Dataset Information

Direct comparison of [11C] choline and [18F] FET PET to detect glioma infiltration: a diagnostic accuracy study in eight patients.

ABSTRACT: BACKGROUND:Positron emission tomography (PET) is increasingly used to guide local treatment in glioma. The purpose of this study was a direct comparison of two potential tracers for detecting glioma infiltration, O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F] FET) and [11C] choline. METHODS:Eight consecutive patients with newly diagnosed diffuse glioma underwent dynamic [11C] choline and [18F] FET PET scans. Preceding craniotomy, multiple stereotactic biopsies were obtained from regions inside and outside PET abnormalities. Biopsies were assessed independently for tumour presence by two neuropathologists. Imaging measurements were derived at the biopsy locations from 10 to 40 min [11C] choline and 20-40, 40-60 and 60-90 min [18F] FET intervals, as standardized uptake value (SUV) and tumour-to-brain ratio (TBR). Diagnostic accuracies of both tracers were compared using receiver operating characteristic analysis and generalized linear mixed modelling with consensus histopathological assessment as reference. RESULTS:Of the 74 biopsies, 54 (73%) contained tumour. [11C] choline SUV and [18F] FET SUV and TBR at all intervals were higher in tumour than in normal samples. For [18F] FET, the diagnostic accuracy of TBR was higher than that of SUV for intervals 40-60 min (area under the curve: 0.88 versus 0.81, p = 0.026) and 60-90 min (0.90 versus 0.81, p = 0.047). The diagnostic accuracy of [18F] FET TBR 60-90 min was higher than that of [11C] choline SUV 20-40 min (0.87 versus 0.67, p = 0.005). CONCLUSIONS:[18F] FET was more accurate than [11C] choline for detecting glioma infiltration. Highest accuracy was found for [18F] FET TBR for the interval 60-90 min post-injection.

SUBMITTER: Verburg N

PROVIDER: S-EPMC6598977 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Direct comparison of [<sup>11</sup>C] choline and [<sup>18</sup>F] FET PET to detect glioma infiltration: a diagnostic accuracy study in eight patients.

Verburg Niels N Koopman Thomas T Yaqub Maqsood M Hoekstra Otto S OS Lammertsma Adriaan A AA Schwarte Lothar A LA Barkhof Frederik F Pouwels Petra J W PJW Heimans Jan J JJ Reijneveld Jaap C JC Rozemuller Annemieke J M AJM Vandertop William P WP Wesseling Pieter P Boellaard Ronald R de Witt Hamer Philip C PC

EJNMMI research 20190628 1

<h4>Background</h4>Positron emission tomography (PET) is increasingly used to guide local treatment in glioma. The purpose of this study was a direct comparison of two potential tracers for detecting glioma infiltration, O-(2-[<sup>18</sup>F]-fluoroethyl)-L-tyrosine ([<sup>18</sup>F] FET) and [<sup>11</sup>C] choline.<h4>Methods</h4>Eight consecutive patients with newly diagnosed diffuse glioma underwent dynamic [<sup>11</sup>C] choline and [<sup>18</sup>F] FET PET scans. Preceding craniotomy, m ...[more]

PMID: 31254208

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Project description:The primary aim of the study was to evaluate the role of [18F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [11C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax; target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology; subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected (n = 95). For both tracers, the location of the "blinded" prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [18F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [18F]Fluciclovine or [11C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [18F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively; whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.

Project description:Accurately defining glioma infiltration is crucial for optimizing radiotherapy and surgery, but glioma infiltration is heterogeneous and MRI imperfectly defines the tumor extent. Currently, it is impossible to determine the tumor infiltration gradient within a FLAIR signal. O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET often reveals high-grade glioma infiltration beyond contrast-enhancing areas on MRI. Here, we studied FET uptake dynamics in tumor and normal brain structures by dual-timepoint (10 min and 40-60 min post-injection) acquisition to optimize analysis protocols for defining glioma infiltration. Over 300 serial stereotactic biopsies from 23 patients (mean age 47, 12 female/11 male) of diffuse contrast-enhancing gliomas were taken from areas inside and outside contrast enhancement or outside the FET hotspot but inside FLAIR. The final diagnosis was G4 in 11, grade 3 in 10, and grade 2 in 2 patients. The target-to-background (TBRs) ratios and standardized uptake values (SUVs) were calculated in areas used for biopsy planning and in background structures. The optimal method and threshold values were determined to find a preferred strategy for defining glioma infiltration. Standard thresholding (1.6× uptake in the contralateral brain) in standard acquisition PET images differentiated a tumor of any grade from astrogliosis, although the uptake in astrogliosis and grade 2 glioma was similar. Analyzing an optimal strategy for infiltration volume definition astrogliosis could be accurately differentiated from tumor samples using a choroid plexus as a background. Early acquisition improved the AUC in many cases, especially within FLAIR, from 56% to 90% sensitivity and 41% to 61% specificity (standard TBR 1.6 vs. early TBR plexus). The current FET-PET evaluation protocols for contrast-enhancing gliomas are limited, especially at the tumor border where grade 2 tumor and astrogliosis have similar uptake, but using choroid plexus uptake in early acquisitions as a background, we can precisely define a tumor within FLAIR that was outside of the scope of current FET-PET protocols.

