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State of the Art
A Structural and Functional Assessment of the Lung via
Multidetector-Row Computed Tomography
Phenotyping Chronic Obstructive Pulmonary Disease
Eric A. Hoffman, Brett A. Simon, and Geoffrey McLennan
Departments of Radiology, Medicine, and Biomedical Engineering, University of Iowa, Iowa City, Iowa; and Department of Anesthesiology
and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland
With advances in multidetector-row computed tomography (MDCT),
it is now possible to image the lung in 10 s or less and accurately
extract the lungs, lobes, and airway tree to the fifth- through sev-
enth-generation bronchi and to regionally characterize lung den-
sity, texture, ventilation, and perfusion. These methods are now
being used to phenotype the lung in health and disease and to
gain insights into the etiology of pathologic processes. This article
outlines the application of these methodologies with specific em-
phasis on chronic obstructive pulmonary disease. We demonstrate
the use of our methods for assessing regional ventilation and perfu-
sion and demonstrate early data that show, in a sheep model, a
regionally intact hypoxic pulmonary vasoconstrictor (HPV) re-
sponse with an apparent inhibition of HPV regionally in the pres-
ence of inflammation. We present the hypothesis that, in subjects
with pulmonary emphysema, one major contributing factor leading
to parenchymal destruction is the lack of a regional blunting of
HPV when the regional hypoxia is related to regional inflammatory
events (bronchiolitis or alveolar flooding). If maintaining adequate
blood flow to inflamed lung regions is critical to the nondestructive
resolution of inflammatory events, the pathologic condition
whereby HPV is sustained in regions of inflammation would likely
have its greatest effect in the lung apices where blood flow is already
reduced in the upright body posture.
Keywords: airways; computed tomography; emphysema; inflammation;
functional imaging
The goal of this article reflects that of the mandate for guest speak-
ers at the Aspen Lung Conference: to provide a state-of-the-art
overview and to introduce a new and possibly controversial hypoth-
esis. The focus of the conference was chronic obstructive pulmonary
disease (COPD), and the goal of this article is to introduce the
breadth of tools now available through advanced multidetector-
rowcomputedtomography(MDCT)thatcanbeusedtogainnew
insights into lung pathologies associated with COPD.
The pathologic events leading to emphysema are insidious
and include structural and physiologic alterations that are char-
acterized by inflammatory processes within the peripheral pul-
monary parenchyma, thickening of arteriolar walls, and paren-
chymal destruction. A growing body of literature documents
that these changes are likely to be associated with alterations
in blood flow dynamics at a regional, microvascular level, and
(Received in original form March 20, 2006; accepted in final form May 30, 2006 )
Supported in part by NIH grants R01-HL-64368-01 and R01-HL-60158-04.
Correspondence and requests for reprints should be addressed to Eric A. Hoffman,
Ph.D., Department of Radiology, University of Iowa, 200 Hawkins Drive, CC701
GH, Iowa City, IA 52242. E-mail: eric-hoffman@uiowa.edu
Proc Am Thorac Soc Vol 3. pp 519–534, 2006
DOI: 10.1513/pats.200603-086MS
Internet address: www.atsjournals.org
thus may serve as a beacon pointing toward the onset of early
emphysema. Furthermore, recent findings in our laboratory have
led us to believe that regional alterations in blood flow parame-
ters may not only serve as an early marker for inflammatory
processes but may also be a major etiologic component of the
pathologic process, leading to emphysema in a subset of the
smoking population (not all smokers have emphysema). We
present preliminary evidence that leads us to a new hypothesis
relating emphysema to an inherent loss of the ability to blunt
regional hypoxic pulmonary vasoconstriction (HPV) when the
regional hypoxia is derived from inflammatory events.
MDCT provides the ability to image the lung with a theoreti-
cal in vivo resolution of approximately 0.5 mm. The whole lung
can be imaged at this resolution in approximately 10 seconds,
which is well within a single breath-hold. Scanner rotation speeds
are on the order of 300 milliseconds per revolution, and recently
there has been the introduction of dual-source CT (Somatom
Definition; Siemens Medical Systems, Erlangen, Germany)
whereby two X-ray guns are placed on the gantry, serving to
double the temporal resolution of the scanner system, and thus
opening up the possibility of dual energy scanning, which allows
for sensitive discrimination between tissue types and contrast
agents, such as iodine and xenon. Dynamic imaging via CT allows
for regional quantitative assessment of parenchymal perfusion
and ventilation. With advances in image-processing methods,
the lung, lobes, bronchial tree, and vascular trees can be ex-
tracted and quantitatively assessed. Density and texture mea-
sures of the lung parenchyma via MDCT imaging are now pro-
viding tools for establishing regional presence and distribution
of lung pathology, which, when coupled with regional measures
of function, may serve as important phenotypes within a popula-
tion, serving as the starting point for the quest to define associ-
ated genotypes.
From the unique opportunity to link structure and function
via MDCT, we have found evidence that, on a very regional
basis, the lung is able to shut off or blunt HPV in the presence
of local inflammation. This article puts forth the following series
of interrelated hypotheses as follows:
• Smoking is associated with regional microinflammatory
events, which in turn cause regional hypoxia.
• Smokers without the ability to shut off regional HPV in the
presence of inflammation are susceptible to emphysema.
• If perfusion to the inflamed hypoxic regions is important
to the evolution of emphysema, then the HPV in regions
of inflammation will be compounded with reduced flow to
the apical lung due to gravitational effects.
Inflammatory parenchymal lung diseases are common and are
significant causes of disability and premature death. These diseases
520 PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY VOL 3 2006
are the result of subacute/chronic or chronic inflammatory pro-
cesses, and are linked to cigarette smoking, either as a cause or
as a modifying agent. Current methods for the assessment of these
disorders include measures of lung function, radiologic techniques
such as CT scanning (1), radionuclear-based ventilation/perfu-
sion lung scans (2–5), use of hyperpolarized 3-He gas (2, 6–8)
in conjunction with magnetic resonance imaging (MRI), or direct
assessment of lung pathology. Much of the focus on mechanisms
of improvement has focused on lung mechanics (9–11). Remy-
Jardin and colleagues (1) have provided a unique observation
via CT demonstrating that longitudinal changes leading to an
emphysema-like lung begin with micronodular and ground-glass
appearances in the lung field correlating to bronchiolitis and
parenchymal inflammation. However, although many individu-
als with these regional inflammatory processes progressed to-
ward an increased emphysema burden (in the inflamed regions),
not all subjects with inflammation evolved toward emphysema,
suggesting that there may be important differences in the ways
individuals react to regional inflammatory processes in the lung.
