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Table of Contents    
Year : 2017  |  Volume : 65  |  Issue : 2  |  Page : 293-301

Potential for differentiation of glioma recurrence from radionecrosis using integrated 18F-fluoroethyl-L-tyrosine (FET) positron emission tomography/magnetic resonance imaging: A prospective evaluation

1 Department of Neurosurgery, Institute of Neuro Sciences, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi, India
2 Department of Molecular Imaging and Nuclear Medicine, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi, India
3 Molecular Imaging and Research Centre, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Timarpur, Delhi, India
4 Institute of Radiation Oncology, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi, India

Date of Web Publication10-Mar-2017

Correspondence Address:
Dr. Aashish Gambhir
Department of Molecular Imaging and Nuclear Medicine, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi - 110076
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/neuroindia.NI_101_16

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 ╗ Abstract 

Purpose: To assess the utility of 18F-fluoroethyl-L-tyrosine (FET) positron emission tomography/magnetic resonance imaging (PET/MRI) in distinguishing recurrence from radionecrosis.
Materials and Methods: Thirty-two patients (25 males, 7 females) of glioma who had already undergone surgery/chemoradiotherapy and had enhancing brain lesions suspicious of recurrence were evaluated using integrated 18F-FET PET/MRI, and followed up with histopathology or clinical follow-up and/or MRI/PET/MRI imaging. Manually drawn regions of interest over areas of maximal enhancement or FET uptake were used to calculate tumor to background ratios [TBRmax, TBRmean], choline: creatine ratio [Cho: Cr ratio], normalized relative cerebral blood volume [N rCBVmean] and apparent diffusion coefficient [ADCmean]. Correlations were evaluated using Pearson's coefficient. Accuracy of each parameter was calculated using independent t-test and receiver operator curve (ROC) analysis while utility of all four parameters together using multivariate analysis of variance (MANOVA) for differentiating recurrence vs. radionecrosis was evaluated. Positive histopathology and imaging/clinical follow up served as the gold standard.
Results: Twenty-four of the 32 patients were diagnosed with recurrent disease and 8 with radiation necrosis. Significant correlations were observed between TBRmaxand N rCBVmean (ρ =0.503; P = 0.003), TBRmean, and N rCBVmean (ρ =0.414; P = 0.018), TBRmaxand ADCmean (ρ = −0.52; P = 0.002), and TBRmeanand ADCmean(ρ = −0.518; P = 0.002). TBRmax, TBRmean, ADCmean, Cho: Cr ratios, and N rCBVmeanwere significant in differentiating recurrence from radiation necrosis with an accuracy of 94.1%, 88.2%, 80.4%, 96.4%, and 89.9%, respectively. MANOVA indicated that combination of all parameters demonstrated better evaluation of recurrence vs. necrosis than any single parameter. The diagnostic accuracy, sensitivity, and specificity using all MRI parameters were 93.75%, 96%, and 85.7%, and using all FET PET/MRI parameters was 96.87%, 100%, and 85.7%, respectively.
Conclusions: Synergetic effect of multiple MR parameters evaluated together in addition to FET PET uptake highlights the fact that integrated 18F-FET PET/MRI might have the potential to impact management of patients with glioma by timely and conclusive recognition of true recurrence from radiation necrosis.

Keywords: Amino acid PET, 18F-fluoroethyl-L-tyrosine (18F-FET), glioma, radiation necrosis, recurrence, simultaneous PET/MRI
Key Message:
Synergetic effect of FET uptake and multiple advanced MRI parameters evaluated together with integrated 18F.FET PET/MRI has the potential to impact management of patients with glioma by helping to non.invasively establish an unequivocal distinction between true recurrence and radiation necrosis.

