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#EP-54
Retrospective analysis for the
11C-methionine and 18F-FDG uptakes
of the primary brain tumor
•Yoshiyasu Hiratsuka, Keiichi Kikuchi, Teruhito Mochizuki
Department of Radiology, Ehime University Graduate School of Medicine, Ehime, Japan
Shiro Ohue
Department of Neurosurgery, Ehime University Graduate School of Medicine, Ehime, Japan
Takeshi Inoue, Hitoshi Miki
Department of Radiology, Ehime Prefectural Central Hospital, Ehime, Japan
ASNR 53rd ANNUAL MEETING
DISCLOSURE
Electronic Poster
Yoshiyasu Hiratsuka
Nothing to disclose
Background
It is well known that the preoperative evaluation and diagnosis of brain tumor is very
important for patient’s management. But sometimes it’s still challenging with using
only imaging modalities because of their complexity and heterogeneity.
PET can reveal the tumor proliferative activity and contribute significantly to
determining a patient’s prognosis. 18F-fluorodeoxyglucose (FDG) is useful extensively
for assessment of the histological grade of brain tumors. On the other hand,
assessment of amino acid metabolism using 11C-methionine (MET) is helpful for
characterizing tumors with the good contrast of uptake between the tumor and
surrounding brain parenchyma.
In our institution and related medical facilities, patients with brain tumor are
additionally performed on FDG-PET/CT and MET-PET/CT before surgical treatment.
Purpose
The purpose of this study is to evaluate the uptakes of MET-PET/CT and FDG-PET/CT for
the primary brain tumor and their diagnostic values in combination with CT and MR
images.
Materials and Methods
Patients Proportion
40 patients
M:F = 20:20, 22 – 85 years (54.0 ± 18.4 years)
Between January 2013 and October 2014
They were suspected to brain tumor by clinical symptoms and neurologic
examination, then performed on brain CT and MRI.
All of them were performed on MET-PET/CT and FDG-PET/CT in addition to
previous imaging examinations.
They had not undergone any treatment or surgical resection/biopsy before
completing the series of image examination.
The preoperative PET/CT examinations with MET and FDG were scheduled and
performed in the same day.
Finally all patients have been diagnosed histologically .
Materials and Methods
Imaging Examinations
- PET scanner: Discovery ST elite (GE Healthcare)
MET PET/CT
Intravenous bolus injection of 5MBq/Kg MET
20 min waiting after injection
Emission data acquisition for 20 min
FDG PET/CT
Fasting for about 6 hrs. before scan
Intravenous bolus injection of 3.5MBq/kg FDG after a blood glucose test
Rest for 90 min after injection
Emission data acquisition for 20 min
• VUE-point and VUE-point2 (3D-OSEM) were used for image reconstruction.
- Brain CT: Brilliance 64, iCT (Philips)
Conventional scanning, without contrast media
Whole brain was scanned with 5mm thickness on axial plane
- Brain MRI: Achieva 1.5T, Achieva 3.0T (Philips), Signa HDxt 1.5T (GE Healthcare)
Axial T1WI, T2WI, FLAIR, DWI, and SWI
Postcontrast axial T1WI, additionally acquired reconstruction images in 3
planes (volumetric acquisition)
Materials and Methods
Image Analysis
Semiquantitive analysis was performed using a lesion-to normal uptake ratios (L/N ratio) for
both MET-PET/CT and FDG-PET/CT images.
Circular ROIs (40.9mm2) were located on the tumor lesion and on the contralateral grey
matter to measure SUV for calculation of L/N ratio.
We properly referred to the CT and MR images for adequate positioning of ROIs.
All image data for measuring SUV were manipulated on the Advantage Workstation 4.5 (GE
Healthcare).
Metabolic tumor volume (MTV) of primary lesion on MET PET/CT were calculated on the
basis of semiautomatically delineated VOIs with an isocontour threshold of 50 % of the
SUVmax by using MIM Maestro (MIM Software Inc.).
L/N ratio =
Statistical analysis
SUVmax on the tumor lesion
Normal gray matter mean SUV
Mann-Whitney's U test: comparison between two independent groups
ROC analysis: diagnostic accuracy for the results of the PET examination
P values <0.05 were considered significant.
JMP ver.11 for Macintosh (SAS Institute Japan) was used for all statistical analysis.
Results
Characteristics of the 40 Patients
WHO grade IV
- Glioblastoma (GBM): 20
- Glioblastoma with oligodendroglial component (GBMO): 5
WHO grade III
- Anaplastic astrocytoma (AA): 1
- Anaplastic oligoastrocytoma (AOA): 4
WHO grade II
- Oligoastrocytoma (OA): 6
- Central neurocytoma (CN): 1
WHO grade I
- Dysembryoplastic neuroepithelial tumor (DNT): 1
other
- Malignant Lymphoma (ML): 2
Table 1. Details of patient characteristics and uptakes of PET/CT
Results
Histology
(WHO grade)
GBM
(grade IV)
GBMO
(grade IV)
AA
(grade III)
AOA
(grade III)
OA
(grade II)
CN
(grade II)
DNT
(grade I)
ML
No. (M:F)
enhance+
(%)
Necrosis
(%)
MET-PET/CT
SUVmax
L/N ratio
FDG-PET/CT
MTV (ml)
SUVmax
L/N ratio
20 (10:10) 17 (85%) 17 (85%) 5.9±2.0
4.1±1.2
17.0±9.4 11.7±3.8 1.4±0.5
5 (1:4)
5 (100%) 5 (100%) 7.7±2.8
5.2±1.6
15.7±9.6 13.0±8.7 1.4±0.9
1 (0:1)
0 (0%)
0 (0%)
2.6
1.6
32.5
5.6
4 (3:1)
1 (25%)
1 (25%)
5.2±2.9
3.8±1.5
34.0±6.9
16.4±12.