Although respiratory textbooks teach that it is teleologically
advantageous to shunt blood away from regions of poor ventila-
tion, when the poor ventilation is caused by inflammatory
processes (i.e., micronodules and ground glass found by Remy-
Jardin and colleagues [1]), the best hope for resolution of the
inflammation is to maintain an adequate blood supply to that
area. In fact, three of the four components of the classic descrip-
tion of the inflammatory response—calor (warmth), rubor (red-
ness), and tumor (swelling)—reflect increased local blood flow
(dolor, or pain, being the fourth). Schuster and colleagues and
Gust and colleagues, in two key papers using positron emission
tomography (PET) imaging to study mechanisms of hypoxemia
in acute lung injury (12, 13), showed that HPV is shut off when
even a very small dose of endotoxin has been delivered to the
lung. Recent work in our laboratory using MDCT, and outlined
below, provides further evidence of local HPV inhibition in the
presence of regional inflammation concomitant with other areas
of the lung maintaining a healthy HPV response.
Recent conclusions from the National Emphysema Treatment
Trial (NETT) (14) show that the subgroup most likely to respond
to surgery with improvement in exercise and quality of life are
subjects with low exercise capabilities and apical predominance
of the disease (15). If a key feature of the disease is the shunting
of perfusion away from inflamed regions of lung, thus reducing
blood flow to regions needing perfusion to resolve the inflamma-
tion, then the normally reduced perfusion to the lung apices in
upright humans likely contributes significantly to susceptibility of
the parenchyma to adverse responses to inflammatory processes
in the confounding presence of unconstrained HPV.
Measures based on airflow or other measures of global lung
function have reached their limits in their ability to provide new
insights into the etiology of the disease, or even in leading us
to an understanding of how lung volume reduction, in late stages
of the disease, provides patient improvements. A number of
articles have been written in which attempts are made to explain
improvements of physiologic status post-LVRS (9, 16) on the
basis of lung mechanics, and we find it difficult to understand how
these relate to the observations from the NETT (15) showing that
subjects with apical but not basal prevalence of disease receive
the greatest benefit from surgery. However, if regional pulmo-
nary perfusion is again brought into consideration, it makes
sense that, if one removes apical lung that is not contributing
well to gas exchange and blood is shunted to less diseased basal
lung, gas exchange will be improved. Furthermore, by removing
a diseased portion of the basal lung when the disease is predomi-
nantly basal, then it is likely that blood will be preferentially
shunted to the contralateral basal lung. Using scintigraphy to
assess regional V
˙
/Q
˙
, Moonen and colleagues (2) have recently
concluded that an important mechanism for improvement in
functional status post-LVRS relates to the reduction of regional
shunt (i.e., blood flow may be directed toward regions of im-
proved ventilation whereas regions receiving blood flow but that
have poor ventilation are removed).
A recent international consensus statement on the diagnosis
and therapy of COPD—the Global Strategy for the Diagnosis,
Management, and Prevention of Chronic Obstructive Lung Dis-
ease (GOLD [Global Initiative for Chronic Obstructive Lung
Disease])—has established diagnostic criteria that currently
do not include CT findings (17). This is not surprising given that
the consensus statement has been developed in part for the
World Health Organization. It is notable that the summary
makes the observation that different inflammatory events occur
“in various parts of the lung,” a reference to the marked hetero-
geneity of the disease which cannot be defined without imaging.
Of interest also are the future recommended research directions,
which include identifying better defining characteristics of COPD,
developing other measures to assess and monitor COPD, and
recognizing the increasing need to identify earlier cases of the
disease, all potential outcomes of improvements to quantitative
lung imaging.
High-resolution volumetric MDCT with parenchymal structural
analysis, bolus contrast–based measurement of pulmonary perfu-
sion parameters, and xenon-enhanced measurement of regional
ventilation can provide objective and reproducible measures to
phenotypically describe the normal and the inflamed lung and
can provide important information regarding regional physiologic
status of the lung before and after interventional procedures such
as LVRS, endobronchial valve insertions to limit gas flow to
proximal lung, and grommet placements to relieve trapped gas.
PHENOTYPING EMPHYSEMA
Evaluation of Disease Progression
It has been well demonstrated that lung function declines with
age (18–21) and perhaps also as a result of inflammation (22).
This has confounded research related to the effects of smoking
cessation on lung health. There are mixed results as to whether
or not smoking cessation halts the progression of emphysema-
tous lung disease (20, 23–27). Work by Bosse and colleagues
(28) attempted to take into account the aging process and sug-
gested that the disease process is slowed if one stops smoking.
However, tests were not sensitive enough to conclude this defini-
tively. There appear to be important sex differences in the effects
of cigarette smoking and cessation (29). No reliable specific
biochemical markers of disease presence or progression have
been identified (30), in part perhaps because of the lack of a
sensitive standard to diagnose and follow the diseases. More
recently, CT parameters have been shown to be likely more
sensitive to disease progression (31). Furthermore, the long time
course of these diseases means that clinical trials using only
whole lung function as primary outcome measures require huge
numbers of subjects for extremely long periods of time.
Anatomic–Physiologic Correlates of Emphysema
The lack of a direct marker for emphysema has meant that
epidemiologic studies have been limited to COPD, and these
perhaps give a limited view as to the epidemiology of emphy-
sema, a specific subset of COPD but not identified as such by
spirometry. The direct effect of cigarette smoking on lung func-
tion has been widely studied, with differences in relative changes
in FEV
1
and the effects of smoking noted (28, 32–35). Although
some studies show an increased rate of loss of FEV
1
for current
smokers, there is a less significant decrease in FEV
1
for reformed
Hoffman, Simon, and McLennan: CT-Based Lung Structure and Function 521
smokers (28, 32). However, more recent studies have found similar
FEV
1
declines with age in both smokers and never-smokers (34,
35). It must be emphasized that these changes are likely related
to bronchial hyperreactivity (36, 37) rather than to emphysema,
highlighting again the need for objective measurement tools to
assess emphysema.
