Real-time quantification of in vivo cerebrospinal fluid velocity using the functional magnetic resonance imaging inflow effect.

In vivo estimation of cerebrospinal fluid (CSF) velocity is crucial for understanding the glymphatic system and its potential role in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Current cardiac or respiratory-gated approaches, such as 4D flow magnetic resonance imaging (MRI), cannot capture CSF movement in real time because of limited temporal resolution and, in addition, deteriorate in accuracy at low fluid velocities. Other techniques like real-time phase-contrast-MRI or time-spatial labeling inversion pulse are not limited by temporal averaging but have limited availability, even in research settings. This study aims to quantify the inflow effect of dynamic CSF motion on functional MRI (fMRI) for in vivo, real-time measurement of CSF flow velocity. We considered linear and nonlinear models of velocity waveforms and empirically fit them to fMRI data from a controlled flow experiment. To assess the utility of this methodology in human data, CSF flow velocities were computed from fMRI data acquired in eight healthy volunteers. Breath-holding regimens were used to amplify CSF flow oscillations. Our experimental flow study revealed that CSF velocity is nonlinearly related to inflow effect-mediated signal increase and well estimated using an extension of a previous nonlinear framework. Using this relationship, we recovered velocity from in vivo fMRI signal, demonstrating the potential of our approach for estimating CSF flow velocity in the human brain. This novel method could serve as an alternative approach to quantifying slow flow velocities in real time, such as CSF flow in the ventricular system, thereby providing valuable insights into the glymphatic system's function and its implications for neurological disorders.

Non-invasive biomarkers for spontaneous intracranial hypotension (SIH) through phase-contrast MRI.

BACKGROUND AND OBJECTIVE: Spontaneous intracranial hypotension (SIH) is an underdiagnosed disease. To depict the accurate diagnosis can be demanding; especially the detection of CSF-venous fistulas poses many challenges. Potential dynamic biomarkers have been identified through non-invasive phase-contrast MRI in a limited subset of SIH patients with evidence of spinal longitudinal extradural collection. This study aimed to explore these biomarkers related to spinal cord motion and CSF velocities in a broader SIH cohort. METHODS: A retrospective, monocentric pooled-data analysis was conducted of patients suspected to suffer from SIH who underwent phase-contrast MRI for spinal cord and CSF velocity measurements at segment C2/C3 referred to a tertiary center between February 2022 and June 2023. Velocity ranges (mm/s), total displacement (mm), and further derivatives were assessed and compared to data from the database of 70 healthy controls. RESULTS: In 117 patients, a leak was located (54% ventral leak, 20% lateral leak, 20% CSF-venous fistulas, 6% sacral leaks). SIH patients showed larger spinal cord and CSF velocities than healthy controls: e.g., velocity range 7.6 ± 3 mm/s vs. 5.6 ± 1.4 mm/s, 56 ± 21 mm/s vs. 42 ± 10 mm/s, p < 0.001, respectively. Patients with lateral leaks and CSF-venous fistulas exhibited an exceptionally heightened level of spinal cord motion (e.g., velocity range 8.4 ± 3.3 mm/s; 8.2 ± 3.1 mm/s vs. 5.6 ± 1.4 mm/s, p < 0.001, respectively). CONCLUSION: Phase-contrast MRI might become a valuable tool for SIH diagnosis, especially in patients with CSF-venous fistulas without evidence of spinal extradural fluid collection.

The Role of Phase-Contrast MRI in Diagnosing Cerebrospinal Fluid Flow Abnormalities.

