Cerebrospinal Fluid Flow Patterns Research Articles

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.

Cerebro-spinal flow pattern in the cervical subarachnoid space of healthy volunteers: Influence of the spinal cord morphology.

Toward further cerebro-spinal flow quantification in clinical practice, this study aims at assessing the variations in the cerebro spinal fluid flow pattern associated with change in the morphology of the subarachnoid space of the cervical canal of healthy humans by developing a computational fluid dynamics model. 3D T2-space MRI sequence images of the cervical spine were used to segment 11 cervical subarachnoid space. Model validation (time-step, mesh size, size and number of boundary layers, influences of parted inflow and inflow continuous velocity) was performed a 40-year-old patient-specific model. Simulations were performed using computational fluid dynamics approach simulating transient flow (Sparlart-Almaras turbulence model) with a mesh size of 0.6, 6 boundary layers of 0.05 mm, a time step of 20 ms simulated on 15 cycles. Distributions of components velocity and WSS were respectively analyzed within the subarachnoid space (intervertebral et intravertebral levels) and on dura and pia maters. Mean values cerebro spinal fluid velocity in specific local slices of the canal range between 0.07 and 0.17 m.s-1 and 0.1 and 0.3 m.s-1 for maximum values. Maximum wall shear stress values vary between 0.1 and 0.5 Pa with higher value at the middle of the cervical spine on pia mater and at the lower part of the cervical spine on dura mater. Intra and inter-individual variations of the wall shear stress were highlighted significant correlation gwith compression ratio (r = 0.76), occupation ratio and cross section area of the spinal cord. The inter-individual variability in term of subarachnoid canal morphology and spinal cord position influence the cerebro-spinal flow pattern, highlighting the significance of canal morphology investigation before surgery.

The Role of Cerebrospinal Fluid Flow in the Subarachnoid Space in Beta‐Amyloid Clearance

AbstractBackgroundRecent studies identified the lymphatic drainage system in the brain. Here, cerebrospinal fluid (CSF) carries waste from brain tissue. However, it is still not well understood how CSF flow in the brain affects waste removal. In this study, we hypothesize that CSF flow patterns in the subarachnoid space will be correlated with beta‐amyloid deposition in the brain.MethodThirteen participants (7 Cognitively Normal and 2 Mild Cognitive Impairment, Age = 68±7.7 yrs. M/F = 5/4) who had prior amyloid PET imaging were recruited for CSF flow MRI from the Wake Forest Alzheimer’s Disease Research Center. The CSF flow patterns during the cardiac cycle were measured using the phase‐contrast MRI at the cerebral aqueduct, pontine cistern and cerebellomedullary cistern (Fig. 1). Images were acquired for 40 cardiac cycles with a pulse oximeter and CSF flow profiles were estimated using the retrospective cardiac gating method. PET Amyloid burden in the whole gray matter (GM) was measured as the standardized update value ratio (SUVR, cerebellar gray matter as a reference region) from the prior PET imaging and corresponding MRI.ResultCSF flow amplitude normalized by the brain tissue volume demonstrated moderate to strong correlations with beta‐Amyloid SUVR in GM (Fig. 2); Pearson’s correlation coefficient (rho) was ‐0.59 (p = 0.036) and ‐0.84 (p = 0.004) at pontine cistern and cerebellomedullary cistern, respectively. The lateral ventricle volume normalized by brain volume was also moderately correlated with GM SUVR (rho = 0.495).ConclusionAt an early stage of AD, the CSF circulation in the subarachnoid space could be correlated with beta‐Amyloid deposition. Therefore, CSF flow in the subarachnoid space could be a useful imaging marker to predict the clearance of beta‐amyloid in the brain.

