Modeling cerebrospinal fluid dynamics across the entire intracranial space through integration of four-dimensional flow and intravoxel incoherent motion magnetic resonance imaging.

BACKGROUND: Bidirectional reciprocal motion of cerebrospinal fluid (CSF) was quantified using four-dimensional (4D) flow magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) MRI. To estimate various CSF motions in the entire intracranial region, we attempted to integrate the flow parameters calculated using the two MRI sequences. To elucidate how CSF dynamics deteriorate in Hakim's disease, an age-dependent chronic hydrocephalus, flow parameters were estimated from the two MRI sequences to assess CSF motion in the entire intracranial region. METHODS: This study included 127 healthy volunteers aged ≥ 20 years and 44 patients with Hakim's disease. On 4D flow MRI for measuring CSF motion, velocity encoding was set at 5 cm/s. For the IVIM MRI analysis, the diffusion-weighted sequence was set at six b-values (i.e., 0, 50, 100, 250, 500, and 1000 s/mm2), and the biexponential IVIM fitting method was adapted. The relationships between the fraction of incoherent perfusion (f) on IVIM MRI and 4D flow MRI parameters including velocity amplitude (VA), absolute maximum velocity, stroke volume, net flow volume, and reverse flow rate were comprehensively evaluated in seven locations in the ventricles and subarachnoid spaces. Furthermore, we developed a new parameter for fluid oscillation, the Fluid Oscillation Index (FOI), by integrating these two measurements. In addition, we investigated the relationship between the measurements and indices specific to Hakim's disease and the FOIs in the entire intracranial space. RESULTS: The VA on 4D flow MRI was significantly associated with the mean f-values on IVIM MRI. Therefore, we estimated VA that could not be directly measured on 4D flow MRI from the mean f-values on IVIM MRI in the intracranial CSF space, using the following formula; e0.2(f-85) + 0.25. To quantify fluid oscillation using one integrated parameter with weighting, FOI was calculated as VA × 10 + f × 0.02. In addition, the FOIs at the left foramen of Luschka had the strongest correlations with the Evans index (Pearson's correlation coefficient: 0.78). The other indices related with Hakim's disease were significantly associated with the FOIs at the cerebral aqueduct and bilateral foramina of Luschka. FOI at the cerebral aqueduct was also elevated in healthy controls aged ≥ 60 years. CONCLUSIONS: We estimated pulsatile CSF movements in the entire intracranial CSF space in healthy individuals and patients with Hakim's disease using FOI integrating VA from 4D flow MRI and f-values from IVIM MRI. FOI is useful for quantifying the CSF oscillation.

Automatic assessment of disproportionately enlarged subarachnoid-space hydrocephalus from 3D MRI using two deep learning models.

Background: Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a key feature for Hakim disease (idiopathic normal pressure hydrocephalus: iNPH), but subjectively evaluated. To develop automatic quantitative assessment of DESH with automatic segmentation using combined deep learning models. Methods: This study included 180 participants (42 Hakim patients, 138 healthy volunteers; 78 males, 102 females). Overall, 159 three-dimensional (3D) T1-weighted and 180 T2-weighted MRIs were included. As a semantic segmentation, 3D MRIs were automatically segmented in the total ventricles, total subarachnoid space (SAS), high-convexity SAS, and Sylvian fissure and basal cistern on the 3D U-Net model. As an image classification, DESH, ventricular dilatation (VD), tightened sulci in the high convexities (THC), and Sylvian fissure dilatation (SFD) were automatically assessed on the multimodal convolutional neural network (CNN) model. For both deep learning models, 110 T1- and 130 T2-weighted MRIs were used for training, 30 T1- and 30 T2-weighted MRIs for internal validation, and the remaining 19 T1- and 20 T2-weighted MRIs for external validation. Dice score was calculated as (overlapping area) × 2/total area. Results: Automatic region extraction from 3D T1- and T2-weighted MRI was accurate for the total ventricles (mean Dice scores: 0.85 and 0.83), Sylvian fissure and basal cistern (0.70 and 0.69), and high-convexity SAS (0.68 and 0.60), respectively. Automatic determination of DESH, VD, THC, and SFD from the segmented regions on the multimodal CNN model was sufficiently reliable; all of the mean softmax probability scores were exceeded by 0.95. All of the areas under the receiver-operating characteristic curves of the DESH, Venthi, and Sylhi indexes calculated by the segmented regions for detecting DESH were exceeded by 0.97. Conclusion: Using 3D U-Net and a multimodal CNN, DESH was automatically detected with automatically segmented regions from 3D MRIs. Our developed diagnostic support tool can improve the precision of Hakim disease (iNPH) diagnosis.