Background Cerebrospinal fluid (CSF) dynamics play a crucial role in maintaining the homeostasis of the central nervous system (CNS). Any disruption in CSF flow can lead to various congenital and acquired conditions, impacting neurological function and overall health. This study aims to analyze the significance of phase-contrast MRI in evaluating abnormalities in CSF flow and its diagnostic utility in various CSF-related disorders. Phase contrast MRI has emerged as a valuable tool for evaluating CSF dynamics non-invasively by examining CSF flow characteristics such as pulsatile flow patterns, hyperdynamic or hypodynamic flow, and disruptions in CSF circulation. Alterations in CSF pulsatility and stroke volume can indicate changes in intracranial compliance, vascular resistance, or CSF production and absorption rates. The findings of this study will advance our understanding of CSF physiology and its relevance in neurological pathologies, potentially leading to improved patient outcomes and management approaches. Materials and methods The study involved 36 patients and was conducted as an observational, prospective study over 18 months (October 2020 to March 2022) at the Department of Radiology, Saveetha Medical College and Hospital, Chennai. We utilized a 1.5 T Philips Multiva MRI scanner by Philips Healthcare in Amsterdam, Netherlands. The study included patients with suspected CSF flow abnormalities and abnormal MRI findings (normal pressure hydrocephalus (NPH), age-related brain atrophy, aqueduct stenosis (AS), Chiari malformation type 1, syringomyelia, or arachnoid cyst), alongside control exhibiting normal neurological symptoms and MRI results. Exclusions involved individuals with febrile seizures, neurological diseases, cerebrovascular accidents, anti-convulsive medication use, cardiac arrhythmia, or MRI contraindications. Post-processing involved analyzing stroke volume (SV), peak systolic velocity (PSV), end diastolic velocity (EDV), and mean flux. Statistical analysis was conducted using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 24.0, Armonk, NY), employing the χ2-test for categorical variables and nonparametric tests like Mann-Whitney U and Kruskal-Wallis H-tests for quantitative variables. A p-value < 0.05 was considered significant. Results The 36 patients, aged 1 to 80 years, were referred by the neurology department and categorized into four subgroups based on clinical history and conventional MRI findings: NPH, AS, age-related brain atrophy, and a normal control group. MRI CSF flowmetry evaluation focused on PSV, PDV, and SV. We found peak diastolic velocity (PDV), PSV, and average blood velocity (ABV) to be significantly higher in NPH compared to the control group (PSV, EDV, and SV: 9.96 +/- 1.73, 4.72 +/- 0.62, and 63 +/- 12.88 for NPH versus 4.8 +/- 0.39, 3.21 +/- 0.55, and 20.72 +/- 5.7 for control, respectively; p = 0.000). Conversely, patients with age-related brain atrophy and AS exhibited lower values (1.6 +/- 0.44, 1.13 +/- 0.09, and 6.33 +/- 2.08 for AS, and 2.07 +/- 0.09, 1.62 +/- 0.33, and 6.8 +/- 2.16 for age-related brain atrophy versus control; p = 0.002). Conclusion MRI CSF flowmetry emerges as a rapid, accurate, and non-invasive diagnostic tool for various neurological disorders associated with abnormal CSF flow. Additionally, this technique may aid in selecting appropriate treatment strategies.

Cerebrospinal Fluid Flow Parameters in Normal Subjects above 40 Years of Age.

Background Cerebrospinal fluid (CSF) flow is altered in many conditions like normal pressure hydrocephalus (NPH), aqueduct stenosis, or Chiari malformation. It is very important to know the normal CSF flow parameters for properly diagnosing these conditions. No data on CSF flow parameters of the Indian population are available. Hence, this study was undertaken to generate normative CSF flow parameters in the Indian population. Aim Our aim was to estimate normal CSF flow parameters across the cerebral aqueduct in Indian subjects over 40 years of age. Settings and Design This observational study was done in the tertiary care institute on subjects undergoing magnetic resonance imaging (MRI) for indications like headache and having normal MRI. Methods Phase-contrast quantitative flow sequence was done in 100 subjects perpendicular to the cerebral aqueduct on 3.0T MRI (Discovery 750w with GEM suit, GE, Milwaukee, WI, United States) using a dedicated 32-channel head coil with 10 cm/s velocity encoding. The region of interest was kept at the cerebral aqueduct in cross-section. The inbuilt software calculated flow-time and velocity-time graphs and calculated peak systolic velocity (PSV), peak diastolic velocity (PDV), systolic flow (SF), and diastolic flow (DF). Stroke volume (SV) was calculated by averaging systolic and DFs. p -Value < 0.05 was considered significant. Results Mean age was 53.72 ± 10.53 (40-78) years with 41 males and 59 females. PSV, PDV, SF, DF, and SV all showed a significant linear correlation with age with p -values of 0.001, 0.004, 0.009, <0.001, and <0.001, respectively. Only PDV ( p = 0.035) and DF ( p = 0.045) varied significantly with sex, values being higher in males. Conclusion All five CSF flow parameters studied vary positively with age, and this variation is linear. Normal decadal median values calculated for these parameters can act as baseline values for the local population and help in defining conditions like NPH.

