Current Understanding of the Anatomy, Physiology, and Magnetic Resonance Imaging of Neurofluids: Update From the 2022 "ISMRM Imaging Neurofluids Study group" Workshop in Rome.

Neurofluids is a term introduced to define all fluids in the brain and spine such as blood, cerebrospinal fluid, and interstitial fluid. Neuroscientists in the past millennium have steadily identified the several different fluid environments in the brain and spine that interact in a synchronized harmonious manner to assure a healthy microenvironment required for optimal neuroglial function. Neuroanatomists and biochemists have provided an incredible wealth of evidence revealing the anatomy of perivascular spaces, meninges and glia and their role in drainage of neuronal waste products. Human studies have been limited due to the restricted availability of noninvasive imaging modalities that can provide a high spatiotemporal depiction of the brain neurofluids. Therefore, animal studies have been key in advancing our knowledge of the temporal and spatial dynamics of fluids, for example, by injecting tracers with different molecular weights. Such studies have sparked interest to identify possible disruptions to neurofluids dynamics in human diseases such as small vessel disease, cerebral amyloid angiopathy, and dementia. However, key differences between rodent and human physiology should be considered when extrapolating these findings to understand the human brain. An increasing armamentarium of noninvasive MRI techniques is being built to identify markers of altered drainage pathways. During the three-day workshop organized by the International Society of Magnetic Resonance in Medicine that was held in Rome in September 2022, several of these concepts were discussed by a distinguished international faculty to lay the basis of what is known and where we still lack evidence. We envision that in the next decade, MRI will allow imaging of the physiology of neurofluid dynamics and drainage pathways in the human brain to identify true pathological processes underlying disease and to discover new avenues for early diagnoses and treatments including drug delivery. Evidence level: 1 Technical Efficacy: Stage 3.

Assessment of liver function by gadoxetic acid avidity in MRI in a model of rapid liver regeneration in rats.

BACKGROUND: This animal study investigates the hypothesis of an immature liver growth following ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) by measuring liver volume and function using gadoxetic acid avidity in magnetic resonance imaging (MRI) in models of ALPPS, major liver resection (LR) and portal vein ligation (PVL). METHODS: Wistar rats were randomly allocated to ALPPS, LR or PVL. In contrast-enhanced MRI scans with gadoxetic acid (Primovist®), liver volume and function of the right median lobe (=future liver remnant, FLR) and the deportalized lobes (DPL) were assessed until post-operative day (POD) 5. Liver functionFLR/DPL was defined as the inverse value of time from injection of gadoxetic acid to the blood pool-corrected maximum signal intensityFLR/DPL multiplied by the volumeFLR/DPL. RESULTS: In ALPPS (n = 6), LR (n = 6) and PVL (n = 6), volumeFLR and functionFLR increased proportionally, except on POD 1. Thereafter, functionFLR exceeded volumeFLR increase in LR and ALPPS, but not in PVL. Total liver function was significantly reduced after LR until POD 3, but never undercuts 60% of its pre-operative value following ALPPS and PVL. DISCUSSION: This study shows for the first time that functional increase is proportional to volume increase in ALPPS using gadoxetic acid avidity in MRI.

Evolution of hypoxia and hypoxia-inducible factor asparaginyl hydroxylase regulation in chronic kidney disease.

BACKGROUND: The roles of hypoxia and hypoxia inducible factor (HIF) during chronic kidney disease (CKD) are much debated. Interventional studies with HIF-α activation in rodents have yielded contradictory results. The HIF pathway is regulated by prolyl and asparaginyl hydroxylases. While prolyl hydroxylase inhibition is a well-known method to stabilize HIF-α, little is known about the effect asparaginyl hydroxylase factor inhibiting HIF (FIH). METHODS: We used a model of progressive proteinuric CKD and a model of obstructive nephropathy with unilateral fibrosis. In these models we assessed hypoxia with pimonidazole and vascularization with three-dimensional micro-computed tomography imaging. We analysed a database of 217 CKD biopsies from stage 1 to 5 and we randomly collected 15 CKD biopsies of various severity degrees to assess FIH expression. Finally, we modulated FIH activity in vitro and in vivo using a pharmacologic approach to assess its relevance in CKD. RESULTS: In our model of proteinuric CKD, we show that early CKD stages are not characterized by hypoxia or HIF activation. At late CKD stages, some areas of hypoxia are observed, but these are not colocalizing with fibrosis. In mice and in humans, we observed a downregulation of the HIF pathway, together with an increased FIH expression in CKD, according to its severity. Modulating FIH in vitro affects cellular metabolism, as described previously. In vivo, pharmacologic FIH inhibition increases the glomerular filtration rate of control and CKD animals and is associated with decreased development of fibrosis. CONCLUSIONS: The causative role of hypoxia and HIF activation in CKD progression is questioned. A pharmacological approach of FIH downregulation seems promising in proteinuric kidney disease.

