Computed

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C. H. JOSEPH

CHANG,1

Tomographic

JUSTO

Evaluation

U. SIBALA, STEVEN AND ARCH

U. FRITZ, JOE W. TEMPLETON

with water Resolution

Experience with a dedicated breast CT scanner (General CT/M) using a contrast medium enhancement technique indicates that CT is superior to mammography, thermography, or physical examination for diagnosing both benign and malignant mammary disease especially in dense, thick, or fibrocystic breasts. CT is capable of diagnosing totally unsuspected early miniature carcinomas. It can identify and differentiate potential precancerous lesions from benign fibrocystic disease, and is the diagnostic tool of choice for evaluating and following severe fibrocystic disease. CT evaluation also affords definitive diagnostic help in instances where the mammographic, thermographic, and/or physical examinations are inconclusive. It can influence immediate surgical intervention or mitigate against an unnecessary biopsy. The study not only demonstrates morphologic changes

Electric

In the breast pool

in mammary

but also

accurately

depicts

an altered

infusion in

of 300

pulsed

detectors,

x-ray

tube,

an array

and a Data General

5/200

Eclipse

Xenon

computer

number

is identified

on

obtained

on hard-copy

minal

and

cathode

ray

tube

Am J Roentgenol © 1978 American

graphic,

and/or

For every the

1976

One

of

with

procedure

is

CT

CT

their

1977,

values

are

general

had

breast

patients

film

groups

physical,

abnormalities.

many four

655

examination,

Two

The

of

mammoother

group

of these patients were cases were studied to

cancer

after

Two

additional

chemotherapy.

to appraise

infusion,

the highest

final

a physical group

thermographic

and

All

December

had

thermography.

selected.

status

Squibb)

After

scanning

lesion,

display.

through

All patients

mammoplasty

cobalt

therapy

patients

or

were

the status of their breast after augmentation silicone. Findings

Breast

Cancer

There were 31 malignant lesions detected in 28 patients; all were histologically proven. Breast carcinoma in a fatty breast is characterized on a CT/M scan as an irregular mass (fig. 1). In moderate to markedly dense fibrocystic breasts, a mass cannot be distinguished from the surrounding tissues. The mass becomes obvious on enhancement with contrast material because of the preferential

iodine

uptake

by

the

tumor

(fig.

2).

Malignant

microcalcifications without an associated mass be identified on initial scans, but can be identified areas of marked enhancement on postinjection (fig. 3).

gas

with

Carcinomas

Dunn camera, operator ter-

ranging

in diameter

from

2 mm

cannot as tiny scans to

9 cm

were diagnosed by CT. Eight were less than 1 cm, seven were 1-2 cm, eight were 2-3 cm, six were 3-5 cm, and two were over 5 cm in the maximum diameter. A tiny 2 x 2 mm carcinoma was totally unsuspected by physical examination, thermography, or mammography. This lesion was diagnosed on CT by identifying high postinjec-

after revision May 25, 1978. Radiology. University of Kansas Medical 1978

the

studied

display.

131 :459-464, September Roentgen Ray Society

were

10 mm.

printout.

and

lumpectomy

Imaging is done at 120 Kvp, 20 mA, and 10 sec per 360 rotation. Reconstruction time per slice is 90 sec. Slice thickness is 1 cm. Images from a 127 x 127 matrix are displayed on a scale of -127 to +128 CT numbers according to calibration Received February 28, 1978; accepted ‘All authors: Department of Diagnostic J. Chang.

October

studied.

patients

check

magnetic tape drive, Diablo disc, and an operator cathode ray tube display. The breast is examined in a water bath. Viewing

and display hardware includes a Versatec printer, and interactive viewing console with a duplicate

III,

(AENO-M-DIP,

within

had asymptomatic dense breasts; in a high risk group. In addition,

breast CT fan-beam x-ray generator, a

high-pressure

J. DWYER

and the exact

breasts.

mammography,

Methods

of 127

meglumine position

for both

were

,

grid

sitting

is repositioned

repeated

iodine

ml diatrizoate

a comfortable

From

and

SAMUEL

at zero. The scanning field is 20 cm in diameter. volume for each picture point is 1.56 x 1.56 x 10

the patient

Computed tomography (CT) has revolutionized radiologic practice. The diagnosis of various benign or malignant breast diseases using computed tomographic techniques represents a new application for this advanced diagnostic tool. Preliminary reports of CT diagnosis of breast disease have been published [1 2]. This paper reports our experiences with a dedicated breast CT scanner (General Electric CT/M) in 655 patients. Results are compared with conventional mammography, breast thermography, and physical examination for histologically proven cases of benign and malignant disease. Experiments are underway to identify and evaluate various computer image processing techniques which are applicable to this class of CT images. Quantitation of CT number change after injection of contrast media and statistical measurement and evaluation of specified regions in the image seem promising. Subjects