Deep learning segmentation of peri-sinus structures from structural magnetic resonance imaging: validation and normative ranges across the adult lifespan.

BACKGROUND: Peri-sinus structures such as arachnoid granulations (AG) and the parasagittal dural (PSD) space have gained much recent attention as sites of cerebral spinal fluid (CSF) egress and neuroimmune surveillance. Neurofluid circulation dysfunction may manifest as morphological changes in these structures, however, automated quantification of these structures is not possible and rather characterization often requires exogenous contrast agents and manual delineation. METHODS: We propose a deep learning architecture to automatically delineate the peri-sinus space (e.g., PSD and intravenous AG structures) using two cascaded 3D fully convolutional neural networks applied to submillimeter 3D T2-weighted non-contrasted MRI images, which can be routinely acquired on all major MRI scanner vendors. The method was evaluated through comparison with gold-standard manual tracing from a neuroradiologist (n = 80; age range = 11-83 years) and subsequently applied in healthy participants (n = 1,872; age range = 5-100 years), using data from the Human Connectome Project, to provide exemplar metrics across the lifespan. Dice-Sørensen and a generalized linear model was used to assess PSD and AG changes across the human lifespan using quadratic restricted splines, incorporating age and sex as covariates. RESULTS: Findings demonstrate that the PSD and AG volumes can be segmented using T2-weighted MRI with a Dice-Sørensen coefficient and accuracy of 80.7 and 74.6, respectively. Across the lifespan, we observed that total PSD volume increases with age with a linear interaction of gender and age equal to 0.9 cm3 per year (p < 0.001). Similar trends were observed in the frontal and parietal, but not occipital, PSD. An increase in AG volume was observed in the third to sixth decades of life, with a linear effect of age equal to 0.64 mm3 per year (p < 0.001) for total AG volume and 0.54 mm3 (p < 0.001) for maximum AG volume. CONCLUSIONS: A tool that can be applied to quantify PSD and AG volumes from commonly acquired T2-weighted MRI scans is reported and exemplar volumetric ranges of these structures are provided, which should provide an exemplar for studies of neurofluid circulation dysfunction. Software and training data are made freely available online ( https://github.com/hettk/spesis ).

Magnetic Resonance Imaging Diagnosis in Normal Pressure Hydrocephalus.

BACKGROUND: Idiopatic normal pressure hydrocephalus (iNPH) is a progressive neurologic syndrome featured by the triad of gait disturbance, mental deterioration and urinary incontinence, associated with ventriculomegaly and normal cerebrospinal fluid (CSF) pressure. The clinical presentation may be atypical or incomplete, or mimicked by other diseases, so conventional neuroradiologic imaging plays an important role in defining this pathology. iNPH pathophysiologic mechanisms have not yet been fully elucidated, although several studies have demonstrated the involvement of the glymphatic system, a highly organized fluid transport system, the malfunction of which is involved in the pathogenesis of several disorders including normotensive hydrocephalus. METHODS: Recent studies have shown how crucial in the diagnosis of this pathology is the definition of morphologic biomarkers, such as ventricular enlargement disproportionate to cerebral atrophy and associated ballooning of frontal horns; periventricular hyperintensities; and corpus callosum thinning and elevation, with callosal angle <90 degrees. RESULTS: Another interesting feature that is becoming a well-recognized factor to look for and useful for the diagnosis of iNPH is disproportionately enlarged subarachnoid space hydrocephalus, which includes enlarged ventricles, tight high-convexity and medial surface subarachnoid spaces, and expanded Sylvian fissures. A correct choice of MRI sequences is important for a proper characterization identification of others diseases that may underlie this pathology. Magnetic resonance imaging allows us to evaluate CSF flow, enabling us to define qualitative and quantitative parameters necessary for the purpose of accurate iNPH diagnosis. CONCLUSIONS: iNPH can represent a real diagnostic challenge; a proper correlation among clinical features, traditional MRI, and CSF dynamics analysis can lead to a correct diagnosis.

