1017

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Benjamin Felson Lecture

Emphysema: Definition, Imaging, and Quantification

William M. Thurlbeck1 and Nestor L. Muller2

This review will discuss imaging of the chest in patients with adopted by the World Health Organization [2] and a Ciba
pulmonary emphysema. Imaging findings must be related to the Guest Symposium [3]. The latter, however, included air
structure of the lung because emphysema is defined in anatomic space enlargement due to dilatation of the alveoli as well as
terms. Accordingly, we first review the anatomic definitions of
that due to destruction of their walls. Neither abnormal
emphysema and its consequences and then review the Imaging
enlargement nor destruction was defined more precisely.
findings, with emphasis on CT, in patients with this disease. The
more severe the morphologic emphysema, the more likely a
radiographic diagnosis will be made, no matter what criteria are
Destruction
used. The criterion of arterial deficiency is specific but insensi-
tive. The criteria used to assess overinflation are sensitive but not Any definition of destruction should be clear, practical,
specific. CT can be used for both qualitative and quantitative and sensitive. Several criteria have been suggested, includ-
assessment of emphysema. The presence and extent of emphy- ing fenestrae (the presence of abnormal holes), the destruc-
sema can be determined by visual assessment of areas of abnor- tive index, the loss of alveolar surface area, mean linear
mally low attenuation or by objective quantification based on the
intercept (Lm) and air space wall per unit volume (AWUV),
attenuation values. Statistically significant correlations between
and loss of alveolar attachments (loss of bronchiolar traction).
emphysema and CT findings have been shown in numerous
studies, but mild morphologic emphysema may be missed by CT,
Fenestrae.-In 1962, Boren [4] described discontinuities of
and occasionally CT scans give false-positive findings. In alveolar walls seen on thick sections of human lungs. These
patients with moderate to severe emphysema, the severity of consisted of holes normally present in alveolar walls of humans
emphysema is underestimated on the basis of CT findings by a and animals (the pores of Kohn) and abnormal holes referred to
factor of approximately three when compared directly with by Boren as fenestrae. He suggested that holes larger than
results of pathologic examination of lung specimens. In spite of 20 iim in diameter were abnormal and constituted evidence of
these limitations, CT is the best way of recognizing emphysema destruction, although why he chose this size is uncertain. Some
in living patients and probably has a significant role in recogniz- 30 years later, Nagai et al. [5], using scanning electron micros-
ing localized emphysema that is amenable to surgical treatment.
copy, quantified alveolar wall discontinuities in nonemphysema-
tous human lungs and found that 94% of holes were 10 j.tm or
less in diameter and that only 0.2% were more than 20 .tm in
Definitions
diameter. These observations substantiated Borens observa-
Emphysema is defined by the American Thoracic Society tion, but clearly standard error of the mean is too expensive and
[1] as follows: Emphysema is a condition of the lung charac- time consuming to be used for practical definition.
terized by abnormal, permanent enlargement of the air The destructive index.-The destructive index (DI) is a
spaces distal to the terminal bronchiole, accompanied by recent innovation [6] suggested as a criterion for alveolar wall
destruction of their walls. Similar definitions have been destruction. The DI is assessed using microscopic slides and

Received April 12, 1994; accepted after revision June 7, 1994.

Presented at the meeting of the Society of Thoracic Radiology, Scottsdale, AZ, March 1994.
This work was supported by the Medical Research Council of Canada, grant MT 7124, and the British Columbia Lung Association.
1Department of Pathology and Laboratory Medicine, Koemer Acute Care Pavilion, GF227, Vancouver Hospital, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5 Canada,
and Department of Pathology, British Columbias Childrens Hospital, Vancouver, BC, Canada. Address correspondence to W. M. Thurlbeck at Vancouver Hospital.
2Department of Radiology, University of British Columbia and Department of Radiology, Vancouver Hospital, 855 W. 12th Ave., Vancouver, BC V5Z 1M9 Canada.
AJR 1994;163:1017-1025 0361-803X/94/1 635-1 017 American Roentgen Ray Society
 1018 THURLBECK AND MULLER AJR:163, November 1994

