Most small cerebral cortical veins demonstrate significant flow pulsatility: a human phase contrast MRI study at 7T

Phase contrast MRI has been used to investigate flow pulsatility in cerebral arteries, larger cerebral veins and the cerebrospinal fluid. Such measurements of intracranial pulsatility and compliance are beginning to inform understanding of the pathophysiology of conditions including normal pressure hydrocephalus, multiple sclerosis and dementias. We demonstrate the presence of flow pulsatility in small cerebral cortical veins, for the first time using phase contrast MRI at 7 Tesla, with the aim of improving our understanding of the haemodynamics of this little-studied vascular compartment. A method for establishing where venous flow is pulsatile is introduced, revealing significant pulsatility in 116 out of 146 veins, across 8 healthy participants, assessed in parietal and frontal regions. Distributions of pulsatility index and pulse waveform delay were characterized, indicating a small, but statistically significant (p<0.05), delay of 59±41 ms in cortical veins with respect to the superior sagittal sinus, but no differences between veins draining different arterial supply territories. Measurements of pulsatility in smaller cortical veins, a hitherto unstudied compartment closer to the capillary bed, could lead to a better understanding of intracranial compliance and cerebrovascular (patho)physiology

Intensity distribution segmentation in ultrafast Doppler combined with scanning laser confocal microscopy for assessing vascular changes associated with ageing in murine hippocampi

Acknowledgements This work was mainly funded by the Agencia Nacional de Investigación e Innovación (ANII), grant FCE_1_2019_1_155539. Te authors also thank the support of PEDECIBA, CSIC-UdelaR and the Institut Franco—Uruguayen de Physique (IFUP), LIA-CNRS-UdelaR. J.P.D., C.N., N.R., A.K. and J.Br. thank SNI-ANII. M.A.F. thanks the support of ANII through POS_NAC_M_2020_1_164127 scholarship. M.M. thanks the support of ANII through POS_FCE_2020_1_1009181 scholarship. N.R. thanks the support of CSIC I+D group grant CSIC2018—FID 13—Grupo ID 722.Peer reviewedPublisher PD

Modeling Cerebral Blood Flow Dependence on Carbon Dioxide and Mean Arterial Blood Pressure in the Immature Brain With Accounting for the Germinal Matrix

Intraventricular hemorrhage (IVH) is one of the most critical complications in the development of preterm infants. The likelihood of IVH is strongly associated with disturbances in cerebral blood flow (CBF) and with microvascular fragility in the germinal matrix (GM). The CBF value and its reactivity to changes in arterial carbon dioxide pressure (pCO2) and mean arterial blood pressure (MABP) are relevant indicators in the clinical assessment of preterm infants. The objective of the present study is mathematical modeling of the influence of pCO2 and MABP on CBF in immature brain, based on clinical data collected from 265 preterm infants with 23–30 gestational weeks. The model was adapted to the peculiarities of immature brain by taking into account the morphological characteristics of the GM capillary network and vascular reactivity, according to gestational and postnatal age. An analysis of model based values of CBF and its reactivity to changes in MABP and pCO2 was performed separately for each gestational week and for the first two days of life both for preterm infants with and without IVH. The developed model for the estimation of CBF was validated against equivalent experimental measurements taken from the literature. A good agreement between the estimated values of CBF, as well as its reaction on changes in MABP and pCO2 and the equivalent values obtained in experimental studies was shown

Mathematical methods for modeling the microcirculation

The microcirculation plays a major role in maintaining homeostasis in the body. Alterations or dysfunctions of the microcirculation can lead to several types of serious diseases. It is not surprising, then, that the microcirculation has been an object of intense theoretical and experimental study over the past few decades. Mathematical approaches offer a valuable method for quantifying the relationships between various mechanical, hemodynamic, and regulatory factors of the microcirculation and the pathophysiology of numerous diseases. This work provides an overview of several mathematical models that describe and investigate the many different aspects of the microcirculation, including geometry of the vascular bed, blood flow in the vascular networks, solute transport and delivery to the surrounding tissue, and vessel wall mechanics under passive and active stimuli. Representing relevant phenomena across multiple spatial scales remains a major challenge in modeling the microcirculation. Nevertheless, the depth and breadth of mathematical modeling with applications in the microcirculation is demonstrated in this work. A special emphasis is placed on models of the retinal circulation, including models that predict the influence of ocular hemodynamic alterations with the progression of ocular diseases such as glaucoma

Cerebral Vascular Tone Regulation: Integration and Impact of Disease

This chapter summarizes the current knowledge regarding the regulation of the tone of cerebral resistance arteries under conditions of normal health and with the development of chronic diseases (e.g., metabolic disease). The work integrates the myogenic (pressure-induced) regulation of vascular tone, the impact of elevated luminal flow or shear stresses, that of local tissue metabolic activity on vascular tone and the concept of neurovascular coupling (linking neuronal activity to the impacts on vascular diameter). In addition, this work summarizes some of the recent work on how diseases such as type 2 diabetes impact the mechanisms of cerebrovascular tone regulation. It is anticipated that the current review will provide the reader with an up-to-date understanding of how the cerebral resistance vessels respond to changes in their local environment and contribute to the regulation of blood flow within the brain

Modelling vascular reactivity to investigate the basis of the relationship between cerebral blood volume and flow under CO2 manipulation.