Queckenstedt's test repurposed for the quantitative assessment of the cerebrospinal fluid pulsatility curve.

PURPOSE: Before the era of spinal imaging, presence of a spinal canal block was tested through gross changes in cerebrospinal fluid pressure (CSFP) provoked by manual compression of the jugular veins (referred to as Queckenstedt's test; QT). Beyond these provoked gross changes, cardiac-driven CSFP peak-to-valley amplitudes (CSFPp) can be recorded during CSFP registration. This is the first study to assess whether the QT can be repurposed to derive descriptors of the CSF pulsatility curve, focusing on feasibility and repeatability. METHOD: Lumbar puncture was performed in lateral recumbent position in fourteen elderly patients (59.7±9.3 years, 6F) (NCT02170155) without stenosis of the spinal canal. CSFP was recorded during resting state and QT. A surrogate for the relative pulse pressure coefficient was computed from repeated QTs (i.e., RPPC-Q). RESULTS: Resting state mean CSFP was 12.3 mmHg (IQR 3.2) and CSFPp was 1.0 mmHg (0.5). Mean CSFP rise during QT was 12.5 mmHg (7.3). CSFPp showed an average 3-fold increase at peak QT compared to the resting state. Median RPPC-Q was 0.18 (0.04). There was no systematic error in the computed metrics between the first and second QT. CONCLUSION: This technical note describes a method to reliably derive, beyond gross CSFP increments, metrics related to cardiac-driven amplitudes during QT (i.e., RPPC-Q). A study comparing these metrics as obtained by established procedures (i.e., infusion testing) and by QT is warranted.

Renal blood flow and oxygenation.

Our kidneys receive about one-fifth of the cardiac output at rest and have a low oxygen extraction ratio, but may sustain, under some conditions, hypoxic injuries that might lead to chronic kidney disease. This is due to large regional variations in renal blood flow and oxygenation, which are the prerequisite for some and the consequence of other kidney functions. The concurrent operation of these functions is reliant on a multitude of neuro-hormonal signaling cascades and feedback loops that also include the regulation of renal blood flow and tissue oxygenation. Starting with open questions on regulatory processes and disease mechanisms, we review herein the literature on renal blood flow and oxygenation. We assess the current understanding of renal blood flow regulation, reasons for disparities in oxygen delivery and consumption, and the consequences of disbalance between O2 delivery, consumption, and removal. We further consider methods for measuring and computing blood velocity, flow rate, oxygen partial pressure, and related parameters and point out how limitations of these methods constitute important hurdles in this area of research. We conclude that to obtain an integrated understanding of the relation between renal function and renal blood flow and oxygenation, combined experimental and computational modeling studies will be needed.

RAQ: A Noise-Resistant Calibration-Independent Compliance Surrogate.

The intracranial pressure (ICP)-volume relationship contains important information for diagnosing hydrocephalus and other space-occupying pathologies. We aimed to design a new parameter which quantifies the relationship and can be calculated from overnight recordings.The new parameter, the respiratory amplitude quotient (RAQ), characterizes the modulation of the pulse amplitude by the respiratory wave in the ICP time course. RAQ is defined as the ratio of the amplitude of the respiratory wave in the ICP signal to the amplitude of the respiration-induced wave in the course of the heartbeat-dependent pulse amplitude.We tested RAQ on synthetically generated ICP waveforms and found a mean difference of <0.5% between the calculated values of RAQ and the theoretically determined values. We further extracted RAQ from datasets obtained by overnight recording in hydrocephalus patients with a stenosis of the aqueduct and a comparison group finding a significant difference between the RAQ values of either group.

