Mural stratification is the abnormal separation of the contrast-enhancing outer gut margin (serosa/muscularis propria) from the contrast-enhancing inner gut margin (Mucosa/muscularis mucosa). Although not specific, with certain disease processes it has significant clinical implications. Radiologists must be aware of the many diseases that can present with mural stratification and must be able to categorize them by their underlying cause for intestinal wall thickening.
Dr. Bender is a Radiologist with Community Radiology
Associates in Silver Spring, MD. Maj. Kende is a Pathologist in
the Department of Hepatic and Gastrointestinal Pathology, Armed
Forces Institute of Pathology, Washington, DC. Maj. McLarney is
a Radiologist at the U.S. Army Hospital, Fort Carson, CO.
An all-encompassing term, "mural stratification" means simply
the abnormal separation of the contrast-enhancing outer gut margin
(serosa/muscularis propria) from the contrast-enhancing inner gut
margin (mucosa/muscularis mucosa) (figure 1). Normally not
distinguishable, these two enhancing, concentric rings can be made
visible by interposing blood, pus, water, cells, or fat. Although a
very sensitive sign of gut abnormality, this radiographic finding
is nonspecific. One must be aware that this nonspecific appearance
may have different clinical implications depending on the disease
process with which it is associated. For example, with gut
ischemia, its presence suggests a surgical, as opposed to a
medical, approach. With idiopathic inflammatory bowel disease, its
presence indicates medical, as opposed to surgical, management. It
is important to learn of the many diseases that can present with
mural stratification and to be able to categorize them by their
underlying cause for intestinal wall thickening. The
pathophysiology of such thickening is the key to suggesting the
clinical management of this finding in any particular disease
The original description of mural stratification, called the
"double halo" sign by Frager et al in 1983, was placed into modern
context in a landmark review by Balthazar in 1991.
This appearance is visible only with cross-sectional imaging.
"Homogenous wall thickening," the double halo, and the "target
sign" are the only direct pieces of evidence radiologists have of
intestinal wall thickening.
With the widespread use of arterial phase abdominal computed
tomography (CT), which optimally demonstrates the target or double
halo sign, Gore et al
coined the phrase "mural stratification" in 1996.
The normal bowel wall resembles a wafer of five layers, which is
rarely visible on abdominal CT. The inner two layers
(mucosa/muscularis mucosa) and the outer two layers (muscularis
propria/serosa) contain a vascular architecture that consists of a
plethora of freely anastomosing vessels. There is a relative
paucity of bridging vessels that penetrate the submucosal fat and
course from the outer to the inner layers (figure 2).
Contrast enhancement of abnormally thickened gut appears as a
separate single inner and outer layer, or double halo, which
corresponds to these anastomotic beds. Logic suggests that the
target sign should be best seen during the arterial phase (figure
Mural stratification occurs when the two contrast-enhancing layers
are separated by a process that can widen the submucosal space,
such as edema, hemorrhage, inflammatory cell infiltration, or
submucosal fatty proliferation.
To date, in the Armed Forces Institute of Pathology (AFIP)
archives, there are no documented cases of malignancy directly
causing this smooth ring-like appearance. However, mural
stratification from ischemia, hemorrhage, or edema proximal to an
obstructing carcinoma or intussuscepting tumor may occur.
Categories of mural stratification
Low-density separation of the rings
The classic appearance of mural stratification, seen in
approximately 50% of patients with ulcerative colitis, is the
separation of the inner and outer contrast-enhancing layers by
low-density or water-density tissue (figure 4).
Low-density separation was reported as a finding highly
characteristic of ulcerative colitis.
It is postulated that fatty proliferation in the submucosal tissues
gives this highly characteristic appearance of mural stratification
to the rectum. The fat thought to be separating these layers is
recognizable on CT by its very low density, which is often equal in
density to the surrounding perirectal fat. The pathologists at the
AFIP have not been able to confirm the fatty nature of this
low-density tissue. Regardless, with contrast enhancement of the
inner and outer rings, there is no difficulty in recognizing the
marked contrast difference seen with mural stratification in this
low pelvic location.
The knowledge that this appearance is most often seen in ulcerative
colitis alerts radiologists to any asymmetric thickening of these
otherwise thin, concentric rings, which is suspect for lymphoma or
adenocarcinoma (figure 4B). Similar asymmetry is seen with
intussusception, which may also mimic mural stratification due to
the fat drawn into the lumen with the inner ring of involved gut.
