DOI: 10.5061/dryad.ng64q
title: Data from: Assessment of dysmyelination with RAFFn MRI: application to murine MPS I

description: Type I mucopolysaccharidosis (MPS I) is an autosomal recessive lysosomal
 storage disorder with neurological features. Humans and laboratory animals
 with MPS I exhibit various white matter abnormalities involving the corpus
 callosum and other regions. In this study, we first validated a novel MRI
 technique, entitled Relaxation Along a Fictitious Field in the rotating
 frame of rank n (RAFFn), as a measure of myelination and dysmyelination in
 mice. We then examined differences between MPS I mice and heterozygotes
 using RAFF5 and histology. RAFF5 (i.e., RAFFn with n = 5) relaxation time
 constants were highly correlated with histological myelin density (R2 =
 0.68, P&lt;0.001), and RAFF5 clearly distinguished between the
 hypomyelinated and dysmyelinated shiverer mouse and the wild-type mouse.
 Bloch-McConnell theoretical analysis revealed slower exchange correlation
 times and smaller exchange-induced relaxation rate constants for RAFF4 and
 RAFF5 compared to RAFF1-3, T1ρ, and T2ρ. These data suggest that RAFF5 may
 assess methylene protons in myelin lipids and proteins, though other
 mechanisms (e.g. detection of myelin-bound water) may also explain the
 sensitivity of RAFF5 to myelin. In MPS I mice, mean RAFF5 relaxation time
 constants were significantly larger for the striatum (P = 0.004) and
 internal capsule (P = 0.039), and marginally larger for the fornix (P =
 0.15). Histological assessment revealed no differences between MPS I mice
 and heterozygotes in myelin density or corpus callosum thickness. Taken
 together, these findings support subtle dysmyelination in the brains of
 mice with MPS I. Dysmyelination may result from myelin lipid abnormalities
 caused by the absence of α-L-iduronidase. Our findings may help to explain
 locomotor and cognitive deficits seen in mice with MPS I.
description: Histology
 imagesZipped folder containing
 photomicrographs of mouse brain sections. Sections are from MPS I mice and
 IDUA heterozygotes, and are stained with the black gold stain. Images have
 been resized and converted to grayscale. Images are scaled to 173 pixels
 per millimeter unless noted otherwise in the filename (“..._NotToScale”).
 Files are titled "histology_[mouse identifier]_[tissue section
 identifier].tif". Mice 13021, 13224, 13255, N3, N4, and N5 are mice
 with MPS I; mice 13257, 13258, N1, N2, and N6 are
 heterozygotes.Histology analysis_for
 DryadExcel spreadsheet
 containing analyzed histological data. The “Optical density” tab contains
 raw optical density values for each tissue section, normalized values,
 normalized means for each animal, and normalized means for each genotype.
 The “Outliers” tab contains analysis of each animal for outlying values
 (see the publication in PLOS ONE for details). The “cc thickness” tab
 contains raw data for corpus callosum thickness, comparison with atlas
 values for each section, animal means, and genotype means. Mice 13021,
 13224, 13255, N3, N4, and N5 are mice with MPS I; mice 13257, 13258, N1,
 N2, and N6 are heterozygotes.MRI relaxation time
 constant mapsZipped folder containing
 MRI relaxation time constant maps. Files are meant to be opened and
 analyzed using the Aedes toolbox for MATLAB. See the publication in PLOS
 ONE for more details. Files are titled "MRI _[mouse identifier]_[MRI
 sequence].t1r [or .t1]". Mice 13021, 13224, 13255, N3, N4, and N5 are
 mice with MPS I; mice 13257, 13258, N1, N2, and N6 are
 heterozygotes.MRI analysis_for
 DryadExcel spreadsheet
 containing analyzed MRI data. The “MRI ROI comparison” tab contains mean
 relaxation time constants for each ROI in each animal for each sequence,
 as well as means for each genotype. The “MRI vs histology” tab contains
 correlation of tissue section-derived normalized optical density with MRI
 relaxation time constants for each MRI sequence. The “Outliers” tab
 contains analysis of each animal for outlying values (see the publication
 in PLOS ONE for details). Mice 13021, 13224, 13255, N3, N4, and N5 are
 mice with MPS I; mice 13257, 13258, N1, N2, and N6 are
 heterozygotes.