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ORIGINAL RESEARCH
Dae Sik Kim, MD
Dong Gyu Na, MD
Keon Ha Kim, MD
Ji-hoon Kim, MD
Eunhee Kim, MD
Bo La Yun, MD
Kee-Hyun Chang, MD
Purpose:
Materials and
Methods:
Results:
1
From the Department of Radiology, Seoul National University College of Medicine (D.S.K., D.G.N., J.H.K., E.K.,
B.L.Y., K.H.C.), and the Department of Radiology and Center for Imaging Science, Samsung Medical Center,
Sungkyunkwan University School of Medicine (K.H.K.),
Seoul, Korea. Received November 29, 2007; revision requested February 27, 2008; revision received May 8;
accepted September 3; final version accepted December
8. Address correspondence to D.G.N., Department of
Neuroradiology, Human Medical Imaging and Intervention
Center, 12-25 Jamwon-dong, Seocho-gu, Seoul 137-902,
Korea (e-mail: [email protected] ).
Conclusion:
䡲 NEURORADIOLOGY
Distinguishing Tumefactive
Demyelinating Lesions from
Glioma or Central Nervous
System Lymphoma: Added Value
of Unenhanced CT Compared with
Conventional Contrast-enhanced MR
Imaging1
To determine retrospectively whether unenhanced computed tomographic (CT) images of the brain have added
value in distinguishing tumefactive demyelinating lesions
(TDLs) from primary glioma or central nervous system
(CNS) lymphoma, compared with conventional contrast material– enhanced magnetic resonance (MR) images only.
This study was approved by the institutional review board,
and informed consent was waived. Unenhanced CT and MR
images in 15 patients with TDLs (seven women, eight men;
mean age, 42 years; range, 27–57 years) and 48 patients with
primary brain tumor (27 women, 21 men; mean age, 48
years; range, 19 –70 years; 10 lymphomas, 38 gliomas) were
retrospectively reviewed. The CT attenuation of regions that
were enhanced or unenhanced at MR imaging was visually
categorized into three grades, and CT attenuation values
were determined quantitatively. The diagnostic accuracy
of MR imaging for differentiating TDLs from tumors was
compared with that of MR imaging plus CT.
The following MR imaging features were found more frequently in patients with TDL than in those with brain
tumor: incomplete rim enhancement, mixed T2-weighted
iso- and hyperintensity of enhanced regions, absence of a
mass effect, and absence of cortical involvement (all P
values ⬍ .05). CT hypoattenuation of MR enhanced regions was observed in 14 (93%) of 15 patients with TDL
but in only two (4%) of 48 patients with tumor. The CT
attenuation of MR enhanced regions was significantly
lower for patients with TDL than for those with tumor
(P ⬍ .001). The diagnostic accuracy of CT plus MR imaging
was significantly higher than that of MR imaging alone
(97% vs 73.0%, respectively; P ⬍ .001), and the diagnostic
accuracy of CT was significantly higher than that of unenhanced T1-weighted MR imaging (95% vs 63%, P ⬍ .001).
Unenhanced CT plus MR imaging was more accurate for
distinguishing TDLs from glioma or CNS lymphoma than
contrast-enhanced MR imaging alone.
娀 RSNA, 2009
姝 RSNA, 2009
Radiology: Volume 251: Number 2—May 2009 ▪ radiology.rsnajnls.org
467
NEURORADIOLOGY: Unenhanced CT of Tumefactive Demyelinating Lesions
T
umefactive demyelinating lesions
(TDLs) are defined as large (usually ⬎2 cm) demyelinating lesions
mimicking brain tumors; they occur as
solitary lesions or as a few separate lesions (1,2). The magnetic resonance
(MR) imaging features suggestive of
TDL include large white matter lesions
with little mass effect or vasogenic
edema (1), incomplete or open-ring enhancement (3,4), vessel-like structures
running through the center of lesions on
dynamic T2*-weighted images, and low
relative cerebral blood volume (5).
Other conventional MR imaging features of TDLs include an ill-defined or
irregular border, mass effect, perilesional edema, central necrosis, variable
enhancement, variable T2-weighted signal intensity, and involvement of gray
matter. However, these are nonspecific
MR imaging features shared by gliomas
(1,3,6–10).
MR imaging is the most sensitive
imaging technique for depicting demyelinating disease, but when a lesion
manifests as a tumefactive lesion mimicking a tumor, especially glioma or central nervous system (CNS) lymphoma,
the correct diagnosis is often not made
until after surgical biopsy or operation.
