Quantitative CT scan studies in aphasia

BRAIN

AND

LANGUAGE

12, 140-164 (1981)

Quantitative

CT Scan Studies in Aphasia

I. Infarct Size and CT Numbers MARGARET A. NAESER Boston University School of Medicine and Aphasia Research Center, Boston Veterans Administration Medical Center

ROBERT W. HAYWARD Palo Alto Veterans Administration

Medical Center and Stanford University School of Medicine

SUSAN A. LAUGHLIN Palo Alto Veterans Administration

Medical Center

AND LESLIE M. ZATZ Palo Alto Veterans Administration

Medical Center and Stanford University School of Medicine

Infarct size (number of I-mm* pixels in the lesion) on CT scans of 30 aphasia patients was obtained with a semiautomated computer program. The mean number of lesion pixels present per slice containing lesion was approximately 500 for mild aphasias (transcortical motor and conduction). 700 for Wernicke’s. 1000 for Broca’s, 1500 for mixed, and 2000 for globals. These differences were significant for I l/l5 of the group pairwise comparisons. When lesion locus was controlled for in the anterior/posterior plane, 73-100% of the aphasia patients were correctly classified as to type of aphasia by a discriminant analysis utilizing only the number of lesion pixels present on two CT slices. Different slice combinations The authors would like to acknowledge Dr. Wm. P. Gordon for assistance with initial AFP program development and the Syntex Medical System for their cooperation throughout the study. We also gratefully acknowledge Dr. Mary Hyde for the statistical work in data analysis, Dr. Harold Goodglass for assistance in preparation of the manuscript and Ted Burr for assistance with photography. This research was supported in part by the Medical Research Service of the Veterans Administration, and in part by USPHS Grants NS06209 and NS07615. Address reprint requests to Dr. M. A. Naeser. V. A. Medical Center (I 16-B). 150 S. Huntington Ave., Boston, MA 02130. 140 0093-934X/81/010140-25$02.00/0 Copyright All rights

@ 1981 by Academic Press, Inc. of reproductmn in any form reserved.

INFARCT

were

used

for different

lation between tion between may CT

aphasia

group

severity of aphasia lesion size and the

be useful scans

SIZE

to predict

the

performed

AND

CT

comparisons.

and lesion CT numbers

prognosis

at 2 months

for

141

NUMBERS

There

was

a significant

size.There was a significant in the lesion. This type

recovery

potential

correcorrelaof analysis

in aphasics

who

have

poststroke.

INTRODUCTION In previous reports (Hayward, Naeser, & Zatz, 1977; Naeser & Hayward, 1978) we have described the relationship between lesion site as demonstrated by CT scans and aphasia type as classified by the Boston Diagnostic Aphasia Exam (BDAE) (Goodglass & Kaplan, 1972). Lesions in specific anatomic sites resulted in specific aphasia syndromes. We have now further studied the lesions themselves, examining both the size and CT numbers of the infarcts. The method of CT scan lesion analysis and the results obtained in patients with mild to severe deficits classified in six aphasia types are the subjects of this report. PROCEDURE The study sample consisted years who had single episode vascular)

as determined

studied patients

were performed were administered

syntactic Laughlin, were motor

classified (tcm),

vere” mixed

CT

scan.

neurological

(26 males. 4 females) infarctions (presumably

exam,

were

globals; CT scans

following 3: mixed,

of severity for ability Wernicke’s

patients

scanner (with scanner utilized each slice was

six aphasia 6; global,

for the tcm

The language is described scores were

and

follow-up.l

2 months to 24 years poststroke. Within the BDAE. Token Test (TT) (Spreen

into the 7; Broca’s,

(33-47s). aphasia,

aphasics

head This mm:

by

patients cerebral

comprehension test under development at the Pieniadz, & Leaper, in preparation). On the basis

nicke’s, 4. The level as “mild” (X2-100% moderate” (65-91s):

the

of 30 right-handed left-hemisphere

who

on the performed

behavior in more were

TT

more

were without

detail

conduction commands “moderate”

severe

than

the

correct. enhancement

water bag) at the Palo Alto a 256 x 256 picture element IO mm thick. The CT number

bone at +500. Each CT scan infarct area was using a Data General Eclipse S/200

time (PAST) of these test

aphasics

CT

on

scans

(Naeser. Peraino. scores, the patients

could

best

5: Wer-

be described

the TT); Broca’s. “mild-to(47-77s); and the globals. “se-

of these aphasia groups. in Naeser and Hayward

SO-65% contrast

The

I week of the CT scan. all & Benton. 1969), and a

groups: nonfluent category-transcortical S: and fluent category-conduction,

and

to follow and mixed,

ages 3 I-X4 occlusive-

Broca‘s

with

group. on

the

the (1978).

but Syntex

exception of The mixed

not

as severe

System

as

60 CT

Veterans Administration Medical Center, (pixel) matrix.Y Each pixel measured I x 1 scale was based on air at -500, water at 0,

and

analyzed with minicomputer.

the Automated The AFP was

Framing a variation

Program (AFP). of the ASI-I post

hoc CT scan analysis program originally written to study the size of ventricles (Jernigan, Zatz, & Naeser, 1979). This program computed the size of the infarct area in pixels by comparing the mean CT number and standard deviation of pixels within a user-deisgnated ’ One analyzed

conduction aphasic had suffered after absorption of the hematoma.

s For Peterson

further explanation and Kieffer (1976)

of and

an intrdcerebral when only

picture element (pixel) McCullough ( 1977).

bleed; however, the low-CT-number representation

the CT scan was area remained. in

CT

scans,

see

142

NAESER

ET AL.

