Cerebrospinal Fluid Flow Research Articles

Dysregulated Neurofluid Coupling as a New Noninvasive Biomarker for Primary Progressive Aphasia.

Accumulation of pathological tau is one of the primary causes of Primary Progressive Aphasia (PPA). The glymphatic system is crucial for removing metabolite waste from the brain whereas impairments in glymphatic clearance in PPA are poorly understood. Thus, this study aims to investigate the role of dysregulated macroscopic cerebrospinal fluid (CSF) movement in PPA. Fifty-six PPA individuals and ninety-four healthy controls were included in our analysis after excluding those with excessive head motions during the scan. The coupling strength between blood-oxygen-level-dependent (BOLD) signals in the gray matter and CSF flow was calculated using Pearson correlation and compared between the groups. Its associations with clinical characteristics including scores from Clinical Dementia Rating (CDR), Mini-Mental State Exam, Geriatric Depression Scale and with morphological measures in the hippocampus and entorhinal cortex were examined. PPA subjects exhibited weaker global BOLD-CSF coupling compared to HCs, indicating impairments in glymphatic function in the patients (p = 0.01). In the PPA but not HC group, global BOLD-CSF coupling correlated with the CDR scores (p = 0.04) and hippocampal volume (p = 0.009). The observed decoupling between global brain activity and CSF flow and its association with symptomatology and brain structural changes in PPA converges with previous reports on the same measure in other neurodegenerative diseases. These findings support the potential role of global BOLD-CSF coupling as a noninvasive marker for glymphatic dysregulation in PPA.

Abstract Su1201: Alteration in cerebrospinal fluid flow in out-of-hospital cardiac arrest patients who underwent target temperature management.

Background: Various parameters of cerebrospinal fluid (CSF) flow measured through magnetic resonance imaging (MRI) flowmetry are utilized to assess the progression of certain diseases. Our study evaluated changes in CSF flow using MRI flowmetry in survivors of out-of-hospital cardiac arrest (OHCA) who underwent target temperature management (TTM). Methods: This prospective observational cohort study was conducted from May 2023 to April 2024 at a single center. We performed Wilcoxon signed-rank tests to compare maximum velocity (V max ), stroke volume (SV), maximum flow (flow max ), and stroke distance measured immediately after return of spontaneous circulation (ROSC) with those measured at 72 h after ROSC. Results: Of the 20 patients enrolled, 7(35.0%), 1(5.0%), 2(10.0%), 5(25.0%) and 5(25.0%) patients had CPC scores of 1, 2, 3, 4, and 5, respectively. V max , SV, flow max , stroke distance measured immediately after ROSC were 3.41 (2.03~4.96), 14.00 (4.00~23.38), 0.09 (0.06~0.22), -0.07 (-0.17~0.05), respectively. V max , SV, flow max , stroke distance measured at 72h after ROSC were 5.26 (2.76~9.28), 24.00 (10.38~42.25), 0.14 (0.08~0.31), -0.07 (-0.18~0.03), respectively. Although V max , SV, and flow max measured at 72 h after ROSC were statistically significantly higher compared to those measured immediately after ROSC (p = 0.002, 0.02, 0.002), there was no significant difference between the stroke distances measured immediately after ROSC and at 72 h after ROSC (p = 0.43). Additionally, the caudocranial direction of CSF flow was observed in 13 (65.0%) patients immediately after ROSC, and in 14 (70.0%) patients 72h after ROSC. Conclusion: This study demonstrated that alterations in cerebrospinal fluid flow were observed in OHCA patients. However, Further studies are needed to determine whether there are differences in alteration in CSF flow based on neurological prognosis.

Global brain activity and its coupling with cerebrospinal fluid flow is related to tau pathology.

