Modulating cerebrospinal fluid flow by magnetohydrodynamic force

Hydrodynamics and thermal analysis of a mixed electromagnetohydrodynamic-pressure driven flow for Phan–Thien–Tanner fluids in a microchannel

Ciliary Beating Compartmentalizes Cerebrospinal Fluid Flow in the Brain and Regulates Ventricular Development

Improved cerebrospinal fluid flow measurements using phase contrast balanced steady-state free precession

Quantitative measurement of cerebrospinal fluid (CSF) flow and volume and longitudinal monitoring of CSF dynamics provide insights into the compensatory characteristics of post-stroke CSF. In this study, we compared the MRI pseudo-diffusion index (D*) of live and sacrificed rat brains to confirm the effect of ventricular CSF flow on diffusion signals. We observed the relationship between the CSF peak velocities and D* through Monte Carlo (MC) simulations to further understand the source of D* contrast. We also determined the dominant CSF flow using D* in three directions. Finally, we investigated the dynamic evolutions of ventricular CSF flow and volume in a stroke rat model (n = 8) from preoperative to up to 45 days after surgery and determined the correlation between ventricular CSF volume and flow. MC simulations showed a strong positive correlation between the CSF peak velocity and D* (r = 0.99). The dominant CSF flow variations in the 3D ventricle could be measured using the maximum D* map. A longitudinal positive correlation between ventricular CSF volume and D* was observed in the lateral (r = 0.74) and ventral-third (r = 0.81) ventricles, respectively. The directional D* measurements provide quantitative CSF volume and flow information, which would provide useful insights into ischemic stroke with diffusion MRI.

Respiration plays a key role in the circulation of cerebrospinal fluid (CSF) around the central nervous system. During inspiration increased venous return from the cranium is believed to draw CSF rostrally. However, this mechanism does not explain why CSF has also been observed to move caudally during inspiration. We show that during inspiration decreased intrathoracic pressure draws venous blood from the cranium and lumbar spine towards the thorax. We also show that the abdominal pressure was associated with rostral CSF displacement. However, a caudal shift of cervical CSF was seen with low abdominal pressure and comparably negative intrathoracic pressures. These results suggest that the effects of epidural blood flow within the spinal canal need to be considered, as well as the cranial blood volume balance, to understand respiratory-related CSF flow. These results may prove useful for the treatment of CSF obstructive pathology and understanding the behaviour of intrathecal drug injections. It is accepted that during inspiration, cerebrospinal fluid (CSF) flows rostrally to compensate for decreased cranial blood volume, caused by venous drainage due to negative intrathoracic pressure. However, this mechanism does not explain observations of caudal CSF displacement during inspiration. Determining the drivers of respiratory CSF flow is crucial for understanding the pathophysiology of CSF flow disorders. To quantify the influence of respiration on CSF flow, real-time phase-contrast magnetic resonance imaging (MRI) was used to record CSF and blood flow, while healthy subjects (5:5 M:F, 25-50 years) performed either a brief expiratory or inspiratory effort between breaths. Transverse images were taken perpendicular to the spinal canal in the middle of the C3 and L2 vertebrae. The same manoeuvres were then performed after a nasogastric pressure catheter was used to measure the intrathoracic and abdominal pressures. During expiratory-type manoeuvres that elevated abdominal and intrathoracic pressures, epidural blood flow into the spinal canal increased and CSF was displaced rostrally. With inspiratory manoeuvres, the negative intrathoracic pressure drew venous blood from C3 and L2 towards the thoracic spinal canal, and cervical CSF was displaced both rostrally and caudally, despite the increased venous drainage. Regression analysis showed that rostral displacement of CSF at both C3 (adjusted R2 =0.53; P<0.001) and L2 (adjusted R2 =0.38; P<0.001) were associated with the abdominal pressure. However, with low abdominal pressure and comparably negative intrathoracic pressure, cervical CSF flowed caudally. These findings suggest that changes in both the cranial and spinal pressures need to be considered to understand respiratory CSF flow.

