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.

Deformed Popliteal Artery Due to Highly Flexed Knee Position Can Cause Kinks, Creating an Unfavorable Hemodynamic State.

BACKGROUND: Endovascular treatment devices of the femoropopliteal artery have evolved, improving clinical results. However, the effects of dynamic changes in the popliteal artery during knee flexion have not been sufficiently investigated. In this study we performed a 3-dimensional analysis to clarify the dynamic changes in the popliteal artery during knee flexion and their effects on hemodynamics.Methods and Results: To analyze dynamic changes in the popliteal artery in the knee flexion position, a computed tomography protocol was developed in the right-angled and maximum flexion knee positions. Thirty patients with lower extremity artery disease were recruited. V-Modeler software was used for anatomical and hemodynamic analyses. Various types of deformations of the popliteal artery were revealed, including hinge points and accessory flexions. Kinks can occur in the maximum flexion position; however, they rarely occur in the right-angled flexion position. In addition, hemodynamic analysis revealed a tendency for lower minimum wall shear stress and a higher maximum oscillatory shear index at the maximum curvature of the popliteal artery. CONCLUSIONS: Kinks in the maximum flexion position suggested that the outcome of endovascular treatment may change in areas such as Japan, where knee flexion is customary. Hemodynamics at the maximum curvature of the popliteal artery indicated that the luminal condition was unfavorable for endovascular treatment.

Uncertainty quantification in cerebral circulation simulations focusing on the collateral flow: Surrogate model approach with machine learning.

Collateral circulation in the circle of Willis (CoW), closely associated with disease mechanisms and treatment outcomes, can be effectively investigated using one-dimensional-zero-dimensional hemodynamic simulations. As the entire cardiovascular system is considered in the simulation, it captures the systemic effects of local arterial changes, thus reproducing collateral circulation that reflects biological phenomena. The simulation facilitates rapid assessment of clinically relevant hemodynamic quantities under patient-specific conditions by incorporating clinical data. During patient-specific simulations, the impact of clinical data uncertainty on the simulated quantities should be quantified to obtain reliable results. However, as uncertainty quantification (UQ) is time-consuming and computationally expensive, its implementation in time-sensitive clinical applications is considered impractical. Therefore, we constructed a surrogate model based on machine learning using simulation data. The model accurately predicts the flow rate and pressure in the CoW in a few milliseconds. This reduced computation time enables the UQ execution with 100 000 predictions in a few minutes on a single CPU core and in less than a minute on a GPU. We performed UQ to predict the risk of cerebral hyperperfusion (CH), a life-threatening condition that can occur after carotid artery stenosis surgery if collateral circulation fails to function appropriately. We predicted the statistics of the postoperative flow rate increase in the CoW, which is a measure of CH, considering the uncertainties of arterial diameters, stenosis parameters, and flow rates measured using the patients' clinical data. A sensitivity analysis was performed to clarify the impact of each uncertain parameter on the flow rate increase. Results indicated that CH occurred when two conditions were satisfied simultaneously: severe stenosis and when arteries of small diameter serve as the collateral pathway to the cerebral artery on the stenosis side. These findings elucidate the biological aspects of cerebral circulation in terms of the relationship between collateral flow and CH.

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.

Cerebrospinal fluid dynamics in idiopathic normal pressure hydrocephalus on four-dimensional flow imaging.

OBJECTIVES: To evaluate complex CSF movements and shear stress in patients with idiopathic normal pressure hydrocephalus (iNPH) on four-dimensional (4D) flow MRI. METHODS: Three-dimensional velocities and volumes of the reciprocating CSF movements through 12 ROIs from the foramen of Monro to the upper cervical spine were measured in 41 patients with iNPH, 23 patients with co-occurrence of iNPH and Alzheimer's disease (AD), and 9 age-matched controls, using 4D flow imaging and application. Stroke volume, reversed-flow rate, and shear stress were automatically calculated. Relationships between flow-related parameters and morphological measurements were also assessed. RESULTS: Stroke volumes, reversed-flow rates, and shear stress at the cerebral aqueduct were significantly higher in patients with iNPH than in controls. Patients with pure iNPH had significantly higher shear stress at the ventral aspect of the cerebral aqueduct than those with co-occurrence of iNPH and AD. The stroke volume at the upper end of the cerebral aqueduct had the strongest association with the anteroposterior diameter of the lower end of the cerebral aqueduct (r = 0.52). The stroke volume at the foramen of Monro had significant associations with the indices specific to iNPH. The shear stress at the dorsal aspect of the cerebral aqueduct had the strongest association with the diameter of the foramen of Magendie (r = 0.52). CONCLUSIONS: Stroke volumes, reversed-flow rates, and shear stress through the cerebral aqueduct on 4D flow MRI are useful parameters for iNPH diagnosis. These findings can aid in elucidating the mechanism of ventricular enlargement in iNPH. KEY POINTS: • The CSF stroke volume and bimodal shear stress at the cerebral aqueduct were considerably higher in patients with iNPH. • The patients with pure iNPH had significantly higher shear stress at the ventral aspect of the cerebral aqueduct than those with co-occurrence of iNPH and AD. • The shear stress at the cerebral aqueduct was significantly associated with the diameter of the foramen of Magendie.