Why Hydrocephalus Patients Suffer When the Weather Changes: A New Hypothesis.

Hydrocephalus patients complain about symptoms related to weather changes, especially changes in atmospheric pressure (pat). We aimed to determine which physical, physiological, and pathophysiological effects can explain this phenomenon. We hypothesized that intracranial pressure (ICP) is influenced by changes of intracranial blood volume caused by autoregulatory changes in arterial diameter as a reaction to changing levels of arterial CO2 partial pressure (paCO2) caused by changes in atmospheric pressure (pat). To test this hypothesis, we investigated the influence of pat on paCO2, and then assessed the influence of paCO2 on ICP by extrapolating data found in the literature. Using conservative assumptions, we found that a change of pat of about 50 hPa will result in a change in ICP of above 1.65 mmHg, which could explain the symptoms patients reported.

Shape irregularity of the intracranial aneurysm lumen exhibits diagnostic value.

BACKGROUND: Morphological irregularity is linked to intracranial aneurysm wall instability and manifests in the lumen shape. Yet there is currently no consent on how to assess shape irregularity. The aims of this work are to quantify irregularity as perceived by clinicians, to break down irregularity into morphological attributes, and to relate these to clinically relevant factors such as rupture status, aneurysm location, and patient age or sex. METHODS: Thirteen clinicians and 26 laypersons assessed 134 aneurysm lumen segmentations in terms of overall perceived irregularity and five different morphological attributes (presence/absence of a rough surface, blebs, lobules, asymmetry, complex geometry of the parent vasculature). We examined rater agreement and compared the ratings with clinical factors by means of regression analysis or binary classification. RESULTS: Using rank-based aggregation, the irregularity ratings of clinicians and laypersons did not differ statistically. Perceived irregularity showed good agreement with curvature (coefficient of determination R2 = 0.68 ± 0.08) and was modeled very accurately using the five morphological rating attributes plus shape elongation (R2 = 0.95 ± 0.02). In agreement with previous studies, irregularity was associated with aneurysm rupture status (AUC = 0.81 ± 0.08); adding aneurysm location as an explanatory variable increased the AUC to 0.87 ± 0.09. Besides irregularity, perceived asymmetry, presence of blebs or lobules, aneurysm size, non-sphericity, and curvature were linked to rupture. No association was found between morphology and any of patient sex, age, and history of smoking or hypertension. Aneurysm size was linked to morphology. CONCLUSIONS: Irregular lumen shape carries significant information on the aneurysm's disease status. Irregularity constitutes a continuous parameter that shows a strong association with the rupture status. To improve the objectivity of morphological assessment, we suggest examining shape through six different morphological attributes, which can characterize irregularity accurately.

Simultaneous Three-Dimensional Vascular and Tubular Imaging of Whole Mouse Kidneys With X-ray µCT.

Concurrent three-dimensional imaging of the renal vascular and tubular systems on the whole-kidney scale with capillary level resolution is labor-intensive and technically difficult. Approaches based on vascular corrosion casting and X-ray micro computed tomography (µCT), for example, suffer from vascular filling artifacts and necessitate imaging with an additional modality to acquire tubules. In this work, we report on a new sample preparation, image acquisition, and quantification protocol for simultaneous vascular and tubular µCT imaging of whole, uncorroded mouse kidneys. The protocol consists of vascular perfusion with the water-soluble, aldehyde-fixable, polymeric X-ray contrast agent XlinCA, followed by laboratory-source µCT imaging and structural analysis using the freely available Fiji/ImageJ software. We achieved consistent filling of the entire capillary bed and staining of the tubules in the cortex and outer medulla. After imaging at isotropic voxel sizes of 3.3 and 4.4 µm, we segmented vascular and tubular systems and quantified luminal volumes, surface areas, diffusion distances, and vessel path lengths. This protocol permits the analysis of vascular and tubular parameters with higher reliability than vascular corrosion casting, less labor than serial sectioning and leaves tissue intact for subsequent histological examination with light and electron microscopy.