Changes in cerebral blood flow (f) and vascular volume (v) are of major interest in mapping cerebral activity and metabolism, but the relation between them currently lacks a sufficient theoretical basis. To address this we considered three models: a uniform reactive tube model (M1); an extension of M1 that includes passive arterial inflow and venous volume (M2); and a more anatomically plausible model (M3) consisting of 19 compartments representing the whole range of vascular sizes and respective CO2 reactivities, derived from literature data. We find that M2 cannot be described as the simple scaling of a tube law, but any divergence from a linear approximation is negligible within the narrow physiological range encountered experimentally. In order to represent correctly the empirically observed slope of the overall v-f relationship, the reactive bed should constitute about half of the total vascular volume, thus including a significant fraction of capillaries and/or veins. Model M3 demonstrates systematic variation of the slope of the v-f relationship between 0.16 and 1.0, depending on the vascular compartment under consideration. This is further complicated when other experimental approaches such as flow velocity are used as substitute measurements. The effect is particularly large in microvascular compartments, but when averaged with larger vessels the variations in slope are contained within 0.25 to 0.55 under conditions typical for imaging methods. We conclude that the v-f relationship is not a fixed function but that both the shape and slope depend on the composition of the reactive volume and the experimental methods used

Modelling vascular reactivity to investigate the basis of the relationship between cerebral blood volume and flow under CO2 manipulation.

Changes in cerebral blood flow (f) and vascular volume (v) are of major interest in mapping cerebral activity and metabolism, but the relation between them currently lacks a sufficient theoretical basis. To address this we considered three models: a uniform reactive tube model (M1); an extension of M1 that includes passive arterial inflow and venous volume (M2); and a more anatomically plausible model (M3) consisting of 19 compartments representing the whole range of vascular sizes and respective CO2 reactivities, derived from literature data. We find that M2 cannot be described as the simple scaling of a tube law, but any divergence from a linear approximation is negligible within the narrow physiological range encountered experimentally. In order to represent correctly the empirically observed slope of the overall v-f relationship, the reactive bed should constitute about half of the total vascular volume, thus including a significant fraction of capillaries and/or veins. Model M3 demonstrates systematic variation of the slope of the v-f relationship between 0.16 and 1.0, depending on the vascular compartment under consideration. This is further complicated when other experimental approaches such as flow velocity are used as substitute measurements. The effect is particularly large in microvascular compartments, but when averaged with larger vessels the variations in slope are contained within 0.25 to 0.55 under conditions typical for imaging methods. We conclude that the v-f relationship is not a fixed function but that both the shape and slope depend on the composition of the reactive volume and the experimental methods used

Development of a novel diffuse correlation spectroscopy platform for monitoring cerebral blood flow and oxygen metabolism: from novel concepts and devices to preclinical live animal studies

New optical technologies were developed to continuously measure cerebral blood flow (CBF) and oxygen metabolism (CMRO2) non-invasively through the skull. Methods and devices were created to improve the performance of near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) for use in experimental animals and humans. These were employed to investigate cerebral metabolism and cerebrovascular reactivity under different states of anesthesia and during models of pathological states. Burst suppression is a brain state arising naturally in pathological conditions or under deep general anesthesia, but its mechanism and consequences are not well understood. Electroencephalography (EEG) and cortical hemodynamics were simultaneously measured in rats to evaluate the coupling between cerebral oxygen metabolism and neuronal activity in the burst suppressed state. EEG bursts were used to deconvolve NIRS and DCS signals into the hemodynamic and metabolic response function for an individual burst. This response was found to be similar to the stereotypical functional hyperemia evoked by normal brain activation. Thus, spontaneous burst activity does not cause metabolic or hemodynamic dysfunction in the cortex. Furthermore, cortical metabolic activity was not associated with the initiation or termination of a burst. A novel technique, time-domain DCS (TD-DCS), was introduced to significantly increase the sensitivity of transcranial CBF measurements to the brain. A new time-correlated single photon counting (TCSPC) instrument with a custom high coherence pulsed laser source was engineered for the first-ever simultaneous measurement of photon time of flight and DCS autocorrelation decays. In this new approach, photon time tags are exploited to determine path-length-dependent autocorrelation functions. By correlating photons according to time of flight, CBF is distinguished from superficial blood flow. Experiments in phantoms and animals demonstrate TD-DCS has significantly greater sensitivity to the brain than existing transcranial techniques. Intracranial pressure (ICP) modulates both steady-state and pulsatile CBF, making CBF a potential marker for ICP. In particular, the critical closing pressure (CrCP) has been proposed as a surrogate measure of ICP. A new DCS device was developed to measure pulsatile CBF non-invasively. A novel method for estimating CrCP and ICP from DCS measurement of pulsatile microvascular blood flow in the cerebral cortex was demonstrated in rats.2018-03-08T00:00:00