Therefore, it appears that the differentiation of TDLs and these brain tumors
by using MR imaging presents a diagnostic challenge. Several previous studies
(6,10–12) on TDL and multiple sclerosis
have reported that unenhanced computed tomography (CT) demonstrates
lesion hypoattenuation. However, to our
knowledge, the ability of CT to help dis-
Advances in Knowledge
䡲 CT hypoattenuation of MR enhancing lesions was found to be
highly specific for distinguishing
tumefactive demyelinating lesions
(TDLs) from primary gliomas or
central nervous system lymphomas.
䡲 The diagnostic accuracy of unenhanced CT for the diagnosis of
TDL was higher than that of unenhanced T1-weighted MR imaging.
468
Kim et al
tinguish TDLs from glioma or CNS lymphoma has not previously been emphasized in the literature. The purpose of
this study was to determine whether
unenhanced CT images of the brain
have added value in distinguishing TDL
from primary glioma or CNS lymphoma, compared with conventional
contrast material– enhanced MR images
only.
Materials and Methods
Institutional review board approval was
obtained for this retrospective study,
and the requirement for informed consent was waived.
Patients
Twenty-one TDLs were histologically
proved with stereotactic biopsy results
at one of two institutions (Seoul National University Hospital and Samsung
Medical Center) between December
1998 and December 2005, and 94 brain
tumors (lymphoma or glioma) were histologically proved with stereotactic biopsy or surgery results at one institution
(Seoul National University Hospital) between December 2004 and December
2005. Among these patients, we considered for inclusion in our study those who
underwent both unenhanced CT and conventional contrast-enhanced MR imaging
before biopsy or surgery. Six patients
with TDL and 46 with brain tumors were
excluded because preoperative CT images were unavailable. Therefore, 15
patients with TDLs (seven women,
eight men; mean age, 42 years; age
range, 27–57 years) and 48 patients
with brain tumors (27 women, 21 men;
mean age, 48 years; age range, 19 –70
years; 10 lymphomas, 23 high-grade gliomas, 15 low-grade gliomas) were eventually included in this study. A radiologist
Implication for Patient Care
䡲 The combination of unenhanced
CT and MR imaging provides significantly higher diagnostic accuracy for the preoperative diagnosis of TDL than conventional contrast-enhanced MR imaging alone.
(D.S.K.) with 2 years of experience in
neuroimaging chose the included patients
by reviewing medical records and imaging data.
CT Imaging
All CT scans were obtained with a helical CT scanner (Genesis HiSpeed, HighSpeed Advantage, or LightSpeed Ultra,
GE Medical Systems, Milwaukee, Wis;
or Somatom Plus, Siemens Medical Systems, Erlangen, Germany). The scanning parameters for unenhanced CT
were 120 kVp and 240 mAs with an
image matrix of 512 ⫻ 512, a 23- or
24-cm field of view, and a 5-mm section
thickness.
Conventional MR Imaging
MR imaging was performed with 1.5-T
units (Signa or CV/i, GE Medical Systems; Magnetom Vision Plus, Siemens).
Transverse and sagittal T1-weighted spinecho images were obtained at the following parameters: repetition time msec/
echo time msec, 200 – 800/15–30; field
of view, 18 –24 cm; section thickness,
3–5 mm; matrix, 256 ⫻ 256 or 256 ⫻
192; acquisition time, 2 minutes 48
seconds. Transverse T2-weighted images were obtained at the following
parameters: 3500 –5000/90 –130; field
of view, 22–24 cm; section thickness,
5 mm; matrix, 256 ⫻ 256 or 256 ⫻
192; acquisition time, 2 minutes 3 seconds or 2 minutes 47 seconds. Transverse
Published online before print
10.1148/radiol.2512072071
Radiology 2009; 251:467– 475
Abbreviations:
CNS ⫽ central nervous system
TDL ⫽ tumefactive demyelinating lesion
Author contributions:
Guarantors of integrity of entire study, D.S.K., D.G.N.,
J.H.K., E.K., B.L.Y., K.H.C.; study concepts/study design
or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final
version approval, all authors; literature research, D.S.K.,
D.G.N., J.H.K., K.H.C.; clinical studies, all authors; statistical analysis, D.S.K., D.G.N., E.K.; and manuscript editing,
D.S.K., D.G.N., J.H.K., B.L.Y.
