MRI relaxation in the presence of fictitious fields correlates with myelin content in normal rat brain.

PURPOSE: Brain myelin plays an important role in normal brain function. Demyelination is involved in many degenerative brain diseases, thus quantitative imaging of myelin has been under active investigation. In previous work, we demonstrated the capability of the method known as Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n (RAFFn) to provide image contrast between white and gray matter in human and rat brains. Here, we provide evidence pointing to myelin being the major source of this contrast. METHODS: RAFFn relaxation time constant (TRAFFn) was mapped in rat brain ex vivo. TRAFFn was quantified in 12 different brain areas. TRAFFn values were compared with multiple other MRI metrics (T1, T2 , continuous wave T1ρ, adiabatic T1ρ and T2ρ, magnetization transfer ratio), and with histologic measurements of cell density, myelin and iron content. RESULTS: Highest contrast between white and grey matter was obtained with TRAFFn in the rotating frames of ranks n = 4 and 5. TRAFFn values correlated strongly with myelin content, whereas no associations between TRAFFn and iron content or cell density were found. CONCLUSION: TRAFFn with n = 4 or 5 provides a high sensitivity for selective myelin mapping in the rat brain.

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.

Do allopatric male Calopteryx virgo damselflies learn species recognition?

There is a growing amount of empirical evidence that premating reproductive isolation of two closely related species can be reinforced by natural selection arising from avoidance of maladaptive hybridization. However, as an alternative for this popular reinforcement theory, it has been suggested that learning to prefer conspecifics or to discriminate heterospecifics could cause a similar pattern of reinforced premating isolation, but this possibility is much less studied. Here, we report results of a field experiment in which we examined (i) whether allopatric Calopteryx virgo damselfly males that have not encountered heterospecific females of the congener C. splendens initially show discrimination, and (ii) whether C. virgo males learn to discriminate heterospecifics or learn to associate with conspecifics during repeated experimental presentation of females. Our experiment revealed that there was a statistically nonsignificant tendency for C. virgo males to show initial discrimination against heterospecific females but because we did not use sexually naïve individuals in our experiment, we were not able to separate the effect of innate or associative learning. More importantly, however, our study revealed that species discrimination might be further strengthened by learning, especially so that C. virgo males increase their association with conspecific females during repeated presentation trials. The role of learning to discriminate C. splendens females was less clear. We conclude that learning might play a role in species recognition also when individuals are not naïve but have already encountered potential conspecific mates.