Elevated fluid and glycosaminoglycan content in the Achilles tendon contribute to higher intratendinous pressure: Implications for Achilles tendinopathy.

BACKGROUND: Tendinopathy alters the compositional properties of the Achilles tendon by increasing fluid and glycosaminoglycan content. It has been speculated that these changes may affect intratendinous pressure, but the extent of this relationship remains unclear. Therefore, we aimed to investigate the impact of elevated fluid and glycosaminoglycan content on Achilles tendon intratendinous pressure and to determine whether hyaluronidase (HYAL) therapy can intervene in this potential relationship. METHODS: Twenty paired fresh-frozen cadaveric Achilles tendons were mounted in a tensile-testing machine and loaded up to 5% strain. Intratendinous resting (at 0% strain) and dynamic pressure (at 5% strain) were assessed using the microcapillary infusion technique. First, intratendinous pressure was measured under native conditions before and after infusion of 2 mL physiological saline. Next, 80 mg of glycosaminoglycans were administered bilaterally to the paired tendons. The right tendons were additionally treated with 1500 units of HYAL. Finally, both groups were retested, and the glycosaminoglycan content was analyzed. RESULTS: It was found that both elevated fluid and glycosaminoglycan content resulted in higher intratendinous resting and dynamic pressures (p < 0.001). HYAL treatment induced a 2.3-fold reduction in glycosaminoglycan content (p = 0.002) and restored intratendinous pressures. CONCLUSION: The results of this study demonstrated that elevated fluid and glycosaminoglycan content in Achilles tendinopathy contribute to increased intratendinous resting and dynamic pressures, which can be explained by the associated increased volume and reduced permeability of the tendon matrix, respectively. HYAL degrades glycosaminoglycans sufficiently to lower intratendinous pressures and may, therefore, serve as a promising treatment.

Ultrasound Shear Wave Elastography in Cardiology.

The advent of high-frame rate imaging in ultrasound allowed the development of shear wave elastography as a noninvasive alternative for myocardial stiffness assessment. It measures mechanical waves propagating along the cardiac wall with speeds that are related to stiffness. The use of cardiac shear wave elastography in clinical studies is increasing, but a proper understanding of the different factors that affect wave propagation is required to correctly interpret results because of the heart's thin-walled geometry and intricate material properties. The aims of this review are to give an overview of the general concepts in cardiac shear wave elastography and to discuss in depth the effects of age, hemodynamic loading, cardiac morphology, fiber architecture, contractility, viscoelasticity, and system-dependent factors on the measurements, with a focus on clinical application. It also describes how these factors should be considered during acquisition, analysis, and reporting to ensure an accurate, robust, and reproducible measurement of the shear wave.

Novel theory and potential applications of central diastolic pressure decay time constant.

Central aortic diastolic pressure decay time constant ( τ ) is according to the two-element Windkessel model equal to the product of total peripheral resistance ( R ) times total arterial compliance ( C ). As such, it is related to arterial stiffness, which has considerable pathophysiological relevance in the assessment of vascular health. This study aimed to investigate the relationship of the constant τ with the product T MBP cPP , given by heart period ( T ) times the ratio of mean blood pressure (MBP) to central pulse pressure ( cPP ). The relationship was derived by performing linear fitting on an in silico population of n1 = 3818 virtual subjects, and was subsequently evaluated on in vivo data (n2 = 2263) from the large Asklepios study. The resulted expression was found to be τ = k ' T MBP cPP , with k ' = 0.7 (R2 = 0.9). The evaluation of the equation on the in vivo human data reported high agreement between the estimated and reference τ values, with a correlation coefficient equal to 0.94 and a normalized RMSE equal to 5.5%. Moreover, the analysis provided evidence that the coefficient k ' is age- and gender-independent. The proposed formula provides novel theoretical insights in the relationship between τ and central blood pressure features. In addition, it may allow for the evaluation of τ without the need for acquiring the entire central blood pressure wave, especially when an approximation of the cPP is feasible. This study adds to the current literature by contributing to the accessibility of an additional biomarker, such as the central diastolic pressure decay time constant, for the improved assessment of vascular ageing.

