Validating the accuracy of real-time phase-contrast MRI and quantifying the effects of free breathing on cerebrospinal fluid dynamics.

BACKGROUND: Understanding of the cerebrospinal fluid (CSF) circulation is essential for physiological studies and clinical diagnosis. Real-time phase contrast sequences (RT-PC) can quantify beat-to-beat CSF flow signals. However, the detailed effects of free-breathing on CSF parameters are not fully understood. This study aims to validate RT-PC's accuracy by comparing it with the conventional phase-contrast sequence (CINE-PC) and quantify the effect of free-breathing on CSF parameters at the intracranial and extracranial levels using a time-domain multiparametric analysis method. METHODS: Thirty-six healthy participants underwent MRI in a 3T scanner for CSF oscillations quantification at the cervical spine (C2-C3) and Sylvian aqueduct, using CINE-PC and RT-PC. CINE-PC uses 32 velocity maps to represent dynamic CSF flow over an average cardiac cycle, while RT-PC continuously quantifies CSF flow over 45-seconds. Free-breathing signals were recorded from 25 participants. RT-PC signal was segmented into independent cardiac cycle flow curves (Qt) and reconstructed into an averaged Qt. To assess RT-PC's accuracy, parameters such as segmented area, flow amplitude, and stroke volume (SV) of the reconstructed Qt from RT-PC were compared with those derived from the averaged Qt generated by CINE-PC. The breathing signal was used to categorize the Qt into expiratory or inspiratory phases, enabling the reconstruction of two Qt for inspiration and expiration. The breathing effects on various CSF parameters can be quantified by comparing these two reconstructed Qt. RESULTS: RT-PC overestimated CSF area (82.7% at aqueduct, 11.5% at C2-C3) compared to CINE-PC. Stroke volumes for CINE-PC were 615 mm³ (aqueduct) and 43 mm³ (spinal), and 581 mm³ (aqueduct) and 46 mm³ (spinal) for RT-PC. During thoracic pressure increase, spinal CSF net flow, flow amplitude, SV, and cardiac period increased by 6.3%, 6.8%, 14%, and 6%, respectively. Breathing effects on net flow showed a significant phase difference compared to the other parameters. Aqueduct-CSF flows were more affected by breathing than spinal-CSF. CONCLUSIONS: RT-PC accurately quantifies CSF oscillations in real-time and eliminates the need for cardiac synchronization, enabling the quantification of the cardiac and breathing components of CSF flow. This study quantifies the impact of free-breathing on CSF parameters, offering valuable physiological references for understanding the effects of breathing on CSF dynamics.

The Effects of Free Breathing on Cerebral Venous Flow: A Real-Time Phase Contrast MRI Study in Healthy Adults.

Quantifying the effects of free breathing on cerebral venous flow is crucial for understanding cerebral circulation mechanisms and clinical applications. Unlike conventional cine phase-contrast MRI sequences (CINE-PC), real-time phase-contrast MRI sequences (RT-PC) can provide a continuous beat-to-beat flow signal that makes it possible to quantify the effect of breathing on cerebral venous flow. In this study, we examined 28 healthy human participants, comprising of 14 males and 14 females. Blood flows in the right/left internal jugular veins in the extracranial plane and the superior sagittal sinus (SSS) and straight sinus in the intercranial plane were quantified using CINE-PC and RT-PC. The first objective of this study was to determine the accuracy of RT-PC in quantifying cerebral venous flow, relative to CINE-PC. The second, and main objective, was to quantify the effect of free breathing on cerebral venous flow, using a time-domain multiparameter analysis method. Our results showed that RT-PC can accurately quantify cerebral venous flow with a 2 × 2 mm2 spatial resolution and 75 ms/image time resolution. The mean flow rate, amplitude, stroke volume, and cardiac period of cerebral veins were significantly higher from the mid-end phase of expiration to the mid-end phase of inspiration. Breathing affected the mean flow rates in the jugular veins more than those in the SSS and straight sinus. Furthermore, the effects of free breathing on the flow rate of the left and right jugular veins were not synchronous. These new findings provide a useful reference for better understanding the mechanisms of cerebral circulation.

Hydrodynamic and Hemodynamic Interactions in Chronic Hydrocephalus.