Computational study on the effects of central retinal blood vessels with asymmetric geometries on optic nerve head biomechanics.

Optic nerve head (ONH) biomechanics are associated with glaucoma progression and have received considerable attention. Central retinal vessels (CRVs) oriented asymmetrically in the ONH are the single blood supply source to the retina and are believed to act as mechanically stable elements in the ONH in response to intraocular pressure (IOP). However, these mechanical effects are considered negligible in ONH biomechanical studies and received less attention. This study investigated the effects of CRVs on ONH biomechanics taking into consideration three-dimensional asymmetric CRV geometries. A CRV geometry was constructed based on CRV centerlines extracted from optical coherence tomography ONH images in eight healthy subjects and superimposed in the idealized ONH geometry established in previous studies. Mechanical analyses of the ONH in response to the IOP were conducted in the cases with and without CRVs for comparison. Obtained results demonstrated that the CRVs induced anisotropic ONH deformation, particularly in the lamina cribrosa and the associated upper neural tissues (prelamina) with wide ranges of spatial strain distributions. These results indicated that the CRVs result in anisotropic deformation with local strain concentration, rather than function to mechanically support in response to the IOP as in the conventional thinking in ophthalmology.

Aging and Sex Differences in Brain Volume and Cerebral Blood Flow.

How do regional brain volume ratios and cerebral blood flow (CBF, mL/min) change with aging, and are there sex differences? This study aimed to comprehensively evaluate the relationships between regional brain volume ratios and CBF in healthy brains. The study participants were healthy volunteers who underwent three-dimensional T1-weighted MRI, time-of-flight MR angiography, and four-dimensional (4D) flow MRI between 2020 and 2022. The brain was automatically segmented into 21 brain subregions from 3D T1-weighted MRI, and CBF in 16 major intracranial arteries were measured by 4D flow MRI. The relationships between segmented brain volume ratios and CBFs around the circle of Willis were comprehensively investigated in each decade and sex. This study included 129 healthy volunteers (mean age ± SD, 48.2 ± 16.8; range, 22-92 years; 43 males and 86 females). The association was strongest between the cortical gray matter volume ratio and total outflow of the intracranial major arteries distal to the circle of Willis (Pearson's correlation coefficient, r: 0.425). In addition, the mean flow of the total inflow and outflow around the circle of Willis were significantly greater in women than men, and significant left-right differences were observed in CBFs even on the peripheral side of the circle of Willis. Moreover, the correlation was strongest between the left cortical gray matter volume ratio and the combined flows of the left anterior and posterior cerebral arteries distal to the circle of Willis (r: 0.486). There was a trend toward greater total intracranial CBF, especially among women in their 40s and younger, who had a larger cortical gray matter volume. This finding may be one of the reasons for the approximately twofold higher incidence of cerebral aneurysms and subarachnoid hemorrhage, and a threefold higher incidence of migraine headaches.

Computational modeling of multiscale collateral blood supply in a whole-brain-scale arterial network.

