Original Paper
Cerebrovasc Dis 2000;10:419423
What Constitutes a True Hyperdense
Middle Cerebral Artery Sign?
C.K. Koo a Evelyn Teasdale a Keith W. Muir b
Departments of a Neuroradiology and b Neurology, Institute of Neurological Sciences, Southern General Hospital,
Glasgow, UK
Key Words
Stroke W Computed tomography W Middle cerebral artery
Abstract
Objectives: The hyperdense MCA sign refers to an
appearance of increased attenuation of the proximal
middle cerebral artery (MCA) that is often associated
with thrombosis of the M1 MCA segment and may be the
only diagnostic feature on computed tomography early
after ischaemic stroke. False positives are recognized,
and correct recognition of this sign has, therefore, as-
sumed greater importance with the advent of thrombo-
lytic therapy for stroke. We sought to define objective cri-
teria for hyperdensity of the MCA. Methods: Brain com-
puted tomographs obtained by a standard protocol in a
neuroradiology department were analyzed by a single
observer. All consecutive scans reported as exhibiting a
hyperdense MCA were compared to controls reported as
having normal scans. Ovoid regions of interest were
placed over the vessels and cerebral cortices, and the
attenuation in Hounsfield units (HU) measured. Absolute
attenuation and ratios of one side to the other were com-
pared. Results: MCA attenuation was unrelated to age in
cases (n = 18) and controls (n = 80). The mean MCA atten-
uation was greater in the affected MCA of cases as com-
pared with controls [54.0 HU (99% confidence interval CI
46.761.2) vs. 41.3 HU (99% CI 39.743.0); p ! 0.00001].
Cases were subdivided into true and false positives by
2000 S. Karger AG, Basel
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Accepted: February 22, 2000
the ratio of denser:less dense MCA (within or without the
95% prediction interval for controls). In all true positives,
the MCA ratio was 1 1.2. 9 of 10 true positives had acute
ischaemic stroke; 1 patient had herpes simplex encepha-
litis, but had MCA attenuation within the 95% CI for con-
trols. False positives had mature cerebral infarction or
non-ischaemic pathologies. The ratio of MCA attenua-
tion to adjacent cerebral cortex was significantly higher
in both true and false positives than in controls. Conclu-
sions: Hyperdense MCAs associated with acute isch-
aemic stroke can be distinguished from normal vessels
and false positives by measurement of absolute attenua-
tion of affected and normal vessels: an absolute density
of 143 HU and a MCA ratio of 1 1.2 defined hyperdensity
and excluded all other pathologies. Confirmation in oth-
er centres is required.
Copyright 2000 S. Karger AG, Basel
Introduction
Unilateral hyperdensity of the middle cerebral artery
(MCA) on brain computed tomography (CT) is recog-
nized as one of the earliest signs of ischaemic stroke and is
thought to signify occlusive thrombus within the MCA. It
has been reported within 90 min after onset of symptoms
[1]. Recognition of such early CT features of ischaemic
stroke is of increasing therapeutic importance with the
licensing of systemic thrombolytic therapy with recombi-
Keith W. Muir, MD, MRCP
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Department of Neurology, Institute of Neurological Sciences
Southern General Hospital
Glasgow G51 4TF (UK)
Tel. +44 141 201 1100, Fax +44 141 201 2993, E-Mail k.muir@clinmed.gla.ac.uk
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Fig. 1. Example of the placement of the ROI.
nant tissue plasminogen activator in the United States
and the use of thrombolysis at stroke centres throughout
Europe and North America. Some authors [25] have
reported that the presence of this sign has a prognostic
significance in terms of subsequent morbidity and mortal-
ity.
However, we and others [68] have noted that a hyper-
dense MCA can also be seen in patients without clinical
evidence of cerebral infarction at presentation or at fol-
low-up. In the absence of an objective definition, the diag-
nosis of hyperdensity of the MCA relies upon subjective
visual recognition by reporting radiologists or neuroradio-
logists. We sought objective features of CTs reported as
showing subjective hyperdensity of the MCA.
Patients and Methods
Consecutive patients between the ages of 11 and 90 years referred
for cranial CT without a diagnosis of stroke and whose CT head scans
were reported by a consultant neuroradiologist to be normal were
prospectively identified and served as controls. Ten patients in each
decade were identified to ensure that there were no systematic age-
related changes. Unselected patients reported as having hyperdense
MCAs on their CT head scans between January 1996 and February
1998 were examined as cases. All CT head scans were carried out
using an Elscint Excel 2400 Elite CT scanner with the following pro-
tocol: 2.5 mm slice width at 5-mm intervals from foramen magnum
to the top of the petrous ridge, 5 mm slice width at 5-mm intervals
from petrous ridge to top of ventricles, and then 10 mm slice width at
10-mm intervals from ventricles to vertex.