BackgroundSpontaneous subarachnoid hemorrhage (SAH) often results in altered cerebrospinal fluid (CSF) flow and secondary hydrocephalus, yet the mechanisms behind these phenomena remain poorly understood. This study aimed to elucidate the impact of SAH on individual CSF flow patterns and their association with secondary hydrocephalus.MethodsIn patients who had experienced SAH, changes in CSF flow were assessed using cardiac-gated phase-contrast magnetic resonance imaging (PC-MRI) at the Sylvian aqueduct and cranio-cervical junction (CCJ). Within these regions of interest, volumetric CSF flow was determined for every pixel and net CSF flow volume and direction calculated. The presence of acute or chronic hydrocephalus was deemed from ventriculomegaly and need of CSF diversion. For comparison, we included healthy subjects and patients examined for different CSF diseases.ResultsTwenty-four SAH patients were enrolled, revealing a heterogeneous array of CSF flow alterations at the Sylvian aqueduct. The cardiac-cycle-linked CSF net flow in Sylvian aqueduct differed from the traditional figures of ventricular CSF production about 0.30–0.40 mL/min. In 15 out of 24 patients (62.5%), net CSF flow was retrograde from the fourth to the third and lateral ventricles, while it was upward at the cranio-cervical junction in 2 out of 2 patients (100%). The diverse CSF flow metrics did not distinguish between individuals with acute or chronic secondary hydrocephalus. In comparison, 4/4 healthy subjects showed antegrade net CSF flow in the Sylvian aqueduct and net upward CSF flow in CCJ. These net CSF flow measures also showed interindividual variability among other patients with CSF diseases.ConclusionsThere is considerable inter-individual variation in net CSF flow rates following SAH. Net CSF flow in the Sylvian aqueduct differs markedly from the traditional ventricular CSF production rates of 0.30–0.40 mL/min in SAH patients, but less so in healthy subjects. Furthermore, the cardiac-cycle-linked net CSF flow rates in Sylvian aqueduct and CCJ suggest an important role of extra-ventricular CSF production.

The cerebral fluid response to exercise, including the arterial and venous cerebral blood flow (CBF) and cerebrospinal fluid (CSF), currently remains unknown. We used time-resolved phase-contrast magnetic resonance imaging to assess changes in CBF and CSF flow dynamics during moderate-intensity rhythmic handgrip (RHG) exercise in young healthy men and women. Our data demonstrated that RHG increases the cerebral arterial inflow and venous outflow while decreasing the pulsatile CSF flow during RHG. Furthermore, changes in blood stroke volume at the measured arteries, veins, and sinuses and CSF stroke volume at the cerebral aqueduct were positively correlated with each other during RHG. Male and female participants exhibited distinct blood pressure responses to RHG, but their cerebral fluid responses were similar. These results collectively suggest that RHG influences both CBF and CSF flow dynamics in a way that is consistent with the Monro-Kellie hypothesis to maintain intracranial volume-pressure homeostasis in young healthy adults. Cerebral blood flow (CBF) increases during exercise, but its impact on cerebrospinal fluid (CSF) flow remains unknown. This study investigated CBF and CSF flow dynamics during moderate-intensity rhythmic handgrip (RHG) exercise in young healthy men and women. Twenty-six participants (12 women) underwent the RHG and resting control conditions in random order. Participants performed 3 sets of RHG, during which cine phase-contrast magnetic resonance imaging (PC-MRI) was performed to measure blood stroke volume (SV) and flow rate in the internal carotid (ICA) and vertebral (VA) arteries, the internal jugular vein (IJV), the superior sagittal (SSS) and straight sinuses (SRS), and CSF SV and flow rate in the cerebral aqueduct of Sylvius. Blood pressure, end-tidal CO2 (EtCO2 ), heart rate (HR), and respiratory rate were simultaneously measured during cine PC-MRI scans. Compared with control conditions, RHG showed significant elevations of HR, mean arterial pressure, and respiratory rate with a mild reduction of EtCO2 (all P < 0.05). RHG decreased blood SV in the measured arteries, veins, and sinuses and CSF SV in the aqueduct (all P < 0.05). Conversely, RHG increased blood flow in the ICA, VA, and IJV (all P < 0.05). At the aqueduct, RHG decreased the absolute CSF flow rate (P = 0.0307), which was calculated as a sum of the caudal and cranial CSF flow rates. Change in the ICA SV was positively correlated with changes in the IJV, SSS, SRS, and aqueductal SV during RHG (all P < 0.05). These findings demonstrate a close coupling between the CBF and CSF flow dynamics during RHG in young healthy adults.