H. GALLAGHER,

mm. The skin exposure dose is 240 mA per breast. The patient lies prone on a canvas table which contains an opening for the dependent breast. The table is tilted into the horizontal position to permit the breast to be freely suspended and positioned within the water bath. The bath is filled with continuously changing water of body temperature. Scans are performed from the chest wall to the nipple. Appropriate slices are determined by looking through a mirror system viewer. After both breasts have been studied, the patient receives a drip

tissues.

The General Electric CT/M is a dedicated scanner. The system includes a three-phase

of the Breast

459

Center,

Kansas City. Kansas 66103. Address

reprint

0361 -803X/78/0900-0459

requests

to c. H.

$00.00

CHANG

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460

Fig.

1.-CT

scans

mass (large arrows).

of

large

cancer

Tentacles

in

(small

fatty

breast

showing

ET AL.

irregular

are clearly visible. A, Preinjection scan. Initial CT number of lesion is 32. B, Postinjection scan. Lesion enhanced to 63. Contrast enhancement (CE) was 31 CT units (6.2% increase in density), indicating cancer.

Patient whose mammogram without demonstrable discrete

Fig.

2.

disease

crete mass not identified. becomes obvious. Contrast in density),

indicating

B, Postinjection enhancement

arrows)

showed

diffuse

mass. A, scan.

dense

Preinjection Cancer

fibrocystic

scan. Dismass (arrow)

was 28 CT units (5.6% increase

cancer. Fig.

tion CT numbers in two pixels. All malignant lesions showed an increase of at least 26 CT numbers after contrast medium enhancement (5.2% increase in density). The range of CT number for cancer is -9 to +35 (mean, 19) on initial scans and +21 to +85 (mean, 53) on postinjection

hancement increase

racy

scans.

(ACT

The

number)

in density).

contrast

of proven

Table

of CT compared

mean 1 shows

to film

medium

cancers the

C,

tions.

enhancement

accu-

and

ther-

All carcinomas but one were diagnosed by CT. This lesion was situated in the lower, most posterior aspect of the breast and could not technically be included in the scan field. Mammography missed seven of the 31 carcinomas, all in dense dysplastic breasts; thermographic examination correctly identified 18. Lesions

Film

fibroadenoma,

and

dence

lesions

of these

fat necrosis, focal duct unilateral gynecomastia,

Diffuse architecture

hancement

The

7

7

11

with

.

The

ducts,

to cancer. contrast

CT

17

CT

near

chest

as benign

number

in table

wall.

lesion.

and

but

mci-

2.

characterized

by

of

breast

the

normal

fibrotic reaction, number

for

However, medium

(77)

7 (58) 30t(97)

.

of breast

previously

is

.

Malignant

are percentages.

aspect

reported

obliteration

initial

cancer.

Lesions

are summarized

by dilated

contrast

indicating

13*

posterior

disease

and

or calcifica-

marked

Suspicious

in parentheses

abscess.

fibrocystic

density

and clustered

1

1

is similar

disease, papilloma,

These

of

in Malignant

Note. - Data on 31 lesions. Numbers . Normal. t Lesion was in lower and most therefore not included in scan. One tiny cancer was erroneously review of scan showed minute cancer.

ease

fibrocystic intraductal

Accuracy

No mass

area

in density).

mammography

masses.

included ectasia,

increase

Thermography CT/M

tiple

findings.

6.2%

scan. tiny

Benign

graphic,

examination

showing

TABLE Diagnostic

creased

clinical

clustered microcalcifications radiograph showing

B, Preinjection scan

(31 CT units,

There were 43 biopsy-proven benign lesions in 41 patients. Benign lesions were referred to surgery for biopsy because of suspicious mammographic, thermoand/or

with 5pecimen

A,

Postinjection

en-

mography.

