Abnormal metabolism of tryptophan has been implicated in modulation of tumor cell proliferation and immunoresistance. a-[ 11 C]Methyl-L-tryptophan (AMT) is a PET tracer to measure cerebral tryptophan metabolism in vivo. In the present study, we have measured tumor tryptophan uptake in 40 patients with primary brain tumors using AMT PET and standard uptake values (SUV). Tryptophan metabolism was further quantified in 23 patients using blood input data. Estimates of the volume of distribution (VD 0 ) and the metabolic rate constant (k 3 0 ) were calculated and related to magnetic resonance imaging (MRI) and histology findings. All grade II to IV gliomas and glioneuronal tumors showed increased AMT SUV, including all recurrent/residual tumors. Gadolinium enhancement on MRI was associated with high VD 0 values, suggesting impaired blood-brain barrier, while k 3 0 values were not related to contrast enhancement. Low-grade astrocytic gliomas showed increased tryptophan metabolism, as measured by k 3 0 . In contrast, oligodendrogliomas showed high VD 0 values but lower k 3 0 as compared with normal cortex. In astrocytic tumors, low grade was associated with high k 3 0 and lower VD 0 , while high-grade tumors showed the reverse pattern. The findings show high AMT uptake in primary and residual/recurrent gliomas and glioneuronal tumors. Increased AMT uptake can be due to increased metabolism of tryptophan and/ or high volume of distribution, depending on tumor type and grade. High tryptophan metabolic rates in low-grade tumors may indicate activation of the kynurenine pathway, a mechanism regulating tumor cell growth. AMT PET might be a useful molecular imaging method to guide therapeutic approaches aimed at controlling tumor cell proliferation by acting on tryptophan metabolism.
Summary: Purpose:We studied the relation between quantitative interictal subdural EEG data and visually defined ictal subdural EEG findings in children with intractable neocortical epilepsy, and determined whether interictal EEG data are predictive of ictal EEG onset zones.Methods: Thirteen children (aged 1.2-15.4 years) underwent prolonged intracranial EEG recording, using 48-to 120-channel subdural electrodes. Three distinct 10-min segments of the continuous interictal EEG recording were selected for each patient, and the spike frequency for each channel was determined by using an automatic spike-detection program. Subsequently the average spike frequency of each electrode was compared with ictal assessment (onset, spread, and no early ictal involvement). In addition, 50 distinct interictal spikes were averaged for each patient, and the amplitude and latency after the leading spike (averaged spike showing the earliest peak) were measured for each electrode and analyzed with respect to ictal EEG findings.Results: Reproducibility of the spike-frequency pattern derived from three 10-min segments was high (Kendall's W, 0.85 ± 0.08). Electrodes showing the highest spike frequency, the highest spike amplitude, and the leading spike were found to be a part of the seizure onset in 13 of 13, 12 of 13, and 10 of 13 cases, respectively. There was significant correlation between ictal assessment and spike frequency as well as spike amplitude. A receiver operating characteristics analysis showed that a cutoff threshold at 14% of the maximal spike frequency resulted in a specificity of 0.90 and a sensitivity of 0.77 for the detection of seizure-onset electrodes.Conclusions: Quantitative interictal subdural EEG may predict ictal-onset zones in children with intractable neocortical epilepsy. Key Words: Clinical neurophysiology-Pediatric epilepsy surgery-Quantitative interictal intracranial electroencephalography-Focal cortical dysplasia-Tuberous sclerosis complex.Cortical resection is an effective treatment for selected children with medically intractable partial epilepsy of neocortical origin (1). To delineate the exact resection margin in patients with neocortical epilepsy, prolonged subdural EEG recordings are frequently used in most epilepsy surgery centers (2). It is generally assumed that epileptogenic cortex includes seizure-onset zones, regions consistently receiving early ictal propagation, regions showing independent frequent interictal epileptiform activity, and structural lesions delineated on neuroimaging (1). Complete resection of seizure-onset zones after prolonged intracranial EEG recording does not necessarily result in a good surgical outcome (3-6).In addition, previous studies reported that >70% of patients with developmental cortical malformations showed interictal epileptiform activity beyond structural lesions and involving several lobes (4,7). Thus the assessment of intracranial interictal epileptiform activity in addition to ictal-onset zones is currently considered important in the presurgical evaluat...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.