Magnetic resonance imaging as a tool for in vivo and ex vivo anatomical phenotyping in experimental genetic models

Abstract

This article describes a suite of computational approaches suitable for deriving various quantitative phenotypes from structural magnetic resonance (MR) images obtained in rodents and used subsequently in genetic studies of complex traits. We begin by introducing the basic principles of genetic studies of complex traits in experimental models. We then illustrate the use of MR-based computational anatomy in vivo and ex vivo, and in combination with histology. This work was carried out in two inbred strains of rats, namely spontaneously hypertensive rats and Brown Norway rats; these are parental strains of the only existing panel of recombinant inbred strains of rats. The rats were scanned in vivo at two time points (at 8 and 12 weeks of age) and ex vivo (at 12 weeks of age). We describe between-strain differences and across-time changes in brain and kidney volumes, as well as regional variations in brain structure using surface- and deformation-based approaches. We conclude by discussing the power of the population-based computational analysis of MR images, and their fusion with histology, in studies of complex traits.

Smoothness-guided 3-D reconstruction of 2-D histological images

“…Such external information is usually supplied by a 3-D imaging modality (e.g., MRI, CT or PET (Mega et al, 1997;Ourselin et al, 2001a;Pitiot et al, 2007;Thompson and Toga, 1996)), or by 2-D block-face images acquired during the sectioning process (Bardinet et al, 2002;Chakravarty et al, 2008;Dauguet et al, 2007;Kim et al, 1997). Those act as an adequate anatomical framework.…”

“…For instance, MR/histology fusion was used to validate the analysis of a genotype/phenotype correlation in a recent study of genetically modified rodents (Pitiot et al, 2007). The proposed system took advantage of both the microscopic details offered by histology and the anatomy provided by MRI to describe morphological differences at the macroscopic level linked to genetic alterations.…”

Brain Morphometry and Longitudinal Relaxation Time of Spontaneously Hypertensive Rats (SHRs) in Early and Intermediate Stages of Hypertension Investigated by 3D VFA-SPGR MRI

“…The spontaneously hypertensive (SHR) rat (Okamoto K and Aoki K, 1963;Smith TL and Hutchins PM, 1979) is a polygenetic inherited primary hypertension model of the equivalent clinical condition and it is a suitable model for studying the contribution of chronic hypertension to SVD pathology. The SHR rat is normotensive at birth and progressively develops hypertension starting around 5-6 weeks of life, reaching a chronic hypertensive state by 24 weeks of age (Pitiot A et al, 2007). The adverse effects of chronic hypertension on brain morphometry in SHR rats have been documented post-mortem by histology (Hong E et al, 1992;Mori S et al, 1995;Sutterer JR et al, 1980;Wyss JM et al, 1992).…”

Enhanced cortical thickness measurements for rodent brains via Lagrangian-based RK4 streamline computation

“…2 Rodent models have allowed various experiments designed for the identification of factors such as toxic material and genetic patterns that affects the shape change and the development of their brains. Thus, the analysis of rodent brains has gained increasing interests 3–5 including the cortical thickness analysis for the rodent brain as well.…”