Comparing with cross-sectional studies, a longitudinal design can significantly reduce the confounding effect of inter-individual morphological variability by using each subject as his or her own control. As a result, longitudinal imaging studies are getting increased interest and popularity in various aspects of neuroscience.

The standard FreeSurfer pipeline is designed for the processing of individual data set, and thus not optimal for the processing of longitudinal data. How to take into account the subject-wise and temporal correlation in a longitudinal data series and get more robust and reliable cortical and subcortical morphological measurements is an active research area in NMR center.

Although better approaches are constantly being sought, as the result of an early attempt, a longitudinal processing pipeline has been designed for the processing of longitudinal data and has shown large success. The basic idea of this longitudinal scheme is to borrow the processing results of an early time point to help the processing of

involves solving many complex nonlinear optimization problems, such as the deformable surface reconstruction, the nonlinear atlas-image registration, and the nonlinear spherical registration. These nonlinear optimization problems are usually solved using iterative methods, and the final results are known to be highly sensitive to the selection of a particular starting point (a.k.a. the initialization). It's our belief that by initializing the processing of a new data set in a longitudinal series using the processed results of an early time point, we can reduce the random variation in the processing procedure and improve the robustness and sensitivity of the overall longitudinal analysis. Such an initialization scheme makes sense also because a longitudinal design is often targeted at detecting small or subtle changes.

The longitudinal processing scheme is coded in the script called "recon-all-long", as compared to the standard FreeSurfer pipeline as described in the "recon-all" script. In the following, we list the major differences between the two scripts or the two processing streams. The two scripts will ultimatedly be combined as a single one. In the following, we assume that the longitudinal series have two time-points, tp1 and tp2, and tp1 has already been processed using the standard FreeSurfer recon-all. To process tp2 in the longitudinal way, "recon-all-long" can be used and the command reads like "recon-all-long -long -tp1 tp1 -subjid tp2 ...". "..." represents standard options as used when processing tp1.

Difference 1: The longitudinal scheme requires aligning the image data of tp2 to tp1. Due to the intra-subject correlation of the two data sets, a linear (volume) registration with a dof of 6 or 9 is enough to get a good alignment between them. The alignment/registration is performed using the FSL FLIRT program, and the registration result (a coordinate transformation matrix) will be used to transfer information from tp1 to tp2 in later steps. As can be seen in the recon-all-long script, the alignment is computed by