MRI contrasts in high rank rotating frames.

PURPOSE: MRI relaxation measurements are performed in the presence of a fictitious magnetic field in the recently described technique known as RAFF (Relaxation Along a Fictitious Field). This method operates in the 2(nd) rotating frame (rank n = 2) by using a nonadiabatic sweep of the radiofrequency effective field to generate the fictitious magnetic field. In the present study, the RAFF method is extended for generating MRI contrasts in rotating frames of ranks 1 ≤ n ≤ 5. The developed method is entitled RAFF in rotating frame of rank n (RAFFn). THEORY AND METHODS: RAFFn pulses were designed to generate fictitious fields that allow locking of magnetization in rotating frames of rank n. Contrast generated with RAFFn was studied using Bloch-McConnell formalism together with experiments on human and rat brains. RESULTS: Tolerance to B0 and B1 inhomogeneities and reduced specific absorption rate with increasing n in RAFFn were demonstrated. Simulations of exchange-induced relaxations revealed enhanced sensitivity of RAFFn to slow exchange. Consistent with such feature, an increased grey/white matter contrast was observed in human and rat brain as n increased. CONCLUSION: RAFFn is a robust and safe rotating frame relaxation method to access slow molecular motions in vivo.

Assessment of dysmyelination with RAFFn MRI: application to murine MPS I.

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.