Neuroradiology

DOI 10.1007/s00234-017-1851-x

DIAGNOSTIC NEURORADIOLOGY

Differential diagnosis of oligodendroglial and astrocytic

tumors using imaging results: the added value of perfusion MR
imaging
Hyun Jung Yoon 1,2 & Kook Jin Ahn 2 & Song Lee 2 & Jin Hee Jang 2 & Hyun Seok Choi 2 &
So Lyung Jung 2 & Bum Soo Kim 2 & Shin Soo Jeun 3 & Yong Kil Hong 3

Received: 13 February 2017 / Accepted: 15 May 2017

# Springer-Verlag Berlin Heidelberg 2017

Abstract involvement ratio was 0.796. The combination of all three

Purpose The purposes of the present study are to assess
whether different characteristics of oligodendrogliomas and
astrocytic tumors are visible on MR imaging and to determine
the added value of perfusion imaging in conventional MR
imaging when differentiating oligodendrogliomas from astro-
cytic tumors.
Methods We retrospectively studied 22 oligodendroglioma and
54 astrocytic tumor patients, including glioblastoma multiforme
(GBM). The morphological tumor characteristics were evaluat-
ed using MR imaging. The rCBV, Ktrans, and Ve values were
recorded. All imaging and clinical values were compared. The
ability to discriminate between the two entities was evaluated
using receiver operating characteristic curve analyses. Separate
comparison analysis between oligodendroglioma and astrocytic
tumors excluding GBM was also performed.
Results The presence of calcification, higher cortex involve-
ment ratio, and lower Ve value were more representative of
oligodendrogliomas than astrocytic tumors (P = <0.001,
0.038, and <0.001, respectively). The area under the curve
(AUC) value of a combination of calcification and cortex
* Kook Jin Ahn
ahn-kj@catholic.ac.kr
1
Department of Radiology and Center for Imaging Science, Samsung
Medical Center, Sungkyunkwan University School of Medicine,
Gangnam-gu Seoul, Republic of Korea
2
Department of Radiology, College of Medicine, Seoul St. Mary’s
Hospital, The Catholic University of Korea, 505, Banpo-dong,
Seocho-gu, Seoul 133-701, Republic of Korea
3
Department of Neurosurgery, College of Medicine, Seoul St. Mary’s
Hospital, The Catholic University of Korea, Seoul, Republic of
Korea
parameters, including Ve, further increased the diagnostic per-
formance (AUC = 0.881). Comparison test of the two AUC
areas revealed significant difference (P = 0.0474). The pres-
ence of calcification and higher cortex involvement ratio were
the only findings suggestive of oligodendrogliomas than as-
trocytic tumors with exclusion of GBMs (P = 0.014 and
<0.001, respectively).
Conclusion Cortex involvement ratio and the presence of cal-
cification with Ve values were diagnostically accurate in iden-
tifying oligodendrogliomas. The Ve value calculated from dy-
namic contrast-enhanced MR imaging could be a supportive
tool for differentiating between oligodendrogliomas and astro-
cytic tumors including GBMs.
Keywords Oligodendroglioma . Magnetic resonance
imaging . Dynamic contrast-enhanced MR imaging . Ktrans . Ve
Introduction
Oligodendroglioma is the third most common glioma and ac-
counts for 5–20% of all glial tumors [1–3]. Differential diag-
nosis of these tumors has become increasingly important with
the recognition that oligodendrogliomas are uniquely sensitive
to chemotherapy and typically present a more indolent clinical
course and prolonged survival compared with astrocytic tu-
mors of the same grade [4–6]. Magnetic resonance (MR) im-
aging is the best currently available technique to diagnose
oligodendrogliomas. Studies have evaluated conventional
MR imaging, including the peripheral location and calcifica-
tions, for its ability to differentiate oligodendrogliomas
[7–12]. Despite the identification of several characteristic fea-
tures, anatomic MR imaging is not sufficiently specific to
permit a confident differentiation between glioma subtypes.
 Neuroradiology