Effect of interstitial fluid pressure on shear wave elastography: an experimental and computational study.

Objective. An elevated interstitial fluid pressure (IFP) can lead to strain-induced stiffening of poroelastic biological tissues. As shear wave elastography (SWE) measures functional tissue stiffness based on the propagation speed of acoustically induced shear waves, the shear wave velocity (SWV) can be used as an indirect measurement of the IFP. The underlying biomechanical principle for this stiffening behavior with pressurization is however not well understood, and we therefore studied how IFP affects SWV through SWE experiments and numerical modeling.Approach. For model set-up and verification, SWE experiments were performed while dynamically modulating IFP in a chicken breast. To identify the confounding factors of the SWV-IFP relationship, we manipulated the material model (linear poroelastic versus porohyperelastic), deformation assumptions (geometric linearity versus nonlinearity), and boundary conditions (constrained versus unconstrained) in a finite element model mimicking the SWE experiments.Main results. The experiments demonstrated a statistically significant positive correlation between the SWV and IFP. The model was able to reproduce a similar SWV-IFP relationship by considering an unconstrained porohyperelastic tissue. Material nonlinearity was identified as the primary factor contributing to this relationship, whereas geometric nonlinearity played a smaller role. The experiments also highlighted the importance of the dynamic nature of the pressurization procedure, as indicated by a different observed SWV-IFP for pressure buildup and relaxation, but its clinical relevance needs to be further investigated.Significance. The developed model provides an adaptable framework for SWE of poroelastic tissues and paves the way towards non-invasive measurements of IFP.

From Corrosion Casting to Virtual Dissection: Contrast-Enhanced Vascular Imaging using Hafnium Oxide Nanocrystals.

Vascular corrosion casting is a method used to visualize the three dimensional (3D) anatomy and branching pattern of blood vessels. A polymer resin is injected in the vascular system and, after curing, the surrounding tissue is removed. The latter often deforms or even fractures the fragile cast. Here, a method is proposed that does not require corrosion, and is based on in situ micro computed tomography (micro-CT) scans. To overcome the lack of CT contrast between the polymer cast and the animals' surrounding soft tissue, hafnium oxide nanocrystals (HfO2 NCs) are introduced as CT contrast agents into the resin. The NCs dramatically improve the overall CT contrast of the cast and allow for straightforward segmentation in the CT scans. Careful design of the NC surface chemistry ensures the colloidal stability of the NCs in the casting resin. Using only 5 m% of HfO2 NCs, high-quality cardiovascular casts of both zebrafish and mice can be automatically segmented using CT imaging software. This allows to differentiate even µ $\umu$ m-scale details without having to alter the current resin injection methods. This new method of virtual dissection by visualizing casts in situ using contrast-enhanced CT imaging greatly expands the application potential of the technique.

Uncertainty quantification of the wall thickness and stiffness in an idealized dissected aorta.

Personalized treatment informed by computational models has the potential to markedly improve the outcome for patients with a type B aortic dissection. However, existing computational models of dissected walls significantly simplify the characteristic false lumen, tears and/or material behavior. Moreover, the patient-specific wall thickness and stiffness cannot be accurately captured non-invasively in clinical practice, which inevitably leads to assumptions in these wall models. It is important to evaluate the impact of the corresponding uncertainty on the predicted wall deformations and stress, which are both key outcome indicators for treatment optimization. Therefore, a physiology-inspired finite element framework was proposed to model the wall deformation and stress of a type B aortic dissection at diastolic and systolic pressure. Based on this framework, 300 finite element analyses, sampled with a Latin hypercube, were performed to assess the global uncertainty, introduced by 4 uncertain wall thickness and stiffness input parameters, on 4 displacement and stress output parameters. The specific impact of each input parameter was estimated using Gaussian process regression, as surrogate model of the finite element framework, and a δ moment-independent analysis. The global uncertainty analysis indicated minor differences between the uncertainty at diastolic and systolic pressure. For all output parameters, the 4th quartile contained the major fraction of the uncertainty. The parameter-specific uncertainty analysis elucidated that the material stiffness and relative thickness of the dissected membrane were the respective main determinants of the wall deformation and stress. The uncertainty analysis provides insight into the effect of uncertain wall thickness and stiffness parameters on the predicted deformation and stress. Moreover, it emphasizes the need for probabilistic rather than deterministic predictions for clinical decision making in aortic dissections.

