changes in pulmonary arterial perfusion due to intrathoracic ... - AJR

VOL.

No.

102,

3

CHANGES DUE

IN

PULMONARY TO INTRATHORACIC IRRADIATION PHILIP

By

M. JOHNSON, and

ARTERIAL PERFUSION NEOPLASIA AND OF THE LUNG*

M.D., HAROLD NEW

T

ROBERT H. SAGERMAN, W. JACOX, M.D.

YORK,

HE response of the tissues of the lung to cancericidal levels of ionizing radiaforms a complex pattern of differential

tion damage

and

repair.

The

capacity clinical

of the lung manifestations

injury.

Nevertheless,

therapists

have

by

caused

are

few

are

first

been

described

and

Merritt5

in

others.’

of

Cooper8 herent are

radiation.3

indicated studies.

limited

to,

not

pensatory offset

ionizing

have in such

Teates

the

tendency

changes in nonirradiated radiation-induced impairment

ventilation,

perfusion,

compliance

abnormality ther, it changes S

Presented

From This

but

also

have

no

serum with ported

or

al-

at the

investigation

Forty-ninth Annual Meeting of Radiology, Presbyterian was supported by U.S.P.H.S.

into

or

the

display

of

arteriolo5X

particles

tional

lung.

Using

JQ5

are of

by is

perfusion

per

the

of that

region.

in the

remains

period, allowing be mapped by

Although

scanning Society, Toronto, New York. and -(02).

The

pulmonary

for

to

volume

the

Ontario,

major

the

of frac-

number

micro-

reasonably

remains

of

intensity to

circulation emission

correlated pulmonary

unit

unit

proportional

lodged

a finite

Lopez_ that the between

measured by differential Since particle distrithe lung is flow-dependent,

of particles

of particles

a quantita-

analysis, found particles

shown by scanning the partition of

radioactivity,

ofthe American Radium Hospital, New York, Grant HE-o3-(oI)

lung

macroaggregates

scan his associates7 radioactive

marked

niques.

by

or

These

of

lungs with

number

lung,

637

scanning,

in the pulmonary of approximately

arterial blood bronchospirometry. bution within

lung

in the

studied

albumin molecules labelled usually iodine I’s’. They are passively transin the blood from the peripheral in-

the two closely

detectable

exchange

conveniently

clumps

of

pul-

it is a major

gas

particles.

site

the

on parameter

a safe, simple technique. lung scan is an analog

tive method Majano and partition of

com-

radiation

reasons:

perfusion

jection

inbut to of

two

is

radioactive

of respiratory function.2 Furmay be difficult to differentiate induced by radiation from those

the Department

it

composed

lung

of

a prospective intrathoracic neoThis

normal

the distribution capillary bed

veolocapillary diffusion so that the net detectable change is slight or nil. Thus the patient with roentgenographic evidence of radiation fibrosis may not only be clinically asymptomatic

for

and

scanning, The

and

for

undertook

for

pulmonary

these

the difficulties These include,

selected

lung,

changes are significant primarily to the extent that they compromise pulmonary function, often in a lung damaged by preexisting disease. Consequently, investigative interest has focused on measuring parameters of respiratory physiology before, and at intervals after, the administration

progression

perfusion.

prerequisite

having

However,

we

arterial

was

oc-

by Groover, Christie and more recently by

1923,

and

well-known,

or

of the effect of (a) and (b) ionizing

monary

an

persistence

Recently,

radio-

observed

by

study plasia

reserve

in whom severe respirahas followed sterilization tumor. changes induced in the

irradiation

Engelstadt4

not

YORK

disease.

in most cases prevents of radiation-induced there

who

casional patient tory insufficiency of an intrathoracic The morphologic lung

remarkable

NEW

M.D.,

constant their scanning clinical

the

detection

Canada,

May

29-31,

photon techuse

of

of pul1967.