As indicated, chronic airflow limitation (COPD) is commonly
seen in emphysema, but it is not essential. Measurements of
lung physiology are not always able to distinguish the abnormali-
ties that result from emphysema from those which result from
the other causes of COPD, such as chronic bronchitis or asthma
(38). The strongest positive association between an index of
airflow limitation, FEV
1
(% predicted) and a pathologically
derived emphysema score comes from the National Institutes
of Health Intermittent Positive-pressure Breathing Trial (39).
There were only 48 subjects in this study, as autopsies were
required for the pathologic assessment to be performed. Pulmo-
nary function tests were performed every 3 months during the
study, and were therefore available at some point before death.
However, these subjects were highly selected; to enter the study,
they were required to have very significant airflow obstruction,
and could not be severely hypoxic; and to complete the study,
they had to die during the observation period. In contrast, a
study examining pathologic lung specimens taken during sur-
gery, and appropriately fixed, showed no relationship between
the pathologic emphysema rating and indices of airflow (40).
Furthermore, an autopsy study enrolling 242 subjects over 6
years demonstrated that, although those subjects with greater
pulmonary disability tended to have a greater degree of patho-
logic emphysema, 17 subjects with greater than 30% pathologic
emphysema had no evidence for clinical COPD (41). Other
pulmonary function tests—namely, diffusing capacity for carbon
monoxide (Dl
CO
) and the exponential description of the defla-
tion pressure/volume curve (K)—have been used to identify,
and to obtain a measure of, severity for pulmonary emphysema.
A number of studies have found that measurement of Dl
CO
has a very weak correlation with the pathologic assessment of
emphysema (42–44). Measurements of elastic recoil pressure
curves in life compared with pathologic assessment of emphy-
sema at subsequent lung resection or postmortem have yielded
conflicting results on the value of static compliance and K as a
measure of emphysema (45–49). More recent studies show a
weak but significant correlation between K and macroscopic
emphysema (r ⫽ 0.49) (47, 48), with K believed to be a measure
of alveolar distensibility. This background highlights the continu-
ing search for a marker for emphysema presence and severity.
Vascular and Intravascular Alterations in Early Stages of
Parenchymal Lung Disease
Increased margination of the neutrophils in the small blood
vessels in the lung has been demonstrated in smokers (50–55).
One of the earliest abnormalities may therefore be regional
change in perfusion of affected lung regions. As the emphysema-
tous lesions develop in the peripheral lung, there is not only
destruction of the terminal air units but also gross destruction
of the microvasculature of the lung (55–57). These changes, in
the vascular bed and alveolar wall, may occur at the same time;
however, it is probable that the changes in vascular perfusion
occur slightly earlier than the alveolar wall changes, in keeping
with a primary role played by the blood neutrophils. In an elastase-
induced emphysema pig model, it has been shown that vascular
perfusion is reduced in early emphysematous lesions using single
photon emission computed tomography (SPECT) scanning (58).
In this model in which the elastase is injected into the lung,
there are initially areas of increased lung density, the result
of edema and alveolar hemorrhage. In a guinea pig model of
emphysema, muscularization of the pulmonary arterioles occurs
well before any evidence of emphysema, suggesting another
potential mechanism for alterations in blood flow as an early
feature in emphysema development (59). Hyde and colleagues
(60) have recently demonstrated that, in the adult rabbit, blood
flow is significantly diverted from inflamed lung. The presence
and magnitude of both pulmonary and bronchial blood flow
have been shown to effect the recovery of the lung from broncho-
constriction and the clearance of aerosol or noxious particles
(61–64). Thus, although there is the notion that blood flow alter-
ations serve as a tag of inflammation, the physiology remains
largely unknown, and its elucidation in the in vivo system will
provide important new information as well as a tool for further
investigations. As we suggest in the first part of this article,
pulmonary perfusion abnormalities may be a primary cause of
emphysema, rather than a secondary phenomenon.
THE SCANNERS
X-Ray CT
Volumetric physiologic imaging had its beginning in the mid-
1970s with the Dynamic Spatial Reconstructor (DSR), which
supported 14 X-ray guns on a continuous rotating gantry and
was purpose-built to provide dynamic volumetric images of the
heart and lungs (65). Much of the work establishing the accuracy
and precision of volumetric lung imaging was performed on the
DSR (65, 66). Commercial imaging technology lagged signifi-
cantly behind this early work. The electron beam CT (EBCT)
(67) emerged in the early to mid-1980s as another purpose-
built scanner that entered the commercial arena. EBCT had no
moving parts and swept an electron beam along parallel X-ray
targets to achieve improved scan speeds of up to 50 milliseconds
per slice pair and eight stacked slices in approximately 224 milli-
seconds. There have been rapid advances in speed and resolution
with the advent of MDCT (68). Its cone-beam spiral CT uses a
two-dimensional (2D) detector array, allowing larger scanning
range in shorter time with higher image resolution (69, 70). The
ability to acquire multiple image slices per rotation with rotation
speeds as short as 0.33 seconds allows for a significant reduction
in acquisition time. Faster scan times will significantly impact
functional imaging protocols where the rate of perfusion of a
contrast agent is measured over time or where gated imaging is
needed. We believe the future of lung assessment resides with
true dynamic low-dose volumetric CT scanners that image at
least one-third of the thorax with 0.5-mm isotropic voxels and
a full rotation scan aperture of 150 milliseconds and that have
superior contrast resolution for radiopaque gas and injected
contrast detection. The system will be likely coupled with a
low-Tesla MR scanner that will be used to complement the
information available from the CT image. Patients will be
scanned frequently by low-Tesla MR and less frequently over
time by use of the CT component. To this end, MDCT has
evolved to where typical scanners now acquire 64 slices in a
single rotation spanning up to 4 cm of the z-axis of the chest,
and manufacturers have shown prototypes supporting up to 256-
slice scanning (Toshiba, Tochigi, Japan) in a single rotation.
A dual X-ray source scanner (Definition; Siemens, Erlangen,
Germany) provides significant increases in speed and opens the
possibility of dual energy scanning. With dual energy scanning
(setting the two X-ray sources at different kV, such as 80 and
140 kV), there is a density shift in regions with interposed con-
trast agents, such as inhaled xenon gas or injected iodinated
contrast agents, without a concomitant shift in normal body
tissues. As such, one can subtract away the tissues from the
images derived from the two imaging chains while leaving behind
the xenon or iodine signal as an index of regional lung function.
522 PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY VOL 3 2006
Customized compounds (71) can now be designed to selectively
target tissues based on particular characteristics of the tissue.