Characterizing cerebrospinal fluid mobility using heavily T2-weighted 3D fast spin echo (FSE) imaging with improved multi-directional diffusion-sensitized driven-equilibrium (iMDDSDE) preparation

Cerebrospinal fluid (CSF) flow patterns and their relationship with arterial pulsation can depict the function of glymphatic system (GS). We propose an improved multi-directional diffusion-sensitized driven-equilibrium (iMDDSDE) prepared heavily T2-weighted 3D FSE (iMDDSDE-HT2) magnetic resonance imaging (MRI) method to noninvasively assess the mobility (MO) of CSF distributed in the ventricles and perivascular spaces (PVS). This method could obtain 3D high resolution (1 mm isotropic) imaging of CSF MO with full brain coverage within five min and distinguish the CSF MO across different pulse phases using a peripheral pulse unit (PPU). The MO curves had the largest amplitude value in the PVS of middle cerebral artery (11.11 × 10−9 m2/s) and the largest amplitude growth rate in the posterior cerebral artery (189%). The average coefficient of variations (CVs) in non-pulse trigger and pulse phase 1 and 3 were 0.11, 0.10 and 0.09 respectively. The MO in older healthy participants was lower compared to the young participants, and the MO in cerebral major artery stenosis patients with acute ischemia stroke (AIS) were lower compared to those without AIS in several ventriclar ROIs (P < 0.05). This sequence is a clinically feasible method to effectively evaluate CSF flow patterns in human brain.

Impact of continuous-flow mechanical circulatory support on cerebrospinal fluid motility.

Mechanical circulatory support (MCS), including ventricular assist devices (VADs), have emerged as promising therapeutic alternatives for end-stage congestive heart failure (CHF). The latest generation of these devices are continuous flow (CF) blood pumps. While there have been demonstrated benefits to patient outcomes due to CF-MCS, there continue to be significant clinical challenges. Research to-date has concentrated on mitigating thromboembolic risk (stroke), while the downstream impact of CF-MCS on the cerebrospinal fluid (CSF) flow has not been well investigated. Disturbances in the CSF pressure and flow patterns are known to be associated with neurologic impairment and diseased states. Thus, here we seek to develop an understanding of the pathophysiologic consequences of CF-MCS on CSF dynamics. We built and validated a computational framework using lumped parameter modeling of cardiovascular, cerebrovascular physics, CSF dynamics, and autoregulation. A sensitivity analysis was performed to confirm robustness of the modeling framework. Then, we characterized the impact of CF-MCS on the CSF and investigated cardiovascular conditions of healthy and end-stage heart failure. Modeling results demonstrated appropriate hemodynamics and indicated that CSF pressure depends on blood flow pulsatility more than CSF flow. An acute equilibrium between CSF production and absorption was observed in the CF-MCS case, characterized by CSF pressure remaining elevated, and CSF flow rates remaining below healthy, but higher than CHF states. This research has advanced our understanding of the impact of CF-MCS on CSF dynamics and cerebral hemodynamics.

Dorsal craniovertebral junction arachnoid cyst

Arachnoid cysts causing symptoms, at the level of the craniovertebral junction (CVJ), are very infrequently reported. Inadequate imaging (either only of brain up to foramen magnum or only cervical spine) often leads to delayed diagnosis in these cases. Those that straddle the CVJ do not cause tonsillar descent and differ from the more common pure retro or supracerebellar posterior fossa cysts that cause tonsillar descent, although they present in an identical manner. We treated the index case by fenestration of the lower end of the cyst into the spinal subarachnoid space instead of the more extensive surgeries hitherto described as we felt that cerebrospinal fluid flow patterns with an intact foramen magnum and help conferred by gravity would prevent re-accumulation.

Cerebrospinal fluid dynamics along the optic nerve.

The cerebrospinal fluid (CSF) plays an important role in delivering nutrients and eliminating the metabolic wastes of the central nervous system. An interrupted CSF flow could cause disorders of the brain and eyes such as Alzheimer's disease and glaucoma. This review provides an overview of the anatomy and flow pathways of the CSF system with an emphasis on the optic nerve. Imaging technologies used for visualizing the CSF dynamics and the anatomic structures associated with CSF circulation have been highlighted. Recent advances in the use of computational models to predict CSF flow patterns have been introduced. Open questions and potential mechanisms underlying CSF circulation at the optic nerves have also been discussed.

Direction and magnitude of cerebrospinal fluid flow vary substantially across central nervous system diseases

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

A preliminary exploration of acute intracranial pressure-cerebrospinal fluid production relationships in experimental hydrocephalus.