Perfusion MR imaging, dynamic contrast-enhanced addition to histology were used in the diagnostic process for
(DCE), and dynamic susceptibility contrast-enhanced (DSC) oligodendroglioma according to the 2016 WHO classification
MR imaging are emerging tools for the assessment of tumor of central nervous system tumors [22]. The 22 patients with
angiogenesis. The use of a combination of these non-invasive histologically low- and high-grade oligodendrogliomas or
parameters, including the relative cerebral blood volume oligoastrocytomas were 1p/19q-codeleted, and these patients
(rCBV) as assessed by DSC MR imaging, which measures were diagnosed as oligodendroglioma, since genotype trumps
the remaining levels of contrast medium in the vasculature, histological phenotype for discordant results [22]. None of the
and the volume transfer coefficient (Ktrans) and the extravas- patients had a clinical history of previous surgery, chemother-
cular extracellular distribution volume (Ve) derived from DCE apy, or radiation therapy. All patients underwent DCE and DSC
MR imaging, which describe the tumor microvasculature by MR using 3-T MR imaging. Non-contrast brain CT was eval-
measuring a range of parameters that reflect specific physio- uated in all patients. Of the 22 oligodendroglioma patients, 15
logical characteristics, has been reported to increase the diag- were low-grade (WHO II) and 7 were high-grade (WHO III).
nostic accuracy of glioma grading [13–15]. A few studies Of the 54 astrocytic tumor patients, 8 were diffuse astrocytomas
have demonstrated the usefulness of perfusion-weighted im- (WHO II) and 46 were high-grade which were composed of 5
aging in histopathological differentiation between astrocytic anaplastic astrocytomas (WHO III) and 41 GBMs (WHO IV)
and oligodendroglial tumors [16, 17]. Recent several studies (Table 1).
have reported that multimodal MR imaging (diffusion, perfu-
sion, and spectroscopy) improved the accuracy in grading of
the oligodendrogliomas and predictability of 1p/19q MR imaging protocol
codeletion status [18–21]. However, these studies only com-
pared imaging features between these two tumors in same- All MR imaging studies were performed using a 3-T unit
grade cases, with exclusion of glioblastoma multiforme (Verio; Siemens Healthcare, Erlangen, Germany), and con-
(GBM), or have been conducted under previous (2007) ver- ventional and perfusion MR images were obtained during
sion of World Health Organization (WHO) classification the same session. The MR imaging protocol included the fol-
which did not reflect 1p/19q codeletion status for lowing sequences: T1-weighted images [gradient-echo,
oligodendrogliomas. 250 ms repetition time (TR)/3.5 ms echo time (TE), 70° flip
Therefore, in this study, we retrospectively evaluated the angle, 220 × 220 field of view (FOV), 5-mm section thick-
imaging features of oligodendrogliomas and astrocytic tumors ness], T2-weighted images (turbo spin-echo, 5500-ms TR/93-
and performed a comparative study between the two tumor ms TE, echo-train factor = 18, 150° flip angle, 220 × 220 FOV,
types using multiple imaging parameters evaluated with 3-T
MR imaging, including DCE and DSC MR imaging, based on Table 1 Demographics and histological characteristics of the study
new 2016 WHO classification system. The purposes of this subjects
study were to determine if there are clear differences between Demographic features Values
oligodendrogliomas and astrocytic tumors on 3-T MR imag-
ing and to determine the added value of perfusion imaging in Mean age ± SD (years) 52.2 ± 17.1 (16–82)
differentiating oligodendrogliomas from astrocytic tumors. Sex
Male 34 (45)
Female 42 (55)
Materials and methods Tumor histology (n = 76)
Oligodendroglioma (n = 22)
Patients Low grade
Oligodendroglioma 15 (68.2)
This study was approved by the Institutional Review Board of High grade
Seoul St. Mary’s Hospital, which allowed us to waive the re- Anaplastic oligodendroglioma 7 (31.8)
quirement for patient informed consent for this retrospective Astrocytic tumor (n = 54)
investigation. From January 2009 to December 2015, we con- Low grade
secutively collected 22 patients (9 males and 13 females, mean Diffuse astrocytoma 8 (14.8)
age = 45 years, range = 28–73 years) with histologically con- High grade
firmed oligodendroglioma cases and 54 patients with astrocytic Anaplastic astrocytoma 5 (9.3)
tumor cases (25 males and 29 females, mean age = 53 years, Glioblastoma multiforme 41 (75.9)
range = 16–82 years), including GBM as classified by an ex-
perienced neuropathologist according to the new WHO classi- The numbers in parentheses are the range or the percentage
fication. Molecular parameters such 1p/19q codeletion status in SD standard deviation
Neuroradiology
5-mm section thickness), fluid-attenuated inversion recovery
[FLAIR; 9000-ms TR/2500-ms inversion time (TI), 95-ms
TE, echo-train factor = 12, 150° flip angle, 220 × 220 FOV,
5-mm section thickness], and DCE and DSC MR imaging. All
patients underwent both DCE and DSC MR imaging.
Dynamic contrast-enhanced MR imaging