How to cite this article:
Sogani SK, Jena A, Taneja S, Gambhir A, Mishra AK, D’Souza MM, Verma SM, Hazari PP, Negi P, Jadhav GK. Potential for differentiation of glioma recurrence from radionecrosis using integrated 18F-fluoroethyl-L-tyrosine (FET) positron emission tomography/magnetic resonance imaging: A prospective evaluation. Neurol India 2017;65:293-301

How to cite this URL:
Sogani SK, Jena A, Taneja S, Gambhir A, Mishra AK, D’Souza MM, Verma SM, Hazari PP, Negi P, Jadhav GK. Potential for differentiation of glioma recurrence from radionecrosis using integrated 18F-fluoroethyl-L-tyrosine (FET) positron emission tomography/magnetic resonance imaging: A prospective evaluation. Neurol India [serial online] 2017 [cited 2023 Mar 27];65:293-301. Available from: https://www.neurologyindia.com/text.asp?2017/65/2/293/201815

Traditionally, the management of high-grade gliomas (HGG) comprises early detection and prompt maximal surgical resection followed by postoperative radiotherapy (RT).[1] Relatively recently, compared to RT alone, Stupp et al., demonstrated the advantage of concurrent temozolomide (TMZ) based chemoradiotherapy (chemoRT) establishing it as the standard of care in glioblastoma multiforme (GBM) management.[2] Despite these advancements, tumor recurrence is frequent, with more than 90% cases showing recurrence at or within 2 cm of the primary site.[3]

However, as a consequence of this therapy intensification, pseudoprogression (PsP), defined as increased contrast enhancement on follow-up magnetic resonance imaging (MRI) with subsequent resolution without alteration of therapy, is being increasingly recognized to the tune of 6–31%.[4],[5] These changes are attributable either to the increased rates of RT necrosis [6] and therapy-induced alterations in the blood–brain barrier affecting contrast leakage. Conventional MRI has little value in differentiating PsP from true early progressive disease (ePD)[7] as both recurrence and radiation necrosis present as enhancing lesion(s) on a contrast enhanced MRI (CE MRI). The established use of anti-angiogenic agent bevacizumab in recurrent GBM further complicates disease progression assessment.[8] However, distinguishing radiation necrosis/PsP from ePD is essential because, while ePD indicates treatment failure necessitating a change in therapy, chemoRT-induced necrosis is often a marker of treatment success.[9]

In this context, advanced MRI techniques have become available such as diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), perfusion MR imaging, and magnetic resonance spectroscopy (MRS) allowing differentiation of recurrence from radiation necrosis/pseudoprogression, albeit with some associated problems.[10],[11],[12],[13]

Further, among several traditional and novel PET tracers such as 2-deoxy-2-(18F) fluoro D-glucose (18F-FDG), 11C-L-methionine (11C-MET), 18Ffluoroethyl-L-tyrosine (18F-FET), 6-[fluoride-18] fluorolevodopa (18F-DOPA), or 3'-deoxy-3'-[18F] fluorothymidine (18F-FLT) investigated,[14],[15] amino-acid based tracers such as 11 C-MET and 18 F-FET appear most promising. While the former suffers from the drawback of a short half-life of 11 C (20 minutes) and requirement of an on-site cyclotron,[16] the latter has been extensively investigated in primary diagnosis, tumor therapy assessment, and recurrence detection.18 F-FET PET in conjunction with MRI has been found to be useful for diagnostic and therapeutic assessment for both neurosurgery [17] and RT planning.[18]

Hence, it appears logical that combination of 18 F-FET PET with MRI might significantly aid in discriminating recurrence from RT necrosis. As fusion of images across modalities requires additional software capabilities and is riddled with registration artifacts, a single session multiparametric analysis is now feasible with the advent of simultaneous integrated PET/MRI.[19] This has ensured accurate spatiotemporal co-registration, significantly reduced time of measurement, with improved patient compliance. Hence, we performed this prospective evaluation aiming to assess the utility of simultaneous 18 F-FET PET/MRI in distinguishing treated cases of glioma with suspected recurrence from radiation necrosis.

 ╗ Materials and Methods Top


In a prospective study, 32 patients (25 males, 7 females; mean age ± SD: 52.53 ± 15.75 years; range: 17–80 years) with a histologically diagnosed glioma after their debulking surgery and after having undergone chemoRT were enrolled for a simultaneous 18 F-FET PET/MRI evaluation. At the time of recruitment in the study, all had a high index of suspicion for recurrence clinically and/or when assessed on the follow up CE MRI.