Non-invasive Intracranial Pressure Waveform Analysis in Chiari Malformation Type 1: A Pilot Trial.

OBJECTIVE: This pilot study aimed to investigate the role of Posterior Fossa Decompression (PFD) on the intracranial pressure (ICP) waveform in patients with Chiari Malformation type 1 (CM1). It also sought to explore the relationship between symptom improvement and ICP waveform behavior. METHODS: This exploratory cohort study evaluated adult patients diagnosed with CM1. The patients underwent PFD using a standard technique at our institution, which involved a 3 × 3 cm posterior craniectomy and excision of the posterior arch of C1. The ICP waveform was measured using an external strain-gauge device connected to a pin attached to the skull. Measurements were collected pre- and post-PFD, and the P2/P1 ratio was calculated pre- and postoperatively. RESULTS: The pilot study comprised 6 participants, 3 men and 3 women, with ages ranging from 39 to 68 years. The primary symptoms were cerebellar ataxia and typical headaches. The study found that most patients who showed clinical improvement, as judged by the Gestalt method, had a postoperative decrease in the P2/P1 ratio. However, 1 patient did not show an improvement in the P2/P1 ratio despite a good clinical outcome. CONCLUSIONS: This study suggests that the P2/P1 ratio may decrease after PFD. However, we highlight the need for further research with a larger sample size to confirm these preliminary results.

Advanced cerebrospinal fluid flow MRI findings of aqueductal stenosis caused by web.

BACKGROUND: The aqueductal web (AW) is one of the causes of aqueductus stenosis (AS). Recent advances in Magnetic resonance (MR) imaging have enabled us to better reveal the cerebrospinal fluid (CSF) flow dynamics and aqueductal anatomy. PURPOSE: The aim of this study is to evaluate the CSF flow dynamics of patients with AW with phase contrast Magnetic resonance imaging (MRI) and compare them with the imaging findings. MATERIALS AND METHODS: We evaluated 23 patients under 65-year-old age. On constructive interference in steady-state (T2 CISS) images, the width of prepontine cistern (PPC) and the width of Sylvian aqueduct (SA) were measured. Localization and number of webs were evaluated. The existence of flow at the aqueduct and the presence of spontaneous third ventriculostomy (STV) were evaluated on sagittal Sampling Perfection with Application optimized Contrast (SPACE) sequences. RESULTS: Of the 23 patients included in the study, 11 were male and 12 were female. The mean age was 34.02 (0.5-64). A total of 31 AWs were detected in 23 patients. Six of 23 patients (26.1%) had STV and 17 of those not. Four of 23 patients (17.4%) had aqueductal flow on SPACE sequences. The PPC distance was significantly wider in patients with STV (median: 6.7-4.5, interquartile range (IQR): 1.35, p = 0.004). In the cases where artifact secondary to flow is observed in SPACE sequences in aqueduct, the Evan index (EI) was significantly lower (median: 0.2955-0.3900, IQR: 0.03-0.14, p < 0.001). CONCLUSION: In patients with a low EI, there may be flow in the SA even if there is a web. In patients with a wide PPC distance, it is necessary to consider the presence of STV and evaluate the presence of flow with the SPACE sequences.

Real-time Quantification of in vivo cerebrospinal fluid velocity using fMRI inflow effect.