has three components: breaks in alveolar walls (DIb), proba- obvious macroscopic emphysema have surface area values
bly corresponding to fenestrae; type II cell metaplasia of alve- within normal limits [14].
olar walls, often accompanied by some alveolar wall fibrosis Mean linear intercept and air space wall per unit volume.-
(Dlf); and classic emphysema (DIe), but the criteria for this Lm is the length of a test line placed over histologic slides of
were not described. Dlf was subsequently found to be irrele- the lung divided by the number of times the line crosses alveo-
vant [7]. The more obvious the macroscopic emphysema, or ar walls (not surfaces). It is an approximation of air space
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emphysema on specimens visualized using the unaided eye, (alveolar ducts, alveolar sacs, and alveoli) size; it is not the
the greaterthe component of DIe (Fig. 1). Thus the Dl proba- mean chord length of alveoli. Alveolar surface area (SA) is cal-
bly has little value when macroscopic emphysema is obvious culated from the formula 4V/Lm [11-15]. In this formula, V is
[8]. However, Saetta et al. [6] showed that DIb could be the volume of the lung in which
Lm is measured. Rearrange-
increased in smokers in whom air space enlargement was not ment ofthis formula shows that SAN (AWUV) is 4/Lm. Lm and
present (defined as an Lm < 350 iim). This observation still AWUV [16, 17] are thus reciprocals. Lm is older and often has
must be explored, because an increased DIb also may be been used as a measure of experimental emphysema. Lm will
present when there are abnormalities in elastic properties of increase if alveolar walls are destroyed, because their loss
the lung in smokers in whom macroscopic emphysema is results in fewer intercepts, or if there is overinflation, which
absent [8-10] or when there is an increased number and size causes a greater distance between intercepts.
of fenestrae in the intervening normal lung in emphysema- Neither Lm nor AWUV is a sensitive method for recogniz-
tous lungs [5]. The measurement is tedious. ing emphysema. Thirty-two percent of patients with emphy-
Loss of alveolar surface area.-The popularization by Wei- sema have normal (nonemphysematous) Lm values [14].
bel [11] and Dunnill [12, 13] of morphometric techniques in Only 26% of surgically resected lungs have abnormal AWUV
the lung made measurement of alveolar surface area practi- values [17], whereas up to 100% [18] of similar lungs have
cal. Loss of alveolar surface area intuitively seems a good macroscopic emphysema (typically 73-87% [9]), and in the
method of measuring destruction. However, even when cor- series in which AWUV was measured, this was 49% [17].
rected for stature-related variations in alveolar surface area, Thus, neither AWUV nor Lm can be regarded as the essen-
measurement of loss of alveolar surface area is an insensi- tial defining characteristic of emphysema [19].
tive test for emphysema; approximately 43% of lungs with Although AWUV and Lm are easy to measure, they require
random sampling of the lung inflated to a standard pressure;
corrections for shrinkage of lung tissue during fixation and
processing; and histologic examination of 100-120 micro-
scopic fields, which takes at least 1 hr.
60 Loss of alveolar attachments (loss of bronchiolar traction).-
Long considered to be a cause of airflow obstruction in
emphysema [20, 21], especially on expiration, loss of alveolar
50 attachments to bronchioles has recently been described as
representing an early stage of the destruction of lung paren-
chyma [22]. Bronchioles are thought to be tethered by their
40 attachment to alveolar walls, and associations have been
described between loss of alveolar wall attachments and the per-
C
C) centage of alveoli destroyed [23] or the presence and severity of
eC) 30 macroscopic emphysema [24, 25]. Although loss of attachments
a- is a cause of airflow obstruction and may be associated with tor-
Dl0
tuosity and irregularity [25] and ellipticality [26] of bronchioles, it
20 is an indirect way of recognizing destruction and emphysema.
The peripheral part ofthe acinus (the gas exchanging unit of the
lung distal to the terminal bronchiole) must be the area involved
10 because this is the part ofthe acinus that abuts bronchovascular
bundles as well as lobular septa and pleura. If loss of attach-
ments is an early stage of emphysema, distal acinar or parasep-
tal emphysema may be more important than is usually thought.
>0-25 30-60
Bronchiolar inflammation may extend to adjacent penbronchiolar
Emphysema score (Panel) alveolar walls and lead to their destruction [22].
The National Institutes of Health definition of destruction.-A
Fig. 1 .-Graph shows destructive index (Di) In patients without emphy- committee of the National Heart, Lung, and Blood Institute stated
sema (emphysema score, 0), with mild emphysema (emphysema score,> in 1985 that destruction in emphysema is defined as nonunifor-
0-25), and with moderate emphysema (emphysema score, 30-60). Dl con-
sists of breaks In alveolar walls (DIb), alveolar wall type ii cell metaplasia
mity in the pattern of air space enlargement so that the orderly
(Dl1), and classic microscopic emphysema (Dlv). When emphysema is ab- appearance of the acinus and its components is disturbed and
sent, total Di consists of breaks in alveolar wails only (Dib). When emphy- may be lost [27]. This means that the acinus looks odd; thus the
sema is mild, Di increases and is mostly breaks; when emphysema is
moderate, Di consists mostly of Die. When emphysema is more severe, Di definition of emphysema is subjective. The committee also
is aimost entirely DIe. Dif Is irrelevant. stated that destruction should not be accompanied by obvious
 AJR:163, November 1994 IMAGING FINDINGS IN EMPHYSEMA 1019