Fortunately, intussusception is generally focal, and the more
proximal extent of the intussusception may show the lumen filled
with fat without an inner-enhancing margin (figure 5).
Inflammatory cell infiltration (intact and broken
Inflammation of the bowel wall can separate the enhancing inner
from the outer wall layers. Although not typically seen in
conditions with inflammation limited to the mucosal surface, it
does occur in ulcerative colitis, as discussed above. Mural
stratification typically occurs when the inflammatory process is
transmural (figure 6).
The prototype is Crohn's disease, of which transmural inflammation
is a hallmark. Although initially reported as being seen in only
15% of patients with Crohn's disease, others report the presence of
mural stratification in up to 50% of cases, which has also been the
authors' experience with CT-
enteroclysis (figure 1).
The intact, concentric rings of mural stratification represent
active inflammation on both CT and MR, and suggest a state of
disease amenable to medical therapy (figure 3).
The opposite condition of unenhancing, thickened gut wall usually
represents scar tissue that no longer contains enhancing vessels.
When found in patients with high-grade or complete obstructive
symptoms, stricturoplasty or surgical resection is often required
Transmural inflammation can be seen in many other inflammatory
or infectious diseases. From the AFIP archives, other examples that
have been found include
, eosinophilic enteritis, cytomegalovirus,
Shigella, Staphylococcus aureus,
(figure 8). In cases of overwhelming infection, severe inflammation
causes blurring or loss of the usually sharp inner and outer
contrast-enhancing rings (figure 9),
which is indicative of a surrounding phlegmon or abscess.
There are three notable variations of mural stratification in
patients with inflammatory cell infiltration of the bowel wall that
have been found in the archives. First, as previously mentioned, in
cases of overwhelming infection, breakdown of the usually complete
concentric ring structure may occur, signaling that surgical or
interventional management may be necessary (figure 9B). This
"broken-ring appearance" can be mimicked by lymphoma and
adenocarcinoma. whether or not it is associated with inflammation
(figure 10). Second, with overwhelming infectious disease, an
intense, "shaggy-wall" appearance can be seen. Examples of this
appearance have been noted in the archive with pseudomembranous
colitis secondary to
, amebiasis, tuberculosis (both
and avium complex) and cytomegalovirus (CMV) (figure 11). Third,
patients with intestinal parasites with wall inflammation caused by
have a "fuzzy-gut" enhancing pattern instead of distinct mural
stratification (figure 12). It is the authors' opinion that the
eggs of schistosomiasis that are discharged into the portal venous
system and come to lie within the intestinal wall cause a
generalized, partial obstruction of the small peripheral venules.
In combination with a mild inflammatory response, venule
obstruction may account for the shaggy, slightly enhancing,
obliteration of the stratified rings.
Ischemia/infarction (edema and hemorrhage)
The most important causes of ischemia infarction are: arterial
occlusion from thrombus or plaque; hypoperfusion in the face of
proximal arterial stenosis potentiated by myocardial infarction,
dehydration, bradycardia, etc.; proximal venous thrombosis or
venous occlusion from torsion or closed loop obstruction; and
Edema and hemorrhage expand the submucosal tissues following
capillary breakdown and create the classic appearance of mural
Described as homogeneous wall thickening or the target sign, mural
stratification can be seen in both cross-section and in
longitudinal fashion as a set of enhancing rings or lines separated
by tissue 10 to 40 HU in density (figure 13).
Although the interposed tissue is usually of slightly higher
density because of hemorrhage, the appearance may be identical to
that seen in inflammatory or infectious enteritis/colitis.
It is important to remember that intestinal ischemia/ infarction is
more often a surgical, as opposed to a medical, condition (figures
6 and 14).
In combination with the other signs of gut ischemia listed
below, mural stratification has a sensitivity of 90% for gut
infarction. The specificity is only 70% to 80%, as it can be seen
with varying degrees of ischemia prior to actual bowel infarction.
Therefore, emergent exploratory laparotomy is indicated in any
patient with signs of ischemia, especially with closed-loop
The clinical goal is to avoid resection of infarcted gut by
surgically relieving the cause while the gut is still viable
The association of mural stratification with free peritoneal fluid,
variable or asymmetric bowel wall enhancement, persistent
enhancement of the bowel wall or segmental arteries, visible
arterial or venous filling defects, increased density of the
mesentery, or bowel obstruction increases the sensitivity and
specificity for bowel infarction (figure 16).