Spontaneous intracranial hypotension (SIH) is characterized by orthostatic headache. Typical abnormal magnetic resonance imaging (MRI) findings have been considered to be the sine qua non of SIH, but a sizeable minority of patients has normal results using conventional MRI. The purpose of this study was to evaluate the difference in cerebrospinal fluid (CSF) flow dynamics between patients and healthy people using cine phase contrast (PC) MRI, and to assess the CSF flow dynamics in patients before and after treatment. From November of 2007 to December of 2012, twenty patients with SIH (10 men and 10 women, mean age=40.9±7.77 years) and 31 age- and gender- matched healthy subjects (15 men and 16 women, mean age=46.3±7.53 years) were enrolled in this retrospective study. Cine PC MRI was performed on the patients and on the healthy subjects to measure the CSF flow in cerebral aqueduct. Patients underwent repeated cine PC MRI at 24 hours and at one month after treatment respectively. Five parameters including peak positive and negative velocity, average flow, and average positive and negative flow were recorded to evaluate their differences. Seventeen patients (85%) received epidural blood patching (EBP) owing to the failure of conservative treatment. All patients experienced resolution of symptoms after treatment. Before treatment, the patients had a significantly lower average CSF flow than the healthy subjects (p＜0.001). The average CSF flow was elevated in patients with SIH at 24 hours after treatment and was significantly increased one month after treatment (p=0.003). By establishment of the receiver operating characteristic (ROC) curve, the best cutoff value for the average CSF flow was determined to be 14.0μl/beat, while the sensitivity and specificity were determined to be 90.3% and 72.2%, respectively. Patients with SIH showed lower CSF flow compared to healthy subjects, but this decreased CSF flow was shown by cine PC MRI to be gradually recovered after treatment. This study provides evidence that cine PC MRI is useful for assessing the dynamic changes of CSF flow in the cerebral aqueduct noninvasively and for demonstrating the effectiveness of treatment in patients with SIH reliably.

Objective To evaluate the application of phase-contrast cine magnetic resonance imaging (MRI) in endoscopic aqueductoplasty for patients with obstructive hydrocephalus.Methods The clinical diagnosis of hydrocephalus due to aqueduct obstruction in 23 patients was confirmed by phase -contrast cine MRI examination.The patients were treated with endoscopic aqueductoplasty.MRI was repeated during follow- up period.The cerebrospinal fluid (CSF) flow velocity in aqueduct was measured to determine whether the aqueduct was obstructed.Results The Results of phase - contrast cine MRI examinations indicated that there was no CSF flow in aqueduct in any patient.Aqueductoplasty was successfully performed in all patients.after one week,the Results of phase - contrast cine MRI examinations showed an average CSF flow velocity of ( 4.74 ± 1.77 ) cm/s.During follow - up period,intracranial hypertension recurred in two patients in whom CSF flow was not seen inside the aqueduct by phase - contrast cine MRI scan and the aqueduct re - occlusion was revealed by endoscopic exploration.Conclusions By measuring CSF flow velocity,phase - contrast cine MRI could accurately identify whether the aqueduct is obstructed.It should play an important role in the diagnosis of obstructive hydrocephalus and evaluation of the effectiveness of aqueductoplasty,and it could be used for follow -up evaluation as well. Key words: Neuroendoscope ; Hydrocephalus ; Aqueductoplasty ; Phase - contrast eine MRI ; Cerebrospinal fluid flow ; Dynamics ;