Project description:PurposeConventional magnetic resonance imaging (MRI) can for glioma assessment be supplemented by positron emission tomography (PET) imaging with radiolabeled amino acids such as O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), which provides additional information on metabolic properties. In neuro-oncology, patients often undergo brain and skull altering treatment, which is known to challenge MRI-based attenuation correction (MR-AC) methods and thereby impact the simplified semi-quantitative measures such as tumor-to-brain ratio (TBR) used in clinical routine. The aim of the present study was to examine the applicability of our deep learning method, DeepDixon, for MR-AC in [18F]FET PET/MRI scans of a post-surgery glioma cohort with metal implants.MethodsThe MR-AC maps were assessed for all 194 included post-surgery glioma patients (318 studies). The subgroup of 147 patients (222 studies, 200 MBq [18F]FET PET/MRI) with tracer uptake above 1 ml were subsequently reconstructed with DeepDixon, vendor-default atlas-based method, and a low-dose computed tomography (CT) used as reference. The biological tumor volume (BTV) was delineated on each patient by isocontouring tracer uptake above a TBR threshold of 1.6. We evaluated the MR-AC methods using the recommended clinical metrics BTV and mean and maximum TBR on a patient-by-patient basis against the reference with CT-AC.ResultsNinety-seven percent of the studies (310/318) did not have any major artifacts using DeepDixon, which resulted in a Dice coefficient of 0.89/0.83 for tissue/bone, respectively, compared to 0.84/0.57 when using atlas. The average difference between DeepDixon and CT-AC was within 0.2% across all clinical metrics, and no statistically significant difference was found. When using DeepDixon, only 3 out of 222 studies (1%) exceeded our acceptance criteria compared to 72 of the 222 studies (32%) with the atlas method.ConclusionWe evaluated the performance of a state-of-the-art MR-AC method on the largest post-surgical glioma patient cohort to date. We found that DeepDixon could overcome most of the issues arising from irregular anatomy and metal artifacts present in the cohort resulting in clinical metrics within acceptable limits of the reference CT-AC in almost all cases. This is a significant improvement over the vendor-provided atlas method and of particular importance in response assessment.

Project description:The standard therapy strategy for high-grade glioma (HGG) is based on the maximal surgery followed by radio-chemotherapy (RT-CT) with insufficient control of the disease. Recurrences are mainly localized in the radiation field, suggesting an interest in radiotherapy dose escalation to better control the disease locally. We aimed to identify a similarity between the areas of high uptake on O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography/computed tomography (PET) before RT-CT, the residual tumor on post-therapy NADIR magnetic resonance imaging (MRI) and the area of recurrence on MRI. This is an ancillary study from the IMAGG prospective trial assessing the interest of FET PET imaging in RT target volume definition of HGG. We included patients with diagnoses of HGG obtained by biopsy or tumor resection. These patients underwent FET PET and brain MRIs, both after diagnosis and before RT-CT. The follow-up consisted of sequential brain MRIs performed every 3 months until recurrence. Tumor delineation on the initial MRI 1 (GTV 1), post-RT-CT NADIR MRI 2 (GTV 2), and progression MRI 3 (GTV 3) were performed semi-automatically and manually adjusted by a neuroradiologist specialist in neuro-oncology. GTV 2 and GTV 3 were then co-registered on FET PET data. Tumor volumes on FET PET (MTV) were delineated using a tumor to background ratio (TBR) ≥ 1.6 and different % SUVmax PET thresholds. Spatial similarity between different volumes was performed using the dice (DICE), Jaccard (JSC), and overlap fraction (OV) indices and compared together in the biopsy or partial surgery group (G1) and the total or subtotal surgery group (G2). Another overlap index (OV') was calculated to determine the threshold with the highest probability of being included in the residual volume after RT-CT on MRI 2 and in MRI 3 (called "hotspot"). A total of 23 patients were included, of whom 22% (n = 5) did not have a NADIR MRI 2 due to a disease progression diagnosed on the first post-RT-CT MRI evaluation. Among the 18 patients who underwent a NADIR MRI 2, the average residual tumor was approximately 71.6% of the GTV 1. A total of 22% of patients (5/23) showed an increase in GTV 2 without diagnosis of true progression by the multidisciplinary team (MDT). Spatial similarity between MTV and GTV 2 and between MTV and GTV 3 were higher using a TBR ≥ 1.6 threshold. These indices were significantly better in the G1 group than the G2 group. In the FET hotspot analysis, the best similarity (good agreement) with GTV 2 was found in the G1 group using a 90% SUVmax delineation method and showed a trend of statistical difference with those (poor agreement) in the G2 group (OV' = 0.67 vs. 0.38, respectively, p = 0.068); whereas the best similarity (good agreement) with GTV 3 was found in the G1 group using a 80% SUVmax delineation method and was significantly higher than those (poor agreement) in the G2 group (OV'= 0.72 vs. 0.35, respectively, p = 0.014). These results showed modest spatial similarity indices between MTV, GTV 2, and GTV 3 of HGG. Nevertheless, the results were significantly improved in patients who underwent only biopsy or partial surgery. TBR ≥ 1.6 and 80-90% SUVmax FET delineation methods showing a good agreement in the hotspot concept for targeting standard dose and radiation boost. These findings need to be tested in a larger randomized prospective study.

Dataset Information

Direct comparison of [11C] choline and [18F] FET PET to detect glioma infiltration: a diagnostic accuracy study in eight patients.

Publications

Direct comparison of [<sup>11</sup>C] choline and [<sup>18</sup>F] FET PET to detect glioma infiltration: a diagnostic accuracy study in eight patients.

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