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

Highlights

• Real-time imaging of CSF velocity cardiac and respiratory components

• Novel technique is simultaneous multi-slice (SMS) phase contrast (PC) EPI

• Respiratory driven CSF velocity for the first time is observed in direction and magnitude

• Inspiration phase CSF movement is directed upwards through the foramen magnum into the basal cisterns and into the ventricular system.

• Expiration phase direction is reversed giving bidirectional respiratory motion

Abstract

Cerebrospinal fluid (CSF) dynamics have been mostly studied with cardiac-gated phase contrast MRI combining signal from many cardiac cycles to create cine-phase sampling of one time-averaged cardiac cycle. The relative effects of cardiac and respiratory changes on CSF movement are not well understood. There is possible respiration-driven movement of CSF in ventricles, cisterns, and subarachnoid spaces which has not been characterized with velocity measurements. To date, commonly used cine-phase contrast techniques of velocity imaging inherently cannot detect respiratory velocity changes since cardiac-gated data acquired over several minutes randomizes respiratory phase contributions. We have developed an extremely fast, real-time, and quantitative MRI technique to image CSF velocity in simultaneous multi-slice (SMS) echo planar imaging (EPI) acquisitions of 3 or 6 slice levels simultaneously over 30 s and observe 3D spatial distributions of CSF velocity. Measurements were made in 10 subjects utilizing a respiratory belt to record respiratory phases and visual cues to instruct subjects on breathing rates. A protocol is able to measure velocity within regions of brain and basal cisterns covered with 24 axial slices in 4 minutes, repeated for 3 velocity directions. These measurements were performed throughout the whole brain, rather than in selected line regions so that a global view of CSF dynamics could be visualized. Observations of cardiac and breathing-driven CSF dynamics show bidirectional respiratory motion occurs primarily along the central axis through the basal cisterns and intraventricular passageways and to a lesser extent in the peripheral Sylvian fissure with little CSF motion present in subarachnoid spaces. During inspiration phase, there is upward (inferior to superior) CSF movement into the cranial cavity and lateral ventricles and a reversal of direction in expiration phase.

Introduction

Cerebrospinal fluid (CSF) velocity is a complex phenomenon and is known to be driven by vascular pulsations (Feinberg and Mark, 1987). Although respiration is known to influence CSF movement (Klose et al., 2000, Schroth and Klose, 1992), it is also known that breathing related susceptibility changes can influence the signal phase (Raj et al., 2000b, Raj et al., 2001b) in echo planar imaging (EPI) in fMRI. In general, MR signal magnitude changes seen with CSF motion have been found to be inherently non-quantitative and cannot show the direction of CSF motion (Bergstrand et al., 1985, Bradley et al., 1986). Spin labeling techniques have shown CSF displacement with breathing and valsalva maneuvers (Yamada et al., 2013, Bhadelia et al., 2013). To date, respiratory-driven CSF velocity has not been directly measured and consequently the relative effects of cardiac and respiratory changes on CSF motion are not well understood. More specifically, the directions and the phases of respiration-driven movement of CSF in distinct compartments of ventricles, cisterns, and cortical subarachnoid spaces are not known. Better understanding of these velocity distributions in time and space are likely occurring through links between cardiothoracic physiology, cerebrovascular, and intracranial CSF dynamics.

Earlier techniques of measuring velocity with phase imaging (Feinberg and Mark, 1987, Enzmann and Pelc, 1992) inherently could not detect respiratory changes since data over several minutes was sorted or regrouped by its time in the cardiac cycle; hence, each image has randomized respiratory phase contributions. Real-time EPI does not require the sorting and grouping of data as images can be acquired in less than 100 ms. Earlier techniques of velocity phase in spin echo EPI were cardiac gated to study cardiac-driven brain motion (Poncelet et al., 1992), and by not being real-time acquisitions, did not reveal respiratory changes in velocity. Conventional EPI time series data have shown signal intensity variations in aqueductal CSF synchronous with respiration (Klose et al., 2000, Schroth and Klose, 1992); however, these sequences could not show the direction of CSF motion nor quantify velocity as the work presented here.

Utilizing a recent development of simultaneous multi-slice (SMS) snapshot echo planar imaging (EPI) (Larkman et al., 2001, Feinberg et al., 2010, Moeller et al., 2010, Setsompop et al., 2012, Feinberg and Setsompop, 2013), time series data at different levels in the brain can be obtained simultaneously without compromising temporal resolution. We have combined SMS-EPI with bipolar gradient pulses (Hahn, 1960, Moran, 1982) for encoding fluid velocity in phase shifts in order to create an extremely fast and quantitative MRI technique to image CSF movement throughout the intraventricular passageways and subarachnoid spaces for real-time CSF imaging (Feinberg et al., 2012, Chen et al., 2014, Beckett et al., 2015). Given CSF velocity can be measured in real time without gating or reordering, we extended the length of the time series to half a minute in order to detect potential changes occurring over several respiratory cycles that would not be readily apparent over a single respiratory cycle. This takes advantage of simultaneous time series data by avoiding errors from normal variations occurring over time and has enabled studies of normal physiological breathing on CSF movement within the brain and subarachnoid spaces. Large regions of the brain and its surrounding CSF spaces were scanned to study CSF dynamics in normal subjects under different breathing conditions.