Generation of renal Epo-producing cell lines by conditional gene tagging reveals rapid HIF-2 driven Epo kinetics, cell autonomous feedback regulation, and a telocyte phenotype.

Erythropoietin (Epo) is essential for erythropoiesis and is mainly produced by the fetal liver and the adult kidney following hypoxic stimulation. Epo regulation is commonly studied in hepatoma cell lines, but differences in Epo regulation between kidney and liver limit the understanding of Epo dysregulation in polycythaemia and anaemia. To overcome this limitation, we have generated a novel transgenic mouse model expressing Cre recombinase specifically in the active fraction of renal Epo-producing (REP) cells. Crossing with reporter mice confirmed the inducible and highly specific tagging of REP cells, located in the corticomedullary border region where there is a steep drop in oxygen bioavailability. A novel method was developed to selectively grow primary REP cells in culture and to generate immortalized clonal cell lines, called fibroblastoid atypical interstitial kidney (FAIK) cells. FAIK cells show very early hypoxia-inducible factor (HIF)-2α induction, which precedes Epo transcription. Epo induction in FAIK cells reverses rapidly despite ongoing hypoxia, suggesting a cell autonomous feedback mechanism. In contrast, HIF stabilizing drugs resulted in chronic Epo induction in FAIK cells. RNA sequencing of three FAIK cell lines derived from independent kidneys revealed a high degree of overlap and suggests that REP cells represent a unique cell type with properties of pericytes, fibroblasts, and neurons, known as telocytes. These novel cell lines may be helpful to investigate myofibroblast differentiation in chronic kidney disease and to elucidate the molecular mechanisms of HIF stabilizing drugs currently in phase III studies to treat anemia in end-stage kidney disease.

Fluid Dynamics in the HeartMate 3: Influence of the Artificial Pulse Feature and Residual Cardiac Pulsation.

Ventricular assist devices (VADs), among which the HeartMate 3 (HM3) is the latest clinically approved representative, are often the therapy of choice for patients with end-stage heart failure. Despite advances in the prevention of pump thrombosis, rates of stroke and bleeding remain high. These complications are attributed to the flow field within the VAD, among other factors. One of the HM3's characteristic features is an artificial pulse that changes the rotor speed periodically by 4000 rpm, which is meant to reduce zones of recirculation and stasis. In this study, we investigated the effect of this speed modulation on the flow fields and stresses using high-resolution computational fluid dynamics. To this end, we compared Eulerian and Lagrangian features of the flow fields during constant pump operation, during operation with the artificial pulse feature, and with the effect of the residual native cardiac cycle. We observed good washout in all investigated situations, which may explain the low incidence rates of pump thrombosis. The artificial pulse had no additional benefit on scalar washout performance, but it induced rapid variations in the flow velocity and its gradients. This may be relevant for the removal of deposits in the pump. Overall, we found that viscous stresses in the HM3 were lower than in other current VADs. However, the artificial pulse substantially increased turbulence, and thereby also total stresses, which may contribute to clinically observed issues related to hemocompatibility.

Extending statistical learning for aneurysm rupture assessment to Finnish and Japanese populations using morphology, hemodynamics, and patient characteristics.

