Cerebrospinal fluid (CSF) plays an essential role in maintaining the homeostasis of the central nervous system. The functions of CSF include: (1) buoyancy of the brain, spinal cord, and nerves; (2) volume adjustment in the cranial cavity; (3) nutrient transport; (4) protein or peptide transport; (5) brain volume regulation through osmoregulation; (6) buffering effect against external forces; (7) signal transduction; (8) drug transport; (9) immune system control; (10) elimination of metabolites and unnecessary substances; and finally (11) cooling of heat generated by neural activity. For CSF to fully mediate these functions, fluid-like movement in the ventricles and subarachnoid space is necessary. Furthermore, the relationship between the behaviors of CSF and interstitial fluid in the brain and spinal cord is important. In this review, we will present classical studies on CSF circulation from its discovery over 2,000 years ago, and will subsequently introduce functions that were recently discovered such as CSF production and absorption, water molecule movement in the interstitial space, exchange between interstitial fluid and CSF, and drainage of CSF and interstitial fluid into both the venous and the lymphatic systems. Finally, we will summarize future challenges in research. This review includes articles published up to February 2016.

The “cerebrospinal fluid (CSF) circulation theory” of CSF flowing unidirectionally and circulating through the ventricles and subarachnoid space in a downward or upward fashion has been widely recognized. In this review, observations of CSF motion using different magnetic resonance imaging (MRI) techniques are described, findings that are shared among these techniques are extracted, and CSF motion, as we currently understand it based on the results from the quantitative analysis of CSF motion, is discussed, along with a discussion of slower water molecule motion in the perivascular, paravascular, and brain parenchyma. Today, a shared consensus regarding CSF motion is being formed, as follows: CSF motion is not a circulatory flow, but a combination of various directions of flow in the ventricles and subarachnoid space, and the acceleration of CSF motion differs depending on the CSF space. It is now necessary to revise the currently held concept that CSF flows unidirectionally. Currently, water molecule motion in the order of centimeters per second can be detected with various MRI techniques. Thus, we need new MRI techniques with high-velocity sensitivity, such as in the order of 10 μm/s, to determine water molecule movement in the vessel wall, paravascular space, and brain parenchyma. In this paper, the authors review the previous and current concepts of CSF motion in the central nervous system using various MRI techniques.

Using the present sequence, we obtained images that accentuated CSF motion, which is largely composed of irregular motion. This method does not require pulse triggering or complex post-processing of images and allows visualization of CSF motion in a short period of time in selected whole imaging planes. It can therefore be applied clinically to diagnose various diseases that cause abnormalities in the CSF space.

Magnetic resonance imaging (MRI) can depict not only anatomical information, but also physiological factors such as velocity and pressure gradient. Measurement of these physiological factors is necessary to understand the cerebrospinal fluid (CSF) environment. In this study we quantified CSF motion in various parts of the CSF space, determined changes in the CSF environment with aging, and compared CSF pressure gradient between patients with idiopathic normal pressure hydrocephalus (iNPH) and healthy elderly volunteers. Fifty-seven healthy volunteers and six iNPH patients underwent four-dimensional (4D) phase-contrast (PC) MRI. CSF motion was observed and the pressure gradient of CSF was quantified in the CSF space. In healthy volunteers, inhomogeneous CSF motion was observed whereby the pressure gradient markedly increased in the center of the skull and gradually decreased in the periphery of the skull. For example, the pressure gradient at the ventral surface of the brainstem was 6.6 times greater than that at the convexity of the cerebrum. The pressure gradient was statistically unchanged with aging. The pressure gradient of patients with iNPH was 3.2 times greater than that of healthy volunteers. The quantitative analysis of 4D-PC MRI data revealed that the pressure gradient of CSF can be used to understand the CSF environment, which is not sufficiently given by subjective impression of the anatomical image.

Purpose:A correlation mapping technique delineating delay time and maximum correlation for characterizing pulsatile cerebrospinal fluid (CSF) propagation was proposed. After proofing its technical concept, this technique was applied to healthy volunteers and idiopathic normal pressure hydrocephalus (iNPH) patients.Methods:A time-resolved three dimensional-phase contrast (3D-PC) sampled the cardiac-driven CSF velocity at 32 temporal points per cardiac period at each spatial location using retrospective cardiac gating. The proposed technique visualized distributions of propagation delay and correlation coefficient of the PC-based CSF velocity waveform with reference to a waveform at a particular point in the CSF space. The delay time was obtained as the amount of time-shift, giving the maximum correlation for the velocity waveform at an arbitrary location with that at the reference location. The validity and accuracy of the technique were confirmed in a flow phantom equipped with a cardiovascular pump. The technique was then applied to evaluate the intracranial CSF motions in young, healthy (N = 13), and elderly, healthy (N = 13) volunteers and iNPH patients (N = 13).Results:The phantom study demonstrated that root mean square error of the delay time was 2.27%, which was less than the temporal resolution of PC measurement used in this study (3.13% of a cardiac cycle). The human studies showed a significant difference (P < 0.01) in the mean correlation coefficient between the young, healthy group and the other two groups. A significant difference (P < 0.05) was also recognized in standard deviation of the correlation coefficients in intracranial CSF space among all groups. The result suggests that the CSF space compliance of iNPH patients was lower than that of healthy volunteers.Conclusion:The correlation mapping technique allowed us to visualize pulsatile CSF velocity wave propagations as still images. The technique may help to classify diseases related to CSF dynamics, such as iNPH.