The present series of in vivo experiments in healthy subjects, were performed to investigate wall stiffness in peripheral vessels and how this modality adapts to iterative increments or sustained reductions in local intravascular pressures. Vascular stiffness was measured as changes in arterial and venous diameters, and in arterial flow, during graded increments in distending pressures in the vasculature of an arm or a lower leg. In addition, effects of intravascular pressure elevation on flow characteristics in veins, and on limb pain were elucidated. Arteries and veins were stiffer (i.e. pressure distension was less) in the lower leg than in the arm. The pressure-induced increase in arterial flow was substantially greater in the arm than in the lower leg, indicating a greater stiffness in the arterioles of the lower leg. Prolonged reduction of intravascular pressures in the lower body, induced by 5 wks of sustained horizontal bedrest (BR), decreased stiffness in the leg vasculature. BR increased pressure distension in the tibial artery threefold and in the tibial vein by 86 %. The pressure-induced increase in tibial artery flow was greater post bedrest, indicating reduced stiffness in the arterioles of the lower leg. Intermittent increases of intravascular pressures in one arm (pressure training; PT) during a 5-wk period decreased vascular stiffness. Pressure distension and pressure-induced flow in the brachial artery were reduced by about 50 % by PT. PT reduced pressure distension in arm veins by 30 to 50 %. High intravascular pressures changed venous flow to arterial-like pulsatile patterns, reflecting propagation of pulse waves from the arteries to the veins either via the capillary network or through arteriovenous anastomoses. High vascular pressures induced pain, which was aggravated by BR and attenuated by PT; the results suggest that the pain was predominantly caused by vascular overdistension. In conclusion, vascular wall stiffness constitutes a plastic modality that adapts to meet demands imposed by a change in the prevailing local intravascular pressure. That increased intravascular pressure leads to increased arteriolar wall stiffness supports the notion that local pressure load may serve as a “prime mover” in the development of vascular changes in hypertension. / medicine doktorsexamen QC 20101109

During each cardiac cycle pulsatile arterial blood inflates the vascular bed of the brain, forcing cerebrospinal fluid (CSF) and venous blood out of the cranium. Excessive arterial pulsatility may be part of a harmful mechanism causing cognitive decline among elderly. Additionally, restricted venous flow from the brain is suggested as the cause of multiple sclerosis. Addressing hypotheses derived from these observations requires accurate and reliable investigational methods. This work focused on assessing the pulsatile waveform of cerebral arterial, venous and CSF flows. The overall aim of this dissertation was to explore cerebral blood flow and intracranial pulsatility using MRI, with respect to measurement, physiological and pathophysiological aspects. Two-dimensional phase contrast magnetic resonance imaging (2D PCMRI) was used to assess the pulsatile waveforms of cerebral arterial, venous and CSF flow. The repeatability was assessed in healthy young subjects. The 2D PCMRI measurements of cerebral arterial, venous and CSF pulsatility were generally repeatable but the pulsatility decreased systematically during the investigation. A method combining 2D PCMRI measurements with invasive CSF infusion tests to determine the magnitude and distribution of compliance within the craniospinal system was developed and applied in a group of healthy elderly. The intracranial space contained approximately two thirds of the total craniospinal compliance. The magnitude of craniospinal compliance was less than suggested in previous studies. The vascular hypothesis for multiple sclerosis was tested. Venous drainage in the internal jugular veins was compared between healthy controls and multiple sclerosis patients using 2D PCMRI. For both groups, a great variability in the internal jugular flow was observed but no pattern specific to multiple sclerosis could be found. Relationships between regional brain volumes and potential biomarkers of intracranial cardiac-related pulsatile stress were assessed in healthy elderly. The biomarkers were extracted from invasive CSF pressure measurements as well as 2D PCMRI acquisitions. The volumes of temporal cortex, frontal cortex and hippocampus were negatively related to the magnitude of cardiac-related intracranial pulsatility. Finally, a potentially improved workflow to assess the volume of arterial pulsatility using time resolved, four-dimensional phase contrast MRI measurements (4D PCMRI) was evaluated. The measurements showed good agreement with 2D PCMRI acquisitions. In conclusion, this work showed that 2D PCMRI is a feasible tool to study the pulsatile waveforms of cerebral blood and CSF flow. Conventional views regarding the magnitude and distribution of craniospinal compliance was challenged, with important implications regarding the understanding of how intracranial vascular pulsatility is absorbed. A first counterpoint to previous near-uniform observations of obstructions in the internal jugular veins in multiple sclerosis was provided. It was demonstrated that large cardiac- related intracranial pulsatility were related to smaller volumes of brain regions that are important in neurodegenerative diseases among elderly. This represents a strong rationale to further investigate the role of excessive intracranial pulsatility in cognitive impairment and dementia. For that work, 4D PCMRI will facilitate an effective analysis of cerebral blood flow and pulsatility.