The details of the patients are available in [Table 1]. Written informed consents for conducting an 18 F-FET PET/MRI scan and scientific evaluation of data was obtained from each individual participant. The study and analysis of data was approved by the local institutional review board.
Table 1: Patient characteristics

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Patients were excluded from the study if they had any primary cerebral pathology, non-glial histopathology, proven cerebral metastasis or a known primary other than a glioma, pregnancy and presence of any standard contraindications for an MRI examination such as magnetic metal implants, pacemakers, etc.

Post 18 F-FET PET/MRI examination, patients having tumors and showing congruent contrast enhancement with FET uptake underwent neurosurgical resection for histopathological confirmation, whereas in patients without FET uptake or patients deemed unfit for surgery, imaging and clinical follow up was performed.


Positron emission tomography/magnetic resonance imaging

Simultaneous PET/MRI was performed on the Biograph mMR (Siemens, Erlangen, Germany), which consists of a 3-T MRI scanner harboring a fully functional PET system equipped with avalanche photodiode technology.[20] MR scanner featuring a high-performance gradient system (45 mT/m) with a slew rate of 200 T/(ms) is equipped with total imaging matrix coil technology, covering the entire body with multiple integrated radiofrequency surface coils.[21]

Imaging protocol

After fasting for at least 4 hours,[22] 207.2 ± 25 MBq (5.6 ± 0.67 mCi) of 18 F-FET was injected intravenously in the antecubital vein. Brain 18 F-FET PET/MRI was acquired immediately after tracer injection for a period of 25 minutes, during which various MRI sequences were carried out over continuous PET acquisition including a transversal T1-weighted ultrashort echo time (UTE) for attenuation correction, transversal two-dimensional (2D)-encoded fluid attenuated inversion recovery (FLAIR) sequence, T2-weighted turbo spin-echo sequence, sagittal three-dimensional (3D)-encoded magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) sequence, diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), and perfusion echo planar imaging (EPI). In each case, 3D 1 H MRS was acquired and included the following parameters: a point-resolved spectroscopy sequence (PRESS), which included six presaturation bands placed around the volume of interest (VOI) to minimize contamination by air filled sinuses, osseous, and cerebrospinal fluid (CSF) containing structures. The details of acquisition protocol and parameters are available in [Table 2].
Table 2: Acquisition protocol and various MR acquisition parameters used in the 25 minute simultaneous dynamic 18F FET PET MRI study

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Post-acquisition, PET, MRI, and PET/MRI images were reviewed at syngo.via platform (Siemens, Germany) using the mMR general workflow.

Image analysis

The 18 F-FET PET-MRI data were analyzed by a radiologist and two nuclear medicine physicians, with more than 5, 10, and 5 years of MRI and Positron Emission Tomography computed tomography (PET/CT) experience, respectively. Diagnosis was made by reaching a consensus.

Region of interest selection

For enhancing lesions, software based T1-weighted post-contrast subtraction series was generated by image-by-image subtraction of the pre-contrast series from each post-contrast series of each patient, hence excluding necrosis/altered blood products. A free hand manual region of interest (ROI) was drawn over the area of maximum enhancement in the most representative slice and stored. Relative cerebral blood volume (rCBV) maps were derived using T2* perfusion imaging data and subsequently normalized with contralateral white matter generating a normalized rCBV (N rCBV) map. For diffusion image, data apparent diffusion coefficient (ADC) maps were generated. The stored free hand ROI drawn on the T1-weighted subtracted image (described above) was duplicated using a copy-paste function over the ADC and N rCBV maps and the FET PET images yielding corresponding simultaneous ADCmean, N rCBVmean and standardized uptake values (SUVmax and SUVmean), respectively. The most representative spectra observed within this ROI was employed for choline/creatine (Cho/Cr) ratio calculation.

ROI size, hence, differed for each patient. In cases with absent/minimal enhancement, PET images showing the area of maximum FET uptake was chosen for drawing the ROI.

For background FET uptake value calculation, the same ROI as the ROI of the brain lesion was placed over the contralateral hemisphere (mirror region), which was obviously not affected.