To acquire the T1-weighted dynamic data set, VIBE (4.3-ms
TR/1.5-ms TE, 15° flip angle, NEX = 1, 4-mm section thick-
ness, 250 × 250-mm FOV, 192 × 138-mm matrix size, number
of phases = 50) was performed. At the fourth acquisition, a
0.1 mmol/kg body weight dose of gadobutrol (Gadovist,
Bayer Healthcare, Berlin, Germany) was administered intra-
venously with the aid of a power injector at a rate of 3 ml/s,
followed by a bolus injection of 25 ml of saline. A series of
1000 images at 50 time points for 20 sections were acquired
with a temporal resolution of approximately 5.5 s.
Dynamic susceptibility contrast MR imaging
DCE MR and DSC MR images were obtained. For DSC MR
imaging, dynamic T2*-weighted images were acquired using
a gradient-echo echo-planar imaging pulse sequence (1880-
ms TR/30-ms TE, 90° flip angle, NEX = 1, 5-mm section
thickness, 25 sections, 230 × 230-mm FOV, 128 × 128-mm
matrix size). After the patients underwent a baseline period of
four imaging volumes (7.6 s), a rapid bolus of contrast agent
was administered intravenously through an 18-G intravenous
catheter at a rate of 3 ml/s using a power injector (Spectris
Solaris, Medrad, Warrendale, USA) and was immediately
followed by a 25-ml saline flush at the same rate. The DSC
data collection comprised a total of 60 series (1 min 58 s).
Gadobutrol was injected at a dose of 0.15 mmol/kg body
weight.
Image analysis
Two radiologists (HJY and KJA) with 6 and 18 years of ex-
perience in neuroimaging reviewed the MR images. During
the retrospective review, the images were read simultaneously.
The two radiologists evaluated the tumors in terms of size,
cortex involvement ratio, the presence of edema, contrast en-
hancement, the heterogeneity of the T2-weighted image, cal-
cification, hemorrhage, and midline cross. The presence or
absence of calcification and hemorrhage was evaluated using
CT in addition to the MR imaging. To assess size, edema,
contrast enhancement, heterogeneity of the T2-weighted im-
age, hemorrhage, and midline cross, the Visually AcceSAble
Rembrandt Images (VASARI) feature set was used: the size of
the overall region of FLAIR hyperintensity (long and axis
diameters in the axial plane); proportions of the edema,
contrast-enhancing component, and evidence of hemorrhage;
and contrast-enhancing tumor and/or non-contrast-enhancing
tumor crossing the midline [23]. The proportions of the ede-
ma, enhancement, and heterogeneity on the T2-weighted im-
age were stratified as <5, 5–33, 34–67, 68–95, and >95%
according to the VASARI criteria. Then, as for edema, con-
trast enhancement, and heterogeneity on the T2-weighted im-
age, we divided the patients into two groups: B<34%^ was
designated the Babsence^ group and B≥34%^ was designated
as the Bpresence^ group. The decisions regarding the conven-
tional imaging features were determined by consensus with
the exception of the cortex involvement ratio. The cortex in-
volvement ratio was expressed as the ratio of the cortex/total
perimeter and was measured independently by the two radiol-
ogists. The mean value of the cortex involvement ratio mea-
sured by the two radiologists was used in the analysis.
The DSC and DCE images were processed using a com-
mercial software package (Nordic ICE, Nordic NeuroLab,
Bergen, Norway). The perfusion parametric maps were ob-
tained, and the CBV map from DSC MR imaging and two
parametric maps from the DCE MRI, the volume transfer
constant, Ktrans, and the fractional volume of the extravascular
extracellular space, Ve, were used [24, 25]. For the DSC MR
imaging, contrast leakage correction as described by
Boxerman et al. was used, and the rCBV was computed via
numeric integration of the curve [26]. Normalization of the
CBV to globally determined mean value was performed auto-
matically by the software. The global mean value is calculated
from all pixels determined to represent normal brain tissue,
excluding noisy and otherwise abnormal dynamic curves. For
the DCE MRI, a perfusion analysis method based on the two-
compartment extended Tofts model was used [24]. The base-
line T1 value was fixed at 1000 ms in this study [27–29]. For
each tumor, the arterial input function was determined in the
intracranial tumor-supplying artery in the region of interest
(ROI). Two neuroradiologists (HJY and KJA) manually de-
fined the ROIs by consensus in the T2WI and coregistered
parametric maps.
Data management and statistical analysis
1. Comparison and univariate analyses
The patients were divided into the following two groups:
the oligodendroglioma group and the astrocytic tumor group.
The conventional MR imaging variables were size, mean cor-
tex involvement ratio, the presence of edema, contrast en-
hancement, heterogeneity on T2-weighted imaging, calcifica-
tion, hemorrhage, and midline cross. The DCE and DSC MR
imaging variables were mean values of rCBV, Ktrans, and Ve.
The intraclass correlation coefficients were calculated as an
index of inter-observer reliability for the cortex involvement
ratio. The aforementioned variables were compared between
the two groups using univariate analysis via the Mann-

