Editorials David

A. Feinberg,

PhD,

MD

Modern Concepts ofBrain Cerebrospinal Fluid Flow’

I

N this

issue

of Radiology,

Poncelet

and

MGH-NMR

co-workers

Center

articles from

of Harvard

by the

Medical

School (1) and Enzmann and Pelc from Stanford Medical School (2) provide exciting new glimpses of brain motion. The findings address a long-standing controversy over the driving force of cerebrospinal fluid (CSF) flow and address the in which

conditions of hydrocephalus flow is impaired. Both articles

display brain velocity with magnetic resonance (MR) phase images. The Haryard study demonstrates a lateral cornpressive velocity component in the thalamic nuclei, while the Stanford study shows

an anterocaudal

motion

of the

cerebellum with the systolic pulse. To present the issues and controversies addressed with these two studies, we must first review prior theories of CSF motion, models of CSF pumps, and earlier MR imaging findings. In 1943,

O’Connell

presented

ful speculations

about

dynamics

on spinal

ments

based

insight-

intracranial tap

CSF measure-

(3):

With each cardiac

systole and during the period before each inspiration there is an increase in the volume of intracranial blood. Now the volume of the cranium cannot increase, and for present purposes the nervous tissues can be regarded as incompressible and undisplaceable. Cerebrospinal fluid must

therefore

be displaced

of the ventricles

and

is diminished nial blood-vessels.

by this .

that the cerebrospinal aided by a vascular

when

the volume

subarachnoid dilation

space

of intracra-

Thus it is believed fluid circulation is pump which drives . .

dynamics,

16.919

Radiology

1992;

Editorials

#{149}

185:630-632

I From the Department of Radiology, New York University Medical Center, 560 First Ave. New York, NY 10016. Received and accepted August 3, 1992. Address reprint requests to the author. 0 RSNA, 1992 See also the articles by Enzmann and Pelc (pp 653-660) and Poncelet et al (pp 645-651) in

this

630

issue.

and

fluid from the ventricles and through the cranial subarachnoid space. There may be a considerable leak back with each stroke of this pump but it is nonetheless considered to be of importance

the transmission

of CSF between

sites at which absorbed

Bering, theory

it is produced

the

through

and

surgical

a

experi-

studies,

duBoulay

argued in favor of a third ventricle pump as the driving force of CSF pulsations and postulated a lateral squeezing of the thalamic nuclei on the third yentricles secondary to brain expansion (5). These two opposing theories of the CSF driving force, brain expansion and choroid plexus expansion, were rooted scientific literature The supporting

since studies,

the however,

had several different sources of experimental error. Intracranial pressure gradients are certainly altered by surgical manipulation of the skull and brain tissue. Pneumoencephalography studies altered brain buoyancy and distorted ventricles by means of air distention. Brain dynamics of interest could not be inferred from distant spinal tap manomeasurements

of CSF

In 1985, a compelling study

from

regions

the

Karolinska

It was demonstrated caudad (antegrade)

all the passageways

systolic

found

pulse

aqueducts

area.

average

The

CSF

normal

demonstrated confirmed ies (10-12).

in

velocity

by its

CSF velocity

patterns

have more recently by several independent Also, circadian variations

been studin

human CSF production have recently been measured with MR velocity imaging (13). CSF motion was not as predicted model,

by the given

third ventricle the MR imaging

the involvement

pump finding

of the lateral

of

ventricles

in ejecting CSF from the brain (9). MR imaging findings also contradicted Bering’s theory, given the compressive mo-

lion of the corpus callosum on the lateral ventricles rather than an outward distention due to choroid plexus expansion. An unexpected finding in our study was an amplified downward

lion

of the brain

stem,

which

to actively drive CSF cisterns and presumably nial cavity. Conservation

was invoked

earlier mo-

appeared

through the basal out of the craof momentum

to explain

the amplified

velocity of the lower brain regions. CSF driving force of the brain stem appears

to be added

volume

expansion

to that

due

This

to net

of the cranial

compartment

The

Institute

It was

(foramen

foramen of Macisterns, while later

vas-

as proposed

by

O’Connell.

MR imaging

demonstrated signal intensity changes of CSF in the aqueduct as a function of cardiac cycle (6). Similarly, the “zebra stripe” method (7) was used at Harvard to detect CSF velocity in the basal cisterns. At this time, Feinberg and Mark (8,9) at the University of California, San Francisco (UCSF), developed a technique of Fourier velocity imaging with which were made the first in vivo measurements of CSF velocity (direction and magnitude) in the cerebral ventrides and passageways. with the arrival of the

brain

the cardiac cycle CSF direction reverses (retrograde), moving into the ventricles and cranial vault. CSF production and flow were measured by multiplying the

cular

pulsation.

of the

caudad, imparting a compressive on all three ventricles and initiat-

ing CSF ejection. that CSF is ejected

in

developed

on animal

encephalography

in the 1950s.

