Differential Spatial Distribution of TSPO or Amino Acid PET Signal and MRI Contrast Enhancement in Gliomas

In this study, dual PET and contrast enhanced MRI were combined to investigate their correlation per voxel in patients at initial diagnosis with suspected glioblastoma. Correlation with contrast enhancement (CE) as an indicator of BBB leakage was further used to evaluate whether PET signal is likely caused by BBB disruption alone, or rather attributable to specific binding after BBB passage. PET images with [18F]GE180 and the amino acid [18F]FET were acquired and normalized to healthy background (tumor-to-background ratio, TBR). Contrast enhanced images were normalized voxel by voxel with the pre-contrast T1-weighted MRI to generate relative CE values (rCE). Voxel-wise analysis revealed a high PET signal even within the sub-volumes without detectable CE. No to moderate correlation of rCE with TBR voxel-values and a small overlap as well as a larger distance of the hotspots delineated in rCE and TBR-PET images were detected. In contrast, voxel-wise correlation between both PET modalities was strong for most patients and hotspots showed a moderate overlap and distance. The high PET signal in tumor sub-volumes without CE observed in voxel-wise analysis as well as the discordant hotspots emphasize the specificity of the PET signals and the relevance of combined differential information from dual PET and MRI images.

Case Report: Detection of Symptomatic Treatment-Related Changes in a Patient With Anaplastic Oligodendroglioma Using FET PET

Following local and systemic treatment of gliomas, the differentiation between glioma relapse and treatment-related changes such as pseudoprogression or radiation necrosis using conventional MRI is limited. To overcome this limitation, various amino acid PET tracers such as O-[2-(18F)-fluoroethyl]-L-tyrosine (FET) are increasingly used and provide valuable additional clinical information. We here report neuroimaging findings in a clincally symptomatic 53-year-old woman with a recurrent anaplastic oligodendroglioma with MRI findings highly suspicious for tumor progression. In contrast, FET PET imaging suggested treatment-related changes considerably earlier than the regression of contrast enhancement on MRI. In patients with oligodendroglioma, the phenomenon of symptomatic treatment-related changes is not well described, making these imaging findings unique and important for clinical decision-making.

RADT-12. USE OF FDOPA PET FOR RADIATION THERAPY TARGETING IN GRADE 2 IDH MUTANT GLIOMA

BACKGROUND Low-grade, IDH mutant (IDHmt) gliomas typically do not enhance on MRI complicating radiotherapy (RT) target delineation. Amino acid PET using 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (FDOPA) has demonstrated avidity in IDHmt gliomas and may assist in RT planning for non-enhancing tumors. This study aims to compare conventional and FDOPA-defined target volumes in grade 2 IDHmt gliomas. METHODS In a prospective pilot study, patients underwent MRI and FDOPA PET using a 3T MRI/PET system followed by standard therapy. Gross tumor volumes (GTV) included the T2/FLAIR abnormality and surgical cavity; clinical target volumes (CTV) included a 1 cm expansion constrained anatomically. Metabolic target volumes (MTVs) were generated using the FDOPA SUV > 1.5-fold normal brain isocurve. Union of GTV and MTV generated a fusion GTV (fGTV); expanding fGTV by 1 cm yielded the fusion CTV (fCTV). Target volumes were compared volumetrically with overlap (Dice coefficient) and surface metrics (Hausdorff distance). Medians are reported with ranges. RESULTS Four patients with grade 2 IDHmt glioma (3 1p/19q codeleted oligodendrogliomas, 1 non-codeleted astrocytoma) received MRI/PET before treatment. All oligodendrogliomas exhibited FDOPA avidity; the astrocytoma showed no avidity. GTV and CTV measured 16.1 cc (4.9 - 82.2 cc) and 76.7 cc (29.5 - 256.1 cc), respectively. The MTV volume outside of GTV was 0.8 cc (0.2 – 6.1 cc), but was covered in each case by the CTV. Addition of FDOPA increased fGTV and fCTV volumes by 5.4% and 17.5%, respectively. Dice coefficient and Hausdorff distances for GTV vs fGTV were 0.96 (0.95 - 0.99) and 11.2 mm (10.0 – 11.9 mm), respectively, and for CTV vs fCTV were 0.87 (0.81 – 0.95) and 10.2 mm (10.0 - 11.0), respectively. CONCLUSIONS FDOPA PET identified tracer-avid regions outside of MRI-defined GTVs in a group of IDHmt gliomas. FDOPA PET provides useful metabolic information for RT planning and warrants further investigation.