Objective To compar the cerebrospinal fluid (CSF) flow between empty sella syndrome (ESS) and normal volunteer in the cerebral aqueduct with MRI in phase contrast cine mode. Methods Thirty-eight ESS patients (ESS group) and 38 normal volunteers (control group ) were involved in this study.The aqueduct CSF flow image was positioned perpendicularly to the midbrain aqueduct at the middle sagittal T1WI or T2WI image. The waveforms were analyzed for the flow direction, flow rate, flow volume rate and cardiac cycle. Results The CSF flow of the aqueduct in control group and ESS group had two directions which was downward flow during the systolic period and upward flow during the diastolic period of the cardiac cycle. The.systolic period downward peak flow rate, diastolic period upward peak flow rate, mean downward flow rate, mean upward flow rate and mean flow rate were (5.231 ± 0.262), (4.902 ± 0.281 ),(3.083 ± 0.191 ), (3.032 ± 0.151 ), (3.151 ± 0.162) cm/s in control group, and (6.244 ± 0.356), (6.091 ±0.430), (3.916 ± 0.196), (3.812 ± 0.273 ), (3.690 ± 0.291 ) cm/s in ESS group respectively,and there was no significant difference between the two groups ( P ＞ 0.05 ). The systolic period downward peak flow volume rate, diastolic period upward peak flow volume rate, mean downward flow volume rate,mean upward flow volume rate and mean flow volume rate were (0.050 ± 0.003 ), (0.050 ± 0.004), (0.030± 0.002), (0.031 ±0.002), (0.030 ± 0.003 ), ( 0.004 ± 0.001 )ml/s in control group, and (0.058 ± 0.003 ), (0.063 ± 0.005),(0.039 ±0.002), (0.038 ±0.003), (0.038 ±0.003), (0.004 ±0.001) ml/s in ESS group respectively,and there was no significant difference between the two groups(P ＞ 0.05 ). The correspond cardiac cycle of systolic period downward peak flow rate, correspond cardiac cycle of diastolic period upward peak flow rate, mean cardiac cycle were (40.890 ± 37.096), (501.026 ± 19.374), (719.511 ± 14.946) ms in control group,and (35.921 ±6.218), (531.553 ± 16.764), (770.700 ±21.579) ms in ESS group,and there was no significant difference between the two groups (P ＞ 0.05 ). Conclusion Part of CSF flows into the area of saddle in ESS patients, but it has no effect on CSF indexes in area of cerebral aqueduct. Key words: Cerebral aqueduct; Magnetic resonance imaging; Empty sella syndrome; Phasecontrast; Cerebrospinal fluid

