Inter-Method Discrepancies in Brain Volume Estimation May Drive Inconsistent Findings in Autism

Previous studies applying automatic preprocessing methods on Structural Magnetic Resonance Imaging (sMRI) report inconsistent neuroanatomical abnormalities in Autism Spectrum Disorder (ASD). In this study we investigate inter-method differences as a possible cause behind these inconsistent findings. In particular, we focus on the estimation of the following brain volumes: gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), and total intra cranial volume (TIV). T1-weighted sMRIs of 417 ASD subjects and 459 typically developing controls (TDC) from the ABIDE dataset were estimated using three popular preprocessing methods: SPM, FSL, and FreeSurfer (FS). Brain volumes estimated by the three methods were correlated but had significant inter-method differences; except TIV_SPM vs. TIV_FS, all inter-method differences were significant. ASD vs. TDC group differences in all brain volume estimates were dependent on the method used. SPM showed that TIV, GM, and CSF volumes of ASD were larger than TDC with statistical significance, whereas FS and FSL did not show significant differences in any of the volumes; in some cases, the direction of the differences were opposite to SPM. When methods were compared with each other, they showed differential biases for autism, and several biases were larger than ASD vs. TDC differences of the respective methods. After manual inspection, we found inter-method segmentation mismatches in the cerebellum, sub-cortical structures, and inter-sulcal CSF. In addition, to validate automated TIV estimates we performed manual segmentation on a subset of subjects. Results indicate that SPM estimates are closest to manual segmentation, followed by FS while FSL estimates were significantly lower. In summary, we show that ASD vs. TDC brain volume differences are method dependent and that these inter-method discrepancies can contribute to inconsistent neuroimaging findings in general. We suggest cross-validation across methods and emphasize the need to develop better methods to increase the robustness of neuroimaging findings.