Authors stated no financial relationship to disclose.
radiology.rsnajnls.org ▪ Radiology: Volume 251: Number 2—May 2009
NEURORADIOLOGY: Unenhanced CT of Tumefactive Demyelinating Lesions
fluid-attenuated inversion-recovery
sequences (8800 –9000/120; inversion
time, 2200 msec; field of view, 22–24
cm; section thickness, 5 mm; acquisition time, 2 minutes 39 seconds) and
contrast-enhanced transverse, sagittal, and/or coronal T1-weighted spinecho sequences (450 –540/11–20; field
of view, 22–24 ⫻ 22–24 cm; section
thickness, 5 mm) were performed after administration of gadopentetate
dimeglumine (Magnevist; Schering,
Berlin, Germany; 0.1 mmol per kilogram of body weight).
Image Analysis
MR imaging.—Two neuroradiologists
(D.G.N. and J.H.K.; with 12 and 4
years of experience in neuroimaging,
Kim et al
respectively) evaluated the MR images
independently and retrospectively. Disagreements were resolved by consensus. CT and MR images were assessed
on a picture archiving and communication system (Marotech, Seoul, Korea).
MR images were evaluated by raters
blinded to the final diagnoses and CT
findings, for the following: signal intensities on unenhanced T1- and T2weighted images for enhanced and unenhanced solid portions, enhancement
patterns, margins, cortical involvement,
mass effect, and presence of vasogenic
edema. T1-weighted lesion signal intensities were categorized as hypointense,
isointense, or hyperintense compared
with the signal intensity of white matter.
T2-weighted lesion signal intensities
were categorized as hypointense, isointense, hyperintense, or as having high
or mixed signal intensities. T2-weighted
isointensity was defined when a lesion
signal intensity was similar to that of
gray matter. High signal intensity was
defined as one similar to that of cerebrospinal fluid. Enhancement patterns
were categorized as none, focal, diffuse,
or rim enhancement (⬎180° of a ring).
The patterns of rim enhancement were
also divided into two subgroups: incomplete and complete. Margins were categorized as well or poorly defined, and
mass effects were graded as none, mild
(presence of sulcal effacement only),
moderate (presence of mild subfalcine
or uncal herniation of ⬍1 cm), or severe
(subfalcine or uncal herniation ⱖ1 cm)
Table 1
Visual Grades and Quantitative CT Attenuation Values for TDL and Glioma or Lymphoma
Visual Grade and CT Attenuation
No. of patients
Visual grade
1
2
3
CT attenuation
Attenuation (HU)
Change in attenuation (HU)
Attenuation ratio
No. of patients
Visual grade
1
2
3
CT attenuation
Attenuation (HU)
Change in attenuation (HU)
Attenuation ratio
No. of patients
CT attenuation
Attenuation (HU)
Change in attenuation (HU)
Attenuation ratio
All Tumors (n ⫽ 48)
Lymphoma (n ⫽ 10)
31
10
2 (6)
21 (68)
8 (26)
0 (0)
8 (80)
2 (20)
35.5 ⫾ 6.7
2.0 ⫾ 6.9
1.1 ⫾ 0.2
30
16 (53)
11 (37)
3 (10)
27.4 ⫾ 10
⫺8.7 ⫾ 10.1
0.8 ⫾ 0.3
48
29.5 ⫾ 7.9
⫺5.3 ⫾ 9.3
0.9 ⫾ 0.3
Tumor (n ⫽ 48)
High-Grade Glioma (n ⫽ 23)
Low-Grade Glioma (n ⫽ 15)
TDL (n ⫽ 15)
P Value*
Patients with Enhancing Lesion Components on T1-weighted MR Images (n ⫽ 45)
17
4
14
1 (6)
10 (59)
6 (35)
1 (25)
3 (75)
0 (0)
14 (100)
0 (0)
0 (0)
35.1 ⫾ 4.3
36.5 ⫾ 7.5
34.0 ⫾ 6.4
25.3 ⫾ 4.3
2.6 ⫾ 2.7
2.4 ⫾ 7.3
⫺0.5 ⫾ 3.3
⫺12.0 ⫾ 4.9
1.1 ⫾ 0.1
1.1 ⫾ 0.3
0.98 ⫾ 0.1
0.7 ⫾ 0.1
Patients with Nonenhancing Lesion Components on T1-weighted MR Images (n ⫽ 43)
2
14
14
13†
2 (100)
0 (0)
0 (0)
10 (71)
1 (7)
3 (21)
4 (29)
10 (71)
0 (0)
13 (100)
0 (0)
0 (0)
20 ⫾ 9.9
25.8 ⫾ 12
30.0 ⫾ 7.9
21 ⫾ 4.9
⫺2.0 ⫾ 4.8
⫺7.1 ⫾ 11.0
⫺4.5 ⫾ 7.8
⫺15.8 ⫾ 5.5
0.7 ⫾ 0.3
0.7 ⫾ 0.3
0.85 ⫾ 0.2
0.61 ⫾ 0.1
Whole Lesion Regions, Including both Nonenhancing and Enhancing Components (n ⫽ 62)
10
23
15
14†
32.4 ⫾ 3.8
⫺0.5 ⫾ 3.6
1.0 ⫾ 0.1
28.7 ⫾ 9.6
⫺6.4 ⫾ 11.7
0.8 ⫾ 0.3
31.3 ⫾ 7.5
⫺4.0 ⫾ 7.1
0.89 ⫾ 0.2
23.3 ⫾ 4.5
⫺13.4 ⫾ 4.8
0.67 ⫾ 0.1
⬍.001
⬍.001
⬍.001
⬍.001
.001
.009
.006
.004
.006
.009
⬍.001
Note.—For visual grades, data in parentheses are percentages. CT attenuation values are means ⫾ standard deviations. Change in CT attenuation was calculated by subtracting the attenuation
of normal gray matter (basal ganglia) from that of the lesion. CT attenuation ratio is the ratio of the attenuation for the lesion to that for normal basal ganglia.
