Neuroradiology Lars-Olof Wahlund, Lars Forssell, MD2

MD #{149} Jan

The Brain MR Imaging’

#{149}

Ingrid

terms: Aging MR studies,

Radiology

1990;

#{149} Brain, 10.1214

anatomy,

PhD

#{149} Ove

10.92.

174:675-679

Almqvist, BA #{149} Hans Wetterberg, MD

#{149} Lennart

in Healthy

Twenty-four healthy aged individuals with above-average intellectual function were studied with use of a low-field-strength (0.02-T) magnetic resonance (MR) imager. The group was carefully selected so as not to include persons with signs of arteriosclerotic diseases, major somatic disease, or a history of brain disease or dementia in the family. The width of the subarachnoid spaces and lateral ventricles, as well as the frequency and degree of brain white-matter lesions, were described with the use of a visual rating scale. White matter lesions were found in less than 9% of the subjects. The lateral brain ventricles were enlarged in 8% of all individuals and the cortical cerebrospinal fluid (CSF) spaces in more than 40% of all individuals. Moreover, Ti and T2 were estimated in different brain areas, and a positive correlation between Ti in the frontal white matter and age was found. A computer-assisted classification procedure was used to estimate brain tissue and CSF areas. The results of this procedure strongly correlated with the visually estimated ventricular size. Index Brain,

MD

Agartz,

S#{227}#{227}f, Dr Mcd,

Aged

M

resonance (MR) imagallows for an excellent visualization of brain anatomy and has been widely used in the study of both the pathologically altered, as well as the normal, brain. Morphologic changes of the aging brain indude widening of the sulci and enlargernent of the ventricles (1). These changes are easily monitored with MR imaging. The technique is also sensitive in detection of lesions in the white matter. The prevalence of these lesions is high in the elderly (1). In many studies with MR imaging of different brain pathologic conditions, the examined control subjects have exhibited white-matter lesions (WMLs) in 30%-80% (1-3). The variation among the studies might be explained by differences in the criteria of the selection of the control subjects. Individuals with diseases that affect the morphology of the brain may have been included in some of the studies. As a part of a larger study on demented patients, we have examined a group of healthy aged individuals. Aged control subjects with a minimal AGNETIC

for

dementia

in an

early

stage,

as

well as a minimal risk for cemebmovasculam changes, were selected. In the pmesent study, we describe the momphology of the brain seen at MR imaging, as well as MR relaxation times, in the selected group of healthy aged individuals. MATERIALS

AND

METHODS

Subjects From the Karolinska Institute, Department of Psychiatry, St G#{244}ran’sHospital, Box 12500, 5-11281 Stockholm, Sweden. Received June 16, 1989; revision requested August 1; revision received October 16; accepted October 26. Supported in part by Claes Groschinsky and the Karolinska Institute. Address reprint requests to LOW. 2 Current address: Department of Geriatrics, Huddinge, Hospital, Huddinge, Sweden. I

e

RSNA,

1990

Twenty-four individuals (16 women and eight men) participated in the study. The mean age was 79 years (range, 75-85 years). An original sample of iOO persons who considered themselves as having an intact memory recruited from

and being healthy were the community. They

were interviewed by one of the authors (H.B. or L.F.) and examined according to the

six items

in Table

MD

.

Individuals:

ing

risk

Basun,

i.

were excluded according to the exclusion criteria: (a) Individuals with a positive family history of dementia or a history of brain trauma, brain disease, or psychiatric disease. (b) Individuals with a history or signs of arteriosclerosin or persons who were receiving any kind of medication. (c) Individuals who did not have normal clinical examination and functional test results, as described in Table i. A final sample of 24 persons remained in the study. The investigation was approved by the local ethics committee. Blood pressure and serum glucose, tnglyceride, and cholesterol levels of the healthy individuals are presented in Table 2. There were no significant differences between the sexes concerning these Persons

following

results.

