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.
authors: Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: David
authors: D
authors: Satzer
authors: Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Christina
authors: C
authors: DiBartolomeo
authors: Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Michael M
authors: MM
authors: Ritchie
authors: Center of Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Christine
authors: C
authors: Storino
authors: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors: Timo
authors: T
authors: Liimatainen
authors: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors: Hanne
authors: H
authors: Hakkarainen
authors: Center of Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Djaudat
authors: D
authors: Idiyatullin
authors: Center of Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Silvia
authors: S
authors: Mangia
authors: Center of Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Shalom
authors: S
authors: Michaeli
authors: Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Ann M
authors: AM
authors: Parr
authors: Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Walter C
authors: WC
authors: Low
mesh_terms: D000818:Animals; D003337:Corpus Callosum / Q000473:pathology; D005260:Female; D006579:Heterozygote; D007068:Iduronidase / Q000235:genetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008059:Mucopolysaccharidosis I / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009186:Myelin Sheath / Q000502:physiology*; D009929:Organ Size; D012399:Rotation; D013997:Time Factors
chemical_list: D007068:Iduronidase