CONTEXT:By occluding the fourth ventricle simultaneously obtaining telemetric data on intracranial pressure (ICP) and cerebrospinal fluid (CSF) production, the authors of this study investigate a variety of physiologic parameters in cases of experimental hydrocephalus.AIMS:The aim of this study is to provide a new context on the disrupted homeostasis in hydrocephalus and guide toward improved treatment based on multiple physiological parameters.MATERIALS AND METHODS:Hydrocephalus was induced in ten 21-day-old Sprague–Dawley rats by blocking the flow of CSF to the fourth ventricle with kaolin. Ten days post induction, when physical signs of ventriculomegaly reached Evan's ratio (ER) of ≥0.46, CSF flow and ICP were measured while manipulating body position (0°, 45°, 90°) and heart rate.RESULTS:In hydrocephalic animals (ER ≥0.46), we found a near-steady average acute ICP (13.638 ± 2.331) compared to age-matched controls (ER <0.30) (13.068 ± 8.781), whose ICP fluctuated with the position. Hydrocephalic and controls exhibited an insignificant degree of parabolic shifts in CSF production when body position was changed from prone to 90° and again when moved back to the prone position, a trend more noteworthy in controls (P = 0.1322 and 0.2772). A Pearson's Correlation found CSF production and ICP to be correlated at baseline 0° posture (P = 0.05) in the control group, but not the hydrocephalic group. Weight appeared to play a role when animals were held at 90°. No significant changes in ICP or CSF flow patterns were observed when the heart rate was increased within either group.CONCLUSIONS:These preliminary findings suggest that our standard assumptions of posture-dependent changes in ICP created using data from physiologic data may be inaccurate in the hydrocephalic patient, and thus describe a need to further explore these relationships.

Analysis of Cerebrospinal Fluid Flowmetry in Evaluating the Efficiency of Endoscopic Third Ventriculostomy in Aqueductal Stenosis

Background: Endoscopic third ventriculostomy (ETV) approach was gaining popularity over shunt placement in obstructive hydrocephalus. Postoperative ETV assessment and patients follow up remains a matter of controversy and challenge to ensure efficiency and patency of ventriculostomy.Aim of the work: To assess whether cerebrospinal fluid (CSF) flow is restored after ETV and similarity to flow in normal aqueduct with patients clinical and ventricular size changes assessment.Patients and Methods: From April 2016 to April 2019, 30 patients with hydrocephalus due to aqueductal stenosis (AS) were treated with ETV. They were followed up for ventriculostomy patency within the 1st, 6th and 9th month after surgery and compared to 22 persons as a control group of normal aqueductal flow with phase contrast magnetic resonance imaging (PC MRI).Results: Twenty-three (23) patients restored pulsatile bidirectional pattern of CSF flow across the ventriculostomy similar to that of aqueductal flow. While one patient had no flow during the 1st follow up and 6 patients showed initial pulsatile flow then developed flow disturbance during the 2nd follow up period. Absolute stroke volume values showed significant statistical difference between ETV and control groups (p value < 0.001). The value of 85 μl showed sensitivity and specificity of 84.3% and 81.7%, respectively as a cutoff value of ETV efficiency.Conclusion: ETV is an efficient technique to restores the physiological pulsatile Cerebrospinal fluid flow. Absolute stroke volume was a good predictor of ETV efficiency.

Classification of Chiari I malformation based on various cerebrospinal fluid flow patterns at the cranial-vertebral junction and selection of surgical procedure

