nine hemoglobins have been isolated from the blood of cutthroat trout. All nine hemoglobins bind oxygen cooperatively and appear to be tetramers with molecular weights of -64,000. The oxygen equilibria and subunit structures of the purified hemoglobins were studied. In addition, the red blood cells of cutthroat trout were examined for the presence of ATP and GTP, which are known to be physiological modulators of hemoglobins in fishes. Five hemoglobins with isoelectric points from 9.1 to 7.0 are classified as cathodal hemoglobins. These five hemoglobins have identical oxygen binding properties by the criteria tested. All have oxygen equilibria which are unaffected by protons and ATP and essentially independent of temperature, with overall enthalpies of oxygenation ~0. Two hemoglobins with isoelectric points near 6.5, classified as a nodal hemoglobins, have oxygen binding properties distinctly different from those of the cathodal hemoglobins. Both are characterized by a Root effect, displaying non-cooperative oxygen binding and low oxygen affinity at pH 6.2. ATP causes a large reduction in the oxygen affinity without affecting the cooperativity of oxygen binding. GTP has a similar but slightly larger effect on both hemoglobins. The oxygen equilibria of the anodal hemoglobins are temperature dependent, with the oxygen affinity being reduced as temperature increases. The overall enthalpy of oxygenation is -14 kcal/mol for both hemoglobins. The two remaining hemoglobins represent only a small percentage of the total hemoglobin. These hemoglobins are tentatively designated as embryonic hemoglobins based primarily on a comparison of their properties to those observed for hemoglobins from newly-hatched rainbow trout (Iuchi, I. (1973) Comp. Biochem. Physiol. 44B, 1087-1101). These two hemoglobins have isoelectric points near 5.9 and oxygen binding properties similar to those of the cathodal hemoglobins. With the possible exception of one of the embryonic hemoglobins (for which globins were not obtained), all the hemoglobins are composed of two different types of globin chains. Six are ∝_2 β_2 tetramers, while two of the cathodal hemoglobins are hybrid tetramers of the type 〖∝∝\u27β〗_2 and ∝∝\u27ββ. Red blood cells of cutthroat trout contain both ATP and GTP, suggesting that, in contrast to rainbow trout, both nucleotides may be important physiological modulators of hemoglobin oxygen affinity in this fish

    Biomedical Photoacoustic Imaging and Sensing Using Affordable Resources

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    The overarching goal of this book is to provide a current picture of the latest developments in the capabilities of biomedical photoacoustic imaging and sensing in an affordable setting, such as advances in the technology involving light sources, and delivery, acoustic detection, and image reconstruction and processing algorithms. This book includes 14 chapters from globally prominent researchers , covering a comprehensive spectrum of photoacoustic imaging topics from technology developments and novel imaging methods to preclinical and clinical studies, predominantly in a cost-effective setting. Affordability is undoubtedly an important factor to be considered in the following years to help translate photoacoustic imaging to clinics around the globe. This first-ever book focused on biomedical photoacoustic imaging and sensing using affordable resources is thus timely, especially considering the fact that this technique is facing an exciting transition from benchtop to bedside. Given its scope, the book will appeal to scientists and engineers in academia and industry, as well as medical experts interested in the clinical applications of photoacoustic imaging

    Les effets du préconditionnement métabolique sur l'oxygénation musculaire et sur la performance en patinage de vitesse longue piste

