Population based MRI and DTI templates of the adult ferret brain and tools for voxelwise analysis

Hutchinson, Elizabeth; Schwerin, Susan C.; Radomski, Kryslaine L.; Sadeghi, Neda; Jenkins, Jeffrey L.; Komlosh, Michal E.; İrfanoğlu, M. Okan; Juliano, Sharon L.; Pierpaoli, Carlo

doi:10.1016/j.neuroimage.2017.03.009

Cited by 32 publications

(28 citation statements)

References 63 publications

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“…1p), closely modeling the effects of human mutations 2–4,17 . Magnetic resonance imaging 18 (MRI) showed that, as in humans 4 , loss of cortical volume and surface area followed an anterior-to-posterior gradient, with the frontal cortex most affected (Fig. 1f–k and Extended Data Table 1).…”

Section: Main Textmentioning

confidence: 92%

“…Each of the 6 MR images was first corrected for B1 shading artifact using a slice inhomogeneity correction 33 and an inverse covariance mapping of grey matter density (unpublished). Next, the Ferret Atlas 18 was registered to each of the MRI images using a tensor b-spline normalized mutual information nonlinear intensity-based registration algorithm 34,35 with a control point spacing of 1 mm. The result of the registration was used to warp the atlas regions to each individual MRI, and from this we calculated the volume of each of the warped regions as reported in Fig.…”

Section: Methodsmentioning

confidence: 99%

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Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size

Johnson

Sun

Kodani

et al. 2018

Nature

143

154

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The human cerebral cortex is distinguished by its large size and abundant gyrification, or folding, yet the evolutionary mechanisms driving cortical size and structure are unknown. While genes essential for cortical developmental expansion have been identified from the genetics of human primary microcephaly (“small head”, associated with reduced brain size and intellectual disability)1, studies of these genes in mice, whose smooth cortex is one thousand times smaller than that of humans, have provided limited insight. Mutations of abnormal spindle-like microcephaly-associated (ASPM), the most common recessive microcephaly gene, reduce cortical volume by ≥50% in humans2–4, but have little effect in mice5–9, likely reflecting evolutionarily divergent functions of ASPM10,11. We used genome editing to create a germline knockout (KO) of Aspm in the ferret (Mustela putorius furo), a species with a larger, gyrified cortex and greater neural progenitor cell (NPC) diversity12–14 than mice, and closer Aspm protein sequence homology to human. Aspm KO ferrets exhibit severe microcephaly (25–40% decreases in brain weight), reflecting reduced cortical surface area without significant change in cortical thickness, as in human patients3,4, suggesting loss of “cortical units”. The mutant ferret fetal cortex displays a massive premature displacement of ventricular radial glial cells (VRG) to the outer subventricular zone (OSVZ), where many resemble outer radial glia (ORG), an NPC subtype essentially absent in mice and implicated in cerebral cortical expansion in primates12–16. These data suggest an evolutionary mechanism whereby Aspm regulates cortical expansion by controlling the affinity of VRG for the ventricular surface, thus modulating the ratio of VRG, the most undifferentiated cell type, to ORG, a more differentiated progenitor.

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Section: Main Textmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size

Johnson

Sun

Kodani

et al. 2018

Nature

143

154

View full text Add to dashboard Cite

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“…Abnormalities were identified and characterized using multiple complementary methods including gross body dimension measurements, targeted immunohistochemistry and noninvasive imaging of the skull by CT and of the brain by MRI. Advanced MRI analysis using morphometric and diffusion techniques has been previously used for the ferret brain during development (Knutsen, Kroenke, Chang, Taber, & Bayly, ; Kroenke, Taber, Leigland, Knutsen, & Bayly, ) and in the adult (Hutchinson et al, ). While research of the Zika virus remains a nascent field in many ways, this study provides a unique perspective by identifying several types of brain abnormalities caused by Zika infection in a human‐relevant species.…”

Section: Introductionmentioning

confidence: 99%

“…Advanced MRI analysis using morphometric and diffusion techniques has been previously used for the ferret brain during development (Knutsen, Kroenke, Chang, Taber, & Bayly, 2013;Kroenke, Taber, Leigland, Knutsen, & Bayly, 2009) and in the adult (Hutchinson et al, 2017). While research of the Zika virus remains a nascent field in many ways, this study provides a unique perspective by identifying several types of brain abnormalities caused by Zika infection in a human-relevant species.…”

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confidence: 99%

The effect of Zika virus infection in the ferret

Hutchinson

Chatterjee

Reyes

et al. 2019

J of Comparative Neurology

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Although initial observations of infections with the Zika virus describe a mild illness, more recent reports show that infections by Zika result in neurotropism. In 2015, substantial congenital malformations were observed, with numerous infants born with microcephaly in Brazil. To study the underlying mechanism and effects of the disease, it is critical to find suitable animal models. Rodents lack an immune system parallel to humans and also have lissencephalic brains, which are likely to react differently to infections. As the smallest gyrencephalic mammal, ferrets may provide an important animal model to study the Zika virus, as their brains share many characteristics with humans. To evaluate the prospect of using ferrets to study Zika virus infection, we injected seven pregnant jills with the PR strain subcutaneously on gestational day 21, corresponding to the initiation of corticogenesis. These injections resulted in mixed effects. Two animals died of apparent infection, and all kits were resorbed in another animal that did not die. The other four animals remained pregnant until gestational day 40, when the kits were delivered by caesarian section. We evaluated the animals using CT, MRI, diffusion tensor imaging, and immunohistochemistry. The kits displayed a number of features compatible with an infection that impacted both the brain and skull. The outcomes, however, were variable and differed within and across litters, which ranged from the absence of observable abnormalities to prominent changes, suggesting differential vulnerability of kits to infection by the Zika virus or to subsequent mechanisms of neurodevelopmental disruption.

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“…Recent pioneering studies using diffusion MR tractography reported that ferrets (Mustela putorius furo), like humans and monkeys, also have abundant U-fibers [23,24]. Ferrets have a long history in research and have relatively well-developed brain structures such as cortical folds (i.e.…”

Section: Introductionmentioning

confidence: 99%

The origin and development of subcortical U-fibers in gyrencephalic ferrets

et al. 2020

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In the white matter of the human cerebrum, the majority of cortico-cortical fibers are of short range, connecting neighboring cortical areas. U-fibers represent connections between neighboring areas and are located in the white matter immediately deep to the cerebral cortex. Using gyrencephalic carnivore ferrets, here we investigated the neurochemical, anatomical and developmental features of U-fibers. We demonstrate that U-fibers were derived from neighboring cortical areas in ferrets. U-fiber regions in ferrets were intensely stained with Gallyas myelin staining and Turnbull blue iron staining. We further found that U-fibers were derived from neurons in both upper and lower layers in neighboring areas of the cerebral cortex and that U-fibers were formed later than axons in the deep white matter during development. Our findings shed light on the fundamental features of U-fibers in the gyrencephalic cerebral cortex. Because genetic manipulation techniques for ferrets are now available, ferrets should be an important option for investigating the development, functions and pathophysiological changes of U-fibers.

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Population based MRI and DTI templates of the adult ferret brain and tools for voxelwise analysis

Cited by 32 publications

References 63 publications

Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size

Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size

The effect of Zika virus infection in the ferret

The origin and development of subcortical U-fibers in gyrencephalic ferrets

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