MR

Imaging

A low-field-strength MR imager operating at 0.02 T (Acutscan hO; Instrumentarium, Helsinki) was used. To obtain a high contrast between brain tissue and cerebrospinal fluid (CSF) and between brain tissue and WMLS, a T2-weighted spin-echo (SE) sequence was used with a repetition time (TR) of 2,000 msec and an echo time (TE) of i50 msec (TR/TE = 2,000/i50). The brains were examined with 12 contiguous transaxial sections. The section thickness was 10 mm. Rating

of CSF

Spaces

The degree of brain atrophy was estimated by rating the width of the different CSF spaces around the brain hemispheres and the size of the lateral ventricles with the use of a visual rating scale (Agartz et al, unpublished data, 1989). The rating scale is presented in Table 3. The CSF spaces rated are presented in Table 4. To describe larger anatomic brain areas, the following clustered items were used: (a) The size of the CSF space around the

Abbreviations: CSF cerebrospinal fluid, IR = inversion recovery, ROI region of interest, SD = standard deviation, SE spin echo, TE echo time, TI = inversion time, TR repetition time, WAIS-R Wechsler Adult Intelligence Scale-revised, WML white-matter lesion.

675

frontal lobes was estimated by items 2 and 5 (Table 4). (b) The size of the total cortical

CSF

space

was

estimated

by

system

items

2, 3, 4, 5, and 6 (Table 4) clustered together. WMLS are demonstrated with MR imaging as focal or confluent areas of high signal intensity on T2-weighted images, often in the deep white matter. These signal intensity changes might be adjacent to the lateral ventricles and are, in these cases, named periventricular hyperintensity. In the present study, these two findings (WMLS and periventricular hyperintensity) are lumped together and called WMLS. The degree of WMLS in the brains was visually estimated as described in Table 5. All images were viewed by two of the authors (L.O.W., l.A.). The ratings were independently and blindly assessed. The raters’ intemreliability was, in the present study, 80%.

Relaxation

Time

inversion

recovery

(IR)

im-

an image

processor

(GOP-

300; Teragon-Context, Linkoping, Sweden). The regions of interest (ROIs) were drawn as irregular forms or marked pixelwise by using the computer (GOP-300). The ROIs were drawn in the image that exhibited

an optimal

white

matter-gray

matter contrast, usually an SE 2,000/100 image (Fig i). Measurements were made from the following areas: left and right frontal white matter, left and right head of caudate nucleus, and left and right thalamus

(the

medioposterior

part).

of estimations

from

right posterior white matter, clustered together and called white matter. Area

the

left

676

Radiology

#{149}

delineation

classifica-

in a previous report an image-processing

based on used, and telligence

system

of CSF and The number of tissue and CSF)

three

Psychometric

were

State

tested

with

Examination,

mean

tamed

indicated

Scale-revised

formation,

Digit

Design, stitution)

(Associative

Statistical The Student

well

t test

Learning

the

rank

and

Serum

as

test, were

tests:

calcium, creatinine,

used

glucose,

sodium,

potassium,

phosphate, ASAT,

triglyceride

RESULTS

Tests

The results of the psychometric tests are presented in Table 6. Three indexes have been calculated from the subtests of the WAIS-R: The FullScale Intelligence Quotient is based

iron, ALAT,

thyroid

mones, vitamin B32, folic Urinalysis: glucose, protein, scopic examination Routine ECG and EEC Chest radiography Psychometric tests (MMSE, WMS)

used, the Quotient

of

Procedures

chloride, albumin,

cholesterol,

on all the six subtests bal Scale Intelligence

Spaces

Physical examination, including neurologic status Blood tests: blood hemoglobin, sedimentation rate, erythrocyte indexes (MCHC, MCV), complete blood cell count

for correlations.

Psychometric

memory

and

Mann-Whit-

for differences, coefficient,

as the Spearman

of CSF

Examination

and

and

Table 1 Procedures Used in Examination 24 Participating Individuals

(7).

were used correlation

of gen-

(InBlock

Analyses

ney U test the Pearson

ob-

level

2.

Object Assembly, and Digit Sub(6) and two subtests of Wechsler Scale

function

The

were

The results of the ratings of the different CSF spaces are presented in Table 7. A representative image from an investigation is shown in Figure

also tested (O.A.) Adult

Similarities,

Reproduction)

that a high

cognitive

Estimation

Mini

(WAIS-R)

Span,

subtests.

values

function.

as described

by Folstein et al (5). They were by an experienced psychologist with six subtests of the Wechsler

Intelligence

the

performance

era!