<h3>Objective:</h3> To investigate the relationship between sleep quality and cerebrospinal fluid (CSF) flow in individuals with Parkinson’s disease (PD). <h3>Background:</h3> Previous studies have emphasized the role of CSF circulation in the clearance of brain waste products, with recent findings demonstrating increased CSF flow during sleep. CSF circulation impairment could play a major role in neurodegenerative proteinopathies such as PD, a commonly encountered feature of which is disrupted sleep. Here, we assessed the relationship between patient-reported sleep quality and imaging assays of CSF flow. <h3>Design/Methods:</h3> Imaging and clinical assessments were completed in 23 PD participants aged 56 to 79 (M_age=66.70; 16 males). The Montreal Cognitive Assessment (MoCA) and Unified Parkinson’s Disease Rating Scale (UPDRS) were administered; subjective sleep measurements were recorded using the Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) items from the Patient-Reported Outcomes Measurement Information System (PROMIS) scale. MRI phase contrast sequences quantified CSF flux (mL/min) via the cerebral aqueduct. Net CSF flow was defined as the difference between caudal and cranial flow, whereas absolute flow was calculated as the sum of total caudal and cranial flow per cardiac cycle. <h3>Results:</h3> Participants had mean MoCA scores of 24.17 (range 13–30) and UPDRS scores of 30.70 (7–59). PROMIS scores for SD and SRI were 20.14 (9–32) and 15.00 (8–24), respectively. Mean CSF measurements were 0.25 mL/min (−0.29–0.88) for net and 8.11 mL/min (3.55–16.34) for absolute flow. Higher SRI scores correlated with greater net CSF flow while awake (r=0.531, p=0.023). Additionally, SRI and age explained 73.4% of variation in absolute CSF flow in a linear regression model (F(3,15)=24.5, p&lt;0.0001). <h3>Conclusions:</h3> Self-reported sleep impairment is associated with increased CSF flow in awake individuals with PD. This study is the first to link patient-reported measures of sleep with alterations to CSF flow. These data support novel outcomes for clinical studies that improve sleep. <b>Disclosure:</b> Mr. Ponzo has nothing to disclose. Dr. Hett has nothing to disclose. Mr. Eisma has nothing to disclose. Mr. Elenberger has nothing to disclose. Mr. Song has nothing to disclose. An immediate family member of Dr. McKnight has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Deciphera. The institution of Dr. McKnight has received research support from RSNA. Dr. Considine has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MDisrupt. Dr. Considine has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Park Dietz &amp; Associates. The institution of Dr. Considine has received research support from NIH. The institution of Dr. Considine has received research support from DoD. The institution of Dr. Considine has received research support from Acadia Pharmaceuticals. Manus Donahue, 13717 has received personal compensation for serving as an employee of Alterity. Manus Donahue, 13717 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alterity. Manus Donahue, 13717 has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Manus Donahue, 13717 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Global Blood Therapeutics. Manus Donahue, 13717 has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. The institution of Manus Donahue, 13717 has received research support from National Institutes of Health. Dr. Claassen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva Neuroscience. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark . The institution of Dr. Claassen has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Alterity. Dr. Claassen has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva Neuroscience. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for HD Insights. The institution of Dr. Claassen has received research support from NIH. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from HDSA. The institution of Dr. Claassen has received research support from Department of Defense. The institution of Dr. Claassen has received research support from Griffin Family Foundation. The institution of Dr. Claassen has received research support from Neurocrine. The institution of Dr. Claassen has received research support from Vaccinex. The institution of Dr. Claassen has received research support from AbbVie. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from Genentech/ Roche. The institution of Dr. Claassen has received research support from Prilenia. The institution of Dr. Claassen has received research support from Neurocrine/ HSG.

BackgroundThe cardiac and respiratory cycles have been suggested as major drivers of cerebrospinal fluid(CSF) flow. The glymphatic system, one of the mechanisms for the clearance of amyloid‐beta and tau proteins, relies heavily on the movement(flow) of the CSF, and thus, investigating the forces that modulate the CSF flow is essential for understanding the glymphatic flux. Because breathing is trainable through exercise and self‐directed methods, various breathing methods may enhance the CSF flow.MethodReal‐time phase‐contrast MRI(pc‐MRI) was used to measure the CSF flow at the foramen magnum on a 3T. Fast resting‐state fMRI(rsfMRI;TR400ms) was conducted on a compact 3T. Under an IRB‐approved protocol, participants were instructed to breathe slowly and deeply, and subsequently switch to their spontaneous breathing. For rsfMRI data preprocessing, we performed motion correction, skull stripping, spatial smoothing(4mm), temporal filtering(0.01 to 0.1Hz), and linear and quadratic temporal trends removal. fMRI time courses were then normalized to Z‐score at each voxel before being averaged. On the pcMRI, the phase was summed in a CSF region‐of‐interest and plotted vs time. Additionally, we confirmed for possible confounding effects such as head motion or motion‐induced susceptibility changes.ResultrsfMRI findings showed that deep breathing promoted large oscillations in the CSF flow in the ventricles, while spontaneous breathing did not(Figure 1). Additionally, deep breathing resulted in large oscillations in lobar cortical regions. Similar results were observed in the pcMRI, with larger CSF velocity through the foramen magnum during the deep breathing compared to the spontaneous breathing(Figure 2A‐B). The cumulative summation result showed that the volume of CSF flow was increased during deep breathing(Figure 2C).ConclusionThis study provides new evidence that slow and deep breathing promotes CSF flow and global brain BOLD signal, which may be useful in promoting circulation in the brain. The study’s findings also open new avenues for research in the field of neurovascular coupling and mechanisms associated with glymphatic clearance. As hampered CSF flow and/or worsen glymphatic clearance have been shown to associate with pathological aging and dementia, including Alzheimer’s disease and Parkinson’s disease, future research is needed explore the potential of breathing training methods as a non‐pharmacological intervention to support brain health.