Not well established in the literature is the usefulness of visible
wall hemorrhage on noncontrast CT studies in patients with ischemic
bowel (figure 17).
This appearance corresponds to the microscopic findings of ischemia
when capillary breakdown and hemorrhage are seen in the mucosal and
submucosal tissues (figure 18). It is not known to what extent
bowel can recover after such ischemic changes have begun.
Unfortunately noncontrast CT is rarely performed in patients with
suspected gut ischemia, which would be necessary to study this
interesting and potentially useful sign.
Frank hemorrhage into the gut wall has the potential to expand
the loosely organized submucosa and separate the contrast-enhancing
mucosa/muscularis mucosa from the muscularis propria/serosa.
Patients who have been anticoagulated are well known to be at
increased risk for intestinal wall hemorrhage.
Blunt trauma is another well-known cause, with submucosal
hemorrhage causing the classic "snow-cone" appearance of the
duodenum at CT.
The appearance of mural stratification as a result of blunt trauma,
although certainly possible, has not been reported. Bleeding into
the gut wall causing mural stratification has been found in the
AFIP archives among cases of thrombotic thrombocytopenic purpura
(figure 19). In the event of hemorrhage, unrelated to ischemia,
mural stratification would again suggest medical management rather
than surgical intervention. Such hemorrhagic conditions generally
resolve spontaneously with medical therapy.
The extreme of mural stratification
The accordion sign
The "accordion sign" was first described in 1991 by Fishman et
and has been used as an axial CT finding characteristic of
pseudomembranous colitis (PMC) (figure 20). Goodman
first reported this gross, irregular, polypoid thickening of the
colon wall as an axial CT finding in 1980 in a case report of PMC.
A review in 1998 by O'Sullivan
carefully spelled out the CT criteria, which this finding
"The accordion sign is a finding that may be seen on [axial]
computed tomographic (CT) scans in patients who have received oral
contrast material. It comprises alternating bands of lower
soft-tissue attenuation and higher contrast material attenuation
within the large bowel."
The author further remarked that "the accordion sign is
relatively unique to PMC [secondary to
]" and that "The sign has been further reported...as a finding
specific for PMC [secondary to
An extension of this definition has been attributed to the
ultrasound findings of pseudomembranous colitis, which could be
labeled the "ultrasound accordion sign" (figure 21A).
These authors postulated that the three-layer appearance
corresponds to "the inner hypoechoic layer [being] the edematous
mucosal layer, while the submucosal layer and muscularis propria
retain a more normal sonographic signature."
Here, the three-layered appearance of the swollen gut has resulted
in the echogenic mucosa, which resemble the bright inner margins
previously discussed as the contrast-enhancing inner layer seen
during the arterial phase on CT. From endoscopic endoluminal
ultrasound, we have learned that the echogenic inner layer
represents the mucosa, to include both its mucin surface coating
(or pseudomembrane) and the underlying lamina propria.
As severe edema extends below the mucosa, penetrating through to
the muscularis propria or serosal tissues, the usual five-layer
appearance becomes three as the echogenicity of the submucosal fat
is replaced by relatively hypoechoic edema or hemorrhage. Ischemia
and the "pseudokidney sign" of lymphoma can mimic this appearance
(figure 21C). It was originally thought that the ultrasound
appearance, in the presence of pancolitis, made the diagnosis of
pseudomembranous colitis secondary to
a high probability. Balondi et al
was the first of only two authors to include other specific
entities in the differential diagnosis. A review of colitides at
the AFIP found several cases of specific entities other than PMC
that demonstrated an accordion sign, whether or not oral contrast
Oral contrast is not necessary to demonstrate an accordion
It is true that the original accordion sign described in 1991
was limited to intraluminal contrast insinuated between edematous
folds. The inner margin was delimited by intraluminal contrast and
the outer margin by the mesenteric fat surrounding the gut. An
identical appearance is seen without intraluminal contrast when
intravenous contrast enhances the inner and outer highly perfused
margins of the gut. It is best seen during the arterial phase with
spiral CT but can be seen on traditional axial scanning early
during contrast administration (figure 22).
