Hajime

Sakuma,

Tsuyoshi

MD

Nakagawa,

Yoshiyuki #{149} Yoichi

#{149}

MD

Nomura, MD #{149}Kan Takeda, MD #{149}Tomoyasu Tamagawa, MS #{149}Yasushi Ishii, MD #{149}Tetsuji

Adult and Neonatal Diffusional Anisotropy with Diffusion-weighted Diffusional anisotropy of human brain was investigated clinically in six adult volunteers, eight premature neonates, and three infants aged 5-10 months. Diffusion-weighted magnetic resonance imaging was performed with gradient b of 450 sec/ 2 The direction of diffusionsensitive

gradients

was

changed

among x, y, and z axes according the orientation of neurofibers in white matter. Ti- and T2-weighted images

also

were

obtained

to

for evalua-

tion

of myelination. Diffusional anisotropy was demonstrated in white matter in the adults. Extensive signal attenuation was observed when gradients were parallel to white matter fibers. Conversely, in neonates, diffusional anisotropy of white matter, in which no myelination was shown on Ti- and T2-weighted images, was weak. Diffusional anisotropy was more distinct after brain maturation, as observed

in adult

white

matter.

Detection of dilfusional anisotropy is useful in evaluating neonatal brain development and various white matter disorders. Index

terms:

Brain,

anatomy,

10.92

M

of self-diffusion of water with magnetic resonance (MR) imaging has gained increasing interest recently because it enables evaluation of the microenvironment of in vivo tissue water. Moseley et a! (1) demonstrated anisotropic water diffusion in white matter of cat brain with a small-bore MR system with extensive gradient strength. They proved that signal attenuation EASUREMENT

by water diffusion in white matter greatly depends on the relationship between the orientation of neurofi-

bers and the direction of the diffusion-sensitive gradients. Greater signal attenuation (faster diffusion) was observed when their direction was parallel, compared with that obtained with perpendicular alignment. Recently,

man by

diffusional

white

anisotropy

matter

Chenevert

was

in hu-

demonstrated

et a! (2).

explanation that random cu!es

was

One

suggested

of the anisotropy motion of water restricted

by

the

myelin

of neoevaluated MR images

(3,4).

are

images

gener-

water diffusion man brain with

we

attempted

MR

From the Department of Radiology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514,Japan (H.S., Y.N., K.T., T. Tagami, TN.); the Department of Radiology, Fukui Medical School, Fukui, Japan (Y.T., Y.I.); and

Yokogawa

Medical

Systems,

Hino,

Tokyo

(T.

Tsukamoto). From the 1990 RSNA scientific assembly. Received November 28, 1990; revision requested January 8, 1991; revision received February 13; accepted February 25. Address reprint requests to H.S. 0 RSNA, 1991

to detect

machine

anisotropic

in white a widely

and

matter used

of huclinical

to investigate

effect of myelination anisotropy in white paring adult, infant, brain.

at 35-40

full-term

the

on diffusional matter by comand neonatal

reflexes

cies

recorded

were

ical Systems,

A pulse

Six

and

volunteers

healthy

neonates

were

cardiac

were

neurologic neonates

aged

23-28

abnormality. included eight

or

with

for

diffusion-weighted

single-echo

were

used

spin-

as a standard

image

(repetition

cycles

time

in adults

with

car-

[TR] of two

and

four

cardiac

in neonates,

300-msec delay after cardiac trigger, 120-msec echo time [TEl, one excitation, 128 phase-encoding steps, 5- or 10-mm thickness). Diffusionweighted SE images were obtained by adding diffusion-sensitive gradient pulses cycles

of 44 msec,

gradient

separation

of 10.8 msec, gradient amplitude of 0.9 G/cm) on either side of a 180#{176} radio-frequency pulse (Fig 1). The direction of diffusion-gradient pulses could be changed between x (readout), y (phase-encoding), and z (section-selection) axes to detect diffusional anisotropy. Moreover, a Ti-

weighted SE sequence (TR of 400 msec, of 20 msec, one excitation, 192 phase-encoding steps, 7-mm and a T2-weighted 2,000

msec,

thickness, SE sequence

TE of 80 msec)

3-mm gap) (TR of

were

obtained

for evaluation of myelination. Diffusional anisotropy was visually evaluated by comparing two or three fusion-weighted

obtained

brain

with

images

different

sion-sensitive

analysis was performed ing a region of interest (RO!) The

to the

neurofiber

apparent

for each =

RO!

coefficient

calculated

following equation (6): -ln (S1/SO)/b, where 0

orientation

relative

quan-

by studyon the

diffusion

was

dif-

were

of diffu-

In addition,

titative images.

that

directions

gradients.

