Dynamics of respiratory and cardiac CSF motion revealed with real-time simultaneous multi-slice EPI velocity phase contrast imaging

PurposeThe cardiac- and respiratory-driven components of cerebrospinal fluid (CSF) motion characteristics and bulk flow are not yet completely understood. Therefore, the present study aimed to characterize cardiac- and respiratory-driven CSF motions in the intracranial space using delay time, CSF velocity waveform correlation, and displacement.MethodsAsynchronous two-dimensional phase-contrast at 3T was applied to measure the CSF velocity in the inferior–superior direction in a sagittal slice at the midline (N = 12) and an axial slice at the foramen magnum (N = 8). Volunteers were instructed to engage in six-second respiratory cycles. The calculated delay time and correlation coefficients of the cardiac- and respiratory-driven velocity waveforms, separated in the frequency domain, were applied to evaluate the propagation of the CSF motion. The cardiac- and respiratory-driven components of the CSF displacement and motion volume were calculated during diastole and systole, and during inhalation and exhalation, respectively. The cardiac- and respiratory-driven components of the velocity, correlation, displacement, and motion volume were compared using an independent two-sample t-test.ResultsThe ratio of the cardiac-driven CSF velocity to the sum of the cardiac- and respiratory-driven CSF velocities was higher than the equivalent respiratory-driven ratio for all cases (P < 0.01). Delay time and correlation maps demonstrated that the cardiac-driven CSF motion propagated more extensively than the respiratory-driven CSF motion. The correlation coefficient of the cardiac-driven motion was significantly higher in the prepontine(P < 0.01), the aqueduct, and the fourth ventricle (P < 0.05). The respiratory-driven displacement and motion volume were significantly greater than the cardiac-driven equivalents for all observations (P < 0.01).ConclusionThe correlation mapping technique characterized the cardiac- and respiratory-driven CSF velocities and their propagation properties in the intracranial space. Based on these findings, cardiac-driven CSF velocity is greater than respiratory-induced velocity, but the respiratory-driven velocity might displace farther.

The mechanisms previously proposed for the progression of syringomyelia associated with Chiari I malformation of the cerebellar tonsils are controversial, leave many clinical observations unexplained, and underlie the prevalence of different operations currently used as initial treatment. To explore the mechanism of syringomyelia progression in this setting, the authors used anatomical and dynamic (phase-contrast and phase-contrast cine) magnetic resonance (MR) imaging, and intraoperative ultrasonography to examine the anatomy and dynamics of movement of the cerebellar tonsils, the wall of the spinal cord surrounding the syrinx, and the movement of cerebrospinal fluid (CSF) and syrinx fluid at rest, during the respiratory and cardiac cycles, and during Valsalva maneuver in seven affected patients. In all patients the cerebellar tonsils occluded the subarachnoid space at the level of the foramen magnum. Syringomyelia extended from the cervical to the lower thoracic segment of the spinal cord. No patient had evidence of a patent communication between the fourth ventricle and the syrinx on anatomical MR images, dynamic MR images, or intraoperative ultrasound studies. Dynamic MR images of three patients revealed abrupt downward movement of the spinal CSF and the syrinx fluid during systole and upward movement during diastole, but limited movement of CSF across the foramen magnum during the cardiac cycle. Intraoperative ultrasound studies demonstrated abrupt downward movement of the cerebellar tonsils during systole that was synchronous with sudden constriction of the spinal cord and syrinx. Decompression of the foramen magnum was achieved via suboccipital craniectomy, laminectomy of C-1 and C-2, and dural grafting, leaving the arachnoid intact. Immediately after surgery, the pulsatile downward thrust of the tonsils and constriction of the spinal cord and syrinx disappeared. Syringomyelia resolved within 1 to 6 months after surgery in all patients. Observations by the authors suggest the following previously unrecognized mechanism for progression of syringomyelia associated with occlusion of the subarachnoid space at the foramen magnum. The brain expands as it fills with blood during systole, imparting a systolic pressure wave to the intracranial CSF that is accommodated in normal subjects by sudden movement of CSF from the basal cisterns to the upper portion of the spinal canal. With obstruction to rapid movement of CSF at the foramen magnum, the cerebellar tonsils, which plug the subarachnoid space posteriorly, move downward with each systolic pulse, acting as a piston on the partially isolated spinal CSF and producing a systolic pressure wave in the spinal CSF that acts on the surface of the spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebrospinal fluid (CSF) dynamics are essential in the waste clearance of the brain. Disruptions in CSF flow are linked to various neurological conditions, highlighting the need for accurate measurement of its dynamics. Current methods typically capture high-speed CSF movements or focus on a single-frequency component, presenting challenges for comprehensive analysis. This study proposes a novel approach using displacement encoding with stimulated echoes (DENSE) MRI to assess the full spectrum of CSF motion within the brain. Through simulations, we evaluated the feasibility of disentangling distinct CSF motion components, including heartbeat- and respiration-driven flows, as well as a net velocity component due to continuous CSF turnover, and tested the performance of our method under incorrect assumptions about the underlying model of CSF motion. Results demonstrate that DENSE MRI can accurately separate these components, and reliably estimate a net velocity, even when periodic physiological motions vary over time. The method proved to be robust for including low-frequency components, incorrect assumptions on the nature of the net velocity component and missing CSF components in the model. This approach offers a comprehensive measurement technique for quantifying CSF dynamics, advancing our understanding of the relative role of various drivers of CSF dynamics in brain clearance.