During the arterial phase of intravenous contrast injection,
intense edema or inflammation of the gut wall causes a wide
separation between the enhancing inner and outer layers of bowel
wall. This appearance is so similar to the original description of
the accordion sign that it should be assimilated into the
definition. As less oral or rectal contrast is used with spiral CT
in patients with acute intestinal disorders, this extreme
appearance of mural stratification may completely replace that
which was previously described on traditional axial scanners,
regardless of whether large or small bowel is involved.
is not the only cause of pseudomembranous colitis
--In the radiology literature, PMC is frequently used as a synonym
for colitis secondary to
. Boland et al,
however, correctly labeled their discussion of the CT findings as
found with "
disease of the colon," apparently realizing other entities could
cause the same appearance. This is important, as there are other
disease entities that cause pseudomembrane formation in the colon,
most notably ischemic disease of the gut.
Radiologists must not confuse or mislead their clinical
colleagues by simply using the term PMC alone even though the
diagnosis suspected is PMC secondary to
. Without a physician-to-physician agreement over such usage, the
colonoscopist can be misled! This is especially true with
teleradiology programs where a lack of familiarity with the local
physicians could lead to such a serious mistake. The critical error
PMC for ischemic PMC, which not infrequently presents with
pseudomembrane formation both in the acute and subacute phases
A delay in the diagnosis of ischemia while waiting for cultures or
while conducting a pharmaceutical trial for
PMC can be devastating.
The causes of PMC are grouped by pathologists into three
The first is the condition known to be caused by
. The second group consists of those entities where there is no
documented role for
in the disease process. Early ischemia, which is typically
pseudomembranous, is the standout in this group.
species round out this group possibly because of a more
ischemic-related pathophysiology than an inflammatory one. The
third group is composed of organisms, substances, or procedures
with an indeterminate relationship to
that have been known to cause PMC. Organisms such as
can be associated with pseudomembrane production, ostensibly
because of associated antibiotic therapy. The use of
chlorpropamide, mercuric compounds, nonsteroidal anti-inflammatory
drugs, or gold has also been reported to produce a pseudomembranous
colitis. Pseu-domembrane production may even occur after
The accordion sign is not diagnostic of
--The only authors to indicate clearly that other entities might
show a similar acute appearance were Fishman et al
and Downey and Wilson.
The former included only typhlitis or neutropenic colitis in their
while the latter used the more complete differential diagnosis of
inflammatory bowel disease, tuberculosis, lymph-angiectasia,
intramural hemorrhage, leukemic infiltration, and ischemic colitis.
The findings of Ros et al
help to limit this differential diagnosis. Of the group of diseases
they listed (i.e., radiation-induced colitis, infectious colitis,
ulcerative colitis, Crohn's disease, and [
] PMC), only the latter two had bowel wall thickening >1.0 cm.
It is present, however, in only the most severe of cases.
The pathophysiology of such an extreme in mural stratification
is thought by the authors to be caused by the rapidity of onset and
the fulminant nature of the inciting process in overcoming the
usual immune defenses, while leaving the anatomic structure of the
colon wall intact. If this is true, then any process that can
progress with great rapidity and overwhelm the homeostasis of
intestinal immunity and expand the gut wall while regarding the
normal boundaries should cause a similar appearance. Ischemia
and/or intramural hemorrhage are the most emergent examples, with a
significant potential to present in this fashion (figures 14,17,19,
and 23). As with
PMC, ischemia and hemorrhage can greatly expand the gut wall but
usually in only the most advanced of cases. Certainly other
infectious diseases and inflammatory enteritides demonstrate this
potential (figures 24 and 25). The relative incidence of these
entities as encountered by the radiologist has remained stable
while that of
PMC has fallen with the advent of prophylactic treatment for PMC in
the intensive care setting. Whether or not an accordion sign
results may well depend on the time to an accurate diagnosis.
Distinct mural stratification of the intestinal tract is a very
sensitive sign of bowel wall abnormality. Although not specific,
with certain disease processes it has significant clinical
implications and can suggest whether medical or surgical management
should be considered first. Understanding which process (i.e.,
blood, pus, water, cells, or fat), is causing the separation of the
contrast-enhancing inner and outer gut layers helps considerably in
suggesting an appropriate category of management.
The most extreme form of mural stratification is the accordion
sign. With the advent of spiral CT and the routine acquisition of
arterial-phase images during emergency CT of the gut without oral
contrast, an extended definition of the accordion sign is
appropriate (figure 22). Radiologists should stress that the
differential diagnosis of the accordion sign includes ischemic and
other infectious or inflammatory enteritides as a minimum. Simply
stating that the accordion sign is characteristic, unique, or even
PMC can be misleading and opens the potential for a delayed
diagnosis of ischemia.