Tumor to background ratios, TBRmax and TBRmean, values were calculated by dividing maximum and mean SUV values of tumor FET uptake with the mean background FET uptake. These values were used for further statistical analysis

Statistical analysis

Correlations between MRI parameters, N rCBVmean, ADCmean, Cho: Cr ratio, and PET parameters, and FET uptake (TBRmax and TBRmean), were evaluated using Pearson product-moment correlation coefficient. Sensitivity, specificity, and accuracy of individual parameters for recurrence detection were also evaluated using independent samples Student's t-test (two-tailed) and receiver operating characteristic (ROC) analysis using binary logistic regression. Decision thresholds were considered optimal when the sum of paired values for sensitivity and specificity reached the maximum. In addition, multivariate analysis was performed using multivariate analysis of variance (MANOVA) to decide whether a model considering a combination of parameters was better than any single parameter. Further, the combination of MRI and PET/MRI parameters was evaluated for diagnostic accuracy. All statistical analyses were performed using the Statistical Package for the Social Sciences (version 18.0, SPSS for Windows, 2009).

 ╗ Results Top

Thirty-two patients enrolled in this study yielded 32 lesions for evaluation. Appropriate neurosurgical resection by an experienced neurosurgeon was performed in 12 patients, with histopathology showing viable tumor tissue in all. Eight patients were classified as radiation necrosis based on their stable clinical state for extended follow-up periods, absence of recent-onset neurologic symptoms, and no significant enlargement of the lesion observed on follow-up MRI images up to a mean period of 12 ± 2 months. Example of one such case is demonstrated in [Figure 1]. Twelve patients were classified as having a recurrent tumor based on the clinical deterioration of neurologic symptoms and/or progressive increase in size of the lesion on CE MRI or PET/MRI during the follow-up period [Table 1] and [Figure 2].
Figure 1: Radiation necrosis: Follow up 18F-FET PET/MRI examinations (a-f; g-l; 10 month apart) of a neurologically stable 69y/F patient with a right parietal GBM post-surgery/chemoRT with recent onset enhancing lesion. Axial subtracted (a and g), post-contrast T1w MPRAGE (b and h), PET/MRI (c and i), CBV maps (d and j), ADC maps (e and k), and MRS spectra (f and l) demonstrate a rim enhancing lesion showing diffuse FET uptake with normal rCBV, no diffusion restriction, and equivocal Cho/Cr ratio suggestive of radiation necrosis showing marginal size increment with reduced FET uptake on follow-up (i)

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Figure 2: Tumor recurrence: A 72y/M with GBM post-surgical excision/chemoRT was referred for recurrence using 18F-FET PET/MRI (a-d), later developed increasing weakness on left upper-lower limbs and again followed up at an interval of 9 months (e-h). Axial T1w MPRAGE (a and e), ADC maps (b and f), FET PET/MRI (c and g) and MRS (d and h) show an increasingly enhancing lesion with significant diffusion restriction, FET uptake, and corresponding high Cho: Cr ratio suggestive of tumor recurrence based on imaging follow up and neurological deterioration

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In evaluation of correlations between FET uptake and MRI parameters, significant moderate correlations were observed between TBRmax and N rCBVmean (ρ =0.503; P = 0.003) [Figure 3]a; and, TBRmean and N rCBVmean (ρ =0.414; P = 0.018). In addition, significant moderate negative correlations were observed between TBRmax and ADCmean (ρ = −0.52; P = 0.002) [Figure 3]b and TBRmean and ADCmean (ρ = −0.518; P = 0.002). No correlation was noted among TBR and Cho: Cr ratio values.
Figure 3: (a) Scatter diagrams demonstrating moderate positive correlation between TBR and N rCBV and (b) moderate negative correlation between TBRmax mean max and ADCmean parameters obtained from analysis. Bar Diagram (c) demonstrating significantly different mean values of ADCmean, N rCBVmean, Cho: Cr ratio, TBRmean and TBRmax parameters between the recurrence (red) and radionecrosis group (blue). ROC analysis curves (d) of various parameters evaluated

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Significant difference was observed between the recurrent vs. radiation necrosis group using all four parameters [Figure 3]c: (a) TBRmax 3.97 ± 1.21 vs. 2.02 ± 0.97, P = 0.001; (b) TBRmean2.54 ± 1.09 vs. 1.24 ± 0.61, P = 0.000; (c) Cho: Cr ratio, 2.72 ± 1.01 vs. 1.02 ± 1.00, P = 0.000; (d) N rCBVmean, 3.24 ± 2.05 vs. 1.51 ± 1.17, P = 0.03; (e) ADCmean1149.57 ± 284.92 (10−6 mm 2/s) vs. 1642.31 ± 519.21 (10−6 mm 2/s), P = 0.03.