area (framed lesion area) with the mean CT number and standard deviation of pixels within a small, anatomically similar, but normal, brain sample from the opposite hemisphere (Fig. 1 and 2). For each CT scan slice, the infarcted areas to be framed were first outlined by the neuroradiologist (R.W.H.) on hard copy film in order to exclude low CT number artifact areas, ventricles, and prominent fissures and sulci in the area to be studied. The radiologist had no prior knowledge of the aphasia type for any of the patients’ scans. If the lesion was not visually separable from an adjacent low CT number area, that CT slice was not studied with the AFP. This occurred in less than 5% of the entire data base. If the lesion was contiguous to, but not part of, a ventricle, the curved border of the infarct was preserved, as it was possible to frame the lesion along the X-Y axes one line at a time. The program required the user to input the coordinates which framed the lesion (there was no limit to the number of coordinates which could be used) and the coordinates of a 13-mm square area (169 pixels) in an anatomical area homologous to the lesion in the right hemisphere. The latter was labeled right-hemisphere healthy tissue sample (R,HTS) (see Fig. 2). The AFP first computed the mean CT number and standard deviation of the R,HTS. The mean CT number of this R,HTS was then used as a standard, and with a t test, was compared to successive 4-pixel samples (2 across x 2 down) in the “framed” region in the left hemisphere. A matrix of probability values for the framed region and a summary of the statistical data for it were then printed out (Fig. 3). Each CT slice with a framable infarct was analyzed with the AFP. The method of labeling the slices (B, B/W, W, SM, SM+ I, SM+2) and the composite lesion sites on these slices for the six aphasia types are illustrated in Figs. 4, 5, 6, and 7.

RESULTS AND DISCUSSION Number of Lesion Slices per Patient within Each Aphasia Group

The mean number of CT slices with a lesion present per patient, for the six aphasia types, are listed in Table I. The maximum number of IO-mmthick slices where a lesioft could be observed was eight, and this occurred only once in a global aphasic. The smallest mean number of slices with lesion observed was in the two mildest aphasia groups, the tcm aphasics and the conduction aphasics. The largest mean number of slices with lesion observed was in the globals. The remainder, the Broca’s, mixed, and Wernicke’s, were intermediate to these. Although a one-way analysis of variance program with post hoc t tests on these data showed there was a significant difference (p < .05) for the mean number of lesion slices in the severe aphasics as compared to the mild aphasics (tcm and conduction), and the moderate aphasics (mixed and Wernicke’s), there was not a significant difference in the severe aphasics and the mild-moderate aphasics (Broca’s) (Table 1). The mean number of slices with lesion reflects the extent of the lesion in a craniocaudal direction. These findings suggest that this extent, considered alone, does not necessarily coincide with the severity of aphasia. It is, rather, the size of the lesion on the individual slices, the mean CT numbers of the lesion, and the neuroanatomical locus of the lesion that contribute to the severity. The remainder of our results in this paper deal specifically with the size of the lesions and the mean CT numbers of those

FIG. 1. Illustration ofX-Y coordinate placement used in “framing” the lesion. Left scan shows XPOS 99 and YPOS 187 for upper right corner of the frame (arrow). The right scan shows XPOS still at 99, but the YPOS 153 for lower right comer of the frame (arrow). The lateral border areas in bone are marked off in a similar manner. CT scan is of a 44year-old male, I year poststroke, with mild tcm aphasia.

144

NAESER

ET AL.

FIG. 2. Approximate location of 169-pixel healthy tissue sample (HTS) placement taken in the right hemisphere (white circle), opposite the left-hemisphere lesion. The mean CT number for this R,HTS was 24.8, SD, 3.7.

lesions. A separate paper concerning the involvement of specific neuroanatomical structures within different aphasia groups is in preparation. I. Lesion Size The lesion sizes (number of lesion pixels at p < .05, p < .Ol, and p < .OOl attenuation less than standard probability levels combined) for each of the six aphasia groups were studied in three ways: (A) mean number of lesion pixels present at each CT slice level; (B) mean number of lesion pixels present per lesion slice; and (C) total lesion pixels per patient.

INFARCT

SIZE AND CT NUMBERS

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187 1’105 v 153 191 179 17:

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165 It& 161 159 157 155 153 54

THRWJGH

99

FIG. 3. Computer printout for the framed lesion area in Fig. I. The mean CT number of all lesion pixels was 16.9 (SD, 3.5). The total number of lesion pixels was 684. There were 100 lesion pixels at p < .05 attenuation less than standard (-), with a mean CT number of 20.7; 180 lesion pixels at p < .Ol attenuation less than standard (=), 19.3; and 404 lesion pixels at p < .OOl attenuation less than standard (*), 15.0. (Each sample on the printout is equivalent to four pixels.) Note the X coordinates range 54-99, and the Y coordinates, 187-153, as marked off in the “frame” in Fig. I.

A. Number of Lesion Pixels Present at Each CT Slice Level The mean number of lesion pixels present at each CT slice level, for each aphasia gorup, is listed in Table 2. The means for each group at each slice were studied with a one-way analysis of variance program. Post hoc t tests revealed 2/1.5 significantly different group pairwise comparisons at slice B; 6/15 at slice B/W; 8/15 at slice W; 7/15 at slice SM, and none at the remainder (Table 3). Slice W yielded the best single slice comparison with 8/15 significant differences. Although this slice separated the globals from all other aphasia groups, it did not separate the tcm from the Broca’s in the nonfluent category, nor the conduction from the Wernicke’s in the fluent category. The two separate slices which correlated the best with severity of aphasia were slices B/W and W. The correlation between lesion size at slice B/W and the BDAE auditory comprehension z score was - .81 (JJ < .OOl, n = 20), the TT score, -.86 (p < ,001, n = 20), and the PAST, -.78 (p < .OOl, n = 19). The correlation between lesion size at slice W and BDAE was -.71 (p < .OOI,n = 28), TT, -.76(p .OOl,n = 28), and PAST, -.85 @ < .OOl, n = 25). The correlations with lesion size at slice W, although very high, were probably not higher because the Broca’s with good comprehension had larger lesions (1026 pixels) than the Wernicke’s (737) with poor comprehension at this slice. However, of course, the Wernicke lesions were in Wernicke’s cortical language area, long known to be the major center associated with language comprehension disturbances, whereas the Broca’s were not (Fig. 5 and 7). In this study, lesions of 500 pixels or less on slices B/W and/or W. which were not at the