The cerebral arterial network covering the brain cortex has multiscale anastomosis structures with sparse intermediate anastomoses (O[102] µm in diameter) and dense pial networks (O[101] µm in diameter). Recent studies indicate that collateral blood supply by cerebral arterial anastomoses has an essential role in the prognosis of acute ischemic stroke caused by large vessel occlusion. However, the physiological importance of these multiscale morphological properties-and especially of intermediate anastomoses-is poorly understood because of innate structural complexities. In this study, a computational model of multiscale anastomoses in whole-brain-scale cerebral arterial networks was developed and used to evaluate collateral blood supply by anastomoses during middle cerebral artery occlusion. Morphologically validated cerebral arterial networks were constructed by combining medical imaging data and mathematical modeling. Sparse intermediate anastomoses were assigned between adjacent main arterial branches; the pial arterial network was modeled as a dense network structure. Blood flow distributions in the arterial network during middle cerebral artery occlusion simulations were computed. Collateral blood supply by intermediate anastomoses increased sharply with increasing numbers of anastomoses and provided one-order-higher flow recoveries to the occluded region (15%-30%) compared with simulations using a pial network only, even with a small number of intermediate anastomoses (≤10). These findings demonstrate the importance of sparse intermediate anastomoses, which are generally considered redundant structures in cerebral infarction, and provide insights into the physiological significance of the multiscale properties of arterial anastomoses.

Age-Related Changes in Cerebrospinal Fluid Dynamics in the Pathogenesis of Chronic Hydrocephalus in Adults.

Cerebrospinal fluid (CSF) dynamics has dramatically changed in this century. In the latest concept of CSF dynamics, CSF is thought to be produced mainly from interstitial fluid excreted from the brain parenchyma and is absorbed in the meningeal lymphatics. Moreover, CSF does not always flow from the ventricles to the subarachnoid space unidirectionally through the foramina of Magendie and Luschka. In an environment of increased intracranial CSF in idiopathic normal pressure hydrocephalus, CSF freely moves through the inferior choroidal point of the choroidal fissure, which interfaces between the inferior horn of the lateral ventricles and the ambient cistern and through the velum interpositum between the third ventricle and the quadrigeminal cistern. The structure of the hippocampus adjacent to the inferior part of the choroidal fissure may be important in preventing the accumulation of waste products in the hippocampus. A recent imaging technology for CSF dynamics, such as four-dimensional flow and intravoxel incoherent motion magnetic resonance imaging, can visualize and quantify the pulsatile complex CSF motion in clinical usage. We present the current concepts of CSF dynamics with advanced magnetic resonance imaging techniques, which will be helpful in the management and understanding of the pathogenesis of chronic hydrocephalus in adults.

Biomechanical effects of hyper-dynamic cerebrospinal fluid flow through the cerebral aqueduct in idiopathic normal pressure hydrocephalus patients.

Normal pressure hydrocephalus (NPH) is an intracranial disease characterized by an abnormal accumulation of cerebrospinal fluid (CSF) in brain ventricles within the normal range of intracranial pressure. Most NPH in aged patients is idiopathic (iNPH) and without any prior history of intracranial diseases. Although an abnormal increase of CSF stroke volume (hyper-dynamic CSF flow) in the aqueduct between the third and fourth ventricles has received much attention as a clinical evaluation index in iNPH patients, the biomechanical effects of this flow on iNPH pathophysiology are poorly understood. This study aimed to clarify the potential biomechanical effects of hyper-dynamic CSF flow through the aqueduct of iNPH patients using magnetic resonance imaging-based computational simulations. Ventricular geometries and CSF flow rates through aqueducts of 10 iNPH patients and 10 healthy control subjects were obtained from multimodal magnetic resonance images, and these CSF flow fields were simulated using computational fluid dynamics. As biomechanical factors, we evaluated wall shear stress on the ventricular wall and the extent of flow mixing, which potentially disturbs the CSF composition in each ventricle. The results showed that the relatively high CSF flow rate and large and irregular shapes of the aqueduct in iNPH resulted in large wall shear stresses localized in relatively narrow regions. Furthermore, the resulting CSF flow showed a stable cyclic motion in control subjects, whereas strong mixing during transport through the aqueduct was found in patients with iNPH. These findings provide further insights into the clinical and biomechanical correlates of NPH pathophysiology.