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    En patinage de vitesse, la position basse, les phases de glisse, les exigences reliées aux virages et les hauts niveaux de force requis à chaque poussée entraînent une restriction du débit sanguin (RDS) dans les muscles principalement sollicités. Cette RDS, qui est à l’origine d’une désoxygénation des muscles locomoteurs ainsi que d’une accélération des processus métaboliques liés à la fatigue, influence la technique gestuelle et la performance. Les athlètes de haut niveau utilisent plusieurs stratégies de conditionnement métabolique dans l’objectif d’optimiser leurs réponses physiologiques et leurs performances. Malgré leur impact sur l’oxygénation musculaire noté dans de nombreux sports, aucune donnée n’est disponible concernant les effets de ces méthodes sur la performance en patinage de vitesse longue piste (PVLP). Considérant les caractéristiques spécifiques des patineurs de différents profils énergétiques et la singularité de leurs réponses physiologiques, l’objectif de cette thèse était d’évaluer les effets de méthodes de conditionnement métabolique sur la performance sur glace en fonction du profil énergétique des athlètes. Le préconditionnement ischémique à distance (RIPC) induit une vasodilatation qui favorise le débit sanguin dans le muscle squelettique et une sympatholyse fonctionnelle qui contribue à assurer une perfusion des tissus actifs en adéquation avec la demande énergétique. Le RIPC contribue également à optimiser la fonction mitochondriale et a mené à des améliorations de performance dans certains contextes sportifs. L’étude 1 a démontré que le RIPC ne mène à aucun gain de performance lors d’un contre-la-montre de 1000 m en PVLP chez des athlètes élites, et que cette technique tend à augmenter l’extraction d’oxygène musculaire chez les athlètes spécialisés en sprint. Ceci pourrait permettre de rehausser le stress métabolique à l’entraînement chez ce type d’athlètes et ainsi optimiser les adaptations chroniques. Un échauffement des muscles respiratoires (IMW) peut retarder l’activation du métaboréflexe respiratoire à l’exercice et favoriser une meilleure oxygénation des muscles locomoteurs. L’étude 2 n’a montré aucune augmentation du volume sanguin local et aucun effet ergogénique en PVLP à la suite d’un IMW. Enfin, la combinaison de différentes stratégies de conditionnement est une pratique courante chez les athlètes élites qui espèrent optimiser leur performance. Étonnamment, les preuves scientifiques concernant l’amalgame de techniques sont très rares dans la littérature. Les résultats de l’étude 3 ne démontrent aucun effet ergogénique de la combinaison du RIPC (chronique) et d’un IMW sur la performance au 600 m en PVLP. En somme, les résultats de ces trois études mettent en évidence la faible variabilité des réponses physiologiques et des performances chez les athlètes de haut niveau, ainsi que les singularités associées à la position des patineurs de vitesse; ni le préconditionnement ischémique, ni l’échauffement des muscles respiratoires, ni la combinaison des deux stratégies n’ont permis d’améliorer la performance chez des patineurs élites et seulement des modifications mineures ont été observées sur le plan de l’oxygénation musculaire. Le niveau de forme très élevé des athlètes, la réalisation d’un échauffement complet et la position extrêmement basse pourraient avoir contribué à atténuer l’efficacité de ces techniques.The speed-skating position leads to blood-flow restriction and deoxygenation in the lower limbs that may enhance the metabolic processes associated with fatigue, thereby affecting technique and performance. Highlevel athletes use several metabolic conditioning strategies to optimize their physiological responses and performances. Despite their potential impact on muscle oxygenation noted in many sports, no data is available regarding the impact of such techniques on long-track speed skating performance. The peculiar histologic muscular characteristics associated with the skaters of different energetic profile and skating specialties may influence the response to conditioning stimulus and therefore, the purpose of our studies was to assess the specific on-ice impact of conditioning strategies with respect to the energetic profile of the skaters. Remote ischemic preconditioning (RIPC) has been found to enhance performance in different contexts, improve vascular function and muscular perfusion (locally and systemically) and to optimize mitochondrial efficiency. In study 1, we found that RIPC has no practical ergogenic impact on 1000-m long-track speed-skating performance in elite athletes and that this technique tends to increase muscle oxygen extraction in sprint athletes. This could increase the metabolic stress in training in this type of athlete and thus, optimize the chronic adaptations. Respiratory muscle fatigue might increase sympathetic vasoconstrictor outflow to working skeletal muscles through a respiratory muscle metaboreflex, thus reducing limbs blood flow and accelerating the development of exercise-induced locomotor muscle fatigue. An inspiratory muscle warm-up (IMW) may reduce inspiratory muscle fatigue and attenuate locomotor muscle deoxygenation during maximal exercises. In study 2, we found that a standard IMW protocol provides no meaningful effect on blood volume and performance in elite speed skaters. Finally, elite athletes in varied sports typically combine ergogenic strategies in the hope of taking advantage of multiple strategies simultaneously in order to enhance physiological responses and competitive performance. However, the scientific evidence for such practices is very scarce. Results of study 3 indicate that combining RIPC (chronic) and IMW has no practical ergogenic impact on 600-m speed-skating performance in elite skaters. Summing up, the results of these three studies highlight the low variability of physiological responses and performance in elite athletes as well as the singularities associated with the position of speed skaters; neither ischemic preconditioning, nor an inspiratory muscles warm-up, nor the combination of these two strategies has improved performance in elite skaters and only minor changes in muscular oxygenation were observed. The very high level of aerobic fitness of the athlete, the practice of a thorough warm-up protocol and the extremely low position may have contributed to lessen the effectiveness of these techniques