Three-dimensional displacement measurement of self-oscillating gel using digital holographic microscopy.

To measure the 3D microdisplacement of a self-oscillating polymer gel driven by the Belousov-Zhabotinsky reaction, we propose, to the best of our knowledge, a new particle detection and tracking method based on a phase image/volume template matching using digital holographic microscopy. We demonstrate the precision of the proposed method and compare it with conventional approaches. The method is applied to 3D measurement of the motions of particles attached to the surface of an oscillating gel. Measurement results show that the local area of the gel oscillates periodically, and the motion propagates throughout the gel. Our method can measure rapid and complex 3D microdisplacement change.

Computational fluid dynamics study of intra-arterial chemotherapy for oral cancer.

BACKGROUND: Intra-arterial chemotherapy (IAC) for oral cancer can deliver a higher concentration of anticancer agent into a tumor-feeding artery than intravenous systemic chemotherapy. However, distribution of anticancer agent into several branches of the external carotid artery (ECA) in IAC has not demonstrated sufficient treatment efficacy. To improve the effectiveness of IAC, the flow distribution of anticancer agent into the branches of the ECA in several IAC methods was investigated using computational fluid dynamics (CFD). METHODS: Patient-specific three-dimensional vessel models were created from CT images of 2 patients with tongue cancer. Catheter models were combined with the vessel models. Thirty-two models were generated with varying vertical and horizontal positions of the catheter tip. With the use of a zero-dimensional resistance model of the peripheral vessel network, conventional IAC and superselective IAC were simulated in 30 and 2 models, respectively. The flow distribution of anticancer agent into the branches of the ECA was investigated in 32 models. Additionally, the blood streamline was traced from the inlet of the common carotid artery toward each outlet to examine the flow of anticancer agent in all models, and the wall shear stress of the vessel was calculated for some models. RESULTS: The CFD simulations could be conducted within a reasonable computational time. In several models, the anticancer agent flowed into the target artery only when the catheter tip was located below the bifurcation of the ECA and each target artery. Furthermore, the anticancer agent tended to flow into the target artery when the catheter tip was shifted toward the target artery. In all ECA branches that had flow of anticancer agent, the blood streamlines to the target arteries contacted the catheter tip. Anticancer agent flowed into only the target artery in patients' models for superselective IAC. However, high wall shear stress was observed at the target artery in one patient's model. CONCLUSIONS: This CFD study showed that location of the catheter tip was important in controlling the anticancer agent in conventional IAC. The distribution rate of anticancer agent into the tumor-feeding artery tended to increase when the catheter tip was placed below and toward the target artery. Although superselective IAC can reliably supply anticancer agent to the target artery, high wall shear stress at the target artery can occur, depending on vessel geometry of the patient, which may cause serious complications during the treatment.

Investigation of blood flow in the external carotid artery and its branches with a new 0D peripheral model.

BACKGROUND: Patient-specific modelling in clinical studies requires a realistic simulation to be performed within a reasonable computational time. The aim of this study was to develop simple but realistic outflow boundary conditions for patient-specific blood flow simulation which can be used to clarify the distribution of the anticancer agent in intra-arterial chemotherapy for oral cancer. METHODS: In this study, the boundary conditions are expressed as a zero dimension (0D) resistance model of the peripheral vessel network based on the fractal characteristics of branching arteries combined with knowledge of the circulatory system and the energy minimization principle. This resistance model was applied to four patient-specific blood flow simulations at the region where the common carotid artery bifurcates into the internal and external carotid arteries. RESULTS: Results of these simulations with the proposed boundary conditions were compared with the results of ultrasound measurements for the same patients. The pressure was found to be within the physiological range. The difference in velocity in the superficial temporal artery results in an error of 5.21 ± 0.78 % between the numerical results and the measurement data. CONCLUSIONS: The proposed outflow boundary conditions, therefore, constitute a simple resistance-based model and can be used for performing accurate simulations with commercial fluid dynamics software.

Computational Fluid Dynamic Study of Nasal Respiratory Function Before and After Bimaxillary Orthognathic Surgery With Bone Trimming at the Inferior Edge of the Pyriform Aperture.