1.6±1.2
9
6 (3:3)
0 (0%)
0 (0%)
3.2±0.7
2.2±0.5
47.3±24.
6.4±1.4
9
0.8±0.2
1 (1:0)
1 (100%) 0 (0%)
2.3
1.4
4.2
3.8
0.6
1 (0:1)
0 (0%)
1.8
1.3
7.3
4.5
0.4
2 (2:0)
2 (100%) 1 (50%)
6.2±1.6
5.0±1.6
9.3±8.3
21.0±3.2 3.2±1.6
0 (0%)
0.5
Fig.1 SUVmax value and L/N ratio on MET-PET/CT
Results
SUVmax
L/N ratio
CN (1)
DNT (1)
OA (6)
AOA (4)
AA (1)
GBMO (5)
GBM (20)
ML (2)
12
10
8
6
4
2
0
0
2
4
6
8
10
12
Fig.2 SUVmax value and L/N ratio on FDG-PET/CT
Results
SUVmax
L/N ratio
CN (1)
DNT (1)
OA (6)
AOA (4)
AA (1)
GBMO (5)
GBM (20)
ML (2)
36
30
24
18
12
6
0
0
6
12
18
24
30
36
Fig.3 MTV on MET-PET/CT
Results
MTV (ml) 90
60
30
0
GBM
(20)
GBMO
(5)
AA
(1)
AOA
(4)
OA
(6)
CN
(1)
DNT
(1)
ML
(2)
Results
L/N ratio
Fig.4 L/N ratio corresponding to tumor malignancy on MET-PET/CT
* : CN, DNT, OA
** : ML, GBM, GBMO, AA, AOA
P<0.05
Benign *
(8)
Malignant **
(32)
The L/N ratio showed clear separation depending
on tumor malignancy. On ROC analysis, AUC and
cut-off value of L/N ratio were calculated as 0.93
and 3.10, respectively.
TPR
Fig.5 ROC analysis
AUC = 0.93
Cut-off = 3.10
FPR
Results
L/N ratio
Fig.6 L/N ratio corresponding to tumor malignancy on FDG-PET/CT
* : CN, DNT, OA
** : ML, GBM, GBMO, AA, AOA
P<0.05
Benign *
(8)
Malignant **
(32)
The gap of L/N ratio between benign and malignant
tumor was smaller than that on MET-PET/CT, but the
difference was significant. The cut-off value of L/N
ratio was 1.00 on ROC analysis, and AUC was also
calculated as 0.92.
TPR
Fig.7 ROC analysis
AUC = 0.92
Cut-off = 1.00
FPR
Fig.8 L/N ratio corresponding to WHO grading on MET-PET/CT
Results
P<0.05
L/N ratio
grade I
(1)
P=0.17
grade II
(7)
P=0.29
grade III
(5)
grade IV
(25)
It was shown that the L/N
ratio on MET-PET/CT was
increased as progressing the
WHO grade. There were not
significant differences
between the L/N ratio of
grade II and grade III, and
between that of grade III
and grade IV.
Results
L/N ratio
Fig.9 L/N ratio between low and high-grade tumor on MET-PET/CT
Low-grade : WHO grade I + grade II
High-grade: WHO grade III + grade IV
P<0.05
Low-grade
(8)
High-grade
(30)
The L/N ratio of MET-PET/CT showed clear separation
between low–grade and high-grade tumors. On ROC
analysis, AUC and cut-off value of L/N ratio were
calculated as 0.92 and 3.10, respectively.
TPR
Fig.10 ROC analysis
AUC = 0.92
Cut-off = 3.10
FPR
Fig.11 L/N ratio corresponding to WHO grading on FDG-PET/CT
Results
P<0.05
L/N ratio
grade I
(1)
P=0.21
grade II
(7)
P=0.18
grade III
(5)
grade IV
(25)
Similar as the MET-PET/CT, it
was shown that the L/N
ratio on FDG-PET/CT was
also increased as WHO
grade advancing. There
were not significant
differences between the L/N
ratio of grade II and grade III,
and between that of grade
III and grade IV.
Results
L/N ratio
Fig.12 L/N ratio between low and high-grade tumor on FDG-PET/CT
P<0.05
Low-grade : WHO grade I + grade II
High-grade: WHO grade III + grade IV
Low-grade
(8)
High-grade
(30)
The L/N ratio showed clear separation between low
–grade and high-grade tumors with a significant
difference, but the gap between those was small
compared to that on MET-PET/CT. AUC and cut-off
value were calculated as 0.92 and 1.00, respectively.