Simultaneous multi-slice (SMS) echo-planar imaging has had a huge impact on the acceleration and routine use of diffusion-weighted MRI (DWI) in neuroimaging studies in particular the human connectome project; but also holds the potential to facilitate DWI of moving subjects, as proposed by the new technique developed in this paper. We present a novel registration-based motion tracking technique that takes advantage of the multi-plane coverage of the anatomy by simultaneously acquired slices to enable robust reconstruction of neural microstructure from SMS DWI of moving subjects. Our technique constitutes three main components: 1) motion tracking and estimation using SMS registration, 2) detection and rejection of intra-slice motion, and 3) robust reconstruction. Quantitative results from 14 volunteer subject experiments and the analysis of motion-corrupted SMS DWI of 6 children indicate robust reconstruction in the presence of continuous motion and the potential to extend the use of SMS DWI in very challenging populations.

Cerebrospinal fluid (CSF) dynamics are thought to play a vital role in central nervous system (CNS) physiology. The objective of this study was to investigate the impact of spinal cord (SC) nerve roots (NR) on CSF dynamics. A subject-specific computational fluid dynamics (CFD) model of the complete spinal subarachnoid space (SSS) with and without anatomically realistic NR and nonuniform moving dura wall deformation was constructed. This CFD model allowed detailed investigation of the impact of NR on CSF velocities that is not possible in vivo using magnetic resonance imaging (MRI) or other noninvasive imaging methods. Results showed that NR altered CSF dynamics in terms of velocity field, steady-streaming, and vortical structures. Vortices occurred in the cervical spine around NR during CSF flow reversal. The magnitude of steady-streaming CSF flow increased with NR, in particular within the cervical spine. This increase was located axially upstream and downstream of NR due to the interface of adjacent vortices that formed around NR.

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.

