A multiscale model for the simulation of cerebral and extracerebral blood flows and pressures in humans.

PURPOSE: Brain hemodynamics is fundamental for the functioning of the human being. Many biophysical factors affect brain circulation, so that a satisfactory understanding of its behavior is challenging. We developed a mathematical model to simulate cerebral and extracerebral flows and pressures in humans. METHODS: The model is composed of an anatomically informed 1-D arterial network, and two 0-D networks of the cerebral circulation and brain drainage, respectively. It takes into account the pulse-wave transmission properties of the 55 main arteries and the main hydraulic and autoregulation mechanisms ensuring blood supply and drainage to the brain. Proper pressure outputs from the arterial 1-D model are used as input to the 0-D models, together with the contribution to venous pressure due to breathing that simulates the drainage effect of the thoracic pump. RESULTS: The model we developed is able to link the arterial tree with the venous pathways devoted to the brain drainage, and to simulate important factors affecting cerebral circulation both for physiological and pathological conditions, such as breathing and hypo/hypercapnia. Finally, the average value of simulated flows and pressures is in agreement with the available experimental data. CONCLUSIONS: The model has the potential to predict important clinical parameters before and after physiological and/or pathological changes.

The Effect of Submaximal Exercise on Jugular Venous Pulse Assessed by a Wearable Cervical Plethysmography System.

The jugular venous pulse (JVP) is a one of the crucial parameters of efficient cardiovascular function. Nowadays, limited data are available regarding the response of JVP to exercise because of its complex and/or invasive assessment procedure. The aim of the present work is to test the feasibility of a non-invasive JVP plethysmography system to monitor different submaximal exercise condition. Twenty (20) healthy subjects (13M/7F mean age 25 ± 3, BMI 21 ± 2) underwent cervical strain-gauge plethysmography, acquired synchronously with the electrocardiogram, while they were carrying out different activities: stand supine, upright, and during the execution of aerobic exercise (2 km walking test) and leg-press machine exercise (submaximal 6 RM test). Peaks a and x of the JVP waveform were investigated since they reflect the volume of cardiac filling. To this aim, the Δax parameter was introduced, representing the amplitude differences between a and x peaks. Significant differences in the values of a, x, and Δax were found between static and exercise conditions (p < 0.0001, p < 0.0001, p < 0.0001), respectively. Particularly, the Δax value for the leg press was approximately three times higher than the supine, and during walking was even nine times higher. The exercise monitoring by means of the novel JVP plethysmography system is feasible during submaximal exercise, and it provides additional parameters on cardiac filling and cerebral venous drainage to the widely used heartbeat rate value.

Modelling physiology of haemodynamic adaptation in short-term microgravity exposure and orthostatic stress on Earth.

Cardiovascular haemodynamics alters during posture changes and exposure to microgravity. Vascular auto-remodelling observed in subjects living in space environment causes them orthostatic intolerance when they return on Earth. In this study we modelled the human haemodynamics with focus on head and neck exposed to different hydrostatic pressures in supine, upright (head-up tilt), head-down tilt position, and microgravity environment by using a well-developed 1D-0D haemodynamic model. The model consists of two parts that simulates the arterial (1D) and brain-venous (0D) vascular tree. The cardiovascular system is built as a network of hydraulic resistances and capacitances to properly model physiological parameters like total peripheral resistance, and to calculate vascular pressure and the related flow rate at any branch of the tree. The model calculated 30.0 mmHg (30%), 7.1 mmHg (78%), 1.7 mmHg (38%) reduction in mean blood pressure, intracranial pressure and central venous pressure after posture change from supine to upright, respectively. The modelled brain drainage outflow percentage from internal jugular veins is 67% and 26% for supine and upright posture, while for head-down tilt and microgravity is 65% and 72%, respectively. The model confirmed the role of peripheral veins in regional blood redistribution during posture change from supine to upright and microgravity environment as hypothesized in literature. The model is able to reproduce the known haemodynamic effects of hydraulic pressure change and weightlessness. It also provides a virtual laboratory to examine the consequence of a wide range of orthostatic stresses on human haemodynamics.

Plethysmography System to Monitor the Jugular Venous Pulse: A Feasibility Study.

Cerebral venous outflow is investigated in the diagnosis of heart failure through the monitoring of jugular venous pulse, an indicator to assess cardiovascular diseases. The jugular venous pulse is a weak signal stemming from the lying internal jugular vein and often invasive methodologies requiring surgery are mandatory to detect it. Jugular venous pulse can also be extrapolated via the ultrasound technique, but it requires a qualified healthcare operator to perform the examination. In this work, a wireless, user-friendly, wearable device for plethysmography is developed to investigate the possibility of monitoring the jugular venous pulse non-invasively. The proposed device can monitor the jugular venous pulse and the electrocardiogram synchronously. To study the feasibility of using the proposed device to detect physiological variables, several measurements were carried out on healthy subjects by considering three different postures: supine, sitting, and upright. Data acquired in the experiment were properly filtered to highlight the cardiac oscillation and remove the breathing contribution, which causes a considerable shift in the amplitude of signals. To evaluate the proper functioning of the wearable device for plethysmography, a comparison with the ultrasound technique was carried out. As a satisfactory result, the acquired signals resemble the typical jugular venous pulse waveforms found in literature.