NIMG-18. [18F]FLUCICLOVINE PET TO DISTINGUISH PSEUDOPROGRESSION FROM TUMOR PROGRESSION IN POST-TREATMENT GLIOBLASTOMA

Differentiation of true tumor progression (TP) from pseudoprogression (PsP) is a major unmet need in patients with glioblastoma. [18F]Fluciclovine is a synthetic amino acid PET radiotracer that is FDA-approved in biochemical recurrence in prostate cancer. The study aim was to assess the value of [18F]Fluciclovine PET in differentiation of histologically confirmed (“true”) TP and PsP in post-treatment of glioblastoma. METHODS: 23 patients with glioblastoma with new contrast-enhancing lesions or lesions showing increased enhancement ( > 25% increase) on standard MRI after completion of radiation underwent 60-minutes dynamic [18F]Fluciclovine PET imaging. Patients subsequently underwent resection of enhancing lesion and tumor percentage vs. treatment-related changes were quantified on histopathology. Patients were considered "true” TP if tumor represented ≥ 50% of the resected specimen, mixed TP-PsP if < 50% and > 10%, and PsP if tumor represented ≤ 10%. Summed 30- to 40-minute post-injection PET images were used to measure SUVpeak and SUVmax (g/mL units). RESULTS: 15 patients with “true” TP, 3 with mixed TP-PsP, and 5 with PsP were included. There was a positive correlation between SUVpeak by PET and tumor percentage by histology (Rho= 0.56, p= 0.006). Patients who demonstrated “true” TP had significantly higher SUVpeak compared to patients with histological PsP (4.8±1.6 vs 2.9± 1.0, p= 0.02, AUC= 0.91, n=20). SUVpeak cut-off of 3.3 provided 93% sensitivity, 80% specificity, and 90% accuracy for differentiation of “true” TP from PsP. Patients with “true” TP/mixed TP-PsP also had significantly higher SUVpeak than patients with PsP (4.6±1.5 vs 2.9± 1.0, p= 0.03, AUC= 0.88, n=23). SUVmax and partial volume-corrected SUVpeak and SUVmax exhibited similar performance. CONCLUSION: Our results indicated that [18F]Fluciclovine PET imaging can accurately differentiate “true” TP from PsP. Further studies are required to confirm these promising early results and determine optimal criteria for interpreting [18F]Fluciclovine PET to distinguish PsP from TP.

Differential Spatial Distribution of TSPO or Amino Acid PET Signal and MRI Contrast Enhancement in Gliomas

In this study dual PET and contrast enhanced MRI were combined to investigate their correlation per voxel in patients at initial diagnosis with suspected glioblastoma. Correlation with contrast enhancement (CE) as an indicator of BBB leakage was further used to evaluate whether PET signal is likely caused by BBB disruption alone, or rather attributable to specific binding after BBB passage. PET images with [18F]GE180 and the amino acid [18F]FET were acquired and normalized to healthy background (TBR). Contrast enhanced images were normalized voxel by voxel with the pre-contrast T1-weighted MRI to generate relative CE values (rCE). Voxel-wise analysis revealed a high PET signal even within the sub-volumes without detectable CE. No to moderate correlation of rCE with TBR voxel-values and a small overlap as well as a larger distance of the hotspots delineated in rCE and TBR-PET images were detected. In contrast, voxel-wise correlation between both PET modalities was strong for most patients and hotspots showed a moderate overlap and distance. The high PET signal in tumor sub-volumes without CE observed in voxel-wise analysis as well as the discordant hotspots emphasize the specificity of the PET signals and the relevance of combined differential information from dual PET and MRI images.