BACKGROUND: During a cardiac cycle, intracranial pressure is related to arterial entry into the cranium and its interaction with intracranial compliance. The arterial inflow is compensated by intracranial compliance and, initially, the flushing of cerebrospinal fluid (CSF) into the cervical subarachnoid spaces. Our objective is to analyze the interactions between intracranial arteriovenous exchange and cerebrospinal fluid oscillations. METHOD: A total of 23 patients (73 ± 8 years) with suspected chronic hydrocephalus (CH) underwent an infusion test and phase-contrast MRI. Rout is an important factor in the diagnosis of CH. Patients were divided into 2 populations: probableCH (Rout: resistance to CSF outflow) (Rout > 12 mmHg/mL/min, 13 patients) and unlikelyCH (Rout < 12 mmHg/mL/min, 10 patients). We measured the intracranial vascular volume (arteriovenous stroke volume: SVvasc) and CSF (CSF stroke volume at upper cervical level: SVCSF) volume variations during the cardiac cycle. RESULTS: In the whole population, we observed a significant correlation between SVvasc and SVCSF (R2 = 0.43; p = 0.0007). In the population unlikelyCH, this correlation was significant (R2 = 0.76; p = 0.001). In the population probableCH, this correlation was not significant (R2 = 0.17, p = 0.16). CONCLUSIONS: These results show that the link between the compliance of the oscillating CSF and the abrupt arterial inflow seems to be altered in CH. CSF oscillations between intracranial and cervical fluid spaces limit the impact of the abrupt arterial inflow.

Cerebral arterial flow dynamics during systole and diastole phases in young and older healthy adults.

BACKGROUND: Since arterial flow is the leading actor in neuro-fluids flow dynamics, it might be interesting to assess whether it is meaningful to study the arterial flow waveform in more detail and whether this provides new important information. Few studies have focused on determining the influence of heart rate variation over time on the arterial flow curve. Therefore, this study aimed to evaluate cerebral arterial flow waveforms at extracranial and intracranial compartments in young and elderly healthy adults, also considering systole and diastole phases. METHODS: Cine phase-contrast magnetic resonance imaging (CINE-PC MRI) was performed on twenty-eight healthy young volunteers (HYV) and twenty healthy elderly volunteers (HEV) to measure arterial blood flows at the extracranial and intracranial planes. A semi-automated protocol using MATLAB scripts was implemented to identify the main representative points in the arterial flow waveforms. Representative arterial profiles were estimated for each group. Moreover, the effects of age and sex on flow times, amplitude-related parameters, and parameters related to systole and diastole phases were evaluated at the extracranial and intracranial compartments. Student's t-test or Wilcoxon's test (depending on the normality of the distribution) was used to detect significant differences. RESULTS: In HYVs, significant differences were observed between extracranial and intracranial levels in parameters related to the AP1 amplitude. Besides the detected differences in pulsatility index (extracranial: 0.92 ± 0.20 vs. 1.28 ± 0.33; intracranial: 0.79 ± 0.15 vs. 1.14 ± 0.18, p < .001) and average flow (715 ± 136 vs. 607 ± 125 ml/min, p = .008) between HYV and HEV, differences in the amplitude value of the arterial flow profile feature points were also noted. Contrary to systole duration (HYV: 360 ± 29 ms; HEV: 364 ± 47 ms), diastole duration presented higher inter-individual variability in both populations (HYV: 472 ± 145 ms; HEV: 456 ± 106 ms). Our results also showed that, with age, it is mainly the diastolic phase that changes. Although no significant differences in duration were observed between the two populations, the mean flow value in the diastolic phase was significantly lower in HEV (extracranial: 628 ± 128 vs. 457 ± 111 ml/min; intracranial: 599 ± 121 vs. 473 ± 100 ml/min, p < .001). No significant differences were observed in the arterial flow parameters evaluated between females and males in either HYV or HEV. CONCLUSION: Our study provides a novel contribution on the influence of the cardiac cycle phases on cerebral arterial flow. The main contribution in this study concerns the identification of age-related alterations in cerebral blood flow, which occur mainly during the diastolic phase. Specifically, we observed that mean flow significantly decreases with age during diastole, whereas mean flow during systole is consistent.

Hemodynamic and Hydrodynamic Pathophysiology in Chiari Type 1 Malformations: Towards Understanding the Genesis of Syrinx.