In vivo estimation of cerebrospinal fluid (CSF) velocity is crucial for understanding the glymphatic system and its potential role in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Current cardiac or respiratory gated approaches, such as 4D flow MRI, cannot capture CSF movement in real time due to limited temporal resolution and in addition deteriorate in accuracy at low fluid velocities. Other techniques like real-time PC-MRI or time-spatial labeling inversion pulse are not limited by temporal averaging but have limited availability even in research settings. This study aims to quantify the inflow effect of dynamic CSF motion on functional magnetic resonance imaging (fMRI) for in vivo, real-time measurement of CSF flow velocity. We considered linear and nonlinear models of velocity waveforms and empirically fit them to fMRI data from a controlled flow experiment. To assess the utility of this methodology in human data, CSF flow velocities were computed from fMRI data acquired in eight healthy volunteers. Breath holding regimens were used to amplify CSF flow oscillations. Our experimental flow study revealed that CSF velocity is nonlinearly related to inflow effect-mediated signal increase and well estimated using an extension of a previous nonlinear framework. Using this relationship, we recovered velocity from in vivo fMRI signal, demonstrating the potential of our approach for estimating CSF flow velocity in the human brain. This novel method could serve as an alternative approach to quantifying slow flow velocities in real time, such as CSF flow in the ventricular system, thereby providing valuable insights into the glymphatic system's function and its implications for neurological disorders.

Determination of spinal tracer dispersion after intrathecal injection in a deformable CNS model.

Background: Traditionally, there is a widely held belief that drug dispersion after intrathecal (IT) delivery is confined locally near the injection site. We posit that high-volume infusions can overcome this perceived limitation of IT administration. Methods: To test our hypothesis, subject-specific deformable phantom models of the human central nervous system were manufactured so that tracer infusion could be realistically replicated in vitro over the entire physiological range of pulsating cerebrospinal fluid (CSF) amplitudes and frequencies. The distribution of IT injected tracers was studied systematically with high-speed optical methods to determine its dependence on injection parameters (infusion volume, flow rate, and catheter configurations) and natural CSF oscillations in a deformable model of the central nervous system (CNS). Results: Optical imaging analysis of high-volume infusion experiments showed that tracers spread quickly throughout the spinal subarachnoid space, reaching the cervical region in less than 10 min. The experimentally observed biodispersion is much slower than suggested by the Taylor-Aris dispersion theory. Our experiments indicate that micro-mixing patterns induced by oscillatory CSF flow around microanatomical features such as nerve roots significantly accelerate solute transport. Strong micro-mixing effects due to anatomical features in the spinal subarachnoid space were found to be active in intrathecal drug administration but were not considered in prior dispersion theories. Their omission explains why prior models developed in the engineering community are poor predictors for IT delivery. Conclusion: Our experiments support the feasibility of targeting large sections of the neuroaxis or brain utilizing high-volume IT injection protocols. The experimental tracer dispersion profiles acquired with an anatomically accurate, deformable, and closed in vitro human CNS analog informed a new predictive model of tracer dispersion as a function of physiological CSF pulsations and adjustable infusion parameters. The ability to predict spatiotemporal dispersion patterns is an essential prerequisite for exploring new indications of IT drug delivery that targets specific regions in the CNS or the brain.

Noninvasive CSF shunt patency evaluation by superb microvascular imaging.

Occlusion of a ventriculoperitoneal shunt system is a potentially life-threatening complication in patients suffering from hydrocephalus. However, there is no imaging established as standard approach in this acute setting. In the present study, we evaluate the use of superb microvascular imaging for investigation of the patency of ventriculoperitoneal shunt systems. Simulation of low flow rates of cerebrospinal fluid through a small diameter CSF shunt system was performed in a dedicated phantom in order to proof the principle of superb microvascular imaging (SMI) being feasible for the measurement of slow CSF flow through the dedicated CSF shunt system. SMI is able to detect low flow rates in CSF shunt systems effectively and fast. Visualization of a Duplex ultrasound flow and Doppler wave pattern in the VP shunt system after the reservoir has been pressed confirms patency. SMI is an effective method for evaluating CSF shunt patency and diagnosing shunt obstruction. This bears the potential to facilitate evaluation of clinically symptomatic VP shunt patients in an acute setting. Further evaluation of ultrasound flow patterns is granted.