Objective To discuss about the classification of Chiari Ⅰ malformation based on different CSF (cerebrospinal fluid) flow patterns at the cranial-vertebral junction (CVJ) and to investigate its surgical strategies and outcomes. Methods A total of 126 patients with Chiari Ⅰ malformation were admitted to Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University from January 2008 to December 2015 and retrospectively enrolled into this study. According to the preoperative findings obtained by using cine phase-contrast MRI (cine PC-MRI) and based on the abnormal CSF flow dynamics at the CVJ, all those patients of Chiari Ⅰ malformation were classified into 3 patterns: type Ⅰ (36 cases), type Ⅱ (48 cases) and type Ⅲ (42 cases). Intraoperative ultrasound to detect cerebrospinal fluid again determined the surgical strategy. In type Ⅰ patients, 34 patients underwent subdural decompression, and the remaining 2 patients underwent subarachnoid decompression due to cerebrospinal fluid obstruction. In type Ⅱ patients, 36 patients underwent subarachnoid decompression and the remaining 12 cases underwent subdural decompression. In type Ⅲ patients, 40 cases underwent subarachnoid decompression, and the remaining 2 cases underwent subdural decompression due to unobstructed cerebrospinal fluid flow. Two weeks after surgery, the patients underwent an imaging review and assessment based on cervical spine modified Japanese Orthopaedic Association (mJOA) score. All patients underwent clinical follow-up. The follow-up included the use of the cervical spine mJOA score to assess the improvement of syringomyelia-related symptoms. The Chicago Chiari Outcome Scale (CCOS) was used to assess postoperative neurological recovery. Results All 126 patients had successful surgery. There were no cases of new neurological deficits after operation. Eight cases (6.3%) had fever, and 5 cases (4.0%) had cerebrospinal fluid leakage, which improved after symptomatic treatment. Two weeks after surgery, imaging examination showed that there was no significant improvement in syringomyelia in 2 patients (type Ⅲ, subarachnoid decompression). Further improvement of symptoms was observed after syringomyelia-thoracic shunt. The mJOA score was improved compared with preoperative conditions (12.7±2.0 vs. 10.7±1.6, P<0.01). The follow-up time of 126 patients was 24.8 ± 10.9 months (12 to 96 months). At the last follow-up, the cervial spine mJOA scores of 126 patients were significantly higher than those before surgery (12.8±1.9 vs. 10.7±1.6, P<0.01), but there was no significant difference when compared with two weeks after surgery (P=0.48). There was no significant difference in CCOS score compared with 2 weeks post surgery (14.7±1.5 vs. 14.4±1.5, P=0.576). Conclusions Chiari malformation type Ⅰ could be classified into 3 subtypes according to cerebrospinal fluid dynamic abnormalities in the cranial-cervical junction area. Type Ⅰ is suitable for subdural decompression and type Ⅲ for subarachnoid decompression. In type Ⅱ, specific decompression methods could be chosen based on intraoperative ultrasound through bone window after craniectomy. The postoperative results seem good. Key words: Arnold-Chiari malformation; Hydrodynamics; Neurosurgical procedures; Treatment outcome; Cerebrospinal fluid; Typing

Surgical management of Chiari I malformation based on different cerebrospinal fluid flow patterns at the cranial-vertebral junction

Chiari I malformation has been shown to present different cerebrospinal fluid (CSF) flow patterns at the cranial-vertebral junction (CVJ). Posterior fossa decompression is the first-line treatment for symptomatic Chiari I malformation. However, there is still controversy on the indication and selection of decompression procedures. This research aims to investigate the clinical indications, outcomes, and complications of the decompression procedures as alternative treatments for Chiari I malformation, based on the different CSF flow patterns at the cranial-vertebral junction. In this study, 126 Chiari I malformation patients treated with the two decompression procedures were analyzed. According to the preoperative findings obtained by using cine phase-contrast MRI (cine PC-MRI), the abnormal CSF flow dynamics at the CVJ in Chiari I malformation was classified into three patterns. After a preoperative evaluation and an intraoperative ultrasound after craniectomy, the two procedures were alternatively selected to treat the Chiari I malformation. The indication and selection of the two surgical procedures, as well as their outcomes and complications, are reported in detail in this work. Forty-eight patients underwent subdural decompression (SDD), and 78 received subarachnoid manipulation (SAM). Ninety patients were diagnosed as having Chiari I malformation with a syrinx. Two weeks after the operation, the modified Japanese Orthopedic Association (mJOA) scores increased from the preoperative value of 10.67±1.61 to 12.74±2.01 (P<0.01). The mean duration of follow-up was 24.8months; the mJOA scores increased from the postoperative value of 12.74±2.01 to 12.79±1.91 at the end of follow-up (P=0.48). More complications occurred in the patients who underwent SAM than in those who received SDD (SAM 11 of 78 (9.5%) vs SDD 2 of 48 (3.5%)). The abnormal CSF flow dynamics at the CVJ in Chiari I malformation can be classified into three patterns. A SAM procedure is more feasible in Chiari I malformation (CM1) patients with pattern III CSF flow dynamics, whereas a SDD procedure is more suitable for CM1 patients with pattern I CSF flow dynamics. In CM1 patients with pattern II CSF flow dynamics, an intraoperative ultrasound after craniectomy could play an important role in the selection of an effective decompression procedure.