    Advanced MRI techniques in the study of cerebellar cortex

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    The cerebellum (from the Latin "little brain") is the dorsal portion of the metencephalon and is located in the posterior cranial fossa. Although representing only 10% of the total brain volume, it contains more than 50% of the total number of neurons of the central nervous system (CNS). Its organization resembles the one found in the telencephalon, with the presence of a superficial mantle of gray matter (GM) known as the cerebellar cortex, covering the cerebellar white matter (WM) in which three pairs of deep cerebellar GM nuclei are embedded. The number of studies dedicated to the study of the cerebellum and its function has significantly increased during the last years. Nevertheless, although many theories on the cerebellar function have been proposed, to date we still are not able to answer the question about the exact function of this structure. Indeed, the classical theories focused on the role of the cerebellum in fine-tuning for muscle control has been widely reconsidered during the last years, with new hypotheses that have been advanced. These include its role as sensory acquisition device, extending beyond a pure role in motor control and learning, as well as a pivotal role in cognition, with a recognized cerebellar participation in a variety of cognitive functions, ranging from mood control to language, memory, attention and spatial data management. A huge contribution to our understanding of how the cerebellum participates in all these different aspects of motor and non-motor behavior comes from the application of advanced imaging techniques. In particular, Magnetic Resonance Imaging (MRI) can provide a non-invasive evaluation of anatomical integrity, as well as information about functional connections with other brain regions. This thesis is organized as follows: - In Chapter 1 is presented a general introduction to the cerebellar anatomy and functions, with particular reference to the anatomical organization of cerebellar cortex and its connections with the telencephalon - Chapter 2 will contain a general overview about some of the major advanced MRI methods that can be applied to investigate the anatomical integrity and functional status of the cerebellar cortex - In Chapter 3 will be presented a new method to evaluate the anatomy and integrity of cerebellar cortex using ultra-high field MRI scanners - Chapters 4, 5 and 6 will contain data obtained from the application of some of the previously described advanced imaging techniques to the study of cerebellar cortex in neurodegenerative and neuroinflammatory disorders affecting the CNS

    Effects of Robotic Knee Exoskeleton on Human Energy Expenditure

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    Applications of Hybrid Diffuse Optics for Clinical Management of Adults After Brain injury

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    Information about cerebral blood flow (CBF) is valuable for clinical management of patients after severe brain injury. Unfortunately, current modalities for monitoring brain are often limited by hurdles that include high cost, low throughput, exposure to ionizing radiation, probe invasiveness, and increased risk to critically ill patients when transportation out of their room or unit is required. A further limitation of current technologies is an inability to provide continuous bedside measurements that are often desirable for unstable patients. Here we explore the clinical utility of diffuse correlation spectroscopy (DCS) as an alternative approach for bedside CBF monitoring. DCS uses the rapid intensity fluctuations of near-infrared light to derive a continuous measure of changes in blood flow without ionizing radiation or invasive probing. Concurrently, we employ another optical technique, called diffuse optical spectroscopy (DOS), to derive changes in cerebral oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) concentrations. Our clinical studies integrate DCS with DOS into a single hybrid instrument that simultaneously monitors CBF and HbO2/Hb in the injured adult brain. The first parts of this dissertation present the motivations for monitoring blood flow in injured brain, as well as the theory underlying diffuse optics technology. The next section elaborates on details of the hybrid instrumentation. The final chapters describe four human subject studies carried out with these methods. Each of these studies investigates an aspect of the potential of the hybrid monitor in clinical applications involving adult brain. The studies include: (1) validation of DCS-measured CBF against xenon-enhanced computed tomography in brain-injured adults; (2) a study of the effects of age and gender on posture-change-induced CBF variation in healthy subjects; (3) a study of the efficacy of DCS/DOS for monitoring neurocritical care patients during various medical interventions such as head-of-bed manipulation and induced hyperoxia; and (4) a first feasibility study for using DCS to study hemodynamics at high altitudes. The work presented in this dissertation thus further develops DCS/DOS technology and demonstrates its utility for monitoring the injured adult brain. It demonstrates the promise of this new clinical tool to help neurocritical care clinicians make more informed decisions and thereby improve patient outcome

    軸方向繊維強化型ゴム人工筋肉を用いた歩行アシスト装具の開発

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    Quantitative photoacoustic tomography: experimental phantom studies

