Purpose The regional uptake of glucose in rat brain in vivo was measured at high resolution using spin-lock magnetic resonance imaging after infusion of the glucose analogue 2-deoxy-D-glucose (2DG). Previous studies of glucose metabolism have used 13C-labeled 2DG and NMR spectroscopy, 18F-labeled fluorodeoxyglucose (FDG) and PET, or chemical exchange saturation transfer (CEST) MRI, all of which have practical limitations. Our goal was to explore the ability of spin-lock sequences to detect specific chemically-exchanging species in vivo and to compare the effects of 2DG in brain tissue on CEST images. Methods Numerical simulations of R1p and CEST contrasts for a variety of sample parameters were performed to evaluate the potential specificity of each method for detecting the exchange contributions of 2DG. Experimental measurements were made in tissue phantoms and in rat brain in vivo which demonstrated the ability of spin-lock sequences for detecting 2DG. Results R1p contrast acquired with appropriate spin-lock sequences can isolate the contribution of exchanging protons in 2DG in vivo and appears to have better sensitivity and more specificity to 2DG-water exchange effects than CEST. Conclusion Spin-lock imaging provides a novel approach to the detection and measurement of glucose uptake in brain in vivo.

Measurements of spin-lock relaxation rates in the rotating frame (R1ρ ) at high magnetic fields afford the ability to probe not only relatively slow molecular motions, but also other dynamic processes, such as chemical exchange and diffusion. In particular, measurements of the variation (or dispersion) of R1ρ with locking field allow the derivation of quantitative parameters that describe these processes. Measurements in deuterated solutions demonstrate the manner and degree to which exchange dominates relaxation at high fields (4.7 T, 7 T) in simple solutions, whereas temperature and pH are shown to be very influential factors affecting the rates of proton exchange. Simulations and experiments show that multiple exchanging pools of protons in realistic tissues can be assumed to behave independently of each other. R1ρ measurements can be combined to derive an exchange rate contrast (ERC) that produces images whose intensities emphasize protons with specific exchange rates rather than chemical shifts. In addition, water diffusion in the presence of intrinsic susceptibility gradients may produce significant effects on R1ρ dispersions at high fields. The exchange and diffusion effects act independently of each other, as confirmed by simulation and experimentally in studies of red blood cells at different levels of oxygenation. Collectively, R1ρ measurements provide an ability to quantify exchange processes, to provide images that depict protons with specific exchange rates and to describe the microstructure of tissues containing magnetic inhomogeneities. As such, they complement traditional T1 or T2 measurements and provide additional insights from measurements of R1ρ at a single locking field. Copyright © 2016 John Wiley & Sons, Ltd.

Purpose A method is described for characterizing magnetically inhomogeneous media and the spatial scales of intrinsic susceptibility variations within samples. The rate of spin-lattice relaxation in the rotating frame, R1ρ, is affected by diffusion effects to a degree that depends on the magnitude of an applied spin-locking field. Appropriate analysis of the dispersion of R1ρ with locking field may be used to characterize susceptibility variations in inhomogeneous tissues. Theory and Methods The contribution of diffusion to R1ρ is quantified by an analytic expression derived by analyzing of the effects of diffusion through periodic variations of magnetic susceptibility and is used to predict the effects of inhomogeneities in simple phantoms. The theory is further applied to imaging to derive parametric images that portray the dimensions of susceptibility inhomogeneities independent of their magnitude. Results Significant dispersion of R1ρ with locking field was predicted and measured experimentally for suspensions of microspheres ranging from 1 to 90 µm in diameter. For scales of practical interest, these dispersion effects occur at much lower locking fields than the range in which chemical exchange effects cause similar dispersion. Conclusion There is good agreement between theory and experiment, and the method has potential for quantitative tissue characterization and functional imaging.

In an aqueous medium containing magnetic inhomogeneities, diffusion amongst the intrinsic susceptibility gradients contributes to the relaxation rate R1ρ of water protons to a degree that depends on the magnitude of the local field variations ΔBz, the geometry of the perturbers inducing these fields, and the rate of diffusion of water, D. This contribution can be reduced by using stronger locking fields, leading to a dispersion in R1ρ that can be analyzed to derive quantitative characteristics of the material. A theoretical expression was recently derived to describe these effects for the case of sinusoidal local field variations of a well-defined spatial frequency q. To evaluate the degree to which this dispersion may be extended to more realistic field patterns, finite difference Bloch-McConnell simulations were performed with a variety of three-dimensional structures to reveal how simple geometries affect the dispersion of spin-locking measurements. Dispersions were fit to the recently derived expression to obtain an estimate of the correlation time of the field variations experienced by the spins, and from this the mean squared gradient and an effective spatial frequency were obtained to describe the fields. This effective spatial frequency was shown to vary directly with the second moment of the spatial frequency power spectrum of the ΔBz field, which is a measure of the average spatial dimension of the field variations. These results suggest the theory may be more generally applied to more complex media to derive useful descriptors of the nature of field inhomogeneities. The simulation results also confirm that such diffusion effects disperse over a range of locking fields of lower amplitude than typical chemical exchange effects, and should be detectable in a variety of magnetically inhomogeneous media including regions of dense microvasculature within biological tissues.

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A novel approach for detecting blood oxygenation level-dependent (BOLD) signals in the brain is investigated using spin locking (SL) pulses to selectively edit the effects of extravascular diffusion in field gradients from different sized vascular structures. We show that BOLD effects from diffusion amongst susceptibility gradients will contribute significantly not only to transverse relaxation rates (R2* and R2) but also to R1ρ, the rate of longitudinal relaxation in the rotating frame. Similar to the ability of 180-degree pulses to refocus static dephasing effects in a spin echo, moderately strong SL pulses can also reduce contributions of diffusion in large-scale gradients and the choice of SL amplitude can be used to selectively emphasize smaller scale inhomogeneities (such as microvasculature) and to drastically reduce the influence of larger structures (such as veins). Moreover, measurements over a range of locking fields can be used to derive estimates of the spatial scales of intrinsic gradients. The method was used to detect BOLD activation in human visual cortex. Eight healthy young adults were imaged at 3 T using a single-slice, SL-prepped turbo spin echo (TSE) sequence with spin-lock amplitudes ω1 = 80 Hz and 400 Hz, along with conventional T2*-weighted and T2-prepped sequences. The BOLD signal varied from 1.1 ± 0.4 % (ω1 = 80 Hz) to 0.7 ± 0.2 % (at 400 Hz), whereas the T2-weighted sequence measured 1.3 ± 0.3 % and the T2* sequence measured 1.9 ± 0.3 %. This new R1ρ functional contrast can be made selectively sensitive to intrinsic gradients of different spatial scales, thereby increasing the spatial specificity of the evoked response.