Prospective measurement of the width of cerebrospinal fluid spaces by cranial ultrasound in neurologically healthy children aged 0-19 months.

BACKGROUND: Ultrasound (US) is often the first method used to look for brain or cerebrospinal fluid (CSF) space pathologies. Knowledge of normal CSF width values is essential. Most of the available US normative values were established over 20 years ago, were obtained with older equipment, and cover only part of the age spectrum that can be examined by cranial US. This prospective study aimed to determine the normative values of the widths of the subarachnoid and internal CSF spaces (craniocortical, minimal and maximal interhemispheric, interventricular, and frontal horn) for high-resolution linear US probes in neurologically healthy infants and children aged 0-19 months and assess whether subdural fluid collections can be delineated. METHODS: Two radiologists measured the width of the CSF spaces with a conventional linear probe and an ultralight hockey-stick probe in neurologically healthy children not referred for cranial or spinal US. RESULTS: This study included 359 neurologically healthy children (nboys = 178, 49.6%; ngirls = 181, 50.4%) with a median age of 46.0 days and a range of 1-599 days. We constructed prediction plots, including the 5th, 50th, and 95th percentiles, and an interactive spreadsheet to calculate normative values for individual patients. The measurements of the two probes and the left and right sides did not differ, eliminating the need for separate normative values. No subdural fluid collection was detected. CONCLUSION: Normative values for the widths of the subarachnoid space and the internal CSF spaces are useful for evaluating intracranial pathology, especially when determining whether an increase in the subarachnoid space width is abnormal.

Reduced cerebrospinal fluid motion in patients with Parkinson's disease revealed by magnetic resonance imaging with low b-value diffusion weighted imaging.

BACKGROUND: Parkinson's disease is characterized by dopamine-responsive symptoms as well as aggregation of α-synuclein protofibrils. New diagnostic methods assess α-synuclein aggregation characteristics from cerebrospinal fluid (CSF) and recent pathophysiologic mechanisms suggest that CSF circulation disruptions may precipitate α-synuclein retention. Here, diffusion-weighted MRI with low-to-intermediate diffusion-weightings was applied to test the hypothesis that CSF motion is reduced in Parkinson's disease relative to healthy participants. METHODS: Multi-shell diffusion weighted MRI (spatial resolution = 1.8 × 1.8 × 4.0 mm) with low-to-intermediate diffusion weightings (b-values = 0, 50, 100, 200, 300, 700, and 1000 s/mm2) was applied over the approximate kinetic range of suprasellar cistern fluid motion at 3 Tesla in Parkinson's disease (n = 27; age = 66 ± 6.7 years) and non-Parkinson's control (n = 32; age = 68 ± 8.9 years) participants. Wilcoxon rank-sum tests were applied to test the primary hypothesis that the noise floor-corrected decay rate of CSF signal as a function of b-value, which reflects increasing fluid motion, is reduced within the suprasellar cistern of persons with versus without Parkinson's disease and inversely relates to choroid plexus activity assessed from perfusion-weighted MRI (significance-criteria: p < 0.05). RESULTS: Consistent with the primary hypothesis, CSF decay rates were higher in healthy (D = 0.00673 ± 0.00213 mm2/s) relative to Parkinson's disease (D = 0.00517 ± 0.00110 mm2/s) participants. This finding was preserved after controlling for age and sex and was observed in the posterior region of the suprasellar cistern (p < 0.001). An inverse correlation between choroid plexus perfusion and decay rate in the voxels within the suprasellar cistern (Spearman's-r=-0.312; p = 0.019) was observed. CONCLUSIONS: Multi-shell diffusion MRI was applied to identify reduced CSF motion at the level of the suprasellar cistern in adults with versus without Parkinson's disease; the strengths and limitations of this methodology are discussed in the context of the growing literature on CSF flow.

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

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

Radiological Analysis of Cerebrospinal Fluid Dynamics at the Craniovertebral Junction Using Time-Spatial Labeling Inversion Pulse Magnetic Resonance Imaging in Patients with Cervical Spinal Canal Stenosis.