* P values for visual grade represent comparison of the proportion of patients with grade 1 signal intensity or CT attenuation between the TDL and tumor groups. All other P values represent
comparisons of CT attenuation values between TDLs and tumors.
†
Not measured in one patient who showed no MR imaging enhancement because CT source data were not available.
Radiology: Volume 251: Number 2—May 2009 ▪ radiology.rsnajnls.org
469
NEURORADIOLOGY: Unenhanced CT of Tumefactive Demyelinating Lesions
(1). Vasogenic edema was considered
to be present when a fingerlike projected area of hyperintensity was seen
in perilesional white matter on T2weighted images. When an unenhanced
Figure 1
Figure 1: Graph of CT attenuation (HU) ratios
of TDLs and tumors. The CT attenuation ratios of
TDLs are significantly lower than those of tumors
for both MR nonenhancing and enhancing components. There is some overlap in CT attenuation
ratios for MR nonenhancing components but nearcomplete distinction between the two groups for
the MR enhancing components. Values are given
as medians (lines), 25th and 75th percentiles (box
plots), and 10th and 90th percentiles (bars).
Kim et al
T2-weighted hyperintense lesion had no
typical feature of vasogenic edema, it
was considered an unenhanced tumor
or TDL.
CT imaging.—Two raters (D.G.N.
and J.H.K.), blinded to the final diagnoses, independently evaluated the CT
images at separate sessions more than 1
month after assessing MR images.
These raters visually determined CT lesion attenuation in enhanced and unenhanced regions, as defined by postcontrast T1-weighted MR images. In determining the CT attenuation of these
lesions, regions with necrosis, hemorrhage, or typical vasogenic edema were
excluded on unenhanced T2-weighted
and postcontrast T1-weighted MR images. The CT attenuation of the lesions
was visually categorized as grade 1 (less
attenuation than cortical and basal ganglia gray matter), grade 2 (similar to
gray matter), or grade 3 (more attenuation than gray matter). When the CT
attenuation of a mass was heterogeneous, the region of higher attenuation
was used to determine the grade.
Coregistration of CT and MR images
was not performed, but the raters carefully compared each pair of CT and MR
images to minimize possible error due
to differences in section position and
scan angle based on reference to anatomic landmarks. For the quantitative
assessment of CT attenuation, one observer (D.S.K.) measured the CT attenuation (in Hounsfield units) of MR en-
Figure 2
Figure 2: MR imaging and CT findings in 54-year-old woman with glioblastoma. A, Axial T2-weighted
and, B, contrast-enhanced axial T1-weighted MR images show a round cystic mass with complete rim enhancement and peritumoral edema in the subcortical white matter of the right frontal lobe. The signal intensity
of the rim is isointense to gray matter on the T2-weighted image (arrow). C, Unenhanced axial CT image demonstrates isoattenuation (grade 2) of the rim (arrowhead).
470
hanced regions, unenhanced regions,
and whole lesion components. CT attenuation was measured for regions of interest in both lesions and contralateral
normal basal ganglia gray matter. Regions of interest were manually drawn
in lesion centers and contralateral normal basal ganglia to minimize possible
errors caused by different imaging
planes of CT and MR images. The
change in CT attenuation was calculated
by subtracting the CT attenuation of
contralateral normal basal ganglia from
that of lesions, and the CT attenuation
ratio was the ratio of the CT attenuation
value of a lesion to that of the contralateral normal basal ganglia.