Benign

carcinoma

mass. (arrow).

is 34 (6.8%

diagnostic

mammography

3.-Miniature

without associated microcalcifications

the is

less

and

inmul-

fibrocystic

dis-

degree

of en-

than

that

for

CT

OF

THE

BREAST

TABLE

Benign

Fibrocystic

disease

CT Numbers Initial

After

Contrast

-16

to

+40

(19)

-12

3

-17

to +25

(10)

-8

1 2 1

+9

-27 to +24 +25

(17)

+24

-17 to +38 +34

(31)

10 14-15 9

(15)

Fibroadenoma

6

-12

to +18

(8)

+15 to +50

(37)

23-36

(29)

Calcified

1 1

Focal duct Intraductal Gynecomastia

ectasia papilloma

fibroadenoma

Abscess Note-Numbers

in parentheses

to

No. Units of Enhancement

Medium

28

Fat necrosis

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2

Lesions

mcidence

Lesion

461

+47 +4

+70

(35)

4-30

to +32 (16)

(14)

3-

9 (6)

+50

3

+30

26

are mea n values.

TABLE Diagnostic

3

in Benign

Accuracy

Lesions

Benign

Film mammography Physical examination Note.

Data on 43 lesions.

-

Hence,

the

week Severe 4.-Diffuse

density

and obliteration

Postinjection

crease

benign scan.

in density),

fibrocystic

of normal

Contrast

indicating

disease

architecture.

enhancement

benign

showing

A, was

diffuse

Preinjection

18 CT

units

(3.6%

B, in-

lesion.

study

to the

Terminal

and

precancerous

is a definite tration

relation

in mammary

between tissue

increased and

high

iodine progesterone

concenlevel.

4

.

not

be

performed

from

with

severe

has

lesion

by

terminal

been

many

duct

considered

epithelial a possible

knowledgeable

investiga-

of in situ hyperplasia

carcihas

been reported [6, 12]. CT has demonstrated and has proven 24 such areas of cellular abnormality of these

(mean,

44

years).

family

history

one

patient

comitant

had

patients had All patients

ease.

solely

numbers

has ous

other

on the

showed

contrast

to

the capability lesions from Receiver

Sensitivity, estimators

to

patient increased The

areas

these

of

specificity, of lesion

enhancement

and

characteristi-

high

contrast the

in the the

accuracy since

enpathol-

specimen.

CT/M

potential disease.

Characteristic

detectability,

per-

from

that

of differentiating benign fibrocystic Operating

ex-

were

group ranged by 24-42 CT

scan

lesions

indicate

dis-

physical

Biopsies

cooperation

find

seem

conThree

fibrocystic

rrtedium

in density).

tiny

had

breast.

CT findings.

33) after

Extraordinary data

of the in this 21) and

multiple

the

and

negative.

basis

a positive brother of

patients

of

biopsy in 19

37 to 69 years

mastectomy. with diffuse

number (mean,

is required initial

Two

parts

otherwise

increase

hancement.

from

thermography,

CT +31

(mean,

(4.8%-8.4%

Our

cancer.

in

were

The initial from -17 to

ogist

breast

Mammography,

formed

ranged

had a previous had breasts

aminations

cally

patients

Of the 19 patients, 12 had of breast cancer; the father and

cancers

1

of menstruation.

atypia

patients. The age

.

a re percentages.

tors [3-11]. Subsequent development noma in these areas of abnormal ductal

malignant lesions (fig. 4). Fat necrosis can mimic a malignant lesion on the mammogram, but the CT study reveals minimal contrast medium enhancement (mean, 6 CT numbers). Noncalcified fibroadenomas, especially younger lesions, may display an increase of 25 CT numbers or more after contrast media enhancement. However, their initial CT reading is lower than cancer, usually less than 10 CT numbers. Additionally, fibroadenomas appear as well defined, smooth, homogenous oval masses. Calcified fibroadenomas show a high initial CT number but display only minimal contrast medium enhancement (3 CT numbers). There was a single case of subacute abscess in this series. Even though this lesion showed a contrast medium enhancement of 26 CT numbers, this was less than would have been expected for a malignant lesion of this size. It also revealed a low initial CT number of 4. The margin of abscess was poorly defined. Table 3 compares the diagnostic accuracy of CT for benign lesions with that of film mammography and physical examination. There were four false positive cases in younger patients with markedly fibrocystic breasts (mean age, 42 years). Our clinical observations and our initial animal study with rats suggest that there

.

1 .

Hyperplasia

disease

hyperplasia

.

in parentheses

should

end

Duct

Fibrocystic

increased scan.

CT

before

Numbers

Mal ignant

21 19

39(91)

CT/M

Fig.

Suspicious

21 (49) 24 (56)

system

precancer-

Analysis are these

not

definitive factors

are

462

CHANG

ET

AU.

1ll

I

99

1.0

>-

I-. -J

90

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-J

70

0 0.

