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									              Ground glass opacity on
              CT scanning of the chest:
                What does it mean?
                                       Jannette Collins, MD and Eric J. Stern, MD

         round glass opacity (GGO) is         Pitfalls in the interpretation of GGO on            examination is not recognized, an erro-

G        described as a “hazy increased
         attenuation of lung, with preser-
vation of bronchial and vascular mar-
                                              CT scanning
                                                 As recognition of GGO is based on a
                                              subjective assessment of lung attenua-
                                                                                                  neous interpretation of pathologic GGO
                                                                                                  can be made.
                                                                                                     Cardiac and respiratory motion also
gins; it is caused by partial filling of air   tion, it is important to understand the             can create pseudo-GGO, which can be
spaces, interstitial thickening, partial      parameters that can interfere with lung             distinguished from pathologic GGO by
collapse of alveoli, normal expiration, or    density and make attenuation measure-               recognizing the blurring and double
increased capillary blood volume.”1           ments unreliable.5,6 Window widths and              images of vessels and fissures. GGO in
GGO is a nonspecific finding, and the           levels that are too narrow can erro-                the gravity dependent portions of the
differential diagnosis of the many            neously create the appearance of GGO                lungs is often seen as a result of micro-
causes of GGO can be lengthy. An              by artificially “blooming” small struc-              atelectasis, which can be differentiated
“ABCs” approach and a “pattern”               tures. In evaluating for GGO, collima-              from pathologic GGO by re-scanning
approach to the interpretation of GGO         tion ideally should be 1.0 to 1.5 mm.               the area of question with the patient in
on HRCT scanning of the lungs have            True GGO can not always be visualized               the prone position.
previously been described.2,3 This paper      with a thicker collimation because of
provides an abbreviated review of the         volume averaging, and a thicker collima-            Infiltrative processes resulting in GGO
physiologic correlates of the HRCT scan       tion sometimes results in a pseudo-GGO                Many patterns of distribution of
findings of GGO, focusing on infiltra-          pattern. GGO is therefore best imaged               ground glass opacity can be seen on
tive processes and their different GGO        with high-resolution CT (HRCT).                     HRCT of the lungs. It is important to
patterns of presentation.                        Lung attenuation normally increases              emphasize that most such disease
   GGO can be patchy, resulting in a          homogeneously with expiration. This                 processes can and do result in more than
mosaic pattern of lung attenuation.           increased attenuation can obscure                   one pattern, often simultaneously; the
Such a pattern can be seen in infiltrative     underlying pathologic GGO. Further-                 patterns change depending upon the
lung disease, airway abnormalities            more, if the expiratory nature of the               acuity or chronicity of the disease
(e.g., asthma, bronchiolitis obliterans),
and chronic pulmonary vascular dis-
ease (e.g., chronic thromboembolic dis-
ease).4 The distinction between these
three entities can be made by observing
the size of the pulmonary vessels in the
area of increased lung attenuation
(increased in both airway disease and
vascular disease, but not in infiltrative
disease), and by examining air trapping
on expiratory scans (indicating airway
disease) (figure 1).                           A                                                   B

                                              FIGURE 1. Asthma. Image shows a 20-year-old woman with wheezing and shortness of breath
 Dr. Collins is in the Department of Radi-    responsive to bronchodilator treatment. (A) Inspiratory HRCT (1.0 mm collimation) was normal. (B)
 ology at the University of Wisconsin Hos-    Expiratory HRCT (1.0 mm collimation) shows a mosaic pattern of lung attenuation. The areas of
 pital and Clinics, in Madison, WI. Dr.       increased attenuation represent normal lung during expiration, while the adjacent abnormal lucent
 Stern is in the Department of Radiology      areas of lung represent air trapping. This pattern of air trapping on expiratory scanning, without
 at Harborview Medical Center, Univer-        associated abnormalities, is seen most often with obliterative bronchiolitis and asthma (small air-
 sity of Washington in Seattle, WA.           ways diseases), and should be differentiated from infiltrative processes where areas of GGO are
                                              seen on the inspiratory images and mosaic attenuation is not accentuated on expiratory imaging.