BACKGROUND: The pathophysiology of this association of type 1 Chiari malformation (CM1) and syrinxes is still unknown. There is an alteration in the dynamics of neurofluids (cerebrospinal fluid, arterial and venous blood) during the cardiac cycle in CM1. Our objective is to quantify CSF or arterial blood or venous blood flow in patients with Chiari syndrome (CS) with and without syrinxes using phase-contrast MRI (PCMRI). METHODS: We included 28 patients with CM1 (9 with syrinxes, 19 without). Morphological MRI with complementary PCMRI sequences was performed. We analyzed intraventricular CSF, subarachnoid spaces CSF, blood, and tonsillar pulsatility. RESULTS: There is a highly significant correlation (p < 0.001) between cerebral blood flow, cerebral vascular expansion volume and venous drainage distribution. Venous drainage distribution is significantly inversely correlated with oscillatory CSF volume at the level of the foramen magnum plane [-0.37 (0.04)] and not significantly correlated at the C2C3 level [-0.37 (0.05)] over our entire population. This correlation maintained the same trend in patients with syrinxes [-0.80 (<0.01)] and disappeared in patients without a syrinx [-0.05 (0.81)]. CONCLUSION: The distribution of venous drainage is an important factor in intracranial homeostasis. Impaired venous drainage would lead to greater involvement of the CSF in compensating for arterial blood influx, thus contributing to syrinx genesis.

Familiarization with Mixed Reality for Individuals with Autism Spectrum Disorder: An Eye Tracking Study.

Mixed Reality (MR) technology is experiencing significant growth in the industrial and healthcare sectors. The headset HoloLens 2 displays virtual objects (in the form of holograms) in the user's environment in real-time. Individuals with Autism Spectrum Disorder (ASD) exhibit, according to the DSM-5, persistent deficits in communication and social interaction, as well as a different sensitivity compared to neurotypical (NT) individuals. This study aims to propose a method for familiarizing eleven individuals with severe ASD with the HoloLens 2 headset and the use of MR technology through a tutorial. The secondary objective is to obtain quantitative learning indicators in MR, such as execution speed and eye tracking (ET), by comparing individuals with ASD to neurotypical individuals. We observed that 81.81% of individuals with ASD successfully familiarized themselves with MR after several sessions. Furthermore, the visual activity of individuals with ASD did not differ from that of neurotypical individuals when they successfully familiarized themselves. This study thus offers new perspectives on skill acquisition indicators useful for supporting neurodevelopmental disorders. It contributes to a better understanding of the neural mechanisms underlying learning in MR for individuals with ASD.

Real-time phase contrast MRI versus conventional phase contrast MRI at different spatial resolutions and velocity encodings.

PURPOSES: To compare the accuracy of real-time phase-contrast echo-planar MRI (EPI-PC) and conventional cine phase-contrast MRI (Conv-PC) and to assess the influence of spatial resolutions (pixel size) and velocity encoding on flow measurements obtained with the two sequences. METHODS: Flow quantification was assessed using a pulsatile flow phantom (diameter: 9.5 mm; mean flow rate: 1150 mm3/s; mean flow velocity: 1.6 cm/s). Firstly, the accuracy of the EPI-PC was checked by comparing it with the flow rate in the calibrated phantom and the pulsation index from Conv-PC. Secondly, flow data from the two sequences were compared quantitatively as a function of the pixel size and the velocity encoding. RESULTS: The mean percentage difference between the EPI-PC flow rate and calibrated phantom flow rate was -2.9 ± 2.1% (Mean ± SD). The pulsatility indices for EPI-PC and Conv-PC were respectively 0.64 and 0.59. In order to keep the flow rate measurement error within 10%, the ROI in Conv-PC had to contain at least 13 pixels, while the ROI in EPI-PC had to contain at least 9 pixels. Furthermore, Conv-PC had a higher velocity-to-noise ratio and could use a higher velocity encoding than EPI-PC (20 cm/s and 15 cm/s, respectively). CONCLUSIONS: The result of this in vitro study confirmed the accuracy of EPI-PC, and found that EPI-PC can adapt to lower spatial resolutions, but is more sensitive to velocity encoding than Conv-PC.

Impact of Shunt Placement on CSF Dynamics.