Factors responsible for the deposition of pathological tau in the brain are incompletely understood. This study links macroscale tau deposition in the human brain to cerebrospinal fluid (CSF) flow dynamics using resting-state functional magnetic resonance imaging (rsfMRI). Low-frequency (<0.1Hz) resting-state global brain activity is coupled with CSF flow and potentially reflects CSF dynamics-related clearance. We examined the correlation between rsfMRI measures of CSF inflow and global activity (gBOLD-CSF coupling) as a predictor, interacting with amyloid beta (Aβ), of tau and cortical thickness (dependent variables) across Alzheimer's Disease Neuroimaging Initiative (ADNI) participants from cognitively unimpaired through mild cognitive impairment (MCI) and Alzheimer's disease (AD). Tau deposition in Aβ+ participants, accompanied by cortical thinning and cognitive decline, is associated with decreased gBOLD-CSF coupling. Tau mediates the relationship between coupling and thickness. Findings suggest that resting-state global brain activity and CSF movements comodulate Alzheimer's tau deposition, presumably related to CSF clearance. A non-invasive functional magnetic resonance imaging (fMRI) assessment of a CSF clearance-related process is carried out. Global brain activity is coupled with CSF inflow in human fMRI during resting state. Global fMRI-CSF coupling is correlated with tau in Alzheimer's disease (AD). This coupling measure is also associated with cortical thickness, mediated by tau.

Directional flow in perivascular networks: mixed finite elements for reduced-dimensional models on graphs

Flow of cerebrospinal fluid through perivascular pathways in and around the brain may play a crucial role in brain metabolite clearance. While the driving forces of such flows remain enigmatic, experiments have shown that pulsatility is central. In this work, we present a novel network model for simulating pulsatile fluid flow in perivascular networks, taking the form of a system of Stokes–Brinkman equations posed over a perivascular graph. We apply this model to study physiological questions concerning the mechanisms governing perivascular fluid flow in branching vascular networks. Notably, our findings reveal that even long wavelength arterial pulsations can induce directional flow in asymmetric, branching perivascular networks. In addition, we establish fundamental mathematical and numerical properties of these Stokes–Brinkman network models, with particular attention to increasing graph order and complexity. By introducing weighted norms, we show the well-posedness and stability of primal and dual variational formulations of these equations, and that of mixed finite element discretizations.

CSF flow measurement in the mesencephalic aqueduct using 2D cine phase-contrast MRI in dogs with communicating internal hydrocephalus, ventriculomegaly, and physiologic ventricular spaces

BackgroundBrachycephalic dogs are overrepresented with ventricular enlargement. Cerebrospinal fluid (CSF) flow dynamics are not completely understood. MRI techniques have been used for the visualization of CSF dynamics including phase-contrast imaging.ObjectivesThis study aimed to determine a causality between CSF flow and ventriculomegaly or hydrocephalus and to compare CSF flow dynamics among dogs with ventriculomegaly, internal hydrocephalus, and physiologic ventricles.AnimalsA total of 51 client-owned dogs were included in the study.MethodsMagnetic resonance imaging (MRI)-based FLASH sequences and phase-contrast images of the brain were obtained, and the ROI was placed at the level of the mesencephalic aqueduct. ECG monitoring was performed parallel to MRI acquisition. Evaluation of flow diagrams and processing of phase-contrast images were performed using commercially available software (Argus VA80A, Siemens AG Healthcare Sector, Erlangen, Germany). Dogs were divided into three groups: Group 1 consisted of brachycephalic dogs with ventriculomegaly (group 1A) or internal hydrocephalus (group 1B), group 2 consisted of brachycephalic dogs with normal ventricles, and group 3 consisted of meso- to dolichocephalic dogs with normal ventricles.ResultsGroup 1 had a higher median Vrost (4.32 cm/s; CI: 2.94–6.33 cm/s) and Vcaud (−6.1 cm/s, CI: 3.99–9.33 cm/s) than group 2 (Vrost: 1.99 cm/s; CI 1.43–2.78 cm/s; Vcaud: 2.91 cm/s, CI: 2.01–4.21 cm/s; p = 0.008; p = 0.03) and group 3 (Vrost:1.85 cm/s, CI: 1.31–2.60 cm/s; Vcaud − 2.46 cm/s, CI 1.68–3.58 cm/s; p = 0.01; p = 0.02). The median Volcaud of group 1 (−0.23 mL/min, CI: 0.13–0.42 mL/min) was higher than that of group 2 (−0.09 mL/min, CI: 0.05 mL/min and 0.15 mL/min) (p = 0.03). Groups 1A and 1B did not differ in Vcaud, Vrost, Volcaud, and Volrost. Group 1A and 1B showed a higher median Vrost (4.01 cm/s, CI: 2.30–7.05 cm/s; 5.94 cm/s, CI: 2.16–7.88 cm/s) than group 2 (1.85 cm/s, CI: 1.24–2.80 cm/s.) (p = 0.03; p = 0.004).Conclusion and clinical importanceIncreased CSF flow velocities in rostral and caudal directions are present in dogs with ventriculomegaly and internal hydrocephalus compared to normal controls.

