MRI Studies of the Cardiac and Respiratory Modulations of the Cranio-spinal CSF Oscillation

Every heartbeat causes cerebrospinal fluid (CSF) to oscillate between the cranium and the spinal canal, facilitating functions like blood circulation and metabolic waste product removal. Toxins are mostly cleared during sleep. However, the mechanism and role of CSF oscillation remain unclear. Our hypothesis suggests that during sleep, toxins in interstitial fluid exchange with cranial CSF, some of which transfer to spinal CSF through craniospinal (cs) CSF mixing. Spinal CSF then clears these toxins through the spinal CSF reabsorption sites. We study the role of respiration in the csCSF oscillation modulation and its impact on the waste clearance process.Cardiovascular modulation of CSF oscillation was non-invasively studied using velocity-encoding phase-contrast MRI. Our lab showed that csCSF flow depends on arterial-venous flow, governed by intracranial compliance. Determining cs compliance distribution is vital for understanding complex CSF-related disorders. Existing invasive techniques cannot assess individual cs compliance. We improved a lumped-parameter model to determine relative cranial and spinal compartment compliances. We explored the link between posture and cs compliance, highlighting the spinal canal's role in regulating intracranial pressure upon postural changes.Recent MRI advancements allow real-time flow measurements, capturing respiration's influence on csCSF oscillation. Our data confirmed that the driving force for cs CSF oscillations A-V during the respiratory cycle. Transitioning from normal to deep abdominal breathing led to an increase in maximal CSF volume oscillating between the cranium and spinal canal.Additionally, fMRI sleep studies reported long unidirectional CSF flow into the ventricles. We propose autonomic regulation due to respiratory depth changes can explain this anomaly. In summary, we see csCSF oscillation as a "brain washing machine" where respiration patterns determine cleaning cycle efficiency

CSF ‐to‐blood toxins clearance is modulated by breathing through cranio–spinal CSF oscillation

Summary Clearance of brain toxins occurs during sleep, although the mechanism remains unknown. Previous studies implied that the intracranial aqueductal cerebrospinal fluid (CSF) oscillations are involved, but no mechanism was suggested. The rationale for focusing on the aqueductal CSF oscillations is unclear. This study focuses on the cranio–spinal CSF oscillation and the factors that modulate this flow. We propose a mechanism where increased cranio–spinal CSF movements enhance CSF‐to‐blood metabolic waste clearance through the spinal CSF re‐absorption sites. A recent study demonstrating that disturbed sleep impairs CSF‐to‐blood but not brain‐to‐CSF clearance, supports the fundamentals of our proposed mechanism. Eight healthy subjects underwent phase‐contrast magnetic resonance imaging to quantify the effect of respiration on the cranio–spinal CSF oscillations. Maximal CSF volume displaced from the cranium to the spinal canal during each respiration and cardiac cycle were derived as measures of cranio–spinal CSF mixing level. Transition from normal to slow and abdominal breathing resulted in a 56% increase in the maximal displaced CSF volume. Maximal change in the arterial–venous blood volume, which is the driving force of the CSF oscillations, was increased by 41% during slow abdominal breathing. Cranio–spinal CSF oscillations are driven by the momentary difference between arterial inflow and venous outflow. Breathing modulates the CSF oscillation through changes in the venous outflow. The amount of toxins being transferred to the spinal canal during each respiratory cycle is significantly increased during slow and deeper abdominal breathing, which explains enhanced CSF‐to‐blood toxins clearance during slow‐wave sleep and poor clearance during disrupted sleep

Role of the spinal canal compliance in regulating posture‐related cerebrospinal fluid hydrodynamics in humans