TE

accord-

is the

to the diffu-

and 11 infants

studied

between

Octo-

ber 1989 and July 1990. The adult teers

equipped

non-diffusion-weighted

gating

infants

originally developed with language for the detection water diffusion. Axial or

(SE) images

diac

of the

coils. A standard head coil was used.

single-section

echo

No

deficien-

images were obSigna system (GE Med-

sequence

ADC(O) METHODS

in any

gradient bird cage

imaging was pulse program of anisotropic

three

months.

Milwaukee)

self-shielded quadrature

and

5-10

or neurologic

neonates. Diffusion-weighted tamed with a 1.5-T

(ADC)

AND

gestation

aged

abnormal

ing

MATERIALS

weeks

infants

(duration

was mole-

sheath. White matter maturation nates and infants has been with Ti- and T2-weighted Ti-weighted

nates

coronal

Radiology

180:229-233

MS

Brain: Myelination MR Imaging’

ally used in monitoring brain development in the first 6 months of life; T2-weighted images are more valuable after 6 months (5). In this study,

1991;

MD

Tsukamoto,

Human and

Brain, growth and development, 10.92 #{149}Brain, MR studies, 10.1214 #{149} Brain, white matter Magnetic resonance (MR), diffusion study Magnetic resonance (MR), technology #{149} Myelm, 10.92 #{149}

Tagami,

years

and

volunhad

The infants premature

no

and neo-

Abbreviations: ADC efficient, ROI = region echo, TE = echo time,

apparent diffusion coof interest, SE = spin TR = repetition time. =

229

sion-gradient direction (in degrees), Si is signal intensity with diffusion-sensitive gradients, SO is signal intensity without diffusion-sensitive gradients, and b is a gradient factor. Gradient factor b in the y axis is calculated as b = -y2(DG)2(213 D + I), where -y is the gyromagnetic ratio, D and

G are the duration spectively,

and I

and the amplitude,

of diffusion-sensitive is the

sensitive

interval

factor

The

the

U

re-

diffusion-

resultant

in the y direction

Slice (Z)

p

gradients,

between

gradients.

RF and Echo

is 450

Phase ‘)

gradient As

sec/mm2.

n____ ________

for the gradient b factors in the x and z directions, the effects of cross terms between the diffusion and imaging gradient pulses must be considered (7). Therefore,

Read (X)

the gradient factors in the x and z direclions are slightly larger than the value estimated in the y direction (493 sec/mm2 in the x direction and 475 seo’mm2 in the z

Diffusion sensi. tive gradient

direction).

To

test

the

accuracy

of the

mea-

surement, diffusion coefficients with water phantoms and acetone phantoms were measured. The values of ADC(O) were determined for 0 = O (parallel orientation) and 90#{176} (perpendicular

frontal

orientation).

white

matter

radiation

were

The

of diffusional

ratio

calculated

Four

ROIs

.

________

I

1#{149}

axis)

(X,YorZ

Figure 1. Diffusion-weighted live gradients was applied

separate

I____

I

experiments

SE pulse to x (readout),

to detect

sequence used y (phase-encoding),

diffusional

anisotropy.

in this RF

=

study. A pair of diffusion-sensiand z (section-selection) axes radio frequency.

in

in

and four in the optic

obtained

in each

subject.

anisotropy

was

as ADC(90#{176})/ADC(O#{176}).

The statistical significance of the difference between the ratio of anisotropy in adults and that in neonates was determined with a Student t test.