Visual assessment of cerebrospinal fluid flow dynamics using 3D T2-weighted SPACE sequence-based classification system.

Flow-related signal void artifacts can be visualized on the T2-weighted (T2W) three-dimensional sampling perfection with application-optimized contrast (3D-SPACE) sequence. Flow void artifacts in the cerebral aqueduct and the fourth ventricle can provide information about cerebrospinal fluid (CSF) flow dynamics. In this study, we aimed to test the performance of the T2W 3D-SPACE sequence in assessing the CSF flow in the aqueduct and/or fourth ventricle. A total of 137 patients (age range = 3-89 years) who underwent CSF flow study were included. The amount of signal loss on T2W 3D-SPACE due to flow in the aqueduct and fourth ventricle was assessed and graded using a 4-point scale of 0 (absence of flow void) to 3 (signal void filling the aqueduct and entire fourth ventricle). A correlation was then sought between the quantitative values obtained by phase-contrast magnetic resonance imaging (PC-MRI) and the amount of signal void in the 3D-SPACE sequence. At the aqueduct level, there was a statistically significant difference in the forward flow velocity and the flow volume among different grades (all P < 0.001). In the grade 3 group, CSF peak systolic flow velocity and mean flow volume were found to be significantly higher than in the other grades (P < 0.001). The mean aqueduct area in the grade 0 group was found to be significantly different from that in the other classes (P < 0.001). The amount of signal loss in the fourth ventricle observed on T2W 3D-SPACE is correlated with the peak systolic velocity and flow volume measured quantitatively in PC-MRI.

The periaxonal space as a conduit for cerebrospinal fluid flow to peripheral organs

Mechanisms controlling the movement of the cerebrospinal fluid (CSF) toward peripheral nerves are poorly characterized. We found that, in addition to the foramina Magendie and Luschka for CSF flow toward the subarachnoid space and glymphatic system, CSF outflow could also occur along periaxonal spaces (termed "PAS pathway") from the spinal cord to peripheral organs, such as the liver and pancreas. When interrogating the latter route, we found that serotonin, acting through 5-HT2B receptors expressed in ependymocytes that line the central canal, triggered Ca2+ signals to induce polymerization of F-actin, a cytoskeletal protein, to reduce the volume of ependymal cells. This paralleled an increased rate of PAS-mediated CSF redistribution toward peripheral organs. In the liver, CSF was received by hepatic stellate cells. CSF efflux toward peripheral organs through the PAS pathway represents a mechanism dynamically connecting the nervous system with the periphery. Our findings are compatible with the traditional theory of CSF efflux into the glymphatic system to clear metabolic waste from the cerebral parenchyma. Thus, we extend the knowledge of CSF flow and expand the understanding of connectivity between the CNS and peripheral organs.

Obstructive hydrocephalus of uncommon etiology: case report and neurosurgical management of aqueductal web presenting in adolescence.

Aqueductal webs are a rare cause of obstructive hydrocephalus. Accurate diagnosis and intervention can prevent neurological complications. Herein, we describe a case of a child presenting with headaches and vomiting. Magnetic resonance imaging (MRI) revealed obstructive tri-ventricular hydrocephalus caused by an aqueductal web. Endoscopic third ventriculostomy (ETV) was successfully performed to restore cerebrospinal fluid (CSF) flow. This case underscores the importance of phase-contrast and T2-weighted cinematic magnetic resonance imaging of cerebrospinal fluid flow for diagnosis of aqueductal webs. These modalities provide valuable insights into CSF dynamics and guidance of appropriate neurosurgical intervention.

Artificial gravity: an effective countermeasure for microgravity-induced headward fluid shift?