OBJECTIVE: Incidental aneurysms pose a challenge for physicians, who need to weigh the rupture risk against the risks associated with treatment and its complications. A statistical model could potentially support such treatment decisions. A recently developed aneurysm rupture probability model performed well in the US data used for model training and in data from two European cohorts for external validation. Because Japanese and Finnish patients are known to have a higher aneurysm rupture risk, the authors' goals in the present study were to evaluate this model using data from Japanese and Finnish patients and to compare it with new models trained with Finnish and Japanese data. METHODS: Patient and image data on 2129 aneurysms in 1472 patients were used. Of these aneurysm cases, 1631 had been collected mainly from US hospitals, 249 from European (other than Finnish) hospitals, 147 from Japanese hospitals, and 102 from Finnish hospitals. Computational fluid dynamics simulations and shape analyses were conducted to quantitatively characterize each aneurysm's shape and hemodynamics. Next, the previously developed model's discrimination was evaluated using the Finnish and Japanese data in terms of the area under the receiver operating characteristic curve (AUC). Models with and without interaction terms between patient population and aneurysm characteristics were trained and evaluated including data from all four cohorts obtained by repeatedly randomly splitting the data into training and test data. RESULTS: The US model's AUC was reduced to 0.70 and 0.72, respectively, in the Finnish and Japanese data compared to 0.82 and 0.86 in the European and US data. When training the model with Japanese and Finnish data, the average AUC increased only slightly for the Finnish sample (to 0.76 ± 0.16) and Finnish and Japanese cases combined (from 0.74 to 0.75 ± 0.14) and decreased for the Japanese data (to 0.66 ± 0.33). In models including interaction terms, the AUC in the Finnish and Japanese data combined increased significantly to 0.83 ± 0.10. CONCLUSIONS: Developing an aneurysm rupture prediction model that applies to Japanese and Finnish aneurysms requires including data from these two cohorts for model training, as well as interaction terms between patient population and the other variables in the model. When including this information, the performance of such a model with Japanese and Finnish data is close to its performance with US or European data. These results suggest that population-specific differences determine how hemodynamics and shape associate with rupture risk in intracranial aneurysms.

Significant Association of Slow Vasogenic ICP Waves with Normal Pressure Hydrocephalus Diagnosis.

OBJECTIVE: We aimed to test whether there is an association of slow vasogenic wave (SVW) occurrence with positive response to external lumbar drainage (ELD) and ventriculoperitoneal shunting and to design a method for the recognition and quantification of SVWs in the intracranial pressure (ICP) signal. MATERIALS AND METHODS: We constructed SVW templates using normalized sine waves. We calculated the cross-correlation between the respective SVW template and the ICP signal. This was followed by shifting the templates forward and performing the cross-correlation analysis again until the end of the recording. Cross-correlation values above a threshold were considered to be indicative of SVWs. This threshold was previously determined and validated on a sample of ICP records of six patients. We calculated the root mean square of the recognized SVW periods as a measure of signal strength. Time-averaged signal strength was calculated over the full recording time (ICPSmean) and over the wave periods (ICPS). RESULTS: We determined ICPS and ICPSmean in recordings of 2 groups of patients presenting with Hakim's triad: 26 normal pressure hydrocephalus (NPH) patients and 20 non-NPH patients. We then tested whether there was an association between ICPS or ICPSmean and the respective diagnosis using a Mann-Whitney test. We found significant association between ICPS (p = 0.014) and ICPSmean (p = 0.022) and the diagnoses. CONCLUSIONS: The described method based on pattern recognition in the time domain is suitable for the detection and quantification of SVWs in ICP signals. We found a significant association between the occurrence of SVWs and independent NPH diagnosis.

Renal arteriovenous oxygen shunting.

PURPOSE OF REVIEW: Renal arteriovenous oxygen shunting has been proposed as a mechanism by which oxygen supplied to the kidney can bypass the renal parenchyma. Shunting could, therefore, play a crucial role in renal hypoxia and hyperoxia. In the absence of suitable quantitative experimental methods, computational modeling has been employed in recent years to estimate the extent and potential impact of oxygen shunting. RECENT FINDINGS: Overestimation of the separation distance between arteries and veins was suggested to be responsible for previous findings that only negligible amounts of oxygen are shunted in the preglomerular vasculature. However, models considering the correct separation distance and wrapping of artery-vein pairs still showed shunting at negligible levels of less than 1% of total renal oxygen delivery. The effect of reverse CO2 shunting on the oxygen-hemoglobin dissociation curve was found to impair, rather than promote, preglomerular oxygen shunting. SUMMARY: Oxygen is unlikely to be shunted along the preglomerular vasculature in sufficient quantities to affect renal oxygenation. There may be substantial shunting at the level of the postglomerular vasculature, but more extensive efforts in structural imaging and computational modeling are needed to quantify it reliably.