Advances in magnetic resonance (MR) imaging techniques enable the accurate measurements of cerebrospinal fluid (CSF) flow in the human brain. In addition, image reconstruction tools facilitate the collection of patient-specific brain geometry data such as the exact dimensions of the ventricular and subarachnoidal spaces (SAS) as well as the computer-aided reconstruction of the CSF-filled spaces. The solution of the conservation of CSF mass and momentum balances over a finite computational mesh obtained from the MR images predict the patients' CSF flow and pressure field. Advanced image reconstruction tools used in conjunction with first principles of fluid mechanics allow an accurate verification of the CSF flow patters for individual patients. This paper presents a detailed analysis of pulsatile CSF flow and pressure dynamics in a normal and hydrocephalic patient. Experimental CSF flow measurements and computational results of flow and pressure fields in the ventricular system, the SAS and brain parenchyma are presented. The pulsating CSF motion is explored in normal and pathological conditions of communicating hydrocephalus. This paper predicts small transmantle pressure differences between lateral ventricles and SASs (approximately 10 Pa). The transmantle pressure between ventricles and SAS remains small even in the hydrocephalic patient (approximately 30 Pa), but the ICP pulsatility increases by a factor of four. The computational fluid dynamics (CFD) results of the predicted CSF flow velocities are in good agreement with Cine MRI measurements. Differences between the predicted and observed CSF flow velocities in the prepontine area point towards complex brain-CSF interactions. The paper presents the complete computational model to predict the pulsatile CSF flow in the cranial cavity.

SPAMM, Cine Phase Contrast Imaging and Fast Spin-echo T2-weighted Imaging in the Study of Intracranial Cerebrospinal Fluid (CSF) Flow

BackgroundSeveral central nervous system diseases are associated with disturbed cerebrospinal fluid (CSF) flow patterns and have typically been characterized in vivo by phase-contrast magnetic resonance imaging (MRI). This technique is, however, limited by its applicability in space and time. Phase-contrast MRI has yet to be compared directly with CSF tracer enhanced imaging, which can be considered gold standard for assessing long-term CSF flow dynamics within the intracranial compartment.MethodsHere, we studied patients with various CSF disorders and compared MRI biomarkers of CSF space anatomy and phase-contrast MRI at level of the aqueduct and cranio-cervical junction with dynamic intrathecal contrast-enhanced MRI using the contrast agent gadobutrol as CSF tracer. Tracer enrichment of cerebral ventricles was graded 0–4 by visual assessment. An intracranial pressure (ICP) score was used as surrogate marker of intracranial compliance.ResultsThe study included 94 patients and disclosed marked variation of CSF flow measures across disease categories. The grade of supra-aqueductal reflux of tracer varied, with strong reflux (grades 3–4) in half of patients. Ventricular tracer reflux correlated with stroke volume and aqueductal CSF pressure gradient. CSF flow in the cerebral aqueduct was retrograde (from 4th to 3rd ventricle) in one third of patients, with estimated CSF net flow volume about 1.0 L/24 h. In the cranio-cervical junction, net flow was cranially directed in 78% patients, with estimated CSF net flow volume about 4.7 L/24 h.ConclusionsThe present observations provide in vivo quantitative evidence for substantial variation in direction and magnitude of CSF flow, with re-direction of aqueductal flow in communicating hydrocephalus, and significant extra-cranial CSF production. The grading of ventricular reflux of tracer shows promise as a clinical useful method to assess CSF flow pattern disturbances in patients.Graphic abstract