NO-HYPE: a novel hydrodynamic phantom for the evaluation of MRI flow measurements.

Accurate and reproducible measurement of blood flow profile is very important in many clinical investigations for diagnosing cardiovascular disorders. Given that many factors could affect human circulation, and several parameters must be set to properly evaluate blood flows with phase-contrast techniques, we developed an MRI-compatible hydrodynamic phantom to simulate different physiological blood flows. The phantom included a programmable hydraulic pump connected to a series of pipes immersed in a solution mimicking human soft tissues, with a blood-mimicking fluid flowing in the pipes. The pump is able to shape and control the flow by driving a piston through a dedicated software. Periodic waveforms are used as input to the pump to move the fluid into the pipes, with synchronization of the MRI sequences to the flow waveforms. A dedicated software is used to extract and analyze flow data from magnitude and phase images. The match between the nominal and the measured flows was assessed, and the scope of phantom variables useful for a reliable calibration of an MRI system was accordingly defined. Results showed that the NO-HYPE phantom is a valuable tool for the assessment of MRI scanners and sequence design for the MR evaluation of blood flows. Overview of the NOvel HYdrodynamic Phantom for the Evaluation of MRI flow measurements (NO-HYPE). Left: internal of the CompuFlow 1000 MR pump unit. Right: Setting of the NO-HYPE before a MRI acquisition session. Soft tissue mimicking material is hosted in the central part of the phantom (light blue chamber). Glass pipes pass through the chamber carrying the blood mimicking fluid.

Paediatric haemodynamic modelling: development and experimental validation using quantitative flow MRI.

BACKGROUND: Congenital vascular disease is one of the leading causes of death in paediatric age. Despite the importance of paediatric haemodynamics, large investigations have been devoted to the evaluation of circulation in adults. The novelty of this study consists in the development of a well calibrated mathematical model of cardiovascular circulation in paediatric subjects. To reach the purpose, a model for adult circulation was modified and recalibrated with experimental data and literature from children to be able to calculate the flow rates and pressures in the brain and neck. METHODS: The haemodynamic model simulates the 76 main arteries, together with the main veins in brain and neck. A proper magnetic resonance imaging (MRI) dataset of 29 volunteers aged 12 ± 5 years (mean ± standard deviation) was used to extract age-dependent physiological and clinical parameters such as heart rate, flow rate, vessel cross section area, and blood pressure. The computational model was calibrated using such experimental data. The paediatric and adult model results were compared. RESULTS: Increase of the vessels stiffness due to aging contributes to a flow rate decrease while blood pressure increases. In accordance, our simulation results show about 16% decrease in mean pressure of internal jugular vein in paediatric rather than adult subjects. The model outcomes indicated about 88% correlation with MRI data. CONCLUSIONS: The mathematical model simulates the paediatric head and neck blood circulation. The model provides detailed information of human haemodynamics including arterial and venous network to study both paediatric and adult blood circulation.

Ultrasound Monitoring of Jugular Venous Pulse during Space Missions: Proof of Concept.

The jugular venous pulse (JVP) is one of the main parameters of cardiac function and is used by cardiologists in diagnosing heart failure. Its waveform comprises three positive waves (a, c and v) and two negative waves (x and y). Recently, it was found that JVP can be extrapolated from an ultrasound (US) video recording of the internal jugular vein (IJV), suggesting its application in space missions, on which US scanners are already widely used. To date, the feasibility of assessing JVP in microgravity (microG) has not been investigated. To verify the feasibility of JVP assessment in microG, we tested a protocol of self-performed B-mode ultrasound on the International Space Station (ISS). The protocol consisted of a video recording of IJV synchronized with electrocardiogram that produces a cross-sectional area time trace (JVP trace) (in cm2). The scans were acquired in six experimental sessions; two pre-flight (BDC1 and -2), two in space (ISS1 and -2) and two post-flight (Houston PF1, Cologne PF2). We measured the mean and standard deviation of the JVP waves and the phase relationship between such waves and P and T waves on the electrocardiogram. We verified that such parameters had the same accuracy on Earth as they did under microG, and we compared their values. The sensitivity, specificity and accuracy of JVP trace in microgravity are higher than those on Earth. The sequence of (a, c, and v) ascents and (x and y) descents along the cardiac cycle in microG is the same as that on Earth. The cause-and-effect relationship between the P and T waves on the electrocardiogram and a and v waves, respectively, of JVP is also confirmed in microG. Our experiment indicated the feasibility of deriving a JVP trace from a B-mode US examination self-performed by an astronaut in microG.