Whitney test for numerical values and Fisher’s exact test for
categorical values.
2. Multivariate and receiver operating characteristic curve
analysis
The cutoff values for mean Ktrans and Ve were determined
via receiver operating characteristic (ROC) curve analysis,
and the mean Ktrans and Ve values were then converted from
decimals to binary numbers to create categorical values.
Subsequently, the statistically significant variables were sub-
jected to a multiple logistic regression analysis using forward
stepwise variable selection. Statistically significant variables
were defined as those with a P value less than 0.1. The area
under the curve (AUC) values for the discrimination between
oligodendroglioma and astrocytic tumor were calculated for
the parameters that were statistically significant. AUC values
were compared with each other using a non-parametric ap-
proach [30].
3. Comparison between the oligodendrogliomas, grade II/III
astrocytomas, and GBMs
We additionally performed separate analysis to inspect the
results when GBMs were separated from astrocytoma group.
All patients were divided into the following three groups:
oligodendroglioma group, grade II and III (hereafter, II/III)
astrocytoma group, and GBM group. The Kruskall-Wallis test
and Pearson’s chi-square test were used to determine the dif-
ferences of numerical variables and categorical variables, re-
spectively, among the three groups. For multiple comparisons,
the Mann-Whitney U test, Pearson’s chi-square, or Fisher’s
exact test was performed. Bonferroni correction was consid-
ered for revision of the results.
4. Blind tests before informing and after informing the re-
sults of the study
We added blind tests to record how many cases the readers
misdiagnosed oligodendrogliomas as GBMs or GBMs as
oligodendrogliomas before they were informed with our re-
sults and to determine the added values of our results for
discriminating oligodendrogliomas from anaplastic astrocyto-
mas and GBMs. For this blind test, a neuroradiologist with
10 years of experience and two resident physicians with 4-
and 3-year radiology experience were recruited. First, they
were asked to choose between oligodendroglioma and high-
grade astrocytoma in randomly selected 35 cases of
oligodendrogliomas (grade II 10 cases and III 6 cases) and
high-grade astrocytomas (anaplastic astrocytoma 3 cases and
GBM 16 cases). Second, the recruited readers were asked to
discriminate oligodendrogliomas from high-grade astrocyto-
mas in the same manner as above after being informed with
Neuroradiology
our results. Sensitivity and specificity were calculated for each
blind test, and the statistical difference between the first and
second tests was tested using the McNemar test. A P value
<0.05 was considered statistically significant. The statistical
analyses were performed with SPSS version 18 statistical soft-
ware for Windows (SPSS; SPSS Inc.; Chicago, IL, USA).
Results
Comparison and univariate analyses
There was no difference between the oligodendroglioma
(n = 22) and astrocytic tumor (n = 54) groups with regard to
sex (P = 0.737), but the patients with oligodendrogliomas were
significantly younger than those with astrocytic tumors (mean
age, 53 for astrocytic tumors and 45 for oligodendrogliomas,
P = 0.012). Additionally, no significant differences were found
between the two groups in terms of lesion size, the presence of
hemorrhage, midline cross, or T2 heterogeneity (P = 0.514,
0.762, 0.220, and 0.386, respectively), whereas the presence
of calcifications, cortex involvement ratio (cortex/total perime-
ter), edema, and enhancement were significantly different be-
tween the two groups (P = <0.001, 0.04, 0.012, and <0.001,
respectively). Overall, the oligodendroglioma group tended to
more frequently demonstrate intratumoral calcification and a
higher cortex involvement ratio than the astrocytic tumor group
(Fig. 1). The oligodendroglioma group had less edema and
enhancement than the astrocytic tumor group (Table 2). The
intraclass correlation coefficient for the cortex involvement ra-
tio showed almost perfect agreement (0.822).
Among the DCE and DSC MR imaging parameters, the
mean Ktrans and Ve values were significantly higher in the
astrocytic tumor group than in the oligodendroglioma group
(P = 0.001 and <0.001 for mean Ktrans and Ve, respectively).
However, there was no significant difference in the rCBV
value between the two groups (P = 0.087) (Table 2 and Fig. 2).
Multivariate and receiver operating characteristic curve
analysis
The optimal cutoff value was 0.022 for mean Ktrans with
62.1% sensitivity and 74.5% specificity. For mean Ve, the
optimal cutoff value was 9.97 with 75.9% sensitivity and