**p < .Ol. ***p < .001.

*p < .05.

tcm Broca’s Mixed Global Conduction

Min/max:

XISD:

No patients: No. lesion slices per patient:

TABLE LESION

1

*

6.0/l .O 517

3.311.4 215

Mildmoderate Broca’s

PER APHASIA

r probability

6.411.5 418

5

Severe Global

GROUP

levels for pairwise comparisons ** n.s. n.s. n.s. *

4.5/1.0 316

6

Moderate Mixed

Nonfluent aphasias

OF CT SLICES WITH

3

NUMBER

7

Mild tcm

MEAN

ns. n.s. n.5. *

3.6/1.8 216

5

Mild Conduction

n.s. * n.s. * n.s.

314

3.81.5

4

Moderate Wernicke’s

Fluent aphasias

INFARCT

lnfer1or PortIon Antenor Horn

Slice B Lateral

Body of Ventricle

147

SIZE AND CT NUMBERS

Anterw

Horn I

Cistern

Slice B/W

Slice W

Body of Lateral Ventricle

(KJ $3 Q Slice SM

Slice SM+l

Slice %A+2

FIG. 4. Lateral (above) and cross-sectional (below) views of relationship of major language areas to shape of ventricles on CT scan slices done IS” to the canthomeatal line. Brodmann’s numbering system refers to the following language areas: 44, Broca’s; 22, Wernicke’s; 40, supramarginal gyrus; and 39, angular gyrus. (Reprinted from Neurology 0 1978, by Harcourt Brace Jovanovich, Inc.) surface of Wernicke’s area, were associated with only a mild comprehension deficit*.g., f.5 to + 1 on the BDAE z score, 82-100% on the TT, and 79-98% on the PAST. The patients had either mild tcm aphasia or conduction aphasia. The data representing the number of lesion pixels at each CT scan level for each aphasia group were subjected to a discriminant analysis, utilizing a planned comparison approach keeping the anterior and/or posterior

cortical

148

NAESER

Slice SM

ET AL.

Shx

Transcortical

,.r..:. .::; / 0 0 Slice

6

Slice

Motor

Aphasia

Slice

.j:.;:,:

@ SM

SM+2

:::.> .;s\ 0

B/W

..:.

. ... . :. ::

Slice

st”4+1

0 Shce

Broca’s

: ::‘, .: :.:.

t 0 SM+i

Slice

SM+2

Aphasia

FIG. 5. Cross-sectional composite CT scan lesion sites for seven transcortical-motor and three Broca’s aphasics. The mean number of lesion pixels present on slice W is labeled above that slice for each group.

lesion loci separate, and using only two groups at a time. For the tcm/ Broca comparison (both primarily anterior lesion loci), 7/7 tcm’s were correctly classified and 3/3 Broca’s (100%). Although lesion size information was entered for all five language slices, only slices B/W and SM were selected in the analysis as steps 1 and 2. For the Broca’s/mixed comparison, 3/3 Broca’s and 4/6 mixed were correctly classified (78%). Slices B and W were selected in the analysis as steps 1 and 2. For mixed/global comparison, 4/6 mixed and 4/5 globals were correctly classified (73%). Only slice SM was selected. For the conduction/Wernicke’s comparison (primarily posterior lesion loci), 4/5 conduction and 4/4 Wernicke’s aphasics were correctly classified (8%). Slices W and SM were selected as steps 1 and 2. Hence, as can be seen from the discriminant analysis, the lesion size data from different slice level combinations was necessary to separate different aphasia groups from one another. One single variable, i.e., lesion size at one level, was not enough.

INFARCT

SIZE

Shce SM

AND

Slice

Mixed

CT

149

NUMBERS

SM+I

Ske

SM+2

Aphasia

i = 2370

Slice

Slce

SM

Global FIG. aphasics. each

6.

Cross-sectional The

mean

number

composite of lesion

CT pixels

SM+l

Slate

SM+Z

Aphasia scan present

lesion

sites

on slice

for

six

W is labeled

mixed above

and

five that

global slice

for

group.

B. Mean Number of Lesion Pixels Present per Lesion Slice The mean number of lesion pixels present per CT slice with lesion for each aphasia group is listed at the bottom of Table 2. As was observed previously, the mild aphasia groups-tcm and conduction-showed the least amount of involvement. The average size of the lesion in the globals was almost four times that in the mild groups. The Broca’s, mixed, and Wernicke’s were intermediate to these. These means for each aphasia group were studied with a one-way analysis of variance program. Post hoc t tests revealed 1 l/15 of the group pairwise comparisons were significantly different (Table 4). The t tests on this single variable-average number lesion pixels per lesion sliceyielded the highest number of significant group pairwise comparisons of all the single variables studied. There was a significant difference between the severe globals and every other group Gr, < .OOl) except for the mixed. This mixed group was also the closest to the globals in severity. The tcm aphasics were significantly different from all other groups except the other