OBJECTIVE: Spondylotic changes in the cervical spine cause degeneration, leading to cervical spinal canal stenosis. This stenotic change can affect cerebrospinal fluid (CSF) dynamics by compressing the dural sac and reducing space in the subarachnoid space. We examined CSF dynamics at the craniovertebral junction (CVJ) using time-spatial labeling inversion pulse magnetic resonance imaging (Time-SLIP MRI) in patients with cervical spinal canal stenosis. METHODS: The maximum longitudinal movement of the CSF at the CVJ was measured as length of motion (LOM) in the Time-SLIP MRI of 56 patients. The sum of ventral and dorsal LOM was defined as the total LOM. Patients were classified into 3 groups depending on their spinal sagittal magnetic resonance imaging findings: control (n = 27, Kang classification grades 0 and 1), stenosis (n = 14, Kang classification grade 2), and severe stenosis (n = 15, Kang classification grade 3). RESULTS: Time-SLIP MRI revealed pulsatile movement of the CSF at the CVJ. The mean total, ventral, and dorsal LOM was 14.2 ± 9, 8.1 ± 5.7, and 3.8 ± 2.9 mm, respectively. The ventral LOM was significantly larger than the dorsal LOM. The total LOM was significantly smaller in the severe stenosis group (6.1 ± 3.4 mm) than in the control (16.0 ± 8.4 mm) or stenosis (11 ± 5.4 mm) groups (P < 0.001, Kruskal-Wallis H-test). In 5 patients, postoperative total LOM was improved after adequate decompression surgery. CONCLUSIONS: This study demonstrates that CSF dynamics at the CVJ are influenced by cervical spinal canal stenosis. Time-SLIP MRI is useful for evaluating CSF dynamics at the CVJ in patients with spinal canal stenosis.

Measurement of changes in cerebrospinal fluid pulsation after traumatic brain injury using echo-planar imaging-based functional MRI.

Traumatic brain injury (TBI) is a major public health concern worldwide, with a high incidence and a significant impact on morbidity and mortality. The alteration of cerebrospinal fluid (CSF) dynamics after TBI is a well-known phenomenon; however, the underlying mechanisms and their implications for cognitive function are not fully understood. In this study, we propose a new approach to studying the alteration of CSF dynamics in TBI patients. Our approach involves using conventional echo-planar imaging-based functional MRI with no additional scan, allowing for simultaneous assessment of functional CSF dynamics and blood oxygen level-dependent-based functional brain activities. We utilized two previously suggested indices of (i) CSFpulse, and (ii) correlation between global brain activity and CSF inflow. Using CSFpulse, we demonstrated a significant decrease in CSF pulsation following TBI (p < 0.05), which was consistent with previous studies. Furthermore, we confirmed that the decrease in CSF pulsation was most prominent in the early months after TBI, which could be explained by ependymal ciliary loss, intracranial pressure increment, or aquaporin-4 dysregulation. We also observed a decreasing trend in the correlation between global brain activity and CSF inflow in TBI patients (p < 0.05). Our findings suggest that the decreased CSF pulsation after TBI could lead to the accumulation of toxic substances in the brain and an adverse effect on brain function. Further longitudinal studies with larger sample sizes, TBI biomarker data, and various demographic information are needed to investigate the association between cognitive decline and CSF dynamics after TBI. Overall, this study sheds light on the potential role of altered CSF dynamics in TBI-induced neurologic symptoms and may contribute to the development of novel therapeutic interventions.

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.

Intrathecal [64Cu]Cu-albumin PET reveals age-related decline of lymphatic drainage of cerebrospinal fluid.