65.5% specificity. In the multiple logistic regression analy-
sis, clinically and statistically significant (P < 0.1) values
were selected as the input variables: age, the presence of
calcification, edema, enhancement, the cortex involvement
ratio, and the binary values of mean Ktrans and Ve. The pres-
ence of calcification, the cortex involvement ratio, and
Ve were independent variables for discriminating between
oligodendrogliomas and astrocytic tumors (Table 2).
The AUC value of a combination of two parameters,
Neuroradiology
Fig. 1 Representative CT and
MR images of a low-grade (WHO
grade II) oligodendroglioma.
Non-enhanced CT (a) and axial
T2-weighted images (b) of a low-
grade oligodendroglioma
demonstrating calcification
within the tumor and wide
involvement in the cortex and
subcortical white matter
calcification and the cortex involvement ratio, was 0.796,
and the combination of all three parameters, including Ve,
increased the diagnostic performance even further
(AUC = 0.881) (Fig. 3). Comparison of the ROC curves
to test the statistical significance of the difference between
the two AUCs revealed that the two compared areas are
significantly different (P = 0.0474).
Comparison between the oligodendrogliomas, grade II/III
astrocytomas, and GBMs
The comparison of the clinical and imaging characteristics
between the oligodendroglioma group, grade II/III astrocyto-
ma group, and GBM group is summarized in Table 3. The
oligodendroglioma and grade II/III astrocytoma groups were
significantly younger than GBM group (P = 0.002 and 0.001,
respectively). The oligodendroglioma group showed higher
prevalence of intratumoral calcifications and a higher cortex
involvement ratio than the grade II/III astrocytoma and GBM
groups (P = 0.014 and 0.001 for calcification, P < 0.001
for cortex involvement ratio). The GBM group showed
higher prevalence of edema and enhancement than the
oligodendroglioma and grade II/III astrocytoma groups
(P = 0.004 and <0.001 for edema, P < 0.001 for enhance-
ment). There were no significant differences in sex, tumor
size, presence of hemorrhage, midline cross, and T2 hetero-
geneity among the three groups (P = 0.595, 0.692, 0.784,
0.257, and 0.108, respectively). The DCE and DSC MR im-
aging parameters, the mean Ktrans, Ve, and rCBV values were
significantly higher in the GBM group than in the
oligodendroglioma and grade II/III astrocytoma group
(P < 0.001 for Ktrans, P < 0.001 for Ve, and P = 0.008 and
0.005 for rCBV, respectively). However, these parameters
demonstrated no significant difference between the
oligodendroglioma group and grade II/III astrocytoma group
(P = 0.505 for Ktrans, P = 0.673 for Ve, and P = 0.347 for rCBV,
respectively).
Blind tests before informing and after informing
the results of our study
The radiologists with shorter experience showed higher rates
of misdiagnosis. However, after being informed with the re-
sults of our study, the rate of correct diagnosis has sharply
increased (Table 4). The differences in sensitivities between
before and after being informed in resident physicians were
statistically significant (P = 0.016 and 0.002 in resident phy-
sician with 4- and 3-year radiology experience, respectively).
The highly trained neuroradiologist also showed better result
after being informed; however, it was not statistically signifi-
cant (s 4).
Discussion
Differentiating oligodendrogliomas from astrocytic tumors is
becoming clinically important because patients with
oligodendrogliomas are more likely to respond to chemother-
apy and typically present a more indolent clinical course and
prolonged survival than patients with astrocytic tumors of
comparable malignancy grades [4–6]. However, neither clear
imaging diagnostic criteria nor reliable imaging biomarkers
exist for oligodendroglioma; in part, diagnosis rests on sub-
jective criteria. Although histopathological evaluation remains
the reference standard for glioma subtyping, this method is
limited because the histologic information obtained from bi-
opsies is often derived from only a small portion of a generally
heterogeneous tumor. The classification and grading of glio-
mas on MR images can be helpful, but the differentiation of
oligodendrogliomas from astrocytic tumors, even with ad-
vanced MR imaging techniques, remains unreliable, because
previous reported studies have been conducted under previous
(2007) version of World Health Organization (WHO) classi-
fication which did not reflect 1p/19q codeletion status for
oligodendrogliomas.
Table 2 Univariate and multivariate logistic analyses to determine clinical and MR imaging parameters for the differentiation of oligodendrogliomas and astrocytic tumors