2 308 22 292 324 6 326 97 I48 400 6 536 356 124 I I08 5 517 304

Slice B/W No. patients x SD Min Max

Slice W No. patients x SD Min Max

Slice SM No. patients x SD

0

Slice B No. patients x SD Min Max

-

tcm

3 945 91

3 1026 273 864 I342

3 994 648 560 1740

2 834 659 368 1300

-

0

Broca’s

Nonfluent

6 1221 711

6 1477 711 640 2376

5 1396 617 732 2096

3 1026 834 280 1928

I 1836 -

Mixed

aphasias

5 2100 398

5 2370 662 I808 3256

4 2446 532 I752 3004

4 2260 696 1268 2824

3 1068 424 580 1356

Global

0

0

5 518 576

4 347 271 68 700

I 716 -

-

-

Conduction

Fluent

0

4 675 615

4 737 406 50 I344

I 816 -

I 336 -

-

-

Wernicke’s

aphasias

TABLE 2 LESION PIXELS AT EACH CT SLICE FOR SIX APHASIA GROUPS PERPATIENT AND MEAN PER LESION SLICE, BELOW

-

NUMBER TOTAL

Slice B-l No. patients x SD Min Max

MEAN t;, 0

INFARCTSIZEANDCTNUMBERS

151

152

NAESER ET AL.

@@(gJ -

Slice

Slice

B

SM

Shce

Shce

Conduction

B/W

SM +l

Slice

Slice

W

SM+Z

Aphasia

R = 737

Slice

Shce

B

Slice

B/W

SM

Sltce

SM+l

Wernicke’s

Slice

Slice

W

SM+Z

Aphasia

FIG. 7. Cross-sectional composite CT scan lesion sites for five conduction and four Wernicke’s aphasics. The mean number of lesion pixels present on slice W is labeled above that slice for each group.

mild group, the conductions. These two mild groups did not share the same lesion location, however, as the tcm’s had primarily anterior lesions (frontal lobe) and the conductions, posterior lesions (parietal lobe) (Fig. 5 and 7). There was no significant difference in overall mean number of lesion pixels per lesion slice for Broca’s vs. Wernicke’s. However, their lesion loci were also quite apart: Broca’s, frontoparietal; and Wernicke’s, temporoparietal (Figs. 5 and 7). Broca’s aphasics had more lesion slices, 5-7, than did the Wernicke’s, 3-4 (Table 1). Thus, the Broca’s lesions were larger in total size than the Wernicke’s, because they covered more slices. However, on a slice-by-slice analysis, the average number of lesion pixels per lesion slice was not significantly different between the Broca’s and the Wernicke’s. The correlation between average number of lesion pixels per lesion slice and score on the BDAE was -.66 @ < .OOl, n = 30), TT, -.72 @ < .OOl, n = 30), and PAST, -.82 0, < .OOl, n = 27).

INFARCT

SIZE

AND TABLE

153

CT NUMBERS 3

t PROBABILITY LEVELS FOR GROUP PAIRWISE COMPARISONS OF MEAN NUMBER LESION PIXELS AT FOUR CT SLICES Nonfluent aphasias tcm Slice B tcm Broca’s Mixed Global Conduction Slice B/W tcm Broca’s Mixed Global Conduction Slice W tcm Broca’s Mixed Global Conduction Slice SM tcm Broca’s Mixed Global Conduction

Fluent aphasias

Broca’s

Mixed

Global

Conduction

Wernicke’s

n.s.

n.s. n.s.

* * n.s.

n.s. n.s. n.s. n.s.

n.s. n.s. n.s. n.s. n.s.

n.s.

** n.s.

*** *** **

n.s. n.s. n.s. **

n.s. n.s. n.s. ** n.s.

n.s.

** n.s.

*** ** **

n.s. n.s. ** ***

n.s. n.s. * *** n.s.

ns.

* n.s.

*** ** *

n.s. n.s. * ***

n.s. n.s. n.s. *** n.s.

*p < .os. **p < .Ol. ***p i ,001

In summary, the smallest average lesion size per lesion slice (500 pixels) was observed in the mildest aphasias, and the largest (2000 pixels) was observed in the most severe aphasias. The intermediate-size lesions (700, 1000, and 1500 pixels) were observed in the mild-moderate and moderate aphasias. However, the smaller lesions (mild aphasias) were not located primarily in major cortical language areas, but rather superior or deep to them. The mild tcm aphasics had frontal lobe lesions in or near Broca’s area of only 326 pixels at slice B/W, and frontal lobe lesions of only 536 at slice W; whereas the Broca aphasics had frontal lobe lesions in or near Broca’s area of 994 pixels at slice B/W, and frontal lobe lesions of 1026 at slice W. Also, the mild conduction aphasics had temporal lobe

154 f PROBABILITY

NAESER

LEVELS

TABLE 4 FOR GROUP PAIRWISE COMPARISONS PIXELS PER LESION SLICE Nonfluent

tcm tcm Broca’s Mixed Global Conduction

ET AL.

Broca’s ***

aphasias Mixed *** **

OF MEAN

Fluent Global *** *** n.s.

Conduction n.s. *** *** ***

NUMBER

LESION

aphasias Wernicke’s * n.s. *** *** n.s.