Cerebrospinal fluid (CSF) circulation is tightly coupled to cerebral blood flow under the fixed-volume constraint of the cranial vault, with cardiac pulsations and respiration acting as dominant physiological drivers. Disruption of these flow dynamics has been implicated in various neurological disorders, motivating the need for imaging methods that capture CSF and vascular flow simultaneously and in real time. Conventional phase contrast MRI (PC-MRI) provides quantitative CSF velocity measurements but relies on cardiac gating and velocity encoding, which limit temporal resolution, dynamic range, and sensitivity to non-cardiac fluctuations. Here, we introduce self-gated ultrafast real-time flow-weighted echo-planar imaging (SURF-EPI), an inflow-weighted approach in which signal intensity reflects the replacement of saturated spins by freshly inflowing, unsaturated water molecules, yielding higher signal with higher flow. This allows simultaneous assessment of arterial inflow, venous outflow, and CSF motion at high temporal resolution. SURF-EPI was acquired at the C2–C3 spinal level, enabling real-time imaging of CSF flow dynamics in the cervical spinal canal alongside arterial and venous blood flow in major cervical vessels (frame-rate: 21.7 Hz). In addition to frequency-domain analyses, we leveraged intrinsic arterial signal fluctuations as a timing reference to reconstruct cardiac-resolved CSF dynamics for individual cardiac cycles without external physiological recordings. Frequency-domain analysis revealed distinct spectral signatures in CSF flow compared with neurovascular flow, including broadened cardiac peaks and enhanced respiratory modulation, particularly within the ventral spinal canal. In contrast, dorsal CSF showed increased power within the cardiac frequency band, higher coherence with cervical vasculature at the cardiac frequency, and reduced non-cardiac contributions. Time-domain analysis showed strong correlation between CSF flow waveforms derived from SURF-EPI and PC-MRI. Beyond ensemble-averaged waveforms, SURF-EPI enabled beat-to-beat analysis, revealing substantial cycle-to-cycle variability in CSF flow that is not captured by time-averaged gated approaches. Together, these findings establish SURF-EPI as a rapid, complementary framework to PC-MRI, enabling real-time neurofluid imaging with integrated time- and frequency-domain characterization of CSF and neurovascular flow 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

Hemodynamic mapping using gas inhalation has received increasing interest in recent years. Cerebrovascular reactivity (CVR), which reflects the ability of the brain vasculature to dilate in response to a vasoactive stimulus, can be measured by CO2 inhalation with continuous acquisition of blood oxygen level-dependent (BOLD) magnetic resonance images. Cerebral blood volume (CBV) can be measured by O2 inhalation. These hemodynamic mapping methods are appealing because of their absence of gadolinium contrast agent, their ability to assess both baseline perfusion and vascular reserve, and their utility in calibrating the functional magnetic resonance imaging (fMRI) signal. However, like other functional and physiological indices, a major drawback of these measurements is their poor sensitivity and reliability. Simultaneous multi-slice echo planar imaging (SMS EPI) is a fast imaging technology that allows the excitation and acquisition of multiple two-dimensional slices simultaneously, and has been shown to enhance the sensitivity of several MRI applications. To our knowledge, the benefit of SMS in gas inhalation imaging has not been investigated. In this work, we compared the sensitivity of CO2 and O2 inhalation data collected using SMS factor 2 (SMS2) and SMS factor 3 (SMS3) with those collected using conventional EPI (SMS1). We showed that the sensitivity of SMS scans was significantly (p=0.01) higher than that of conventional EPI, although no difference was found between SMS2 and SMS3 (p=0.3). On a voxel-wise level, approximately 20-30% of voxels in the brain showed a significant enhancement in sensitivity when using SMS compared with conventional EPI, with other voxels showing an increase, but not reaching statistical significance. When using SMS, the scan duration can be reduced by half, whilst maintaining the sensitivity of conventional EPI. The availability of a sensitive acquisition technique can further enhance the potential of gas inhalation MRI in clinical applications.