Variables Oligodendrogliomas (n = 22) Astrocytic tumors (n = 54) Univariate Multivariate

Total WHO II WHO III Total WHO II WHO III WHO IV P value P value OR 95% CIs

Mean age 45.4 ± 12.5 42.1 ± 12.5 49.6 ± 11.5 53.3 ± 18.2 39.1 ± 19.8 38.2 ± 10.7 57.9 ± 16.3 0.012
(years) ± SD (28–73) (28–73) (38–63) (16–82) (21–82) (29–53) (16–82)
(range)
Sex (M/F) 9:13 7:8 2:5 25:29 2:6 3:2 20:21 0.737
Size (mm) 48.1 ± 22.9 46.2 ± 24.9 52.4 ± 18.5 45.9 ± 16.0 47.8 ± 29.7 48.2 ± 13.7 45.2 ± 14.8 0.514
Edema 0.012
Yes 10 (45.5) 7 (46.7) 3 (42.9) 37 (68.5) 0 (0) 2 (40) 35 (85.4)
No 12 (54.5) 8 (53.3) 4 (57.1) 17 (31.5) 8 (100) 3 (60) 6 (14.6)
Calcification <0.001 <0.001 9.43 2.02–43.48
Yes 10 (45.5) 6 (40) 4 (57.1) 4 (7.4) 1 (12.5) 0 (0) 3 (7.3)
No 12 (54.5) 9 (60) 3 (42.9) 50 (92.6) 7 (87.5) 5 (100) 38 (92.7)
Enhancement <0.001
Yes 7 (31.8) 4 (26.7) 3 (42.9) 42 (77.8) 2 (25) 3 (60) 37 (90.2)
No 15 (68.2) 11 (73.3) 4 (57.1) 12 (22.2) 6 (75) 2 (40) 4 (9.8)
Hemorrhage 0.762
Yes 5 (22.7) 3 (20) 2 (28.6) 17 (31.5) 0 (0.0) 2 (40.0) 15 (36.6)
No 17 (77.3) 12 (80) 5 (71.4) 37 (68.5) 8 (100.0) 3 (60.0) 26 63.4)
Midline cross 0.220
Yes 6 (27.3) 2 (13.3) 4 (57.1) 11 (20.4) 1 (12.5) 3 (60.0) 7 (17.1)
No 16 (72.7) 13 (86.7) 3 (42.9) 43 (79.6) 7 (87.5) 2 (40.0) 34 (82.9)
T2 heterogeneity 0.386
Yes 19 (80.8) 12 (80) 7 (100) 46 (85.2) 3 (37.5) 5 (100.0) 38 (92.7)
No 3 (19.2) 3 (20) 0 (0) 8 (14.8) 5 (62.5) 0 (0.0) 3 (7.3)
Cortex involvementa 0.30 ± 0.09 0.27 ± 0.10 0.33 ± 0.086 0.27 ± 0.08 0.27 ± 0.07 0.26 ± 0.11 0.27 ± 0.08 0.04 0.038 2.16 1.305–3.577
(cortex/total
perimeter)
Ktrans (mean) 0.03 ± 0.05 0.03 ± 0.02 0.05 ± 0.06 0.06 ± 0.05 0.03 ± 0.02 0.02 ± 0.02 0.07 ± 0.06 0.001
Ve (mean) 10.0 ± 10.1 8.2 ± 3.8 13.6 ± 16.4 27.3 ± 36.3 8.4 ± 3.5 6.2 ± 2.8 33.7 ± 39.8 <0.001 <0.001 16.13 3.53–76.93
rCBV (mean) 1.92 ± 0.65 1.92 ± 0.64 1.93 ± 0.71 2.48 ± 1.40 1.55 ± 0.37 1.59 ± 0.83 2.78 ± 1.47 0.087

All values are presented as the mean ± SD or the number (%) unless otherwise indicated. Data in italics are p-values less than < 0.05 in Univarite analysis
SD standard deviation, OR odds ratio, CI confidence interval
a
Mean of the two values reported by the two radiologists
Neuroradiology
Neuroradiology
Fig. 2 Representative MR images with perfusion and T2-weighted
images of an anaplastic oligodendroglioma and glioblastoma multiforme
(GBM). From left to right, the T2-weighted image, CBV, Ktrans, and Ve
map examples are displayed for comparison. a Anaplastic
oligodendroglioma (WHO grade III) demonstrates a faint focal increase
In our study based on new WHO classification system, dif-
ferentiation between oligodendrogliomas and astrocytic tumors
Fig. 3 Receiver operating characteristic curves for discriminating
between oligodendrogliomas and astrocytic tumors using the
parameters of presence of calcification and the cortex involvement ratio.
The results of analyses are shown with or without Ve. The AUC was
significantly higher for the combination that included Ve (0.881)
compared to without Ve (0.796)
in the CBV value at the periphery of the tumor. Maps from dynamic
contrast-enhanced MR images show a moderate increase in Ktrans and a
minimal increase in the Ve value. b All values are markedly increased in
GBM
was possible by conventional and DCE-MR imaging. Still, the
characteristic imaging findings of oligodendrogliomas reported
in previous studies under 2007 WHO classification were also
observed. Basically, such tumors presented as round or oval
masses involving the cortex or subcortical white matter, and
calcification was frequently observed, as previous reports noted
in 20–91% of cases [8, 11, 12]. Occasionally, cystic degenera-
tion and hemorrhage were observed. Additionally, ill-defined
enhancement following intravenous contrast material adminis-
tration was observed in some oligodendrogliomas and was as-
sociated with higher-grade tumors, similar to the results of prior
studies [8, 31, 32]. Characteristic conventional imaging find-
ings, such as the higher cortex involvement ratio and the pres-
ence of calcification, significantly differed in the comparative
analysis between oligodendrogliomas and astrocytic tumors in
this study. The patients in the oligodendroglioma group were
significantly younger than in the astrocytic tumor group, which
is also in line with previous reports. Moreover, the AUC value
of a combination of conventional MR imaging features, includ-
ing the presence of calcification and the cortex involvement
ratio, was 0.796, which indicates that the combination of two
parameters provides good diagnostic performance for discrim-
inating between oligodendrogliomas and astrocytic tumors.
In this study, DCE-MR imaging was useful for differenti-
ating oligodendrogliomas from astrocytic tumors. Univariate
analysis showed significant differences in mean values of
Table 3 Comparison of the clinical and imaging characteristics between the oligodendroglioma, grade II and III astrocytoma, and GBM