TPR
Fig.13 ROC analysis
AUC = 0.92
Cut-off = 1.00
FPR
Fig.14 L/N ratio of glioma on MET-PET/CT
Results
P<0.05
L/N ratio
P=0.27
grade II
(6)
P<0.05
L/N ratio
P=0.29
grade III
(5)
grade IV
(25)
grade II
(6)
TPR
grade II glioma : OA
grade III glioma : AA, AOA
Grade IV glioma : GBM, GBMO
grade III+IV
(30)
There was significant difference between grade II and grade III +
grade IV gliomas (cut-off: 3.10).
Fig.15 ROC analysis
AUC = 0.90
Cut-off = 3.10
FPR
Fig.16 L/N ratio of glioma on FDG-PET/CT
Results
L/N ratio
grade II
(6)
P<0.05
P=0.27
grade III
(5)
P<0.05
L/N ratio
P=0.19
grade IV
(25)
grade II
(6)
TPR
grade II glioma : OA
grade III glioma : AA, AOA
Grade IV glioma : GBM, GBMO
grade III+IV
(30)
There was also significant difference between grade II and grade III
+ grade IV gliomas (cut-off: 1.10).
Fig.17 ROC analysis
AUC = 0.90
Cut-off = 1.10
FPR
Fig.18 L/N ratio corresponding to tumor grade and character on MET-PET/CT
Results
L/N ratio
P<0.05
P=0.35
Low-grade,
Necrosis (-), and
Enhancement (-)
(6)
P<0.05
High-grade,
Necrosis (-), and
Enhancement (-)
(7)
High-grade,
Necrosis (+) or
Enhancement (+)
(23)
The L/N ratio of high-grade glioma with necrosis or enhancement was higher than that
without necrosis and enhancement, and the difference is significant. On the other hand,
there was not significant difference between low-grade glioma without necrosis and
enhancement and high-grade glioma without necrosis and enhancement.
Fig.19 L/N ratio corresponding to tumor grade and character on FDG-PET/CT
Results
L/N ratio
P<0.05
P=0.13
Low-grade,
Necrosis (-), and
Enhancement (-)
(6)
P=0.26
High-grade,
Necrosis (-), and
Enhancement (-)
(7)
High-grade,
Necrosis (+) or
Enhancement (+)
(23)
Similar as the MET-PET/CT, there was no significant difference between low-grade glioma
without necrosis and enhancement and high-grade glioma without necrosis and enhancement.
Clinical Case 1
a
Fig. 20 30M, case of GBM. (a) plain CT, (b) MRI Gd-T1WI, (c)
MET-PET/CT, and (d) FDG-PET/CT.
There was the round-shape tumor with Gd-enhancement in the
Lt. temporal lobe (a, b). Necrotic change was shown inside of
the tumor. The solid part of the tumor had uptake on MET (c)
and FDG-PET/CT image(d). In this case, the MET-PET/CT showed
better contrast and tumor was depicted more clearly compared
to the FDG-PET/CT.
b
c
d
Clinical Case 2
a
c
b
d
Fig. 21 30M, case of GBM
On FLAIR image (a), high
intensity lesion was clearly
depicted in the Lt. middle
cerebellar peduncle. The
lesion had no obvious
enhancement or necrotic
change on post-contrast T1WI
(b), but focally increased
uptakes of MET (c) and FDG (d)
were seen .
Clinical Case 3
a
c
b
d
Fig. 22 33M, case of GBM
High intensity lesion of FLAIR
was seen in the midbrain (a).
On postcontrast T1WI, no
strong enhancement or
necrosis was depicted (b).
There was no uptake of MET
and FDG, and we could not
indicate that the tumor had
malignant potential
preoperatively.
Summary/Discussion
It was confirmed that the MET and FDG-PET/CT could evaluate accurately the tumor
malignancy and distinguish between benign and malignant tumors including gliomas.
Furthermore, in this study, MET-PET/CT and FDG-PET/CT had approximately same
quality for evaluation of the brain tumor malignancy.
The cut-off points of L/N ratio which could discriminate between benign and malignant
tumor were 3.10 on MET-PET/CT and 1.00-1.10 on FDG-PET/CT, respectively.
In this research, the correlation between MTV and tumor malignancy was not shown.
On the other hand, it was indicated that there was partly limitation to distinguish the
high-grade glioma without obvious malignant sign on MRI from low-grade glioma using
only uptakes of MET-PET/CT and FDG-PET/CT.
It was important for preoperative evaluation of glioma to separate high-grade glioma
from low-grade glioma because tumor malignancy would have a serious influence for
patient’s treatment and prognosis, and it would be necessary to make further
investigation.
Conclusion
MET-PET/CT and FDG-PET/CT might be potentially useful for the preoperative
evaluation of brain tumor grading and their malignancy.
It is suggested to be helpful for the proper preoperative diagnosis on primary brain
tumors by evaluating with the results of MET-PET/CT and FDG-PET/CT, in addition to
conventional CT and MR images .
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