Time-SLIP Reveals Intramedullary Flow in Syringomyelia

Case Presentation Magnetic resonance imaging (MRI) using a time-spatial labeling inversion pulse (Time-SLIP) method permits visualization of cerebrospinal fluid (CSF) dynamics noninvasively. Time-SLIP enables quantitative and qualitative CSF flow analysis without any limitations in flow velocity or direction. An 85-year-old old male: Syringomyelia (C7-T12) Conventional MRI revealed syringomyelia with multiple syrinx cavities. Time SLIP can detect the CSF flow dynamics in both the intra- and peri-spinal cord simultaneously. The basic CSF flow pattern in the syringomyelia cavity was pulsatile motion in the Cranio-caudal direction and harmonious with the flow in subarachnoid space (Figure 1). Time-SLIP also detected over flow through septum or web. The unique flow across the intramedullary compartments indicated several paths throughout the septum of syrinx (Figure 2). These findings may improve our understanding of disease pathology of syringomyelia and be useful in surgical planning MRI imaging technique 1.5-T MR imager with quadrature-detected phased-array coils Sphygmographic gated single-shot half Fourier fast spin-echo (FSE) sequence. Representative imaging parameters TR: 12−13P−P intervals, TE: 80 msec, BBTI: 1500-4400 msec (100 msec interval), Tag pulse thickness: 30 mm, ETS 6.5 msec, MTX: 256 × 288, FOV: 25 × 25 cm, Slice thickness 5 mm.

Expansion, folding, and abnormal lamination of the chick optic tectum after intraventricular injections of FGF2

Comparative research has shown that evolutionary increases in brain region volumes often involve delays in neurogenesis. However, little is known about the influence of such changes on subsequent development. To get at this question, we injected FGF2--which delays cell cycle exit in mammalian neocortex--into the cerebral ventricles of chicks at embryonic day (ED) 4. This manipulation alters the development of the optic tectum dramatically. By ED7, the tectum of FGF2-treated birds is abnormally thin and has a reduced postmitotic layer, consistent with a delay in neurogenesis. FGF2 treatment also increases tectal volume and ventricular surface area, disturbs tectal lamination, and creates small discontinuities in the pia mater overlying the tectum. On ED12, the tectum is still larger in FGF2-treated embryos than in controls. However, lateral portions of the FGF2-treated tectum now exhibit volcano-like laminar disturbances that coincide with holes in the pia, and the caudomedial tectum exhibits prominent folds. To explain these observations, we propose that the tangential expansion of the ventricular surface in FGF2-treated tecta outpaces the expansion of the pial surface, creating abnormal mechanical stresses. Two alternative means of alleviating these stresses are tectal foliation and the formation of pial holes. The latter probably alter signaling gradients required for normal cell migration and may generate abnormal patterns of cerebrospinal fluid flow; both abnormalities would generate disturbances in tectal lamination. Overall, our findings suggest that evolutionary expansion of sheet-like, laminated brain regions requires a concomitant expansion of the pia mater.

Quantitative analysis of intraspinal cerebrospinal fluid flow in normal adults.

The present study quantitatively analyzed intraspinal cerebrospinal fluid flow patterns in 19 normal adults using fast cine phase-contrast magnetic resonance imaging. Results showed increased downward flow velocity and volume compared with upward flow, and the average downward flow volume of intraspinal cerebrospinal fluid decreased from top to bottom at different intervertebral disc levels. Upward and downward cerebrospinal fluid flow velocity reached a peak at the thoracic intraspinal anterior region, and velocity reached a minimum at the posterior region. Overall measurements revealed that mean upward and downward flow volume positively correlated with the subarachnoid area. Upward peak flow velocity and volume positively correlated with spinal anteroposterior diameter. However, downward peak flow velocity and volume exhibited a negative correlation with spinal anteroposterior diameter. Further flow measurements showed that flow velocity in upward and downward directions was associated with subarachnoid anteroposterior diameter, respectively. The present experimental results showed that cerebrospinal fluid flow velocity and volume varied at different intraspinal regions and were affected by subarachnoid space area and anteroposterior diameter size.

