Measuring histological form change with finite element methods: An application using diazo‐oxo‐norleucine (DON)‐treated rats

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Abstract
Analyses of drug‐induced anatomical malformations routinely rely on linear measurements as a data base. Morphometric approaches utilizing these measures become inappropriate at the histological level at which a constant external referencing system is impossible to achieve. The purpose of this study was to quantify anatomical form change in the craniofacial region of late embryonic rats induced by a known teratogen, diazo‐oxo‐norleucine (DON), independent of any global referencing system. A sample of 17 untreated specimens of 17‐day gestation served as the control. A second group, equivalent in number and age, received 2.0 mg DON on day 15. Homologous landmarks were identified in each specimen and craniofacial regions were partitioned with respect to these bounding nodes into nasal, oral, and mandibular elements. Form change was viewed as the continuous deformation of a reference craniofacial region from a 15‐day untreated specimen into each final 17‐day geometry. An interactive graphics program generated spatially invariant measures of form change through finite element methods. A local coordinate system was established for each element. A point within each region of the 15‐day reference specimen was selected and the spatial relationship between this point and bounding nodes was quantified through interpolation functions. Size and shape variables were derived from a Lagrangian strain tensor, and values were compared between groups. Results showed that all three craniofacial regions were smaller in size among DON‐treated specimens, but only oral and mandibular region shapes were different from controls. The finite element approach was considered superior to other histological morphometric techniques since an entire geometry was described and a visual description of form change as well as spatially invariant measures of size and shape change were derived.