Statistical Analysis
Statistical analysis was performed with
commercially available software (SPSSPC, version 12.0; SPSS, Chicago, Ill).
Sensitivity, specificity, positive and negative predictive values, and accuracy in
the diagnosis of TDLs was determined
for MR imaging alone and for the combined modalities of MR imaging and unenhanced CT. TDLs and brain tumor
groups were compared with respect to
both the interval between CT and MR
imaging and that between preoperative
CT or MR imaging and biopsy or surgery, by means of unpaired t test. The
␹2 test or the Fisher exact test was used
to compare visually graded CT attenuation values and MR imaging features,
which included lesion locations, T1- and
T2-weighted signal intensities of solid
portions, enhancing patterns, margins,
cortical involvement, mass effects, and
the presence of vasogenic edema in tumors and TDLs. The mean CT attenuation values of MR enhanced or unenhanced regions were compared with
those of contralateral basal ganglia in
TDLs by means of paired t test. The
unpaired t test was used to compare
mean values for CT attenuation, changes
in CT attenuation, and CT attenuation
ratios for patients with brain tumors
and those with TDLs. The McNemar
test was used to compare the diagnostic
values of conventional MR imaging and
combined MR imaging and unenhanced CT. Differences were considered significant when P values were
radiology.rsnajnls.org ▪ Radiology: Volume 251: Number 2—May 2009
NEURORADIOLOGY: Unenhanced CT of Tumefactive Demyelinating Lesions
less than .05. For visually assessed CT
lesion attenuation grades, interobserver
agreement was evaluated with the ␬
agreement index.
Kim et al
Figure 3
Results
Patient Demographic Data
The mean interval between CT and MR
imaging was 2.5 days ⫾ 4.5 (standard
deviation) for patients with TDL and 2.4
days ⫾ 4.2 for those with brain tumor
(P ⫽ .914). The mean duration between
preoperative CT and stereotactic biopsy
was 8.1 days ⫾ 8.8 for patients with
TDL and 10.5 days ⫾ 11.0 for those
with brain tumor (P ⫽ .441). In two
patients with TDLs, steroid therapy was
performed before biopsy. All patients
with TDL received intravenous steroid
therapy after surgical biopsy, and there
was no recurrence of symptoms or radiologic aggravation during a follow-up
period (4.2 years ⫾ 2.7).
MR Imaging Features of TDL and Glioma
or CNS Lymphoma
The T2-weighted signal intensities of
the enhancing components of the 14
TDLs were isointense (n ⫽ 3), mixed
iso- and hyperintense (n ⫽ 4), or hyperintense (n ⫽ 7); those of the 31 tumors
were mixed iso- and hypointense (n ⫽
1), isointense (n ⫽ 14), or hyperintense
(n ⫽ 16). The T2-weighted signal intensities of the unenhanced components of
the 13 TDLs were all hyperintense;
those of the 30 tumors were isointense
(n ⫽ 1), hyperintense (n ⫽ 26), or
mixed iso- and hyperintense (n ⫽ 3).
Mixed T2-weighted iso- and hyperintensity of MR enhanced regions and T2weighted hyperintensity of MR unenhanced regions, respectively, were significantly more common in patients with
TDL than in those with tumor (P ⫽ .002
and P ⫽ .024, respectively).
The unenhanced T1-weighted signal
intensities of the enhancing components
of the 13 TDLs (an unenhanced T1weighted image was not available in one
patient with TDL) were hypointense
(n ⫽ 9), isointense (n ⫽ 4), or mixed
iso- and hypointense (n ⫽ 4); those of
the 31 tumors were hypointense (n ⫽
Figure 3: MR imaging and CT findings in 30-year-old woman with TDL. A, Axial T2-weighted and, B, contrast-enhanced axial T1-weighted MR images show a round mass with complete rim enhancement and perilesional edema in left frontal white matter. The signal intensity of the rim is isointense to gray matter on the T2weighted image (arrow). C, Unenhanced axial CT image shows hypoattenuation (grade 1) of the rim; the margin of the enhanced rim on the MR image is not discernible on unenhanced CT image.