fibrosis. Their meaning is uncertain because fibrosis, assessed 100% specificity and 90% sensitivity between grades 0, I, and
histochemically and biochemically, is present in irregular, distal II compared with grades Ill and IV panacinar emphysema),
acinar, and centnlobular emphysema [28]. The qualification of different measurements of emphysema have been used both
obvious fibrosis was added to exclude the air space enlargement radiologically and pathologically to reach these conclusions.
that occurs in end stage (honeycomb) lung. In general, in all the studies of radiologic-pathologic correla-
We conclude that no good reason exists for altering the
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original definition of emphysema or macroscopic emphysema.

Macroscopic is an unfortunate, perhaps pejorative, term
because it implies a casual examination of the lung. Nothing
could be further from the truth; careful examination is required.
The minimum

standards

sema
description
requirements
of inflated lung; knowledge

much
are careful examination

to grade the emphysema

severe. Paper-mounted
better,
of centrilobular
and
emphysema
these
of a slice
of the normal appearance;
as mild, moderate,
and

led
by Leopold and
or
whole lung sections [29] show emphy-
to the original classic
0
Normal Non-smoker Smoker DI? (Dlbt)

Gough [30]. Sensitivity is increased further ifthe lung is exam-

med with a hand lens or dissecting microscope, and this
examination is facilitated if air space walls are rendered
opaque by barium sulphate [31] or Bouins fluid [32]. If many
lungs are to be examined for epidemiologic purposes [33], 7
then a simple pictorial grading system in which emphysema is
scored from 0 to 100 at intervals of 5 or 10 [34] will suffice.
I
This is usually referred to as the panel-grading system and
often has been used to correlate pathologic with CT findings.
Scores of 5-25 indicate mild emphysema; 30-50, moderate
emphysema; and equal to or greater than 60, severe emphy-
Lint AWUV4
sema. For more detailed purposes such as functional-ana- Emphysema Di? (Diet Dibt)
Lmt AWUV4
tomic correlation, gross examination should be supplemented
by histologic examination of random and specific blocks of tis-
Fig. 2.-Diagrams show various concepts of emphysema. A normal
sue and by more objective assessments such as Lm mea-
nonsmoker (upper left) shows an air space of normal size with three
surements. Not unexpectedly, the prevalence of emphysema breaks. A smoker (upper right) shows normal air space size with more
in random cases depends on the care with which the lung is breaks (Dib), Increasing destructive index (DI). Air space enlargement (low-
er left) shows increase in mean linear distance (Lm), reduction in air space
examined. For example, inclusion of minimal grades of wall per unit volume (AWUV), and normal number of breaks. In emphysema
emphysema increased the prevalence of emphysema from (lower right), air space shows obvious morphologic abnormalities (wavy
50% to 73% in one autopsy series [35], and another study lines), Increase In size of air spaces, and more breaks. Die = classic micro-
scopic emphysema.
found that emphysema was almost universally present even in
young subjects [36]. Another study has defined a category of
trace emphysema [37], and the inclusion or exclusion of this
category affects the prevalence of emphysema.