0

0.25

w

::

!

a:

(0

I-

I-

0.0 0.0

0.25 FALSE

Fig.

5.-Receiver

0.5 POSITIVE

operating

0.75

1.0

PROBABILITY

characteristic

curve

10

I

for

CT/M using contrast medium enhancement (ACT number). I = cancer plus severe terminal duct hyperplasia vs. benign lesions. II = cancer vs. benign fibrocystic disease. Ill = cancer vs. severe terminal duct hyperplasia. IV = cancer plus severe terminal duct hyperplasia vs. benign

disease.

Ill

fibrocystic

cancer

plus

disease

plus

other

benign

lesions

(less

Fig. probability

6.-Receiver coordinates.

hyperplasia

fibroad-

enoma).

dependent on the decision criteria of the observer. Decision criteria reflect the bias of the observer toward one diagnosis or another, as well as such factors as the probability of occurrence of the disease in a particular patient population. Observer bias may be separated from the inherent ability to detect lesions by a mathematical technique known as receiver operating characteristic (ROC) analysis. This technique is well established in medical imaging [13-15] and affords an objective evaluation of bias and detectability for any diagnostic imaging test. The ROC curve is a plot of the false positive percentage versus the true positive percentage for a decision task with a variable decision criterion. For the CT study, ROC curves were plotted for several different decision criteria using the maximum contrast medium enhancement (LCT number) to assign a scan to malignant or benign categories. When cancer and severe terminal duct hyperplasia were grouped together in a single category, curve I resulted (fig. 5). When only cancer and benign fibrocystic disease were considered (all other diseases being ignored), curve II resulted. Curve III describes the process of differentiating between cancer and severe terminal duct hyperplasia. Maximum accuracy for curve I was found to be 84%, with a sensitivity of 98% and a specificity of 70%. Histograms of CT values for all four diagnostic categories were examined. They showed that the categories used for curve I, the basic curve for CT, were distributed nearly normally, with a slight skew toward low values. Therefore, an ROC curve plotted in normal-normal probability coordinates traced a straight line with slope equal to the variance ratio. This corresponds to a situation in

30

FALSE

cystic

which with

cancer severe

disease

which

vs. severe terminal

other

our

analysis

more

When

data

of

bias.

Figure

quite

well.

This

was

IV

benign

=

fibro-

fibroadenoma).

the intercept of detectability

6 shows

will

removed distribution less skewed,

direction of greater was again found

traced

of the

a straight

other

the

make

future

from

ROC

the

data

CT

is made

set

of

of CT numbers and ROC curve

separability at an extreme

line

ROC

(curve point

IV). on

at 98% and specificusing normal-normal

whose

curves.

information used other processes

on maximum

slope

This

was

equal

suggested

that

to differentiate fibroadebefore the decision based

might

offer

gain in performance. This is being at present. It must be emphasized that with

sensitivity

duct

fibrocystic

and documents the with unequal variances

the curve, with sensitivity remaining ity improving to 87%. The ROC plot

patients, excellent that the

vs.

(less

normal

hyperplasia.

is an estimate

categories, the lesions became

numerical noma from

benign

of the ROC curve,

fibroadenoma

coordinates

in

terminal

tractable.

I shifted in the Best accuracy

to that

vs.

duct

lesions

diagonal,

99

curve

severe

hyperplasia

to these coordinates normal ROC curve

described

diagnostic for benign

duct

benign

is independent

curves plotted fact that the

90

characteristic

parameter

negative

70 PROBABILITY

cancer plus lesions. II = cancer

terminal

plus

a single the

operating I =

vs. benign =

50

POSITIVE

some

actively

significant investigated

a sample

of

only

98

the AOC curves are only approximate, but the fit of curve I to the measured data suggests ROC function is a good description of potential and

specificity

of the

CT study.

Discussion Higher

iodine

and

iodide

concentration

in the

normal and diseased breasts in humans and well documented [16-18]. Increased radioiodine in surgical specimens from human breasts

of carcinoma has also been

tissue

of

animals is uptake

and fibroadenomas reported [16].

Our

CT

OF

THE

BREAST

463

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MTF

Fig.

7.-Contrast

mammary

medium

enhancement

(ACT

number)

in various

lesions.

2

I

Fig.

9.-CT/M

3

SPATIAL

FREQUENCY

modulation

transfer

(cm”) function.

cc Li 01

D

z

CT/M

CONTRAST

LINEARITY U

5.0 IODINE

Fig. tration

8.-Relationship

between

CT number

and

iodine

concen-

in water.

results showing ious mammary (fig.