*p < .05. **p < .01. ***p < ,001.

lesions deep to Wernicke’s area of only 347 pixels at slice W and parietal lobe lesion of only 518 pixels at slice SM; whereas the Wernicke’s aphasics had temporal lobe lesions at Wernicke’s area of 737 pixels at slice W, and parietal lobe lesions of 675 at slice SM (see Table 2 and Fig. 5 and 7). Hence, lesion location and lesion size both contributed to differences in aphasia type and the severity of these aphasia types. Correlational studies between quantitative CT scan infarct data and cerebral angiograms have yet to be published. Our findings in this study, however, would suggest that the smaller lesions (500 pixels or less per slice) observed with the tcm and conduction aphasics might be a result of the occlusion of small branch arteries, or more distal portions of major branches of the left middle cerebral artery. The somewhat larger lesions such as those observed with Broca’s aphasia (1000 pixels per slice) and Wernicke’s aphasia (700 pixels per slice) might be a result of the occlusion of at least two or more branch arteries or more proximal portions of major branches of the left middle cerebral artery. In cerebral angiography studies, Broca’s aphasia has been associated with occlusion of the entire superior division of the left middle cerebral artery, and Wernicke’s aphasia, with occlusion of the entire inferior division (Altemus, Roberson, Fisher, & Pessin, 1976). The largest lesions (almost 2000 lesion pixels per slice), which were observed in the global aphasics in this study, were perhaps a result of the entire occlusion of the left middle cerebral artery and/or the left internal carotid artery (with minimal amount of collateral blood flow). The latter was found to be the case in a recent CT scan/ cerebral angiogram study done with aphasics (Yarnell, Monroe, & Sobel, 1976). In summary, it would appear that the size and location of the lesion on CT scans, and hence, the severity of aphasia, may be related to the size and distribution of the arteries involved and amount of collateral blood flow. More research in this area is necessary to confirm this.

INFARCT

t PROBABILITY

LEVELS

SIZE

FOR GROUP

tcm Broca’s Mixed Global Conduction

Broca’s

155

CT NUMBERS

TABLE 5 PAIRWISE COMPARISONS PER PATIENT

Nonfluent tcm

AND

OF TOTAL

Fluent

aphasias Mixed *

n.s.

n.s.

Global * * n.s.

Conduction n.s. n.s. * **

LESION

PIXELS

aphasias Wernicke’s n.s. n.s. n.s. * ns.

*p < .05. **p < .Ol. ***p < ,001. C. Total Lesion Pixels per Patient The means for the total lesion pixels per patient for each aphasia group are listed at the bottom of Table 2. When the major aphasia categoriesnonfluent and fluent-are kept separate, the parallel between rank order of total number of lesion pixels and severity of aphasia is striking. These six means were studied with a one-way analysis of variance program. Post hoc t tests revealed 6/15 significantly different group pairwise comparisons (Table 5). These significant differences were found between the major severity-of-aphasia group differences only-i.e., mild (tcm and conduction) vs. moderate (mixed) and severe (global); and severe (global) vs. mild-moderate (Broca’s) and moderate (Wernicke’s), but not between mild vs. moderate groups-e.g., tcm/Broca’s and conduction/Wernicke’s. It was possible to compute the lesion size in cubic cemtimeters from total lesion pixels (Table 2) because each lesion pixel approximated one voxel (three-dimensional pixel) of tissue, i.e., I x 1 x 10 mm (IO mm was the slice thickness) or 10 mm3 or 0.01 cm3. Thus, the average total volume lesion size for each aphasia group computed from total number lesion pixels was the following: tcm group (1588 total pixels), 15.9 cm3; Broca’s (5723 total pixels), 57 cm3; mixed, 68.5 cm3; globals, 124.8 cm3; conductions, 18.2 cm3; and Wernicke’s, 27.3 cm3. It should be noted that the total number of lesion pixels computed with the AFP analysis can only approximate the total lesion size due to problems with partial voluming of voxels. For example, if the mean CT number of a 4-voxel sample was significantly (lo < .05) lower than the mean CT number of the HTS, all four voxels of IO-mm depth were assigned to infarct area. However, it is possible that part of each voxel was brain, and part, infarct-e.g., 3 mm brain, 7 mm infarct. However, with the AFP analysis, the entire IO-mm depth of the 4-voxel sample was

156

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ET AL.

always assigned to infarct, not part brain, part infarct. This was, of course, done for each case throughout the study, so all aphasia types were treated uniformly. It is possible, however, that the smaller-lesion, mild aphasia cases had, in addition to fewer lesion pixels, greater numbers of partially volumed pixels within the lesion as well. For more information on this possibility, see Part II,E, below. A more accurate estimate of lesion size can now be computed from a recently developed CT scan program, ASI-II, where partially volumed voxel information is retained (Jernigan et al., 1979). The correlation between total lesion pixels per patient and the score on the BDAE was -.63 (p < .OOl, it = 30), the TT, -.70 0, < .OOl, n = 30), and PAST, -.81 (p < .OOl, n = 27). These correlations are similar to that found by Kertesz, Lesk, and McCabe (1977) (-.67), where total lesion size was traced out with a planimeter on 65 radionuclide brain scans of aphasics and correlated with “Aphasia Quotients” from the Western Aphasia Battery. II. CT Numbers The CT numbers discussed in detail here will include the following: (A) R,HTS CT numbers, (B) overall lesion CT numbers, (C) R,HTS minus L,lesion CT-number difference (R-L difference), (D) correlation between lesion size and lesion CT number, and (E) center of lesion CT numbers (p < .OOl level pixels, only). A. R,HTS

CT Numbers

The overall mean CT numbers for the R,HTSs taken opposite the various lesion sites for each aphasia group are listed at the top in Table 6. The overall mean CT number for the 133 R,HTSs was 21.1 (SD 3.7, minimum 13.8, and maximum, 34.5). These CT numbers are all within the expected range for mixed normal grey and white matter for the Syntex scanner. The highest mean CT numbers were obtained for the R,HTSs taken at the top slice (SM+3) where the average was 26.3, SD 4.7. This is compatible with other studies which have found increased CT numbers near the apex of the skull (DiChiro, Brooks, Dubal, & Chew, 1978). There were no significant differences between the groups at any given slice level. B. Overall Lesion

CT Numbers

The lesions associated with mild aphasia (smallest lesions) had mean CT numbers lower than in the normal R,HTS; those associated with more moderate and severe aphasia (larger lesions), even lower, more abnormal CT numbers (closer to CSF and water levels). The overall lesion CT numbers were significantly different 9/15 of the