BACKGROUND: CSF dynamics are disturbed in chronic hydrocephalus (NPH). We hypothesise that these alterations reflect a disturbance of intracranial compliance. The aim of our study is to investigate the variations in intracranial hydrodynamics in NPH after ventricular shunt surgery. PATIENTS AND METHOD: We included 14 patients with definite NPH. All patients improved after ventriculoperitoneal shunting. The patients underwent an analysis of intracranial haemodynamics by phase-contrast MRI (pcMRI) preoperatively, at 6 months postoperatively, and at 1 year postoperatively. We analysed the dynamics of intraventricular CSF at the level of the aqueduct of Sylvius (SVAQU) and CSF at the level of the high cervical subarachnoid spaces (SVCERV). We calculated the ratio between SVAQU and SVCERV, called CSFRATIO, which reflects the participation of intraventricular pulsatility in overall intracranial CSF pulsatility. RESULTS: SVAQU significantly (p = 0.003) decreased from 240 ± 114 µL/cc to 214 ± 157 µL/cc 6 months after shunt placement. Six months after shunt placement, SVCERV significantly (p = 0.007) decreased from 627 ± 229 µL/cc to 557 ± 234 µL/cc. Twelve months after shunt placement, SVCERV continued to significantly (p = 0.001) decrease to 496 ± 234 µL/cc. CSFRATIO was not changed by surgery. CONCLUSIONS: CSF dynamics are altered by shunt placement and might be a useful marker of the shunt's effectiveness-especially if pressure values start to rise again. The detection of changes in CSF dynamics would require a reference postoperative pcMRI measurement for each patient.

Insights on the Hydrodynamics of Chiari Malformation.

BACKGROUND: We propose that the appearance of a ptosis of the cerebellar tonsils and syringomyelia is linked to its own hemohydrodynamic mechanisms. We aimed to quantify cerebrospinal fluid (CSF) and cerebral blood flow to highlight how neurofluid is affected by Chiari malformations type 1(CMI) and its surgery. METHODS: We retrospectively included 21 adult patients with CMI who underwent pre- and postoperative phase contrast MRI (PCMRI) during the period from 2001 to 2017. We analyzed intraventricular CSF, subarachnoid spaces CSF, blood, and tonsils pulsatilities. RESULTS: In preoperative period, jugular venous drainage seems to be less preponderant in patients with syringomyelia than other patients (venous correction factor: 1.49 ± 0.4 vs. 1.19 ± 0.1, p = 0.05). After surgery, tonsils pulsatility decreased significantly (323 ± 175 µL/cardiac cycle (CC) vs. 194 ± 130 µL/CC, p = 0.008) and subarachnoid CSF pulsatility at the foramen magnum increased significantly (201 ± 124 µL/CC vs. 363 ± 231 µL/CC, p = 0.02). After surgery, we found a decrease in venous flow amplitude (5578 ± 2469 mm3/s vs. 4576 ± 2084 mm3/s, p = 0.008) and venous correction factor (1.98 ± 0.3 vs. 1.20 ± 0.3 mm3/s, p = 0.004). CONCLUSIONS: Phase-contrast MRI could be a useful additional tool for postoperative evaluation and follow-up, and is complementary to morphological imaging.

Efficacy of benzodiazepines and related drugs in patients over 75 years of age and impact on cognition.

BACKGROUND: In France, despite the known risks, the use of benzodiazepines and related (BZD) is excessive, particularly in older populations. Over the age of 70, 1 person in 2 uses BZD on a long-term basis (more than 3 years), whereas it is recommended not to exceed 12 weeks. To compensate for the numerous undesirable effects and to maintain a positive benefit-risk balance, these treatments must be very effective and improve significantly the quality of life. AIMS: This study aims to determine whether the efficacy of BZD outweighs their adverse effects in older population. METHODS: In a population of 109 patients with cognitive impairment and hospitalized in Saint-Quentin (France), we recorded the use of BZD and medical background. Neuropsychological and geriatric assessments allowed cognitive and thymic evaluation. RESULTS: In our cohort of 109 patients, 50% of the subjects were BZD + and 78% were women. Patients in the BZD + group were no longer anxious but had poorer cognitive and executive performance than controls. DISCUSSION: Long-term treatment of anxiety in patients aged 75 and over with BZD appears to be effective. The deleterious impact of BZD on cognition has been demonstrated. CONCLUSIONS: These results tend to consider non-medicinal therapies as serious alternatives to BZD for treating anxiety in the older population.