MRI
Over the past 10 years, there has been renewed interest in
applying MRI to the lung. Of particular interest has been the
use of hyperpolarized helium (HP 3-He) MRI. Methods include
the following: measures of peripheral airspace size (72–75),
visualization of ventilation distribution at high spatial resolution
(76–79), and assessment of gas flow patterns within the lobar
and segmental airways (80–82). Furthermore, the speed of depo-
larization of HP 3-He enables direct measurement of regional
partial pressure of oxygen and thus allows for an inference of
regional gas exchange (83–85). Critical to HP 3-He, and its more
recent counterpart, HP Xe, is the need to quantitate the resultant
images. We believe that MDCT may serve as a gold standard
against which these quantitative measures can be developed.
SCANNING PROTOCOLS
Within the Appendix, we provide the scanning protocols associ-
ated with our anatomic and functional imaging studies. These
protocols include the radiation estimations. Radiation dose re-
mains the limiting factor in determining the benefit of the tech-
nology relative to the risk when applied to a particular study.
Hoffman and coworkers have discussed radiation dose consider-
ations more fully elsewhere (86).
QUANTITATIVE IMAGE ANALYSIS
Critical to taking full advantage of MDCT (and MRI) is the
ability to objectively evaluate the information content of the
images. In the case of the lung, the starting point is reliable
detection of the lungs, lobes, airways, and blood vessels, followed
by an analysis of parenchymal density and texture, and finally
a regional quantification of regional ventilation and perfusion
parameters.
Over the past 25 to 30 years, quantitative imaging has been
the focus in our laboratory to study the lung, and has included
biplane fluoroscopy methods for estimating lung stress–strain
(pleural pressure) (87, 88) and X-ray CT methods for the purpose
of evaluating the normal physiology of the lung. CT has been
validated as a tool for assessing lung volume (89), regional air
content (90, 91), regional lung expansion (91–93), airway seg-
mentation (93–95), and vessel segmentation (96, 97). These stud-
ies were focused on the use of purpose-built scanner systems
(the DSR [98]) and the electron beam CT scanner (67). More
recently, with the emergence of MDCT scanners, a Bioengineer-
ing Research Partnership Grant from the NIH (HL-064368,
E.A.H. and G.M.) has served to bring together investigators
from multiple institutions from around the world to establish
MDCT as a comprehensive imaging modality to assess both
structure and function of the human lung, to establish the normal
range of airway and vascular structure, parenchymal density,
and texture together with regional characteristics of ventilation
and perfusion. Perfusion is assessed via dynamic imaging of first-
pass kinetics of a bolus injection of iodinated contrast agent and
ventilation via the wash-in and washout characteristics of stable,
radio-dense xenon gas. A cohort of normal human subjects are
being imaged over 4 decades of age range, both male and female,
across a broad spectrum of racial and ethnic backgrounds to
establish an atlas of the normal lung, against which an unknown
lung can be statistically compared for abnormality.
Respiratory Gating
To detect early pathology and small, incremental progression of
disease, one must take great care to appropriately calibrate the
scanner on a regular basis, taking into account the imaging char-
acteristics of the scanner and image reconstruction algorithms.
Perhaps even more important, however, is to also take great
care that the lung is imaged at standardized volumes, just as one
coaches a patient in the pulmonary function laboratory. To this
end, we have established a respiratory gating methodology that
allows us to accurately gate image acquisition to lung volume
in human subjects, using either a pneumotachograph, an induc-
tance plethysmograph (Respitrace; Research Instrumentation
Associates, Inc., Chesterland, OH), or turbine flowmeter signal.
With modified scanner software, one is able to reduce the scanner
pitch (table increment per 360⬚ gantry rotation divided by beam
collimation) down to 0.1 for retrospective respiratory-gated
spiral imaging. Within our laboratory, we have built a fully inte-
grated software/hardware solution using the pneumotachometer
and inductance plethysmograph and are currently building a
second system based on the turbine for Xe imaging in humans.
We use software written in LabView (National Instruments,
Austin, TX) to record patient physiology (including airway pres-
sure, ECG, blood pressures, etc.) and then we are able to gate
the scanner on and off according to the physiologic parameters of
interest. Scanner manufacturers are currently providing simple
pneumatic belts for respiratory gating. Little work has currently
been done to verify the accuracy of these belts under various
conditions, such as shifts from abdominal to ribcage breathing
and prone versus supine scanning.
The segmentation of the lung, lobes, airway, and pulmonary
vascular bed is described together with methods for assessing
lung texture (parenchymal pathologies), perfusion, and ventila-
tion in the following sections.
Lung Segmentation
Automated segmentation of the lungs from a 3D set of CT
images is a crucial first step in the quantitative analysis of pulmo-
nary physiology or pathophysiology. With large 3D image vol-
umes becoming commonplace, routine manual segmentation to
identify regions of interest (ROIs) is too cumbersome and time-
consuming. In addition, manual analysis has significant interob-
server and intraobserver variability.
We have developed and validated a segmentation method to
accurately extract the lungs from CT images (99) (Figure 1). This
approach, which can be used automatically or semiautomatically,
relies on thresholding to obtain approximate initial lung masks.
These lung masks are refined using topologic analysis (e.g., to
delete cavities and small disconnected pieces) and specialized
processing to enforce anatomic constraints (e.g., using a graph
search to find the most likely location of the line separating the
left and right lung). Experimental studies using images acquired
from humans have shown our method to be very accurate:
computer-generated and manually defined lung areas (in pixels)
correlated very well in individual slices (r ⫽ 0.99).
Lobe Segmentation
Zhang and colleagues (100) have developed a semiautomatic
method for identifying the fissures in CT images (Figure 1). This
method uses a combination of anatomic features and CT image
features to identify the fissures on 2D transverse slices. These
features are combined into a cost function that reflects the likeli-
hood that a pixel lays on the fissure. A graph search, which is
a heuristic cost-based search technique, is used to find a path
between the endpoints. Graph searching finds the minimum cost
path between the two endpoints, where the cost function defini-
tion reflects the problem of interest. The user must initialize the
process once for each fissure of interest, but once the procedure
has been initialized, the entire 3D surface can be automatically
identified. The overall root mean square error between manual
Hoffman, Simon, and McLennan: CT-Based Lung Structure and Function 523
Figure 1. Results of vascular
(upper left), lobe (middle), and
airway (lower right) segmenta-
tion. After the airways are
identified (segmented) and the
centerline and branchpoints
are identified, then the airway
tree is automatically labeled.
