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PC-MRI measurements of net CSF flow through the cerebral aqueduct strongly depend on respiration
Jolanda M Spijkerman1, Lennart J Geurts1, Jeroen CW Siero1,2, Jeroen Hendrikse1, Peter R Luijten1, and Jaco JM Zwanenburg1

1Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands, 2Spinoza Center for Neuroimaging, Amsterdam, Netherlands

Synopsis

In this work the influence of respiration on net CSF flow measurements was investigated.

In 12 volunteers net CSF flow was measured in the cerebral aqueduct using PC-MRI at 7T, with respiratory gating on expiration and on inspiration, and without respiratory gating. Repeated measurements were performed. Net flow over the cardiac cycle was determined.

Net CSF flow (mean±sd) was -0.64±0.32 mL/min (caudal) during expiration, +0.12±0.49 mL/min (cranial) during inspiration, and -0.31±0.18 mL/min without respiratory gating. Two outliers, with reversed (cranial) net CSF flow, were observed when no respiratory gating was performed. Repeatability was best for gating on inspiration.

Introduction

Cerebrospinal fluid (CSF) plays an important role in maintaining homeostasis and in the clearance system of the brain1,2. With aging and in disease CSF dynamics are altered3–5. Net CSF flow over the cardiac cycle through the cerebral aqueduct may serve as a measure for CSF production in the lateral ventricles, and can be measured using PC-MRI6,7. It has been shown that CSF flow dynamics depend also on respiration8–12. In this work the influence of respiration on net CSF flow measurements was investigated.

Methods

Twelve volunteers (7 male, age 19-39 years) were scanned at 7T (Philips Healthcare) with a 32ch receive head coil and volume transmit coil (Nova Medical).

Single-slice PC-MRI measurements were performed in the cerebral aqueduct (Figure 1) with encoding velocity (venc) 15 cm/s, acquired resolution 0.45×0.45×3 mm3, TR/TE 12/5.9 ms, 36-45 frames per cardiac cycle, depending on cardiac rate, scan time 1:28-1:52 min /4:26-5:38 min without/with respiratory gating, depending on cardiac rate. Measurements were performed with respiratory gating on (1) expiration and (2) inspiration, and compared to no gating. All measurements were repeated.

Background correction was performed13, and phase unwrapping was performed if necessary14. The cerebral aqueduct was determined automatically within a manually drawn brain stem region-of-interest (Figure 1). Net CSF flow through the aqueduct was obtained. Stroke volumes were determined by averaging the systolic (caudal) and diastolic (cranial) flow volumes.

To assess repeatability, the difference, absolute difference, and the Intraclass Correlation Coefficient (ICC) of net CSF flow and stroke volume between the repeated measurements were determined.

Repeated-measures ANOVA was performed to compare net CSF flows during gating on inspiration, expiration, and no respiratory gating, for both measurements separately. Significance level was p<0.05, Bonferroni correction was applied for the pairwise comparisons (3 tests).

The relation between respiration-induced net CSF flow variation and cardiac-induced CSF pulsatility, was explored by linear regression analysis between the net flow difference (inspiration minus expiration) (dependent variable) and the average stroke volume of inspiration and expiration (independent variable), for both measurements separately.

Results

During expiration relatively large caudal net CSF flow was found, while the median net CSF flow was reversed (flow in cranial direction) during inspiration (Figure 2).

The difference in net CSF flow between respiratory conditions (expiration, inspiration, no gating) was significant (p=0.001 for both measurements). The difference in net CSF flow between expiration and inspiration is very similar between the repeated measurements (pairwise comparisons, Table 1).

For net CSF flow ICC is smallest during gating on inspiration (Table 2). Stroke volumes were similar for all respiratory conditions.

Linear regression analysis revealed a significant association between net CSF flow difference and average stroke volume (Figure 3).

Discussion

The observed net CSF flow difference between inspiration and expiration is in line with literature, which showed cranial CSF motion during inspiration, and caudal motion during expiration for real-time measurements8–12. The influence of respiration on net CSF flow may be explained by changes in thoracic and intracranial pressure over the respiratory cycle, affecting the intracranial blood volume11. Furthermore, a larger CSF pulsatility over the cardiac cycle was associated with larger respiratory-induced variation in net CSF flow. Thus, these distinct parameters of the CSF flow dynamics may reflect the compliance of the intracranium (brain, blood vessels and CSF) to pressure changes, in a similar way.

It is perhaps illustrative that the results without respiratory gating were significantly different from inspiration (but not expiration) gating in the first measurement, while this was opposite in the second measurement. This suggests that, without respiratory gating, net CSF flow may be closer to either inspiration or expiration, and respiration effects may not average out over the acquisition.

The average net CSF flow acquired without respiratory gating is in line with values found in literature, ranging between 0.26–0.74 mL/min6,15–20. Our results are on the lower end of this range. The use of high spatial and temporal resolutions together with the high SNR (7T) may have reduced the influence of partial volume and noise and, thus, the overestimation of the net flow.

Repeatability of net flow measurements was best for respiratory gating on inspiration. The low repeatability without respiratory gating is in line with literature19.

Stroke volumes are in line with values found in literature (30–50 μL/cycle)4,21–23.

The main limitation of this study is the limited number of subjects.

Conclusion

Net CSF flow was increased during expiration, and reversed (cranial) during inspiration. Net CSF flow difference between inspiration and expiration correlated significantly to stroke volume. Care should be taken in linking net CSF flow measurements to CSF production.

Acknowledgements

This work was supported by the European Research Council, ERC grant agreement n°337333.

References

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Figures

Figure 1: Slice planning of the PC-MRI scan (single slice, yellow) for volunteer 5, relative to a whole-brain 3D T1-weighted TFE scan (A) and a whole-brain 3D T2-weighted 3D balanced gradient echo scan (B), and the corresponding, manually drawn, brain stem region-of-interest (orange) in the magnitude image (C), and the automatically determined aqueduct ROI (red) (D) The cerebral aqueduct is indicated by the white arrow.

Figure 2: A: Boxplots showing the mean net CSF flows, during gating on expiration (Exp), no respiratory gating (No), and gating on inspiration (Insp). Outliers are represented by the circle symbol. Except for one outlier, only negative (caudal) flows were measured during expiration, while during inspiration mainly positive (cranial) flows were measured. B: Mean net CSF flow for each subject. Generally, net CSF flow measured without respiratory gating is in between the net flows measured during expiration and inspiration. C: net CSF flow measured in each subject during the first and second measurement.

Table 1: CSF net flow differences (mean ± SEM) between the respiratory conditions, and the corresponding p-values, for the pairwise comparisons of the repeated measures ANOVA, for the first and the repeated net CSF flow measurements during gating on expiration, gating on inspiration, and no respiratory gating. Significant p-values are represented by the asterisk symbol.

Table 2: Repeatability of net CSF flow and CSF stroke volume (mean ± standard deviation (SD)) during gating on expiration (Exp) no respiratory gating (No), and gating on inspiration (Insp), showing the results for the first and second measurement, the average of the first and second measurement, the difference (mean ± SD) and absolute difference (mean (range)) between the first and second measurement, and the Intraclass Correlation Coefficient (ICC) between both measurements..

Figure 3: Regression analysis between the net CSF flow difference for inspiration minus expiration (dependent variable), and the average stroke volume for expiration and inspiration (independent variable), for measurement 1 (A) and measurement 2 (B). A positive association was consistently found for both measurements

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)
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