Diffusion tensor imaging findings suggestive of white matter alterations in a canine model of mucopolysaccharidosis type I

Abstract

Purpose We investigated fractional anisotropy (FA) and radial diffusivity (RD) in a canine model of mucopolysaccharidosis (MPS). We hypothesized that canines affected with MPS would exhibit decreased FA and increased RD values when compared to unaffected canines, a trend that has been previously described in humans with white matter diseases. Methods Four unaffected canines and two canines with MPS were euthanized at 18 weeks of age. Their brains were imaged using high-resolution diffusion tensor imaging (DTI) on a 7T small-animal magnetic resonance imaging system. One hundred regions of interest (ROIs) were placed in each of four white matter regions: anterior and posterior regions of the internal capsule (AIC and PIC, respectively) and anterior and posterior regions of the centrum semiovale (ACS and PCS, respectively). For each specimen, average FA and RD values and associated 95% confidence intervals were calculated from 100 ROIs for each brain region. Results For each brain region, the FA values in MPS brains were consistently lower than in unaffected dogs, and the RD values in MPS dogs were consistently higher, supporting our hypothesis. The confidence intervals for affected and unaffected canines did not overlap in any brain region. Conclusion FA and RD values followed the predicted trend in canines affected with MPS, a trend that has been described in humans with lysosomal storage and dysmyelinating diseases. These findings suggest that the canine model parallels MPS in humans, and further indicates that quantitative DTI analysis of such animals may be suitable for future study of disease progression and therapeutic response in MPS.

Quantitative diffusion tensor imaging analysis does not distinguish pediatric canines with mucopolysaccharidosis I from control canines

“…In a prior study, we found that FA values in 18-week-old MPS canine brains were consistently lower, and RD values consistently higher, than in age-matched unaffected dogs. 10 However, our findings in the current study on 7-week-old canines follow a different pattern. The major findings in this study were twofold.…”

Attention and corpus callosum volumes in individuals with mucopolysaccharidosis type I

“…We investigated abnormalities in attention and white matter (WM) in mucopolysaccharidosis (MPS) type I, given atypical WM findings in canine models 1,2 and our recent studies of MPS I and II. 3,4 MPS I is an autosomal recessive metabolic disorder in which lysosomal-enzyme (α-L-iduronidase) deficiency promotes cellular accumulation of glycosaminoglycans, resulting in multisystem dysfunction.…”

Companion animal models of neurological disease

“…Quantitative neuroimaging techniques have been employed for decades to further characterize structural nervous system abnormalities, pathophysiological mechanisms, and biochemical aberrations associated with various companion animal LSD variants, as well as to catalog morphological and functional correlates of therapeutic interventions ( Middleton et al, 2018 ; Choi et al, 2015 ; Li et al, 2018 ; Kumar et al, 2016 ; Vite et al, 2001 ; Vite et al, 2013 ; Magnitsky et al, 2010 ). High-field morphometric MRI scans are frequently used to longitudinally quantify grey and white matter volumetric changes that occur in LSD and their treatment ( Vite et al, 2001 ; Vite et al, 2013 ).…”

“…High-field morphometric MRI scans are frequently used to longitudinally quantify grey and white matter volumetric changes that occur in LSD and their treatment ( Vite et al, 2001 ; Vite et al, 2013 ). Diffusion tensor MR imaging (DTI), and magnetization transfer MR imaging (MTI) are widely used techniques that have proven beneficial for assessment of the structure, integrity, and organization of white matter tracts in canine and feline LSD, and in some cases have revealed useful imaging biomarkers for specific LSD variants ( Middleton et al, 2018 ; Choi et al, 2015 ; Li et al, 2018 ; Kumar et al, 2016 ; Magnitsky et al, 2010 ). Proton magnetic resonance spectroscopy may also be employed to identify unique spectral signatures that correlate with accumulation of undigested metabolic substrates within tissues ( Magnitsky et al, 2010 ).…”