BackgroundAltered interstitial and cerebrospinal fluid (CSF) dynamics have been linked to impaired amyloid clearance in animal models of Alzheimer’s disease (AD). Recent dynamic PET studies using tau and amyloid PET tracers [18F]THK5117 and [11C]PiB have sought to quantify CSF dynamics in humans [de Leon 2017, Schubert 2019]. The aim of this work was to examine the relationships between [11C]PiB and [15O]H2O semi‐quantitative measures of CSF dynamics, efflux and influx, respectively; amyloid load; and cognitive status.MethodNineteen participants consisting of n=5 cognitively normal (CN; 71.6±8.9 years, 3 female), 9 mild cognitive impairment (MCI; 68.6±9.9 years, 2 female), and 5 Alzheimer’s disease (AD; 67.0±9.0 years, 0 female) subjects underwent [11C]PiB PET (0‐90min post‐injection, 34 frames), [15O]H2O PET (0‐3min post‐injection, 20 frames), and 1.5T T1 MR imaging. MR images were processed using FreeSurfer 7.1 (FS). Amyloid load status (PiB‐/+) was assessed using a FS Global [11C]PiB 50‐70min SUVR (cerebellar gray matter [GM] reference) and a cutoff of 1.35 SUVR. FS lateral ventricle ROIs were eroded using a 5mm kernel to minimize partial volume contamination from neighboring tissue and used to calculate three semi‐quantitative ventricular CSF outcomes: [11C]PiB ventricular SUVR50‐70 (cerebellar GM reference), [11C]PiB ventricular AUC35‐90 (cerebellar GM reference), and [15O]H2O ventricular influx ratio (IR; 1.0‐3.0min, whole brain reference). Relationships between PET outcomes were assessed using Spearman’s correlations, and group differences across cognitive and amyloid statuses were assessed using the Mann‐Whitney U test.ResultEleven subjects were classified as PiB+ (1/5 CN, 5/9 MCI, 5/5 AD). Both [11C]PiB ventricular outcomes were significantly correlated with [15O]H2O IR ([11C]PiB SUVR50‐70 p&lt;0.001; [11C]PiB AUC35‐90 p&lt;0.001). In this population, no significant differences were observed across any pair of diagnostic groups for any of the three ventricular outcome measures (Figure 1). However, significant differences were observed between PiB‐ and PiB+ groups across all three ventricular CSF outcomes (Figure 2; [11C]PiB SUVR50‐70 p=0.033; [11C]PiB AUC35‐90 p=0.041; [15O]H2O IR p=0.001).ConclusionThe results observed in this population suggest CSF dynamics are altered early in the AD pathophysiological spectrum and are associated with amyloid load. In addition, ventricular CSF dynamics measured using [15O]H2O IR provided greater discriminatory power than [11C]PiB CSF outcomes.

Simultaneous Multi-Slice (SMS) magnetic resonance imaging (MRI) is a rapidly evolving technique for increasing imaging speed. Controlled aliasing techniques utilize periodic undersampling patterns to help mitigate the loss in signal-to-noise ratio (SNR) in SMS MRI. To evaluate the performance of different undersampling patterns, a quantitative description of the image SNR loss is needed. Additionally, eddy current effects in echo planar imaging (EPI) lead to slice-specific Nyquist ghosting artifacts. These artifacts cannot be accurately corrected for each individual slice before or after slice-unaliasing. In this work, we propose a hybrid-space sensitivity encoding (SENSE) reconstruction framework for SMS MRI by adopting a three-dimensional representation of the SMS acquisition. Analytical SNR loss maps are derived for SMS acquisitions with arbitrary phase encoding undersampling patterns. Moreover, we propose a matrix-decoding correction method that corrects the slice-specific Nyquist ghosting artifacts in SMS EPI acquisitions. Brain images demonstrate that the proposed hybrid-space SENSE reconstruction generates images with comparable quality to commonly used split-slice-generalized autocalibrating partially parallel acquisition reconstruction. The analytical SNR loss maps agree with those calculated by a Monte Carlo based method, but require less computation time for high quality maps. The analytical maps enable a fair comparison between the performances of coherent and incoherent SMS undersampling patterns. Phantom and brain SMS EPI images show that the matrix-decoding method performs better than the single-slice and slice-averaged Nyquist ghosting correction methods under the hybrid-space SENSE reconstruction framework.