Figure 4
Figure 4: MR imaging and CT findings in 65-year-old woman with lymphoma. A, Axial T2-weighted and,
B, contrast-enhanced axial T1-weighted MR images demonstrate bilateral lesions with diffuse enhancement
in the white matter of both parieto-occipital lobes. Signal intensities of the enhancing lesions are hyperintense
on the T2-weighted image. C, Unenhanced axial CT image demonstrates isoattenuation (grade 2) of the lesion
in the left parietal lobe (arrowhead).
23), isointense (n ⫽ 4), or mixed isoand hypointense (n ⫽ 4). The T1weighted signal intensities of the nonenhancing components of the 13 TDLs
were hypointense (n ⫽ 12), isointense
(n ⫽ 1), or mixed iso- and hypointense
(n ⫽ 2); those of the 30 tumors were
hypointense (n ⫽ 21), isointense (n ⫽
1), or mixed intensities (n ⫽ 11). T1weighted hypointensity of the MR unenhanced components was significantly
more common in patients with TDL
Radiology: Volume 251: Number 2—May 2009 ▪ radiology.rsnajnls.org
than in those with tumor (12 of 14
[86%] vs 21 of 48 [44%], P ⫽ .006).
However, there was no significant difference in T1-weighted hypointensity or
isointensity of the MR enhanced components between patients with TDL and
patients with tumor (nine of 14 [64%]
vs 23 of 48 [48%] [P ⫽ .281] and four of
14 [29%] vs four of 48 [8%] [P ⫽ .069],
respectively).
The enhancement patterns in the 15
patients with TDL were none (n ⫽ 1),
471
NEURORADIOLOGY: Unenhanced CT of Tumefactive Demyelinating Lesions
Kim et al
Figure 5
Figure 5: MR imaging and CT findings in 32-year-old man with TDL. A, Axial T2-weighted and, B, contrastenhanced axial T1-weighted MR images demonstrate white matter lesions with heterogeneous enhancement in the
parietal lobe and corpus callosum. The signal intensity of the enhancing components of the right parietal lobe is
mixed (isointense plus hyperintense) on the T2-weighted image. C, Unenhanced axial CT image shows hypoattenuation (grade 1) of both the enhanced and unenhanced components of the lesions (arrows).
Figure 6
Figure 6: MR imaging and CT findings in 52-year-old man with glioblastoma. A, Axial T2-weighted and,
B, contrast-enhanced axial T1-weighted MR images show a round solid mass with diffuse enhancement and
peritumoral edema in the periventricular white matter of the left frontal lobe. C, Unenhanced axial CT image
shows hyperattenuation (grade 3) of the mass (arrow).
Figure 7
Figure 7: MR imaging and CT findings in 54-year-old man with TDL. A, Axial T2-weighted and, B, contrast-enhanced axial T1-weighted MR images show a round mass with diffuse enhancement and perilesional
edema in the white matter of the right temporal lobe. C, Unenhanced axial CT image shows hypoattenuation
(grade 1) of the mass (arrow) relative to the gray matter of the basal ganglia/cortex.
472
focal (n ⫽ 12), and diffuse (n ⫽ 2). Rim
enhancement (complete in six and incomplete in four) was found in nine of
12 patients with TDL with focal enhancement (one patient had multiple lesions with complete and incomplete rim
enhancement). The enhancement patterns in the 48 patients with tumor were
none (n ⫽ 17), focal (n ⫽ 13), and diffuse (n ⫽ 18). Complete rim enhancement was found in four of 13 patients
with tumor with focal enhancement. Focal, complete, and incomplete rim enhancement were more common in patients with TDL than in those with tumor (P ⫽ .001, .009, and .002,
respectively). The MR imaging features
of margins, the degree of mass effects,
and the presence of vasogenic edema
were not significantly different for TDLs
and brain tumors (all P values ⬎ .05).
Visual Grades and Quantitative
Assessment of CT Attenuation
Table 1 and Figure 1 demonstrate the
visual grades for CT attenuation and the
CT attenuation values of TDLs and
brain tumors. In regions of MR enhancement, grade 1 CT attenuation was
significantly more common in TDLs
than in tumors (P ⬍ .001), and grade 2
and 3 CT attenuation was found only in
tumors (Figs 2–7). In terms of the visual
assessments of the CT attenuation of
lesions, excellent agreement was found
between the two readers in the MR enhanced and unenhanced regions (␬ values, 0.885 and 0.911, respectively).