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157

TABLE6 MEAN CT NUMBERS” AND t PROBABILITY LEVELS FOR PAIRWISE COMPARISONS BETWEEN APHASIA GROUPS Nonfluent aphasias tcm No. lesion slices CT number R, HTS x SD

Min Max CT number L. lesion x SD

Min Max tcm Broca’s Mixed Global Conduction CT number R-L difference x SD

Min Max tcm Broca’s Mixed Global Conduction

Broca’s

Mixed

Fluent aphasias Global

Conduction

Wernicke’s

23

IX

27

32

I8

I5

21.2 4.2 15.6 29.3

19.4 3.1 15.6

21.8 2.8 15.8 26.0

20.6 4.7 13.8 34.5

22.5 3.1 16.4 28.6

20.6 2.35 16.8 25.5

13.3 2.4 8.7 17.6

Il.3

17.1 3.1

12.8 3.4 8.9 18.6

14.6 5.3 6.9 25.0

6.6 2.0 3.6

II.1

25.1

IO.1 3.3 6.0 15.6

**

9.3 1.4 7.7 12.3

***

n.s. **

8.5 1.5 4.7

II.8 *** n.s.

4.5 6.4 28.4

*

10.5 24.2

n.s. *

n.s. *** *** ***

n.s. * n.s. n.s. ***

9.3 2.1 6.0 12.6

5.4 .86 3.4 6.3

7.8 I.7 5.6 10.6

***

n.s. n.s.

** *** *** ***

n.s. * n.s. * ***

o CT number scale is -500, +500. *p < .05. **p < .Ol.

***p < ,001.

aphasia group pairwise comparisons (see Table 6, middle). The conduction aphasics had the highest lesion CT numbers. They were significantly different from all other aphasia groups except the other mild group, the tcm’s. Within the fluent category, there was a significant difference (p < .OOl) between the conduction and the Wernicke’s aphasics. This difference in lesion CT number was the only statistically significant quantitative

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difference between these two groups observed in this framed lesion study. Although the Wernicke’s aphasics did have larger lesions (overall mean, 728 pixels per slice) than the conduction aphasics (504 pixels), this difference in size was not statistically significant. Upon visual inspection of slice W (Fig. 7), the Wernicke’s ahasics also had more cortical surface area involvement in Wernicke’s area than did the conductions. Hence, it would appear that the larger lesion size, the cortical lesion location, and the significantly lower lesion CT numbers may all have contributed to the more severe aphasia associated with the Wernicke’s than with the conduction aphasics. C. R-L CT Number Difference The difference between the CT numbers for the R,HTS minus the L,lesion (R-L difference) was only 5.4 and 6.6 for the mild aphasia groups, conduction and tcm, respectively (smallest lesion sizes). The R-L difference for all other aphasia groups was greater than either of these two groups. The one-way analysis of variance program with subsequent t tests revealed there was a significant difference between the conduction aphasics’ mean R-L difference (5.4) and all other aphasia groups, including the other mild aphasia group, tcm (6.6) and the other fluent group, the Wernicke’s (7.8) (see Table 6, bottom). However, even more striking than just the number of significant differences observed between the groups with R-L difference figures, was the small standard deviations observed within these R-L CT number differences-e.g., for the tcm group the mean lesion CT number was 14.6, SD 5.3. However, for the same group, the R-L CT number difference was 6.7, SD 2.0. This same pattern was observed for every aphasia group-i.e., a lower SD for the R-L CT number difference (Table 6, bottom). Hence, although the patients in this study were scanned through a water bag, and daily water scans had been done for calibration, the range in R,HTS was wide, from slices 1 to 8, and from patient to patient-13.8 (a global) to 34.5 (also a global)-and hence the range in absolute lesion CT numbers was also wide-6.0 (a Broca’s) to 28.4 (a global). Thus, as can be seen here, there can be instances where one patient’s R,HTS CT number (13.8) is lower than another patient’s lesion CT number (28.4). Hence, it is recommended that future studies involving lesion CT number analysis utilize within-patient comparisons to define lesion area, rather than absolute CT numbers. Note, CT numbers are machine dependent and variable within the same CT scanner-e.g., higher white- and grey-matter CT numbers are observed near bone (Zatz & Alvarez, 1977). Thus, although the range of lesion CT numbers observed in our study (10.1-17.1) with the Syntex scanner were similar to those observed in infarcts reported by Alcala,