Tightened Sulci in the High Convexities as a Noteworthy Feature of Idiopathic Normal Pressure Hydrocephalus.

OBJECTIVE: The presence of tightened sulci in the high-convexities (THC) is a key morphological feature for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH), but the exact localization of THC has yet to be defined. The purpose of this study was to define THC and compare its volume, percentage, and index between iNPH patients and healthy controls. METHODS: According to the THC definition, the high-convexity part of the subarachnoid space was segmented and measured the volume and percentage from the 3D T1-weighted and T2-weighted magnetic resonance images in 43 patients with iNPH and 138 healthy controls. RESULTS: THC was defined as a decrease in the high-convexity part of the subarachnoid space located above the body of the lateral ventricles, with anterior end on the coronal plane perpendicular to the anterior commissure-posterior commissure (AC-PC) line passing through the front edge of the genu of corpus callosum, the posterior end in the bilateral posterior parts of the callosomarginal sulci, and the lateral end at 3 cm from the midline on the coronal plane perpendicular to the AC-PC line passing through the midpoint between AC and PC. Compared to the volume and volume percentage, the high-convexity part of the subarachnoid space volume per ventricular volume ratio < 0.6 was the most detectable index of THC on both 3D T1-weighted and T2-weighted magnetic resonance images. CONCLUSIONS: To improve the diagnostic accuracy of iNPH, the definition of THC was clarified, and high-convexity part of the subarachnoid space volume per ventricular volume ratio <0.6 proposed as the best index for THC detection in this study.

Aging-related volume changes in the brain and cerebrospinal fluid using artificial intelligence-automated segmentation.

OBJECTIVES: To verify the reliability of the volumes automatically segmented using a new artificial intelligence (AI)-based application and evaluate changes in the brain and CSF volume with healthy aging. METHODS: The intracranial spaces were automatically segmented in the 21 brain subregions and 5 CSF subregions using the AI-based application on the 3D T1-weighted images in healthy volunteers aged > 20 years. Additionally, the automatically segmented volumes of the total ventricles and subarachnoid spaces were compared with the manually segmented volumes of those extracted from 3D T2-weighted images using the intra-class correlation and Bland-Altman analysis. RESULTS: In this study, 133 healthy volunteers aged 21-92 years were included. The mean intra-class correlations between the automatically and manually segmented volumes of the total ventricles and subarachnoid spaces were 0.986 and 0.882, respectively. The increase in the CSF volume was estimated to be approximately 30 mL (2%) per decade from 265 mL (18.7%) in the 20s to 488 mL (33.7%) in ages above 80 years; however, the increase in the volume of total ventricles was approximately 20 mL (< 2%) until the 60s and increased in ages above 60 years. CONCLUSIONS: This study confirmed the reliability of the CSF volumes using the AI-based auto-segmentation application. The intracranial CSF volume increased linearly because of the brain volume reduction with aging; however, the ventricular volume did not change until the age of 60 years and above and then gradually increased. This finding could help elucidate the pathogenesis of chronic hydrocephalus in adults. KEY POINTS: • The brain and CSF spaces were automatically segmented using an artificial intelligence-based application. • The total subarachnoid spaces increased linearly with aging, whereas the total ventricle volume was around 20 mL (< 2%) until the 60s and increased in ages above 60 years. • The cortical gray matter gradually decreases with aging, whereas the subcortical gray matter maintains its volume, and the cerebral white matter increases slightly until the 40s and begins to decrease from the 50s.

Usefulness of intravoxel incoherent motion MRI for visualizing slow cerebrospinal fluid motion.