Mechanical compliance of a compartment is defined by the change in its volume with respect to a change in the inside pressure. The compliance of the spinal canal regulates the intracranial pressure (ICP) under postural changes. Understanding how gravity affects ICP is beneficial for poorly understood cerebrospinal fluid (CSF)‐related disorders. The aim of this study was to evaluate postural effects on cranial hemo‐ and hydrodynamics. This was a prospective study, which included 10 healthy volunteers (three males, seven females, mean ± standard deviation age: 29 ± 7 years). Cine gradient‐echo phase‐contrast sequence acquired at 0.5 T, “GE double‐doughnut” scanner was used. Spinal contribution to overall craniospinal compliance (CSC), craniospinal CSF stroke volume (SV), magnetic resonance (MR)‐derived ICP (MR‐ICP), and total cerebral blood flow (TCBF) were measured in supine and upright postures using automated blood and CSF flows quantification. Statistical tests performed were two‐sided Student's t‐test, Cohen's d, and Pearson correlation coefficient. MR‐ICP and the craniospinal CSF SV were significantly correlated with the spinal contribution to the overall CSC (r = 0.83, p < 0.05) and (r = 0.62, p < 0.05), respectively. Cranial contribution to CSC increased from 44.5% ± 16% in supine to 74.9% ± 8.4% in upright posture. The average MR‐ICP dropped from 9.9 ± 3.4 mmHg in supine to −3.5 ± 1.5 mmHg. The CSF SV was over 2.5 times higher in the supine position (0.55 ± 0.14 ml) than in the upright position (0.21 ± 0.13 ml). In contrast, TCBF was slightly higher in the supine posture (822 ± 152 ml/min) than in the upright posture (761 ± 139 ml/min), although not statistically significant (p = 0.16). The spinal‐canal compliance contribution to CSC is larger than the cranial contribution in the supine posture and smaller in the upright posture. Thereby, the spinal canal plays a role in modulating ICP upon postural changes. The lower pressure craniospinal CSF system was more affected by postural changes than the higher‐pressure cerebral vascular system. Craniospinal hydrodynamics is affected by gravity and is likely to be altered by its absence in space. Level of Evidence 4 Technical Efficacy Stage

Patient-specific cranio-spinal compliance distribution using lumped-parameter model: its relation with ICP over a wide age range

Abstract Background The distribution of cranio-spinal compliance (CSC) in the brain and spinal cord is a fundamental question, as it would determine the overall role of the compartments in modulating ICP in healthy and diseased states. Invasive methods for measurement of CSC using infusion-based techniques provide overall CSC estimate, but not the individual sub-compartmental contribution. Additionally, the outcome of the infusion-based method depends on the infusion site and dynamics. This article presents a method to determine compliance distribution between the cranium and spinal canal non-invasively using data obtained from patients. We hypothesize that this CSC distribution is indicative of the ICP. Methods We propose a lumped-parameter model representing the hydro and hemodynamics of the cranio-spinal system. The input and output to the model are phase-contrast MRI derived volumetric transcranial blood flow measured in vivo, and CSF flow at the spinal cervical level, respectively. The novelty of the method lies in the model mathematics that predicts CSC distribution (that obeys the physical laws) from the system dc gain of the discrete-domain transfer function. 104 healthy individuals (48 males, 56 females, age 25.4 ± 14.9 years, range 3–60 years) without any history of neurological diseases, were used in the study. Non-invasive MR assisted estimate of ICP was calculated and compared with the cranial compliance to prove our hypothesis. Results A significant negative correlation was found between model-predicted cranial contribution to CSC and MR-ICP. The spinal canal provided majority of the compliance in all the age groups up to 40 years. However, no single sub-compartment provided majority of the compliance in 41–60 years age group. The cranial contribution to CSC and MR-ICP were significantly correlated with age, with gender not affecting the compliance distribution. Spinal contribution to CSC significantly positively correlated with CSF stroke volume. Conclusions This paper describes MRI-based non-invasive way to determine the cranio-spinal compliance distribution in the brain and spinal canal sub-compartments. The proposed mathematics makes the model always stable and within the physiological range. The model-derived cranial compliance was strongly negatively correlated to non-invasive MR-ICP data from 104 patients, indicating that compliance distribution plays a major role in modulating ICP