PURPOSE: This study aimed to evaluate the influence of maxillary impaction orthognathic surgery on nasal respiratory function and the efficacy of bone trimming at the inferior edge of the pyriform aperture. MATERIALS AND METHODS: The participants were 10 patients (3 male and 7 female patients) with mandibular prognathism who underwent bimaxillary orthognathic surgery with maxillary impaction. The surgical procedures performed were Le Fort I osteotomy with bone trimming at the inferior edge of the pyriform aperture and bilateral sagittal split osteotomy. Three-dimensional models of the nasal cavity were reconstructed from preoperative and postoperative computed tomography images. Furthermore, we remodeled the nasal valve region based on the postoperative models by adding a 1-mm and 2-mm stenosis to investigate the effects of bone trimming at the inferior edge of the pyriform aperture on the pressure effort. The 3-dimensional models were simulated with computational fluid dynamics, and the results of the pressure effort and the cross-sectional area (CSA) were compared for the anterior, middle, and posterior parts of the nasal cavity. The Wilcoxon signed rank test and Spearman rank correlation coefficients were used for statistical comparisons (P < .05). RESULTS: In the preoperative and postoperative models, there were considerable correlations between the CSA and the pressure effort in each part of the nasal cavity. The postoperative pressure effort showed a tendency to decrease and the CSA showed a tendency to increase in each part of the nasal cavity. In four 2-mm stenosis models, the pressure effort in the anterior nasal cavity was larger than the preoperative pressure effort and the CSA of the anterior nasal cavity was smaller than the preoperative CSA. CONCLUSIONS: Bone trimming at the inferior edge of the pyriform aperture appears to be useful for avoiding nasal respiratory complications with maxillary impaction.

Numerical Study of Cerebroarterial Hemodynamic Changes Following Carotid Artery Operation: A Comparison Between Multiscale Modeling and Stand-Alone Three-Dimensional Modeling.

Free outflow boundary conditions have been widely adopted in hemodynamic model studies, they, however, intrinsically lack the ability to account for the regulatory mechanisms of systemic hemodynamics and hence carry a risk of producing incorrect results when applied to vascular segments with multiple outlets. In the present study, we developed a multiscale model capable of incorporating global cardiovascular properties into the simulation of blood flows in local vascular segments. The multiscale model was constructed by coupling a three-dimensional (3D) model of local arterial segments with a zero-one-dimensional (0-1-D) model of the cardiovascular system. Numerical validation based on an idealized model demonstrated the ability of the multiscale model to preserve reasonable pressure/flow wave transmission among different models. The multiscale model was further calibrated with clinical data to simulate cerebroarterial hemodynamics in a patient undergoing carotid artery operation. The results showed pronounced hemodynamic changes in the cerebral circulation following the operation. Additional numerical experiments revealed that a stand-alone 3D model with free outflow conditions failed to reproduce the results obtained by the multiscale model. These results demonstrated the potential advantage of multiscale modeling over single-scale modeling in patient-specific hemodynamic studies. Due to the fact that the present study was limited to a single patient, studies on more patients would be required to further confirm the findings.

Arterial location-specific calcification at the carotid artery and aortic arch for chronic kidney disease, diabetes mellitus, hypertension, and dyslipidemia.

Several risk factors for arterial calcification have been reported but controversial. The aim of this study was to clarify the interactions among chronic kidney disease (CKD), diabetes mellitus (DM), hypertension, and dyslipidemia in altering the risk of arterial calcification in the three different arterial locations and the intramural location at the internal carotid artery (ICA) origins. Calcified burdens at the ICA origins, the aortic arch, and its orifices were evaluated in a retrospective fashion by using computed tomography angiography in 397 patients. The multivariate analyses were adjusted for age, gender, CKD, DM, hypertension, dyslipidemia, and current smoking status. Additionally, subgroup analyses in each variable were conducted. Our multivariate logistic regression analyses revealed that CKD was significantly associated with the outside-wall calcification at the ICA origins, whereas DM was only associated with the inside-ICA-wall calcification. Additionally, we found that DM increased the association between CKD and arterial calcification at the aortic arch and its orifices, and the outside-wall at the ICA origins. Hypertension was significantly associated with the calcification at the orifices of the aortic arch branches synergistically with CKD. Dyslipidemia did not have any significant association with calcification in any of the three vascular beds. CKD had the highest prevalence risk of calcification in common with the three different vascular beds. CKD in combination with DM, as well as hypertension in combination with CKD, were key relationships affecting the risk of arterial calcification, especially at the aortic arch and its orifices.

Development of a 3D Vascular Network Visualization Platform for One-Dimensional Hemodynamic Simulation.