Philip

638 monary

provided

arterial vestigation

as

perfusion of

as

such

This tients

Robert

to

the

the state

is

inform

valuable pulmonary

other

cidental

underwent

in

quent report of pulmonary

of

the

will present perfusion

subjected

to graded

a-

or

of irradiation

to

and

2

after an intravenous m acroaggregated

others

were

studied

injection albumin

of labelled

that

of

protein

seldom

0.5

mg.

blocked

administered Thyroidal

by

Lugol’s

beginning

panion

one

chest

the radiothe amount I’s’

solution

given

group,

was

roentgenographic fibrosis or pleural

were

and

the

findings therapy.

arterial

of

the

involving

5 of these

pa-

perfusion

tumor

was

commensurate the roentgenowas

found

in

i i

patients (Fig. I, ii and B). In patients ischemia was disproportionate, being more extensive than would be anticipated from the size of the tumor (Fig. 2, A and B). All 9 patients had carcinoma of the lung involving the hilus; the tumor was primary in 8 patients and metastatic in i. However, 3 additional patients with neoplastic involvement of the hilus failed to exhibit disI

TABLE

32

STATUS

PATIENTS

OF

PULMONARY

PRIOR

TO

PERFUSION

RADIATION

IN

THERAPY

Perfusion Type

of Neoplasm

Ischemia

Nor-

mal

ID

I>D

at intervals

of the

Conversely,

due

OR

in 32 Of this

neoplasms

In

scanupon

uniformity and for

noted.

densities thickening

size

PER-

LUNG

UM

al. Regional ischemia or less extensive than,

graphic

obtained

presence, intensity and extent of ischemia. When ischemia was found, the aeration and other roentgenographic features of the region

had

THE

A com-

scan. Follow_up when possible

evaluated for arterial perfusion

OF

or mediastinum. pulmonary

norm with,

Carcinoma

IO

were

ARTERIAL

NEOPLASM

patients

25

performed.

LTS

I summarizes prior to radiation

lung

was

All scans were begun immediately after injection of the tracer using a rectilinear scanner with a inch scintillation crystal, focussed collimator and pulse height analyzer. Scanning speeds ranged from I 20 to 200 cm. per minute.

ischemic

Table patients

not

PULMONARY

TO

for

for

beforehand.

ofradiotherapy

DUE

INITIAL

thereafter.

Scans pulmonary

FUSION

area.

also Densimetric

was

RESU IN

1968

affected

evaluated

in perfusion.

ALTERATIONS

exceeded of

roentgenogram

at the time of each ning was performed

completion

of

j.Lc of with

300

uptake day

be-

of treatment. lung scanning

I’s’. The specific activity pharmaceutical was such

days

of photoscans

MARCH,

ofthe

were

analysis

tients

METHOD

after a second course patient underwent

Jacox

ofperfusion

scans changes

the

therapy,

fore and Each

W.

MEDIASTIN

quantitative data changes in animals

AND

state

Harold

interval

A subse-

The patients studied included 20 with bronchogenic carcinoma, 7 with carcinoma of the breast, 4 with pulmonary metastases, 2 with intrathoracic lymphoma and i with carcinoma of the esophagus. Two patients were studied more than a year after radiation

to the

in-

hemithorax.6 MATERIAL

and

fibrosis. in 34 pa-

lung.

doses

Sagerman

Follow-up

the indiseases,

intentional

irradiation

H.

of pulmonary

neoplasia and radiation report presents our results

who

one

Johnson,

boembolism,

throm

tion

M.

to were

tumor, related

of

lung Hilar 2#{176} Carcinoma

(o)

(ii)

(0)

(3)

(8)#{176}

of

Total ischemia, patient (total= a). b Metastasis hilus.

8

(6)

lung

1=

9

(3)”

Lymphoma, intrathoracic Carcinoma of esophagus Carcinoma of breast

a

3

20

(9)

Peripheral

4

I

2

,b

I

I

0

0

I

i

o

o

6

6

o

o

12

II

9

32

D= roentgenographic in this group had simulated

O

density. previous

bronchogenic

radiation carcinoma

therapy involving

No.

ioa,

\OL.

Changes

3

in Pulmonary

Arterial

639

Perfusion

U I

.

. .

A Fio.

B

I .

the

parity

between

i schem

tumor

size

and

roentgenographic by the

extent

lung

of

FUSION

Table

ii

patients

IN

PULMONARY

ARTERIAL

ATTRIBUTABLE

TO

summarizes

the

whose

treatment

lungs of

were

neoplasia.

PER

received

in i8 dur-

findings irradiated In

i6

were least

these patients for the second

IRRADIATiON

Of after

.

performed once after were time.

studies

the

i6

u ndergoing In 2 other

of

treatment patients who

in the

past,

only

obtained.

were

patients

radiation

with

before treatment treatment; 2

therapy

radiation

follow_up

patients

I

extent of the tumor is commensurate (B). Patient AV, a 7 year old male.

scan

studies and at

i a.