The lobar fissures are identified
by the geometry of the seg-
mented blood vessels as shown
by the red and green arrow-
heads shown in the upper left
panel. L ⫽ left, R ⫽ right, B ⫽
broncus, UL ⫽ upper lobe, M ⫽
middle lobe, LL ⫽ lower lobe.
tracing of the fissure and our semiautomatic method is about
2 pixels. Under development are methods to automatically initi-
ate the lobe segmentation process through the development of
a standard lung atlas representing the average shape of the
normal human lung. The individual is then matched to the atlas
and the location of the fissures in the atlas serve as the initial
guess for the search initiation. More recent work from the labora-
tory has used an anatomic pulmonary atlas with a priori knowl-
edge about lobar fissure shapes from a set of presegmented
training datasets to achieve a fully automatic lobe segmentation
(101).
Airway Lumen and Wall Segmentation
Airways of interest range in size from 1- to 15-mm inside diame-
ter, and the software determines the borders of the inner and
outer airway walls (102). The small airways have very thin walls,
typically on the order of 10 to 15% of the inner diameter. The
established full-width at half-maximum method for measure-
ment can give very inaccurate results for these small thin-walled
structures. To address this problem, we use a new method of
estimating the airway wall locations. We first assess the point
spread function of the particular scanner/slice selection/recon-
struction algorithm of interest and then use a model-based de-
convolution to account for blur introduced in the scanning pro-
cess. This approach was shown to be more accurate than
previously used wall detection methods, especially for thin-
walled structures. Phantom studies have demonstrated the new
method to be applicable across a wide variety of airway sizes
(102, 103). As shown in Figure 2, once the airway tree has
been identified in 3D, airway paths can be “straightened” into
a pathway “pipe” view to allow for assessment of the local geo-
metry perpendicular to the airway centerline.
To identify the airway tree structure, Tschirren and colleagues
(104, 105) have developed an automated segmentation, skele-
tonization, and branchpoint matching method. The airway tree
is identified using a seeded region growing algorithm, starting
from an automatically identified seed point within the trachea.
The algorithm is designed so that it can overcome subtle gray-
level changes (e.g., those caused by beam hardening). On the
other hand, a “leaking” into the surrounding lung tissue can be
avoided. The implementation of the algorithm uses graph algo-
rithms that make it fast and memory friendly. The method reli-
ably segments the first five to six airway generations. The binary
airway tree is then skeletonized to identify the 3D centerlines
524 PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY VOL 3 2006
Figure 2. Once the
three-dimensional air-
way tree has been iden-
tified and labeled, paths
can be identified and
straightened so as to
provide luminal and
wall dimensions mea-
sured as a function of
the distance along the
path and perpendicular
to the local long axis.
The airway cross-section
corresponding to the
yellow vertical line in the
upper panel is shown in
the lower left panel. The
green arrow in the lower
left panel can be rotated
about the centerline of
the airway to alter the
cut plane shown in the
straightened airway pre-
sented in the upper panel.
of individual branches and to determine the branchpoint loca-
tions. A sequential 3D thinning algorithm reported by Palagyi
and colleagues (106) was customized for our application. False
branches are pruned, and the resulting skeleton is guaranteed
to lie in the middle of the cylindrically shaped airway segments.
Branchpoints are used to define airway tree segments, which
are then automatically labeled with a modified standardized
nomenclature that we have established that takes into account
the most common variability between individuals. This nomen-
clature (shown in Figure 1) can be applied to images of multiple
lung volumes of the same individual to allow us to track the
change in airway dimensions along an airway path as well as the
change in airway dimensions with change in lung volume. Our
airway segmentation methods have been shown to be robust
in the presence of significant emphysema and when applied to
images acquired using low-dose scanning protocols. In Figure 3,
we demonstrate the ability to extract an airway tree of a subject
with interstitial lung disease in which there is considerable mixed
pathology, including emphysema, honeycombing, traction bron-
chiectasis, and fibrosis.
Parenchymal Analysis
Computer-based methods for objective quantitation of MDCT
datasets to compare normal and diseased lung parenchyma are
increasingly being used in conjunction with 2D datasets. A cor-
nerstone of lung assessment for emphysema by MDCT scanning
has become known as the density mask. The basis of the density
mask is that a CT scanner, if properly calibrated, reconstructs
air with a Hounsfield unit (HU ⫽ standardized unit of X-ray
attenuation) of ⫺1,000, water as 0, and blood/tissue as approxi-
mately ⫹55. Because the lung is composed of only air or blood/
tissue densities and because the HU is linear between these two
values, one is able to assess the percentage of air and percentage
of blood/tissue in each reconstructed voxel. Because emphysema
is defined as an enlargement of the peripheral airspaces associ-
ated with parenchymal destruction, the HU of a voxel becomes
an index of presence and severity of the disease. By empirically
defining a given lung density at full inspiration as emphysema,
one can set a density threshold (HU) below which all voxels are
considered to be emphysema (107–114). This is the so-called
density mask. It has been observed that the density mask for
severe emphysema in 5-mm-thin or thinner slices falls at approxi-
mately ⫺950 HU, moderate emphysema at approximately ⫺910
HU, and mild at approximately ⫺850 HU. By identifying where
the lung is in the image and then dividing the lung into left and
right, apical, mid, and basal regions, and then dividing these
regions into the “core” and “peel,” we are able to begin to es-
tablish phenotypes for populations (distinguished, for instance,
by sex, ethnicity, ␣
1
-antitrypsin deficiency, and now possibly sub-
populations of smokers), differentiating populations based on
Hoffman, Simon, and McLennan: CT-Based Lung Structure and Function 525
Figure 3. Demonstration of the ability to
extract a detailed airway tree from com-
puted tomography (CT) scans of a patient
with significant mixed-lung pathology.
The images show emphysema, honey-
combing, traction bronchiectasis, and
fibrosis.
characteristics of the pattern and severity of emphysema. Adams
and coworkers have pointed out the importance of imaging with-
out contrast agent when using HU as a measure of emphysema
(107). A density-masking approach alone is not sufficient to
accurately distinguish normal from diseased lung (115–117), es-
pecially in the case of early or mixed pathologic processes. The
density mask is, however, particularly useful in characterizing
mild/moderate and severe emphysema and has been used in the
NETT to identify subgroups of patients who show benefit from
LVRS (15). With the increased use of CT to screen for lung
cancer (118) and coronary calcium (119), Reddy and colleagues
have demonstrated the utility of using these same scans to char-
acterize the presence and distribution of emphysema (120, 121).
