Hybrid PET MRI of brain tumours: spatial relationship of tumour volume in FET PET and 3D MRSI
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) cm3 and (39±28) cm3 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

1. Pauleit D, Floeth F, Hamacher K, et al. O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain 128, 678-687, 2005.

2. Langen K-J, Hamacher K, Weckesser M, et al. O-(2-[18F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications. Nucl Med Biol 33, 287-294, 2006.

3. Stadlbauer A, Prante O, Nimsky C, et al. Metabolic imaging of cerebral gliomas: spatial correlation of changes in O-(2-18F-fluoroethyl)-L-tyrosine PET and proton magnetic resonance spectroscopic imaging. J Nucl Med 49, 721-729, 2008.

4. Ebel A, Maudsley A A, Detection and correction of frequency instabilities for volumetric 1H echo-planar spectroscopic imaging. MRM 53, 465-469, 2005.

5. Maudsley A A, Darkazanli A, Alger J R, et al. Comprehensive processing, display and analysis for in vivo MR spectroscopic imaging. NMR Biomed 19, 492-503, 2006.

Figures

Fig. 1 Example for an astrocytoma WHO II. Voxels with increased (red) Cho/NAA-ratio, (green) FET uptake and (yellow) overlap of both are overlaid onto a T1 data set after contrast agent administration. The number of voxels with elevated Cho/NAA ratio exceeds the number of FET positive voxels.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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