Quantitative magnetic resonance imaging of brain atrophy in a mouse model of Niemann-Pick type C disease.

In vivo magnetic resonance imaging (MRI) was used to investigate regional and global brain atrophy in the neurodegenerative Niemann Pick Type C1 (NPC1) disease mouse model. Imaging experiments were conducted with the most commonly studied mouse model of NPC1 disease at early and late disease states. High-resolution in vivo images were acquired at early and late stages of the disease and analyzed with atlas-based registration to obtain measurements of twenty brain region volumes.

Dynamic contrast enhanced magnetic resonance imaging of an orthotopic pancreatic cancer mouse model.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has been limitedly used for orthotopic pancreatic tumor xenografts due to severe respiratory motion artifact in the abdominal area. Orthotopic tumor models offer advantages over subcutaneous ones, because those can reflect the primary tumor microenvironment affecting blood supply, neovascularization, and tumor cell invasion. We have recently established a protocol of DCE-MRI of orthotopic pancreatic tumor xenografts in mouse models by securing tumors with an orthogonally bent plastic board to prevent motion transfer from the chest region during imaging.

(1) H magnetic resonance spectroscopy of neurodegeneration in a mouse model of niemann-pick type C1 disease.

Purpose: To evaluate brain metabolite levels as in vivo indicators of disease progression in a widely studied mouse model of Niemann-Pick type C1 (NPC1) disease with quantitative (1) H magnetic resonance spectroscopy (MRS).

Materials And Methods: Single voxel MRS experiments were carried out in vivo in a mouse model of NPC1 disease and in control mice in two brain regions (central and posterior) at two timepoints (presymptomatic and endstage) to examine changes in metabolite levels in NPC1 disease. Concentrations of nine metabolites were quantified by fitting a simulated basis set of metabolite signals to the acquired spectra.

A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations.

We have identified a point mutation in Npc1 that creates a novel mouse model (Npc1(nmf164)) of Niemann-Pick type C1 (NPC) disease: a single nucleotide change (A to G at cDNA bp 3163) that results in an aspartate to glycine change at position 1005 (D1005G). This change is in the cysteine-rich luminal loop of the NPC1 protein and is highly similar to commonly occurring human mutations. Genetic and molecular biological analyses, including sequencing the Npc1(spm) allele and identifying a truncating mutation, confirm that the mutation in Npc1(nmf164) mice is distinct from those in other existing mouse models of NPC disease (Npc1(nih), Npc1(spm)).

In vivo assessment of neurodegeneration in Niemann-Pick type C mice by quantitative T2 mapping and diffusion tensor imaging.

Purpose: To quantitatively and noninvasively assess neurological disease progression in a mouse model of Niemann-Pick type C (NPC) disease by measuring white matter status with magnetic resonance imaging (MRI) techniques of T2 mapping and diffusion tensor imaging (DTI).

Materials And Methods: Quantitative T2 and DTI experiments were performed in vivo in NPC disease model and control mice at three timepoints to quantify differences and changes in white matter with measurements of T2 relaxation and DTI parameters. Histological staining for myelin content was also performed at two timepoints to compare with the MRI findings.

MRI detects therapeutic effects in weanling Niemann-Pick type C mice.

To noninvasively evaluate the early effects of Niemann-Pick type C (NPC) disease, diffusion tensor imaging (DTI) was carried out in the brains of very young (23-day-old) mice. The diffusion of water in white matter tracts of Npc1(-/-) mice at this young age was already abnormal, exhibiting decreased anisotropy, as quantified by fractional anisotropy (FA), compared with their wild-type littermates, the controls. Postmortem histological staining revealed myelin deficiencies in Npc1(-/-) mice, consistent with the reduction in FA measured in vivo.