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    Photoacoustic tomography (PAT) is a promising non-invasive imaging modality exhibiting high resolution, good contrast and specificity to light-absorbing molecules (chromophores). One of the outstanding challenges the technique faces is that PAT images, though dependent on optical absorption, are not its direct representation because they are coloured by the unknown light fluence. Theoretical studies have succeeded in quantifying optical absorption and chromophore concentration by employing model-based inversions (MBI) that can deal with the non-linearity of the problem and the fluence-related distortion. However, experimental translation has been scarce. The aim was to perform quantitative PAT (qPAT) in a rigorous experimental phantom study to show that highly-resolved 3D estimation of chromophore distributions can be achieved. The first consideration was finding a tissue-relevant and stable matrix material and chromophores. Thermoplastic PVCP was fully assessed. Its stability, intrinsic optical properties, thermoelastic efficiency and low-frequency acoustic properties were suitable. The limitation was the lack of photostability of embedded pigments. Separately, we fully characterised aqueous solutions of sulphate salts and found them to be suitable chromophores for qPAT and potential surrogates for oxy- and deoxyhemoglobin. For a phantom made of sub-mm tubes filled with sulphate solutions in an intralipid-rich background, 3D high resolution estimates of chromophore concentrations were obtained through an efficient diffusion-approximation MBI. Uncertainties in optical inputs of the MBI were tackled by assessing in silico their effect on quantification accuracy and then mitigated in the designed experiment through careful measurements. A faithful representation of the multiwavelength photoacoustic tomography images was sought by employing broadband, near-omnidirectional and high-sensitivity sensors and a detection configuration and reconstruction that overcame the limited-view problem. Estimation of the chromophore ratio, analogous to the much sought-after blood oxygenation, gave a mean absolute error of 3.4 p.p., whilst normalised estimates of the two main chromophore distributions gave errors of 13.2% and 17.2%

    Methods and Apparatus for In Vivo Identification and Characterization of Vulnerable Atherosclerotic Plaques

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    Methods and apparatus for analyzing the chemical composition of vulnerable plaques with an intravascular catheter having a near-infrared light source, a fiber-optic probe, a mechanism for directing the light from the light source into a blood vessel, and detectors for detecting light reflected or scattered by the tissue. The light source may be a tunable laser, and may transmit an incident beam having a wavelength ranging from 1400 to 4100 nm. A computer may be included to receive and process the spectral data in the analysis of the vulnerable plaques. A catheter system may be configured to provide near-IR spectrometric imaging of arteries to non-destructively locate and determine lipid pool and fibrous cap size and composition. Additionally, mediators and cellular components may be also determined that are typically associated with vulnerable plaques which have an increased risk of rupture. The lipid pool, fibrous cap, and inflammatory response may serve as an in vivo marker for vulnerable atherosclerotic plaques. Methods are further provided for prospectively identifying and characterizing vulnerable plaques which may include the steps of focusing near-IR light onto a blood vessel wall; detecting the scattered light in the region; and analyzing the resulting spectra across the full preselected wavelength range, particularly in the ranges that include identifying peaks for vulnerable plaque constituents

    Investigation of dynamic functional connectivity in cerebral small vessel disease