BACKGROUND: In the cerebrospinal fluid (CSF) dynamics, the pulsations of cerebral arteries and brain is considered the main driving force for the reciprocating bidirectional CSF movements. However, measuring these complex CSF movements on conventional flow-related MRI methods is difficult. We tried to visualize and quantify the CSF motion by using intravoxel incoherent motion (IVIM) MRI with low multi-b diffusion-weighted imaging. METHODS: Diffusion-weighted sequence with six b values (0, 50, 100, 250, 500, and 1000 s/mm2) was performed on 132 healthy volunteers aged ≥ 20 years and 36 patients with idiopathic normal pressure hydrocephalus (iNPH). The healthy volunteers were divided into three age groups (< 40, 40 to < 60, and ≥ 60 years). In the IVIM analysis, the bi-exponential IVIM fitting method using the Levenberg-Marquardt algorithm was adapted. The average, maximum, and minimum values of ADC, D, D*, and fraction of incoherent perfusion (f) calculated by IVIM were quantitatively measured in 45 regions of interests in the whole ventricles and subarachnoid spaces. RESULTS: Compared with healthy controls aged ≥ 60 years, the iNPH group had significantly lower mean f values in all the parts of the lateral and 3rd ventricles, whereas significantly higher mean f value in the bilateral foramina of Luschka. In the bilateral Sylvian fossa, which contain the middle cerebral bifurcation, the mean f values increased gradually with increasing age, whereas those were significantly lower in the iNPH group. In the 45 regions of interests, the f values in the bilateral foramina of Luschka were the most positively correlated with the ventricular size and indices specific to iNPH, whereas that in the anterior part of the 3rd ventricle was the most negatively correlated with the ventricular size and indices specific to iNPH. Other parameters of ADC, D, and D* were not significantly different between the two groups in any locations. CONCLUSIONS: The f value on IVIM MRI is useful for evaluating small pulsatile complex motion of CSF throughout the intracranial CSF spaces. Patients with iNPH had significantly lower mean f values in the whole lateral ventricles and 3rd ventricles and significantly higher mean f value in the bilateral foramina of Luschka, compared with healthy controls aged ≥ 60 years.

Do blood flow patterns in the left atriums differ between left upper lobectomy and other lobectomies? A computational study.

Background: Left atrial (LA) hemodynamics after lung lobectomies with pulmonary vein (PV) resection is widely understood to be a risk factor for LA thrombosis. A recent magnetic resonance imaging study showed that left upper lobectomy (LUL) with left superior pulmonary vein resection tended to cause LA flow patterns distinct from those of other lobectomies, with flow disturbances seen near the PV stump. However, little is known about this flow pattern because of severe image resolution limitations. The present study compared flow patterns in the LA after LUL with the flow patterns of other lobectomies using computational simulations. Methods: The computational simulations of LA blood flow were conducted on the basis of four-dimensional computed tomography images of four lung cancer patients prior to lobectomies. Four kinds of PV resection cases were constructed by cutting each one of the PVs from the LA of each patient. We performed a total of five cases (pre-resection case and four PV resection cases) in each patient and evaluated global flow patterns formed by the remaining PV inflow, especially in the upper LA region. Results: LUL tended to enhance the remaining left inferior PV inflow, with impingements seen in the right PV inflows in the upper LA region near the PV stump. These flow alterations induced viscous dissipation and the LUL cases had the highest values compared to other PV resection cases, especially in the LV systole in three patients, and reached three to four times higher than those in pre-resection cases. However, in another patient, these tendencies were weaker when PV inflow was stronger from the right side than from the left side, and the degree of flow dissipation was lower than those in other PV resection cases. Conclusion: These findings suggest marked variations in LA flow patterns among patients after lobectomies and highlights the importance of patient-specific assessment of LA hemodynamics after lobectomies.

Computational fluid dynamics assessment of congenital tracheal stenosis.