Introdução- Os movimentos respiratórios têm influência na circulação fetal. Sua presença indica um sistema nervoso intacto, não deprimido, refletindo o bem-estar do concepto. Acredita-se que, em apnéia, a pressão exercida pelos órgãos intratorácicos no coração fetal, em particular os pulmões não expandidos, limita a distensibilidade ventricular. O padrão de fluxo das veias pulmonares, um parâmetro para avaliação Doppler-ecocardiográfica da função diastólica fetal, é determinado pelos eventos que ocorrem do lado esquerdo do coração, sendo influenciado pelas mudanças dinâmicas na pressão do átrio esquerdo criadas pela contração e pelo relaxamento do átrio e do ventrículo esquerdos. A impedância ao fluxo da veia pulmonar para o átrio esquerdo é representada pelo índice de pulsatilidade. Objetivo- Testar a hipótese de que o índice de pulsatilidade do fluxo venoso pulmonar fetal é menor na presença dos movimentos respiratórios fetais do que em apnéia. Métodos- Examinados 22 fetos normais de mães sem doença sistêmica, em apnéia (controles) e na presença de movimentos respiratórios fetais (casos). Os fetos foram examinados pela ecocardiografia pré-natal com Doppler e mapeamento de fluxo em cores. O índice de pulsatilidade da veia pulmonar foi obtido colocando-se a amostra volume do Doppler pulsado sobre a veia pulmonar superior direita ou inferior esquerda, e aplicando-se a fórmula velocidade máxima (sistólica ou diastólica)-velocidade pré-sistólica/velocidade média. Resultados- Os fetos apresentaram idade gestacional média de 28,9 ± 2,9 semanas. Na avaliação realizada nos fetos em apnéia as médias das velocidades sistólica, diastólica e pré-sistólica foram, respectivamente, 0,35 ± 0,08 m/s, 0,26 ± 0,07 m/s, 0,09 ± 0,03 m/s. Na avaliação realizada na presença de movimentos respiratórios fetais as médias das velocidades sistólica, diastólica e pré-sistólica foram, respectivamente, 0,33 ± 0,1 m/s, 0,28 ± 0,08 m/s, 0,11 ± 0,04 m/s. O índice de pulsatilidade da veia pulmonar médio, nos fetos em apnéia, foi de 1,25 ± 0,23 (1,69 a 0,82), e na presença de movimentos respiratórios fetais foi de 0,97 ± 0,2 (1,53 a 0,61). Conclusão- Demonstramos significante diminuição da impedância ao fluxo venoso pulmonar, representada pelo índice de pulsatilidade vascular, durante os movimentos respiratórios fetais, refletindo modificações da dinâmica atrial esquerda e da melhora complacência ventricular esquerda. / Introdution- Respiratory movements influence fetal circulation. Their presence indicates an intact, non-depressed nervous system, reflecting a good fetal clinical status. In apnea, the pressure of intrathoracic organs on the fetal heart, mainly the non-expanded lungs, limits ventricular distensibility. Flow pattern in pulmonary veins, a Doppler echocardiographic parameter in the assessment of fetal diastolic function, is determined by events occurring in the left heart and is influenced by dynamic changes in left atrial pressures created by left atrium and ventricle contraction and relaxation. Impedance to pulmonary venous flow to the left atrium is represented by the pulsatility index. Objective- To test the hypothesis that fetal pulmonary venous flow pulsatility index is lower during fetal respiratory movements than in apnea. Methods- Twenty-two normal fetuses of mothers without systemic disease were examined in apnea (controls) and in the presence of fetal respiratory movements (cases). Fetuses were examined by prenatal Doppler echocardiography with color flow mapping. The pulsatility index of the pulmonary vein was obtained placing the pulsed Doppler sample volume over the right upper or left lower pulmonary vein , and applying the formula [maximum velocity (systolic or diastolic)–pre-systolic velocity]/mean