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    Tese de mestrado integrado em Engenharia Biomédica e Biofísica (Biofísica Médica e Fisiologia de Sistemas), Universidade de Lisboa, Faculdade de Ciências, 2020A doença dos pequenos vasos cerebrais ou Small Vessel Disease (SVD) é a principal causa de disfunção cognitiva em idosos e refere-se a um conjunto de processos patológicos e neurológicos que afetam os pequenos vasos do cérebro. As suas manifestações clínicas variam desde deficiências cognitivas, que podem levar a uma deterioração cognitiva progressiva e até demência, e incapacidades físicas, incluindo perda funcional em fases mais avançadas da doença. A neuroimagiologia é uma ferramenta essencial no diagnóstico e caracterização da SVD, em particular, a ressonância magnética funcional em repouso (rs-fMRI) já demonstrou potencial para fornecer biomarcadores da SVD, revelando interrupções da conectividade funcional (CF) em redes neuronais. No entanto, até o momento, apenas um estudo explorou as flutuações temporais da CF comumente observadas – a chamada conectividade funcional dinâmica (dFC). Em contraste com a CF, a dFC tem em consideração a natureza dinâmica da atividade cerebral, analisando-a em escalas de tempo mais rápidas de segundos a minutos. De facto, diversos estudos de dFC reportaram que esta abordagem pode fornecer uma maior compreensão das propriedades fundamentais das redes cerebrais e servir como um biomarcador de diversas doenças, uma vez que as alterações relacionadas com as mesmas nas propriedades dinâmicas da CF parecem ter origem neuronal. Deste modo, neste trabalho, o objetivo foi investigar a dFC medida por rs-fMRI em dois grupos de pacientes com SVD – do tipo esporádico (sSVD) e arteriopatia cerebral autossómica dominante com enfartes subcorticais e leucoencefalopatia (CADASIL) - em comparação com um grupo saudável. Para tal, a dFC foi estimada entre pares de regiões do cérebro em cada tempo de repetição, TR, com o método de Phase Coherence. Neste método, os padrões de dFC para todos os pontos de tempo foram obtidos calculando o alinhamento de fase entre cada par de regiões do cérebro, estimando a fase do sinal de cada ponto de tempo, em cada uma das 90 regiões do cérebro, com a transformada de Hilbert. De seguida, os padrões de dFC ao longo do tempo e de todos os sujeitos foram analisados utilizando o método Leading Eigenvector Dynamics Analysis (LEiDA), que considera apenas o autovetor principal de cada padrão de dFC obtido, reduzindo deste modo a dimensionalidade dos dados. Este vetor captura a orientação principal das fases do sinal sobre todas as áreas, onde cada elemento do mesmo representa a projeção da fase do sinal em cada área do cérebro no autovetor principal. Em seguida, o algoritmo k-médias foi aplicado a todos os autovetores principais de dFC para obter um número finito de estados de dFC, cada um representando um padrão dFC recorrente, para um k (número de estados) variável. Como este trabalho teve como objetivo explorar se existem estados de dFC que diferenciam pacientes SVD do grupo saudável, e não determinar o número ideal de estados de dFC, o número de estados foi variado de 2 a 20. Para cada k, examinámos as diferenças em termos de probabilidade de ocorrência, duração e perfis de transição dos estados de dFC entre o grupo de doentes e o grupo de controlos saudáveis. Adicionalmente, os estados de dFC foram correlacionados com sete redes neuronais de repouso comuns, nomeadamente a rede somatomotora, a rede de atenção ventral e dorsal, a rede visual, a rede frontoparietal, a rede límbica e a rede de modo padrão. Posteriormente, a fim de determinar se as alterações nas propriedades de dFC, encontradas neste trabalho, poderiam ser potenciais biomarcadores de declínio cognitivo causadas pela SVD, foi realizado uma análise de correlação entre as pontuações dos testes neuropsicológicos em quatro domínios relevantes (função executiva, velocidade de processamento, memória de trabalho e memória de longo prazo) e as propriedades de dFC dos pacientes. Do mesmo modo, uma análise de correlação entre os mapas probabilísticos dos tratos de substância branca mais frequentemente lesionados destes pacientes e as propriedades de dFC foi, também, realizada com o objetivo de determinar se as alterações nas propriedades de dFC, encontradas nos pacientes quando comparadas com o grupo saudável, poderiam estar correlacionadas com lesões estruturais dos mesmos. Quando comparado com o grupo de controlos saudáveis, o grupo de doentes apresentou uma probabilidade de ocorrência significativamente maior num estado de dFC fracamente conectado, composto por áreas clinicamente relevantes. Este estado compreende áreas dos lobos frontais e parietais e está significativamente associado a redes neuronais envolvidas na integração de informações sensoriais e processos específicos para o controlo da atenção, nomeadamente a rede somatomotora, a rede de atenção ventral e dorsal. Estas mesmas redes foram anteriormente identificadas, em estudos de CF, como afetadas em pacientes com SVD, mas também em indivíduos com deficiências cognitivas e com doença de Alzheimer. Além disso, estudos de dFC em doenças relacionadas com a SVD, como a demência e a doença de Alzheimer, relataram que os pacientes também apresentaram maiores probabilidades de ocorrência em estados fracamente e esparsamente conectados, com ausência de fortes conexões positivas e negativas. Em particular, o único estudo de dFC em SVD também descobriu que os pacientes com SVD tiveram mais ocorrências num estado fracamente conectado nas