Use of real-time phase-contrast MRI to quantify the effect of spontaneous breathing on the cerebral arteries.

Quantification of the effect of breathing on the cerebral circulation provides a better mechanistic understanding of the brain's circulatory system and is important in the early diagnosis of certain neurological diseases. However, conventional cine phase-contrast (CINE-PC) MRI cannot be used in this field of study because it only provides an average cardiac cycle flow curve reconstructed from multiple cardiac cycles. Unlike CINE-PC, phase-contrast echo-planar imaging (EPI-PC) can be used to quantify the blood flow rate in "real-time" and thus assess the effect of breathing on blood flow. Here, we first used post-processing software (developed in-house) to determine the feasibility of quantifying cerebral arterial blood flow with EPI-PC (relative to CINE-PC) in 16 participants. In a second step, we developed a new time-domain method for quantifying the intensity and the phase shift of the effects of breathing on the mean flow rate, stroke volume, cardiac period and amplitude of cerebral blood flow (in 10 participants). Our results showed that EPI-PC can quantify cerebral arterial blood flow rate with much the same degree of accuracy as CINE-PC but is more strongly influenced by differences in magnetic susceptibility. We found that breathing affected the mean flow rate, stroke volume and cardiac period of cerebral arterial blood flow.

Diffusion and Flow MR Imaging to Investigate Hydrocephalus Patients Before and After Endoscopic Third Ventriculostomy.

INTRODUCTION: In patients with noncommunicating hydrocephalus, dilation of the ventricles stresses white matter fibers and alters the cerebral blood flow (CBF) and cerebrospinal fluid (CSF) dynamics. The purpose of this work was to investigate, non-invasively, how endoscopic third ventriculostomy (ETV) impacts white matter, CSF oscillations, and CBF. METHODS: Eleven patients presenting with chronic headaches and noncommunicating hydrocephalus due to aqueductal stenosis were treated by ETV. Phase Contrast-MRI (PCMRI) and Diffusion Tensor Imaging (DTI) were performed before and after surgery to evaluate CSF and CBF as well as white matter stresses in the Corpus Callosum (CC) and Corona Radiata (CR). ETV success was confirmed by quantification of the CSF oscillations through the aperture in the third ventricle. RESULTS: All patients improved after surgery. CSF stroke volume was five times greater than normal ventricular stroke volume. Decrease in cervical CSF oscillations and increase in CBF were observed after ETV. In CR, fiber anisotropy decreased, while water diffusion increased. In CC, anisotropy did not vary, while water diffusion also increased. CONCLUSION: Even if static ICP typically do not increase, CSF and blood flow are impacted. PCMRI and DTI can provide useful information to help neurosurgeons select patients with good chance to improve after ETV.

Compliance of the cerebrospinal space: comparison of three methods.

BACKGROUND: Cerebrospinal compliance describes the ability of the cerebrospinal space to buffer changes in volume. Diminished compliance is associated with increased risk of potentially threatening increases in intracranial pressure (ICP) when changes in cerebrospinal volume occur. However, despite various methods of estimation proposed so far, compliance is seldom used in clinical practice. This study aimed to compare three measures of cerebrospinal compliance. METHODS: ICP recordings from 36 normal-pressure hydrocephalus patients who underwent infusion tests with parallel recording of transcranial Doppler blood flow velocity were retrospectively analysed. Three methods were used to calculate compliance estimates during changes in the mean ICP induced by infusion of fluid into the cerebrospinal fluid space: (a) based on Marmarou's model of cerebrospinal fluid dynamics (CCSF), (b) based on the evaluation of changes in cerebral arterial blood volume (CCaBV), and (c) based on the amplitudes of peaks P1 and P2 of ICP pulse waveform (CP1/P2). RESULTS: Increase in ICP caused a significant decrease in all compliance estimates (p < 0.0001). Time courses of compliance estimators were strongly positively correlated with each other (group-averaged Spearman correlation coefficients: 0.94 [0.88-0.97] for CCSF vs. CCaBV, 0.77 [0.63-0.91] for CCSF vs. CP1/P2, and 0.68 [0.48-0.91] for CCaBV vs. CP1/P2). CONCLUSIONS: Indirect methods, CCaBV and CP1/P2, allow for the assessment of relative changes in cerebrospinal compliance and produce results exhibiting good correlation with the direct method of volumetric manipulation. This opens the possibility of monitoring relative changes in compliance continuously.