ALTERATIONS

ing

(A) The as shown

Left Superior Sulcus Tumor. ischemia it has produced

:

#{149}

‘.‘“

I

.

.

studied

therapy,

before

there

was

and no

de-

I

11G.

2.

with

veals

Bronchogenic obstructive

total

ischemia

Carcinoma Arising features. However,

of the left lung.

in Left aeration

Hi/us. of the

See also Figure

(A) Chest roentgenogram lung elsewhere appears ,

patient

OS.

discloses normal.

(B)

a large hilar mass The lung scan re-

Philip

640

M.

Johnson,

Robert

H.

Sagerman

IN

i8

PATIENTS

Harold

W.

AFTER

RADIATION

Tumor

Dose

Days

z0 Carcinoma

Change from Initial and Roentgenogram

Follow-

(rads)

A.

MARCH,

1968

THERAPY

Treatment

Case

Jacox

II

TABLE

RESULTS

and

up

at

Scan

of Lung

OS

‘4

3,000

BP

4,000

19

WP

4,400

35

Al

4,500

30

3O.

Restored

8mo.

shrinkage No change; normal; 2,500r days given 15 months

3 mo. 7, 12 mo.

perfusion;

Increased

ischemia;

Increased

ischemia

treated

in

tumor in

12

earlier

fibrosis and

past

fibrosis;

(dose

un-

known)

RC

4,900

MM

5,000

26 35

I, 7, 2,5mo.

AW

5,000

43

o,8mo.

mo.

22

Increased

None;

ischemia and

Ischemia

months; changed 1*

2,400

NS 2#{176} Carcinoma WS

B.

I

17

fibrosis

at

emphysema

8

un-

II

6

200

,

fibrosis

ischemia;

total

i.mo.

No

change;

normal

of Lung 1,500

No

omo.

12

change;

irregular

perfusion

bilaterally C.

Carcinoma MS

of Esophagus 38

5,400

D. Carcinoma

No

mo.

I

change; lower left

slight

ischemia

of

lung

of Breast

LH GH

3

,

200

25

100

36

4,

No change;

mo. imo.

II

No

normal

change

except

?

silent

embolus SM

4,400

31

0,

9,

22 mo.

Transient

ischemia

and

clouding

Of apex

RR RK

4,500

30

I.5m0.

4,500

32

6mo.

JH

5

34

I

,

200

,

No change; Ischemia fibrosis

5 mo.

normal ofapex,

Progressive

Post-Treatment

Study

Unknown

54

Ischemia

yr.

of

2,200r

8yr.

20

reticulum

tectable

cell

sarcoma

of lung

interval

arterial

perfusion

and

change in

8.

pulmonary of

these

pa-

tients were treated with intent to cure. A de novo appearance of ischemia (Fig. 3, AD; and 4, A-D) or increase in pre-existing ischemia was observed in 7 patients. In i patient pulmonary perfusion showed significant

net

improvement

I

fibrosis

(carcinoma

and

kin’s

disease)

fibrosis

(Hodg-

yr.

thorax.

in Seven

45

r

4,200

and

breast)

Ischemia

SB

I =

of apex

Only

LB

*

slight

and pleural

ischemia

thickening E.

marked;

following

treat-

ment (Fig. 5, A and B). Evidence of ischemia was found in the patients treated previously (Fig. 6, A and B). Roentgenographic changes compatible with “radiation pneumonitis,” radiation fibrosis or pleural thickening were observed in

all

veloped

9

patients

or

increased

manifesting

ischemia.

newly

de-

These

in-

VOL.

No.

102,

Changes

3

of

cluded the

4 patients lung, I with

and

with

tion

of the

treatment with

given

the

with primary intrathoracic

carcinoma

received

with intent

postirradiation

pleura

did

marked (Fig.

3,

in Pulmonary

exceed,

than,

the

carcinoma lymphoma breast.

All

supervoltage to cure.

changes

not

and

Arterial

in

the

usually

degree

had

radiaHowever, lung

or

were of

Perfusion

arterial

flow.

physical monary

bulk artery,

ischemia

fusion DISCUSSION

results

of

this

study

tumors

tion fusion

scanning caused

cm.

of

of

diameter

are

However,

when

a lung

the

there

is

hilus

extensive

There hilar

a

impairment

ipsilateral tients in

two

neoplasm

by

equipment, lesions

usually tumor great of

lung, as this series.

are

that

probability

2

observed

in 9 of

mechanisms

by

flow

reduce

the

i 2

pa-

lateral

pulmonary

found within

a

ever, porting

of perfollowed \Vag-

that inflation a segmental

preservation

second

arterial

the

c, A

and

of “adequate” of the questioned

canine

lung. whether

a bronchus may the accompanying

not

artery.