2024 Recommendations for Validation of Noninvasive Arterial Pulse Wave Velocity Measurement Devices.

BACKGROUND: Arterial stiffness, as measured by arterial pulse wave velocity (PWV), is an established biomarker for cardiovascular risk and target-organ damage in individuals with hypertension. With the emergence of new devices for assessing PWV, it has become evident that some of these devices yield results that display significant discrepancies compared with previous devices. This discrepancy underscores the importance of comprehensive validation procedures and the need for international recommendations. METHODS: A stepwise approach utilizing the modified Delphi technique, with the involvement of key scientific societies dedicated to arterial stiffness research worldwide, was adopted to formulate, through a multidisciplinary vision, a shared approach to the validation of noninvasive arterial PWV measurement devices. RESULTS: A set of recommendations has been developed, which aim to provide guidance to clinicians, researchers, and device manufacturers regarding the validation of new PWV measurement devices. The intention behind these recommendations is to ensure that the validation process can be conducted in a rigorous and consistent manner and to promote standardization and harmonization among PWV devices, thereby facilitating their widespread adoption in clinical practice. CONCLUSIONS: It is hoped that these recommendations will encourage both users and developers of PWV measurement devices to critically evaluate and validate their technologies, ultimately leading to improved consistency and comparability of results. This, in turn, will enhance the clinical utility of PWV as a valuable tool for assessing arterial stiffness and informing cardiovascular risk stratification and management in individuals with hypertension.

Enhancing Multichannel Laser-Doppler Vibrometry Signals with Application to (Carotid-Femoral) Pulse Transit Time Estimation.

Pulse-wave velocity (PWV) can be used to quantify arterial stiffness, allowing for a diagnosis of this condition. Multi-beam laser-doppler vibrometry offers a cheap, non-invasive and user-friendly alternative to measuring PWV, and its feasibility has been previously demonstrated in the H2020 project CARDIS. The two handpieces of the prototype CARDIS device measure skin displacement above main arteries at two different sites, yielding an estimate of the pulse-transit time (PTT) and, consequently, PWV. The presence of multiple beams (channels) on each handpiece can be used to enhance the underlying signal, improving the quality of the signal for PTT estimation and further analysis. We propose two methods for multi-channel LDV data processing: beamforming and beamforming-driven ICA. Beamforming is done by an SNR-weighted linear combination of the time-aligned channels, where the SNR is blindly estimated from the signal statistics. ICA uses the beamformer to resolve its inherent permutation and scale ambiguities. Both methods yield a single enhanced signal at each handpiece, where spurious peaks in the individual channels as well as stochastic noise are well suppressed in the output. Using the enhanced signals yields individual PTT estimates with a low spread compared to the baseline approach. While the enhancement is introduced in the context of PTT estimation, the approaches can be used to enhance signals in other biomedical applications of multi-channel LDV as well.

Growth and remodeling of the dissected membrane in an idealized dissected aorta model.