Air Space Enlargement

The definition of air space enlargement by the National
6 C
Heart, Lung, and Blood Institutes committee [27] is an a)
0
increase in air space size as compared with the air space of
0.
normal lungs. Data concerning Lm and AWUV measure- g4
ments are now sufficient for these measurements to be used is

in practice. The term macroscopic emphysema assumes 21

a)
that the air spaces are enlarged. The values available from >
0
nonemphysematous lungs can be used to assess whether a
particular lesion shows air space enlargement. 2 3 4
Emphysema severity group
The concepts arising from these definitions are shown in
Figure 2.
Fig. 3.-As emphysema increases in severity (emphysema severity
group), radiologic signs of emphysema increase in frequency. Overinf Ia-
tion (Inf), expressed as 0-4+, increases through the groups. Arterial defi-
Radiographic Diagnosis ciency (AD), a qualitative assessment, is present in mild emphysema, but
Radiologic-pathologic correlations have been reviewed in also is present in only minority of most other groups. Percentage of cases
with mixed increased markings (IM) and AD emphysema and percentage
detail [9, 36, 38]. Although considerable precision has been with iM emphysema also are shown. In emphysema severity groups 4 and
claimed in several studies (including one [39] that showed 5, 100% of cases show radlologic evidence of emphysema [40].
 1020 THURLBECK AND MULLER AJR:163, November 1994

tions, the severer the emphysema, the more likely the radio- Lohela et al. include the criteria of both Sutinen et al. [45] and
logic diagnosis will be made. Figure 3 shows many of the Nicklaus et al. [42]. Lohela et al. also showed a specificity of
problems. Overinflation is expressed quantitatively (on a 74% and a sensitivity of 61% for subjective opinions of the
scale of 0 to 4+) and increases progressively with increasing radiologic diagnosis of emphysema.
severity of emphysema [40]. Arterial deficiency and increased
markings were described as present or absent. Arterial def i-
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CT Diagnosis
ciency was recognized when segmental vessels tapered
more rapidly than normal as they proceeded distally and Studies have shown that CT findings correlate with the
when the peripheral markings were sparse. By contrast, presence and severity of morphologic emphysema better
increased markings were recognized when the peripheral than do results of pulmonary function tests [46, 47]. Our
pulmonary vascular markings were not only increased in size review of the diagnostic accuracy of CT is limited to studies
but were more numerous, particularly peripherally [40]. The that correlated CT findings with pathologic specimens. CT
presence of arterial deficiency had a low sensitivity but a high allows direct visualization of areas of lung destruction and is
specificity [41]. In addition, this sign is poorly reproducible superior to chest radiography in showing the presence,
between and within observers, especially by a nonradiologist extent, and severity of emphysema. On CT scans, emphy-
[42]. When increased markings are included, the diagnosis of sema is characterized by the presence of areas of abnor-
emphysema was made in 100% of patients with moderate mally low attenuation (Fig. 4).
and severe emphysema. Emphysema with increased mark- The first CT-pathologic correlation in emphysema was
ings was found especially in patients with cor pulmonale. The reported in 1984 by Hayhurst et al. [48], who compared the
classic appearance of emphysema (arterial deficiency and CT appearance of the lungs with resected lung specimens
overinflation) diminishes or disappears in patients with from six patients who had mild centrilobular emphysema and
chronic airflow obstruction who have heart failure [43]. Arte- from five patients without emphysema. They assessed the
rial deficiency in the upper zones of the lung indicates centri- frequency distribution of the attenuation values on CT scans
lobular emphysema; in the lower zones, arterial deficiency and showed that patients with emphysema had more pixels
indicates panacinar emphysema [41]. with attenuation values between -900 H and -1 000 H than
The meaning of the radiologic diagnosis of emphysema is did patients without emphysema (p < .001 Wilcoxon
, test).
also an issue. A radiologic diagnosis may indicate that the
chronic airflow obstruction in a given patient is due to emphy-
sema. For a given severity of emphysema, a radiologic diag-
nosis of emphysema is more likely to be made when
obstruction of airflow is symptomatic [41], even if the radiolo-
gist is unaware of the clinical features of the case. The radio-
logic diagnosis of emphysema is usually on-off-a patient
either has emphysema or does not. Morphologic emphy-
sema, conversely, recognizes various grades of the disease.
The radiologic diagnosis should be quantified in some way-
for example, as a mean of radiologic variables. For instance,
the data of Lohela et al. [44] can be analyzed more closely
and the mean number of radiologic signs calculated (Table 1).
The mean number of radiologic signs increases with the
severity of morphologic emphysema, and the assessments of