10.0 I mq /mI)

CONCENTRATION

contrast medium enhancement lesions support these previous

in varfindings

7).

S

Marked contrast medium enhancement, over 25 CT numbers (5% increase in density), was noted in malignant lesions, severe terminal duct epithelial hyperplasia (possible precancerous lesions), fibroadenoma, and abscess. However, only minimal (less than 10 CT numbers) contrast medium enhancement was demonstrated in the predominantly fibrotic and cystic lesions. This suggests that

increased

only

be

contrast

due

metabolic

to

status

medium

increased of

enhancement

vascularity,

epithelial

cell.

but Marked

concentration

of

for

serum

delivery

iodine.

of

opaque

may

not

to

the

also

hyperplasia,

especially with atypia and malignant changes, induce higher iodine concentration. intravenous infusion of 300 ml of contrast over a 10 mm period results in a prolonged method

Fig.

It seems

to

media

for

seems

10.-Logarithmic

showing =

enhanced

without

breast.

CT

the

of

breast

C

cancer

(black

arrows)

with contrast

=

medium;

medium.

Maximum

found

contrast

to be linear

Beyond begins requires tion. For

medium

enhancement

best

strand

the

effect

smaller

in CT

sponding tion

up to a CT number

this point, the CT number to level off. An enhancement an increase of 0.4 mg/mI lesions

increase

be

contrast

of

(white arrow).

images

is

achieved after 300 ml rather than 100 or 200 ml. The relation between CT number and iodine concentration in water, investigated by using a phantom, was

to

medium maximum

histograms CT

than

number

increase

transfer

copper

uptake

be

of

one

seen

is higher.

obtained

by

wire,

allows

in tissues

80 (fig.

8).

less rapidly and of 5 CT numbers in iodine concentra-

volume still

in absorption

function,

of 30 gauge

of iodine

the may

of about

rises

smaller

pixel,

if the

The

imaging calculation

than

an

corre-

modulaa

single of the

the spatial

CHANG

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464

resolution provided by the matrix (fig. 9). For a very small lesion which takes up iodine very strongly, the CT number may show a statistically significant increase in only one or two pixels. Thus the numerical data as well as the image are important in accurate diagnosis. The correlation of numerical changes in CT number by contrast medium enhancement with clinical condition strongly suggests that significant diagnostic information is contained in the values of the CT numbers. Further image processing should be useful to extract this quantitative information which is not appreciated on the displayed or hard-copy black and white image. A color representation of the data enables an observer to better appreciate minor differences in a large dynamic range of CT numbers and to better discern differences in CT values at extremes of the dynamic range. The logarithmic histogram distribution (the logarithm of the frequency of occurrence of CT number versus CT number) clearly shows the increase with contrast medium in the number of pixels having high CT number (fig. 10).

ET AU. likeness 5.

breast:

2. Gisvold of

a preliminary

JJ, Karsell

computerized

MM,

Association lesions

1 24 : 827-829,

EC: Clinical

1977

evaluation Mayo

mammography.

Clin

1977

Barclay of

with

Radiology

tomographic

Proc 52:181-185,

3. Black

report.

PA, McCullough

atypical subsequent

TH, Cutler

SJ, Hankey

characteristics risk

of

of breast

BJ, Asire benign cancer.

29:339-343, 1972 4. Cheatle GU: Desquamative and dysgenetic epithelial plasia in breast: their situation and characteristic,

AJ:

breast

Cancer

hypertheir

induced

by tar. Br J Surg

13:509-532,

EK:

Carcinoma Med

in mammary

J 40 : 57-82,

lobule

and

its

origin.

1933

6. Foote FW, Stewart FW: Comparative studies of cancerous versus noncancerous breasts. Ann Surg 121 :6-53, 1945 7. Humphrey U, Swerdlow M: Relationship of benign breast disease to carcinoma of the breast. Surgery 52 :841 -846, 1962 8.

Kern

WH,

ciated

Brooks

with

AN:

breast

24:668-675,

Atypical

cancer

epithelial

and

fibrocystic

hyperplasia

asso-

disease.

Cancer

1969

9. Muir A: The evolution of carcinoma of the mamma. J Pathol Bacteriol 52 : 1 55-1 72, 1941 10. Ryan JA, Coady CJ: Ductal proliferation in breast cancer. CanJSurg 5:12-19, 1952 11 . Willings SA, Jensen HM: An atlas of subgross pathology of the human cerous

breast

lesions.

12. Moskowitz with

14.

with J NatI

special Cancer

M, Wirman

subsequent

2:34-35,

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