While transitioning from the acute to chronic phase, the wall of a dissected aorta often expands in diameter and adaptations in thickness and microstructure take place in the dissected membrane. Including the mechanisms, leading to these changes, in a computational model is expected to improve the accuracy of predictions of the long-term complications and optimal treatment timing of dissection patients. An idealized dissected wall was modeled to represent the elastin and collagen production and/or degradation imposed by stress- and inflammation-mediated growth and remodeling, using the homogenized constrained mixture theory. As no optimal growth and remodeling parameters have been defined for aortic dissections, a Latin hypercube sampling with 1000 parameter combinations was assessed for four inflammation patterns, with a varying spatial extent (full/local) and temporal evolution (permanent/transient). The dissected membrane thickening and microstructure was considered together with the diameter expansion over a period of 90 days. The highest success rate was found for the transient inflammation patterns, with about 15% of the samples leading to converged solutions after 90 days. Clinically observed thickening rates were found for 2-4% of the transient inflammation samples, which represented median total diameter expansion rates of about 5 mm/year. The dissected membrane microstructure showed an elastin decrease and, in most cases, a collagen increase. In conclusion, the model with the transient inflammation pattern allowed the reproduction of clinically observed dissected membrane thickening rates, diameter expansion rates and adaptations in microstructure, thus providing guidance in reducing the parameter space in growth and remodeling models of aortic dissections.

In Vivo Material Properties of Human Common Carotid Arteries: Trends and Sex Differences.

INTRODUCTION: In vivo estimation of material properties of arterial tissue can provide essential insights into the development and progression of cardiovascular diseases. Furthermore, these properties can be used as an input to finite element simulations of potential medical treatments. MATERIALS AND METHODS: This study uses non-invasively measured pressure, diameter and wall thickness of human common carotid arteries (CCAs) acquired in 103 healthy subjects. A non-linear optimization was performed to estimate material parameters of two different constitutive models: a phenomenological, isotropic model and a structural, anisotropic model. The effect of age, sex, body mass index and blood pressure on the parameters was investigated. RESULTS AND CONCLUSION: Although both material models were able to model in vivo arterial behaviour, the structural model provided more realistic results in the supra-physiological domain. The phenomenological model predicted very high deformations for pressures above the systolic level. However, the phenomenological model has fewer parameters that were shown to be more robust. This is an advantage when only the physiological domain is of interest. The effect of stiffening with age, BMI and blood pressure was present for women, but not always for men. In general, sex had the biggest effect on the mechanical properties of CCAs. Stiffening trends with age, BMI and blood pressure were present but not very strong. The intersubject variability was high. Therefore, it can be concluded that finding a representative set of parameters for a certain age or BMI group would be very challenging. Instead, for purposes of patient-specific modelling of surgical procedures, we currently advise the use of patient-specific parameters.

Application of an automated analysis framework for pulsed-wave Doppler cardiac ultrasound measurements to generate reference data in adult zebrafish.

High-frequency cardiac ultrasound is the only well-established method to characterize in vivo cardiovascular function in adult zebrafish noninvasively. Pulsed-wave Doppler imaging allows measurements of blood flow velocities at well-defined anatomical positions, but the measurements and results obtained using this technique need to be analyzed carefully, taking into account the substantial baseline variability within one recording and the possibility for operator bias. To address these issues and to increase throughput by limiting hands-on analysis time, we have developed a fully automated processing pipeline. This framework enables the fast, unbiased analysis of all cardiac cycles in a zebrafish pulsed-wave Doppler recording of both atrioventricular valve flow as well as aortic valve flow without operator-dependent inputs. Applying this automated pipeline to a large number of recordings from wild-type zebrafish shows a strong agreement between the automated results and manual annotations performed by an experienced operator. The reference data obtained from this analysis showed that the early wave peak during ventricular inflow is lower for female compared with male zebrafish. We also found that the peaks of the ventricular inflow and outflow waves as well as the peaks of the regurgitation waves are all correlated positively with body surface area. In general, the presented reference data, as well as the automated Doppler measurement processing tools developed and validated in this study will facilitate future (high-throughput) cardiovascular phenotyping studies in adult zebrafish ultimately leading to a more comprehensive understanding of human (genetic) cardiovascular diseases.

The impact of geometry, intramural friction, and pressure on the antegrade longitudinal motion of the arterial wall: A phantom and finite element study.

