Phase-contrast MRI Measurement of Systolic Cerebrospinal Fluid Peak Velocity (CSFV^Peak) in the Aqueduct of Sylvius: A Noninvasive Tool for Measurement of Cerebral Capacity

After obtaining the approval of the local University Ethics Committee and written informed consent, 11 healthy awake men underwent three consecutive MRI measurements of CSFV^Peakin the aqueduct of Sylvius. Wearing a tightly fitting face mask the volunteers breathed without CPAP and subsequently with 6 and 12 cm H²O CPAP at normocapnia (end-tidal carbon dioxide concentration [ET^CO(2)) = 40 mmHg). Before taking the readings a minimum of 5 min for stabilization at each level was allowed. A high-flow CPAP device (CF-800: Draeger; Luebeck, Germany) was used to apply a CPAP of 6 and 12 cm H²O at 21% oxygen in a randomized order. All airway pressure measurements were taken directly from the face mask. Flow adjustments provided an inspiratory and expiratory pressure swing of no more than 1 cm H (²) O. The volunteers were trained to breathe at a constant ET^CO(2) (40 mmHg) supported by voice command when necessary.

ET^CO(2), noninvasive blood pressure (systolic arterial pressure and mean arterial pressure), and pulsoxymetrically measured hemoglobin-oxygen saturation (Sp^O(2)) were monitored during the investigative period (Odam/Mag-Life/Bruker, Wissembourg, France).

Measurements of systolic CSFV^Peakin the aqueduct of Sylvius were performed on a 1.5 Tesla whole-body scanner (Magnetom VISION; Siemens, Erlangen, Germany) using a standard circular polarized head coil. A two-dimensional gradient echo sequence (2D-FISP) (repitition time [TR] = 100 ms, echo time [TE] = 12 ms, [Greek small letter alpha] = 10 [degree sign], acquisition matrix = 256 x 512, field of view [FOV] = 160 mm) with flow velocity encoding in slice-select direction was used. For this high-resolution axial technique, which is sensitive to through-plan flow, the maximum detectable flow velocity was 20 cm/s. Electrocardiography triggering was used for prospective gating of the acquisition. The disadvantage of prospective gating, however, is that the acquisition is stopped within approximately 200 ms of the next R wave for accurate detection of the next trigger. Thus, the diastolic phase particularly is not evaluated. [5]Cardiac gating produced a series of phase- contrast images at different cardiac phases. From these phase- contrast images a blinded investigator measured the systolic CSFV^Peakin the aqueduct of Sylvius using region-of-interest measurements (Figure 1and Figure 2).

Data are presented as the mean +/- SD. Analysis of variance for repeated measurements and the Student t test for paired samples were used for data analysis, with Bonferroni correction for multiple testing. A P < 0.05 was considered statistically significant.

All volunteers (n = 11, aged 33 +/- 7 yr) completed the study without complications. At a CPAP level of 6 cm H²O the systolic CSFV (^Peak) remained unchanged, whereas at a CPAP of 12 cm H²O the systolic CSFV^Peakdecreased significantly (P < 0.05) (Figure 3, Figure 4, Figure 5).

At a CPAP of 12 cm H²O mean arterial blood pressure increased significantly, whereas systolic arterial pressure, heart rate, Sp (^O)(2) and ET^CO(2) concentration remained unchanged, regardless of the applied CPAP level (Table 1).

The results of our study show that, when measuring systolic CSFV (^Peak) in the aqueduct of Sylvius in an experimental human model of increased intracranial pressure phase-contrast, MRI is a reliable method for detecting changes in cerebral capacity.

With regard to CSF circulation, the inflow of arterial blood during cardiac systole increases the intracranial volume and is compensated by immediate venous egress and CSF displacement to the spinal canal, [6]whereas the cephalocaudal displacement of brain at the foramen magnum [7]contributes only a little to this volume compensation. Recent MRI studies using phase-contrast technique have shown a pulsatile CSF flow in a to-and-fro manner in the aqueduct of Sylvius and the cervical subarachnoid space. [8] 

The systolic increase in cerebral blood volume, displacing CSF caudally across the foramen magnum, occurs slightly earlier than CSF egress from the third to the fourth ventricle. However, both locations (e.g., cervical subarachnoid space and aqueduct of Sylvius) show similar CSF flow velocity profiles. [8]Assuming a negligible change in the cross sectional area of both locations during systole, changes in CSF flow must cause corresponding changes in CSFV^Peak. Therefore, we measured the CSFV^Peakin the aqueduct of Sylvius to assess systolic CSF displacement, which predominantly determines the cerebral capacity or intracranial reserve for accommodating increased systolic cerebral blood volume.