Cerebrospinal fluid (CSF) production and absorption concept significantly changed in the early 2010s from “third circulation theory” and “classical bulk flow theory” to a whole new one as follows: First, CSF is mainly produced from interstitial fluid excreted from the brain parenchyma, and CSF produced from the choroid plexus plays an important role in maintaining brain homeostasis. Second, CSF is not absorbed in the venous sinus via the arachnoid granules, but mainly in the dural lymphatic vessels. Finally, the ventricles and subarachnoid spaces have several compensatory direct CSF pathways at the borders attached to the choroid plexus, e.g., the inferior choroidal point of the choroidal fissure, other than the foramina of Luschka and Magendie. In idiopathic normal pressure hydrocephalus (iNPH), the lateral ventricles and basal cistern are enlarged simultaneously due to the compensatory direct CSF pathways. The average total intracranial CSF volume increased from about 150 mL at 20 years to about 350 mL at 70 years due to the decrease in brain volume with aging and further increased above 400 mL in patients with iNPH. CSF movements are composed of a steady microflow produced by the rhythmic wavy movement of motile cilia on the ventricular surface and dynamic pulsatile flow produced by the brain and cerebral artery pulsation, respiration, and head movement. Pulsatile CSF movements might totally decrease with aging, but it in the ventricles might increase at the foramina of Magendie and Luschka dilation. Aging CSF dynamics are strongly associated with ventricular dilatation in iNPH.

Functional cerebral blood volume mapping with simultaneous multi-slice acquisition

To the Editor: We read with great interest the paper titled “Review of Cerebrospinal Fluid Physiology and Dynamics: A Call for Medical Education Reform.”1 The classic theory of cerebrospinal fluid (CSF) circulation presupposes that CSF is produced in the choroid plexus and then circulates from the ventricles along the subarachnoid spaces to be reabsorbed at the level of the dural sinuses through the pacchionian granulations. This paradigm has been challenged by the studies of Bulat–Klarika–Oreskovic2,3 according to which CSF, driven by osmotic and hydrostatic forces, is continuously produced and absorbed in the entire CSF system. The last hypothesis is well integrated into the recent description of the “glymphatic system,” a wide perivascular pathway supporting CSF and interstitial fluid exchange.4,5 Basal cisternostomy has been proposed as a novel treatment for severe brain trauma (sTBI), based on the idea that sTBI produces an impairment of CSF circulation using the perivascular network, leading to a shift of fluid toward the parenchyma, now referred to as CSF-shift oedema that finally results in brain swelling.6 The opening of basal cisterns (often clogged by subarachnoid blood) could restore this circulation, thereby alleviating the brain oedema. Our group has developed an interest in the application of cisternostomy in the setting of surgery for sTBI.7,8 We believe that our clinical experience with TBI surgery strongly supports the modern theories focusing on the existence of an extensive perivascular pattern that communicates with the cisternal subarachnoid space. The results from our clinical series showed that cisternostomy contributed effectively to the treatment of raised intracranial hypertension after sTBI. This surgical maneuver, in most cases, provides remarkable brain relaxation and continued cisternal drainage (approximately for 1 week), prevented the worsening and allowed the resolution of brain oedema, and in most cases obviated the need for prolonged ventilation and treatment with mannitol, hypertonic saline, or hypothermia.7 In comparison, the previous gold standard namely hemicraniectomy only provided increase space for the prolapse of the brain outside the confines of the cranium and did not address the brain edema to any degree. Another observation that seems to support this hypothesis is the huge quantity of CSF (approximately 200 mL/day) that can be drained through the cisternal drain in these patients. The fact that this large quantity of CSF is obtained because of the perivascular network (that is in communication with the basal cisterns) needs to be proved clinically, although there are several laboratory studies that indicate it quite well.9 One of the main criticisms to this promising surgical technique is that CSF can also be drained from the ventricles. However, it is widely acknowledged in common neurosurgical practice that external ventricular drainage rarely provides enough CSF (like the cisternal drain), quite frequently malfunctions and is often insufficient in the control of raised intracranial hypertension in sTBI.10 The effects of cisternal drainage in terms of control of intracranial pressure and outcome in the few series published to date attest to its utility in sTBI when compared with the decompressive craniectomy.11 These observations lends credence to the fascinating idea that cisternal drainage could ultimately address the issue of brain edema, although further clinical research needs to be performed across larger patient cohorts. Fundamental to the application of cisternostomy in general neurosurgical practice is an acceptance of the basic CSF physiology as proposed by Atchley et al.1 In addition, further clinical studies in this field has the potential of developing clinical interventions along these lines for a host of neurological pathologies including chronic hydrocephalus, aneurysmal subarachnoid hemorrhage, and even neurodegenerative disease.