TABLE 1: Mean Number of Radiologic Signs of Emphysema

with Increasing Pathologic Emphysema

Emphysema Score (Panel-Grading Method)

0-5 10-20 30-50 60+

Criteria of Sutinen 0.85 1.79 2.19 2.50

et al. [45]
Criteria of Nicklaus 0.98 2.13 2.80 3.30
et al. [42}b
Note.-Adapted from data of Lohela et al. [44].
aCritena of Sutinen et al. include (1) blunting of costophrenic angle and/or
diaphragm at or below 11th rib posteriorly, (2) irregular lucencies, (3) increased Fig. 4.-59-year-old woman with centriiobular emphysema. High-reso-
retrostemal space, and (4) flattening or concavity of the diaphragm. lution T scan (1 .5-mm collimation, high-spatial-frequency algorIthm) of
bCritena of Nicklaus et al. include the four used by Sutinen et al. plus arterial left upper lobe of lung shows localized areas of low attenuation near cen-
deficiency. ter of secondary lobules.
 AJR:163, November 1994 IMAGING FINDINGS IN EMPHYSEMA 1021

In 1986, Foster et al. [49] reported findings in 25 patients compared findings on 10-mm- and 1.5-mm-collimation CT
who had CT while they were alive and who had lungs fixed scans with the pathologic findings in the corresponding
postmortem by inflation. The CT scans were obtained with 1- transverse slice of lung. The CT scans were assessed by two
cm collimation at 1-cm intervals through the chest. Three independent observers, and the diagnosis was based on the
radiologists independently assessed the CT scans for the presence of areas of low attenuation. Emphysema was
extent of nonperipheral areas of low attenuation, peripheral assessed on CT scans and pathologically by superimposing
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areas of low attenuation, pulmonary vascular pruning, and a grid with squares corresponding to 1 cm2 on the CT scan.
pulmonary vascular distortion. The CT criterion that best cor- The extent of emphysema was expressed by the percentage
related with the presence and severity of centrilobular of grid squares containing emphysema, and the severity was
emphysema was the presence of nonperipheral areas of low expressed by averaging the severity (0-4) in the grid
attenuation (r= .84 in the upper part ofthe lung and r= .78 in squares. In addition, the severity of emphysema was
the lower part of the lung). The criterion of nonperipheral assessed pathologically using the panel of standards [34].
areas of low attenuation allowed recognition of 13 of 15 Correlation between the CT assessment of emphysema and
patients with centrilobular emphysema and produced two of the pathologic panel score was high for the 10-mm-collimation
1 0 false-positive results. (r= .81 p < .001) and the 1 .5-mm-collimation
, (r= .85, p < .001)
Bergin et al. [50] assessed the accuracy of the CT diagno- scans. Lower correlations were found between the CT scans
sis of emphysema in 32 patients who had surgery. The CT and the pathologic grid scores (r = .70 for the 10-mm-collima-
scans were obtained with 10-mm collimation at 10-mm inter- tion scans, r= .72 for the 1 .5-mm-collimation scans, p < .001).
vals through the chest and were reviewed independently by The extent and severity of emphysema were consistently
two chest radiologists and a chest physician. The presence of underestimated on the basis of CT findings. Furthermore, in