Preconditioned extracellular vesicles from hypoxic microglia reduce poststroke AQP4 depolarization, disturbed cerebrospinal fluid flow, astrogliosis, and neuroinflammation.

Background: Stroke stimulates reactive astrogliosis, aquaporin 4 (AQP4) depolarization and neuroinflammation. Preconditioned extracellular vesicles (EVs) from microglia exposed to hypoxia, in turn, reduce poststroke brain injury. Nevertheless, the underlying mechanisms of such effects are elusive, especially with regards to inflammation, AQP4 polarization, and cerebrospinal fluid (CSF) flow. Methods: Primary microglia and astrocytes were exposed to oxygen-glucose deprivation (OGD) injury. For analyzing the role of AQP4 expression patterns under hypoxic conditions, a co-culture model of astrocytes and microglia was established. Further studies applied a stroke model, where some mice also received an intracisternal tracer infusion of rhodamine B. As such, these in vivo studies involved the analysis of AQP4 polarization, CSF flow, astrogliosis, and neuroinflammation as well as ischemia-induced brain injury. Results: Preconditioned EVs decreased periinfarct AQP4 depolarization, brain edema, astrogliosis, and inflammation in stroke mice. Likewise, EVs promoted postischemic CSF flow and cerebral blood perfusion, and neurological recovery. Under in vitro conditions, hypoxia stimulated M2 microglia polarization, whereas EVs augmented M2 microglia polarization and repressed M1 microglia polarization even further. In line with this, astrocytes displayed upregulated AQP4 clustering and proinflammatory cytokine levels when exposed to OGD, which was reversed by preconditioned EVs. Reduced AQP4 depolarization due to EVs, however, was not a consequence of unspecific inflammatory regulation, since LPS-induced inflammation in co-culture models of astrocytes and microglia did not result in altered AQP4 expression patterns in astrocytes. Conclusions: These findings show that hypoxic microglia may participate in protecting against stroke-induced brain damage by regulating poststroke inflammation, astrogliosis, AQP4 depolarization, and CSF flow due to EV release.

Transverse sinus pathologies, vestibular migraine and intracranial hypertension without papilledema.

BACKGROUND: In the absence of papilledema, the presentation of migraine and idiopathic intracranial hypertension (IIH) is very similar. In this respect, an IIH could be presented as a vestibular migraine. Our main objective in this case report is to demonstrate the similarities between IIH and vestibular migraine. CASES: This is a report of 14 patients who have IIH without papilledema presented as vestibular migraine to the clinic and followed from 2020 to 2022. RESULTS: The common presentation of patients was ear-facial pain, dizziness, and frequent pulsatile tinnitus. One-fourth of the patients reported episodes of true episodic vertigo. The average age was 37.8, the average BMI was 37.4, and the average lumbar puncture-opening pressure was 25.6 cm H2O. Transverse sinus venous flow alterations caused neuroimaging findings of sigmoid sinus dehiscence, empty sella, or tonsillar ectopia. Most patients improved with carbonic anhydrase inhibitors, and one patient was treated with a dural sinus stent. CONCLUSION: A transverse sinus stenosis, even in the non-dominant site, may elevate the CSF pressure in obese individuals. This stenosis causes dural sinus-related pulsatile tinnitus with characteristics different from those of an arterial origin. Dizziness is a common complaint in patients with IIH, just like VM. In our opinion, episodic vertigo in these patients is the direct effect of CSF flow alterations into the inner ear's vestibule. Patients with mild elevations will be presented to the clinic, similar to migraines with or without the presence of pulsatile tinnitus. Treatment requires lowering intracranial pressure and managing migraine symptoms.

Surgical management of syringomyelia associated with spinal arachnoid web: strategies and outcomes.