The of

B;

by irradiation.

arising in through

pulmonary

in

mechanism

blood

at

pulmonary

in

data,

the

it

neovascular

in

the

bronchial

absence seems

of

shunting

pressure

via

arising by

the

is the

systemic

artery

channels

is supplied

may

tumor

with

carcinoma impair

of

which

effect of the on the pulnarrow the yes-

A and

associates9 catheter

flow, caused ischemia As a result they have

of

perfusion

may

air

per-

undetectable. is located

of the

bronchus,

under

the

is

tumor

restoration ischemic lung

a totally

ner and his of a balloon

produce pulmonary defici ts commensurate Due to the limited resolu-

present deficits

in

indicate

first

of the which

sel by compression or direct invasion. That reduction of tumor bulk may lead to improved perfusion is shown by the response

shrinkage

The

The

in patient OS (Fig. 2, and B), in whom partial

less

A-D).

peripheral lung arterial perfusion with their size.

641

into col-

tumor,

which

arteries.

How-

quantitative unlikely

supthat

such

.____&_

-

3. Carcinoma of Breast. (A) Preirradiation chest roentgenogram and (B) lung scan show slight apical pleural thickening and irregular perfusion of the apices respectively. The latter is a common finding. A tumor dose of 4,500 r in 4.5 weeks was then given to the right breast, supraclavicular and internal mammary regions with supervoltage equipment. (C) Six months after completion of treatment, the right apex shows increased pleural thickening and (D) there is markedly impaired perfusion by lung scanning. Pa-

FIG.

tient

RK,

a o

year

old female.

Philip

642

shunts It

are would

if there

is

a relationship

I. i

,.

Robert

neoplasms

utility

between surgical

and

perfusion of

The

Johnson,

H.

hemodynam i cally significant. appear desirable to determine

pulmonary ability

M.

of the

that

involve

lung

scan

altered resectthe

hilus.

in detecting

and

Harold

postirradiation in our results. in

whom

ated

region

what

lower

Guttmann.2

W.

Jacox

MARCH,

perfusion changes There were 9 of

ischemia

of the than This

occurred

in

1968

is evident i

8

the

patients irradi-

lung-an that may

incidence somereported by Bate and reflect

the

shorter

al ruen tgenogra1 and ( B) Iu ng scan prior to trcatten t and carcinoma from the right mid_lung. l)cspite emphysema, pulmonarv perfusion is nortial except in the upper third of the left lung. (C) l’ollow-up roentgenogram and (I)) scan wcre obtained 1fl()flthS after delivery of 5,000 r tumor dose to the tumor bed in 3 days using stipervultage equi)ment. Fibrosis and ischernia in the irradiated region are discrete, localized and commensurate. Patient AW, a 69 year old male. .

111flth

(n

1110111(1

after

resection

oJ Liiii,

of

Pe;iphe;a/. (. 1 ) I n bronchogenic

Sagerman

a I cm.

I ti

i

\OL.

No.

502,

Changes

3

in Pulmonary

Arterial

643

Perfusion

,.

5. Net Improvement of Peifusion Following Radiotherapy. (A) l’ollow-up roentgenogram and (B) scan in patient OS 3 months after delivery of3,ooo r tumor dose in 14 days using supervoltage equipment. Cornparison with initial examination (Fig. 2, 4 and B) shows marked reduction in tumor volume and return of perfusion to the lower half of the left lung. However, the appearance of ischernia in the upper half of the right lung suggests compromise of the right pulmonary artery by tumor extending across the mediastinum.

FIG.

The mean

patient

died shortly

period

sociated

general

follow_up

in our

roentgenographic

pleural

tion

of

thereafter.

or

was

pulmonary

present was

less

tion of perfusion. gional ischemia

series.

reaction

in these marked

Since cannot

As-

ferred

from

of

would

appear

evidence to

radia-

9 patients

but

than

altera-

the

the extent necessarily

of be

scan

in rein-

more

radiation

the

chest

roentgenogram,

reasonable widely

in

of

chest,

the

who

present

tion ciency

pneumonitis” after treatment.

it

to employ patients

clinical

lung

undergoing particularly

symptoms or

the

respiratory No other

irthose

of

“radia-

insuffimethod of

I

6. Ischemia and Radiation Fibrosis Following received tumor doses of 2,200 r in 20 days and tively. She had Hodgkin’s granuloma involving tinal fibrosis, chiefly left-sided. (B) Lung scan lung except in the lower third.