Care must be taken when one uses CT to quantitate parenchymal
characteristics because scanner miscalibration and reconstruc-
tion kernels can cause some variations in the measurements
(122–124). Furthermore, because the X-ray is not a single energy,
beam-hardening artifacts, if not well corrected for by the manu-
facturers, can cause additional errors.
As our image analysis methods have evolved, we have inte-
grated the tools into a PC-based comprehensive lung image
analysis package called Pulmonary Analysis Software Suite
(PASS). In addition to the traditional density mask discussed
above, we have incorporated an additional measure, one pro-
posed by Mishima and colleagues (125), which has been termed
the “fractal dimensions” or “alpha.” Alpha is the slope of the
log–log relationship of hole size versus percentage of holes at
that size. The notion is that initially a random set of holes evolves
in lung regions and, as such, the log–log plot of hole size versus
percentage of holes is linear. However, once the initial holes
have evolved, there is a greater likelihood that these holes will
have destabilized the lung mechanically and the small holes will
combine to form bigger holes as opposed to more small holes
appearing. Thus, the slope of the log–log plot diminishes. In this
way, alpha becomes an index of disease severity.
Texture (Adaptive Multiple-Feature Method)
High-resolution CT (HRCT) enhances the resolving power of
the image (126–130), allowing detection of less severe emphy-
sema. Various computer-assisted texture-based methods have
successfully been used for tissue characterization. Traditional
methods of texture analysis can be grouped into statistical, struc-
tural, and hybrid methods (131). Methods for tissue classification
typically rely on region gray-scale statistical measures (i.e., mean,
variance, frequency histogram) or textural measures (autocorre-
lation, co-occurrence matrices, run-length matrices, etc.) (107–
111, 132–141).
Although simple density measures are adequate for the as-
sessment of moderate to severe emphysema, this simple measure
is inadequate in assessing early pathologic changes, detecting
changes where the pathology is mixed, or detecting more com-
plex patterns such as ground glass. We have developed and
patented a unique method of texture analysis of the lung for the
objective assessment of pathologic processes in which simple
lung density measures are inadequate for detection or differenti-
ation of processes. Our Adaptive Multiple-Feature Method
(AMFM) assesses as many as 22 independent textural features
from HRCT scans to classify a tissue pattern (116, 142, 143).
The AMFM is 100% reproducible and performs as well as experi-
enced human observers who have been told the patient diagnosis.
Recently, a goal of extending the AMFM feature set from 2D
to 3D (144) has been motivated by the emergence of MDCT
scanners with the ability to acquire volumetric image datasets
526 PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY VOL 3 2006
with near isotropic (near equal dimensions in all three orthogo-
nal directions) voxels. We have used images from the normal
population studied through our Bioengineering Research Part-
nership (BRP) grant together with heavy smokers studied at the
University of Iowa in the National Lung Screening Trial. The
3D ROIs from lung regions (50 subjects total) of normal never-
smokers were identified together with normal lung from normal
smokers, mild emphysema from smokers with mild COPD, and
moderate to severe emphysema regions from smokers with
moderate to severe COPD. Lung status was defined based on
American Thoracic Society GOLD criteria for characterizing
COPD derived from spirometry-based FEV
1
/FVC measures. Al-
though 2D performed as well as 3D for GOLD 2 and GOLD
3 emphysema, the 3D feature set provides a highly significant
improvement in differentiating normal-appearing lung sampled
from nonsmokers versus GOLD class 0 smokers.
Functional Imaging
Numerous methods have been developed to assess ventilation
and perfusion, or their functional outcome, gas exchange. Al-
though clearly useful, pulmonary function tests are global mea-
surements of airflow, lung volumes, and gas exchange from which
are inferred primary structural and functional alterations. Im-
aging techniques such as PET (145) and the newly emerging
hyperpolarized gas imaging via MRI (146–152) offer unique,
complementary regional information to X-ray CT and, as they
develop, are expected to offer enhancements to the knowledge
base that we propose to build into the lung atlas via MDCT.
Ventilation assessed by CT. Regional ventilation is measured
from time course of CT density change during a multibreath
wash-in and washout of radio-dense Xe gas (153). Studies to
date have demonstrated that the optimal imaging time is at end
expiration when conducting airways are filled with alveolar gas
(154). Average regional time constants are similar for repeat
runs reducing inspired Xe gas concentrations from 55 to 30%,
but the coefficient of variation at 30% Xe is significantly greater
than at 40% and higher concentrations. The addition of 30%
krypton gas to 30% Xe gas provides the same contrast enhance-
ment and signal-to-noise ratio as 40% Xe (155). Krypton has
none of the unwanted side effects of higher concentrations of
Xe gas. Of particular note is the observation that wash-in and
washout time constants are not equal, as previously assumed.
Washout is longer, specifically at higher Xe concentrations and
in dependent basal lung regions (154).
Perfusion assessed by CT. Dynamic imaging methods have
been used to estimate arterial, venous, and capillary transit times
and capillary flow distributions (156–163). These methods in-
volve two types of image data collection regimes: inlet–outlet
detection is typically used for conducting vessels and whole
organ analysis; the other data collection regime is referred to
as residue detection. Residue detection is typically used alone or
in conjunction with inlet detection for analysis of microvascular
regions wherein the individual vessels are below the resolution
of the imaging system. Various approaches for determining
blood flow and/or mean transit time have been described (157,
160–170).
To assess regional parenchymal perfusion, we place a catheter
in the right ventricular outflow tract in animals and in the supe-
rior vena cava in humans. A sharp (0.5 cc/kg over 2 s) bolus of
iodinated contrast agent (Visipaque; GE Healthcare, Milwau-
kee, WI) is delivered during ECG gated axial scanning. Scanning
commences one to two heartbeats before contrast injection, with
lungs held at functional residual capacity. By sampling the recon-
structed time-attenuation curves within the region of a pulmo-
nary artery and the lung parenchyma, we are able to calculate
regional mean transit times as well as blood flow normalized to
air or tissue content (171). We are able to deconvolve the signals
such that we can estimate the timing of flow within the microvas-
cular bed (162, 172).
We have begun imaging normal human subjects to establish
the image-based atlas of blood flow in the normal human lung.
