Neuro-radiology

Neuroradiology(1992) 35:10-15

9 Springer-Verlag1992

Cerebrospinal fluid flow II. Physiology of respiration-related pulsations G. Schroth and U. Klose Department of Neuroradiology,Universityof Ttibingen,Federal Republic of Germany Received:26 March 1991

Summary. Cerebrospinal fluid (CSF) flow in the cerebral aqueduct and spinal canal was analysed using real-time magnetic resonance imaging measurement techniques. Respiration-induced rhythmic modulation of the cardiacrelated oscillating CSF pulsation in the cerebral aqueduct and spinal canal was found. Deep inspiration was immediately followed by a marked increase in downward CSF flow in the cervical spinal canal, whereas a delay of about two heart beats was seen before downward flow from the third to the fourth ventricle increased. This pattern was also detected during yawning and was followed by a marked increase of blood flow in the internal jugular vein. Key words: Cerebrospinal fluid flow - Magnetic resonance imaging - Real time - Yawning

Cardiac-related pulsations of the cerebrospinal fluid (CSF) can be investigated using ECG-gated FLASH magnetic resonance imaging (MRI) [1-6]. However, because 256 exitationts are required to obtain an image with a 256 x 256 matrix other components of the CSF flow are lost. By measurements on animals [7] and humans [8, 9] it was established in the last century that CSF pressure also changes with respiration. However, the resulting changes in CSF flow have not been studied by X-ray contrast cinecisternography or cineventriculography [10-14] nor by cine-MRI [1-3, 6]. We have studied respiration-related CSF dynamics by employing a new real-time MRI technique [15, 16].

Methods

phase-encoding gradient amplitude in each case. To obtain a resolution of 256 pixels in the phase-encoding direction, 256 separate measurements must be made. This results in a long investigation (256 x repetition time), which can be shortened by the use of gradient echos, but still remains in the range of a few s. Thus, in principle, real time detection of movement is impossible using this techniques. However, repetition of measurements can be omitted if no resolution of the second direction in the plane is necessary and no phase encoding gradient is used (Fig. 1), resulting in a reduction of investigation time to 20 ms. With this real time acquisition and evaluation (RACE) technique, real time analysis of movement is possible [5, 16]. For real time detection of CSF flow a slice was selected perpendicular to the cerebral aqueduct or spinal canal, following rapid localization images in the sagittal plane. This slice was then visualised using a 2D FLASH sequence (TR 75 ms, TE 10 ms, flip angle 90 ~ which highlights flow by wash-in of fully relaxed protons [6]. This image is included at the top of the later figures. Next, RACE was applied to the slice selected: a 1D FLASH measurement with TR, TE and flip angle identical to the

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Fig.1. Pulse diagram of RACE. No phase-encoding gradient, as used in FLASH,is activated

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Fig.2. RACE phantom experiment (FLASH 1D, TR 75 ms, TE 10 ms, flip angle 90 ~ The horizontal axis shows 1D Fourier transform in read-out direction; the vertical axis represents a measurement time of approximately 5 s from top to bottom (between arrowheads). Three acrylic tubes are fixed on a wagon moving sinusoidally backwards and forwards through the magnetic field, with frequencies of 1 Hz and amplitudes of 0, 20, 40 and 60 ram. The middle column (a closed tube filled with water) indicates the oscillation of the wagon. The right and left tubes are perfused with water, flowing in opposite directions (arrows) with a net velocity of 10 cm/s

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Fig.3. RACE with additional presaturation pulses. Two selective radiofrequency impulses precede the real-time measurement. Directional information can be obtained with the first saturation pulse, parallel cranially or caudally to the plane examined. The second pulse, saturating protons in the measuring plane, enables better localization of the signal in the plane selected

2D F L A S H sequence but without a phase encoding gradient; only one line of data is obtained during each such measurement. After Fourier transformation, this gives a projection of the 2D sectional image on an axis in the readout direction. In order to examine the time-course of a movement, 256 such separate me asurements of the same slice are made in direct succession. Thus, 256 lines are ac-