Spinal arachnoid web (SAW) is a rare disease entity characterized as band-like arachnoid tissue that can cause spinal cord compression and syringomyelia. This study aimed to analyze the surgical management of the spinal arachnoid web in patients with syringomyelia, focusing on surgical strategies and outcomes. A total of 135 patients with syringomyelia underwent surgery at our department between November 2003 and December 2022. All patients underwent magnetic resonance imaging (MRI), with a special syringomyelia protocol (including TrueFISP and CINE), and electrophysiology. Among these patients, we searched for patients with SAW with syringomyelia following careful analysis of neuroradiological data and surgical reports. The criteria for SAW were as follows: displacement of the spinal cord, disturbed but preserved CSF flow, and intraoperative arachnoid web. Patients were evaluated for initial symptoms, surgical strategies, and complications by reviewing surgical reports, patient documents, neuroradiological data, and follow-up data. Of the 135 patients, 3 (2.22%) fulfilled the SAW criteria. The mean patient age was 51.67 ± 8.33 years. Two patients were male, and one was female. The affected levels were T2/3, T6, and T8. Excision of the arachnoid web was performed in all cases. No significant change in intraoperative monitoring was noted. Postoperatively, none of the patients presented new neurological symptoms. The MRI 3 months after surgery revealed that the syringomyelia improved in all cases, and caliber variation of the spinal cord could not be detected anymore. All clinical symptoms improved. In summary, SAW can be safely treated by surgery. Even though syringomyelia usually improves on MRI and symptoms also improve, residual symptoms might be observed. We advocate for clear criteria for the diagnosis of SAW and a standardized diagnostic (MRI including TrueFISP and CINE).

Sex-specific age-related changes in glymphatic function assessed by resting-state functional magnetic resonance imaging.

The glymphatic system that clears out brain wastes, such as amyloid-ß (Aß) and tau, through cerebrospinal fluid (CSF) flow may play an important role in aging and dementias. However, a lack of non-invasive tools to assess the glymphatic function in humans hindered the understanding of the glymphatic 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 used to measure the glymphatic process and found to correlate with various pathologies of Alzheimer's disease (AD), including Aß pathology. Using resting-state fMRI data from a large group of 719 healthy aging participants, we examined the sex-specific changes of the gBOLD-CSF coupling, as a measure of glymphatic function, over a wide age range between 36-100 years old. 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.

Cerebrospinal Fluid Flow and Brain Motion in Chiari I Malformation: Past, Present, and Future.

Cranio-spinal volume and pressure changes associated with the cardiac-cycle and respiration are altered in Chiari I malformation (CMI) due to obstruction of cerebrospinal fluid (CSF) flow at the foramen magnum. With the introduction of motion-sensitive MRI sequences, it was envisioned that these could provide noninvasive information about volume-pressure dynamics at the cranio-cervical junction in CMI hitherto available only through invasive pressure measurements. Since the early 1990s, multiple studies have assessed CSF flow and brain motion in CMI. However, differences in design and varied approaches in the presentation of results and conclusions makes it difficult to fully comprehend the role of MR imaging of CSF flow and brain motion in CMI. In this review, a cohesive summary of the current status of MRI assessment of CSF flow and brain motion in CMI is presented. Simplified versions of the results and conclusions of previous studies are presented by dividing the studies in distinct topics: 1) comparing CSF flow and brain motion between healthy subjects (HS) and CMI patients (before and after surgery), 2) comparing CSF flow and brain motion to CMI severity and symptoms, and 3) comparing CSF flow and brain motion in CMI with and without syringomyelia. Finally, we will discuss our vision of the future directions of MR imaging in CMI patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: 5.

Brain washing and neural health: role of age, sleep, and the cerebrospinal fluid melatonin rhythm.