Long-duration spaceflight is associated with pathophysiological changes in the intracranial compartment hypothetically linked to microgravity-induced headward fluid shift. This study aimed to determine whether daily artificial gravity (AG) sessions can mitigate these effects, supporting its application as a countermeasure to spaceflight. Twenty-four healthy adult volunteers (16 men) were exposed to 60 days of 6° head-down tilt bed rest (HDTBR) as a ground-based analog of chronic headward fluid shift. Subjects were divided equally into three groups: no AG (control), daily 30-min intermittent AG (iAG), and daily 30-min continuous (cAG). Internal carotid artery (ICA) stroke volume (ICASV), ICA resistive index (ICARI), ICA flow rate (ICAFR), aqueductal cerebral spinal fluid flow velocity (CSFV), and intracranial volumetrics were quantified at 3 T. MRI was performed at baseline, 14 and 52 days into HDTBR, and 3 days after HDTBR (recovery). A mixed model approach was used with intervention and time as the fixed effect factors and the subject as the random effect factor. Compared with baseline, HDTBR was characterized by expansion of lateral ventricular, white matter, gray matter, and brain + total intracranial cerebral spinal fluid volumes, increased CSFv, decreased ICASV, and decreased ICAFR by 52 days into HBTBR (All Ps < 0.05). ICARI was only increased 14 days into HDTBR (P < 0.05). Neither iAG nor cAG significantly affected measurements compared with HDTBR alone, indicating that 30 min of daily exposure was insufficient to mitigate the intracranial effects of headward fluid shift. Greater AG session exposure time, gravitational force, or both are suggested for future countermeasure research.NEW & NOTEWORTHY Brief exposure to continuous or intermittent artificial gravity via short-arm centrifugation was insufficient in mitigating the intracranial pathophysiological effects of the headward fluid shift simulated during head-down tilt bed rest (HDTBR). Our results suggest that greater centrifugation session duration, gravitational force, or both may be required to prevent the development of spaceflight-associated neuro-ocular syndrome and should be considered in future ground-based countermeasure studies.

Phase-contrast MRI analysis of cerebral blood and CSF flow dynamic interactions

BackgroundFollowing the Monro-Kellie doctrine, the Cerebral Blood Volume Changes (CB_VC) should be mirrored by the Cerebrospinal Fluid Volume Changes (CSF_VC) at the spinal canal. Cervical level is often chosen to estimate CB_VC during the cardiac cycle. However, due to the heterogeneity in the anatomy of extracranial internal jugular veins and their high compliance, we hypothesize that the intracranial level could be a better choice to investigate blood and cerebrospinal fluid (CSF) interactions. This study aims to determine which level, intracranial or extracranial, is more suitable for measuring arterial and venous flows to study cerebral blood and CSF dynamics interactions.MethodsThe spinal CSF and cerebral blood flow measured at intracranial and extracranial levels were quantified using cine phase-contrast magnetic resonance imaging (PC-MRI) in 38 healthy young adults. Subsequently, CSF_VC and CB_VC were calculated, and by linear regression analysis (R2 and slope), the relationship between CB_VC at both levels and the spinal CSF_VC was compared. The differences between extracranial and intracranial measurements were assessed using either a paired Student’s t-test or Wilcoxon’s test, depending on the normality of the data distribution.ResultsThe CB_VC amplitude was significantly higher at the extracranial level (0.89 ± 0.28 ml/CC) compared to the intracranial level (0.73 ± 0.19 ml/CC; p < 0.001). CSF oscillations through the spinal canal do not completely balance blood volume changes. The R2 and the slope values obtained from the linear regression analysis between CSF and blood flows were significantly higher in magnitude for the intracranial CB_VC (R2: 0.82 ± 0.16; slope: − 0.74 ± 0.19) compared to the extracranial CB_VC (R2: 0.47 ± 0.37; slope: -0.36 ± 0.33; p < 0.001). Interestingly, extracranial CB_VC showed a greater variability compared to intracranial CB_VC.ConclusionOur results confirmed that CSF does not completely and instantaneously balance cerebral blood expansion during the cardiac cycle. Nevertheless, the resting volume is very small compared to the total intracranial volume. To our knowledge, this study is the first to demonstrate these findings using cerebral blood flow measured intracranially below the Circle of Willis. Additionally, our findings show that cerebral arterial and venous flow dynamic measurements during the cardiac cycle obtained by PC-MRI at the intracranial plane strongly correlate with CSF oscillations measured in the spinal canal. Therefore, the intracranial vascular plane is more relevant for analyzing cerebral blood and CSF interactions during the cardiac cycle compared to measurements taken at the cervical vascular level.