areas of low attenuation and vascular disruption on CT scans one of five patients with no emphysema seen on pathologic
was used to assess emphysema. The extent of emphysema examination, the CT scan was interpreted by one of the
seen on CT scans was quantified as normal (0), less than observers as showing mild emphysema; in six of 33 patients
25% involvement of the lung parenchyma (1), between 25% with emphysema, the emphysema was missed on CT scans
and 50% involvement (2), between 50% and 75% involve- by both observers. The six patients with emphysema missed
ment (3), and greater than 75% involvement on all slices (4); on CT scans included four with mild centrilobular emphy-
the score was expressed as a percentage of maximum. The sema and two with mild to moderate panacinar emphysema.
observers quantified the extent of emphysema for the entire The authors concluded that CT consistently underestimated
lung and for the resected lobe. Severity of emphysema seen the extent of centriacinar and panacinar emphysema
in the pathologic specimens was assessed using a modifica- because most of the lesions less than 0.5 cm in diameter
tion of the panel-grading method [34]. The correlations were missed [32]. Thus, mild emphysema may be missed
between the CT scores for the total lung and the pathologic on CT scans (Fig. 5), and the severity of emphysema may be
emphysema scores were .81 and .88 for the two radiologists underestimated (Fig. 6).
and .63 for the chest physician (all p < .001). The correlations Kuwano et al. [18] determined the accuracy of CT scans
between the CT scores for the resected lobes and the patho- obtained with 1-mm collimation and with 5-mm collimation in
logic specimens were 0.71 for both the radiologists and .57 the assessment of emphysema in 42 patients whose lobes
for the chest physician. In all cases, the CT scores were lower were resected. The extent of emphysema was assessed both
than the corresponding pathologic scores. on CT scans and in the resected lobes using the panel of
Miller et al. [32] obtained preoperative CT scans in 38 standards. The diagnosis of emphysema on CT scans was
patients undergoing lobectomy or pneumonectomy. They based on the presence of areas of low attenuationand vascu-

Fig. 5.-61 -year-old man who underwent left

upper iobectomy for bronchogenic carcinoma.
A, CT scan (10-mm collimation) at level of
aortic arch shows only a few questionable 10-
callzed areas of low attenuation (arrows) con-
sistent with emphysema, which had not been
identified prospectively on CT scan.
B, Pathologic specimen cut in same transverse
plane at same level as CT scan shows numerous
localized areas of centriiobular emphysema
(arrows). Even In retrospect, most of these ar-
eas cannot be seen on CT scan.
 1022 THURLBECK AND MULLER AJR:163, November 1994

Fig. 6.-64-year-oid man who underwent left

upper lobectomy for bronchogenic carcinoma.
A, High-resolution CT scan (1-mm collimation,
high-spatial-frequency reconstruction algorithm)
shows localized areas of low attenuation
(arrows) consistent with centrilobular emphyse-
ma. Nodule represents bronchogenic carcinoma.
B, Pathologic specimen cut 1 cm above tumor
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in same transverse plane as CT scan shows ob-

vious moderately severe centriiobular emphyse-
ma. Although emphysema was seen on CT scan,
severity was underestimated.