Comparison of anti-siphon devices-how do they affect CSF dynamics in supine and upright posture?

BACKGROUND: Three different types of anti-siphon devices (ASDs) have been developed to counteract siphoning-induced overdrainage in upright posture. However, it is not known how the different ASDs affect CSF dynamics under the complex pressure environment seen in clinic due to postural changes. We investigated which ASDs can avoid overdrainage in upright posture best without leading to CSF accumulation. METHODS: Three shunts each of the types Codman Hakim with SiphonGuard (flow-regulated), Miethke miniNAV with proSA (gravitational), and Medtronic Delta (membrane controlled) were tested. The shunts were compared on a novel in vitro setup that actively emulates the physiology of a shunted patient. This testing method allows determining the CSF drainage rates, resulting CSF volume, and intracranial pressure in the supine, sitting, and standing posture. RESULTS: The flow-regulated ASDs avoided increased drainage by closing their primary flow path when drainage exceeded 1.39 ± 0.42 mL/min. However, with intraperitoneal pressure increased in standing posture, we observed reopening of the ASD in 3 out of 18 experiment repetitions. The adjustable gravitational ASDs allow independent opening pressures in horizontal and vertical orientation, but they did not provide constant drainage in upright posture (0.37 ± 0.03 mL/min and 0.26 ± 0.03 mL/min in sitting and standing posture, respectively). Consequently, adaptation to the individual patient is critical. The membrane-controlled ASDs stopped drainage in upright posture. This eliminates the risk of overdrainage, but leads to CSF accumulation up to the volume observed without shunting when the patient is upright. CONCLUSIONS: While all tested ASDs reduced overdrainage, their actual performance will depend on a patient's specific needs because of the large variation in the way the ASDs influence CSF dynamics: while the flow-regulated shunts provide continuous drainage in upright posture, the gravitational ASDs allow and require additional adaptation, and the membrane-controlled ASDs show robust siphon prevention by a total stop of drainage.

Renal oxygenation: preglomerular vasculature is an unlikely contributor to renal oxygen shunting.

The primary aim of this study was to assess the plausibility of preglomerular arterial-to-venous oxygen shunting in the kidney. To this end, we have developed a segment-wise three-dimensional computational model that takes into account transport processes in arteries, veins, cortical tissue, and capillaries. Our model suggests that the amount of preglomerular oxygen shunting is negligible. Consequently, it is improbable that preglomerular shunting contributes to the hypothesized regulation of renal oxygenation. Cortical tissue oxygenation is more likely determined by the interplay between oxygen supply, either from the preglomerular vasculature or from capillaries, and oxygen consumption. We show that reported differences in permeability to oxygen between perfused and unperfused tissue may be explained by what we refer to as advection-facilitated diffusion. We further show that the preglomerular vasculature is the primary source of oxygen for the tissue when cortical consumption is high or renal arterial blood is highly oxygenated, i.e., under hyperoxemic conditions. Conversely, when oxygen demand in the tissue is decreased, or under hypoxemic conditions, oxygen is supplied predominantly by capillaries.

Arterial, venous, and cerebrospinal fluid flow: simultaneous assessment with Bayesian multipoint velocity-encoded MR imaging.