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CT NUMBERS

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Gado, and Torack (1978), 10.7-14.3 with an EMI scanner, direct comparison is not possible. Hence, it is further recommended that because it is not possible to do studies involving CT number comparisons on patients scanned on separate scanners at this time, perhaps examination of R-L CT number differences may be a more feasible approach to cross-scanner comparisons in the future, assuming the scanners have the same Hounsfield CT number scale (-500, +500 or -1000, +lOOO). Because the correlations had been high between the number of lesion pixels at slices B/W and W, and the aphasia test scores, similar correlations between lesion CT numbers at each slice and aphasia test scores were also done. The correlations between lesion CT numbers at each slice and the TT, BDAE, and PAST scores were nonsignificant. However, when the R-L differences were studied, the correlations were highly significant. At slice W, this correlation with the BDAE was -.63 (p < .OOl, n = 28); and with the TT, also -.63 (p < .OOl, n = 28) and with the PAST, -.76 (p < .OOi, n = 25). D. Correlation between CT Numbers and Lesion Size The lesion sizes in 500-pixel increments and their lesion CT numbers and R-L CT number differences are listed in Table 7 (n = 127 lesion slices). This table shows that for the lesion CT numbers there is a general cutoff with lesions which contain less than 500 pixels (mild aphasias) vs. those that are greater than 500 lesion pixels. Lesions which had less than 500 pixels generally had the highest lesion CT numbers (mean, 14.8). Lesions which were greater than 500 pixels had lower lesion CT numbers (means, 11.1-12.7). The R-L CT number differences, however, showed agradualincrease from smaller to larger R-L differences in correlation with smaller to larger lesion sizes. The correlation between number of lesion pixels and CT number was - .30 (p < .Ol, n = 127); and the correlation between number of lesion pixels and the R-L CT number difference was +.60 (p < .OOl, n = 127). These correlations on a slice by slice basis, as well as overall, are listed in Table 8. The correlation between number of lesion pixels and the R-L CT number difference was the highest at slice W (+ .78, p < .OOl, n = 28). This is probably because almost every patient (28/30) had a focal lesion somewhere on this slice, as well as on the slice above and/or below it. Hence, the lesions observed on this slice were the least partially volumed-i.e., the lesion pixels probably represented totally infarcted area (10 mm thick infarct) rather than part infarct and part normal tissue area. This slice was positioned midway within the distribution of the left middle cerebral artery, hence, the more frontal portion of the scan included lesions resulting from probable occlusion of the superior division branches of the left middle cerebral artery, and the temporoparietal portion of the scan included lesions resulting from probable occlusion of the inferior division branches of the left middle cerebral artery.

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TABLE 7 AND R-L CT NUMBER DIFFERENCES 500-PIXEL LESION SIZE

CT NUMBERS=

Lesion

Number of lesions Mean lesion CT number SD Min Max Mean R-L number difference SD Min

size (No.

FOR EACH

of lesion

SUCCESSIVE

pixels)

I-500

501-1000

1001-1500

1501-2000

2001-2500

2501+

35

33

23

14

13

9

14.8 4.7 8.3 25.0

12.7 7.3 6.4 18.2

11.4 3.5 6.0 18.1

12.0 4.2 6.4 19.0

11.1 2.7 7.3 15.5

12.1 2.2 7.0 14.5

6.4 1.7 3.4 10.6

7.6 1.7 3.7 10.9

9.0 1.6 5.7 11.7

9.1 2.2 5.1 12.3

9.3 2.0 6. I 11.8

10.4 1.8 7.6 12.6

CT-

’ CT number

scale is -500.

+500.

Thus, there was a signicant correlation between the size of the lesion and the absolute CT number of the lesion (p < .Ol), and an even higher significant correlation between the size of the lesion and the R-L CT number difference 0) < .OOl), overall, and especially at slice W. This might be a useful index for evaluating stable infarcts (more than 2 months postonset) on CT scans. A R-L CT-number difference of only 5 or 6 CT units, especially at slice W, should be compatible with smaller lesions (500 CORRELATIONS

Lesion size at each slice B-l B B/W W SM SM + I SM + 2 Overall *p < .05. **p < .Ol. ***p < ,001.

(SLICE

TABLE 8 BY SLICE AND OVERALL) BETWEEN LESION NUMBER AND R-L CT NUMBER DIFFERENCES Correlations with lesion CT numbers .60 n.s. -.28 ns. -.37 n.s. -.37 n.s. -.29 n.s. -.I1 n.s. -.05 n.s. - .30**

with

.09 ns. .39 n.s. .61** .78*** .56** .50* .38 n.s. .60***

SIZE AND LESION

Correlations R-L CT number differences

No. of lesion observations 4 12 20 28 28 19 16 127

CT

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161

CT NUMBERS

pixels), less severe involvement, and a good prognosis for recovery from aphasia. Studies will need to be done with more aphasics to judge the value of these quantitative measurements. E. Center of Lesion CT Numbers Standard Pixels, Only)

(p < .OOl Attenuation

Less Than

The lowest CT number pixels (p < .OOl attenuation less than standard) were always located within the center of the lesion; these were the least partially volumed voxels as well (asterisks in Fig. 3). The mean CT numbers for these p < .OOl lesion pixels (and the mean R-L CT number differences) were the following: conduction, 15.3 (7.2 difference); tcm, 12.8 (8.4); mixed, 11.8 (IO); Wernicke’s, 10.6 (IO); globals, 9.7 (10.9); and Broca’s, 8.0 (11.3). Within each lesion area on each CT scan slice the percentage of lesion pixels which consisted of these lowest CT number pixels was computed. Significant differences @ < .Ol) between the aphasia groups were found for these percentages between the severe aphasics (mixed, 72% of lesion contained lowest CT number pixels and global, 71%) vs. the mild and moderate aphasics (conduction, only 44%, and tcm, 54%; Wernicke’s, 55%, and Broca’s, 59%). These results indicated that those aphasics with the largest lesions-i.e., those with an overall mean number of lesion pixels from 1500 to 2000 (Table 2) had the lowest CT numbers within 70% of the lesion area, whereas the smallest lesions (500 pixels) had the lowest CT numbers within only 44-54% of the lesion area. It is possible that for any given lesion, a fixed amount of perimeter area (5 mm) is supplied by collateral blood flow. Thus, the larger the lesion, the smaller the proportion of marginally injured pixels with respect to the number of totally injured pixels in the center. More patients would need to be studied at controlled postinfarction intervals to learn more about the relationship of percentage lesion with lowest CT number pixels and severity of damage. SUMMARY The major findings of this quantitative study of infarct size and CT numbers on CT scans of six groups of aphasics are: I. Infarct Size A. Number

of Lesion Pixels Present

at Each CT Slice Level

1. Infarct size alone on a single CT slice was not adequate to distinguish all aphasia groups from one another. However, using slice W, 8 of 15 aphasia group pairs could be distinguished by lesion size. 2. There were significant correlations (p < .OOl) between lesion size on slices B/W and W, and severity of aphasia (BDAE auditory comprehension z score, TT, and PAST).