internal

move force

of Monro, aqueduct, gendie) and basal

a neurosurgeon,

based

wave,

ments and claimed that pulsatile expansion of the choroid plexus was the dominant driving force of CSF pulsations (4). Expansion of the choroid plexus within the lateral ventricle should result in a net positive CSF pressure and outward distention of the compliant yentricular walls, differing substantially from an inward compressive force due to brain expansion. To explain pulsatile CSF motion visualized on cine pneumo-

metric Index terms: Brain, hydrocephalus, 10.82 Brain, MR, 13.1214, 15.1214 ‘ Cerebrospinal fluid, MR, 16.1214 . Cerebrospinal fluid, flow

Motion

that

Stanford

study

the dynamics

further

of brain

stem

explains

motion.

sagittally oriented phase images found an anterocaudal motion

cerebellum

and

lower

brain

In

they of the

stem

that

occurs slightly earlier in the cardiac cycle than the caudal motion of the dien-

cephalon readily

and explained

high

brain by timing

stem.

This

is

difference

of systolic arterial pulsation between the anterior and posterior cerebral circulations. The finding is consistent with the slightly earlier onset of CSF caudal motion in the basal cistern than in the aqueduct, initiated by the posterior and

anterior

cerebral

circulations,

respec-

lively. The findings in the Harvard article are important in demonstrating a compressive lateral velocity component at the level of the thalami and third ventricle that is weaker than the caudal velocity component. This is indeed similar to the lateral motion hypothesized by duBoulay, and while it likely contributes to CSF motion at this level, the stronger caudal velocity component covers a larger region of brain parenchyma, affecting all three ventricles. In general, there appears to be a compressive motion of brain parenchyma on the lateral, third, and fourth ventricles. There are some limitations of these

MR imaging

studies.

Phase

imaging

methods, when applied to CSF velocity, are hampered by low spatial resolution, which causes a partial volume effect. Within a voxel containing spins of dif-

ferent velocity, there is destructive interference of the corresponding spin phases (intravoxel incoherent motion), which can greatly reduce the magnitude of the measured velocity. The low spatial resolution on the echo-planar images of the Harvard experiment will suffer such errors in CSF quantitation unless spatial resolution is substantially increased. The Fourier velocity method of UCSF (8) differs substantially from phase imaging by producing a quantita-

live velocity

spectrum.

This

spectrum

separates spin phases of different velocity and is thus immune to the partial volume errors of mixed CSF velocities and brain parenchyma in narrow CSF passageways. The lime-consuming Fourier method, however, is unnecessary for measuring brain parenchyma velocity alone, given its bulk motion and corresponding single spin phase within a

voxel. Accuracy in these MR imaging experiments is determined from velocity resolulion and temporal resolution, the latter being the measurement time in the cardiac cycle. In general, temporal resolution is the lime required for two idenlical gradient pulses that encode a phase shift when spins move parallel to

the direction

of the magnetic

gradient.

Therefore, temporal resolution does not include the lime of spatial phase encoding or signal readout and simply equals 2T + d, where T is the duration of each gradient pulse and d is dead time between the two pulses. The temporal resolulion in the Stanford experiment, 108 msec, however, is more than twice this time, since two consecutive signals are used. The UCSF and Harvard studies used the same spin-echo pulse sequence for velocity encoding, but differed substanlially in temporal resolution (90-120 msec and 45-85 msec, respectively), due to different maximal gradients as discussed below.

Volume

185

#{149} Number

3

Velocity resolution can be defined as the signal phase shift per velocity, 4i/v. The phase shift 4 = k’yT(T + d) Cv, where 4 is phase between -180 and +18f degrees, T and C are the duration and

strength

of the

gradient

pulses,

re-

spectively, and k-y are constants. The above T2 dependence is important in that improvement in temporal resolulion, smaller T, will result in a large loss of velocity resolution unless C is greatly increased (ie, reducing T by haLf requires

more

than

fourfold

increase

in

C). Therefore, the ability to detect subtle timing differences in brain and CSF motion is currently limited by MR imaging

gradient

hardware

rather

than

bio-

logic considerations. The Harvard and Stanford studies were performed with C of 10 mT/m, while the earlier UCSF experiment

used

4 mT/rn,

explaining

its

poorer temporal resolution below tamed with higher mT/rn) provided that are commonly head imaging but

resolution. Temporal 20 msec could be obC values (50-60 by small gradient coils used for echo-planar where fast gradient

switching

not

would

be required,

alley-

ating major technical difficulties. The Harvard experiment also demonstrates the need to isolate brain motion from head motion. Head motion is driven by cardiac pulsations simultaneous with internal brain motion, and so these two velocities are additive in the MR imaging velocity measurement. If the velocity coordinate system can be changed from the external environment to the

moving

coordinate

system

of the

head, then total head motion can be eliminated from the brain velocity measurement. In other words, head velocity must be independently measured and subtracted from brain velocity. The authors

assume

the

scalp,

skull,

and

brain

move together in a rigid fashion in head motion. The skull produces no signal, so head velocity must be measured in the scalp. This correction method appears to have worked well and eliminated what was initially believed to be a net cephalic motion of the cortex during cardiac systole. When considering the Stanford experiment, the cephalic molion of the parietal and frontal lobes might to a large extent be reduced correction for head motion.

