Abstract: Imaging of the human brain has seen explosive growth in the last two decades mainly through the various modalities of MRI. The massive amount of data requires automatic and robust tools for analysis. FreeSurfer (FS, surfer.nmr.mgh.harvard.edu) is one of the preeminent tools used for neuroimage analysis. FS has more than 44,000 downloads, and the core FS manuscripts have been cited more than 22,000 times. FS is part of the analysis core for many NIH-funded large-scale data acquisition projects such as the Human Connectome Project (HCP), Alzheimer's Disease Neuroimaging Initiative (ADNI), Framingham Heart Study (FHS), The Adolescent Brain Cognitive Development (ABCD), as well as the UK BioBank. One third of the 600+ ADNI-based publications cite FS. Simply put, much of the innovative research done in neuroimaging would not be possible without FS. Started in 1998, FS is best known for providing detailed and automated anatomical analysis of T1-weighted MRI images, especially for the cortical surface. However, FS anatomical analysis provides an ideal substrate for all modes of brain imaging including functional MRI, diffusion MRI, PET, optical/NIRS, as well as EEG/MEG. FS provides tools to perform these analyses as well as software to integrate with other analysis tools (e.g., SPM, FSL, AFNI). FS has been used for presurgical planning and even in the operating room. The original grant mostly centered around Sequence Adaptive Multimodal Segmentation (SAMSEG). SAMSEG uses parametric Bayesian generative modeling to segment brain images. The SAMSEG framework fits atlas priors and multivariate Gaussian intensity models to brain images (including MRI artifacts such as bias fields). SAMSEG can take any modality or combination of modalities as input. Since it adapts its intensity model, it is robust to differences in scanner. Since it is a generative model, it is easy to extend to encompass more segmentation details. For example, the SAMSEG framework has been used to segment hippocampal subfield, amygdalar nuclei, thalamic nuclei, and extracerebral structures. The main vision for the renewal is to extend the SAMSEG framework to accommodate longitudinal models, incorporate more anatomical details, and to use SAMSEG output as a basis for cortical surface placement that is, like SAMSEG, modality independent and capable of using any combination of modalities. In addition, we propose a series of new tools that will assist in the individual and group analysis of large studies by creating study-specific models. In addition to this new technical development, we are requesting support for software engineering, maintenance, and user support – mundane and not innovative, but high-impact this type of support is critical to the thousands of researchers who rely on FreeSurfer.

Narrative: This work will support the popular FreeSurfer neuroimaging analysis software program used by thousands of researchers world-wide. FreeSurfer uses cutting edge algorithms to automatically extract a host of biomarkers from brain imaging data which can be used for research, pharmaceutical evaluation, and diagnosis. This proposal will allow for continued support of FreeSurfer from the developers as well as new development to make FreeSurfer faster, more robust, and easier to interpret.