Source-to-Target Automatic Rotating Estimation (STARE) – a publicly-available, blood-free quantification approach for PET tracers with irreversible kinetics: Theoretical framework and validation for [18F]FDG

Abstract Background The molecular diagnosis of gliomas such as isocitrate dehydrogenase (IDH) status (wild-type [wt] or mutation [mut]) is especially important in the 2016 WHO classification. Positron emission tomography (PET) has afforded molecular and metabolic diagnostic imaging. The present study aimed to define the interrelationship between the 2016 WHO classification of gliomas and the integrated data from PET images using multiple tracers, including 18F-fluorodeoxyglucose ( 18F-FDG), 11C-methionine ( 11C-MET), 18F-fluorothymidine ( 18F-FLT), and 18F-fluoromisonidazole ( 18F-FMISO). Methods This retrospective, single-center study comprised 113 patients with newly diagnosed glioma based on the 2016 WHO criteria. Patients were divided into four glioma subtypes (Mut, Codel, Wt, and glioblastoma multiforme [GBM]). Tumor standardized uptake value (SUV) divided by mean normal cortical SUV (tumor-normal tissue ratio [TNR]) was calculated for 18F-FDG, 11C-MET, and 18F-FLT. Tumor-blood SUV ratio (TBR) was calculated for 18F-FMISO. To assess the diagnostic accuracy of PET tracers in distinguishing glioma subtypes, a comparative analysis of TNRs and TBR as well as the metabolic tumor volume (MTV) were calculated by Scheffe’s multiple comparison procedure for each PET tracer following the Kruskal–Wallis test. Results The differences in mean 18F-FLT TNR and 18F-FMISO TBR were significant between GBM and other glioma subtypes (p < 0.001). Regarding the comparison between Gd-T1WI volumes and 18F-FLT MTVs or 18F-FMISO MTVs, we identified significant differences between Wt and Mut or Codel (p < 0.01). Conclusion Combined administration of four PET tracers might aid in the preoperative differential diagnosis of gliomas according to the 2016 WHO criteria.

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CBMT-03. EVALUATION OF PET TRACERS TO DIFFERENTIATE IDH1 MUTANT GBM

Neuro-Oncology ◽

10.1093/neuonc/noz175.125 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi33-vi33

Author(s):

Andrei Molotkov ◽

Angeliki Mela ◽

Peter D Canoll ◽

Akiva Mintz

Keyword(s):

Amino Acid ◽

Pet Imaging ◽

Causal Link ◽

Amino Acid Derivative ◽

Normal Brain ◽

Pet Tracers ◽

Pet Tracer ◽

Altered Glucose ◽

Pet Ct ◽

18F Fdg

Abstract OBJECTIVE PET/CT offers the unique potential to noninvasively evaluate biomarker expression and aberrant metabolism. 18F-FDG has driven PET/CT to the forefront of cancer imaging, as altered glucose metabolism is a hallmark of oncogenesis. However, 18F-FDG is suboptimal for GBM due to high physiologic uptake in normal brain. The development of alternative tracers has reignited the field of PET/CT in GBM and offers hope for diagnosis and molecular staging in GBM. We hypothesize that fundamental differences in metabolism and oncogene expression present in IDH1 mutatant gliomas can be shown using PET imaging, as has been suggested in some correlative clinical studies. Our objective was therefore to establish a causal link between IDH1 mutation in GBM and uptake of targeted PET tracers in a unique proneural GBM transgenic model characterized by p53, IDH1 mutations and PDGF expression. METHODS We examined the uptake of 3 blood-brain-barrier (BBB) penetrant tracers that have been used in GBM: (a) 18F-FDG, a surrogate for increased glycolysis; (b) 18F-Fluciclovine, an amino acid derivative transported into cells through the energy-independent L-type amino acid transporter (LAT) system and is approved by the FDA for prostate cancer; and (c) 11C-ER176, a tracer that binds the TSPO receptor that is generally expressed on activated microglia as well as GBM. RESULTS We did not observe significant differences in 18F-FDG uptake between wt and IDH mutant GBM cells. However, we found that IDH mutant GBM cells demonstrated significantly increased 18F-Fluciclovine (47%) and 11C-ER176 (53%) versus IDH wt cells. CONCLUSION We have established a causal link between IDH mutation status and uptake of (a) 18F-Fluciclovine, a promising FDA approved PET tracer and (b) 11C-ER176, a second generation TSPO ligand. Thus, we are performing further studies in orthotopic syngeneic GBM models to determine if PET imaging can non-invasively demonstrate molecular characterization and therapeutic stratification in glioma.

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NI-15 THE USEFULNESS OF PET IMAGING IN MOLECULAR DIAGNOSIS OF GLIOMA

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.127 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii28-ii28

Author(s):

Tomoya Ogawa ◽

Keisuke Miyake ◽

Takeshi Fujimori ◽

Daisuke Ogawa ◽

Masaki Okada ◽

...