ar disruption. The correlations between the CT emphysema recognize breaks in the alveolar wall (DIb) and were probably
scores and the pathologic specimens were .68 for the 1 -mm- referring to DIe.
collimation scans and .76 for the 5-mm-collimation scans. Gould et al. [1 9] compared the lowest fifth percentile of
The severity of emphysema found pathologically was consis- Hounsfield numbers with both the lowest AWUV value on five
tently underestimated on the 5-mm-collimation scans but not microscopic fields and the percentage of the lung involved by
on the 1 -mm-collimation scans. Significant interobserver and emphysema. They studied 28 patients and found correlations
intraobserver variations were noted, and their average score between the Hounsfield numbers and AWUV (r = -.77), and
was used. The authors concluded that high-resolution CT (1-mm r = .50 for the extent of emphysema. In their hands, diffusing
collimation) can help identify the presence of mild emphysema. capacity for carbon monoxide provided better correlations with
However, a major limitation of this study was that no patients AWUV and the extent of emphysema than did CT findings.
had either a CT or pathology score of less than 10. The Most studies correlating CT findings with results of patho-
authors attributed this to the fact that they examined five logic examination of resected specimens assess the accu-
slices with both CT and pathology studies and thus were racy of CT in the diagnosis of centrilobular emphysema.
likely to find minimal grades of emphysema. It seems unlikely Results can be assessed from two studies from different labo-
that this is the whole explanation, because their experience is ratories [32, 49] that together show a specificity of 83% and a
unique. More to the point, it is clear from the data that there is sensitivity of 80%. However, the patterns of abnormality seen
no correlation between pathology and CT scores of less than on CT scans differ for the various forms of emphysema [51].
20. Correlations from their data can be calculated, and these In centrilobular emphysema, the abnormalities are usually
show r2 values of .13 for 1-mm-collimation scans and .00 for most severe in the upper parts of the lung and include irregu-
5-mm-collimation scans. These findings explain the low corre- lar small round or confluent areas of low attenuation inter-
lations in all cases for both types of scans despite apparently spersed with normal lung (Fig. 4). The localized areas of low
good correlation between CT and pathologic findings. Thus, attenuation are located near the center of the secondary pul-
contrary to the claims of the authors, mild emphysema was monary lobule.
consistently missed on CT scans. The authors also reported Panacinar emphysema involves mainly the lower lung
a correlation between CT and the DI; they clearly could not zones and is characterized on CT scans by diffuse areas of

Fig. 7.-49-year-oid woman who underwent

left lung transplantation for severe panacinar em-
physema due to alpha 1-antiprotease deficiency.
A, CT scan of native right lung shows simplifi-
cation of lung parenchyma with diffuse areas of
low attenuation and paucity of vascular marldngs
compared with normal transplanted left lung.
B, Chest radiograph is shown for comparison
with CT scan.
 AJR:163, November 1994 IMAGING FINDINGS IN EMPHYSEMA 1023

low attenuation with little intervening normal lung (Fig. 7). In high-resolution CT, were able to identify even mild emphy-
severe panacinar emphysema, the simplification of lung sema when they scanned 20 postmortem lung specimens.
parenchyma leads to diffuse areas of low attenuation with a The correlation coefficient between the in vitro score and the
paucity of vascular markings that allow distinction between pathologic grade was .91 with a slope close to 1 This excel-
, .