As part of our work to determine the differences between the
normal lung and the lung of smokers, we have imaged a series
of never-smokers and smokers, both falling within a GOLD
category 0. As shown in Figure 4, in preliminary studies we have
found that smokers, even if defined as normal by pulmonary
function tests, have increased heterogeneity (coefficient of varia-
tion) of local mean transit times of the contrast agent. With
voxels on the order of 0.4 ⫻ 0.4 ⫻ 0.4 mm, the increased coeffi-
cient of variation shows up only when sampling of regional blood
flow occurs in regions no larger than 3 ⫻ 3 voxels, indicating
that the level of early disruption of blood flow is at the level of
the microvasculature.
HPV AND ITS FAILURE IN THE PRESENCE OF
INFLAMMATION
By combining the ability to assess regional lung density, ventila-
tion, and perfusion, we now provide the initial evidence for our
hypothesis introduced at the beginning of this article: in subjects
with pulmonary emphysema, one major contributing factor lead-
ing to parenchymal destruction is the lack of a regional blunting
of HPV when the regional hypoxia is related to regional inflam-
matory events (bronchiolitis or alveolar flooding).
One of the fundamental homeostatic mechanisms by which
the lung preserves oxygenation in the face of injury is HPV.
HPV causes pulmonary arterial blood vessels to constrict in
response to local hypoxia, thus redistributing blood flow away
from poorly ventilated regions and toward lung regions that are
well ventilated. This response optimizes local V
˙
/Q
˙
matching and
minimizes shunt as a mechanism of hypoxemia.
Both ventilation and perfusion were measured in units of
ml/min in sheep being evaluated under a protocol, approved by
the University of Iowa Animal Care and Use Committee, to
develop imaging methods to evaluate the functional status of
the lung after placement of endobronchial valves used in humans
as an alternative to LVRS.
Studies reported here were performed at the Iowa Compre-
hensive Lung Imaging Center using a Siemens Sensation 64
MDCT scanner, modified to allow for external scan gating to the
respiratory signal, and anesthetized, supine sheep were studied.
Figure 5 shows data from one sheep with the original gray-scale
images shown in the left column, the ventilation coded image in
the middle column, and the perfusion image shown in the right
column. Images taken before valve placement are in the upper
row and post–valve placement data are shown in the lower row.
Of interest are the following: (1) the sheep arrived in the labora-
tory with pneumonia, (2) loss of ventilation post–valve place-
ment is evident in the lower middle panel,(3 ) reflex loss of blood
flow in response to the loss of ventilation due to the valve is
evident in the lower right panel, and (4 ) perfusion shunted away
from the region of the valve served to preferentially enhance
perfusion in the unventilated region in the dependent lung where
there was evidence of pneumonia. Other data in the laboratory
have shown that when a sheep is exposed to inspired hypoxia
(15% O
2
), perfusion is reduced everywhere except in the region
of pneumonia, and in the region of pneumonia, perfusion is
enhanced.
These studies reflect earlier findings of Gust and colleagues
and Schuster and colleagues (13, 173) in which endotoxin was
shown to block HPV when assessing regional perfusion via use
of PET. These data, coupled with the findings of perfusion
Hoffman, Simon, and McLennan: CT-Based Lung Structure and Function 527
Figu r e 4. Anormalnon-
smoker and GOLD 0
sm oke r showi n g consi d-
erable increase in paren-
chymal perfusion hetero-
geneity. When sampling
at increasingly coarse
sample sizes, the differ-
ence in the coefficients of
variation (COV) between
the two groups disap-
pears when the region-
of-interest size is larger
that 3 ⫻ 3voxels(ⵑ 1.2
mm on a side , about one-
fifth to one-tenth the size
of an adult ascinus) (174).
Color coding ranges
from 0 (blue)to15(red)
ml/min.
disruption in smokers shown in Figure 4, indicating likely perfusion
disturbance in response to inflammation, have led us to hypothesize
that the normal response to hypoxia caused by inflammatory pro-
cesses is to block HPV, by a process not here stipulated, so as to
ensure that the cascade of events serving to fight inflammation and
Figure 5. Before (base-
line; top row) and after
(post valve; bottom row)
endobronchial valve
placement. The left col-
umn provides a view of
one CT section at the
level of the diaphragm
dome. Note the signifi-
cant dependent pneu-
monia (A ). The center
column demonstrates
ventilation overlayed
in color as assessed by
xenon-CT. Note that
there is little ventilation
in either the baseline or
the post valve in the re-
gion of the dependent
pneumonia. By design,
there is a large region
where ventilation was
eliminated by the valve
placement (B ). The right
column shows a color
overlay of the perfusion
measurements. Note
that in the region (C )
coinciding with region B
from the central column
(no ventilation due to
valve placement), there
is a regional loss of perfusion, indicating an intact hypoxic pulmonary vasoconstrictor (HPV) response. At the same time, in the region of pneumonia
(D ) where there is little or no ventilation, blood flow is enhanced after valve placement. Presumably, blood flow shunted away from the valve-
based HPV is shunted straight toward the region of inflammation, presumably because the inflammation has served to blunt HPV in this region,
leaving this region as the path of least resistance for the blood flow diverted from the region effected by HPV. Thus, this image demonstrates that
lung has the ability to locally modulate HPV based on local inflammation.
infection can manifest itself. We further hypothesize that, in a
subset of smokers, there is an inability to block HPV in the face
of inflammation and this failure sets the individual up for the
evolution of the tissue destruction, which is a hallmark of emphy-
sema. Indeed, Remy-Jardin and colleagues (1) have demonstrated,
528 PROCEEDINGS OF THE AMERICAN THORACIC SOCIETY VOL 3 2006
as discussed earlier, in a small cohort of subjects, that, in a subset
of smoker who show decline over time in pulmonary function tests,
this decline is correlated with the development of emphysema in
regions showing signs of ground glass and micronodules at an
earlier time point. Not all smokers with ground glass and mi-
cronodules developed emphysema in these regions but these
subjects also did not show a decline in pulmonary function tests.
CONCLUSIONS
We have demonstrated that MDCT provides for a comprehen-
sive means of imaging the lung. It provides for a sensitive and
objective method of assessing the lung parenchyma, airway, and
functional status at the lung periphery, including measures of
both ventilation and perfusion. With a combination of highly
detailed anatomic information together with function measures,
we are able to evaluate regional pathologic processes for the
refined assessment of COPD phenotypes. We note that with the
growing set of powerful tools available in the clinical setting,
it becomes important to carefully establish new questions and
apply appropriate imaging modalities. One must take care to
apply these modalities appropriately, which brings a critical need
for interdisciplinary interactions among pulmonologists, physiol-
ogists, radiologists, physicists, engineers, and many more.