RESULTS Diffusion coefficients of water and acetone at 21#{176}C are shown in Table 1. The measured diffusion coefficients (1.85 x iO- mm2/sec ± 0.02 x mean ± standard deviation, for water and 4.12 x iO- mm2/sec ± 0.03 x iO for acetone in x direction) were in agreement

(2.07 water

0.05

x iOand x i0-

with reported values mm2/sec ± 0.05 x 1O 3.88 x i0 mm2/sec ± for acetone)

coefficients

were

for

(2). Diffusion

fairly

constant

when

the direction of diffusion-sensitive gradients was changed among x, y, and z axes. White matter myelination of brain in adults appeared normal on Ti- and

T2-weighted anisotropy in white

MR images. was matter

images. When of diffusion-sensi-

the

attenuation by water diffusion was greater than when the direction of the gradients was perpendicular to the

(Fig 2). Diffusional

anisotropy

was most obvious in white where the fiber was aligned to either

pus

callosum,

ternal

230

the capsule.

Radiology

#{149}

x, y, or z axis,

optic

radiation,

Directional

matter parallel such

and

in the

peared

normal

radiation

for

aged white

(Table

2).

5-10 months, matter ap-

their

ages.

High

imradia-

tion and the centrum semiovale. The development of white matter myelination was normal. On diffusion-

weighted images, diffusional anisotropy of white matter was well demonstrated,

in-

optic infants of the

white mat± 0.16 x

signal intensity on Ti-weighted ages was observed in the optic

brain

as cor-

difference

± 0.14 x iO in frontal ter and 0.48 x iO mm2/sec In three maturation

tive gradients was parallel to the onentation of white matter fibers, signal

fibers

sec

io

Diffusional

clearly demonstrated of all adults on the

diffusion-weighted relative direction

of diffusion was confirmed by calculating the ADCs in various areas in white matter of the adult brain. ADCs of white matter varied considerably, depending on the relative alignment of the direction of the diffusion-sensitive gradients and the orientation of the fibers. In six adult brains, the mean ADC(O#{176})was 1.24 x iO sec ± 0.16 x i0in frontal lobe white matter and 1.25 x iO mm2/sec ± 0.20 x i#{248}-in the optic radiation. The mean ADC(90#{176}) was 0.48 x iO mm2,

as shown

(Fig 3). Areas

diffusional

anisotropy

in adult

showing on

distinct diffusion-

weighted MR images seemed to be larger than areas with increased sig-

nal intensity on Ti-weighted images. The directional difference of ADC in ROl-image analysis was great. In three infant brains, the mean ADC(O#{176})was 1.37 x iO mm2/sec ± 0.11 x iO- in frontal white matter and 1.47 x iO- mm2/sec ± 0.17 x iO in the optic radiation. The mean ADC(90#{176})was 0.61 x iO mm2/sec ± 0.14 x iO-3 in frontal white matter and 0.67 x iO- mm2/sec ± 0.20 x iO in the optic radiation. These findings were similar to those in adult white matter. In all premature neonates, signal intensity on Ti-weighted images was slightly increased in the brain stem and the posterior limb of the internal capsule. No increased signal intensity on Ti-weighted images was observed in deep and cortical white matter, including the optic radiation. On diffusion-weighted images, diffusional anisotropy was weak in deep and cortical white matter in neonates compared with myelinated adult white matter (Fig 4). Diffusional anisotropy

seemed

relatively

the optic radiation other areas of deep ROI-image analysis,

obvious

in

compared with white matter. In ADCs showed July

1991

b.

Figure gradient. (arrows)

2.

MR images in brain (b, c) Diffusion-weighted was changed between

the direction

of the diffusion-sensitive

greatest. For example, plied perpendicular

C.

of a healthy 25-year-old subject. (a) Axial SE image (TR = 1,800 msec, TE = images (TR = 1,800 msec, TE = 120 msec, b = 450 sec/mm2). The direction readout axis (anterior-to-posterior direction in b) and phase-encoding axis

gradient

optic radiation to the fibers (c).

has

low

is parallel signal

to the orientation

intensity

of white

(b, arrows).

In contrast,

matter less

fibers, diffusion

signal

120 msec) without diffusion-sensitive of the diffusion-sensitive gradient (left-to-right direction in c). When

attenuation

by water

is hyperintense

when

(6,12,13).