Keyword(s):

Molecular Diagnosis ◽

Standardized Uptake Value ◽

Wild Type ◽

Pet Tracers ◽

Significant Difference ◽

The Central Nervous System ◽

Classification Of Tumors ◽

18F Fdg ◽

Supratentorial Glioma

Abstract OBJECTIVE After WHO 2016 Classification of Tumors of the Central Nervous System have published, molecular diagnosis became part of the diagnostic criteria. In this study, we investigated the correlation between PET images and molecular diagnosis of glioma. METHODS We performed retrospective review of newly diagnosed supratentorial glioma patients who preoperatively underwent all four PET examinations (18F-FDG, 11C-MET, 18F-FLT and 18F-FMISO) from April 2009 to March 2019. The standardized uptake value (SUV) from the accumulation of each PET tracers, TNR (tumor to contralateral normal tissue ratio) of 18F-FDG,11C-MET and 18F-FLT, TBR (tumor to blood values ratio) of 18F-FMISO were measured. We investigated the correlation between these PET images and molecular diagnosis of glioma. RESULTS Data from total of 79 patients which were 42 cases of IDH wild type glioblastoma, 2 cases of IDH mutated glioblastoma, 9 cases of IDH wild type astrocytoma, 13 cases of IDH mutated astrocytoma and 13 cases of IDH mutated and 1p/19q co-deleted oligodendroglioma were included in this study. Both TNR of 11C-MET(p<0.01) and 18F-FLT(p<0.01), and also TBR of 18F-FMISO(p<0.01) in IDH wild type gliomas showed significantly higher than IDH mutated gliomas. In WHO Gr2-3 gliomas, only TNR of 18F-FLT showed a significant difference between IDH wild type gliomas and IDH mutated gliomas(p<0.01). TNR of 18F-FLT(p<0.01) and TBR of 18F-FMISO(p<0.01) in 1p/19q co-deleted gliomas were significantly lower than gliomas without 1p/19q co-deletion, but there were no significant differences in WHO Gr2-3 gliomas. Among IDH mutated gliomas, TNR of 11C-MET in 1p/19q co-deleted gliomas showed significantly higher uptake than gliomas without 1p/19q co-deletion(p<0.05). CONCLUSION Preoperative PET evaluation of each PET tracers may be useful for the molecular diagnosis of glioma.

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Mind wandering as data augmentation: How mental travel supports abstraction

Behavioral and Brain Sciences ◽

10.1017/s0140525x1900311x ◽

2020 ◽

Vol 43 ◽

Author(s):

Myrthe Faber

Keyword(s):

Machine Learning ◽

Data Augmentation ◽

Mental Content ◽

Mind Wandering ◽

Theoretical Framework ◽

Important Addition

Abstract Gilead et al. state that abstraction supports mental travel, and that mental travel critically relies on abstraction. I propose an important addition to this theoretical framework, namely that mental travel might also support abstraction. Specifically, I argue that spontaneous mental travel (mind wandering), much like data augmentation in machine learning, provides variability in mental content and context necessary for abstraction.

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Adaptive and Maladaptive Neural Plasticity Due to Facial Nerve Palsy

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000244 ◽

2016 ◽

Vol 224 (2) ◽

pp. 102-111 ◽

Cited By ~ 1

Author(s):

Carsten M. Klingner ◽

Stefan Brodoehl ◽

Gerd F. Volk ◽

Orlando Guntinas-Lichius ◽

Otto W. Witte

Keyword(s):

Facial Nerve ◽

Neural Plasticity ◽

Cortical Plasticity ◽

Brain Plasticity ◽

Motor Nerve ◽

Predictive Coding ◽

Theoretical Framework ◽

Cortical Reorganization ◽

Nerve Lesion ◽

Peripheral Facial Palsy

Abstract. This paper reviews adaptive and maladaptive mechanisms of cortical plasticity in patients suffering from peripheral facial palsy. As the peripheral facial nerve is a pure motor nerve, a facial nerve lesion is causing an exclusive deefferentation without deafferentation. We focus on the question of how the investigation of pure deefferentation adds to our current understanding of brain plasticity which derives from studies on learning and studies on brain lesions. The importance of efference and afference as drivers for cortical plasticity is discussed in addition to the crossmodal influence of different competitive sensory inputs. We make the attempt to integrate the experimental findings of the effects of pure deefferentation within the theoretical framework of cortical responses and predictive coding. We show that the available experimental data can be explained within this theoretical framework which also clarifies the necessity for maladaptive plasticity. Finally, we propose rehabilitation approaches for directing cortical reorganization in the appropriate direction and highlight some challenging questions that are yet unexplored in the field.

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