Earliest effects of sudden occlusions on pressure profiles in selected locations of the human systemic arterial system.

We have developed a numerical simulation method for predicting the time dependence (wave form) of pressure at any location in the systemic arterial system in humans. The method uses the matlab-Simulink environment. The input data include explicitly the geometry of the arterial tree, treated up to an arbitrary bifurcation level, and the elastic properties of arteries as well as rheological parameters of blood. Thus, the impact of anatomic details of an individual subject can be studied. The method is applied here to reveal the earliest stages of mechanical reaction of the pressure profiles to sudden local blockages (thromboses or embolisms) of selected arteries. The results obtained with a purely passive model provide reference data indispensable for studies of longer-term effects due to neural and humoral mechanisms. The reliability of the results has been checked by comparison of two available sets of anatomic, elastic, and rheological data involving (i) 55 and (ii) 138 arterial segments. The remaining arteries have been replaced with the appropriate resistive elements. Both models are efficient in predicting an overall shift of pressure, whereas the accuracy of the 55-segment model in reproducing the detailed wave forms and stabilization times turns out dependent on the location of the blockage and the observation point.

Protective properties of the arterial system against peripherally generated waves.

An anatomically detailed model consisting of a network of electric transmission lines is developed to simulate propagation of the pulse waves in humans. The simulations show that the real arterial tree geometry, together with the elastic and rheological parameters of particular segments, ensure an efficient protection of vital organs against pulse waves generated at peripheral locations. Because locomotive movements are the most obvious source of such disturbances, additional cyclic perturbations are applied to the model femoral arteries. It is shown that the impact of such peripherally generated pulse waves onto the pressure profiles at the ascending aorta and at other vital locations of the system is surprisingly weak independently of synchronization/desynchronization with the heart action period. This may witness to an intrinsically protective nature of the arterial tree anatomy in addition to its known functionality of the optimal blood supply at possibly low lumen volume. The extent of the protection is also studied in the presence of a complete arterial embolism at the left common carotid artery.

Clinical Applicability of Assessment of Jugular Flow over the Individual Cardiac Cycle Compared with Current Ultrasound Methodology.

There is growing interest in measuring cerebral venous outflow with ultrasound (US). However, results obtained with the current US Doppler methodology, which uses just a single value of cross-sectional area (CSA) of the vessel, are highly variable and inconclusive. The product of CSA and time-averaged velocity in the case of pulsatile vessels may be a possible source of error, particularly for a pulsatile vein like the internal jugular vein (IJV), where the cardiac pump transmits a sequence of well-established waves along the conduit. We herein propose a novel technique for US IJV flow assessment that accurately accounts for IJV CSA variations during the cardiac cycle. Five subjects were investigated with a high-resolution real-time B-mode video, synchronized with an electrocardiography trace. In this approach, CSA variations representing the pulsatility of the IJV are overlapped with the velocity curve obtained by the usual spectral Doppler trace. The overlap is then phased point by point using the electrocardiography pacemaker. This allows us to experimentally measure the velocity variation in relation to the change in CSA precisely, ultimately enabling calculation of IJV flow. (i) The sequence of CSA variation with respect to the electrocardiography waves corresponds exactly to the jugular venous pulse as measured in physiology. (ii) The methodology permits us to phase the velocity and CSA, which is ultimately what is currently lacking to precisely calculate the flow in the IJV with US. (iii) The time-averaged flow, calculated with the described technique, is very close to that calculated assuming a constant IJV CSA, whereas the time-dependent flow shows differs as much as 40%. (iv) Finally, we tested the accuracy of the technique with a methodology that may allow for universal assessment of the accuracy of each personal US-based evaluation of flow rate.

An ultrasonographic technique to assess the jugular venous pulse: a proof of concept.

The purpose of the work described here was to investigate the feasibility of assessing the jugular venous pulse (JVP) using ultrasound (US) equipment. Three young healthy subjects underwent a B-mode US scan of the internal jugular vein (IJV) to acquire a sonogram sequence in the transverse plane. On each acquired sonogram, the IJV contour was manually traced, and both the cross-sectional area (CSA) and the perimeter were measured. The CSA data set represents the US jugular diagram (USJD). The arterial distension waveform of the subjects was compared with its USJD. The correlation between the CSA and the perimeter was assessed during the cardiac cycle to verify IJV distension. For each subject, a short sonogram sequence of a few seconds was recorded, and the USJD obtained exhibited periodic behavior. Furthermore, for all subjects, the CSA was found to be correlated with the perimeter (Pearson coefficient, R > 0.9), indicating that the IJV in supine position is distended. We compared 390 manually traced contours of the IJV cross-sectional area with corresponding values semi-automatically calculated by an algorithm developed in-house. For all subjects, the sensitivity, specificity and accuracy were around 95%, 85% and 90% respectively. We found that a diagram reflecting the JVP can be obtained by analyzing a B-mode sonogram sequence of the IJV; such a diagram can result in a new methodology to assess the IJV functionality.