Abstract
Cerebellar and hindbrain malformations, such as cerebellar hypoplasia (CH), vermis hypoplasia, and Dandy–Walker malformation, occur in dogs as well as in humans. Neuroimaging is essential for a precise description of these malformations and defining translational animal models. Neuroimaging is increasingly performed in puppies, but there is a lack of data on developmental changes in the caudal fossa, which can impair assessment of caudal fossa size in this age group. The purpose of this study was to validate caudal fossa ratio (CFR) in dogs and to explore CFR in Eurasier dogs with genetic CH. CFR was calculated from midsagittal brain images of 130 dogs as caudal fossa area/total cranial cavity area. In addition, the volume of the caudal fossa was measured in 64 randomly selected dogs from this group. Repeated measurements were used to investigate inter- and intra-rater variability and influence of imaging modality. Furthermore, the influence of age, weight, and breed was explored. The CFR was a reliable parameter with negligible influence from the examiners, imaging modality, and weight of the dog. The midsagittal area of the caudal fossa and the volume of the caudal fossa correlated closely with each other. In this study, we observed a smaller CFR in puppies. The CFR in adult dogs lies within 0.255 and 0.330, while CFR is smaller in puppies up to 4 months of age. Besides age, there was also an effect of breed, which should be explored in larger data sets. Measurements of CFR in Eurasier dogs with genetic CH caused by a mutation in the very-low-density-lipoprotein-receptor gene revealed the presence of two variants, one with an enlarged caudal fossa and one with a normal to small caudal fossa. This observation indicates that there is phenotypic heterogeneity and interaction between the developing cerebellum and the surrounding mesenchyme in this animal model.
Highlights
Animal models of human disease provide insights into pathophysiology at a molecular level, and gene discovery in dogs has become an important resource
In human medicine, neuroimaging techniques have helped to improve the definitions of hindbrain and cerebellar malformations
Data confirm the reliability of caudal fossa ratio (CFR) as a robust parameter for assessment of caudal fossa size
Summary
Animal models of human disease provide insights into pathophysiology at a molecular level, and gene discovery in dogs has become an important resource. Caudal Fossa Ratio classification systems to a classification system that is based on embryonic development [1,2,3,4] This system was produced by modern neuroimaging techniques as well as increased understanding of correlations between gene mutations and certain brain imaging phenotypes. The recognition of phenotypic heterogeneity of certain gene mutations and the fact that different gene mutations may result in nearly identical neuroimaging findings has further contributed to the understanding of these mutations [4, 5]. Many of these data are derived from animal studies [2]
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