velocity. Results- Mean gestational age was 28.9 ± 2.9 weeks. During fetal apnea, mean systolic, diastolic and pre-systolic velocities were, respectively, 0.35 ± 0.08 m/s, 0.26 ± 0.07 m/s and 0.09 ± 0.03 m/s. In the presence of fetal respiratory movements, mean systolic, diastolic and pre-systolic velocities were, respectively, 0.33 ± 0.1 m/s, 0.28 ± 0.08 m/s and 0.11 ± 0.04 m/s. Pulsatility index pulmonary vein in apnea was 1.25 ± 0.23 (1.69 to 0.82), and during fetal respiratory movements it was 0.97 ± 0.2 (1.53 to 0.61). Conclusion- We showed a significant reduction in impedance of pulmonary venous flow, represented by pulmonary vein pulsatility index, during fetal respiratory movements, reflecting modifications of the left atrial dynamics and enhancement of left ventricular compliance.

Introdução- Os movimentos respiratórios têm influência na circulação fetal. Sua presença indica um sistema nervoso intacto, não deprimido, refletindo o bem-estar do concepto. Acredita-se que, em apnéia, a pressão exercida pelos órgãos intratorácicos no coração fetal, em particular os pulmões não expandidos, limita a distensibilidade ventricular. O padrão de fluxo das veias pulmonares, um parâmetro para avaliação Doppler-ecocardiográfica da função diastólica fetal, é determinado pelos eventos que ocorrem do lado esquerdo do coração, sendo influenciado pelas mudanças dinâmicas na pressão do átrio esquerdo criadas pela contração e pelo relaxamento do átrio e do ventrículo esquerdos. A impedância ao fluxo da veia pulmonar para o átrio esquerdo é representada pelo índice de pulsatilidade. Objetivo- Testar a hipótese de que o índice de pulsatilidade do fluxo venoso pulmonar fetal é menor na presença dos movimentos respiratórios fetais do que em apnéia. Métodos- Examinados 22 fetos normais de mães sem doença sistêmica, em apnéia (controles) e na presença de movimentos respiratórios fetais (casos). Os fetos foram examinados pela ecocardiografia pré-natal com Doppler e mapeamento de fluxo em cores. O índice de pulsatilidade da veia pulmonar foi obtido colocando-se a amostra volume do Doppler pulsado sobre a veia pulmonar superior direita ou inferior esquerda, e aplicando-se a fórmula velocidade máxima (sistólica ou diastólica)-velocidade pré-sistólica/velocidade média. Resultados- Os fetos apresentaram idade gestacional média de 28,9 ± 2,9 semanas. Na avaliação realizada nos fetos em apnéia as médias das velocidades sistólica, diastólica e pré-sistólica foram, respectivamente, 0,35 ± 0,08 m/s, 0,26 ± 0,07 m/s, 0,09 ± 0,03 m/s. Na avaliação realizada na presença de movimentos respiratórios fetais as médias das velocidades sistólica, diastólica e pré-sistólica foram, respectivamente, 0,33 ± 0,1 m/s, 0,28 ± 0,08 m/s, 0,11 ± 0,04 m/s. O índice de pulsatilidade da veia pulmonar médio, nos fetos em apnéia, foi de 1,25 ± 0,23 (1,69 a 0,82), e na presença de movimentos respiratórios fetais foi de 0,97 ± 0,2 (1,53 a 0,61). Conclusão- Demonstramos significante diminuição da impedância ao fluxo venoso pulmonar, representada pelo índice de pulsatilidade vascular, durante os movimentos respiratórios fetais, refletindo modificações da dinâmica atrial esquerda e da melhora complacência ventricular esquerda. / Introdution- Respiratory movements influence fetal circulation. Their presence indicates an intact, non-depressed nervous system, reflecting a good fetal clinical status. In apnea, the pressure of intrathoracic organs on the fetal heart, mainly the non-expanded lungs, limits ventricular distensibility. Flow pattern in pulmonary veins, a Doppler echocardiographic parameter in the assessment of fetal diastolic function, is determined by events occurring in the left heart and is influenced by dynamic changes in left atrial