quired separated by equal intervals of the repetition time, normally 20--75 ms. The result of these measurements is displayed as a 2D sectional image so that the horizontal axis represents the position of the protons in the readout direction, and the vertical axis corresponds to the time course of the series of 2 5 6 R A C E measurements. Through observing the variation of signal intensity in the vertical axis corresponding to an overall time period of 5-15 s, time-dependent alterations of flow can be analysed with a time resolution of the repetition time. Figure 2 demonstrates a simple example of the possibilities and the high flow-sensitivity of this method. The flow phantom used for this experiments has already been described [6]. In the interpretation of R A C E signals, which are projected on one inplane axis, two problems remain: determination of the direction of the flow into the measuring plane, and of the exact local CSF-flow induced signal increase in the second direction in-plane. As Fig. 3 shows, an attempt was made to filter out the CSF flow signal and to solve the problem of the direction of flow by introducing two additional selective "saturation" radio-frequency impulses prior to the actual excitation. R A C E CSF-flow signals in the cerebral aqueduct are superimposed on the straight and superior sagittal sinuses as well as the central and superior cerebellar veins. R A C E data analysis can be improved if the region of the cerebral aqueduct is selected by presaturation of the anterior and posterior structures of the mesencephalon and cerebellum (Fig. 4) or by projection in the other (Y-axis) direction (Fig. 11). During investigation of CSF flow in the cervical spinal canal, superimposition of blood flow in the deep cervical veins can be suppressed by saturation within the measurement plane (Fig. 4). Determination of the direction of flow through saturation pulses parallel to the measuring plane and its application in 2D F L A S H sequences has been discussed previously [4-6]. Figure 5 shows its use in R A C E phantom measurements. G o o d experimental agreement between calculated flow and magnitude changes of the R A C E signal was found. The phase information of the complex signal was not analysed routinely. Whereas in 2D images sufficient phase correction can be used to avoid phase variations due to magnetic field shifts and incomplete gradient refocussing, this is difficult in the 1D R A C E technique. Depending on the repetition time, which determines time resolution, R A C E measurement require about 520 s. Data on real time CSF flow were obtained in 7 volunteers and 70 patients. R A C E enables quantitative flow measurement [16] if extensive calibration measurements are performed; for demonstration of dependence of CSF flow in respiration, qualitative assessment of CSF velocity and direction was sufficient.

Results

When a section in which the spinal cord abutted the meninges posteriorly, obliterating the posterior subarachnoid space, was chosen, study of the time-varying signal in the course of a R A C E measurement allowed selective ana-

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Hg.4. Effect of in-plane saturation for RACE of CSF flow in the cerebral aqueduct (top) and the cervical spinal canal (bottom) Fig.5. RACE phantom measurement (75 ms/10 ms/90 ~ without (top) and with (bottom) presaturation of a 10-mm-thick slice adjacent in + Z direction to the measuring plane. Flow through the six tubes is directed from - Z to + Z ( - Z direction) and from + Z to - Z ( + Z direction). Complete saturation of + Z flow is obtained in net flow velocities of 3 and 10 cm/s. Less signal decrease due to partial presaturation is seen with turbulent, high velocity + Z flow of 30 cm/s

lysis of the m o v e m e n t of the CSF in the anterior subarachnoid space (Figs. 6-10). The periodic changes in CSF flow with the cardiac cycle, identified using the ECG-triggered F L A S H - 2 D technique [6], were found in R A C E as a rhythmic rise and fall in signal intensity with a frequency of about 1 Hz (Figs. 6, 7). This cardiac-related CSF pulsation was superimposed on an additional c o m p o n e n t with a frequency of several seconds, identified as relating to inspiration and expiration. The respiration-induced modulation of cardiac-related CSF flow is subtle during normal shallow respiration but clearly increased during forced respiration (Fig. 6). 8072

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Fig.6. Top: The selected part of the FLASH 2D image through the cervical spinal canal chosen by in-plane presaturation pulses (TR 75 ms, TE 10 mS; flip angle 90~ Their chronological course is projected onto an image line with the RACE technique (below). Through lengthening TR to 200 ms investigation time is 50 s (top to bottom). The 50 transverse lines in the middle of the image (between small arrows) are classified with the cardiac-related pulsation of the CSF in the anterior subarachnoid space. CSF pulsation and blood flow in the jugular vein (long arrow) demonstrate rhythmic modulations synchronous with respiration, clearly increased during forced respiration (right) as compared to normal respiration (left)