Age-related cognitive decline is associated with dysfunctional lymphatic drainage of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. In this study, intrathecal [64Cu]Cu-albumin positron emission tomography (PET) was applied in mice to evaluate lymphatic drainage of CSF and its variation with age. [64Cu]Cu-albumin PET was performed at multiple time points after intrathecal injection of [64Cu]Cu-albumin at an infusion rate of 700 nl/min in adult and aged mice (15-25 months old). CSF clearance and paravertebral lymph nodes were quantified after injection and during the stationary phase. Stationary phase of the next day followed the initial perturbed state by injection of 6 ul (1/7 of total CSF volume) and CSF clearance half-time from the subarachnoid space was 93.4 ± 19.7 and 123.3 ± 15.6 min in adult and aged mice (p = 0.01), respectively. While the % injected dose of CSF space were higher, the activity of the paravertebral lymph nodes were lower in the aged mice on the next day. [64Cu]Cu-albumin PET enabled us to quantify CSF-lymphatic drainage across all levels of brain spinal cords and to visualize and quantify lymph node activity due to CSF drainage. [64Cu]Cu-albumin PET revealed the age-related decrease of the lymphatic drainage of CSF due to this decreased drainage from the subarachnoid space, especially during the stationary phase, in aged mice.

Near-Infrared Fluorescence Tomography and Imaging of Ventricular Cerebrospinal Fluid Flow and Extracranial Outflow in Non-Human Primates.

The role of the lymphatics in the clearance of cerebrospinal fluid (CSF) from the brain has been implicated in multiple neurodegenerative conditions. In premature infants, intraventricular hemorrhage causes increased CSF production and, if clearance is impeded, hydrocephalus and severe developmental disabilities can result. In this work, we developed and deployed near-infrared fluorescence (NIRF) tomography and imaging to assess CSF ventricular dynamics and extracranial outflow in similarly sized, intact non-human primates (NHP) following microdose of indocyanine green (ICG) administered to the right lateral ventricle. Fluorescence optical tomography measurements were made by delivering ~10 mW of 785 nm light to the scalp by sequential illumination of 8 fiber optics and imaging the 830 nm emission light collected from 22 fibers using a gallium arsenide intensified, charge coupled device. Acquisition times were 16 seconds. Image reconstruction used the diffusion approximation and hard-priors obtained from MRI to enable dynamic mapping of ICG-laden CSF ventricular dynamics and drainage into the subarachnoid space (SAS) of NHPs. Subsequent, planar NIRF imaging of the scalp confirmed extracranial efflux into SAS and abdominal imaging showed ICG clearance through the hepatobiliary system. Necropsy confirmed imaging results and showed that deep cervical lymph nodes were the routes of extracranial CSF egress. The results confirm the ability to use trace doses of ICG to monitor ventricular CSF dynamics and extracranial outflow in NHP. The techniques may also be feasible for similarly-sized infants and children who may suffer impairment of CSF outflow due to intraventricular hemorrhage.

Combined Cerebrospinal Fluid Hydrodynamics and Fourth Ventricle Outlet Morphology to Improve Predictive Efficiency of Prognosis for Chiari Malformation Type I Decompression.

OBJECTIVE: To identify the morphological characteristics together with cerebrospinal fluid (CSF) hydrodynamics on preoperative magnetic resonance imaging that improve the prediction of foramen magnum decompression (FMD) treatment outcome for Chiari malformations type I (CM-I) patients compared with the CSF hydrodynamics-based model. METHODS: This retrospective study included CM-I patients who underwent FMD, phase-contrast cine magnetic resonance, and static MR between January 2018 and March 2022. The relationships of the preoperative CSF hydrodynamic quantifications derived from phase-contrast cine magnetic resonance and morphological measurements from static magnetic resonance imaging, clinical indicators with different outcomes, were analyzed with logistic regression analysis. The outcomes were determined using the Chicago Chiari Outcome Scale. The predictive performance was evaluated with receiver operating characteristic, calibration, decision curves and area under the receiver operating characteristic curve, net reclassification index, and integrated discrimination improvement and was compared with CSF hydrodynamics-based model. RESULTS: A total of 27 patients were included. 17 (63%) had improved outcomes and 10 (37%) had poor outcomes. The peak diastolic velocity of the aqueduct midportion (odd ratio, 5.17; 95% confidence interval: 1.08, 24.70; P = 0.039) and the fourth ventricle outlet diameter (odd ratio, 7.17; 95% confidence interval: 1.07, 48.16; P = 0.043) were predictors of different prognoses. The predictive performance improved significantly than the CSF hydrodynamics-based model. CONCLUSIONS: Combined CSF hydrodynamic and static morphologic MR measurements can better predict the response to FMD. A higher peak diastolic velocity of the aqueduct midportion and broader fourth ventricle outlet were associated with satisfying outcomes after decompression in CM-I patients.