Visualisation of cerebrospinal fluid flow patterns in albino Xenopus larvae in vivo

BackgroundIt has long been known that cerebrospinal fluid (CSF), its composition and flow, play an important part in normal brain development, and ependymal cell ciliary beating as a possible driver of CSF flow has previously been studied in mammalian fetuses in vitro. Lower vertebrate animals are potential models for analysis of CSF flow during development because they are oviparous. Albino Xenopus laevis larvae are nearly transparent and have a straight, translucent brain that facilitates the observation of fluid flow within the ventricles. The aim of these experiments was to study CSF flow and circulation in vivo in the developing brain of living embryos, larvae and tadpoles of Xenopus laevis using a microinjection technique.MethodsThe development of Xenopus larval brain ventricles and the patterns of CSF flow were visualised after injection of quantum dot nanocrystals and polystyrene beads (3.1 or 5.8 μm in diameter) into the fourth cerebral ventricle at embryonic/larval stages 30-53.ResultsThe fluorescent nanocrystals showed the normal development of the cerebral ventricles from embryonic/larval stages 38 to 53. The polystyrene beads injected into stage 47-49 larvae revealed three CSF flow patterns, left-handed, right-handed and non-biased, in movement of the beads into the third ventricle from the cerebral aqueduct (aqueduct of Sylvius). In the lateral ventricles, anterior to the third ventricle, CSF flow moved anteriorly along the outer wall of the ventricle to the inner wall and then posteriorly, creating a semicircle. In the cerebral aqueduct, connecting the third and fourth cerebral ventricles, CSF flow moved rostrally in the dorsal region and caudally in the ventral region. Also in the fourth ventricle, clear dorso-ventral differences in fluid flow pattern were observed.ConclusionsThis is the first visualisation of the orchestrated CSF flow pattern in developing vertebrates using a live animal imaging approach. CSF flow in Xenopus albino larvae showed a largely consistent pattern, with the exception of individual differences in left-right asymmetrical flow in the third ventricle.

Pocket Brain Review

Neuroanatomy teaching most often takes the form of detailed didactic lectures, consolidated by application of new knowledge in the anatomy laboratory where cadaveric specimens can be closely examined, and are often accompanied by clinical vignettes and imaging correlates. Such exposure to neuroanatomy is undoubtedly effective, but for learners then proceeding to further training where neuroanatomy is frequently relevant, portable, accessible, and accurate learning aids are invaluable. The emergence and now ubiquitous availability of smartphones and tablets provides an opportunity for all areas of medical education, and may be particularly amenable to the areas requiring memorization of structures in three dimensions, such as anatomy. Pocket Brain is a new application from eMedia Interactive Ltd. that aims to facilitate neuroanatomy education, through the use of interactive 3D multi-layer models and labeled cross sections of the brain. The app also includes labeled cross sections and animations of the four major tracts. Maneuvering through the application is intuitive, and as tested (version 1.2 on the iPhone 4s with iOS 6.0, and on the iPad 1 with iOS 5.1.1) the application runs well without hang time or crashes. Where the iPhone version shines, the iPad version is even better for demonstration and discussion purposes with its larger screen. Figure 1 Snapshot of 3D Brain Layers within the Pocket Brain application. Pocket Brain includes a glossary that is aimed at a relatively introductory level (i.e., anatomy students, medical students, nursing, and allied health) as well as eight clinical cases that allow the user to localize the lesion and form a diagnosis. The ability to view the brain from different angles in three-dimensional space and to peel off layers in the process makes it useful for illustrating the relative locations of structures (i.e., arterial supply and cranial nerves when discussing aneurysms). However, the level of detail available is limited, particularly on the labeling of vascular structures, which limits the app’s usefulness as a learning tool beyond the level of senior medical or anatomy student, and restricts its utility for localization at the clinic or ward. Similarly, the cross-sectional views are simplified, with a sufficient level of detail for introductory learners, but not for those beyond the senior medical or anatomy student level. I would recommend Pocket Brain for students learning neuroanatomy at the introductory level. For residents and consultants in neurology and neurosurgery, though, Pocket Brain will have limited utility in the clinic and at the bedside from a teaching perspective. The true potential of this application is in future version updates. The foundation for a broadly useful application for both medical education as well as clinical localization is there. Future updates could include more detailed vascular anatomy (i.e., middle cerebral artery branch labels with vascular territories for vascular lesion localization), connectivity between nuclei (i.e., movement disorder pathways), and cerebrospinal fluid flow patterns (including common points of obstruction and the clinical consequences). Anatomical details for specific clinical syndromes (i.e., internuclear ophthalmoplegia) would make Pocket Brain more useful to senior learners. Pocket Brain is among the first useful applications for neuroanatomy education, but the limitations cited above should be considered. While certainly useful for students new to neuroanatomy, the potential for more anatomical detail in future updates makes this application worth watching for expanded appeal to neurologists and to the broader neurosciences community.