Recent advancements in computational performance and medical simulation technology have made significant strides, particularly in predictive diagnosis. This study focuses on the blood flow simulation reduced-order models, which provide swift and cost-effective solutions for complex vascular systems, positioning them as practical alternatives to 3D simulations in resource-limited medical settings. The paper introduces a visualization platform for patient-specific and image-based 1D-0D simulations. This platform covers the entire workflow, from modeling to dynamic 3D visualization of simulation results. Two case studies on, respectively, carotid stenosis and arterial remodeling demonstrate its utility in blood flow simulation applications.

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.

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.

Higher cerebral blood flow on four-dimensional flow magnetic resonance imaging in young women.

We investigated the reduction in regional brain volume and cerebral blood flow (CBF) with aging and explored potential sex differences in healthy brains. Three-dimensional (3D) T1-weighted magnetic resonance imaging (MRI), time-of-flight magnetic resonance angiography, and four-dimensional (4D) flow MRI were performed on 129 healthy volunteers aged 22-92 years. The brains of healthy volunteers were segmented into 21 subregions using 3D T1-weighted MRI and CBFs in 16 major intracranial arteries were measured using 4D flow MRI. The cortical gray matter volume decreased linearly with aging, whereas the cerebral white matter volume increased until the 40s and then decreased, and the subcortical gray matter volume changed little with aging. The cortical gray matter volume was significantly associated with the total CBF of the major intracranial arteries distal to the circle of Willis; however, the cerebral white matter and subcortical gray matter volumes were not. Generally, women have higher total CBF than men, particularly in their 40s and younger, despite the smaller intracranial volume and smaller diameters of intracranial arteries than men. This may contribute to the higher incidence of subarachnoid hemorrhage due to cerebral aneurysms and migraine in women.

Variability of computational fluid dynamics solutions for pressure and flow in a giant aneurysm: the ASME 2012 Summer Bioengineering Conference CFD Challenge.

Stimulated by a recent controversy regarding pressure drops predicted in a giant aneurysm with a proximal stenosis, the present study sought to assess variability in the prediction of pressures and flow by a wide variety of research groups. In phase I, lumen geometry, flow rates, and fluid properties were specified, leaving each research group to choose their solver, discretization, and solution strategies. Variability was assessed by having each group interpolate their results onto a standardized mesh and centerline. For phase II, a physical model of the geometry was constructed, from which pressure and flow rates were measured. Groups repeated their simulations using a geometry reconstructed from a micro-computed tomography (CT) scan of the physical model with the measured flow rates and fluid properties. Phase I results from 25 groups demonstrated remarkable consistency in the pressure patterns, with the majority predicting peak systolic pressure drops within 8% of each other. Aneurysm sac flow patterns were more variable with only a few groups reporting peak systolic flow instabilities owing to their use of high temporal resolutions. Variability for phase II was comparable, and the median predicted pressure drops were within a few millimeters of mercury of the measured values but only after accounting for submillimeter errors in the reconstruction of the life-sized flow model from micro-CT. In summary, pressure can be predicted with consistency by CFD across a wide range of solvers and solution strategies, but this may not hold true for specific flow patterns or derived quantities. Future challenges are needed and should focus on hemodynamic quantities thought to be of clinical interest.

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.

Development of a Model for Plaque Induction in Rat Carotid Arteries.

Objective Plaque induction through intimal injury using a balloon catheter in small animals and by artificial ligation of the carotid artery in large animals have been reported. However, these reports have not yet succeeded in inducing stable plaques nor creating a high degree of intimal thickening to be used as animal models. We have previously developed a plaque induction model in rats but have failed to obtain a plaque incidence frequency that can be used as a model. Thus, in the current study, we aimed to create a versatile disease model to examine the pharmacokinetics of drug administration, determine the efficacy of treatment, and examine the process of intimal thickening. We also attempted to create an improved model with shorter, more frequent, and more severe intimal thickening. Materials and Methods The common carotid artery of male Wistar rats was surgically exposed and completely ligated with a wire and 6-0 nylon thread. Then, the wire was removed to create a partial ligation. To create a high frequency and high degree of intimal thickening, 72 rats were divided into two groups: a single lesion group with a 0.25-mm wire and a single ligature point, and a tandem lesion group with a 0.3-mm wire and two ligature points. Each group was further divided into normal diet and high cholesterol diet groups. The presence and frequency of intimal thickening were examined for each group after 4, 8, and 16 weeks of growth. Results In the single lesion group, intimal thickening was observed in 42% of the 4-week group and 75% of the 8-week group. In the tandem lesion group, intimal thickening was observed in 75% of the 4-week group and 50% of the 8-week group. In addition, 50% of the individuals reared for 16 weeks developed intimal thickening. Conclusion We successfully induced intimal thickening in the carotid arteries of rats with high frequency in the single lesion and tandem lesion groups. The results also showed that the tandem lesion group tended to induce intimal thickening earlier than the single lesion group.

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.