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.

[Visualization of Cerebrospinal Fluid Dynamics by Respiratory Motion Using Phase Dispersion: Optimization of Spatial and Temporal Resolutions].

PURPOSE: The purpose of this study was to investigate the optimal spatial resolution and temporal resolution of dynamic improved motion-sensitized driven-equilibrium steady-state free precession for visualization of respiratory-driven cerebrospinal fluid (CSF) dynamics. METHODS: We investigated the differences in the visualization using the midsagittal cross-sections of nine healthy volunteers by three imaging conditions. (A: spatial resolution 0.49×0.49×5 mm, temporal resolution 1000 ms; B: 0.49×0.49×5 mm, 430 ms; and C: 0.78×0.78×5 mm, 200 ms). First, we calculated the CSF of the third and fourth ventricles and the signal-to-noise ratio (SNR) of the pons. Next, we calculated the signal intensity ratio (SIR) of the CSF flowing at 10 cm/s or more and the CSF flowing at 10 cm/s or less due to respiration. We also calculated the difference between the inspiration and expiration SIR. Furthermore, 1) the presence of flow in the third and fourth ventricles centered on the cerebral aqueduct and 2) the change in flow due to respiration was investigated by a three-point scale visual assessment by seven radiological technologists. RESULTS: The SNR was the highest in A, the next highest in B, and the lowest in C in all cases. There were significant differences between A and B, and A and C in CSF of the third and fourth ventricles. However, there was no significant difference between B and C. The CSF signal intensity changed with respiration. The SIR of the third ventricle was higher on inspiration and lower on expiration. Conversely, the SIR of the fourth ventricle was lower on inspiration and higher on expiration. There was a significant difference between A and C and B and C in each SIR (p<0.05). The difference between inspiration and expiration SIR was the highest in B, the next highest in A, and the lowest in C in both the third and fourth ventricles. Significant differences were found between A and C, and between B and C (p<0.05). There was no significant difference in the presence of flow in the third and fourth ventricles centered on the cerebral aqueduct (p=0.264). On the other hand, there was a significant difference between the imaging conditions in the change in flow due to respiration, with B having a higher value than the others (p<0.001). CONCLUSION: The optimal spatial and temporal resolutions were 0.49×0.49×5 mm and 430 ms, respectively. The results also suggest that it is important to carefully set the imaging conditions for the spatial and temporal resolutions because of the use of phase dispersion in this method.

Characterising spinal cerebrospinal fluid flow in the pig with phase-contrast magnetic resonance imaging.

