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Landmark-Free Three-dimensional Quantification of Morphological Variation and Shape Change in the Mouse Mandible: Methodological Development and Application


Objectives: Current methodologies in the field of morphometrics still employ the use of 2-dimensional images followed by a landmark-based Procrustes superimposition method to evaluate differences in shape, which can be tedious, subject to operator error, and fail to capture the true nature of shape variation between samples. The primary objective of this study is to address these limitations through the exploration and application of current methodologies used in neuroimaging and brain mapping to the field of morphometrics. By collaborating with Paul Thompson and his team at the Laboratory of Neuroimaging (LONI), we aim to:

1. Generate a 3D surface image of the mouse mandible and create an average surface for a cross sectional sample of parental strains in the Hybrid Mouse Diversity Panel (HMDP), as well as a developing longitudinal sample within a single strain.

2. Apply and modify the latest technologies used in brain mapping research to identify regional shape differences between the mandibles of these samples in 3 dimensions without the use of landmark identification, with the ultimate goal of identifying heritable quantitative traits.

3. Develop a useful, intuitive and visual method for evaluation of shape differences.

Methods: A total of fifty-three mice were studied. Ten mice, equally divided across five parental inbred strains, were obtained from the HMDP, as well as an additional 43 animals at various ages from the C57BL/6 strain. Skulls were subsequently scanned using μCT, then DICOM files transferred into a Beta version of Dolphin Imaging ® 11.7 Software. Hemi-mandibles were segmented from the entire skull and surface meshes were created using the same software. Topological correction of each hemi-mandible was performed before parametric registration and resampling of the surfaces to the same number of mesh points. Once registered to each other, a population average was then created and used as a reference template for shape comparison. Shapes were compared using the independently validated neuroimaging techniques of medial axis and tensor-based morphometrics.

Results: Population averages were created for the mandibles and four specific areas of significant shape change were identified in both the interstrain and intrastrain samples. Visual heat maps were also created to display shape differences.

Conclusions: Tensor-based morphometric evaluation of mandibular shape has far superior visualization and localization potential when compared to the current method using landmark-based analysis, while offering a more reliable solution as it eliminates the need for consistent landmark placement. Coupled with medial thickness computation, followed by additional refinement, this methodology could potentially be applied to a variety of applications concerned with evaluating shape difference in three dimensions.

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