With appropriate selection of the axial plane through the cervical spinal canal precise separation of the R A C E signals from the anterior and lateral subarachnoid space was possible (Fig. 8). During inspiration the CSF flow increases anteriorly, whereas it increases laterally during expiration. However, a definite increase in caudad CSF flow in the spinal canal can be detected only when thoracic respiration predominates. If respiration is deliberately abdominal or if abdominal pressure is increased by a Valsalva manoeuvre, caudad CSF flow ceases (Fig. 9). Analysis over an extended period reveals that the cardiac-related CSF pulsation in the cerebral aqueduct also rise and fall with inspiration and expiration (Fig. 10), but this modulation of the pulsation is less p r o n o u n c e d than in the spinal canal. Moreover, the increase in CSF pulsation occurs 2-3 s after the beginning of inspiration, while the increase in the anterior cervical subarachnoid space can be identified immediately after inspiration begins (Fig. 11). The R A C E technique enables real time observation of CSF pulsation over an extended time period. However, due to technical restrictions (local resolution in only one plane, difficulties in identifying the phase shift of the CSF protons), quantitive study and exact analysis of the timecourse of CSF flow with respect to the heart beat and respiration are difficult. In order to confirm the results of the R A C E technique by another method, a modified E C G triggered F L A S H - 2 D sequences was used. The repetition time was doublet that used in our previous investigations [4-6]. Thus the triggered time period was lengthened f r o m 20 x 75 ms to 20 x 150 ins, giving a total of 3 s. If, during

13

Fig. 8. RACE (75 ms/10 ms/90 ~ shows CSF flow in the anterior (arrowhead) and both lateral CSF channels (arrows) during normal respiration (b), inspiration (e), and expiration (d) Fig. 9. The lower figures show the projection of CSF pulsations in the anterior cervical subarachnoid space (betweensmall arrows) on an image line (RACE 75 ms/10 ms/90 ~ Left: Normal respiration, Right: Increase in CSF pulsation with the start of inspiration (arrowhead); disappearance during 3 s Valsalva manoeuvre (between two largearrows); reappearance of pulsations after Valsalva manoeuvre (lower third of image). The central bright line is an artefact caused by movement of the neck during the Vatsalva manoeuvre Fig. 10 a-d. CSF dynamics in the aqueduct (RACE 75 ms/10 ms, 90 ~ To avoid superimposition with blood flow in the superior sagittal sinus the signals of the axial image (a FLASH 2D/75 ms/10 ms/90 ~ effect of inplane saturation not shown) are projected laterally onto the Y-axis of the magnetic field during normal respiration (b), inspiration (e), and expiration (d) Fig. 11. Projection of the axial slices of the cervical spinal canal (FLASH-2D with saturation pulses in the measuring plane, 75 ms/10 ms/90 ~ using RACE shows the inspiratory and expiratory rise and fall of CSF flow signals in the anterior subarachnoid space during normal respiration (left) Right: increased flow signals can be detected immediately after the start of inspiration (arrowhead)

application of this sequence, inspiration or expiration begins synchronously with every third or fourth heart beat which corresponds approximately to the normal rhythm of respiration - precise analysis of CSF flow changes as a reaction to the action of respiration can be made. Figure 12 shows the CSF dynamics in the cerebral aqueduct during inspiration and expiration. The mean phase of the CSF protons is shifted to the negative side with the onset of inspiration (i. e., at the end of expiration). During inspiration (Fig. 12 a) the mean phase shifts slowly in the positive direction. At the third heart beat the mean phase of the aqueduct CSF protons is positive, indicating bulk caudocranial CSF flow from the third to the fourth ventricle. The phase maximum of the third heart beat after the beginning of inspiration (2400 ms after the Rwave of the ECG) is therefore followed by a peak of signal intensity. However, the mean phase of the protons shifts to the positive side at the start of expiration (at the end of inspiration, Fig. 12b); the phase maxima at 450 and 1500 ms after the R-wave of the ECG are followed by high signal peaks. This is because during early expiration the increased systolic, cardiac-related caudad CSF pulsation and bulk flow from the third to the fourth ventricle summate and many unsaturated protons enter the measuring plane. Thus, in the aqueduct, with a time delay of about two heart beats, inspiration leads to an increase of the pulsatile flow component directed downwards from the third

to the fourth ventricle, whereas in expiration the backflow component of the cardiac-related CSF pulsation is increased. In the cervical spinal canal, the increase of caudad CSF flow follows inspiration without delay. Thus the modified, triggered 2D-FLASH sequence confirms RACE measurements. After a delay of two to four heart beats, inspiration leads to an acceleration of CSF flow from the third to the fourth ventricle, whereas backflow from the fourth to the third is increased during late expiration. The same effects, but without the delay seen in the aqueduct, can also be observed in the cervical spinal canal during predominantly thoracic respiration. During abdominal breathing or a Valsalva manoeuvre, inspiratory caudad CSF flow ceases.