Relationship between pineal cyst size and aqueductal CSF flow measured by phase contrast MRI.

BACKGROUND: Most patients with pineal cysts referred for neurosurgical consultation have no specific symptoms or objective findings except for pineal cyst size to help in management decisions. Our purpose was to assess the relationship between pineal cyst size and aqueductal CSF flow using PC-MRI. METHODS: Eleven adult patients with pineal cysts (>1 cm) referred for neurosurgical consultations were included. Cyst volume was calculated using 3D T1 images. Phase contrast magnetic resonance imaging (PC-MRI) in axial plane with velocity encoding of 5 cm/sec was used to quantitatively assess CSF flow through the cerebral aqueduct to determine the aqueductal stroke volume, which was then correlated to cyst size using Pearson's correlation. Pineal cysts were grouped by size into small (6/11) and large (5/11) using the median value to compare aqueductal stroke volume using Mann-Whitney test. RESULTS: Patients were 39±13 years (mean±SD) of age, and 10/11 (91%) were female. There was significant negative correlation between cyst volume and aqueductal stroke volume (r=0.74; P=0.009). Volume of small cysts (4954±2157 mm3) was significantly different compared to large cysts (13,752±3738 mm3; P=0.008). The aqueductal stroke volume of patients harboring large cysts 33±8 µL/cardiac cycle was significantly lower than that of patients with small cysts 96±29 µL/cardiac cycle (P=0.008). CONCLUSIONS: Aqueductal CSF flow appears to decrease with increasing pineal cyst size. Our preliminary results provide first evidence that even in the absence of objective neurological findings or hydrocephalus; larger pineal cysts already display decreased CSF flow through the cerebral aqueduct.

Ophthalmic Artery and Superior Ophthalmic Vein Blood Flow Dynamics in Glaucoma Investigated by Phase Contrast Magnetic Resonance Imaging.

PRECIS: Ophthalmic artery (OA) and superior ophthalmic vein (SOV) blood flow were quantified by phase contrast magnetic resonance imaging (PC MRI) and seemed lower in glaucoma. Venous flow dynamics was different in glaucoma patients with a significantly decreased pulsatility. INTRODUCTION: Studies using color Doppler imaging and optical coherence tomography flowmetry strongly suggested that vascular changes are involved in the pathophysiology of glaucoma, but the venous outflow has been little studied beyond the episcleral veins. This study measured the OA and the SOV flow by PC MRI in glaucoma patients compared with controls. METHODS: Eleven primary open-angle glaucoma patients, with a mean±SD visual field deficit of -2.3±2.7 dB and retinal nerve fiber layer thickness of 92±13 µ, and 10 controls of similar age, were examined by PC MRI. The mean, maximal and minimal flow over cardiac cycle were measured. The variation of flow (ΔQ) was calculated. RESULTS: The OA mean±SD mean flow was 13.21±6.79 in patients and 15.09±7.62 mL/min in controls (P=0.35) and the OA maximal flow was 25.70±12.08 mL/min in patients, and 28.45±10.64 mL/min in controls (P=0.22). In the SOV the mean±SD mean flow was 6.46±5.50 mL/min in patients and 7.21±6.04 mL/min in controls (P=0.81) and the maximal flow was 9.06±6.67 in patients versus 11.96±9.29 mL/min in controls (P=0.47). The ΔQ in the SOV was significantly lower in patients (5.45±2.54 mL/min) than in controls (9.09±5.74 mL/min) (P=0.04). DISCUSSION: Although no significant difference was found, the mean and maximal flow in the OA and SOV seemed lower in glaucoma patients than in controls. The SOV flow waveform might be affected in glaucoma, corroborating the hypothesis of an impairment of venous outflow in those patients.

A novel non-invasive method for estimating the local wave speed at a single site in the internal carotid artery.