Combined amino acid PET-MRI for identifying recurrence in post-treatment gliomas: together we grow

Purpose The aim of this study is to compare the diagnostic accuracy of amino acid PET, MR perfusion and diffusion as stand-alone modalities and in combination in identifying recurrence in post-treatment gliomas and to qualitatively assess spatial concordance between the three modalities using simultaneous PET-MR acquisition. Methods A retrospective review of 48 cases of post-treatment gliomas who underwent simultaneous PET-MRI using C11 methionine as radiotracer was performed. MR perfusion and diffusion sequences were acquired during the PET study. The following parameters were obtained: TBRmax, TBRmean, SUVmax, and SUVmean from the PET images; rCBV from perfusion; and ADCmean and ADCratio from the diffusion images. The final diagnosis was based on clinical/imaging follow-up and histopathology when available. ROC curve analysis in combination with logistic regression analysis was used to compare the diagnostic performance. Spatial concordance between modalities was graded as 0, 1, and 2 representing discordance, < 50% and > 50% concordance respectively. Results There were 35 cases of recurrence and 13 cases of post-treatment changes without recurrence. The highest area under curve (AUC) was obtained for TBRmax followed by rCBV and ADCratio. The AUC increased significantly with a combination of rCBV and TBRmax. Amino acid PET showed the highest diagnostic accuracy and maximum agreement with the final diagnosis. There was discordance between ADC and PET in 22.9%, between rCBV and PET in 16.7% and between PET and contrast enhancement in 14.6% cases. Conclusion Amino acid PET had the highest diagnostic accuracy in identifying recurrence in post-treatment gliomas. Combination of PET with MRI further increased the AUC thus improving the diagnostic performance.

18F-FACBC PET/MRI in the evaluation of human brain metastases: a case report

Background Patients with metastatic cancer to the brain have a poor prognosis. In clinical practice, MRI is used to delineate, diagnose and plan treatment of brain metastases. However, MRI alone is limited in detecting micro-metastases, delineating lesions and discriminating progression from pseudo-progression. Combined PET/MRI utilises superior soft tissue images from MRI and metabolic data from PET to evaluate tumour structure and function. The amino acid PET tracer 18F-FACBC has shown promising results in discriminating high- and low-grade gliomas, but there are currently no reports on its use on brain metastases. This is the first study to evaluate the use of 18F-FACBC on brain metastases. Case presentation A middle-aged female patient with brain metastases was evaluated using hybrid PET/MRI with 18F-FACBC before and after stereotactic radiotherapy, and at suspicion of recurrence. Static/dynamic PET and contrast-enhanced T1 MRI data were acquired and analysed. This case report includes the analysis of four 18F-FACBC PET/MRI examinations, investigating their utility in evaluating functional and structural metastasis properties. Conclusion Analysis showed high tumour-to-background ratios in brain metastases compared to other amino acid PET tracers, including high uptake in a very small cerebellar metastasis, suggesting that 18F-FACBC PET can provide early detection of otherwise overlooked metastases. Further studies to determine a threshold for 18F-FACBC brain tumour boundaries and explore its utility in clinical practice should be performed.

Combined Amino Acid Pet-Mri for Differentiating Recurrence from Radiation Necrosis in Gliomas- Together We Grow

PURPOSE: To compare the diagnostic accuracy of amino acid PET, MR perfusion and diffusion as stand-alone modalities and in combination in differentiating recurrence from radiation necrosis in post-treatment gliomas and to qualitatively assess spatial concordance between the three modalities using simultaneous PET-MR acquisition.METHODS: A retrospective review of 48 cases of post-treatment gliomas who underwent simultaneous PET-MRI using C11 Methionine as radiotracer was performed. MR perfusion and diffusion sequences were acquired during the PET study. The following parameters were obtained: TBRmax, TBRmean, SUVmax and SUVmean from the PET images, rCBV from perfusion, ADCmean and ADCratio from the diffusion images. The final diagnosis was based on clinical/imaging follow-up and histopathology when available. ROC curve analysis in combination with logistic regression analysis was used to compare the diagnostic performance. Spatial concordance between modalities was graded as 0,1 and 2 representing discordance, <50% and >50% concordance respectively.RESULTS: There were 35 cases of recurrence and 13 cases of radiation necrosis. The highest area under curve(AUC) was obtained for TBRmax followed by rCBV and ADCratio. The AUC increased significantly with a combination of rCBV and TBRmax. Amino acid PET showed the highest diagnostic accuracy and maximum agreement with the final diagnosis. There was discordance between ADC and PET in 22.9%, between rCBV and PET in 16.7% and between PET and contrast enhancement in 14.6% cases.CONCLUSIONAmino acid PET had the highest diagnostic accuracy in differentiating radiation necrosis from recurrence. Combination of PET with MRI further increased the AUC thus improving the diagnostic performance.