BACKGROUND: Detecting changes in pulsatile cerebrospinal fluid (CSF) flow may assist clinical management decisions, but spinal CSF flow is relatively understudied. Traumatic spinal cord injuries (SCI) often cause spinal cord swelling and subarachnoid space (SAS) obstruction, potentially causing pulsatile CSF flow changes. Pigs are emerging as a favoured large animal SCI model; therefore, the aim of this study was to characterise CSF flow along the healthy pig spine. METHODS: Phase-contrast magnetic resonance images (PC-MRI), retrospectively cardiac gated, were acquired for fourteen laterally recumbent, anaesthetised and ventilated, female domestic pigs (22-29 kg). Axial images were obtained at C2/C3, T8/T9, T11/T12 and L1/L2. Dorsal and ventral SAS regions of interest (ROI) were manually segmented. CSF flow and velocity were determined throughout a cardiac cycle. Linear mixed-effects models, with post-hoc comparisons, were used to identify differences in peak systolic/diastolic flow, and maximum velocity (cranial/caudal), across spinal levels and dorsal/ventral SAS. Velocity wave speed from C2/C3 to L1/L2 was calculated. RESULTS: PC-MRI data were obtained for 11/14 animals. Pulsatile CSF flow was observed at all spinal levels. Peak systolic flow was greater at C2/C3 (dorsal: - 0.32 ± 0.14 mL/s, ventral: - 0.15 ± 0.13 mL/s) than T8/T9 dorsally (- 0.04 ± 0.03 mL/s; p < 0.001), but not different ventrally (- 0.08 ± 0.08 mL/s; p = 0.275), and no difference between thoracolumbar levels (p > 0.05). Peak diastolic flow was greater at C2/C3 (0.29 ± 0.08 mL/s) compared to T8/T9 (0.03 ± 0.03 mL/s, p < 0.001) dorsally, but not different ventrally (p = 1.000). Cranial and caudal maximum velocity at C2/C3 were greater than thoracolumbar levels dorsally (p < 0.001), and T8/T9 and L1/L2 ventrally (p = 0.022). Diastolic velocity wave speed was 1.41 ± 0.39 m/s dorsally and 1.22 ± 0.21 m/s ventrally, and systolic velocity wave speed was 1.02 ± 0.25 m/s dorsally and 0.91 ± 0.22 m/s ventrally. CONCLUSIONS: In anaesthetised and ventilated domestic pigs, spinal CSF has lower pulsatile flow and slower velocity wave propagation, compared to humans. This study provides baseline CSF flow at spinal levels relevant for future SCI research in this animal model.

Correlation between individual physical characteristics and spinal cerebrospinal fluid volume.

Spinal cerebrospinal fluid (CSF) volume is the primary determinant for the spread of spinal anesthesia. However, it cannot generally be obtained during spinal anesthesia, and patient physical characteristics are always adopted to obtain a suitable spinal spread. In this study, we sought to explore the relationship between individual physical characteristics and thoracosacral CSF volume to provide a theoretical basis for more accurate spinal anesthesia. In total 35 healthy volunteers were enrolled in this study. Three-dimensional magnetic resonance imaging was used to reconstruct and measure the spinal CSF volume. Physical characteristics and spinal CSF volume were recorded. Bivariate and multiple linear regression analyses were used to analyze the correlation between the individual physical characteristics and thoracosacral CSF volume. Total of 31 participants were included in the final analysis. Bivariate linear correlation analysis showed that the volume of thoracosacral CSF was correlated with both individual dorso-sacral distance and height (both p < 0.01), but not with abdominal girth (p > 0.05). Multiple linear regression analyses revealed that the adjusted R2 values were 0.404 for the regression equation between thoracosacral CSF volume, dorso-sacral distance, and abdominal girth. Our study showed that dorso-sacral distance and abdominal girth were essential factors contributing to thoracosacral CSF volume. A longer dorso-sacral distance and smaller abdominal girth mean larger spinal CSF volume.

The role of the parenchymal vascular system in cerebrospinal fluid tracer clearance.