Longitudinal motion of the carotid arterial wall, as measured with ultrasound, has shown promise as an indicator of vascular health. The underlying mechanisms are however not fully understood. We have found, in in vivo studies, that blood pressure has a strong relation to the antegrade longitudinal displacement in early systole. Further, we have identified that a tapered geometry and the intramural friction in-between two parts of a vessel wall influence the longitudinal displacement. We therefore studied the interaction between pressure, vessel geometry and intramural friction, tapered and straight ultrasound phantoms in a paralleled hydraulic bench study and corresponding numerical models. Profound antegrade longitudinal motion was induced in the innermost part of both tapered phantoms and the numerical models, but to a lesser extent when intramural friction was increased in the simulations. Strong correlations (R = 0.82-0.96; p < 1e-3; k = 9.3-14 µm/mmHg) between longitudinal displacement and pulse pressure were found in six of seven regions of interest in tapered phantoms. The motion of the straight phantom and the corresponding numerical model was smaller, on average zero or close to zero. This study demonstrates that tapering of the lumen, low intramural friction, and pressure might be important conducive features to the antegrade longitudinal motion of the arterial wall in vivo.

Fluid-Structure Interaction Modeling of the Aortic Hemodynamics in Adult Zebrafish: A Pilot Study Based on Synchrotron X-Ray Tomography.

OBJECTIVE: The zebrafish is increasingly used as a small animal model for cardiovascular disease, including vascular disorders. Nevertheless, a comprehensive biomechanical understanding of the zebrafish cardiovascular circulation is still lacking and possibilities for phenotyping the zebrafish heart and vasculature at adult - no longer optically transparent - stages are limited. To improve these aspects, we developed imaging-based 3D models of the cardiovascular system of wild-type adult zebrafish. METHODS: In vivo high-frequency echocardiography and ex vivo synchrotron X-ray tomography were combined to build fluid-structure interaction finite element models of the fluid dynamics and biomechanics inside the ventral aorta. RESULTS: We successfully generated a reference model of the circulation in adult zebrafish. The dorsal side of the most proximal branching region was found as the location of highest first principal wall stress and was also a location of low wall shear stress. Reynolds number and oscillatory shear were very low compared to mice and humans. SIGNIFICANCE: The presented wild-type results provide a first extensive biomechanical reference for adult zebrafish. This framework can be used for advanced cardiovascular phenotyping of adult genetically engineered zebrafish models of cardiovascular disease, showing disruptions of the normal mechano-biology and homeostasis. By providing reference values for key biomechanical stimuli (including wall shear stress and first principal stress) in wild-type animals, and a pipeline for image-based animal-specific computational biomechanical models, this study contributes to a more comprehensive understanding of the role of altered biomechanics and hemodynamics in heritable cardiovascular pathologies.

Arterial pulse wave modeling and analysis for vascular-age studies: a review from VascAgeNet.

Arterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propagation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life.

Pulse wave velocity: A clinical measure to aid material parameter estimation in computational arterial biomechanics.

Determining proper material parameters from clinical data remains a large, though unavoidable, challenge in patient-specific computational cardiovascular modeling. In an attempt to couple the clinical and modelling practice, this study investigated whether pulse wave velocity (PWV), a clinical arterial stiffness measure, can guide in determining appropriate parameter values for the Gasser-Ogden-Holzapfel (GOH) constitutive model. The reduction and uncertainty analysis was demonstrated on a cylindrical descending thoracic aorta model. Starting from discretized ranges of GOH parameters and using a full factorial design, the parameter sets yielding a physiological PWV (3.5-12.5 m/s) at diastolic pressure (80 mmHg; PWV80) were selected and their PWV at dicrotic notch pressure (110 mmHg; PWV110) was determined. These PWV measures were applied to determine the reduction of the 7D GOH parameter space, the 2D subspaces and the remaining uncertainty in case only PWV80 or both measurements are available. The resulting 12,032 parameter sets lead to a 7D parameter space reduction of ≥ 82.5 % using PWV80, which increased to 96.0 % when including PWV110, in particular at 3.5-8.5 m/s. A similar trend was observed for the remaining uncertainty and the 2D subspaces comprised of medial collagen fiber parameters, while scarce reductions were found for the adventitial and elastin parameters. In conclusion, PWV80 and PWV110 are complementary measures with the potential to reduce the GOH parameter space in arterial models, in particular for media- and collagen-related parameters. Moreover, this approach has the advantage that it allows the estimation of the remaining uncertainty after parameter space reduction.

