Landmarking the brain for geometric morphometric analysis: an error study

Abstract

Neuroanatomic phenotypes are often assessed using volumetric analysis. Although powerful and versatile, this approach is limited in that it is unable to quantify changes in shape, to describe how regions are interrelated, or to determine whether changes in size are global or local. Statistical shape analysis using coordinate data from biologically relevant landmarks is the preferred method for testing these aspects of phenotype. To date, approximately fifty landmarks have been used to study brain shape. Of the studies that have used landmark-based statistical shape analysis of the brain, most have not published protocols for landmark identification or the results of reliability studies on these landmarks. The primary aims of this study were two-fold: (1) to collaboratively develop detailed data collection protocols for a set of brain landmarks, and (2) to complete an intra- and inter-observer validation study of the set of landmarks. Detailed protocols were developed for 29 cortical and subcortical landmarks using a sample of 10 boys aged 12 years old. Average intra-observer error for the final set of landmarks was 1.9 mm with a range of 0.72 mm-5.6 mm. Average inter-observer error was 1.1 mm with a range of 0.40 mm-3.4 mm. This study successfully establishes landmark protocols with a minimal level of error that can be used by other researchers in the assessment of neuroanatomic phenotypes.

Figure 1. Landmarks and the associated error analyzed in this study.

Left lateral view of a 3D reconstruction of the brain (anterior is to the left). Projected positions of landmarks are shown with numbers corresponding to Table 2. Cortical surface landmarks are white with white wireframe; subcortical landmarks are purple with purple wireframe. The size of the pink ellipses around each landmark indicate the magnitude of average precision (error) at anatomic scale. Landmarks for which no ellipse is visible had average error less than the 1.5 mm radius of the landmark marker. Note that the greatest magnitudes of error were associated with cortical surface landmarks.

Figure 2. Histogram of the intra-observer precision of each landmark.

This histogram indicates the level of intra-observer precision associated with each landmark using the original (P1) and modified (P2) protocols. The error bar is equal to one standard deviation above and below the mean. Landmark numbers correspond with the landmark numbers in Table 2.

Figure 3. Histogram of the inter-observer precision of each landmark.

This histogram indicates the level of inter-observer precision associated with each landmark using the original (P1) and modified (P2) protocols. Landmark numbers correspond with the landmark numbers in Table 2.