However,

weighted

images

by eddy

the

diffusion

is

gradient

is ap-

diffusionwere

current,

deteriorated

especially

when

the

diffusion-sensitive gradient was applied on phase-encoding and sectionselection axes. Recently, detection of anisotropy of in vivo water diffusion

has become possible ager, and excellent mance was achieved shielded

gradient

Moseley lent

coils.

et a! (1,14)

with

differences. the mean

In

significantly nates (P

lower < .01).

ADC(0#{176}) was 1.36 x iO mm2/sec ± 0.22 x iOin frontal white matter and 1.25 x iO- mm2/sec ± 0.30 x iO-

in the optic radiation. The mean ADC(90#{176})was 1.19 x iO mm2/sec ± 0.24 x iO- in frontal white matter and 0.84 x iO- mm2/sec ± 0.25 x i03 in the optic di.ffusional

radiation. anisotropy-that

The

ratios of is, aver-

aged ADC(90#{176})/ADC(O#{176}) in neonates, infants aged 5-10 months, and adults-are summarized in Figure In neonates,

the

ADC(O#{176})was

0.88

white

optic white mean

matter

0.10 in frontal

white

matter,

which

was significantly lower than that in neonates (P < .01). The mean ADC(90#{176})/ADC(O#{176}) of the optic radiation in adults (0.39 ± 0.13) was also Volume

gradient

radiation. The ratio decreased as matter matured. In adults, the ADC(90#{176})/ADC(O#{176}) was 0.38 ±

180

#{149} Number

1

in neo-

(8). was

In addition,

diffusion performed

measurement

with

orientation of the They demonstrated efficient measured

Calif) that with self-

early

we

weighted images of human brain with a clinical MR system equipped with ordinary self-shielded gradient coils. Because the gradient b factor in this study was limited (450 seVmm2), our diffusion-weighted

images

were

not

so heavily weighted as those shown by Moseley et al (1,14) (b factor 1,413 sec/mm2). The images obtained, =

a pulsed in the

history of nuclear MR diffusion measurements (9,10). Cleveland et al (ii) studied water diffusion of rat muscle by changing the relative direction of diffusion-sensitive

Fremont, equipped

of cat

(GE

fusion weighted. For this report, attempted to obtain diffusion-

Several factors exist that affect the signal intensity of nuclear MR. One factor is water-proton diffusion, which has been investigated for more than 25 years with the nuclear MR of anisotropic

mean ADC(90#{176})/ ± 0.11 in frontal and 0.67 ± 0.11 in the

that

MR unit

shielded gradient coils (Acustar; GE Medical Systems). The images obtamed in that study were heavily dif-

DISCUSSION

method

5.

than

excel-

images

a CSI 2.0-T

Medical Systems, had a small bore

slight directional neonatal brains,

showed

diffusion-weighted

brain

only eight

with an MR imgradient perforby means of self-

however, diffusional

matter

successfully anisotropy

of human

Evaluation

with

demonstrated in the white

adult MR

brain. imaging

of

normal and abnormal neonatal brain gradients to the development has been performed images (3muscle fiber 0#{176}-90#{176}.with Ti- and T2-weighted that diffusion at 0#{176} is 1.39-fold

co-

larger than that measured at 90#{176}. In the past 5 years, spatial mapping of in vivo water diffusion with MR imaging techniques has been developed

5). In studies strength MR

with a 1.5-T high-fieldsystem, the increase

in

signal intensity on Ti-weighted images preceded the decrease in signal intensity on the T2-weighted images. It was hypothesized that Ti shortenRadiology

231

#{149}

a. Figure

C.

b.

3.

along

Diffusion-weighted images in brain readout axis (a, anterior-to-posterior

the

matter

also was observed

creased

signal

intensity

in adults.

The

on TI-weighted

extent images

of a healthy 5-month-old direction) and phase-encoding

infant.

of white

anisotropic

4.

to-right

Diffusion-weighted

(b) directions.

relatively

obvious

age (c), signal

images

Diffusional

anisotropy

intensity

in neonatal

anisotropy

diffusion

seemed

is observed

is increased

only

water content (5). The changes

of mature in signal

matter

was

that

was

in adults.

Radiology

#{149}

significantly

Ti-

and

higher

T2-

than

areas

with

in-

gradient

matter

of neonates

directional

differences

limb of the internal

(arrows)

was

compared

applied

with

that

of ADC are smaller

in anterior-to-posterior

in white

(a) and

matter

than in adults.

of adults.

left-

Although

On TI-weighted

im-

capsule.

