Positron emission tomography (PET) represents molecular imaging for non-invasive phenotyping of physiological and biochemical processes in various oncological diseases. PET imaging with 18 F-fluorodeoxyglucose ( 18 F-FDG) for glucose metabolism evaluation is the standard imaging modality for the clinical management of lymphoma. One of the 18 F-FDG PET applications is the detection and pre-treatment staging of lymphoma, which is highly sensitive. 18 F-FDG PET is also applied during treatment to evaluate the individual chemo-sensitivity and accordingly guide the response-adapted therapy. At the end of the therapy regiment, a negative PET scan is indicative of a good prognosis in patients with advanced Hodgkin's lymphoma and diffuse large B-cell lymphoma. Thus, adjuvant radiotherapy may be alleviated. Future PET studies using non-18 F-FDG radiotracers, such as 68 Ga-labeled pentixafor (a cyclic pentapeptide that enables sensitive and high-contrast imaging of C-X-C motif chemokine receptor 4), 68 Ga-labeled fibroblast activation protein inhibitor (FAPI) that reflects the tumor microenvironment, and 89 Zr-labeled atezolizumab that targets the programmed cell death-ligand 1 (PD-L1), may complement 18 F-FDG and offer essential tools to decode lymphoma phenotypes further and identify the mechanisms of lymphoma therapy.

Background PET imaging has been widely used in diagnosis of neurological disorders; however, its application to pediatric population is limited due to lacking pediatric age–specific PET template. This study aims to develop a pediatric age–specific PET template (PAPT) and conduct a pilot study of epileptogenic focus localization in pediatric epilepsy. Methods We recruited 130 pediatric patients with epilepsy and 102 age-matched controls who underwent 18F-FDG PET examination. High-resolution PAPT was developed by an iterative nonlinear registration-averaging optimization approach for two age ranges: 6–10 years (n = 17) and 11–18 years (n = 50), respectively. Spatial normalization to the PAPT was evaluated by registration similarities of 35 validation controls, followed by estimation of potential registration biases. In a pilot study, epileptogenic focus was localized by PAPT-based voxel-wise statistical analysis, compared with multi-disciplinary team (MDT) diagnosis, and validated by follow-up of patients who underwent epilepsy surgery. Furthermore, epileptogenic focus localization results were compared among three templates (PAPT, conventional adult template, and a previously reported pediatric linear template). Results Spatial normalization to the PAPT significantly improved registration similarities (P < 0.001), and nearly eliminated regions of potential biases (< 2% of whole brain volume). The PAPT-based epileptogenic focus localization achieved a substantial agreement with MDT diagnosis (Kappa = 0.757), significantly outperforming localization based on the adult template (Kappa = 0.496) and linear template (Kappa = 0.569) (P < 0.05). The PAPT-based localization achieved the highest detection rate (89.2%) and accuracy (80.0%). In postsurgical seizure-free patients (n = 40), the PAPT-based localization also achieved a substantial agreement with resection areas (Kappa = 0.743), and the highest detection rate (95%) and accuracy (80.0%). Conclusion The PAPT can significantly improve spatial normalization and epileptogenic focus localization in pediatric epilepsy. Future pediatric neuroimaging studies can also benefit from the unbiased spatial normalization by PAPT. Trial registration. NCT04725162: https://clinicaltrials.gov/ct2/show/NCT04725162

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