pressures created by left atrium and ventricle contraction and relaxation. Impedance to pulmonary venous flow to the left atrium is represented by the pulsatility index. Objective- To test the hypothesis that fetal pulmonary venous flow pulsatility index is lower during fetal respiratory movements than in apnea. Methods- Twenty-two normal fetuses of mothers without systemic disease were examined in apnea (controls) and in the presence of fetal respiratory movements (cases). Fetuses were examined by prenatal Doppler echocardiography with color flow mapping. The pulsatility index of the pulmonary vein was obtained placing the pulsed Doppler sample volume over the right upper or left lower pulmonary vein , and applying the formula [maximum velocity (systolic or diastolic)–pre-systolic velocity]/mean velocity. Results- Mean gestational age was 28.9 ± 2.9 weeks. During fetal apnea, mean systolic, diastolic and pre-systolic velocities were, respectively, 0.35 ± 0.08 m/s, 0.26 ± 0.07 m/s and 0.09 ± 0.03 m/s. In the presence of fetal respiratory movements, mean systolic, diastolic and pre-systolic velocities were, respectively, 0.33 ± 0.1 m/s, 0.28 ± 0.08 m/s and 0.11 ± 0.04 m/s. Pulsatility index pulmonary vein in apnea was 1.25 ± 0.23 (1.69 to 0.82), and during fetal respiratory movements it was 0.97 ± 0.2 (1.53 to 0.61). Conclusion- We showed a significant reduction in impedance of pulmonary venous flow, represented by pulmonary vein pulsatility index, during fetal respiratory movements, reflecting modifications of the left atrial dynamics and enhancement of left ventricular compliance.

Introdução- Os movimentos respiratórios têm influência na circulação fetal. Sua presença indica um sistema nervoso intacto, não deprimido, refletindo o bem-estar do concepto. Acredita-se que, em apnéia, a pressão exercida pelos órgãos intratorácicos no coração fetal, em particular os pulmões não expandidos, limita a distensibilidade ventricular. O padrão de fluxo das veias pulmonares, um parâmetro para avaliação Doppler-ecocardiográfica da função diastólica fetal, é determinado pelos eventos que ocorrem do lado esquerdo do coração, sendo influenciado pelas mudanças dinâmicas na pressão do átrio esquerdo criadas pela contração e pelo relaxamento do átrio e do ventrículo esquerdos. A impedância ao fluxo da veia pulmonar para o átrio esquerdo é representada pelo índice de pulsatilidade. Objetivo- Testar a hipótese de que o índice de pulsatilidade do fluxo venoso pulmonar fetal é menor na presença dos movimentos respiratórios fetais do que em apnéia. Métodos- Examinados 22 fetos normais de mães sem doença sistêmica, em apnéia (controles) e na presença de movimentos respiratórios fetais (casos). Os fetos foram examinados pela ecocardiografia pré-natal com Doppler e mapeamento de fluxo em cores. O índice de pulsatilidade da veia pulmonar foi obtido colocando-se a amostra volume do Doppler pulsado sobre a veia pulmonar superior direita ou inferior esquerda, e aplicando-se a fórmula velocidade máxima (sistólica ou diastólica)-velocidade pré-sistólica/velocidade média. Resultados- Os fetos apresentaram idade gestacional média de 28,9 ± 2,9 semanas. Na avaliação realizada nos fetos em apnéia as médias das velocidades sistólica, diastólica e pré-sistólica foram, respectivamente, 0,35 ± 0,08 m/s, 0,26 ± 0,07 m/s, 0,09 ± 0,03 m/s. Na avaliação realizada na presença de movimentos respiratórios fetais as médias das velocidades sistólica, diastólica e pré-sistólica foram, respectivamente, 0,33 ± 0,1 m/s, 0,28 ± 0,08 m/s, 0,11 ± 0,04 m/s. O índice de pulsatilidade da veia pulmonar médio, nos fetos em apnéia, foi de 1,25 ± 0,23 (1,69 a 0,82), e na presença de movimentos respiratórios fetais foi de 0,97 ± 0,2 (1,53 a 0,61). Conclusão- Demonstramos