Impairment of spinal CSF flow precedes immune cell infiltration in an active EAE model

Accumulation of immune cells and proteins in the subarachnoid space (SAS) is found during multiple sclerosis and in the animal model experimental autoimmune encephalomyelitis (EAE). Whether the flow of cerebrospinal fluid (CSF) along the SAS of the spinal cord is impacted is yet unknown. Combining intravital near-infrared (NIR) imaging with histopathological analyses, we observed a significantly impaired bulk flow of CSF tracers within the SAS of the spinal cord prior to EAE onset, which persisted until peak stage and was only partially recovered during chronic disease. The impairment of spinal CSF flow coincided with the appearance of fibrin aggregates in the SAS, however, it preceded immune cell infiltration and breakdown of the glia limitans superficialis. Conversely, cranial CSF efflux to cervical lymph nodes was not altered during the disease course. Our study highlights an early and persistent impairment of spinal CSF flow and suggests it as a sensitive imaging biomarker for pathological changes within the leptomeninges.

Significant individual variation in cardiac-cycle-linked cerebrospinal fluid production following subarachnoid hemorrhage

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.

A Prospective Study of CSF Flow Dynamics Across Foramen Magnum in Adult Chiari Malformation/Syringomyelia Complex and its Clinical Correlation with Outcomes after Surgery

Abstract Introduction Chiari I malformation refers to cerebellar tonsillar descent below the foramen magnum and is frequently associated with syringomyelia. Prior cerebrospinal fluid (CSF) flow studies correlated the clinical severity of these lesions with general flow velocity or bulk flow at the foramen magnum; however, these techniques have not assessed the effect on surgical outcomes. The study aims to present clinical and radiological factors and CSF flow parameters (pre- and postoperative) that affect the surgical outcome. Materials and Methods The institutional ethics committee approved the study. We collected the prospective clinical data, including pre- and postoperative symptoms. Functional grades were determined along with the change in clinical improvement based on clinical examination notes, the change in functional grade was calculated, and the radiologic data were analyzed according to the degree of clinical improvement. The surgical procedure included suboccipital bony decompression with duroplasty. Patients were followed up at 1 month, 3 months, and 1 year. Results There were a total of 25 patients. The mean age of the patients was 45.52 ± 13.37 years, with 40% being males and 60% being females. After the surgery, there was a significant increase in the anterior and posterior CSF flows at the foramen magnum. Most had a resolution in the headache and sensory symptoms, while the lower cranial nerve and motor symptoms had a minor resolution at follow-up. Age, sex, and headache do not correlate with the outcome or syrinx improvement. Motor power in the lower limb (preintervention) and syrinx shape (preintervention) were significantly associated with the variable “anterior flow at the foramen magnum” (preintervention; p &lt; 0.05). Average flow, cervicomedullary angle (postintervention), sensory symptom progression, and CSF flow change anterior to the foramen magnum were significantly associated with the variable “anterior flow at the foramen magnum” (postintervention; p &lt; 0.05). Conclusion Even after surgery, persistent foramen magnum CSF outflow obstruction has a robust negative correlation with the outcome. The Chiari outcome predictability index has shown a significant correlation with patient outcomes and can be used to inform patients about the expected outcome. The results of the present study will be helpful in stratifying patients according to their desired outcomes.

The spine-brain axis: is spinal anatomy associated with brain volume?