Object Syringomyelia causes progressive myelopathy. Most patients with syringomyelia have a Chiari I malformation of the cerebellar tonsils. Determination of the pathophysiological mechanisms underlying the progression of syringomyelia associated with the Chiari I malformation should improve strategies to halt progression of myelopathy. Methods The authors prospectively studied 20 adult patients with both Chiari I malformation and symptomatic syringomyelia. Testing before surgery included the following: clinical examination; evaluation of anatomy by using T 1 -weighted magnetic resonance (MR) imaging; evaluation of the syrinx and cerebrospinal fluid (CSF) velocity and flow by using phase-contrast cine MR imaging; and evaluation of lumbar and cervical subarachnoid pressure at rest, during the Valsalva maneuver, during jugular compression, and following removal of CSF (CSF compliance measurement). During surgery, cardiac-gated ultrasonography and pressure measurements were obtained from the intracranial, cervical subarachnoid, and lumbar intrathecal spaces and syrinx. Six months after surgery, clinical examinations, MR imaging studies, and CSF pressure recordings were repeated. Clinical examinations and MR imaging studies were repeated annually. For comparison, 18 healthy volunteers underwent T 1 -weighted MR imaging, cine MR imaging, and cervical and lumbar subarachnoid pressure testing. Compared with healthy volunteers, before surgery, the patients had decreased anteroposterior diameters of the ventral and dorsal CSF spaces at the foramen magnum. In patients, CSF velocity at the foramen magnum was increased, but CSF flow was reduced. Transmission of intracranial pressure across the foramen magnum to the spinal subarachnoid space in response to jugular compression was partially obstructed. Spinal CSF compliance was reduced, whereas cervical subarachnoid pressure and pulse pressure were increased. Syrinx fluid flowed inferiorly during systole and superiorly during diastole on cine MR imaging. At surgery, the cerebellar tonsils abruptly descended during systole and ascended during diastole, and the upper pole of the syrinx contracted in a manner synchronous with tonsillar descent and with the peak systolic cervical subarachnoid pressure wave. Following surgery, the diameter of the CSF passages at the foramen magnum increased compared with preoperative values, and the maximum flow rate of CSF across the foramen magnum during systole increased. Transmission of pressure across the foramen magnum to the spinal subarachnoid space in response to jugular compression was normal and cervical subarachnoid mean pressuree and pulse pressure decreased to normal. The maximum syrinx diameter decreased on MR imaging in all patients. Cine MR imaging documented reduced velocity and flow of the syrinx fluid. Clinical symptoms and signs improved or remained stable in all patients, and the tonsils resumed a normal shape. Conclusions The progression of syringomyelia associated with Chiari I malformation is produced by the action of the cerebellar tonsils, which partially occlude the subarachnoid space at the foramen magnum and act as a piston on the partially enclosed spinal subarachnoid space. This creates enlarged cervical subarachnoid pressure waves that compress the spinal cord from without, not from within, and propagate syrinx fluid caudally with each heartbeat, which leads to syrinx progression. The disappearance of the abnormal shape and position of the tonsils after simple decompressive extraarachnoidal surgery suggests that the Chiari I malformation of the cerebellar tonsils is acquired, not congenital. Surgery limited to suboccipital craniectomy, C-1 laminectomy, and duraplasty eliminates this mechanism and eliminates syringomyelia and its progression without the risk of more invasive procedures.