Discussion

As early as 1886, Knoll [7] proved that pressure fluctuations in the cisterna magna of the rabbit changed not only with the heart beat, but also with respiration. Expiration was accompanied by an increase in CSF pressure, while a drop in pressure occurred with inspiration. After Quinke [17] introduced spinal puncture into clinical practice at the end of the 19th century, Becher [8, 9] was able to confirm in humans the animal experiments showing the depen-

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dence of intracranial pressure fluctuations on heart beat and respiration. Since the pressure fluctuations were measured with an open water manometer, the results were relatively coarse; however, they were later confirmed by many other researchers [18, 19]. Through precise measurements with membrane manometers, Ewig and Lullies [20] showed a CSF pressure drop in the lumbar dural sac throughout inspiration, with a pressure increase during expiration, in thoracic respiration. During abdominal breathing an inspiratory increase and an expiratory decrease were observed. Using ECG-gated FLASH-2D measurements it was possible to confirm that the cardiac-related oscillating CSF motion in the cervical spinal canal is superimposed

Fig.13. CSF dynamics in the cervical spinal canal during normal respiration (left) and during yawning (right). Initial rapid CSF flow downwards during deep inspiration (large arrow); absent flow during abdominal contraction (between small arrowheads); increased blood flow in the internal jugular vein (between large arrowheads)

on a bulk flow moving in separate channels, directed mainly downwards in the anterior subarachnoid space and upwards laterally [4-6]. In addition, through modification of the FLASH-2D technique (Fig. 12) and with the help of R A C E it can be shown that the opposed components of CSF flow are not only anatomically separate, but alternate with time: caudad CSF flow in the anterior cervical subarachnoid space dominates during inspiration, whereas expiration is accompanied by an increase in cephalad flow. Caudad flow acceleration occurs immediately on beginning inspiration (Fig. 11), but ceases with abdominal compression (Fig. 9). In the aqueduct the cardiac-related CSF pulsation is affected in a similar way by respiration. The systolic pulsatile flow component downwards from the third to the fourth ventricle is increased during inspiration, but after a delay of 2-3 cardiac cycles (Fig. 10), whereas during the late phase of expiration backflow from the fourth to the third is accelerated. These observations can be interpreted as follows [21]. During thoracic inspiration, the spinal epidural veins are emptied, because of the inspiratory partial vacuum in the thoracic cavity; this leads to rapid caudad acceleration of CSF flow in the spinal canal. The increased inspiratory venous inflow to the heart does not reach the brain until passing through the lungs. This results in acceleration of the CSF pulsation in the aqueduct 2-3 cardiac cycles later. However, during predominantly abdominal breathing or a Valsalva manoeuvre outflow from the large veins caudal to the diaphragm is obstructed. This results in a volume-pressure increase in the epidural venous plexus of the thoracolumbar spinal canal, which can thus be discounted as a compliance system for craniospinal CSF pulsation. Not all components of the "third circulation" [22] in the spinal and intracranial subarachnoid space can be assessed, even with RACE. However, Fig. 13 shows that even minute changes in CSF flow following complex, physiological stimuli can be detected and explained.

15 In a patient examined late in the evening R A C E showed reproducible changes in spinal CSF flow while yawning (Fig. 13): rapid flow in the anterior cervical subarachnoid space at the beginning of the yawn, ceasing after a few seconds. Using the saturation technique in this patient, who had asymmetrical internal jugular veins with small on the right and large on the left, blood flow in the vein was seen to increase significantly for several seconds. Yawning begins with a deep thoracic inspiration, followed by an increase in intra-abdominal pressure after closure of the glottis, with simultaneous reflex opening of the mouth. The result of the initial deep thoracic inspiration is rapid caudad CSF flow in the spinal canal due to emptying of the epidural veins, ending after closure of the glottis and the increase in pressure in the abdomen. The inspiratory increase in blood volume blood reaches the intracranial system two or three heart beats later, after its passage through the lungs. Compliance of the craniospinal CSF system is stopped meanwhile, because of the rise in abdominal pressure. Therefore, only the expressible intracranial venous blood confers compliance, resulting in faster blood flow in the internal jugular vein. The slow course of the yawning reflex could be teleologically interpreted as ensuring the necessary delay between the emptying of the spinal veins and the arrival of the increased inspiratory blood volume in the cranial cavity two to three heart beats later. Its accompaniment by pleasurable sensations can be seen as an additional indication to the body that it must not cut short this physiologically necessary interval.