The diagnostic accuracy, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (area under the curve; AUC) of the evaluated individual parameters for the identification of tumor recurrence are demonstrated in [Table 3]. The corresponding ROC curves for these parameters are shown in [Figure 3]d.
Table 3: Diagnostic performance for recurrence detection of individual 18F-FET PET/MRI parameters

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MANOVA was carried out for all of the above mentioned parameters in order to evaluate if a combination of these parameters demonstrated better evaluation of the recurrence vs. necrosis diagnostic dilemma than any single parameter statistically. There was a statistically significant difference between the two groups, Hotelling's Trace = 0.957, F (8, 24) =3.282, P = 0.014; partial η2= 0.489.

The diagnostic accuracy, sensitivity, and specificity for recurrence detection using all three MRI parameters were 93.75%, 96%, and 85.7%, respectively. Addition of FET PET TBR values improved these values further to 96.87%, 100%, and 85.7%, respectively.

 ╗ Discussion Top

The current benchmark to distinguish true recurrence from RT necrosis remains histopathology, which is not only invasive but is also marred by complications such as infection, hematoma formation, and neurologic sequel.[23] Hence, it has become an imminent necessity to develop novel noninvasive imaging techniques with high accuracy to reliably perform this distinction. With the development of integrated simultaneous PET/MRI, we aimed at assessing this clinical predicament using multimodal image analysis in a prospective design.

The results obtained using individual PET and MRI parameters were found to be in agreement with published literature.

Dynamic susceptibility-weighted CE MRI (DSC) allows one to quantify relative cerebral blood volume reflecting the vascular environment surrounding a tumor. We observed moderate positive correlations between the FET uptake and N rCBV mean that suggested the presence of coupled vascularity and tumor amino acid uptake with mitotic activity and endothelial proliferation. Similar results have been demonstrated using 11 C-Methionine.[24] However, we observed that both these parameters showed inadequate spatial congruence, as also demonstrated earlier by Filss et al.[25] We found N rCBVmean above cut-off value of 1.78 to be statistically significant for tumor recurrence, although with a lower specificity. Other studies have shown 0.71–1.75[26],[27] as cut-off values to reliably distinguish radiation necrosis from tumor recurrence with variability owing to variation of techniques employed for calculation.

Similarly, we observed moderate negative correlations between TBR values and ADCmean suggesting increased FET uptake in areas of high mitotic potential and consequently increased cellular density yielding lower ADC values. Though this has been proven directly using stereotactic biopsy,[28] several researchers have reported poor correlation [29] citing factors such as tissue compression and ischemia contributing to restricted diffusion in GBM.[30] Although significant correlations observed are a departure from published literature, they may be attributable to simultaneous acquisition and accurate ROI copied from areas of enhancement. The use of contrast-enhanced SWI as a guide to identify regions for ADC measurements has been reported to enhance the ability of DWI to differentiate tumor recurrence from PsP.[31] Statistically significant difference of ADC values was noted between the recurrence and RT necrosis groups, similar to the result reported retrospectively by Hein et al.,[32] and prospectively by Asao et al.[33]

Recurrent brain tumors are known to demonstrate elevated Cho with decreased N-acetyaspartate (NAA) in comparison to RT necrotic areas with a reported diagnostic yield of 96.2%,[13],[34] which is similar to our results. However, no significant positive correlation was observed between Cho: Cr ratios and TBR, suggesting that they constituted independent parameters evaluating different aspects of tumor biology. In addition, we noted that FET images were useful in guiding MRS voxel selection.