Variables Oligodendrogliomas Grade II/III astrocytoma GBM (n = 41) P valueb P value (oligo)/(GII/III astro)c P value (oligo)/(GBM)c P value (GII/III astro)/(GBM)c
(n = 22) (n = 13)

Mean age (years) ± SD 45.4 ± 12.5 (28–73) 38.7 ± 15.25 (21–82) 57.9 ± 16.3 (16–82) <0.001 0.104 0.002 0.001
(range)
Sex (M/F) 9:13 5:8 20:21 0.595
Size (mm) 48.1 ± 22.9 48 ± 21.7 45.2 ± 14.8 0.692
Edema <0.001 0.116 0.004 <0.001
Yes 10 (45.5) 2 (15.4) 35 (85.4)
No 12 (54.5) 11 (84.6) 6 (14.6)
Calcification 0.001 0.014 0.001 1
Yes 10 (45.5) 1 (7.7) 3 (7.3)
No 12 (54.5) 12 (92.3) 38 (92.7)
Enhancement <0.001 0.726 <0.001 <0.001
Yes 7 (31.8) 5 (38.5) 37 (90.2)
No 15 (68.2) 8 (61.5) 4 (9.8)
Hemorrhage 0.784
Yes 5 (22.7) 2 (15.4) 15 (36.6)
No 17 (77.3) 11 (84.6) 26(63.4)
Midline cross 0.257
Yes 6 (27.3) 4 (30.8) 7 (17.1)
No 16 (72.7) 9 (69.2) 34 (82.9)
T2 heterogeneity 0.108
Yes 19 (80.8) 8 (61.5) 38 (92.7)
No 3 (19.2) 5 (38.5) 3 (7.3)
Cortex involvementa 0.30 ± 0.09 0.27 ± 0.09 0.27 ± 0.08 <0.001 <0.001 <0.001 0.842
(cortex/total perimeter)
Ktrans (mean) 0.03 ± 0.05 0.03 ± 0.02 0.07 ± 0.06 <0.001 0.505 <0.001 <0.001
Ve (mean) 10.0 ± 10.1 7.3 ± 3.2 33.7 ± 39.8 <0.001 0.673 <0.001 <0.001
rCBV (mean) 1.92 ± 0.65 1.57 ± 0.6 2.78 ± 1.47 0.003 0.347 0.008 0.005