References 1. Bergstrand G, Bergstroem M, Nordell B, et al (1985) Cardiac gated MR imaging of cerebrospinal fluid flow. J Comput Assist Tomogr 9:1003-1006 2. Feinberg DA, Marks AS (1987) Human brain motion and cerebrospinal fluid circulation demonstrated with MR velocity imaging, Radiology 163:793-799 3. Quencer RM, Post MD, Hinks RS (1990) Cine MR in the evaluation of normal and abnormal CSF flow: intracranial and intraspinal studies. Neuroradiology 32:371-391 4. Schroth G, Klose U, Gawehn J, Petersen D, Varallay G (1987) ECG-related pulsations of the CSF. Society of Magnetic Resonance in Medicine, 6th Annual Meeting, New York, Book of Abstracts, p 119 5. Schroth G, Klose U, Grodd W (1989) Spinal CSF pulsations. In: Nadjimi M (ed) Imaging of brain metabolism, spine and cord, Springer, Berlin Heidelberg New York, pp 53-58

6. Schroth G, Klose U (1992) Cerebrospinal flow. I. Physiology of cardiac-related pulsations. Neuroradiology 35:1-9 7. Knoll P (1886) Ueber die Druckschwankungen in der Cerebrospinalfluessigkeit und den Wechsel in der Blutfuelle des centralen Nervensystems. Sitzungsber Kaisefl Akad Wiss Wien MathNaturwiss Classe 1886:217-248 8. Becher E (1919) Beobachtungen ueber die Abhaengigkeit des Lumbaldruckes yon der Kopfhaltung. Dtsch Z Nervenheilkd 63: 89-96 9. Becher E (1924) Ueber Druckverhaeltnisse im Liqour cerebrospinalis. Grenzgeb Med Chir 35:324-332 10. Di Chiro G (1964) Movement of the cerebrospinal fluid in human beings, Nature 204:290-291 11. Di Chiro G (1966) Observations on the circulation of the cerebrospinal fluid. Acta Radiol 5:988-1002 12. Di Chiro G, Hammock MK, Bleyer WA (1976) Spinal descent of cerebrospinal fuid in man, Neurology 26:1-8 13. Du Boulay GH (1966) Pulsatile movements in the CSF pathways. BrJ Radio139:255-262 14. Du Boulay GH, O'Connell J, Currie J, Bostick T, Verity P (1972) Further investigations on pulsatile movements in the cerebrospinal fluid pathways. Acta Radio113: 496-523 15. Klose U, Schroth G, Mueller E, Grodd W (1988) Echtzeit-Darstellungsmoeglichkeiten yon Liquorbewegungen in der Kernspintomographie. In: Niisslin F (ed) Medizinische Physik, Deutsche Gesellschaft fuer Med. Physik, Ttibingen, pp 562-567 16. Mueller E, Laub G, Graumann R, Loeffler W (1988) RACE-real time acquisition and evaluation of pulsatile blood flow on a whole body MRI unit. Society of Magnetic Resonance in Medicine, 7th Annual Meeting, San Francisco, Book of Abstracts, p 729 17. Quinke H (1877) Ueber den Druck in Transsudaten. Arch Klin Med 21:453-468 18. Ewig W, Lullies H (1924) Der Einfluss der Atmung auf die Druckschwankungen im Cerebrospinalkanal. Z Exp Med 43: 764781 19. Fleck U (1932) Zur Bewertung des Liquordrucks. Dtsch Med Wochenschr 1:737-740 20. Ewig W, Lullies H (1924) Ueber die pulsatofischen Druckschwankungen im Lumbalkanal. Z Exp Med 43:782-790 21. Sharpey-Schafer EP (1965) Effect of respiratory acts on the circtflation. In: Hamilton WF, Dow P (eds) Physiology, section 2, vol 3. Circulation. Waverly Press, Baltimore, pp 1875-1886 22. Milhorat TH (1975) The third circulation revisited. J Neurosurg 42:628-645

Prof. G. Schroth Department of Neuroradiology Eberhard-Karls-Universit ~it Hoppe-Seyler-Strasse 3 W-7400 Tabingen Federal Republic of Germany