Assessment of Early Diastolic Intraventricular Pressure Difference in Children by Blood Speckle-Tracking Echocardiography.

BACKGROUND: The lack of reliable echocardiographic techniques to assess diastolic function in children is a major clinical limitation. Our aim was to develop and validate the intraventricular pressure difference (IVPD) calculation using blood speckle-tracking (BST) and investigate the method's potential role in the assessment of diastolic function in children. METHODS: Blood speckle-tracking allows two-dimensional angle-independent blood flow velocity estimation. Blood speckle-tracking images of left ventricular (LV) inflow from the apical 4-chamber view in 138 controls, 10 patients with dilated cardiomyopathies (DCMs), and 21 patients with hypertrophic cardiomyopathies (HCMs) <18 years of age were analyzed to study LV IVPD during early diastole. Reproducibility of the IVPD analysis was assessed, IVPD estimates from BST and color M mode were compared, and the validity of the BST-based IVPD calculations was tested in a computer flow model. RESULTS: Mean IVPD was significantly higher in controls (-2.28 ± 0.62 mm Hg) compared with in DCM (-1.21 ± 0.39 mm Hg, P < .001) and HCM (-1.57 ± 0.47 mm Hg, P < .001) patients. Feasibility was 88.3% in controls, 80% in DCM patients, and 90.4% in HCM patients. The peak relative negative pressure occurred earlier at the apex than at the base and preceded the peak E-wave LV filling velocity, indicating that it represents diastolic suction. Intraclass correlation coefficients for intra- and interobserver variability were 0.908 and 0.702, respectively. There was a nonsignificant mean difference of 0.15 mm Hg between IVPD from BST and color M mode. Estimation from two-dimensional velocities revealed a difference in peak IVPD of 0.12 mm Hg (6.6%) when simulated in a three-dimensional fluid mechanics model. CONCLUSIONS: Intraventricular pressure difference calculation from BST is highly feasible and provides information on diastolic suction and early filling in children with heart disease. Intraventricular pressure difference was significantly reduced in children with DCM and HCM compared with controls, indicating reduced early diastolic suction in these patient groups.

Transmural Wave Speed Gradient May Distinguish Intrinsic Myocardial Stiffening From Preload-Induced Changes in Operational Stiffness in Shear Wave Elastography.

BACKGROUND: Shear wave elastography (SWE) is a promising technique to non-invasively assess myocardial stiffness based on the propagation speed of mechanical waves. However, a high wave propagation speed can either be attributed to an elevated intrinsic myocardial stiffness or to a preload-induced increase in operational stiffness. OBJECTIVE: Our objective was to find a way to discriminate intrinsic myocardial stiffening from stiffening caused by an increased pressure in SWE. METHODS: We used the finite element method to study the shear wave propagation patterns when stiffness and/or pressure is elevated, compared to normal stiffness and pressure. Numerical findings were verified in a few human subjects. RESULTS: The transmural wave speed gradient was able to distinguish changes in intrinsic stiffness from those induced by differing hemodynamic load (a speed of ±3.2 m/s in parasternal short-axis (PSAX) view was associated with a wave speed gradient of -0.17 ± 0.15 m/s/mm when pressure was elevated compared to 0.04 ± 0.05 m/s/mm when stiffness was elevated). The gradient however decreased when stiffness increased (decrease with a factor 3 in PSAX when stiffness doubled at 20 mmHg). The human data analysis confirmed the presence of a wave speed gradient in a patient with elevated ventricular pressure. CONCLUSION: Cardiac SWE modeling is a useful tool to gain additional insights into the complex wave physics and to guide post-processing. The transmural differences in wave speed may help to distinguish loading-induced stiffening from intrinsic stiffness changes. SIGNIFICANCE: The transmural wave speed gradient has potential as a new diagnostic parameter for future clinical studies.