Although the CT attenuation values
of MR enhanced or unenhanced regions
were significantly lower than those of
basal ganglia in TDLs (P ⬍ .001), in
tumors the CT attenuation values of MR
enhanced regions were not significantly
different from those of basal ganglia
(P ⫽ .155). However, the CT attenuation values of MR unenhanced regions
in tumors were significantly lower than
those of basal ganglia (P ⬍ .001). The
mean values for absolute CT attenuation, change in CT attenuation, and
CT attenuation ratio were significantly
lower in TDLs than in brain tumors for
MR enhanced regions, MR unenhanced
regions, and whole lesions (all P values ⬍ .01).
radiology.rsnajnls.org ▪ Radiology: Volume 251: Number 2—May 2009
NEURORADIOLOGY: Unenhanced CT of Tumefactive Demyelinating Lesions
Kim et al
Table 2
Test Parameters of MR Imaging with Added Value of Unenhanced CT for Distinguishing TDL from Glioma or Lymphoma
MR Imaging Features or MR or CT
Criteria
Incomplete rim enhancement
Mixed T2 iso- and hyperintensity
of enhancing components
Absence of mass effect
Absence of cortical involvement
At least one MR imaging feature
At least two MR imaging
features
CT criterion*
Combined MR imaging and CT
criteria†
Tumor (n ⫽ 48)
High-Grade
Lymphoma Glioma
(n ⫽ 10)
(n ⫽ 23)
Low-Grade
Glioma
(n ⫽ 15)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
1 (2)
12 (25)
16 (33)
0 (0)
1 (10)
5 (50)
6 (60)
0 (0)
0 (0)
3 (13)
6 (26)
1 (2)
2 (4)
1 (10)
0 (0)
0 (0)
0 (0)
All (n ⫽ 48)
Sensitivity
(%)
Specificity
(%)
PPV
(%)
NPV
(%)
Accuracy
(%)
4 (27)
27
100
100
81
83
.002
0 (0)
0 (0)
4 (27)
4 (27)
4 (27)
3 (20)
12 (80)
14 (93)
27
20
80
93
100
98
75
67
100
75
50
47
81
80
92
97
83
79
76
73
.002
.039
⬍.001
...
0 (0)
1 (4)
0 (0)
1 (7)
8 (53)
14 (93)
53
93
98
96
88
88
87
98
87
95
...
...
0 (0)
0 (0)
13 (87)
87
100
100
96
97
...
TDL (n ⫽ 15)
P Value
Note.—Unless otherwise indicated, data are numbers of patients, with percentages in parentheses. NPV ⫽ negative predictive value, PPV ⫽ positive predictive value.
* Visual CT attenuation of grade 1 for MR enhancing components.
†
At least one of four MR imaging criteria plus CT criterion.
Diagnostic Value of MR Imaging and
Unenhanced CT for TDL
Table 2 demonstrates the diagnostic
value of MR imaging criteria and added
value of the CT criterion (visual grade 1
CT attenuation of MR enhanced region). The specificity and accuracy for
the diagnosis of TDL were significantly
increased by the combined modalities of
MR imaging and unenhanced CT versus
MR imaging alone with the use of at
least one of the MR imaging criteria
(P ⬍ .001). The sensitivity and accuracy
were also increased by the combined
modalities of MR imaging and unenhanced CT versus MR imaging alone
with the use of least two MR imaging
criteria, but this difference was not statistically significant (P ⫽ .125 and P ⫽
.375, respectively). The diagnostic accuracy of unenhanced T1-weighted imaging for the diagnosis of TDL was 55%
(T1-weighted hypointensity of enhanced
region) and 63% (T1-weighted hypointensity of unenhanced region).
Discussion
The results of our study suggest that
CT hypoattenuation of MR enhanced
regions is specific for distinguishing
TDLs from primary glioma or CNS
lymphoma and that the combined modalities of MR imaging and unenhanced CT are significantly more accurate than MR imaging alone for differentiating these entities. The CT
attenuation of both MR enhancing and
nonenhancing components was less
than that of cortical and basal ganglia
gray matter for all TDLs. Although the
tumors also frequently had CT hypoattenuation, this was not present in the
enhancing components on the MR images. Our data also suggest that MR
imaging features that significantly distinguish TDL include incomplete rim
enhancement (open ring), mixed T2weighted iso- and hyperintensity of
enhancing components, absence of
mass effect, and absence of cortical
involvement.