Conflict of Interest Statement : E.A.H. is the founder and co-owner of VIDA Diag-
nostics, which is commercializing some of the software that has evolved out of
his research group. He is also a member of the CT Medical Advisory Board for
Siemens Medical Solutions. B.A.S. does not have a financial relationship with a
commercial entity that has an interest in the subject of this manuscript. G.M. is
co-owner of VIDA Diagnostics, which is commercializing some software develop-
ments coming out of his laboratory. In addition, he is a clinical investigator for
Asthmatx and Emphasys.
Acknowledgment : The authors thank the entire research team of their Bioengin-
eering Research Partnership grant whose combined efforts have made possible
the findings reported within this paper. Of particular note are the contributions of
Drs. Joseph Reinhardt and Milan Sonka and Juerg Tschirren, who made significant
contributions to the image processing, and Drs. Deokiee Chon, Osama Saba, and
David Riker, who have made significant contributions to the experimental side of
the studies reported here. Abby Russi helped in the preparation of this manuscript.
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APPENDIX
Scan Protocols
Scan protocols together with estimated dose calculations used
for these studies are provided in Tables 1 through 3.
Volume Scans
Our current volumetric protocol consists of 100 milliampere-
seconds (mAs), 120 kV, and 1-mm collimation, with an effective
slice thickness of 1.3 mm, overlap of 0.65 mm, and pitch of 1.2
mm. The slice parameter mode is 32 ⫻ 0.6 mm. We will use
512 ⫻ 512 slice matrices. The subject is apneic at a controlled
lung volume (40 and 95% VC). We carefully check the calibra-
tion of the scanner on a weekly basis. To estimate the effective
dose, we have used the WinDOSE program developed by Profes-
sor Willi Kalender (University of Erlangen, Germany) and the
CT dose index (CTDI) for the Siemens Sensation 64. The total
effective dose (He) is the primary measure that our radiation
safety committee evaluates. The radiation dose, as outlined in
Table 1, from the procedures is equal to the risk that the average
American experiences from exposure to 40 months of natural
background radiation.
Xenon Regional Ventilation
Reference whole lung scans obtained at static inflations of 40
and 95% VC are used for axial scan locations. A ventilation
study is performed at 20 time points with 80 kVp and 150 mAs.
The slice parameter mode is 20 ⫻ 1.2 mm so that a 2.4 cm (or
greater depending on the axial extent of the field-of-view on
future scanner configurations) z-axis coverage is achieved. To
estimate the effective dose, we have used the WinDOSE pro-
gram and the CTDI for the Siemens Sensation 64. The total
effective dose (He) is the primary measure that the radiation
safety committee evaluates. The radiation dose, as outlined in
Table 2, from the procedures is equal to the risk that the average
American experiences from exposure to 14 months of natural
background radiation.
The ECG signal is replaced by a signal from our custom data
acquisition and control program to trigger the scanner at specific
points during the ventilatory cycle. The subject breathes sponta-
neously with a mouthpiece connected to our lung volume con-
troller and two-way switching valve (room air and the Xe En-
hancer set to provide 30% Xe/30% O
2
). The subject is instructed
to maintain a constant breathing pattern by watching a graphical
TABLE 1. RADIATION DOSE ESTIMATES FOR TWO
VOLUME SCANS
Volume scans 64 slice
Two scans Male Female
Organs, dose (mrad)
Lung 2,060 2,100
Breast 0 1,920
Skeleton 1,040 1,200
Esophagus 1,430 1,600
Red marrow 630 680
Skin 3,900 3,900
H
E,
mrem 690 1,060
TABLE 2. RADIATION DOSE ESTIMATES FOR
VENTILATION STUDY
Ventilation 150 mAs 80 kV
15 scans Male Female
Organs, dose (mrad)
Lung 830 848
Breast 0 900
Skeleton 330 382.5
Esophagus 406 410
Red marrow 150 180
Skin 18,000 18,000
H
E,
mrem 236.25 360
display with target lines. To deliver xenon gas, we use an En-
hancer 9000, which allows for xenon recycling. CO
2
is scrubbed
from the exhalate and xenon and oxygen are sensed and replaced
to maintain a constant concentration of the inspired gas. The
scanner is activated via our PC software programmed in the
LabView (National Instruments) environment and three gated
images are taken as the pre-Xe baseline. The switching valve
connects the subject to 30% Xe gas. The subject inhales nine
breaths of Xe.
Bolus Contrast Regional Perfusion
Scanning is in the axial mode at the same slice locations as in
the ventilation study. To obtain regional perfusion (Q) with
contrast injection, the scanner is set up as in the Xe protocols
described above, with an ECG trigger signal, and the subject
remains apneic during scanning. A Medrad power injector sys-
tem (Mark V Power Injector; Medrad, Indianola, PA) is used
to give a 2-second bolus of contrast (0.5 ml/kg, up to a total
volume of 50 ml). The lung volume controller is used to start
breath-hold at normal functional residual capacity. Two to three
baseline images are obtained followed by dye injection. A total
of 12 stacked image sets, one per heartbeat, are obtained to
follow the contrast agent (Visipaque; GE Healthcare, Milwau-
kee, WI) through the lung fields. The scanner is setup in axial,
ECG triggering mode, using 80 kVp, 150 mAs, 360⬚ rotations,
0.5-second scan time, 512 ⫻ 512 matrix, and the field of view
adjusted to fit the lung field of interest. The slice parameter
mode is 20 ⫻ 1.2 mm so that a 2.4-cm portion of the lung field
will be examined. To estimate the effective dose, we used the
WinDOSE program and the CTDI for the Siemens Sensation
64. The total effective dose (He) is the primary measure that
our radiation safety committee evaluates. The radiation dose
from the procedures, as outlined in Table 3, is equal to the risk
that the average American experiences from exposure to 19
months of natural background radiation.
TABLE 3. RADIATION DOSE ESTIMATES FOR
VENTILATION STUDY
Blood flow 150 mAs 80 kV
20 scans Male Female
Organs, dose (mrad)
Lung 1,320 1,140
Breast 0 960
Skeleton 660 580
Esophagus 540 620
Red marrow 200 240
Skin 24,200 24,200
H
E,
mrem 315 480
