Jörg Mauler1, Karl-Josef Langen1,2, Andrew A. Maudsley3, Omid Nikoubashman4, Christian Filss1, Gabriele Stoffels1, and N. Jon Shah1,5
1Forschungszentrum Jülich, Jülich, Germany, 2Department of Nuclear Medicine, Faculty of Medicine, RWTH Aachen University, Aachen, Germany, 3Miller School of Medicine, University of Miami, Miami, FL, United States, 4Department of Neuroradiology, RWTH Aachen University, Aachen, Germany, 5Department of Neurology, Faculty of Medicine, JARA, RWTH Aachen University, Aachen, Germany
Synopsis
Gliomas are characterised by
an elevated expression of amino acid transporters and cell turnover. The
spatial overlap of the corresponding volumes was analysed in 46 subjects, based
on O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake, measured with PET and by
means of the choline to N-acetyl-aspartate (Cho/NAA) ratio, determined by
simultaneously acquired, 3D spatially resolved MR spectroscopic imaging data.
The overlap between the respective volumes averaged out to (30±23) % with
tumour volumes of (14±15) cm3 and (39±28) cm3 in case of
FET uptake and increased Cho/NAA-ratio, respectively. Thus the imaging
modalities may represent different metabolic properties of gliomas.Purpose
MR
imaging is the method of choice for diagnosis of brain tumours but tumour
delineation can be difficult and may be improved by adding metabolic information
obtained from PET using O-(2-[18F]fluorethyl)-L-tyrosine (FET)
1. The
increased expression of amino acid transporters leads to an increased FET
accumulation in tumour cells
2. Another feature of gliomas is the
increased cell turnover, which is indicated by a raised level of choline containing
compounds (Cho) released from cell membranes and a reduced N-acetyl-aspartate (NAA)
concentration as an indicator of neuronal loss. Such metabolites can be
detected, in a 3D spatially resolved, manner by MR spectroscopic imaging (MRSI).
A previous analysis of the areas of increased 18FET uptake and Cho/NAA
ratio obtained from 2D spatially resolved MRSI, reported more than 75 % congruency
in 15 patients
3. In the present hybrid PET MR study, the congruency
of 18FET uptake and elevated Cho/NAA ratio is analysed in 3D in a
series of 46 patients with brain tumours.
Methods
The study was approved by the
local ethical committee. Informed consent was obtained from all patients before
the measurement. Out of a series of 117 patients with brain tumours
investigated by FET PET and MRSI in a hybrid PET MR scanner, 46 subjects (18 female, 28 male) of 48 ±15 years average age with suspected gliomas (WHO grade
II-IV) were included in this analysis. 35 were excluded because of negative
findings in FET PET and 36 were excluded because of unsuitable tumour
location/bad data quality. Every patient
was administered 3 Mbq/kg body weight of FET. While PET data were acquired in
list mode over 50 min, a T1-weighted MPRAGE data set (with/without contrast
agent), a T2+FLAIR data and a high resolution MR spectroscopic image data set
with full brain coverage by means of a volumetric echo planar SI (EPSI)
sequence with TE=17.6 ms and 16 min total acquisition time 4 were acquired
simultaneously. All measurements were performed on a Siemens (Erlangen,
Germany) 3T TIM TRIO equipped with the Siemens BrainPET insert inside the 3T
magnet. 3D volumes representing the distribution of NAA and Cho were determined
by employing the MIDAS software package 5. The volumes of suspected
tissue were delineated based on FET uptake values greater than the 1.6 fold of
the background uptake 1 and by Cho/NAA-ratios outside the 95 %
confidence interval of the distribution of normal tissue.
By
means of the Dice coefficient, the overlap of the volumes of suspicious
tissue depicted by the Cho/NAA-ratio and FET uptake, respectively, was
evaluated at the spatial resolution of the MRSI data set (64x64x32 vxl,
5.6x5.6x10 mm3 each).
The
distances between the centres of gravity of the tumour volumes determined with
each method were calculated.
Results
The
centres of gravity determined with both methods were located at (19±15) mm
distance from each other. The overlap between the volumes defined by increased
FET uptake and Cho/NAA-ratio averaged out at (30±23) % with tumour volumes of
(14±15) cm
3 and (39±28) cm
3 in case of FET uptake and
increased Cho/NAA-ratio, respectively (Fig. 1).
Discussion
Metabolically
active tumour tissue delineated by increased FET uptake exhibits considerable
differences compared with the area of elevated Cho/NAA-ratio measured by 3D
spatially resolved MRSI. This finding is in contrast to previously reported
results showing excellent overlap
3. Although the low extent of
congruency is partially caused by the significantly different tumour volumes,
to which Dice’s coefficient is sensitive, a similarity of FET uptake and
Cho/NAA mapping was not found.
Conclusions
Although
both FET uptake and Cho/NAA mapping are associated with proliferating tumour
tissue, the two methods appear to reflect different metabolic properties of
gliomas. The clinical relevance of these findings needs to be explored in
future studies by comparing the histological and molecular parameters of the
tumour tissue especially in mismatch areas.
Acknowledgements
We thank Sulaiman Sheriff for his excellent technical support and
Cornelia
Frey, Silke Frensch and Suzanne Schaden
for the reliable support of the data acquisition. We
gratefully acknowledge
Philipp Lohmann's help on creating the tumour masks.References
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