The measurement of CSF flow through the aqueduct in normal and hydrocephalic children: from where does it come, to where does it go?

Despite 100years of study, the theories of cerebrospinal fluid (CSF) formation and absorption remain controversial. Measuring CSF flow through the aqueduct using magnetic resonance imaging (MRI) provides a unique insight into the physiology of CSF hydrodynamics. The published data in adults tend to refute rather than support the prevailing theories of CSF flow. There are limited data regarding this metric in children. This paper seeks to measure the aqueduct flow in normal and hydrocephalic children to help formulate a more complete theory of CSF flow. Twenty-four children with communicating hydrocephalus aged from 4months to 16years underwent MRI flow quantification of the aqueduct measuring the net flow. The patients were compared to 19 controls. The controls revealed two different flow patterns: (1) an infantile pattern characterized by flow directed into the ventricular system and (2) a mature pattern with flow directed out of the ventricles, similar to the published findings in adults. In infants with communicating hydrocephalus, the aqueduct flow changed direction but was of similar magnitude compared with the controls (p = 0.001). In the older hydrocephalic children, the flow was elevated 7-fold, but the direction was unchanged compared to the controls (p = 0.002). There is an abrupt change in the aqueduct CSF flow pattern at the age of 2years from an infantile pattern to a mature pattern. These findings together with the findings in hydrocephalic children do not support the current theories of CSF hydrodynamics. A new theory of CSF circulation based on capillary absorption is presented.

Three-dimensional computational prediction of cerebrospinal fluid flow in the human brain

A three-dimensional model of the human cerebrospinal fluid (CSF) spaces is presented. Patient-specific brain geometries were reconstructed from magnetic resonance images. The model was validated by comparing the predicted flow rates with Cine phase-contrast MRI measurements. The model predicts the complex CSF flow patterns and pressures in the ventricular system and subarachnoid space of a normal subject. The predicted maximum rostral to caudal CSF flow in the pontine cistern precedes the maximum rostral to caudal flow in the ventricles by about 10% of the cardiac cycle. This prediction is in excellent agreement with the subject-specific flow data. The computational results quantify normal intracranial dynamics and provide a basis for analyzing diseased intracranial dynamics.

Insight into the patterns of cerebrospinal fluid flow in the human ventricular system using MR velocity mapping

The patterns of cerebrospinal fluid (CSF) flow within the human ventricular system are still not fully understood in all their complexity. Knowledge is based on either the interpretation of CSF flow curves or computational simulations. Both approaches only provide an incomplete insight into the spatial and temporal dynamics of CSF flow. Time-resolved three-dimensional magnetic resonance velocity mapping has previously been used to investigate normal and pathologic blood flow patterns in the human vascular system. Here we used this technique to study the spatial and temporal dynamics of CSF flow in the ventricular system of 40 normal volunteers. Classification of the patterns of CSF flow based on calculation of three-dimensional particle path lines over the cardiac cycle revealed one uniform flow pattern for the lateral ventricles, three categories for the third and two categories for the fourth ventricle. We found no significant aging effects on either the presence of a specific CSF flow pattern or on CSF flow velocities. Our results provide the first detailed demonstration of the patterns of CSF flow within the human ventricular system.