APPLIED RADIOLOGY, December 1998                                                                                                              17
 Causes of a diffuse pattern of
 GGO on CT scanning

 • Acute rejection of lung
 • Adult respiratory distress syndrome
 • Edema
 • Extrinsic allergic alveolitis
 • Hemorrhage
 • Infectious pneumonia

                 Table 1                      FIGURE 2. Acute rejection of lung transplanta-   FIGURE 4. Extrinsic allergic alveolitis.
                                              tion. A 38-year-old man presents with increas-   Imaging of a 50-year-old farmer with an
                                              ing shortness of breath 3 weeks after            acute onset of increasing shortness of
process. We have categorized the etiolo-      bilateral lung transplantation. HRCT (1.0 mm     breath. HRCT (1.0 mm collimation) shows
gies of GGO according to the most com-        collimation) shows diffuse bilateral GGO, cor-   diffuse bilateral GGO, correlating with the
                                              relating with a pathologic diagnosis of severe   clinical diagnosis of acute farmer’s lung.
monly seen patterns of distribution:
                                              acute rejection.
   Diffuse pattern of GGO—Disease
processes commonly resulting in a dif-
fuse pattern of GGO on CT scanning
are listed in table 1. Acute rejection is
common after lung transplantation.
However, differentiating between
reperfusion edema, infection, and rejec-
tion can be difficult both clinically and
radiographically. HRCT is reported to
be 65% sensitive and 85% specific in
making the diagnosis of acute rejection
in the lung transplant population.7 The
only significant HRCT finding in acute
rejection (seen in 65% of these patients)     FiGURE 3. Early adult respiratory distress       FIGURE 5. Diffuse alveolar hemorrhage. A
                                              syndrome (ARDS). A 12-year-old boy with          45-year-old man presents with increasing
is GGO, which is patchy and localized
                                              acute shortness of breath and hypoxemia,         shortness of breath 2 months after bone mar-
in mild rejection and widespread in           requiring intubation and mechanical venti-       row transplantation. Helical CT scan (10 mm
severe rejection (figure 2). The main          lation after receiving chemotherapy for lym-     collimation) shows diffuse bilateral GGO.
differential diagnosis in this group of       phoma. HRCT (1.0 mm collimation) shows
patients is cytomegalovirus pneumo-           diffuse bilateral GGO. Pulmonary artery          correlates histologically with mononu-
nia, which can have an identical radio-       wedge pressure was normal, and trans-            clear cell infiltration of the alveolar
graphic appearance.                           bronchial lung biopsy and bronchoalveolar        walls.11 The distribution of GGO can be
   Adult respiratory distress syndrome        lavage showed no evidence of infection.          diffuse, patchy, or centrilobular (figure
(ARDS) is a form of nonhydrostatic pul-       The patient went on to develop severe            4) in this condition.
monary edema, characterized by leaky          ARDS with complications of barotrauma.              Pulmonary hemorrhage can be diffuse,
capillary membranes. These leaks lead                                                          patchy, or focal, depending on the under-
to extravasation of protein-rich fluid into    ings in patients with hydrostatic pul-           lying cause, of which there are many.12 In
the interstitial and alveolar spaces of the   monary edema include areas of GGO,               the acute phase, CT scans show consoli-
lung. Among the common causes of              interlobular septal thickening, peri-            dation or GGO (figure 5). In the subacute
ARDS are aspiration, contusion, smoke         bronchovascular interstitial thickening,         phase, CT shows 1- to 3-mm nodules that
inhalation, and sepsis. CT scan findings       increased vascular caliber, pleural effu-        are distributed in a uniform fashion, com-
of ARDS include bilateral and gravity-        sion, and thickening of fissures.10               monly accompanied by GGO and inter-
dependent lung opacities.8 Early in the          Extrinsic allergic alveolitis, also           lobular septal thickening.13
course of ARDS, all patients demon-           called hypersensitivity pneumonitis, is             Infectious pneumonia of any cause
strate GGO on CT, which persists on fol-      a complex immunologic reaction by                (e.g., bacterial, viral, mycobacterial, fun-
low-up CT in 50% of patients (figure 3).9      the lung, primarily to inhaled organic           gal, and parasitic) can cause GGO to
   Both cardiogenic and non-cardio-           antigens. The clinical presentation may          appear on HRCT scans. A diffuse pattern
genic edema occurs when the capacity          be acute, subacute, or chronic. HRCT             of GGO in the absence of associated CT
of the lung lymphatics to drain capillary     scan findings will vary with the stage            scan findings is a characteristic presenta-
transudate is exceeded. Etiologies            of disease. In the acute and subacute            tion for cytomegalovirus pneumonia
include venous and lymphatic obstruc-         phases, findings include GGO (in                  (CMV) and Pneumocystis carinii pneu-
tion, increased capillary permeability,       82%), small nodules (55%), a reticular           monia (PCP). CMV is the most common
and hypoproteinemia.5 HRCT scan find-          pattern (36%), and air trapping.11 GGO           viral pathogen to cause substantial mor-

