Assessment of dysmyelination with RAFFn MRI: Application to murine MPS I

David Satzer, Christina DiBartolomeo, Michael M. Ritchie, Christine Storino, Timo Liimatainen, Hanne Hakkarainen, Djaudat Idiyatullin, Silvia Mangia, Shalom Michaeli, Ann M. Parr, Walter C. Low

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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<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, T, and T. 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.

Original languageEnglish (US)
Article numbere0116788
JournalPLoS One
Volume10
Issue number2
DOIs
StatePublished - Feb 13 2015

Fingerprint

mucopolysaccharidosis
Mucopolysaccharidoses
Magnetic resonance imaging
Relaxation time
myelin sheath
Iduronidase
Lipids
Myelin Sheath
Histology
mice
Capsules
Protons
Rate constants
Brain
Animals
Water
Corpus Callosum
Heterozygote
heterozygosity
Proteins

Cite this

Satzer, D., DiBartolomeo, C., Ritchie, M. M., Storino, C., Liimatainen, T., Hakkarainen, H., ... Low, W. C. (2015). Assessment of dysmyelination with RAFFn MRI: Application to murine MPS I. PLoS One, 10(2), [e0116788]. https://doi.org/10.1371/journal.pone.0116788

Assessment of dysmyelination with RAFFn MRI : Application to murine MPS I. / Satzer, David; DiBartolomeo, Christina; Ritchie, Michael M.; Storino, Christine; Liimatainen, Timo; Hakkarainen, Hanne; Idiyatullin, Djaudat; Mangia, Silvia; Michaeli, Shalom; Parr, Ann M.; Low, Walter C.

In: PLoS One, Vol. 10, No. 2, e0116788, 13.02.2015.

Research output: Contribution to journalArticle

Satzer D, DiBartolomeo C, Ritchie MM, Storino C, Liimatainen T, Hakkarainen H et al. Assessment of dysmyelination with RAFFn MRI: Application to murine MPS I. PLoS One. 2015 Feb 13;10(2). e0116788. https://doi.org/10.1371/journal.pone.0116788
Satzer, David ; DiBartolomeo, Christina ; Ritchie, Michael M. ; Storino, Christine ; Liimatainen, Timo ; Hakkarainen, Hanne ; Idiyatullin, Djaudat ; Mangia, Silvia ; Michaeli, Shalom ; Parr, Ann M. ; Low, Walter C. / Assessment of dysmyelination with RAFFn MRI : Application to murine MPS I. In: PLoS One. 2015 ; Vol. 10, No. 2.
@article{48e08f832d724022ac32f854dac29474,
title = "Assessment of dysmyelination with RAFFn MRI: Application to murine MPS I",
abstract = "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<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.",
author = "David Satzer and Christina DiBartolomeo and Ritchie, {Michael M.} and Christine Storino and Timo Liimatainen and Hanne Hakkarainen and Djaudat Idiyatullin and Silvia Mangia and Shalom Michaeli and Parr, {Ann M.} and Low, {Walter C.}",
year = "2015",
month = "2",
day = "13",
doi = "10.1371/journal.pone.0116788",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

TY - JOUR

T1 - Assessment of dysmyelination with RAFFn MRI

T2 - Application to murine MPS I

AU - Satzer, David

AU - DiBartolomeo, Christina

AU - Ritchie, Michael M.

AU - Storino, Christine

AU - Liimatainen, Timo

AU - Hakkarainen, Hanne

AU - Idiyatullin, Djaudat

AU - Mangia, Silvia

AU - Michaeli, Shalom

AU - Parr, Ann M.

AU - Low, Walter C.

PY - 2015/2/13

Y1 - 2015/2/13

N2 - 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<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.

AB - 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<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.

UR - http://www.scopus.com/inward/record.url?scp=84923012757&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923012757&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0116788

DO - 10.1371/journal.pone.0116788

M3 - Article

C2 - 25680196

AN - SCOPUS:84923012757

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e0116788

ER -