OBJECTIVES: The current understanding of cerebral waste clearance (CWC) involves cerebrospinal fluid (CSF) participation but lacks convincing evidence for the direct participation of the parenchymal vascular system. The objective of this study was to evaluate the role of the parenchymal vascular system in CSF tracer clearance in rats. METHODS: We used superparamagnetic iron oxide-enhanced susceptibility-weighted imaging (SPIO-SWI) and quantitative susceptibility mapping (QSM) methods to simultaneously study 7 T MRI signal changes in parenchymal veins, arteries, and their corresponding para-vascular spaces in 26 rats, following intra-cisterna magna (ICM) infusion of different CSF tracers (FeREX, Ferumoxytol, Fe-Dextran) to determine the amount of tracer in the artery and vein quantitatively. RESULTS: We observed that the parenchymal venous system participated in CSF tracer clearance following ICM infusion of different MRI tracers with different concentrations of iron. Parenchymal venous participation was more obvious when 75 µg iron was injected. In the parenchymal veins, the relative mean (± SE) value of the susceptibility increased by 13.5 (± 1.0)% at 15 min post-tracer infusion (p < 0.01), and 33.6 (± 6.7)% at 45 min post-tracer infusion (p = 0.01), compared to baseline. In contrast to the parenchymal veins, a negligible amount of CSF tracer entered the parenchymal arteries: 1.3 (± 2.6)% at 15 min post-tracer infusion (p = 0.6), and 12 (± 19)% at 45 min post-tracer infusion (p = 0.5), compared to baseline. CONCLUSIONS: MRI tracers can enter the parenchymal vascular system and more MRI tracers were observed in the cerebral venous than arterial vessels, suggesting the direct participation of parenchymal vascular system in CWC. KEY POINTS: • MRI results revealed that the parenchymal venous system directly participates in cerebrospinal fluid tracer clearance following ICM infusion of MRI tracer. • Different sizes of MRI tracers can enter the parenchymal venous system.

Blood and cerebrospinal fluid flow oscillations measured with real-time phase-contrast MRI: breathing mode matters.

BACKGROUND: Cervical blood and cerebrospinal fluid (CSF) flow rates can be quantified with Phase-contrast (PC) MRI, which is routinely used for clinical studies. Previous MRI studies showed that venous and CSF flow alterations are linked to various pathological conditions. Since it is well known that, besides the heart beating, the thoracic pump influences the blood and CSF dynamics, we studied the effect of different respiration modes on blood and CSF flow rates using a real-time (RT)-PC prototype. METHODS: Thirty healthy volunteers were examined with a 3 T scanner. A RT-PC sequence was acquired at the first cervical level to quantify the flow rates of internal carotid arteries, internal jugular veins (IJVs) and CSF. Each RT-PC acquisition was repeated three times, while the subjects were asked to breathe in three different ways for 60 s each: freely (F), with a constant rate (PN) and with deep and constant respiration rate (PD). The average flow rates were computed, they were removed from the respective signals and integrated in the inspiratory and expiratory phases (differential volumes). Finally, the power spectral density was computed for each detrended flow rate. High- and very-high frequency peaks were identified on the spectra while their frequencies were compared to the respiratory and cardiac frequencies estimated using a thoracic belt and a pulse oximeter. The area under the spectra was computed in four 0.5 Hz-wide ranges, centered on the high-frequency peak, on very-high frequency peak and its 2nd and 3rd harmonics, and then they were normalized by the flow rate variance. The effect of breathing patterns on average flow rates, on systolic and diastolic peaks, and on the normalized power was tested. Finally, the differential volumes of inspiration were compared to those of expiration. RESULTS: The frequencies of the high- and very-high spectral peaks corresponded to the respiratory and cardiac frequencies. The average flow rate progressively decreased from F to PN to PD breathing, and the cardiac modulations were less predominant especially for the IJVs. The respiratory modulation increased with PD breathing. The average volumes displaced in the inspiratory phases were not significantly different from those of the expiratory one. CONCLUSIONS: The spectral analyses demonstrated higher respiratory modulations in PD compared to free breathing, even prevailing the cardiac modulation in the IJVs, showing an increment of the thoracic pump affecting the flow rate shape.

Impact of age on the cerebrospinal fluid spaces: high-convexity and medial subarachnoid spaces decrease with age.