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3. When anterior and/or posterior lesion loci were controlled, a series of discriminant analyses were successful (73- 100%) in distinguishing between paired aphasia groups by using only lesion size information from two separate CT slices. Different slice combinations were necessary for different group comparisons. B. Mean Number of Lesion Pixels per Lesion Slice

1. There was a significant difference in 1 l/15 of the group pairwise comparisons. The mild tcm and conduction aphasics had approximately 500 lesion pixels per lesion slice; the severe globals, 2000, and the remainder were intermediate to these. 2. There was a significant correlation (p < .OOl) between mean number of lesion pixels per lesion slice and severity of aphasia (BDAE, TT, and PAST). C. Total Number of Lesion Pixels per Patient

1. There was a significant correlation (p < .OOl) between total lesion pixels per patient and severity of aphasia (BDAE, TT, PAST). However, only 6/15 significantly different group pairwise comparisons were observed. II. CT Numbers A. R,HTS CT Numbers

1. There were no significant differences observed between the groups for the R,HTSs taken from variable locations-wide ranges were observed in each group. B. Lesion CT Numbers

1. There was a significant difference in 9/15 of the group pairwise comparisons, including the conduction/Wernicke’s comparison. The smallest lesions had higher CT numbers, and the intermediate and larger lesions, the lowest CT numbers. 2. There was no significant correlation between lesion CT number and severity of aphasia. C. R-L CT Number Differences

1. There was a significant difference in lo/l5 group pairwise comparisons. The mild aphasics with lesions of 500 pixels per lesion slice had lesions with CT numbers only approximately 6.4 CT units below the R,HTS, whereas all the other groups had larger R-L CT number differences. 2. There was a significant correlation (p < .OOl) between R-L CT number difference at slice W and severity of aphasia (BDAE, TT, and PAST).

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SIZE AND CT NUMBERS

163

D. Correlation between CT Numbers and Lesion Sizes I. There was a significant correlation between mean lesion CT number and lesion size (p < .Ol), and between R-L CT number difference and lesion size (p < .OOl). E. Center of Lesion CT Numbers (p < ,001 Attenuation Less Than Standard Pixels, Only) 1. With the mixed and global aphasics (larger lesions, 1500-2000 lesion pixels per lesion slice), approximately 70% of each lesion contained pixels with the lowest CT numbers. However, with the other aphasics, each lesion contained only 44-5% of these lowest CT number pixels. Results from this study would thus indicate that an aphasic patient who had a CT scan done at approximately 2 months poststroke would be likely to have a mild aphasia, perhaps a tcm or conduction type, if the following quantitative CT scan criteria were met: 1. The infarct was present on only three or four CT slices (adjacent IO mm thick slices). 2. There were only approximately 500 lesion pixels or less per lesion slice. 3. The 500-pixel lesion was centered primarily superior or deep to the cortical language area of Broca (at slice W) or Wernicke (at slice SM). 4. The lesion had a mean R-L CT number difference of only 5 or 6 CT number units. Results from this study would further indicate that, generally, the severity of aphasia would increase as these quantitative values presented here also increased, although the relationship of these quantitative values to specific neuroanatomical structures must always be considered. REFERENCES Alcala. H., Gado, M., & Torack, R. M. 1978. The effect of size, histologic elements, and water content on the visualization of cerebral infarcts. Archives ofNeurology. 35, l-7. Altemus, L. R., Roberson, G. H., Fisher. C. M., & Pessin, M. 1976. Embolic occlusion of the superior and inferior divisions of the middle cerebral artery with angiographicclinical correlation. American Journal of Roentgenology, 126, 576-581, DiChiro, G., Brooks, R. A., Dubal, L., & Chew, E. 1978. The apical artifact: Elevated attentuation values toward the apex of the skull. Journal of Computer Assisted Tomography,

2, 65-70.

Goodglass, H., & Kaplan, E. 1972. The assessment of aphasia and related disorders. Philadelphia: Lea & Febiger. Hayward, R. W., Naeser, M. A., & Zatz, L. M. 1977. Cranial Computed Tomography in aphasia. Radiology, 123, 653-660. Jernigan, T. L., Zatz, L. M., & Naeser, M. A. 1979. Semiautomated methods for quantitating CSF volume on Cranial Computed Tomography. Radiology, 132, 463-466. Kertesz, A., Lesk, D., & McCabe, P. 1977. Isotope localization of infarcts in aphasia. Archives

of Neurology,

34, 590-60

1.

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McCullough, E. C. 1977. Factors affecting the use of quantitative information from a CT scanner. Rndiology, 124, 99-107. Naeser, M. A., & Hayward, R. W. 1978. Lesion localization in aphasia with Cranial Computed Tomography and the Boston Diagnostic Aphasia Exam. Neurology, 28, 545-55

I.

Naeser, M. A., Peraino, M., Laughlin, S. A., Pieniadz, J., & Leaper, C. The Palo Alto Syntax Test: A sentence level comprehension test for aphasics, in preparation. Peterson, H. O., & Kieffer, S. A. 1976. Computed tomography of the head (Addendum to Neuroradiology chapter). In A. B. Baker & L. H. Baker (Eds.), Clinical neurology. Hagerstown: Harper & Row. Vol. I, pp. 257-290. Spreen, O., & Benton, A. L. 1969. Neurosensory center comprehensive examination for aphasia. Victoria: Department of Psychology, University of Victoria. Yarnell, P., Monroe, P., & Sobel, L. 1976. Aphasia outcome in stroke: A clinical neuroradiological correlation. Stroke, 7, 516-522. Zatz, L. M., & Alvarez, R. E. 1977. An inaccuracy in computed tomography: The energy dependence of CT values. Radiology, 124, 91-98.