The high specificity of incomplete
rim enhancement and the absence of a
mass effect on MR images are consistent with previous studies (1,3), but
the absence of vasogenic edema was
not significantly different between
TDLs and gliomas or lymphomas. In
our study, the T2-weighted signal intensities of nonenhancing components
were hyperintense in TDLs but variable
in gliomas and lymphomas. T2-weighted
signal intensities of enhanced regions
Radiology: Volume 251: Number 2—May 2009 ▪ radiology.rsnajnls.org
were variable in both TDLs and tumors,
but mixed (iso- and hyperintense) T2weighted signal intensity of enhanced
regions was observed exclusively in
TDLs. The mixed T2-weighted signal intensity of enhanced regions of TDL
may be related to various physiopathologic changes in demyelinating
lesions (6,13,14).
Although hypointensity was the
most common T1-weighted signal intensity of TDLs, the T1-weighted signal intensity of lesions may vary depending on
the pathologic status of demyelinating
process (15–17). Because brain tumors
may have variable T1-weighted signal
intensities, depending on histologic
characteristics, there seems to be substantial overlap in T1-weighted signal
intensity between TDLs and tumors.
The MR imaging features of focal enhancement and complete rim enhancement, T2-weighted hyperintensity of
unenhanced regions, and T1-weighted
signal intensity of unenhanced regions
were not used as MR imaging diagnostic
criteria for TDL, because they were
nonspecific MR imaging features and
because they decreased diagnostic accuracy when used as diagnostic criteria.
Our quantitative CT attenuation
data showing lower CT attenuation
473
NEURORADIOLOGY: Unenhanced CT of Tumefactive Demyelinating Lesions
values for TDLs than for tumors support our results concerning the visual
grades of TDLs and also support previously reported results that showed
similar or lower CT attenuation values
for TDLs compared with white matter
(6,10–12). Although the T1- or T2weighted signal intensities of MR enhanced TDLs were variable and not
significantly different from those of tumors, CT hypoattenuation (grade 1) of
MR enhanced regions was highly specific for TDLs. This indicates that CT
hypoattenuation of MR enhanced regions is able to provide diagnostic information unavailable with MR imaging alone. Because about half of tumors with no MR enhancement may
show CT hypoattenuation similar to
that of TDLs, the added value of unenhanced CT may be limited for tumefactive lesions without contrast enhancement on MR images.
In our study, MR imaging did not
demonstrate sufficiently high diagnostic
accuracy for distinguishing TDLs from
tumors when any combination of MR
imaging criteria were used; that is, one
of the four MR imaging criteria showed
low specificity and any two of the four
MR imaging criteria showed low sensitivity, which explains the difficulty experienced in practice when differentiating
TDLs from gliomas or lymphomas with
MR imaging alone. However, our study
suggests that a combination of MR imaging and unenhanced CT provides a
high level of diagnostic accuracy for differentiating TDLs from tumors and will
help avoid unnecessary surgery in patients with TDL.
Advanced MR imaging techniques
may have a potential to help distinguish
TDLs from tumors. However, they may
not provide a complete answer to the
diagnostic question of how to distinguish TDLs from tumors. Decreased
magnetization transfer ratio (18,19), increased accumulation of N-isopropyl-p[123I]-iodoamphetamine at brain single
photon emission tomography (20), and
similar diffusion characteristics at diffusion MR imaging are found in both TDLs
and brain tumors (21,22). Because MR
spectroscopy of TDLs and tumors may
have similar findings (19,23,24) and low
474
Kim et al
cerebral blood volume on perfusion MR
images can be found in lymphomas and
low-grade gliomas, there seems to be
substantial overlap between MR spectroscopic and perfusion imaging findings in active demyelination and tumors. Therefore, unenhanced CT may
still have a cost-effective and complementary diagnostic role.
Our study had several limitations.
First, our results cannot be generalized
to brain tumors other than gliomas and
lymphomas, and our study did not assess the added value of unenhanced CT
compared with conventional MR imaging in each subcategory of brain tumors.
Second, many nonneoplastic neurologic
diseases other than TDL can mimic
brain neoplasms on MR images (25).
This study was a retrospective study of
a highly selected patient cohort, so that
the reported sensitivities and specificities may not be broadly generalizable to
a prospective clinical cohort. Third, we
did not evaluate the diagnostic accuracies of advanced imaging techniques because these MR imaging techniques
were not performed in many patients
included in this study. Fourth, coregistration of CT and MR images was not
performed for the measurement of CT
attenuation values.
In conclusion, CT hypoattenuation
of MR enhanced lesions was highly specific for distinguishing TDL from glioma
or CNS lymphoma; MR imaging plus unenhanced CT was significantly more accurate than MR imaging alone for differentiating TDL from glioma or lymphoma. This pilot finding will need to be
validated in a larger, prospective cohort.
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