PURPOSE: The severity of congenital tracheal stenosis (CTS) is commonly evaluated based on the degree of stenosis. However, it does not always reflect the clinical respiratory status. We applied computational fluid dynamics (CFD) to the assessment of CTS. The aim of this study was to evaluate its validity. METHODS: CFD models were constructed on 15 patients (12 preoperative models and 15 postoperative models) with CTS before and after surgery, using the computed tomographic data. Energy flux, needed to drive airflow, measured by CFD and the minimum cross-sectional area of the trachea (MCAT) were quantified and evaluated retrospectively. RESULTS: The energy flux correlated positively with the clinical respiratory status before and after surgery (rs = 0.611, p = 0.035 and rs = 0.591, p = 0.020, respectively). Although MCAT correlated negatively with the clinical respiratory status before surgery (rs = -0.578, p = 0.044), there was not significant correlation between the two after surgery (p = 0.572). CONCLUSIONS: The energy flux measured by CFD assessment reflects the respiratory status in CTS before and after surgery. CFD can be an additional objective and quantitative evaluation tool for CTS.

Fluid dynamic assessment of positive end-expiratory pressure in a tracheostomy tube connector during respiration.

High-flow oxygen therapy using a tracheostomy tube is a promising clinical approach to reduce the work of breathing in tracheostomized patients. Positive end-expiratory pressure (PEEP) is usually applied during oxygen inflow to improve oxygenation by preventing end-expiratory lung collapse. However, much is still unknown about the geometrical effects of PEEP, especially regarding tracheostomy tube connectors (or adapters). Quantifying the degree of end-expiratory pressure (EEP) that takes patient-specific spirometry into account would be useful in this regard, but no such framework has been established yet. Thus, a platform to assess PEEP under respiration was developed, wherein three-dimensional simulation of airflow in a tracheostomy tube connector is coupled with a lumped lung model. The numerical model successfully reflected the magnitude of EEP measured experimentally using a lung phantom. Numerical simulations were further performed to quantify the effects of geometrical parameters on PEEP, such as inlet angles and rate of stenosis in the connector. Although sharp inlet angles increased the magnitude of EEP, they cannot be expected to achieve clinically reasonable PEEP. On the other hand, geometrical constriction in the connector can potentially result in PEEP as obtained with conventional nasal cannulae.

Airway performance in infants with congenital tracheal stenosis associated with unilateral pulmonary agenesis: effect of tracheal shape on energy flux.

Congenital tracheal stenosis (CTS) with unilateral pulmonary agenesis (UPA) is characterized by the absence of one or both lungs in the hemithorax and is often associated with airway distortion. Some UPA patients have high mortality and morbidity even postoperatively, and it remains unclear whether surgery increases the energy flux needed to drive airflow. Here, we used pre- and postoperative patient-specific airway models to numerically investigate tracheal flow in patients with CTS, especially flow associated with right UPA (CTS-RUPA). Airflow was simulated with the large-eddy model, and energy flux was investigated to quantify airway performance and the contribution of surgical intervention. Although energy flux decreased postoperatively, clinical respiratory status did not improve. Standard surgical intervention for CTS, which expands the minimal cross-sectional area, decreased energy flux, i.e., improved airway performance. The simulation also included artificial airways with a straightened bend or reduced tracheal lumen roughness. The numerical results clearly showed interindividual differences in the percent reduction of energy flux caused by straightening the tracheal bend versus correcting tracheal lumen roughness. Although this study was limited to small sample size, these numerical results indicated that energy flux alone is insufficient to evaluate breathing performance in patients with CTS-RUPA but it can be used to estimate airway performance.

On the Impact of Left Upper Lobectomy on the Left Atrial Hemodynamics.