BACKGROUND: Impaired cerebrospinal fluid (CSF) dynamics may contribute to the pathophysiology of neurodegenerative diseases, and play a crucial role in brain health in older people; nonetheless, such age-related changes have not been well elucidated. Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a neuroimaging phenotype of idiopathic normal-pressure hydrocephalus, originating from impaired CSF dynamics, and closely associated with aging. This study aimed to investigate the pathophysiology of DESH and determine age-related changes in CSF dynamics. METHODS: Using magnetic resonance imaging, we investigated the pathophysiology of DESH by quantitatively evaluating the volumes of DESH-related regions (ventricles [VS], Sylvian fissure [SF], and subarachnoid spaces at high convexity and midline [SHM]) and brain parenchyma in community-dwelling individuals aged ≥ 65 years. DESH-related regions were assessed using a visual rating scale, and volumes measured using voxel-based morphometry. Brain parenchyma volumes were measured using FreeSurfer software. RESULTS: Data from 1,356 individuals were analyzed, and 25 (1.8%) individuals had DESH. Regarding the relationships between the volume of each CSF space and age, VS and SF volumes increased with age, whereas SHM volume did not increase. VS and SF volumes increased as the whole brain volume decreased, whereas SHM volume did not increase even if the whole brain volume decreased; that is, SHM did not expand even if brain atrophy progressed. Moreover, lower Mini-Mental State Examination scores were significantly associated with lower SHM volume and higher VS volume. These associations remained significant even when individuals with DESH were excluded. CONCLUSIONS: This study showed that the volume of high-convexity and medial subarachnoid spaces did not expand and tended to decrease with age; the human brain continuously progresses toward a "DESH-like" morphology with aging in community-dwelling older persons (i.e., DESH might be an "accelerated aging stage" rather than an "age-related disorder"). Our results indicated that brain atrophy may be associated with the development of "DESH-like" morphology. In addition, this morphological change, as well as brain atrophy, is an important condition associated with cognitive decline in older adults. Our findings highlight the importance of investigating the aging process of CSF dynamics in the human brain to preserve brain health in older people.

Effect of Normal Breathing on the Movement of CSF in the Spinal Subarachnoid Space.

BACKGROUND AND PURPOSE: Forced respirations reportedly have an effect on CSF movement in the spinal canal. We studied respiratory-related CSF motion during normal respiration. MATERIALS AND METHODS: Six healthy subjects breathed at their normal rate with a visual guide to ensure an unchanging rhythm. Respiratory-gated phase-contrast MR flow images were acquired at 5 selected axial planes along the spine. At each spinal level, we computed the flow rate voxelwise in the spinal canal, together with the associated stroke volume. From these data, we computed the periodic volume changes of spinal segments. A phantom was used to quantify the effect of respiration-related magnetic susceptibility changes on the velocity data measured. RESULTS: At each level, CSF moved cephalad during inhalation and caudad during expiration. While the general pattern of fluid movement was the same in the 6 subjects, the flow rates, stroke volumes, and spine segment volume changes varied among subjects. Peak flow rates ranged from 0.60 to 1.59 mL/s in the cervical region, 0.46 to 3.17 mL/s in the thoracic region, and 0.75 to 3.64 mL/s in the lumbar region. The differences in flow rates along the canal yielded cyclic volume variations of spine segments that were largest in the lumbar spine, ranging from 0.76 to 3.07 mL among subjects. In the phantom study, flow velocities oscillated periodically during the respiratory cycle by up to 0.02 cm/s or 0.5%. CONCLUSIONS: Respiratory-gated measurements of the CSF motion in the spinal canal showed cyclic oscillatory movements of spinal fluid correlated to the breathing pattern.

Assessing pulsatile waveforms of paravascular cerebrospinal fluid dynamics within the glymphatic pathways using dynamic diffusion-weighted imaging (dDWI)