18                                                                                                      APPLIED RADIOLOGY, December 1998
 Causes of a patchy pattern of
 GGO on CT scanning

 • Acute rejection of lung
 • Adult respiratory distress syndrome
 • Bronchiolitis obliterans organizing
   pneumonia (BOOP)
 • Bronchioloalveolar cell carcinoma
 • Extrinsic allergic alveolitis                FIGURE 6. Cytomegalovirus pneumonia.            FIGURE 8. Lipoid pneumonia. Image is of a
 • Hemorrhage                                   Imaging of a 42-year-old man with acute         46-year-old man with a 6-month history of
 • Infectious pneumonia                         respiratory symptoms 3 months after bone        mild dyspnea and chronic rhinitis, treated
 • Pulmonary alveolar proteinosis               marrow transplantation. Helical CT scan         with oily nose drops. HRCT (1.0 mm colli-
                                                (10 mm collimation) shows diffuse bilateral     mation) shows bilateral patchy areas of
                                                GGO, areas of septal thickening (straight       GGO with a background of intralobular and
                  Table 2                       arrows), and ill-defined small nodular opaci-    interlobular septal thickening, producing the
                                                ties (curved arrows). Small bilateral pleural   “crazy paving” pattern first described with
bidity and mortality in patients with           effusions are present.                          alveolar proteinosis. (Figure courtesy of
AIDS,14 and is a relatively common com-                                                         Tomas Franquet, MD, Barcelona, Spain.)
plication in organ transplant recipients. In
patients with AIDS and CMV pneumo-
nia, CT scanning will show GGO, dense
consolidation, bronchial wall thickening
or bronchiectasis, and interstitial reticula-
tion without air-space disease (although
GGO may occur in isolation).15 In organ
transplant recipients with CMV pneumo-
nia, CT scanning shows small nodules,
consolidation, GGO, and irregular lines
(figure 6). The presence of an isolated
                                                FIGURE 7. Pneumocystis carinii pneumo-          FIGURE 9. Invasive aspergillosis. Image is of a
ground glass infiltrate without additional
                                                nia in a 39-year-old man with AIDS. HRCT        49-year-old man with acute myelogenous
findings in patients with AIDS is highly                                                         leukemia and fever. Helical CT scan (7.0 mm
                                                (1.5 mm collimation) shows patchy bilateral
suggestive of PCP(figure 7).16                                                                   collimation) shows a triangular area of consoli-
                                                areas of GGO and a small cystic lesion in
   Patchy GGO patterns—Many of the              the left upper lobe (arrows).                   dation abutting the peripheral right lung and
causes of a patchy distribution of GGO                                                          involving both the right middle and lower lobes.
on HRCT scanning, listed in table 2,            plasm, trauma, or pulmonary infarction,         This distribution and shape is characteristic of
may also result in a diffuse pattern of         a focal pattern of opacity results. Certain     hemorrhagic infarction caused by the angio-
GGO. Pulmonary alveolar proteinosis is          infections, such as lobar pneumonia, also       invasive fungal agent aspergillosis. The sur-
a disease of the lung that results in fill-      may result in a focal pattern of GGO.           rounding GGO, creating the “halo sign”,
ing in of the alveoli by a periodic acid-          Bronchoalveolar lavage is a procedure        represents hemorrhage and is highly specific for
                                                                                                early invasive aspergillosis in leukemic patients.
Schiff-positive proteinaceous material          used to diagnose pulmonary diseases and
that is rich in lipid.17,18 HRCT scanning       to identify predictors of prognosis. The
of this disorder shows GGO, with an             technique involves injection of normal          consolidation. Table 4 lists the processes
overlying branching pattern of white            saline through a bronchoscope that is           known to produce the halo sign. It was
linear structures forming geometric             generally wedged into the lingular or           first reported as a sign of early invasive
shapes and outlining polygonal, triangu-        middle lobe bronchus. Most, but not all         pulmonary aspergillosis in patients with
lar, and square forms.19,20 This pattern is     of the fluid is aspirated back into the          leukemia.23 The GGO represents a
often referred to as “crazy paving,” and        scope and examined for inflammatory
is characteristic, but not pathogno-            and immune mediator cells and specific             Causes of a focal pattern of GGO
monic, of the diagnosis of alveolar pro-        proteins.22 The residual fluid demon-              on CT scanning
teinosis (figure 8).21 Other processes that      strates a segmental or lobar distribution
can show a crazy paving pattern at              of GGO on CT scanning, which should               • Bronchiolitis obliterans organizing
HRCT scanning include ARDS, lipoid              suggest the possibility of recent bron-             pneumonia (BOOP)
pneumonia, and PCP.                             choalveolar lavage, especially if the             • Bronchoalveolar lavage
   Focal GGO patterns—There is over-            GGO is observed in the right middle lobe          • Bronchioloalveolar cell carcinoma
lap between causes of diffuse, patchy,          or lingula.5                                      • Hemorrhage
and focal distributions of GGO (table 3)           The “halo” pattern of GGO—A                    • Pulmonary infection
with chest CT scanning. When pul-               “halo” of GGO occasionally can be seen
monary hemorrhage is due to focal neo-          around a nodule or focal area of lung                              Table 3