The left atrium (LA) functions to transport oxygenated blood from the pulmonary veins (PVs) to the left ventricle (LV). LA hemodynamics has received much attention because thrombosis in the LA in pathological states, such as atrial fibrillation, is a major factor leading to thromboembolic stroke. In the last 5 years, multiple cohort studies have revealed that left upper lobectomy (LUL) with PV resection risks thrombus formation in the PV stump even in the normal LA without a history of cardiac disease; the causal mechanism is, however, an open question. The present study investigated the potential effect of an LUL on LA hemodynamics associated with thrombus formation through computational simulation using four-dimensional computed tomography (4D-CT) images. Time series of patient-specific LA geometries before and after LUL were extracted from the 4D-CT images and these motions were estimated through non-rigid registration. Adopting the LA geometries and prescribed moving wall boundary conditions, the LA blood flow was determined using a Cartesian-grid computational fluid dynamics solver. The obtained results show that the LUL resulted in blood flow impingement from the left and right PV inflows into the LA upper region throughout most of the cardiac cycle. This characteristic alteration of the LA hemodynamics generated fine-scale vortices with viscous energy dissipations, enhancing the flow stasis associated with thrombus formation in the PV stump. These findings show that an LUL affects the hemodynamics not only in the PV stump but also throughout the LA region. They also highlight the importance of computational analysis of LA hemodynamics in understanding the underlying mechanism of LUL-induced thrombus formation.

A subject-specific assessment of measurement errors and their correction in cerebrospinal fluid velocity maps using 4D flow MRI.

PURPOSE: Phase-contrast MRI (PC-MRI) of cerebrospinal fluid (CSF) velocity is used to evaluate the characteristics of intracranial diseases, such as normal-pressure hydrocephalus (NPH). Nevertheless, PC-MRI has several potential error sources, with eddy-current-based phase offset error being non-negligible in CSF measurement. In this study, we assess the measurement error of CSF velocity maps obtained using 4D flow MRI and evaluate correction methods. METHODS: CSF velocity maps of 10 patients with NPH were acquired using 4D flow MRI (velocity-encoding = 5 cm/s). Distributed phase offset error was estimated for a whole 3D background field by polynomial fitting using robust regression analysis. This estimated phase offset error was then used to correct the CSF velocity maps. The estimated error profiles were compared with those obtained using an existing 2D correction approach involving local background information near the region of interest. RESULTS: The residual standard error of the polynomial fitting against the phase offset error extracted from the measured velocities was within 0.2 cm/s. The spatial dependencies of the phase offset errors showed similar tendencies in all cases, but sufficient differences in these values were found to indicate requirement of velocity correction. Differences of the estimated errors among other correction approaches were in the order of 10-2 cm/s, and the estimated errors were in good agreement with those obtained using existing approaches. CONCLUSION: Our method is capable of estimating the measurement error of CSF velocity maps obtained from 4D flow MRI and provides quantitatively reasonable characteristics for the main CSF profile in the cerebral aqueduct in patients with NPH.

Development of a mesoscopic framework spanning nanoscale protofibril dynamics to macro-scale fibrin clot formation.

Thrombi form a micro-scale fibrin network consisting of an interlinked structure of nanoscale protofibrils, resulting in haemostasis. It is theorized that the mechanical effect of the fibrin clot is caused by the polymeric protofibrils between crosslinks, or to their dynamics on a nanoscale order. Despite a number of studies, however, it is still unknown, how the nanoscale protofibril dynamics affect the formation of the macro-scale fibrin clot and thus its mechanical properties. A mesoscopic framework would be useful to tackle this multi-scale problem, but it has not yet been established. We thus propose a minimal mesoscopic model for protofibrils based on Brownian dynamics, and performed numerical simulations of protofibril aggregation. We also performed stretch tests of polymeric protofibrils to quantify the elasticity of fibrin clots. Our model results successfully captured the conformational properties of aggregated protofibrils, e.g., strain-hardening response. Furthermore, the results suggest that the bending stiffness of individual protofibrils increases to resist extension.