PURPOSE: To measure arterial, venous, and cerebrospinal fluid (CSF) velocities simultaneously by using Bayesian multipoint velocity-encoded magnetic resonance (MR) imaging and to compare interacquisition reproducibility relative to that of standard phase-contrast MR imaging for sequential measurements of arterial, venous, and CSF velocities. MATERIALS AND METHODS: This study was approved by the local ethics committee, and informed consent was obtained from all subjects. Simultaneous measurement of blood and CSF flow was performed at the C1-C2 level in 10 healthy subjects (mean age, 24.4 years ± 2.7; five men, five women) by using accelerated Bayesian multipoint velocity-encoded MR imaging. Data were compared with those obtained from two separate conventional phase-contrast MR imaging acquisitions, one optimized for arterial and venous blood flow (velocity encoding range, ±50 cm/sec) and the other optimized for CSF flow (velocity encoding range, ±10 cm/sec), with an imaging time of approximately 2 minutes each. Data acquisition was repeated six times. Intraclass correlation coefficient (ICC) and linear regression were used to quantify interacquisition reproducibility. RESULTS: There was no significant difference in arterial blood flow measured with Bayesian multipoint velocity-encoded MR imaging and that measured with phase-contrast MR imaging (mean ICC, 0.96 ± 0.03 vs 0.97 ± 0.02, respectively). Likewise, there was no significant difference between CSF flow measured with Bayesian multipoint velocity-encoded MR imaging and that measured with phase-contrast MR imaging (mean ICC, 0.97 ± 0.02 vs 0.96 ± 0.05, respectively). For venous blood flow, the ICC with Bayesian multipoint MR imaging was significantly larger than that with conventional phase-contrast MR imaging (mean, 0.75 ± 0.23 vs 0.65 ± 0.26, respectively; P = .016). CONCLUSION: Bayesian multipoint velocity-encoded MR imaging allows for simultaneous assessment of fast and slow flows in arterial, venous, and CSF lumina in a single acquisition. It eliminates the need for vessel-dependent adjustment of the velocity-encoding range, as required for conventional sequential phase-contrast MR imaging measurements.

Incorporating Unresolved Stresses in Blood Damage Modeling: Energy Dissipation More Accurate Than Reynolds Stress Formulation.

OBJECTIVE: Reynolds Averaged Navier Stokes (RANS) models are often used as the basis for modeling blood damage in turbulent flows. To predict blood damage by turbulence stresses that are not resolved in RANS, a stress formulation that represents the corresponding scales is required. Here, we compare two commonly employed stress formulations: a scalar stress representation that uses Reynolds stresses as a surrogate for unresolved fluid stresses, and an effective stress formulation based on energy dissipation. METHODS: We conducted unsteady RANS simulations of the CentriMag blood pump with three different closure models and a Large Eddy Simulation (LES) for reference. We implemented both stress representations in all models and compared the resulting total stress distributions in Eulerian and Lagrangian frameworks. RESULTS: The Reynolds-stress-based approach overestimated the contribution of unresolved stresses in RANS, with differences between closure models of up to several orders of magnitude. With the dissipation-based approach, the total stresses predicted with RANS deviated by about 50% from the LES reference, which was more accurate than only considering resolved stresses. CONCLUSION: The Reynolds-stress-based formulation proved unreliable for estimating scalar stresses in our RANS simulations, while the dissipation-based approach provided an accuracy improvement over simply neglecting unresolved stresses. SIGNIFICANCE: Our results suggest that dissipation-based inclusion of unresolved stresses should be the preferred choice for blood damage modeling in RANS.

Influence of age on the relation between body position and noninvasively acquired intracranial pulse waves.

The capacitive measurement of the head's dielectric properties has been recently proposed as a noninvasive method for deriving surrogates of craniospinal compliance (CC), a parameter used in the evaluation of space-occupying neurological disorders. With the higher prevalence of such disorders in the older compared to the younger population, data on the head's dielectric properties of older healthy individuals would be of particularly high value before assessing pathologic changes. However, so far only measurements on young volunteers (< 30 years) were reported. In the present study, we have investigated the capacitively obtained electric signal known as W in older healthy individuals. Thirteen healthy subjects aged > 60 years were included in the study. W was acquired in the resting state (supine horizontal position), and during head-up and head-down tilting. AMP, the peak-to-valley amplitude of W related to cardiac action, was extracted from W. AMP was higher in this older cohort compared to the previously investigated younger one (0°: 5965 ± 1677 arbitrary units (au)). During head-up tilting, AMP decreased (+ 60°: 4446 ± 1620 au, P < 0.001), whereas it increased during head-down tilting (- 30°: 7600 ± 2123 au, P < 0.001), as also observed in the younger cohort. Our observation that AMP, a metric potentially reflective of CC, is higher in the older compared to the younger cohort aligns with the expected decrease of CC with age. Furthermore, the robustness of AMP is reinforced by the consistent relative changes observed during tilt testing in both cohorts.