APPLIED RADIOLOGY, December 1998                                                                                                               19
                                                                                                     Causes of a peripheral pattern of
                                                                                                     GGO on CT scanning

                                                                                                     • Bronchiolitis obliterans organizing
                                                                                                       pneumonia (BOOP)
                                                                                                     • Collagen vascular disease
                                                                                                     • Contusion
                                                                                                     • Desquamative interstitial
                                                                                                     • Drug toxicity
                                                                                                     • Eosinophilic pneumonia
FIGURE 10. Bronchiolitis obliterans organiz-        FIGURE 12. Desquamative interstitial pneu-
                                                                                                     • Fibrosis
ing pneumonia. Image is of a 50-year-old            monitis. Image is of a 77-year-old man with a
                                                                                                     • Sarcoidosis
man with increasing shortness of breath after       3-month history of increasing shortness of
bilateral lung transplantation. HRCT (1.0 mm        breath. HRCT (1.5 mm collimation) shows
collimation) shows bilateral patchy areas of        bilateral areas of GGO and consolidation in a                   Table 5
GGO in both a bronchovascular and periph-           peripheral distribution without evidence of
eral distribution.                                  honeycombing or traction bronchiectasis.
                                                                                                    bleeding into the air spaces and lung
                                                                                                    interstitium. Generally, the cause is a
                                                    patients who have undergone lung trans-         compression injury with significant
                                                    plantation and transbronchial lung              kinetic energy absorption adjacent to the
                                                    biopsy,25 but they may be seen in any           site of chest wall injury. The CT scan
                                                    patient after lung biopsy.                      appearance of lung contusion is that of
                                                       A peripheral pattern of GGO—                 ill-defined areas of GGO, consolidation,
                                                    Processes that are known to result in a         or both, usually with a peripheral, non-
                                                    peripheral lung distribution of GGO             anatomic distribution (figure 11).32,33
                                                    with HRCT scanning are listed in table              Desquamative interstitial pneumonitis
                                                    5. This particular distribution pattern         is characterized by alveolar filling with
                                                    can be very helpful in narrowing the dif-       macrophages. The HRCT scan findings
                                                    ferential diagnosis, especially when            consist of GGO with a lower lung zone
FIGURE 11. Contusions. Image is of a 22-            combined with other clinical data and           (73%) and a peripheral (59%) predomi-
year-old man involved in a motor vehicle acci-      associated CT scan findings.                     nant distribution (figure 12). Usual inter-
dent. Helical CT scan (10 mm collimation)              Bronchiolitis obliterans organizing          stitial pneumonitis, or idiopathic