Cerebrospinal fluid flow driven by arterial pulsations in axisymmetric perivascular spaces: Analogy with Taylor's swimming sheet.

Cerebrospinal fluid (CSF) flow in the perivascular space (PVS), which surrounds the arteries in the brain, is of paramount importance in the removal of metabolic waste. Despite a number of experimental and numerical studies regarding CSF flow, the underlying mechanics of CSF flow are still debated, especially regarding whether an arterial pulsation can indeed produce net CSF flow velocity. Furthermore, the relationship between CSF flow and arterial wall pulsation has not been fully defined. To clarify these questions, we numerically investigated the CSF flow in the PVS in an axisymmetric channel with a pulsating boundary, where CSF is modeled as an incompressible, Newtonian viscous fluid in non-porous space. Our numerical results show that the net CSF flow velocity driven by the arterial pulsation is consistent with that of previous animal experiments. However, the peak oscillatory velocity is two orders of magnitude larger than the net velocity. Interestingly, the net CSF flow velocity collapses on the analytical solution derived from the lubrication theory in analogy with Taylor's swimming sheet model.

Effects of Left Ventricular Hypertrophy and Myocardial Stiffness on Myocardial Strain Under Preserved Ejection Fraction.

Despite numerous experimental observations regarding heart failure with preserved ejection fraction (HFpEF), which is characterized mainly by left ventricular hypertrophy and a left ventricular ejection fraction over 50%, myocardial dynamics under HFpEF have not yet been fully clarified, particularly regarding the relationship between myocardial strain distribution and myocardial work. To address this issue, we numerically investigated radial distribution of myocardial strain during a cardiac cycle with fixed internal volume at the end of the systolic and diastolic phases under different mechanical conditions, such as those involving myocardial thickness and elasticity of myocardial fibers. The myocardium was a modeled as a visco-hyperelastic continuous material. This model was taken into account that active contractile stress along the myocardial fiber direction depends on membrane potential change. Our numerical results showed that both radial and circumferential strains decreased as wall thickness increased, which reflected cardiac hypertrophy, but that myocardial work became larger than that observed with thin ventricular walls. Further, the change in left ventricular diastolic internal pressure caused circumferential strain, while fiber stiffness contributed to radial strain. Since peak circumferential strain was well estimated by the maximum difference between total internal and myocardial volumes, measuring the epicardial contraction rate should be helpful in understanding patients with HFpEF.

Computational modeling of braided-stent deployment for interpreting the mechanism of stent flattening.

This study develops a computational model of the braided stent for interpreting the mechanism of stent flattening during deployment into curved arteries. Stent wires are expressed using Kirchhoff's rod theory and their mechanical behavior is treated using a corotational beam formulation. The equation of motion of the braided stent is solved in a step-by-step manner using the resultant elastic force and mechanical interactions of wires with friction. Examples of braided-stent deployment into idealized arteries with various curvatures are numerically simulated. In cases of low curvature, the braided stent expands from a catheter by releasing the bending energy stored in stent wires, while incomplete expansion is found at both stent ends (ie, the fish-mouth phenomenon), where relatively little bending energy is stored. In cases of high curvature, much torsional energy is stored in stent wires locally in the midsection of the curvature and the bending energy for stent self-expansion is not fully released even after deployment, leading to stent flattening. These findings suggest that the mechanical state of the braided stent and its transition during deployment play an important role in the underlying mechanism of stent flattening. NOVELTY STATEMENT: This study developed a computational mechanical model of the braided stent for interpreting stent flattening, which is a critical issue observed during deployment into highly curved arteries. Mechanical behaviors of the stent wires are appropriately treated by corotational beam element formulation with considering multiple contacts. We conducted numerical examples of the stent deployment into curved arteries and found that the mechanical state of the braided stent during deployment associated with occurrences of the stent flattening. We believe this finding gives new insight into the mechanism of stent flattening and would advance the design of the stent and its deployment protocol.