In general, intracranial

the pulsatile blood

facilitates

escape

increase

volume

motion. The resulting of brain parenchyma drives CSF out of the downward motion of

with

drives

in brain

compressive force on the ventricles brain, and the the brain stem

of CSF from the cranial

vault. As shown by the Stanford study, the anatomic distribution of expansile arteries and their relative timing of systolic expansion are important determining the directionality and brain motion. All of the

ing velocity

studies

show

factors

in

of CSF MR

uniform

imag-

bulk

motion of large brain regions. While there is perhaps a wafting motion of the cerebral and cerebellar lobes, brain expansion per se, with enlargement of the cerebral hemispheres, has not been demonstrated. MR velocity imaging

studies

consistently

show

large

oscilla-

bidirectional CSF flow, permitting rapid mixing between chambers, as opposed to traditional views of unidireclional flow from the site of production (the choroid plexus) to the site of absorption (the arachnoid villi). Abnormal brain motion in hydrocephalic states is currently being invesligated. A very interesting recent study (14) shows that patients with normalpressure hydrocephalus (NPH) have markedly increased lateral brain molion, while control subjects had weak lateral motion. These findings suggest that abnormal brain motion may be the basis of NPH pathophysiology, as well tory

as providing

a specific

diagnostic

pa-

rameter. It can be postulated that increased lateral brain motion at the level of the third ventricle results in increased CSF pressure, which resists CSF ejection through the foramen of Monro. Alternalively, it can be postulated that at a more distant site, derangement of the caudal motion of the brain stem would reduce and delay the subsequent expulsion of CSF out of the cranial vault, perhaps

blocking

CSF

movement

at the

incisura. With this marked reduction of CSF venting action, pulsatile expansion of the brain’s vascular compartment will not be fully accommodated. A decrease in the global venous drainage would have similar effects. Markedly increased vascular expansile force on brain parenchyma will then be directed centrally toward the ventricular system and, as noted by others (12), an increase in aqueductal CSF velocity may occur. Increased aqueductal CSF flow is consistent with increased ventricular uptake on delayed images of nuclear cisternograms, an accepted diagnostic sign of NPH.

It should

be noted

that

an abnor-

mal inward force on the ventricles differs from the outward force of obstruclive hydrocephalus, as the former would not lead to an immediate expansion of the ventricular system. In either case, however, the increased pressure on periventricular brain parenchyma and blood vessels could cause ischemic damage to the parenchyma and eventually decrease its volume. Evaluation of total brain system dynamics, combining diagnostic parameters of brain motion, CSF velocity, and

vascular

factors

will no doubt

lead to

more specific evaluation of hydrocephalus, useful for guidance and assessment of neurosurgical management. To further define the normal kinematics of brain and CSF motion, MR imaging studies

that

measure

all three

velocity

Radiology

#{149} 631

components,

and

covering

cord,

will likely

the

entire

3.

brain

be needed.

Discrep-

ancies in MR velocity imaging studies may be due to variances in temporal, spatial, and velocity resolutions, as well as findings specific to age-biased popu-

lalions.

4.

In summary, functional MR imof the brain (including these stud-

aging ies of brain and CSF motion, functional mapping of brain activity, and diffusion imaging of acute ischemic events) is re-

shaping

our understanding

physiology

diagnose

and

disease

improving

states.

ability

6. to

#{149}

Enzmann

DR, PeIc

NJ.

7.

Phase-contrast

imaging in measurement of brain Radiology 1992; 185:653-660.

632

Radiology

#{149}

8.

MR motion.

duBoulay

GH.

the CSF pathways.

of normal our

JEA.

Vascular

factors

in in-

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movements BrJ Radiol 1966;

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MID,

Hinks

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Normal spinal

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Nitz

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WG, Watanabe AS, et al. of cerebrospinal fluid: assessment with phase-contrast velocity MR imaging performed with retrospective cardiac gating. Radiology 1992; 183:395-405. Nielsson C, Sthlberg F, Thomsen C, Hen-

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Bergstrand G, Bergstrom M, Nordell B, et al. Cardiac gated MR imaging of cerebrospinal fluid flow. J Comput Assist Tomogr 1985; 9:1003-1006. Edelman RR, Wedeen VJ, Davis KR, et al. Multiphasic MR imaging: a new method for direct imaging of pulsatile CSF flow. Radiology 1986; 161:779-783. Feinberg DA, Mark AS. Cerebrospinal fluid flow evaluated by inner volume magnetic resonance velocity imaging. Acta Radiol Suppl (Stockh) 1986; 369:766. Feinberg DA, Mark AS. Human brain molion and cerebrospinal fluid circulation demonstrated with MR velocity imaging. Radiology 1987; 163:793-799.

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1992