Furthermore, several publications have reported a need for a multimodal analysis combining FET PET and different advanced MRI techniques [13],[35] such as MRS with DWI.[34],[36] However, the use of FET alone, or a fusion based or simultaneously integrated FET PET/MRI evaluation has remained limited to the assessment of cerebral metastasis.[37] In this regard, in our analysis using Hotelling's Trace MANOVA, we observed a significant multivariate effect for the combined use of all four parameters in distinguishing recurrence from RT necrosis. Further, improved accuracy and sensitivity was noted with addition of FET PET findings to advanced MRI parameters clearly demonstrating the usefulness of a statistical analysis of this combinatorial analysis.

Apart from discerning the role of simultaneous FET PET/MRI in recurrence vs. radiation necrosis, the authors were also in complete agreement regarding the adequacy of both PET and MRI image quality obtained in an acquisition time of approximately 25 minutes, which is considerably shorter than usually required for a separate acquisition and image fusion.

One should exercise caution in interpreting these results owing to our small sample size and the inability to achieve histological confirmation of disease recurrence in 12 patients, although 50% of these showed rapid neurological deterioration and the remaining demonstrated increasing lesion size on follow- up evaluations [Figure 2]. It has been extensively reported that ePD is more likely to be associated with symptoms than PsP.[38] Tumor factors such as O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status, known to be more frequently associated with the development of PsP,[39] were not evaluated and remain a subject of future evaluations.

 ╗ Conclusion Top

Simultaneous PET/MRI evaluation for recurrent glioma is feasible and useful with improvement in diagnostic accuracy. Synergetic effect of multiple MR parameters evaluated together in addition to FET PET uptake highlights the fact that integrated18F-FET PET/MRI might have the potential to impact management of patients with a glioma by timely and conclusive recognition of true recurrence from radiation necrosis.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 ╗ References Top