Cerebrospinal fluid (CSF) in the paravascular spaces of the surface arteries (sPVS) is a vital pathway in brain waste clearance. Arterial pulsations may be the driving force of the paravascular flow, but its pulsatile pattern remains poorly characterized, and no clinically practical method for measuring its dynamics in the human brain is available. In this work, we introduce an imaging and quantification framework for in-vivo non-invasive assessment of pulsatile fluid dynamics in the sPVS. It used dynamic Diffusion-Weighted Imaging (dDWI) at a lower b-values of 150s/mm2 and retrospective gating to detect the slow flow of CSF while suppressing the fast flow of adjacent arterial blood. The waveform of CSF flow over a cardiac cycle was revealed by synchronizing the measurements with the heartbeat. A data-driven approach was developed to identify sPVS and allow automatic quantification of the whole-brain fluid waveforms. We applied dDWI to twenty-five participants aged 18-82 y/o. Results demonstrated that the fluid waveforms across the brain showed an explicit cardiac-cycle dependency, in good agreement with the vascular pumping hypothesis. Furthermore, the shape of the CSF waveforms closely resembled the pressure waveforms of the artery wall, suggesting that CSF dynamics is tightly related to artery wall mechanics. Finally, the CSF waveforms in aging participants revealed a strong age effect, with a significantly wider systolic peak observed in the older relative to younger participants. The peak widening may be associated with compromised vascular compliance and vessel wall stiffening in the older brain. Overall, the results demonstrate the feasibility, reproducibility, and sensitivity of dDWI for detecting sPVS fluid dynamics of the human brain. Our preliminary data suggest age-related alterations of the paravascular pumping. With an acquisition time of under six minutes, dDWI can be readily applied to study fluid dynamics in normal physiological conditions and cerebrovascular/neurodegenerative diseases.

Quantifying tissue optical properties of human heads in vivo using continuous-wave near-infrared spectroscopy and subject-specific three-dimensional Monte Carlo models.

SIGNIFICANCE: Quantifying subject-specific optical properties (OPs) including absorption and transport scattering coefficients of tissues in the human head could improve the modeling of photon propagation for the analysis of functional near-infrared spectroscopy (fNIRS) data and dosage quantification in therapeutic applications. Current methods employ diffuse approximation, which excludes a low-scattering cerebrospinal fluid compartment and causes errors. AIM: This work aims to quantify OPs of the scalp, skull, and gray matter in vivo based on accurate Monte Carlo (MC) modeling. APPROACH: Iterative curve fitting was applied to quantify tissue OPs from multidistance continuous-wave NIR reflectance spectra. An artificial neural network (ANN) was trained using MC-simulated reflectance values based on subject-specific voxel-based tissue models to replace MC simulations as the forward model in curve fitting. To efficiently generate sufficient data for training the ANN, the efficiency of MC simulations was greatly improved by white MC simulations, increasing the detectors' acceptance angle, and building a lookup table for interpolation. RESULTS: The trained ANN was six orders of magnitude faster than the original MC simulations. OPs of the three tissue compartments were quantified from NIR reflectance spectra measured at the forehead of five healthy subjects and their uncertainties were estimated. CONCLUSIONS: This work demonstrated an MC-based iterative curve fitting method to quantify subject-specific tissue OPs in-vivo, with all OPs except for scattering coefficients of scalp within the ranges reported in the literature, which could aid the modeling of photon propagation in human heads.

The effect of prolonged spaceflight on cerebrospinal fluid and perivascular spaces of astronauts and cosmonauts.

Long-duration spaceflight induces changes to the brain and cerebrospinal fluid compartments and visual acuity problems known as spaceflight-associated neuro-ocular syndrome (SANS). The clinical relevance of these changes and whether they equally affect crews of different space agencies remain unknown. We used MRI to analyze the alterations occurring in the perivascular spaces (PVS) in NASA and European Space Agency astronauts and Roscosmos cosmonauts after a 6-mo spaceflight on the International Space Station (ISS). We found increased volume of basal ganglia PVS and white matter PVS (WM-PVS) after spaceflight, which was more prominent in the NASA crew than the Roscosmos crew. Moreover, both crews demonstrated a similar degree of lateral ventricle enlargement and decreased subarachnoid space at the vertex, which was correlated with WM-PVS enlargement. As all crews experienced the same environment aboard the ISS, the differences in WM-PVS enlargement may have been due to, among other factors, differences in the use of countermeasures and high-resistive exercise regimes, which can influence brain fluid redistribution. Moreover, NASA astronauts who developed SANS had greater pre- and postflight WM-PVS volumes than those unaffected. These results provide evidence for a potential link between WM-PVS fluid and SANS.