regiões do domínio sensório-motor, quando comparado ao grupo saudável. Deste modo, podendo indicar que mudanças dinâmicas na CF nestas áreas podem ser particularmente importantes para esta doença. É também importante ressaltar que as probabilidades de transição entre este estado fronto-parietal fracamente conectado para o estado de coerência global, fortemente conectado, foram significativamente correlacionadas com melhor desempenho no domínio cognitivo da velocidade de processamento. Estas descobertas estão de acordo com resultados anteriores de estudos de dFC em indivíduos com melhores e piores desempenhos cognitivos, onde indivíduos com melhores desempenhos cognitivos tiveram maior número de transições para este estado de coerência global. Da mesma forma, as probabilidades de transição do estado fortemente conectado para o estado fronto-parietal fracamente conectado, foram significativamente correlacionadas com um pior desempenho neste mesmo domínio cognitivo. De facto, défices na velocidade de processamento estão entre as primeiras e mais proeminentes manifestações cognitivas da SVD, com diversos estudos demonstrando associações entre o declínio na velocidade de processamento e medidas quantitativas de ressonância magnética. Assim, estudos futuros devem investigar com maior detalhe transições entre estes estados, de modo a determinar se alterações nesta propriedade de dFC podem ser biomarcadores do declínio cognitivo na SVD. Em relação à análise dos mapas probabilísticos dos tratos de substância branca mais frequentemente lesionados nestes pacientes, embora nenhuma correlação significativa tenha sido encontrada com as alterações nas propriedades da dFC encontradas neste trabalho, é interessante notar que vários estudos têm relatado associações entre estas lesões e o declínio cognitivo. O facto de a substância branca ser organizada no cérebro por tratos, conectando regiões cerebrais funcionais entre si, espera-se que danos a esses tratos levem a défices funcionais. Efetivamente, dois dos tratos frequentemente lesionados nestes pacientes, conectando regiões frontais, foram anteriormente relacionados com um pior desempenho cognitivo na velocidade de processamento em pacientes com SVD e demência. É, portanto, tentador sugerir que estes mesmo tratos frequentemente lesionados nos pacientes com SVD aqui estudados, poderiam ter alguma influência no pior desempenho no teste da velocidade de processamento encontrado neste estudo, que foi correlacionado com uma maior probabilidade de transição para o estado fracamente conectado, composto por regiões do lobo frontal e parietal. A compreensão dessa relação poderia ajudar a prever em quais das regiões do cérebro a patologia da substância branca causaria maiores défices funcionais, permitindo uma prevenção e terapia precoce. No geral, os nossos resultados fornecem um novo suporte de que a conectividade funcional dinâmica pode fornecer biomarcadores mais sensíveis da SVD e deste modo, futuras investigações deverão explorar o seu potencial para prever o declínio cognitivo relacionado com a mesma.Cerebral small vessel disease (SVD) is the leading contributor to cognitive dysfunction in the elderly and it refers to a set of pathological and neurological processes that affect the smallest vessels of the brain. Its clinical manifestations vary from cognitive impairments, which can lead to progressive cognitive deterioration and even dementia, and physical disabilities, including functional loss in more advanced stages. Neuroimaging is a crucial tool in the diagnosis and characterization of SVD; in particular, resting-state functional magnetic resonance imaging (rs-fMRI) has demonstrated potential to deliver sensitive biomarkers of SVD, by revealing disruptions in functional connectivity (FC) across brain networks. However, so far only one study has explored the commonly observed FC temporal fluctuations – so-called dynamic FC (dFC). Here we aim to further investigate dFC measured by rs-fMRI in two groups of patients with SVD – sporadic SVD (sSVD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) – compared with a healthy control group. For this purpose, dFC was estimated at each repetition time point, TR, using Phase Coherence between the BOLD signals in pairs of brain regions, and dFC patterns were then analysed over time and subjects using the Leading Eigenvector Dynamics Analysis (LEiDA) approach. Then, a finite number of dFC states, each representing a recurrent dFC pattern, was obtained by k-means clustering with varying k (number of clusters). For each k, we examined differences between SVD and healthy control groups in terms of the occurrence, duration and switching profiles of dFC states. Additionally, the correlations between each dFC state and seven common resting-state networks (RSNs) were computed. SVD patients showed a significant higher probability of a weakly connected dFC state, consisting of clinically relevant areas, when compared with healthy controls. This state comprises frontal and parietal areas and is significantly associated with the somatomotor, dorsal attention and ventral attention RSNs, which are involved in the integration of sensory information and specific processes for attention control. Further, the fact that the state is weakly connected agrees with the only previous study on dFC in SVD. Overall, our findings contribute with novel support that dFC may provide sensitive biomarkers of SVD and should be further explored in terms of its potential to predictive cognitive decline
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