All values are presented as the mean ± SD or the number (%) unless otherwise indicated. Data in italics are p-values less than < 0.05 in Univarite analysis
SD standard deviation, GBM glioblastoma multiforme
a
Mean of the two values reported by the two radiologists.
b
Analyzed by Kruskall-Wallis test and Pearson’s chi-square test
c
Analyzed by Mann-Whitney U test, Pearson’s chi-square, or Fisher’s exact for multiple comparisons
Neuroradiology
Neuroradiology
Table 4 Blind tests for discriminating oligodendrogliomas from anaplastic astrocytomas and GBMs in three readers with different neuroradiology
knowledge level
Before informing
Sensitivity (%) Specificity (%)
Reader 1 81.3 84.2
Reader 2 50 89.5
Reader 3 25 68.4
Before informing, the statistical difference between reader 1 versus 2 and reader 1 versus 3 in sensitivity and specificity: P = 0.063 and 1.000, 0.004, and
0.125, respectively
Ktrans and Ve, and multivariate analysis revealed that Ve is a
significant independent risk factor. As mentioned in detail
previously, Ktrans is the volume transfer constant in unit time
for the transfer of contrast medium from a vessel into the
extravascular extracellular space (EES), which reflects the
intratumoral microvascular permeability [15]. Ve is the volume
fraction of the contrast medium leaking into the EES [15].
Based on these results, we conclude that the Ktrans and Ve
values in each group are consistent with one another and that
the vascular characteristics of oligodendrogliomas are quite
different from those of astrocytic tumors including GBM, be-
cause the Ktrans and Ve values of astrocytic tumors were higher
than those of oligodendrogliomas. Several explanations for
this phenomenon have been suggested. Schiffer et al. de-
scribed the unique vascularity of oligodendrogliomas [33].
Subsequently, Lev et al. posited that different perfusion pat-
terns in astrocytic tumors and oligodendrogliomas are likely to
be associated with the fine capillary network typically
observed in oligodendrogliomas [34]. Moreover, a recent
study attempting to differentiate oligodendrogliomas from
astrocytic tumors using perfusion CT [35] showed that
oligodendrogliomas had significantly lower permeability sur-
face area-product values than astrocytic tumors. Those authors
reported that high-grade oligodendroglial tumors showed sig-
nificantly lower surface permeability than astrocytomas of the
same grade on perfusion CT, whereas there was no difference
in surface permeability between low-grade oligodendroglial
tumors and low-grade astrocytomas. In the ROC curve anal-
ysis, the combination of all three parameters, including Ve,
increased the diagnostic performance (AUC = 0.881). Thus,
based on our results, clinical and conventional MR imaging
analyses with a pharmacokinetic approach may be sufficiently
powerful to classify glial tumors. When we performed addi-
tional comparison analysis between the oligodendroglioma
and grade II/III astrocytoma group to inspect the results with
separation of GBMs, the presence of calcification and higher
cortex involvement ratio were significantly different between
the oligodendroglioma and grade II/III astrocytoma. Perfusion
parameters including Ve were not significantly different be-
tween the two groups. In this analysis, we found that the
perfusion parameters may be useful for differentiation
After informing P values
Sensitivity (%) Specificity (%) Sensitivity (%) Specificity (%)
100 100 0.248 0.248
93.8 73.7 0.016 0.250
87.5 84.2 0.002 0.250
between the GBM and others, and verified the indispensable
role of conventional MR imaging analysis in differentiating
between oligodendrogliomas and astrocytic tumors.
Therefore, pharmacokinetic analysis using DCE MRI can be
considered as an important supplementary tool when
distinguishing oligodendrogliomas from GBMs, which is dif-
ficult in clinical practice, and it was well verified on the results
of blind tests.
In our study, the mean rCBV values of WHO grade II and III
oligodendrogliomas were not significantly different from those
of astrocytic tumors with the same WHO grades, although the
values were higher in oligodendrogliomas. This finding is not
perfectly in agreement with a report by Saito et al. [16], which
showed that the mean rCBVmax of astrocytic tumors, with the
exception of GBM, was significantly lower than that of oligo-
dendroglial tumors. We assumed that this mild discrepancy
may be due to new WHO classification system. Also, since
GBMs which composed the largest proportion of tumors in
astrocytic tumor group showed the highest value among all
glial tumors, rCBV failed to differentiate oligodendrogliomas
from astrocytic tumors in our study. The finding that rCBV
may not be helpful for differentiating oligodendrogliomas from
astrocytic tumors is remarkable because GBMs represent the
majority of astrocytic tumors in adults, and we often encounter
MR images of GBMs without pathologic information, includ-
ing the WHO grade, in clinical practice.
This study has several limitations. First, the study population
was relatively small. Second, because the conventional MR
imaging analysis, with the exception of the cortex involvement
ratio, was performed subjectively, there is always a risk of
misclassification. We attempted to reduce this risk using the
consensus of two experts. Finally, the parameters derived from
the DCE and DSC MR images in the astrocytic tumor group
might have been overestimated because the 54 non-
oligodendroglioma patients included 41 GBMs. However, our
ultimate goal was to differentiate oligodendrogliomas from as-
trocytic tumors including GBM regardless of the WHO grade,
because GBMs represent the majority of astrocytic tumors in
adults and we commonly encounter MR images of GBMs
without pathologic information including the WHO grade, in
clinical practice.

Our results suggest that conventional MR imaging features,
such as the higher cortex involvement ratio, and the presence of
calcification along with the lower Ve values from the DCE MR
imaging are diagnostically accurate in differentiating
oligodendrogliomas from astrocytic tumors on 2016 WHO
classification. Additionally, we observed an added value of
the pharmacokinetic features derived from DCE MR imaging
in depicting differences in microvascular permeability between
oligodendrogliomas and astrocytic tumors. We conclude that
DCE MRI can be used as an important and non-invasive im-
aging technique for differentiating oligodendrogliomas from
astrocytic tumors.
Compliance with ethical standards
Funding No funding was received for this study.
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical approval All procedures performed in studies involving hu-
man participants were in accordance with the ethical standards of the
institutional review board of Seoul St. Mary’s and with the 1964
Helsinki declaration and its later amendments or comparable ethical stan-
dards. For this type of study, formal consent is not required.
Informed consent Statement of informed consent was not applicable
since the manuscript does not contain any patient data.
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