Central blood pressure estimation in type 1 diabetes: impact and implications of peripheral calibration method.

OBJECTIVE: Peripheral blood pressure (BP) waveforms are used for noninvasive central BP estimation. Central BP could assist in cardiovascular risk assessment in patients with type 1 diabetes mellitus (T1DM). However, correct calibration of peripheral BP waveforms is important to accurately estimate central BP. We examined differences in central BP estimated by radial artery tonometry depending on which brachial BP (SBP/DBP vs. MAP/DBP) is used for calibration of the radial waveforms, for the first time in T1DM. METHODS: A cross-sectional study in T1DM patients without known cardiovascular disease. Radial artery BP waveforms were acquired using applanation tonometry ( SphygmoCor ) for the estimation of central SBP, central pulse pressure (PP) and central augmentation pressure, using either brachial SBP/DBP or MAP/DBP for the calibration of the radial pressure waveforms. RESULTS: Fifty-four patients (age: 46 ±â€Š9.5 years; T1DM duration: 27 ±â€Š8.8 years) were evaluated. Central BP parameters were significantly higher when brachial MAP/DBP-calibration was used compared with brachial SBP/DBP-calibration (7.5 ±â€Š5.04, 7.5 ±â€Š5.04 and 1.5 ±â€Š1.36 mmHg higher central SBP, central PP and central augmentation pressure, respectively, P  < 0.001). CONCLUSION: In patients with T1DM, there are significant differences in central BP values estimated with radial artery tonometry, depending on the method used for calibration of the radial waveforms. Brachial MAP/DBP-calibration resulted in consistently higher central BP as compared to using brachial SBP/DBP, leading to patient re-stratification. Hence, the accuracy of noninvasive estimation of central BP by radial tonometry is dependent on calibration approach, and this problem must be resolved in validation studies using an invasive reference standard to determine which method best estimates true central BP.

Computational fluid dynamics model to predict the dynamical behavior of the cerebrospinal fluid through implementation of physiological boundary conditions.

Cerebrospinal fluid (CSF) dynamics play an important role in maintaining a stable central nervous system environment and are influenced by different physiological processes. Multiple studies have investigated these processes but the impact of each of them on CSF flow is not well understood. A deeper insight into the CSF dynamics and the processes impacting them is crucial to better understand neurological disorders such as hydrocephalus, Chiari malformation, and intracranial hypertension. This study presents a 3D computational fluid dynamics (CFD) model which incorporates physiological processes as boundary conditions. CSF production and pulsatile arterial and venous volume changes are implemented as inlet boundary conditions. At the outlets, 2-element windkessel models are imposed to simulate CSF compliance and absorption. The total compliance is first tuned using a 0D model to obtain physiological pressure pulsations. Then, simulation results are compared with in vivo flow measurements in the spinal subarachnoid space (SAS) and cerebral aqueduct, and intracranial pressure values reported in the literature. Finally, the impact of the distribution of and total compliance on CSF pressures and velocities is evaluated. Without respiration effects, compliance of 0.17 ml/mmHg yielded pressure pulsations with an amplitude of 5 mmHg and an average value within the physiological range of 7-15 mmHg. Also, model flow rates were found to be in good agreement with reported values. However, when adding respiration effects, similar pressure amplitudes required an increase of compliance value to 0.51 ml/mmHg, which is within the range of 0.4-1.2 ml/mmHg measured in vivo. Moreover, altering the distribution of compliance over the four different outlets impacted the local flow, including the flow through the foramen magnum. The contribution of compliance to each outlet was directly proportional to the outflow at that outlet. Meanwhile, the value of total compliance impacted intracranial pressure. In conclusion, a computational model of the CSF has been developed that can simulate CSF pressures and velocities by incorporating boundary conditions based on physiological processes. By tuning these boundary conditions, we were able to obtain CSF pressures and flows within the physiological range.