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Purpose: Electrical epidural spinal cord stimulation (SCS) is used as a treatment for chronic pain as well as to partially restore motor function after a spinal cord injury. Monitoring the spinal cord activity during SCS with fMRI could provide important and objective measures of integrative responses to treatment. Unfortunately, spinal cord fMRI is severely challenged by motion and susceptibility artifacts induced by the implanted electrode and bones. This pilot study introduces multi-band sweep imaging with Fourier transformation (MB-SWIFT) technique for spinal cord fMRI during SCS in rats. Given the close to zero acquisition delay and high bandwidth in 3 dimensions, MB-SWIFT is demonstrated to be highly tolerant to motion and susceptibility-induced artifacts and thus holds promise for fMRI during SCS. Methods: MB-SWIFT with 0.78 × 0.78 × 1.50 mm3 spatial resolution and 3-s temporal resolution was used at 9.4 Tesla in rats undergoing epidural SCS at different frequencies. Its performance was compared with spin echo EPI. The origin of the functional contrast was also explored using suppression bands. Results: MB-SWIFT was tolerant to electrode-induced artifacts and respiratory motion, leading to substantially higher fMRI sensitivity than spin echo fMRI. Clear stimulation frequency-dependent responses to SCS were detected in the rat spinal cord close to the stimulation site. The origin of MB-SWIFT fMRI signals was consistent with dominant inflow effects. Conclusion: fMRI of the rat spinal cord during SCS can be consistently achieved with MB-SWIFT, thus providing a valuable experimental framework for assessing the effects of SCS on the central nervous system. publishedVersion

Purpose The desire to quantitatively discriminate the extra- and intracellular tissue 1 H2 O MR signals has gone hand-in-hand with the continual, historic increase in MRI instrument magnetic field strength [B0 ]. However, recent studies have indicated extremely valuable, novel metabolic information can be readily accessible at ultra-low B0 . The two signals can be distinguished, and the homeostatic activity of the cell membrane sodium/potassium pump (Na+ ,K+ ,ATPase) detected. The mechanism allowing 1 H2 O MRI to do this is the newly discovered active transmembrane water cycling (AWC) phenomenon, which we found using paramagnetic extracellular contrast agents at clinical B0 values. AWC is important because Na+ ,K+ ,ATPase can be considered biology's most vital enzyme, and its in vivo steady-state activity has not before been measurable, let alone amenable to mapping with high spatial resolution. Recent reports indicate AWC correlates with neuronal firing rate, with malignant tumor metastatic potential, and inversely with cellular reducing equivalent fraction. We wish to systematize the ways AWC can be precisely measured. Methods We present a theoretical longitudinal relaxation analysis of considerable scope: it spans the low- and high-field situations. Results We show the NMR shutter-speed organizing principle is pivotal in understanding how trans-membrane steady-state water exchange kinetics are manifest throughout the range. Our findings illuminate an aspect, apparent population inversion, which is crucial in understanding ultra-low field results. Conclusions Without an appreciation of apparent population inversion, significant misinterpretations of future data are likely. These could have unfortunate diagnostic consequences.

Purpose The desire to quantitatively discriminate the extra‐ and intracellular tissue 1H2O MR signals has gone hand‐in‐hand with the continual, historic increase in MRI instrument magnetic field strength [B 0]. However, recent studies have indicated extremely valuable, novel metabolic information can be readily accessible at ultra–low B 0. The two signals can be distinguished, and the homeostatic activity of the cell membrane sodium/potassium pump (Na+,K+,ATPase) detected. The mechanism allowing 1H2O MRI to do this is the newly discovered active transmembrane water cycling (AWC) phenomenon, which we found using paramagnetic extracellular contrast agents at clinical B 0 values. AWC is important because Na+,K+,ATPase can be considered biology’s most vital enzyme, and its in vivo steady‐state activity has not before been measurable, let alone amenable to mapping with high spatial resolution. Recent reports indicate AWC correlates with neuronal firing rate, with malignant tumor metastatic potential, and inversely with cellular reducing equivalent fraction. We wish to systematize the ways AWC can be precisely measured. Methods We present a theoretical longitudinal relaxation analysis of considerable scope: it spans the low‐ and high–field situations. Results We show the NMR shutter‐speed organizing principle is pivotal in understanding how trans–membrane steady–state water exchange kinetics are manifest throughout the range. Our findings illuminate an aspect, apparent population inversion, which is crucial in understanding ultra‐low field results. Conclusions Without an appreciation of apparent population inversion, significant misinterpretations of future data are likely. These could have unfortunate diagnostic consequences.

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 2nd 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. Magn Reson Med 73:254–262, 2015. © 2014 Wiley Periodicals, Inc.

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.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.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.TRAFFn with n = 4 or 5 provides a high sensitivity for selective myelin mapping in the rat brain.

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).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.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.RAFFn is a robust and safe rotating frame relaxation method to access slow molecular motions in vivo.

Apparent transverse-relaxation rate constants (R₂⁺ = 1/T₂⁺) were measured in various regions of the healthy human brain using a multiecho adiabatic spin-echo sequence at five different magnetic fields, 1.5, 1.9, 3, 4.7, and 7 T. The R₂⁺ values showed a clear dependence on magnetic field strength (B(0) ). The regional distribution of the R ₂⁺ was well explained by the sum of three components: (1) regional nonhemin iron concentration ([Fe]), (2) regional macromolecular mass fraction (f(M) ), and (3) a region-independent factor. Accordingly, R₂⁺ = α[Fe] + βf(M) + γ, where coefficients α, β, and γ were experimentally determined at each magnetic field by a least square fitting method using multiple regression analysis. Although the coefficient α linearly increased with B(0) , β showed a quadratic dependence on top of a field-independent component. The coefficient γ also increased slightly with B(0) on top of a field-independent component. The linear dependence of α on B(0) was consistent with that observed for the transverse-relaxation rate of water protons in ferritin solutions as found previously by others. The quadratic dependence of β on B(0) was accounted for by isochronous and anisochronous exchange mechanisms using intrinsic-relaxation parameters obtained from the literature.