420 Cerebrovasc Dis 2000;10:419423
Measurements were taken on an Omni Pro workstation using
magnified images. In all scans, the attenuation values in Hounsfield
units (HU) of the MCAs, basilar arteries (BAs), and cerebral cortex
adjacent to each MCA were measured by placing an ovoid region of
interest (ROI) over the appropriate areas (fig. 1). Care was taken in
particular to ensure that the boundaries of the ROI did not extend
beyond the margins of the arteries. Measurements were taken from
the M1 segments of the MCAs and the most distal visible portion of
the BA. The densest segments of the visualized arteries were mea-
sured to minimize partial volume effect. All initial measurements
were made by a single observer, and measurements were repeated in
a subset of scans 3 months later by the original observer and another
blinded observer to ascertain intra- and interobserver errors.
Inferential statistical analyses were conducted using one-way
ANOVA with post hoc multiple pairwise comparisons by the Scheff
technique.
Results
In 57 of 140 consecutive normal scans one or both
MCAs could not be identified (41%). Scans from 80 con-
trols (10 in each decade from 10 to 90 years of age) and 18
cases were studied; three normal scans were excluded by
age. Patients with hyperdense MCAs had a mean age of
49 B (SD) 22 (range 1083) years.
In control scans, the MCA attenuation did not corre-
late with age (r = 0.19). Absolute attenuation was mea-
surable in the hyperdense vessel in all cases and in the
contralateral MCA in 16 of 18 cases.
Affected MCAs in cases had a mean attenuation of
54.0 HU (99% confidence interval CI, 46.761.2) versus
41.9 HU (99% CI 37.361.1) in unaffected vessels and
41.3 HU (99% CI 39.743.0) in controls (p ! 0.0001;
fig. 2). In view of the overlap of attenuation values in
some outliers, the ratio of the denser MCA to the contra-
lateral MCA was calculated for cases and controls. Using
this MCA ratio, cases appeared to be subdivided into two
groups: those with MCA ratio within the 95% prediction
interval of controls and those outwith this prediction
interval (fig. 3 ). These were termed false and true posi-
tives, respectively. In the true-positive group, the MCA
attenuation was greater than in both controls and false
positives (p ! 0.00001 and p = 0.00018, respectively;
fig. 4). MCA attenuation in the false positives did not dif-
fer significantly from that of controls (p = 0.07). The ratio
more:less dense MCA in controls was very consistent
(coefficient of variation 6.6%), and in all true hyperdense
MCA cases the ratio was greater than 1.2. In the 2 cases in
whom the MCA ratios could not be measured, the
MCA:BA ratio was significantly higher than in controls
and was greater than 1.5 in both cases.
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Fig. 2. Attenuation of MCAs in controls and subjectively hyperdense Fig. 3. True- and false-positive hyperdense MCAs separated by ratio
cases. of more:less dense MCA versus controls.

All but 1 of the cases in the true-positive group had a

diagnosis of ischaemic stroke; the case not diagnosed as
having ischaemic stroke had herpes simplex encephalitis
and had MCA attenuation within the 95% CI for control
values. All other 9 true-positive cases had definite acute
ischaemic stroke; in addition, absence of flow in the MCA
was confirmed in all of 5 patients who underwent addi-
tional vascular imaging (angiography in 2 cases, magnetic
resonance angiography in 2, and transcranial Doppler
ultrasound in 1).
Of 9 cases in the false-positive group, 2 had cerebral
infarctions several days old, 1 had herpes simplex enceph-
alitis, 1 had polycythaemia, and 4 had no identifiable
intracranial pathology (fig. 5). The cause of subjective
MCA hyperdensity was explored with the ratio of MCA
density to adjacent cerebral cortex (fig. 6). True- and
false-positive groups both had a significantly greater ratio Fig. 4. Attenuation of MCAs in true- and false-positive groups versus
of MCA:cortex than did controls. controls.
The mean attenuation of BAs was 42.9 (range 37.2
48.6) HU in cases and 39.7 (range 37.142.4) HU in con-
trols. Values were more variable than those of MCAs in Intra- and interobserver errors were estimated from 10
both cases and controls (coefficients of variation [CV] randomly chosen cases. The mean intra-observer differ-
23.5 and 20.0%, respectively, vs. 13.8% for MCAs in con- ence in attenuation was 2.80 B (SD) 3.84 HU, the CV
trols and 15.4% for unaffected MCAs in cases) and did was 9.3%. Intra-observer error correlated with absolute
not show a consistent relationship with those of the corre- density (r = 0.46, p = 0.04). The mean interobserver dif-
sponding MCAs. This variability was caused by several ference was 1.58 B 2.61 HU, the CV was 6.4%. Interob-
outliers with markedly low attenuation values, probably server error did not correlate with density (r = 0.04, p =
reflecting measurement difficulty; when these were elimi- 0.86).
nated, the BA values were similar to those of MCAs (CV
17.0%).

