How much are clinical fMRI reports influenced by standard postprocessing methods? An investigation of normalization and region of interest effects in the medial temporal lobe

Abstract

Recent evidence has indicated that standard postprocessing methods such as template-based region of interest (ROI) definition and normalization of individual brains to a standard template may influence final outcome of functional magnetic resonance imaging investigations. Here, we provide the first comprehensive investigation into whether ROI definition and normalization may also change the clinical interpretation of patient data. A series of medial temporal lobe epilepsy patients were investigated with a clinical memory paradigm and individually delineated as well as template-based ROIs. Different metrics for activation quantification were applied. Results show that the application of template-based ROIs can significantly change the clinical interpretation of individual patient data. This relates to sensitivity for brain activation and hemispheric dominance. We conclude that individual ROIs should be defined on nontransformed functional data and that use of more than one metric for activation quantification is beneficial.

Figure 1

Example of delineation of individual nonnormalized ROIs on nonnormalized functional EPI images. Two adjacent coronal slices are shown (Patient GR) in radiological convention. (A) Anatomical images, (B) interpolated nonnormalized functional images, (C) nonnormalized functional images with individual ROIs (not interpolated), and (D) Same as (C) but with MTL activation overlaid (thresholded ROI analysis).

Figure 2

Comparison of normalized ROIs (patient KO). From left to right: coronal section of normalized functional EPI image (radiological convention), individual normalized ROIs shown in green, mean group ROIs shown in purple, standard ROI shown in blue. The dotted line indicates the upper border of the sub‐ROIs used to analyze neuroanatomical coverage of basal MTL (see text).

Figure 3

Comparison of MTL activation covered by the different ROIs (patient KO). Same conventions as in Figure 2. Individual MTL activations identified in the thresholded whole brain analysis are shown (and formed the functional ROI). Activity outside ROIs is shown in brown.

Figure 4

Example of the influence of ROI definitions on lateralization results (Patient ZN). Same ROI conventions as in Figure 2. Brain activation as detected by the ROIs is shown (thresholded whole brain analysis). A significant left dominance changes to a significant right dominance with the standard ROI (blue).

Figure 5

Mismatch in basal extension of the Standard ROI (upper row, blue color), basal extension of the temporal lobe of the MNI 152 anatomical template (upper row) and basal extension of the temporal lobe of the EPI template (lower row). Corresponding transversal sections.