Kristiansen K, Hagen S, Kollevold T, Torvik A, Holme I, Nesbakken R, et al. Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: A prospective multicenter trial of the Scandinavian Glioblastoma Study Group. Cancer 1981;47:649-52.  Back to cited text no. 1
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;52:987-96.  Back to cited text no. 2
Santra A, Kumar R, Sharma P, Bal C, Kumar A, Julka PK, et al. F-18 FDG PET-CT in patients with recurrent glioma: Comparison with contrast enhanced MRI. Eur J Radiol 2012;81:508-13.  Back to cited text no. 3
Yaman E, Buyukberber S, Benekli M, Oner Y, Coskun U, Akmansu M, et al. Radiation induced early necrosis in patients with malignant gliomas receiving temozolomide. Clin Neurol Neurosurg 2010;112:662-7.  Back to cited text no. 4
Brandes AA, Franceschi E, Tosoni A, Blatt V, Pession A, Tallini G, et al. MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol 2008;26:2192-7.  Back to cited text no. 5
Peca C, Pacelli R, Elefante A, Del Basso De Caro ML, Vergara P, Mariniello G, et al. Early clinical and neuroradiological worsening after radiotherapy and concomitant temozolomide in patients with glioblastoma: Tumour progression or radionecrosis? Clin Neurol Neurosurg 2009;111:331-4.  Back to cited text no. 6
Young RJ, Gupta A, Shah AD, Graber JJ, Zhang Z, Shi W, et al. Potential utility of conventional MRI signs in diagnosing pseudoprogression in glioblastoma. Neurology 2011;76:1918-24.  Back to cited text no. 7
Robins HI, Lassman AB, Khuntia D. Therapeutic advances in malignant glioma: Current status and future prospects. Neuroimaging Clin N Am 2009;19:647-56.  Back to cited text no. 8
Kruser TJ, Mehta MP, Robins HI. Pseudoprogression after glioma therapy: A comprehensive review. Expert Rev Neurother 2013;13:389-403.  Back to cited text no. 9
Hamstra DA, Galban CJ, Meyer CR, Johnson TD, Sundgren PC, Tsien C, et al. Functional diffusion map as an early imaging biomarker for high-grade glioma: Correlation with conventional radiologic response and overall survival. J Clin Oncol 2008;26:3387-94.  Back to cited text no. 10
Hu LS, Baxter LC, Smith KA, Feuerstein BG, Karis JP, Eschbacher JM, et al. Relative cerebral blood volume values to differentiate high-grade glioma recurrence from posttreatment radiation effect: Direct correlation between image-guided tissue histopathology and localized dynamic susceptibility weighted contrast-enhanced perfusion MR imaging measurements. AJNR Am J Neuroradiol 2009;30:552-8.  Back to cited text no. 11
Lee HY, Na DG, Song IC, Lee DH, Seo HS, Kim JH, et al. Diffusion-tensor imaging for glioma grading at 3-T magnetic resonance imaging: Analysis of fractional anisotropy and mean diffusivity. J Comput Assist Tomogr 2008;32:298-303.  Back to cited text no. 12
Bobek-Billewicz B, Stasik-Pres G, Majchrzak H, Zarudzki L. Differentiation between brain tumor recurrence and radiation injury using perfusion, diffusion weighted imaging and MR spectroscopy. Folia Neuropathol 2010;48:81-92.  Back to cited text no. 13
Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Müller HW, et al. O-(2-[18F] fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain 2005;128:678-87.  Back to cited text no. 14
Tripathi M, Sharma R, Varshney R, Jaimini A, Jain J, Souza MM, et al. Comparison of F18 FDG and C11 methionine PET/CT for the evaluation of recurrent primary brain tumors. Clin Nucl Med 2012;37:158-63.  Back to cited text no. 15
Juhász C, Dwivedi S, Kamson DO, Michelhaugh SK, Mittal S. Comparison of amino acid positron emission tomographic radiotracers for molecular imaging of primary and metastatic brain tumors. Mol Imaging 2014;13.  Back to cited text no. 16
Plotkin M, Blechschmidt C, Auf G, Nyuyki F, Geworski L, Denecke T, et al. Comparison of F-18 FET-PET with F-18 FDGPET for biopsy planning of non-contrast-enhancing gliomas. Eur Radiol 2010;20:2496-502.  Back to cited text no. 17
Niyazi M, Geisler J, Siefert A, Schwarz SB, Ganswindt U, Garny S, et al. FET-PET for malignant glioma treatment planning. Radiother Oncol 2011;99:44-8.  Back to cited text no. 18
Drzezga A, Souvatzoglou M, Eiber M, Beer AJ, Fürst S, Martinez-Möller A, et al. First clinical experience with integrated whole-body PET/MR: Comparison to PET/CT in patients with oncologic diagnoses. J Nucl Med 2012;53:845-55.  Back to cited text no. 19
Pichler BJ, Judenhofer MS, Catana C, Walton JH, Kneilling M, Nutt RE, et al. Performance test of an LSO-APD detector in a 7-T MRI scanner for simultaneous PET/MRI. J Nucl Med 2006;47:639-47.  Back to cited text no. 20
Delso G, Fürst S, Jakoby B, Ladebeck R, Ganter C, Nekolla SG, et al. Performance measurements of the Siemens mMR integrated whole-body PET/MR scanner. J Nucl Med 2011;52:1914-22.  Back to cited text no. 21