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a
Fig. 5. Examples of (a) true-positive (acute
ischaemic stroke) and (b) false-positive
(herpes encephalitis) CT scans.
Fig. 6. Ratios of MCA density to adjacent cortex in true- and false-
positive groups versus controls.
Discussion
Conventional intra-arterial contrast angiography and
magnetic resonance angiography in patients with acute
stroke have associated the presence of a hyperdense MCA
on unenhanced cranial CT with the presence of thrombot-
ic arterial occlusion, usually of the M1 segment of the
MCA [5, 912]. However, subjective hyperdensity of the
MCA can also be seen in patients without evidence of
thrombosis [68]. Our results confirm that subjective
interpretation of MCA hyperdensity, even when unilater-
al, is not specific for arterial occlusion and suggest that
422 Cerebrovasc Dis 2000;10:419423
b
objective criteria can be established to define true hyper-
dense MCAs. When a combination of absolute attenuation
and the ratio of the dense MCA to the contralateral MCA
was used, we retained 100% specificity of the sign for acute
ischaemic stroke cases. In our series, values of absolute
MCA attenuation 143 HU and a ratio of more:less dense
MCA of 1.2 or higher achieved this goal. Where reliable BA
attenuation could be determined and the contralateral
MCA could not, an MCA:BA ratio 11.5 was usable. Intra-
and interobserver errors were acceptable.
Several authors [4, 10, 11, 13] have emphasized the
importance of unilateral hyperdensity of the MCA, with
respect to early confirmation of a clinical diagnosis of
ischaemic stroke and also with respect to the prognosis. In
the era of thrombolytic treatment for acute stroke, the rec-
ognition of early radiological features of ischaemia has
assumed greater importance. CT remains the most wide-
spread diagnostic tool in acute stroke, and since the pres-
ence of hyperacute extensive parenchymal low density on
CT probably mitigates against thrombolysis (as recog-
nized in the inclusion criteria for major thrombolytic
trials) [14], the hyperdense MCA sign is one of the only
CT features that can confirm a diagnosis of ischaemic
stroke in patients suitable for thrombolysis. However,
since the risk of intracerebral haemorrhage is increased
substantially by thrombolytic therapy [14, 15], it is as
important to avoid inappropriate use of recombinant tis-
sue plasminogen activator in patients without stroke as it
is to identify those who may benefit from treatment.
Whilst ideally the diagnosis of ischaemic stroke should be
confirmed by perfusion imaging techniques such as sin-
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gle-photon emission CT or perfusion magnetic resonance
imaging or major intracranial vessel occlusion demon-
strated by CT angiography, magnetic resonance angiogra-
phy, or transcranial Doppler ultrasound, these techniques
remain far less readily available than routine CT.
Patients in the false-positive group represented a heter-
ogeneous set of pathologies. They included cases of sub-
acute stroke and herpes encephalitis, in whom a contrast
effect was evident from increased density of the MCA in
relation to the adjacent cerebral cortex. The cases of
herpes encephalitis emphasize the importance of objec-
tive radiological diagnosis of the hyperdense MCA sign,
since this condition could present with signs suggestive of
stroke, when there is absence of a clear history.
Thin-section CT scanning through the ROI is impor-
tant when an accurate measurement of the attenuation
values is required. Otherwise, significant errors may be
introduced through partial volume effect. In addition,
thick sections (e.g. 510 mm) may make it difficult to
determine the course of the MCA with accuracy. Even
with this protocol, the MCA density on the normal side
could not be ascertained in 2 cases in this series, and
amongst controls, one or both MCAs could not be identi-
fied in over 40%. The majority of these scans were in
patients under 50 years of age, as would be anticipated,
since the cerebrospinal fluid spaces are smaller. In addi-
tion, there remain significant intra-observer measure-
ment errors that become larger the further the attenuation
strays from the mean. The error can be reduced by use of
ratios.
Yock [16] presented 4 patients in whom small focal
densities were noted along the expected courses of cere-
bral arteries (anterior cerebral arteries in 2 patients and
MCAs in 2). Peak attenuation values ranged from 84 to
214 HU. They were interpreted as calcified emboli. In the
study of Schuknecht et al. [17], a density range of 77
89 HU was obtained for the vessel segments recognized as
subjectively dense, and 4253 HU for normal arteries. In
both instances, these values were higher than the mea-
surements we obtained. Methodological differences may
explain this variation e.g. three adjacent ROIs of one
pixel size were targeted to the relevant vessel segments by
Schuknecht et al. [17]. In our patients, we found this
method to lead to substantial variation in density mea-
surements for each vessel, and we, therefore, feel the use
of the larger ovoid ROI to be more reproducible. Ascer-
tainment of normal ranges of MCA density in other insti-
tutions is required, however, before our results could be
translated into routine clinical practice.
The suggested criteria based upon our observations
require to be tested prospectively to determine their sensi-
tivity and specificity.

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