Objectives Local wave speed is a biomarker which provides an objective analysis of the cardiovascular function. The aim of this study was to determine the local wave speed in the internal carotid artery by a new non-invasive method that measures blood velocity waveform at only one site. Methods For this purpose, the cepstral analysis was employed to determine the arrival time of the reflection wave and the wave speed in the carotid artery. To validate our model, we applied it experimentally in vivo on young and old healthy subjects. The blood velocity waveform was measured by using phase-contrast magnetic resonance for 22 subjects. Results Our experimental results correlated with reference values reported in previous studies conducted on the internal arterial carotid usually adopting the invasive method. They also correlated with those obtained by using the foot-to-foot method (R2=0.72). The wave speed obtained by the method developed in this study and that of the foot-to-foot method increased with age (p<0.001). Conclusions The method developed in this study can be applied in the other arteries and it can also be used with other techniques such as ultrasound imaging.

Extracranial versus intracranial hydro-hemodynamics during aging: a PC-MRI pilot cross-sectional study.

BACKGROUND: Both aging and changes in blood flow velocity between the extracranial (intraspinal) and intracranial regions of cerebral vessels have an impact on brain hydro-hemodynamics. Arterial and venous cerebral blood flows interact with cerebrospinal fluid (CSF) in the both the cranial and spinal systems. Studies suggest that increased blood and CSF flow pulsatility plays an important role in certain neurological diseases. Here, we investigated the changes in blood-CSF flow pulsatility in the cranial and spinal systems with age as well as the impact of the intracranial compartment on flow patterns. METHOD: Phase-contrast magnetic resonance imaging (PC-MRI) was performed in 16 young and 19 elderly healthy volunteers to measure the flows of CSF and blood. CSF stroke volume (SV), blood SV, and arterial and venous pulsatility indexes (PIs) were assessed at intra- and extracranial levels in both samples. Correlations between ventricular and spinal CSF flow, and between blood and CSF flow during aging were also assessed. RESULTS: There was a significant decrease in arterial cerebral blood flow and intracranial venous cerebral blood flow with aging. We also found a significant increase of intracranial blood SV, spinal CSF SV and arterial/venous pulsatility indexes with aging. In regard to intracranial compartment impact, arterial and venous PIs decreased significantly at intracranial level in elderly volunteers, while young adults exhibited decrease in venous PI only. Intracranial venous PI was paradoxically lower than extracranial venous PI, regardless of age. In both sample groups, spinal CSF SV and aqueductal CSF SV were positively correlated, and so were extracranial blood and spinal CSF SVs. CONCLUSION: The study demonstrates that aging changes blood flow but preserves blood and CSF interactions. We also showed that many parameters related to blood and CSF flows differ between young and elderly adults.

Decreased Cerebrospinal Fluid Flow Is Associated With Cognitive Deficit in Elderly Patients.

Background: Disruptions in cerebrospinal fluid (CSF) flow during aging could compromise protein clearance from the brain and contribute to the etiology of Alzheimer's Disease (AD). Objective: To determine whether CSF flow is associated with cognitive deficit in elderly patients (>70 years). Methods: We studied 92 patients admitted to our geriatric unit for non-acute reasons using phase-contrast magnetic resonance imaging (PC-MRI) to calculate their ventricular and spinal CSF flow, and assessed their global cognitive status, memory, executive functions, and praxis. Multivariable regressions with backward selection (criterion p < 0.15) were performed to determine associations between cognitive tests and ventricular and spinal CSF flow, adjusting for depression, anxiety, and cardiovascular risk factors. Results: The cohort comprised 71 women (77%) and 21 (33%) men, aged 84.1 ± 5.2 years (range, 73-96). Net ventricular CSF flow was 52 ± 40 µL/cc (range, 0-210), and net spinal CSF flow was 500 ± 295 µL/cc (range, 0-1420). Ventricular CSF flow was associated with the number of BEC96 figures recognized (ß = 0.18, CI, 0.02-0.33; p = 0.025). Spinal CSF flow was associated with the WAIS Digit Span Backward test (ß = 0.06, CI, 0.01-0.12; p = 0.034), and categoric verbal fluency (ß = 0.53, CI, 0.07-0.98; p = 0.024) and semantic verbal fluency (ß = 0.55, CI, 0.07-1.02; p = 0.024). Conclusion: Patients with lower CSF flow had significantly worse memory, visuo-constructive capacities, and verbal fluency. Alterations in CSF flow could contribute to some of the cognitive deficit observed in patients with AD. Diagnosis and treatment of CSF flow alterations in geriatric patients with neurocognitive disorders could contribute to the prevention of their cognitive decline.