Tests

All subjects

Mental

the three verbal subtests the Performance Scale InQuotient is based on the

group

class (brain tissue or CSF) was divided by the number of pixels in the whole brain (brain tissue and CSF).

Table 2 Blood Pressure and Healthy Individuals

hor-

acid, syphilis pH, micro-

WAIS-R,

and

Note.-MCHC mean corpuscular hemoglobin concentration, MCV mean corpuscular volume, ASAT aspartate aminotransferase, ALAT alanine aminotransferase, ECG = electrocardiogram, EEC electroencephalogram, MMSE = Mini Mental State Examination, WAIS-R Wechsler Adult Intelligence Scale-Revised, WMS Wechsler Memory Scale.

Veris

Levels

of Glucose,

Triglycerides,

and Cholesterol

Table Visual

are given

in 24

Level

Systolic blood pressure Diastolic blood pressure Glucose (mmol/L) Triglycerides (mmol/L) Cholesterol (mmol/L) as mean

(mm Hg) (mm Hg)

± standard

157 85 5.4 1.2 6.1 deviation

(SD),

with

ranges

± ± ± ± ±

25 (120-190) 1 1 (70-100) 0.9 (3.4 ± 5.5) 0.4 (0.6-2.4) 0.2(4.2-8.2) in parentheses.

3 Rating

Ventricular

Scale

Used

for

Size in Healthy

Estimation of Size Aged Individuals

Alteration Normal Normal

Width

Width

(4).

Serum

Parameter

Note-Values

of computer-assisted

The

was assessed. To standardize the calculated areas, the number of pixels in each

these were posterior

To assess the accuracy of the visual rating scale, a method for planimetric measurements of the CSF spaces and brain tissue was invented. A transaxial section through the basal ganglia was selected, and two different pulse sequences were obtained, one T2-weighted (SE 2,000/200) and one Ti-weighted (IR 1,500/40/600). These images were then used as a basis for tissue classification according to the tion, as described For this purpose,

objective

and

Measurements

method

used.

CSF

from the subarachnoid space or lateral ventricles was not included when delineating the ROIs, and if this was not possible, these regions were not included in the statistical analysis. Due to the limited number

was

to recognize two classes, and CSF. In this way, an auto-

tissue was obtained. in each class (brain

Visual

ages with different inversion times (TIs) were used for Ti calculations (IR 1,500/ 40/50, 300, 600 [TRITE/TI]). The relaxation time calculations were made with least-squares nonlinear regression analysis by using

matic, brain pixels

Memory

Estimations

One transaxial section through the basa! ganglia was selected, and in this section, three T2-weighted images with a different TE (single-section and singleecho technique) were obtained to calculate T2 (SE 2,000/100, 150, and 200). Three Ti-weighted

(GOP-300)

was trained brain tissue

Width

width width or size

or size or size, slightly enlarged larger than normal or size considerably larger than normal or size extremely larger than normal

of Subarachnoid

Spaces

and

Score 1 1.5 2 2.5 3

March

1990

The

male

subjects

larger ventricles female subjects sex differences concerned the

persons

had

(score, space ened

2). In three cases, the CSF of the temporal lobes was wid(score, 2). When the size of the

space

Table 4 Visually

Rated

Brain

1 2 3 4 5

Frontal

sulci

6

Parietal

sulci

Note-Numbers

ence

correspond

to those

in

total

cortex moderately

(score, (score,

Relaxation

ventricles

had

were

changes changes

No

considered

Time

between

8. Ti and

have a normal total cortical CSF space (score, 1). Two individuals hibited multiple, discrete lesions (score, 2) (Fig 3), and all the other

cantly frontal right

longer white frontal

Area

Measurements

Table

of Psychometric Persons

of 24

Tests

Test

Mean

MMSE FSIQ VSIQ PSIQ AL VR

28 111 113 105 15 8

Range 27-30 96-146 95-150 81-132 8-21 4-13

Note.-MMSE Mini Mental State Examination, FSIQ = Full-Scale Intelligence Quotient from WAIS-R, VSIQ Verbal Scale Intelligence Quotient from WAIS-R, PSIQ Performance Scale Intelligence Quotient from WAIS-R, AL Associative Learning from Wechsler Memorefer-

ry

2.