significante diminuição da impedância ao fluxo venoso pulmonar, representada pelo índice de pulsatilidade vascular, durante os movimentos respiratórios fetais, refletindo modificações da dinâmica atrial esquerda e da melhora complacência ventricular esquerda. / Introdution- Respiratory movements influence fetal circulation. Their presence indicates an intact, non-depressed nervous system, reflecting a good fetal clinical status. In apnea, the pressure of intrathoracic organs on the fetal heart, mainly the non-expanded lungs, limits ventricular distensibility. Flow pattern in pulmonary veins, a Doppler echocardiographic parameter in the assessment of fetal diastolic function, is determined by events occurring in the left heart and is influenced by dynamic changes in left atrial pressures created by left atrium and ventricle contraction and relaxation. Impedance to pulmonary venous flow to the left atrium is represented by the pulsatility index. Objective- To test the hypothesis that fetal pulmonary venous flow pulsatility index is lower during fetal respiratory movements than in apnea. Methods- Twenty-two normal fetuses of mothers without systemic disease were examined in apnea (controls) and in the presence of fetal respiratory movements (cases). Fetuses were examined by prenatal Doppler echocardiography with color flow mapping. The pulsatility index of the pulmonary vein was obtained placing the pulsed Doppler sample volume over the right upper or left lower pulmonary vein , and applying the formula [maximum velocity (systolic or diastolic)–pre-systolic velocity]/mean velocity. Results- Mean gestational age was 28.9 ± 2.9 weeks. During fetal apnea, mean systolic, diastolic and pre-systolic velocities were, respectively, 0.35 ± 0.08 m/s, 0.26 ± 0.07 m/s and 0.09 ± 0.03 m/s. In the presence of fetal respiratory movements, mean systolic, diastolic and pre-systolic velocities were, respectively, 0.33 ± 0.1 m/s, 0.28 ± 0.08 m/s and 0.11 ± 0.04 m/s. Pulsatility index pulmonary vein in apnea was 1.25 ± 0.23 (1.69 to 0.82), and during fetal respiratory movements it was 0.97 ± 0.2 (1.53 to 0.61). Conclusion- We showed a significant reduction in impedance of pulmonary venous flow, represented by pulmonary vein pulsatility index, during fetal respiratory movements, reflecting modifications of the left atrial dynamics and enhancement of left ventricular compliance.

yes / Purpose To characterize the intracranial volumetric changes that influence the cerebrospinal fluid (CSF) pulse in the Aqueduct of Sylvius (AoS). Materials and methods Neck MRI data were acquired from 12 healthy adults (8 female and 4 males; mean age = 30.9 years), using a 1.5 T scanner. The intracranial arterial, venous and CSF volumes changes, together with the aqueductal CSF (aCSF) volume, were estimated from flow rate data acquired at C2/C3 level and in the AoS. The correlations and temporal relationships among these volumes were computed. Results The aCSF volumetric changes were strongly correlated (r = 0.967, p < 0.001) with the changes in intracranial venous volume, whose peak occurred 7.0% of cardiac cycle (p = 0.023) before peak aCSF volume, but less correlated with the intracranial arterial and CSF volume changes (r = −0.664 and 0.676 respectively, p < 0.001). The intracranial CSF volume change was correlated with the intracranial venous volume change (r = 0.820, p < 0.001), whose peak occurred slightly before (4.2% of CC, p = 0.059). Conclusion The aCSF pulse is strongly correlated with intracranial venous volume, with expansion of the cortical veins occurring prior to aCSF flow towards the third ventricle. Both caudal-cranial aCSF flow and venous blood retention occur when arterial blood volume is at a minimum.