The brain lacks a classic lymphatic drainage system. How it is cleansed of damaged proteins, cellular debris, and molecular by-products has remained a mystery for decades. Recent discoveries have identified a hybrid system that includes cerebrospinal fluid (CSF)-filled perivascular spaces and classic lymph vessels in the dural covering of the brain and spinal cord that functionally cooperate to remove toxic and non-functional trash from the brain. These two components functioning together are referred to as the glymphatic system. We propose that the high levels of melatonin secreted by the pineal gland directly into the CSF play a role in flushing pathological molecules such as amyloid-ß peptide (Aß) from the brain via this network. Melatonin is a sleep-promoting agent, with waste clearance from the CNS being highest especially during slow wave sleep. Melatonin is also a potent and versatile antioxidant that prevents neural accumulation of oxidatively-damaged molecules which contribute to neurological decline. Due to its feedback actions on the suprachiasmatic nucleus, CSF melatonin rhythm functions to maintain optimal circadian rhythmicity, which is also critical for preserving neurocognitive health. Melatonin levels drop dramatically in the frail aged, potentially contributing to neurological failure and dementia. Melatonin supplementation in animal models of Alzheimer's disease (AD) defers Aß accumulation, enhances its clearance from the CNS, and prolongs animal survival. In AD patients, preliminary data show that melatonin use reduces neurobehavioral signs such as sundowning. Finally, melatonin controls the mitotic activity of neural stem cells in the subventricular zone, suggesting its involvement in neuronal renewal.

Depiction of detailed surgical anatomy and CSF flow information using a single MRI technique.

We describe a novel MRI sequence (T2 SPACE) capable of demonstrating detailed structural anatomy and functional CSF flow information simultaneously. While traditionally, a variety of sequences are utilised for this purpose, we have highlighted the advantages of this technique over traditional approaches, using example of a patient with CSF loculation in prepontine/suprasellar cistern, causing third ventricular compression and hydrocephalus. The sequence depicted the surgical anatomy by showing the web/cyst wall as well as CSF flow entering the cyst potentially causing increased pressure.

Imaging in Chiari I Malformation.

Chiari I Malformation represents a hindbrain anomaly best demonstrated radiographically with MRI. Brain and spine MRI provide optimal anatomic detail of cerebellar tonsillar descent below the foramen magnum and may reveal additional imaging features including ventriculomegaly (potentially leading to the diagnosis of hydrocephalus), characteristics of intracranial hypertension or hypotension, spinal cord syrinx, scoliosis, and/or tethered spinal cord. Specialized imaging sequences provide enhanced visualization of ventral and dorsal cervicomedullary cisterns and cerebrospinal fluid flow. Although these studies contribute critical information for evaluation, their impact on surgical decision-making remains uncertain. Additional radiographic measures (pBC2 and clival-axial angle) may impact surgical planning and risk assessment.

Tetraventricular hydrocephalus with aqueductal flow void: an overlooked entity having consistent improvement following endoscopic third ventriculostomy.

BACKGROUND: Tetraventricular Hydrocephalus (TetHCP) is a heterogeneous group of cerebrospinal fluid (CSF) flow disorders having varying success rates with Endoscopic third ventriculostomy (ETV). This is report on the efficacy and rationale of ETV in a specific subset of primary TetHCP with aqueductal CSF flow voids. METHODS: Patients of primary acquired TetHCP presenting with increasing head size and/or headache having aqueductal CSF flow void on sagittal Magnetic Resonance Imaging (MRI) were included in this study. All of them underwent ETV. All patients were evaluated for clinical improvement & MRI at 3 months, and need for any additional procedure, in contrast to those without CSF flow void. The pathophysiology of hyperdynamic CSF circulation and its correlation to ETV was further reviewed. RESULTS: Eleven patients had tetraventricular hydrocephalus and aqueductal flow void, with age ranging from 10 months to 59 years. Two patients who could undergo quantitative flow study confirmed the hyperdynamic flow across the aqueduct. Following ETV, all showed clinical improvement. MRI at 3 months showed CSF flow void across the third ventricular stoma in addition to across the aqueduct. None of these patients required any redo procedures for a mean follow-up of 39.2 months. In contrast, there was 30% failure rate after ETV among 10 patients of tetraventricular hydrocephalus without aqueductal flow void. CONCLUSION: Tetraventricular hydrocephalus with aqueductal CSF flow void may be a unique entity with hyperdynamic CSF circulation and relative resistance at fourth ventricular outlets. ETV is highly efficacious in these patients, resulting in consistent clinico-radiological improvement.