Scale,

Wechsler

VR

Visual

Memory

Reproduction

sexes

T2 did

not

dif-

when estimated in side. The T2 in the matter was signifi-

than the T2 in the left matter, as well as in the white matter (P < .003).

The computer-assisted area measurements of the lateral ventricles in one selected section correlated significantly (r5 = .82, P < .0009) with the rating scores of the size of the lateral ventricles (item 1) (Fig 4). The ratio of the area of the ventricles to that of the whole brain was 0.053 ± 0.014 (mean ± SD) for those individuals, with the estimated ventricle size (item 6) rated as 1.0 and 0.094 ± 0.027 if the size of the ventricles was rated

6

Results Healthy

the

The mean and 1 SD of Ti and T2 times from brain areas are present-

ed in Table

ex-

no

solitary

Values

differences

were found. the estimated the different

was

to have

)

1 or small 1.5).

fer significantly the left or right posterior white

Structure

Lateral ventricles Interhemispheric fissure anterior to the corpus callosum Left and right sylvian fissures Occipital sulci

the

23 persons

persons

large or larger spaces, and one mdividual had a considerably enlarged CSF space; none was considered to

CSF Spaces

Item

enlarged

around

estimated,

1. ROIs, marked in an SE 2,000/100 image, used for estimation of the relaxation times in different brain areas (left and right frontal white matter, left and right head of caudate nucleus, left and right dorsomedial thalamus, and posterior white matter).

significantly

Two

CSF

Figure

had

compared with the (P < .02). No other were detected that remaining CSF spaces.

Table

from

Scale.

7

Visually

Estimated

Degree

of WMLS

CSF Spac es and Score

Table Visual

5

Brain

Rating

Scale

Used

for Describing

Degree

Alteration No

white

matter

1

changes

matter changes changes

:

1

1.5

2

2.5

3

13 15 22 0 13

9 6 2 12 9

2 3 0 11 2

0 0 0 1 0

0 0 0 0 0

1.5 2 2.5 3

changes

WMLS

Note-Values with the respective

of

individuals

are numbers score.

T

.p,-

,,

Ventricles Temporal lobes Frontal lobes Totalcortex

Score

Small solitary white matter changes Multiple discrete or large solitary white Multiple, partly confluent white matter Multiple, large confluent white matter

Structure

of WMLS

.

I

A

-t

,-‘: 0

-4

A p

7’

.

.

Figure tion were

2.

Transaxial

of the size considered

Volume

174

sections

of the CSF spaces normal (score,

Number

#{149}

3

of the brain in the 1).

V

of an 80-year-old

brain.

Four

sections

healthy are

shown,

volunteer. and

These both

the

T2-weighted lateral

ventricles

images and

(2,000/150) the

different

were used for estimasubarachnoid

Radiology

spaces

677

#{149}

as 1.5. Moreover, subjects

the

(0.105

ratio

± 0.034)

cantly

larger

(0.063

± 0.023)

in male

was

signifi-

women, a finding that the findings of Creasey

subjects

Two

than in female (P < .005).

individuals

nificant

sults Correlations Theme were no correlations between the size of either of the CSF spaces and the clinical parameters. There were no correlations between the results of the Mini Mental State Examination and any of the CSF spaces. Age did not correlate with the size of the CSF spaces, the degree of the WMLs, or the clinical and psychometnic tests findings. Concerning

Ti

and

T2 in the

were

exhibited

(score,

indicated

the

re-

frequency

WMLs is not dependent alone. Other factors (eg, rotic risk factors, family

dementia, previous brain diseases) may also play a role in the development of these changes. This emphasizes the importance of the selection of and the description of an agematched control group when compared with elderly demented patients.

sig-

2). These

that

of

on age arteniosciehistory of

in-

vestigated areas, only the frontal white matter (both left and right) correlated significantly with age (r .64,P