First small sample studies indicate that disturbances of spinal morphology may impair craniospinal flow of cerebrospinal fluid and result in neurodegeneration. The aim of this study was to evaluate the association of cervical spinal canal width and scoliosis with grey matter, white matter, ventricular and white matter hyperintensity volumes of the brain in a large study sample. Four hundred participants underwent whole-body 3 T magnetic resonance imaging. Grey matter, white matter and ventricular volumes were quantified using a warp-based automated brain volumetric approach. Spinal canal diameters were measured manually at the cervical vertebrae 2/3 level. Scoliosis was evaluated using manual measurements of the Cobb angle. Linear binomial regression analyses of measures of brain volumes and spine anatomy were performed while adjusting for age, sex, hypertension, cholesterol levels, body mass index, smoking and alcohol consumption. Three hundred eighty-three participants were included [57% male; age: 56.3 (±9.2) years]. After adjustment, smaller spinal canal width at the cervical vertebrae 2/3 level was associated with lower grey matter (P = 0.034), lower white matter (P = 0.012) and higher ventricular (P = 0.006, inverse association) volume. Participants with scoliosis had lower grey matter (P = 0.005), lower white matter (P = 0.011) and larger brain ventricular (P = 0.003) volumes than participants without scoliosis. However, these associations were attenuated after adjustment. Spinal canal width at the cervical vertebrae 2/3 level and scoliosis were not associated with white matter hyperintensity volume before and after adjustment (P > 0.864). In our study, cohort smaller spinal canal width at the cervical vertebrae 2/3 level and scoliosis were associated with lower grey and white matter volumes and larger ventricle size. These characteristics of the spine might constitute independent risk factors for neurodegeneration.

Management of Extradural Dead Space During Cranioplasty—A Scoping Review

Background: Cranioplasty after craniectomy restores cerebral spinal fluid (CSF) flow dynamics, protects the brain from trauma, and restores skull contour. However, post-cranioplasty extradural dead space may persist, leading to infection and necessitating further surgical interventions. The purpose of this scoping review was to identify and analyze the existing peer-reviewed literature discussing the management of extra-dural dead space during cranioplasty. Methods: A systematic review of the literature was performed via searches of Embase, Cochrane, and PubMed in accordance with PRISMA guidelines. Included studies focused on managing extradural dead space in supratentorial cranioplasty using rigid implants or autologous bone. Studies solely using soft tissue repairs or non-primary studies were excluded. Data extraction covered study characteristics, management techniques, complications, and patient outcomes. Results: Out of 2196 articles, 135 underwent full-text review, and 28 were included, discussing 117 patients. Indications for dead space management included intractable infection (86%), syndrome of the trephined (25%), high-volume dead space (18%), persistent CSF leak (18%), and scarred dura (7%). Management techniques included muscle flaps (46%), omental flaps (14%), fat grafts (7%), and placement of non-organic materials (11%). Complications occurred in 32% of studies, including flap failure, hematoma, and CSF leak. Muscle flaps had a 22% complication rate but led to a high rate of infection resolution (97%). Conclusions: Managing extradural dead space with vascularized flaps during cranioplasty can reduce infection risk but may be associated with high complication rates. The lack of standardized practices and limited high-quality studies highlight the need for further research to establish the safety, efficacy, and best patient selection criteria for these techniques.

Alteration in cerebrospinal fluid flow based on the neurological prognosis of out-of-hospital cardiac arrest patients.

We evaluated alterations in cerebrospinal fluid (CSF) flow based on the neurological prognosis of out-of-hospital cardiac arrest (OHCA) patients. This prospective observational study was conducted from May 2023 to June 2024. Stroke distance was measured using magnetic resonance imaging flowmetry immediately and at 72h after return of spontaneous circulation (ROSC), with negative values indicating caudocranial direction. The caudocranial direction of CSF flow was observed in 17 (56.7%) patients immediately after ROSC, and in 20 (66.7%) patients at 72h after ROSC. There was no significant difference in the occurrence of caudocranial CSF flow immediately after ROSC between the groups with good and poor neurological prognosis [6 (50.0%) vs. 11 (61.1%); p = 0.55]. However, the occurrence of caudocranial CSF flow at 72h after ROSC was significantly higher in the group with poor neurological prognosis compared to the group with good neurological prognosis [3 (25.0%) vs. 17 (94.4%); p < 0.001]. This study demonstrated that the occurrence of caudocranial CSF flow at 72h after ROSC was significantly higher in the group with poor neurological prognosis compared to the group with good neurological prognosis.

RGS22 maintains the physiological function of ependymal cells to prevent hydrocephalus.

Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid (CSF) flow by beating their motile cilia coordinately. The ependymal denudation or ciliary dysfunction causes hydrocephalus. Here, we report that the deficiency of regulator of G-protein signaling 22 (RGS22) results in severe congenital hydrocephalus in both mice and rats. Interestingly, RGS22 is specifically expressed in ependymal cells within the brain. Using conditional knock-out mice, we further demonstrate that the deletion of Rgs22 exclusively in nervous system is sufficient to induce hydrocephalus. Mechanistically, we show that Rgs22 deficiency leads to the ependymal denudation and impaired ciliogenesis. This phenomenon can be attributed to the excessive activation of lysophosphatidic acid receptor (LPAR) signaling under Rgs22-/- condition, as the LPAR blockade effectively alleviates hydrocephalus in Rgs22-/- rats. Therefore, our findings unveil a previously unrecognized role of RGS22 in the central nervous system, and present RGS22 as a potential diagnostic and therapeutic target for hydrocephalus.

Towards non-invasive imaging through spinal-cord generated magnetic fields.

Non-invasive imaging of the human spinal cord is a vital tool for understanding the mechanisms underlying its functions in both healthy and pathological conditions. However, non-invasive imaging presents a significant methodological challenge because the spinal cord is difficult to access with conventional neurophysiological approaches, due to its proximity to other organs and muscles, as well as the physiological movements caused by respiration, heartbeats, and cerebrospinal fluid (CSF) flow. Here, we discuss the present state and future directions of spinal cord imaging, with a focus on the estimation of current flow through magnetic field measurements. We discuss existing cryogenic (superconducting) and non-cryogenic (optically-pumped magnetometer-based, OPM) systems, and highlight their strengths and limitations for studying human spinal cord function. While significant challenges remain, particularly in source imaging and interference rejection, magnetic field-based neuroimaging offers a novel avenue for advancing research in various areas. These include sensorimotor processing, cortico-spinal interplay, brain and spinal cord plasticity during learning and recovery from injury, and pain perception. Additionally, this technology holds promise for diagnosing and optimizing the treatment of spinal cord disorders.

A brain-wide solute transport model of the glymphatic system.

Brain waste is largely cleared via diffusion and advection in cerebrospinal fluid (CSF). CSF flows through a pathway referred to as the glymphatic system, which is also being targeted for delivering drugs to the brain. Despite the importance of solute transport, no brain-wide models for predicting clearance and delivery through perivascular pathways and adjacent parenchyma existed. We devised such a model by upgrading an existing model of CSF flow in the mouse brain to additionally solve advection-diffusion equations, thereby estimating solute transport. We simulated steady-state transport of 3 kDa dextran injected proximal to the perivascular space (PVS) of the middle cerebral artery, mimicking in vivo experiments. We performed a sensitivity analysis of 11 biological properties of PVSs and brain parenchyma by repeatedly simulating solute transport with varying parameter values. Parameter combinations that led to a large total pressure gradient, poor CSF perfusion or a steep solute gradient were deemed unrealistic. Solute concentrations in parenchyma were most sensitive to changes in pial PVS size, as this parameter linearly affects volume flow rates. We also found that realistic transport requires both highly permeable penetrating PVSs and high-resistance parenchyma. This study highlights the potential of brain-wide models to provide insights into solute transport processes.

Sex-specific age-related differences in cerebrospinal fluid clearance assessed by resting-state functional magnetic resonance imaging

Cerebrospinal fluid (CSF) flow may assist the clearance of brain wastes, such as amyloid-β (Aβ) and tau, and thus play an important role in aging and dementias. However, a lack of non-invasive tools to assess the CSF dynamics-related clearance in humans hindered the understanding of the relevant changes in healthy aging. The global infra-slow (<0.1 Hz) brain activity measured by the global mean resting-state fMRI signal (gBOLD) was recently found to be coupled by large CSF movements. This coupling has been found to correlate with various pathologies of Alzheimer's disease (AD), particularly Aβ pathology, linking it to waste clearance. Using resting-state fMRI data from a group of 719 healthy aging participants, we examined the sex-specific differences of the gBOLD-CSF coupling over a wide age range between 36-100 years of age. We found that this coupling index remains stable before around age 55 and then starts to decline afterward, particularly in females. Menopause may contribute to the accelerated decline in females.