Aqueductal Cerebrospinal Fluid Stroke Volume Flow in a Rodent Model of Chronic Communicating Hydrocephalus: Establishing a Homogeneous Study Population for Cerebrospinal Fluid Dynamics Exploration.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a cause of dementia that can be reversed when treated timely with cerebrospinal fluid (CSF) diversion. Understanding CSF dynamics throughout the development of hydrocephalus is crucial to identify prognostic markers to estimate benefit/risk to shunts. OBJECTIVE: To explore the cerebral aqueduct CSF flow dynamics with phase-contrast magnetic resonance imaging (MRI) in a novel rodent model of adult chronic communicating hydrocephalus. METHODS: Kaolin was injected into the subarachnoid space at the convexities in Sprague-Dawley adult rats. 11.7-T Bruker MRI was used to acquire T2-weighted images for anatomic identification and phase-contrast MRI at the cerebral aqueduct. Aqueductal stroke volume (ASV) results were compared with the ventricular volume (VV) at 15, 60, 90, and 120 days. RESULTS: Significant ventricular enlargement was found in kaolin-injected animals at all times (P < 0.001). ASV differed between cases and controls/shams at every time point (P = 0.004, 0.001, 0.001, and <0.001 at 15, 60, 90, and 120 days, respectively). After correlation between the ASV and the VV, there was a significant correlation at 15 (P = 0.015), 60 (P = 0.001), 90 (P < 0.001), and 120 days. Moreover, there was a significant positive correlation between the VV expansion and the aqueductal CSF stroke between 15 and 60 days. CONCLUSIONS: An initial active phase of rapid ventricular enlargement shows a strong correlation between the expansion of the VV and the increment in the ASV during the first 60 days, followed by a second phase with less ventricular enlargement and heterogeneous behavior in the ASV. Further correlation with complementary data from intracranial pressure and histologic/microstructural brain parenchyma assessments are needed to better understand the ASV variations after 60 days.

Enhanced in vitro model of the CSF dynamics.

BACKGROUND: Fluid dynamics of the craniospinal system are complex and still not completely understood. In vivo flow and pressure measurements of the cerebrospinal fluid (CSF) are limited. Whereas in silico modeling can be an adequate pathway for parameter studies, in vitro modeling of the craniospinal system is essential for testing and evaluation of therapeutic measures associated with innovative implants relating to, for example, normal pressure hydrocephalus and other fluid disorders. Previously-reported in vitro models focused on the investigation of only one hypothesis of the fluid dynamics rather than developing a modular set-up to allow changes in focus of the investigation. The aim of this study is to present an enhanced and validated in vitro model of the CSF system which enables the future embedding of implants, the validation of in silico models or phase-contrast magnetic resonance imaging (PC-MRI) measurements and a variety of sensitivity analyses regarding pathological behavior, such as reduced CSF compliances, higher resistances or altered blood dynamics. METHODS: The in vitro model consists of a ventricular system which is connected via the aqueduct to the cranial and spinal subarachnoid spaces. Two compliance chambers are integrated to cushion the arteriovenous blood flow generated by a cam plate unit enabling the modeling of patient specific flow dynamics. The CSF dynamics are monitored using three cranial pressure sensors and a spinal ultrasound flow meter. Measurements of the in vitro spinal flow were compared to cervical flow data recorded with PC-MRI from nine healthy young volunteers, and pressure measurements were compared to the literature values reported for intracranial pressure (ICP) to validate the newly developed in vitro model. RESULTS: The maximum spinal CSF flow recorded in the in vitro simulation was 133.60 ml/min in the caudal direction and 68.01 ml/min in the cranial direction, whereas the PC-MRI flow data of the subjects showed 122.82 ml/min in the caudal and 77.86 ml/min in the cranial direction. In addition, the mean ICP (in vitro) was 12.68 mmHg and the pressure wave amplitude, 4.86 mmHg, which is in the physiological range. CONCLUSIONS: The in vitro pressure values were in the physiological range. The amplitudes of the flow results were in good agreement with PC-MRI data of young and healthy volunteers. However, the maximum cranial flow in the in vitro model occurred earlier than in the PC-MRI data, which might be due to a lack of an in vitro dynamic compliance. Implementing dynamic compliances and related sensitivity analyses are major aspects of our ongoing research.