panacinar emphysema and normal lung parenchyma. How- lent correlation is not surprising because conventional post-
ever, mild or moderately severe panacinar emphysema is mortem radiographs also show emphysema well [54].
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often impossible to distinguish from adjacent normal paren-

chyma on CT scans [32]. Spouge et al. [52] determined the
value of CT in assessing the presence of pathologically Objective Quantification of Emphysema by CT
proved panacinar emphysema. They studied five patients Although the visual assessment of emphysema correlates
without emphysema and 10 patients with panacinar emphy- well with the pathologic scores, the overall extent of emphy-
sema, four of whom had severe emphysema requiring lung sema is difficult to estimate visually because of the wide range
transplantation. Conventional 10-mm-collimation CT scans of volumes represented in different images. This difficulty can
were obtained in 14 patients and high-resolution CT (1.5-mm- be circumvented by highlighting areas of abnormally low
collimation high-spatial-frequency reconstruction algorithm) attenuation using a computer program. Hayhurst et al. [48]
in nine. Emphysema was assessed pathologically using the first showed that patients with emphysema had more pixels
panel-grading method. The correlation with pathology was with attenuation values between -900 H and -1000 H than did
r= .90 for conventional CT and r= .96 for high-resolution CT patients without emphysema (p < .01). The GE 9800 scanner
(p < .01 ). The extent of panacinar emphysema was consis- has a standard software program called density mask that
tently underestimated, although less so on high-resolution highlights voxels within any desired range. Muller et al. [55]
CT scans (slope, 0.67) than on conventional CT scans compared the density mask with the visual assessment of
(slope, 0.47). A radiologic diagnosis of emphysema was emphysema in 28 patients undergoing lung resection for
made in six of nine patients with emphysema using conven- tumor. The pathologic score was obtained using a modification
tional CT (sensitivity, 67%) and in five of seven patients with of the panel-grading system. Pathologically, seven patients
high-resolution CT (sensitivity, 71%). Thus, the sensitivity of had no emphysema, and 21 had emphysema scores ranging
the diagnosis of panacinar emphysema was slightly less from 5 to 100. In each patient, a single representative CT scan
than that found in centrilobular emphysema, but underesti- was compared with the corresponding pathologic specimen of
mation of extent was about the same. tissue. The authors assessed the accuracy of density masks,
Distal acinar emphysema is characterized by areas of low highlighting all voxels with attenuation values less than -920,
attenuation in the subpleural lung regions and adjacent to -910, and -900 H. Correlation between the three different
vessels and interlobular septa (Fig. 8). Because centrilobular density mask scores and the pathologic assessment of
and distal acinar emphysema produce localized areas of low emphysema was good (all r > .83, p < .001). The best correla-
attenuation, they are easier to recognize on CT scans than tions were observed by highlighting all voxels with attenuation
panacinar emphysema [32, 52]. equal to or less than -910 H. The correlation between the den-
As expected, the correlation of isolated lung specimen sity mask and the pathologic score of emphysema was 0.89.
findings on CT scans with pathologic findings is better than By comparison, the correlation between the mean of visual
that for CT scans obtained in vivo. Hruban et al. [53], using scores by two independent observers and the pathologic
score of emphysema was .90 (p < .001). When the density
mask at -910 H was used, three cases with emphysema
scores of 10 were missed, and emphysema was diagnosed in
V one normal lung. By comparison, two independent chest radi-
ologists on two separate occasions missed two cases of
emphysema with pathologic scores of 10. The first observer
missed one additional case and the second observer missed
four additional cases with pathologic scores ranging from 5 to
20. Each observer diagnosed mild emphysema (visual score
10) in one healthy subject.
The density mask allows objective quantification ofthe total
volume of lung showing emphysema on CT scans and the
percentage of lung involved with emphysema. Measurements
of attenuation on CT have several limitations, including scan-
ner type; calibration; kilovoltage; reconstruction algorithm;
volume averaging; patients size; and the location, environ-
ment, and size of the area being assessed. In spite of these
limitations, because the visual assessment is based on areas
Fig. 8.-SO-year-old man with distal acinar emphysema. High-resolu- of low attenuation, once this attenuation is determined, these
tion CT scan shows localized areas of low attenuation predominantly in
subpleural lung regions. Note presence of distal aclnar emphysema along
areas can be highlighted and emphysematous changes can
azygos fissure. be quantified objectively. Recently, computer programs have
 1024 THURLBECK AND MULLER AJR:163, November 1994

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