.

ADC(90) A.DC(O)

El

Adult

Infant Neonatal

brain brain

(n=6) (>5

brain

months,

n=3)

(n=8)

1.0

0.8 0.6 0.4

ob-

scure compared with that in adults. In the quantitative analysis, the ADC in neonatal white matter, measured with the gradients parallel to the fibers, did not differ significantly from that seen in adults. In contrast, the ADC in neonates measured with the perpendicular gradients

in white

in the optic radiation, in the posterior

white matter intensity on

in neonates

Diffusion-sensitive

weak

Ti- and T2-weighted images reflect the concentrations of various biochemical compounds and water. In our study, diffusional anisotropy of white

to be larger

(arrows) was of white

C.

brain.

seems

ing of myelinated white matter was caused by the increase of various proteins, cholesterol, or glycolipids in the developing myelin sheath. Decreased signal intensity on T2-weighted images was explained by the decrease in

232

water

b.

Figure

than

showing

gradient anisotropy

(c).

a.

the

matter

The direction of the diffusion-sensitive axis (b, left-to-right direction). Diffusional

0.2 0

Frontal

white matter

Optic radiation

Figure 5. Comparison of average ratio of diffusional anisotropy neonates, infants, and adults. Mean values in myelinated white tic radiation in the adults were significantly less than in neonates

(ADC[90#{176}VADC[0#{176}]) among matter of frontal lobe and op(*). SD = standard devia-

lion. July 1991

weighted images obtained concurrently showed no evidence of development of myelination in the corresponding suggested

that

area. These diffusional

findings anisotropy

was closely related to neonatal brain maturation, especially with development of myelination. In addition, as shown in the optic radiation, diffusional anisotropy could be observed earlier than the increase of signal intensity on Ti-weighted images. This finding led to the possibility of earlier detection of neonatal brain development with diffusion-weighted MR imaging. Diffusion-weighted imaging provided new information about the microscopic structure of white matter, which could not be assessed with ordinary

Ti-

and

T2-weighted

images.

Several technical limitations have been discussed in diffusion-weighted imaging; the first is fragility to the slightest motion. Profound sleep and careful fixation sary to perform

of the head successful

there

In conclusion,

weighted were

is a limitation

tiple-section data acquisition. planar imaging is the solution these motion artifact problems

in mu!-

Echofor (15).

excellent

images obtained

uation

of neonatal

#{149} Number

1

Le Bihan D, Breton E, Lallemand D, et al. MR imaging of intravoxel incoherent molions: application of diffusion and perfusion in neurogenic disorders. Radiology

7.

Le Bihan D. Magnetic resonance imaging of perfusion. Magn Reson Med 1990; 14: 283-292. Stejeskal EO, TannerJE. Spin diffusion measurements: spin-echoes in the presence of a time-dependent field gradient. J Chem Phys 1965; 42:288-292. Stejeskal EO. Use of spin echo in pulsed magnetic-field gradient to study anisotropic, restricted diffusion and flow. Chem Phys 1965; 43:3597-3603. Cooper RL, Chang DB, Young AC, et al. Restricted diffusion in biophysical systems: experiment. Biophys J 1974; 14:161-177. Cleveland GG, Chang DC, Hazelwood CF. Rorshach HE. Nuclear magnetic resonance measurements of skeletal muscle anisotropy of the diffusion coefficient of the intracellular water. Biophys J 1976; 16:

1986;

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b value

development

of various

9.

10.

11.

white

#{149}

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a gradient

brain

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6.

brain

sec/mm2 by using a clinical i.5-T MR system. Diffusional anisotropy was closely related to the development of white matter in neonatal brain. Detection of diffusional anisotropy has clinical potential in the eva!-

tal and infant

Volume

no exgra-

diffusion-

of human with

im-

of 450

are necesdiffusion-

weighted imaging of infants. Cardiac gating is indispensable, and delay after an R wave of cardiac trigger must be chosen carefully to minimize motion artifact from brain pulsation. Therefore,

Eddy current artifact is another portant problem in diffusionweighted imaging. In our study, substantial eddy current problem isted because of the self-shielded dient coils.

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Radiology

#{149} 233