shows bilateral areas of GGO and consolida-
                                                    pneumonia (BOOP) is a disease charac-           pulmonary fibrosis, results in a similar
tion in a typical peripheral non-segmental dis-
tribution. There are both posterior and anterior
                                                    terized histologically by the presence of       distribution of GGO on CT scanning but
rib fractures adjacent to the sites of contusion.   granulation tissue plugs within respira-        typically with more areas of honey-
                                                    tory bronchioles and alveolar ducts, and        combing and traction bronchiectasis
peripheral ring of hemorrhage or hem-               organizing pneumonia extending into             (figure 13).
orrhagic infarction surrounding target              the surrounding alveoli.26 CT scans                 Pulmonary toxicity has been associ-
lesions of pulmonary aspergillosis (fig-             show patchy GGO (in 8 to 75% of                 ated with numerous drugs and a variety
ure 9). Several infectious and noninfec-            patients), nodules, or areas of consoli-        of radiographic and CT patterns. CT
tious causes of the CT halo sign have               dation with a predominantly peripheral          scanning shows nodular areas of GGO
since been reported.24 In most patients,            (50% of patients), bilateral, and non-          and consolidation, often with a periph-
hemorrhagic nodules can be distin-                  segmental distribution (figure 10).27-29         eral distribution.35,36
guished from nonhemorrhagic nodules                    Collagen vascular diseases are multi-            Pulmonary eosinophilia occurs with a
by the presence of a halo of GGO.                   system disorders characterized by               variety of conditions or diseases, or can
   Another cause of focal GGO, or a                 vascular changes, fibrosis, and inflam-           be idiopathic. Chronic idiopathic
nodule with a surrounding halo of GGO,              mation of connective tissue. Specific            eosinophilic pneumonia is characterized
is the post-biopsy pseudo nodule. These             diseases include progressive systemic           by multiple dense areas of opacity on
pseudo nodules have been described in               sclerosis (scleroderma), systemic lupus         chest radiographs and CT scans. In one
                                                    erythematosus, polymyositis/dermato-            study of patients with chronic
                                                    myositis, rheumatoid arthritis, and Sjo-        eosinophilic pneumonia, the most com-
 Causes of a “halo” pattern of                      gren’s syndrome. GGO is seen on CT              mon HRCT finding was GGO, usually
 GGO on CT scanning                                 scanning in 63 to 100% of these                 adjacent to areas of consolidation, with
                                                    patients,30 and is a sign of active inflam-      a peripheral distribution.37 Acute idio-
 • Invasive pulmonary aspergillosis                 mation in the absence of significant hon-        pathic eosinophilic pneumonia is char-
 • Neoplasm, hemorrhagic                            eycombing, bronchiectasis, or other             acterized by diffuse GGO and
 • Post-biopsy pseudo nodule                        signs of lung fibrosis.31                        micronodules on chest radiographs and
                                                       Pulmonary contusion results from             CT scans, often in a bronchovascular
                   Table 4                          trauma to the chest wall and lung, with         distribution.38

20                                                                                                           APPLIED RADIOLOGY, December 1998
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FIGURE 13. Usual interstitial pneumonitis.         FIGURE 14. Sarcoidosis. Image is of a 33-
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                                                         PHONE: 732-695-0600 N FAX: 732-695-9501 N EMAIL:
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