PurposePET/MRI quantitative accuracy for neurological applications is challenging due to accuracy of the PET attenuation correction. In this work, we proposed and evaluated an automatic pipeline for assessing the quantitative accuracy of four different MRI = based attenuation correction (PET MRAC) approaches.MethodsThe proposed pipeline consists of a synthetic lesion insertion tool and the FreeSurfer neuroimaging analysis framework. The synthetic lesion insertion tool is used to insert simulated spherical, and brain regions of interest (ROI) into the PET projection space and reconstructed with four different PET MRAC techniques, while FreeSurfer is used to generate brain ROIs from T1 weighted MRI image. Using a cohort of 11 patients’ brain PET dataset, the quantitative accuracy of four MRAC(s), which are: DIXON AC, DIXONbone AC, UTE AC, and Deep learning trained with DIXON AC, named DL-DIXON AC, were compared to the PET-based CT attenuation correction (PET CTAC). MRAC to CTAC activity bias in spherical lesions and brain ROIs were reconstructed with and without background activity and compared to the original PET images.ResultsThe proposed pipeline provides accurate and consistent results for inserted spherical lesions and brain ROIs inserted with and without considering the background activity and following the same MRAC to CTAC pattern as the original brain PET images. As expected, the DIXON AC showed the highest bias; the second was for the UTE, then the DIXONBone, and the DL-DIXON with the lowest bias. For simulated ROIs inserted in the background activity, DIXON showed a −4.65% MRAC to CTAC bias, 0.06% for the DIXONbone, −1.70% for the UTE, and - 0.23% for the DL-DIXON. For lesion ROIs inserted without background activity, DIXON showed a −5.21%, −1% for the DIXONbone, −2.55% for the UTE, and - 0.52 for the DL-DIXON. For MRAC to CTAC bias calculated using the same 16 FreeSurfer brain ROIs in the original brain PET reconstructed images, a 6.87% was observed for the DIXON, −1.83% for DIXON bone, −3.01% for the UTE, and - 0.17% for the DL-DIXON.ConclusionThe proposed pipeline provides accurate and consistent results for synthetic spherical lesions and brain ROIs inserted with and without considering the background activity; hence a new attenuation correction approach can be evaluated without using measured PET emission data.