Vander Borght T, Asenbaum S, Bartenstein P, Halldin C, Kapucu O, Van Laere K, et al. EANM procedure guidelines for brain tumour imaging using labelled amino acid analogues. Eur J Nucl Med Mol Imaging 2006;33:1374-80.  Back to cited text no. 22
Kreth FW, Muacevic A, Medele R, Bise K, Meyer T, Reulen HJ. The risk of haemorrhage after image guided stereotactic biopsy of intra-axial brain tumours: A prospective study. Acta Neurochir 2001;143:539-45.  Back to cited text no. 23
Sadeghi N, Salmon I, Decaestecker C, Levivier M, Metens T, Wikler D, et al. Stereotactic comparison among cerebral blood volume, methionine uptake, and histopathology in brain glioma. AJNR Am J Neuroradiol 2007;28:455-61.  Back to cited text no. 24
Filss CP, Galldiks N, Stoffels G, Sabel M, Wittsack HJ, Turowski B, et al. Comparison of 18F-FET PET and perfusion-weighted MR imaging: A PET/MR imaging hybrid study in patients with brain tumors. J Nucl Med 2014;55:540-5.  Back to cited text no. 25
Hu LS, Baxter LC, Smith KA, Feuerstein BG, Karis JP, Eschbacher JM, et al. Relative cerebral blood volume values to differentiate high-grade glioma recurrence from post treatment radiation effect: Direct correlation between image-guided tissue histopathology and localized dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging measurements. AJNR Am J Neuroradiol 2009;30:552-8.  Back to cited text no. 26
Gahramanov S, Raslan AM, Muldoon LL, Hamilton BE, Rooney WD, Varallyay CG, et al. Potential for differentiation of pseudoprogression from true tumor progression with dynamic susceptibility weighted contrast-enhanced magnetic resonance imaging using ferumoxytol vs. gadoteridol: A pilot study. Int J Radiat Oncol Biol Phys 2011;79:514-23.  Back to cited text no. 27
Herholz K, Pietrzyk U, Voges J, Schröder R, Halber M, Treuer H, et al. Correlation of glucose consumption and tumor cell density in astrocytomas: A stereotactic PET study. J Neurosurg 1993;79:853-8.  Back to cited text no. 28
Rahm V, Boxheimer L, Bruehlmeier M, Berberat J, Nitzsche EU, Remonda L, et al. Focal changes in diffusivity on apparent diffusion coefficient MR imaging and amino acid uptake on PET do not colocalize in nonenhancing low-grade gliomas. J Nucl Med 2014;55:546-50.  Back to cited text no. 29
Rose S, Fay M, Thomas P, Bourgeat P, Dowson N, Salvado O, et al. Correlation of MRI-derived apparent diffusion coefficients in newly diagnosed gliomas with [18F]-fluoro-l-dopa PET: What are we really measuring with minimum ADC? AJNR Am J Neuroradiol 2013;34:758-64.  Back to cited text no. 30
Al Sayyari A, Buckley R, McHenery C, Pannek K, Coulthard A, Rose S. Distinguishing recurrent primary brain tumor from radiation injury: A preliminary study using a susceptibility-weighted MR imaging-guided apparent diffusion coefficient analysis strategy. AJNR Am J Neuroradiol 2010;31:1049-54.  Back to cited text no. 31
Hein PA, Eskey CJ, Dunn JF, Hug EB. Diffusion-weighted imaging in the follow-up of treated high-grade gliomas: Tumor recurrence versus radiation injury. AJNR Am J Neuroradiol 2004;25:201-9.  Back to cited text no. 32
Asao C, Korogi Y, Kitajima M, Hirai T, Baba Y, Makino K, et al. Diffusion-weighted imaging of radiation induced brain injury for differentiation from tumor recurrence. AJNR Am J Neuroradiol 2005;26:1455-60.  Back to cited text no. 33
Zeng QS, Li CF, Zhang K, Liu H, Kang XS, Zhen JH. Multivoxel 3D proton MR spectroscopy in the distinction of recurrent glioma from radiation injury. J Neurooncol 2007;84:63-9.  Back to cited text no. 34
Matsusue E, Fink JR, Rockhill JK, Ogawa T, Maravilla KR. Distinction between glioma progression and post-radiation change by combined physiologic MR imaging. Neuroradiology 2010;52:297-306.  Back to cited text no. 35
Zeng QS, Li CF, Liu H, Zhen JH, Feng DC. Distinction between recurrent glioma and radiation injury using magnetic resonance spectroscopy in combination with diffusion-weighted imaging. Int J Radiat Oncol Biol Phys 2007;68:151-8.  Back to cited text no. 36
Galldiks N, Stoffels G, Filss CP, Piroth MD, Sabel M, Ruge MI, et al. Role of O-(2-18F-Fluoroethyl)-L-Tyrosine PET for differentiation of local recurrent brain metastasis from radiation necrosis. J Nucl Med 2012;53:1367-74.  Back to cited text no. 37
Taal W, Brandsma D, de Bruin HG, Bromberg JE, Swaak-Kragten AT, Smitt PA, et al. Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide. Cancer 2008;113:405-10.  Back to cited text no. 38
Brandes AA, Franceschi E, Tosoni A, Blatt V, Pession A, Tallini G, et al. MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol 2008;26:2192-7.  Back to cited text no. 39


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