FIG.

Remote Irradiation. Patient SB, a 31 year old female, had r in 45 days, 8 and i years before examination respecthe mediastinum. (A) Roentgenogram reveals paramediasdiscloses moderately impaired perfusion of the entire left

4,200

Philip

6 comparable

tecting blood

ease

M.

with

ate

ischemia

to

treatment,

tumors

of the patients

hilus

also in

changes

in general

tions 4.

prior 4.

2

past.

attributable to in 7 of 16 pa-

Ischemia additional patients Roentgenographic injury

to lung

observed in these 9 patients were less marked than altera-

for

EMIRGIL,

uniquely

provided

lesions

of the

lung,

7. AppI. Physiol., R. and

ENGELSTADT,

quences term

Pearl Barbara

S.

Bruce

Varian, Cravitz.

1961,

iO,

RAD.

in

331-338.

B. Pulmonary lesions radium irradiation.

&

of

THERAPY,

after

J.

AM.

1940,

43,

of pulmonary report.

AM.

&

NUCLEAR

irradiation;

J.

second

ROENTGENOL.,

MED.,

5966,

long R&D.

96,

652-

619. 9.

gratefully of

car372-

GROOVER,

THERAPY

authors

69,

T. A., CHRISTIE, A. C., and MERRITT, E. A. Intrathoracic changes following roentgen treatment of breast carcinoma. AM. J. ROENTGENOL. & RAD. THERAPY, 1923, 10, 47I-476. 6. JOHNSON, P. M., SAGERMAN, R. H., and DOMBROWSKI, C. S. Quantitation of perfusion changes in irradiated mouse lung. To be published. 7. LOPEZ-MAJANO, V., CHERNICK, V., WAGNER, H. N., JR., and DUTFON, R. E. Comparison of radioisotope scanning and differential oxygen uptake of lungs. Radiology, 1964, 83, 697-698. 8. TEATES, D., and COOPER, G., JR. Some conse-

Philip

The

in lung

for

676-681. 5.

breast

M. Johnson, M.D. 622 West i68th Street New York, New York 10032

LungenFortsch. Nuk/ear-

C., and HEINEMANN, H. 0. Effects of chest on pulmonary function

ROENTGENOL.

mediastinum.

assistance

W. Experimen-

BUCHWALD,

D., and GUTTMANN, R. J. Changes and pleura following 2-mev therapy cinoma of breast. Radiology, 1957,

man.

with

1968

MARCH,

BATE,

irradiation

peripheral

by lung scanning commends greater use of this simple procedure in patients receiving and

Jacox

383. 3.

treatment.

in perfusion. The information

radiotherapy

V. R., and

BABLER,

roentgen

in

the

were

present

commensurate

of radiation-induced

pleura

but

was with

after

found

treated

in-

disproportion-

ischemia demonstrable

examined

was

2.

lesion.

was

tients

lung,

lung

was

Pulmonary

3.

W.

Entzundung und Fibrose des ger#{252}stes durch ionisierende Strahlen. a. d. Geb. d. Rontgenstrahlen u. d. medizin, 1966, io, 192206.

was patients

34

in

whereas

irradiation

Harold

RE FERENCES 1.

chest or breast. with neoplasms

of the

of that

of the

and

de-

pulmonary

perfusion

scanning

ischemia

size

or

lung I 2

the

for

Sagerman

CONCLUSIONS

arterial

neoplasms In 9 of

2.

the

AND

by

volving

in

H.

telle

Pulmonary

.

exists

changes

SUMMARY I

Robert

or simplicity

regional flow.

evaluated

Johnson,

acknowledge R.

Cecilia

Parker,

McRae

the M.D.,

and

10.

H. N., JR., LOPEZ-MAJANO, V., Tow, D. E., and LANGAN, J. K. Radioisotope scanning of lungs in early diagnosis of bronchogenic carcinoma. Lancet, 1965, I, 344. WARREN, S., and SPENCER, J. Radiation reaction in lung. AM. J. ROENTGENOL. & R&D. THERWAGNER,

APY,

1940,

43,

682-701.