Quantitative PET/MR imaging is challenged by the accuracy of synthetic CT (sCT) generation from MR images. Deep learning-based algorithms have recently gained momentum for a number of medical image analysis applications. In this work, a novel sCT generation algorithm based on deep learning adversarial semantic structure (DL-AdvSS) is proposed for MRI-guided attenuation correction in brain PET/MRI. The proposed DL-AdvSS algorithm exploits the ASS learning framework to constrain the synthetic CT generation process to comply with the extracted structural features from CT images. The proposed technique was evaluated through comparison to an atlas-based sCT generation method (Atlas), previously developed for MRI-only or PET/MRI-guided radiation planning. Moreover, the commercial segmentation-based approach (Segm) implemented on the Philips TF PET/MRI system was included in the evaluation. Clinical brain studies of 40 patients who underwent PET/CT and MR imaging were used for the evaluation of the proposed method under a two-fold cross validation scheme. The accuracy of cortical bone extraction and CT value estimation were investigated for the three different methods. Atlas and DL-AdvSS exhibited similar cortical bone extraction accuracy resulting in a Dice coefficient of 0.78 ± 0.07 and 0.77 ± 0.07, respectively. Likewise, DL-AdvSS and Atlas techniques performed similarly in terms of CT value estimation in the cortical bone region where a mean error (ME) of less than -11 HU was obtained. The Segm approach led to a ME of -1025 HU. Furthermore, the quantitative analysis of corresponding PET images using the three approaches assuming the CT-based attenuation corrected PET (PETCTAC) as reference demonstrated comparative performance of DL-AdvSS and Atlas techniques with a mean standardized uptake value (SUV) bias less than 4% in 63 brain regions. In addition, less that 2% SUV bias was observed in the cortical bone when using Atlas and DL-AdvSS approaches. However, Segm resulted in 14.7 ± 8.9% SUV underestimation in the cortical bone. The proposed DL-AdvSS approach demonstrated competitive performance with respect to the state-of-the-art atlas-based technique achieving clinically tolerable errors, thus outperforming the commercial segmentation approach used in the clinic.