We used CPAP breathing for experimentally increasing extra- and intracranial CSF pressure, because a small but significant increase in lumbar CSF pressure (P^csf; 7 vs. 11 mmHg) has been previously reported in volunteers during CPAP breathing. [9] 

The intrathoracic transmission rate of positive airway pressure depends on lung and chest wall compliance [10]and is reported to be approximately 50% in young volunteers. Three main routes for pressure transmission from the thoracoabdominal cavity to the CSF compartment have been described, namely the jugular veins, [11]numerous non-valved anastomoses between the epidural and vertebral veins and the veins of the thoracoabdominal cavity, [12]and the intervertebral foramina. [13]In humans and animals, however, the percentage contribution of each route to changes in P^csfhas not yet been precisely determined.

Independent of the route of pressure transmission, any increase in P^csfincreases outflow resistance for systolic craniocaudal CSF displacement. Consequently, slowing of craniocaudal CSF flow, which reduces cerebral capacity, should decrease CSFV^Peakin the aqueduct of Sylvius.

Therefore, in the current study, finding CSFV^Peakslightly reduced at a CPAP of 6 cm H²O but significantly reduced at a CPAP of 12 cm H²O indicates that a significant increase in P^csf, as during CPAP of 12 cm H²O, [9]significantly impairs cerebral capacity.

Methodical inaccuracies, however, may influence measurements of systolic CSFV^Peakin the aqueduct of Sylvius because of the small size of this structure (normal, 2 or 3 mm). [14]When investigating steady and unsteady flow, inaccuracies between 5 [15]and 7.5% [16]have been described; but in our study control systolic CSFV^Peakvalues (-5.1 +/- 2.7 cm/s) were in good accordance with previously reported data (-2.0 to -5.2 cm/s). [5,17] 

Arterial and venous (AV) waveform amplitudes in combination account for 56% of the variance of the CSF waveform amplitude at the C2-C3 disk level in healthy subjects. [6]A similar influence on the variance of aqueductal CSF waveform amplitudes, which has not been investigated in previous studies or in the current study, is, however, assumable and must therefore be regarded as another possible source of methodical inaccuracy. Furthermore, evaluation of diastolic CSF flow velocity profiles was not reliably possible because of prospective, instead of continuous, retrospective cardiac gating in our study.

In conclusion, in a human model of experimentally increased intracranial pressure by breathing at CPAP concentrations of 6 and 12 cm H (²) O we found a significant reduction in CSFV^Peakin the aqueduct of Sylvius at a CPAP of 12 cm H²O. Decreased CSFV^Peakindicates a slowing of CSF displacement to the spinal canal, which impairs cerebral capacity for accommodating increased cerebral blood volume. Measurement of CSFV^Peakin the aqueduct of Sylvius by means of phase-contrast MRI is a promising noninvasive method, which may prove useful in neuroanesthesiologic research.

The authors thank those volunteers at Innsbruck University Hospital whose participation made this study possible.

MR signal sensitivity to motion has first been described by Hahn et al. [18] 

When protons move in a magnetic field gradient, they exhibit a change in precession angle (so-called phase shift) related to their velocity along the gradient direction. The total phase shift of a proton thereby increases quadratically with time. In phase-contrast MRI this quadratic phase evolution, in combination with special flow velocity encoding gradients, is used to discriminate moving from stationary protons. For quantification of flow velocity, the phase of the MR signal from a baseline measurement is subtracted from that of a measurement made sensitive to flow velocity by the use of velocity encoding gradients.

Usually, two-dimensional gradient echo sequences are used for quantitative flow velocity measurements in which the direction of the velocity encoding gradients are chosen according to the direction of the measured flow. In the current study a two-dimensional fast imaging with steady state precession (2D-FISP) sequence from the commercially available flow quantification package implemented in the Magnetom VISION system (Siemens) was used.

For quantitative velocity measurements of pulsatile CSF flow cardiac gating is necessary. In prospective electrocardiographic gating, which was used in the current study, the acquisition is stopped within approximately 200 ms of the next R wave to enable the accurate detection of the next trigger. Thus, the diastolic phase in particular is not evaluated.