Nonaqueous magnetization following adiabatic and selective pulses in brain: T1 and cross-relaxation dynamics.

Inversion pulses are commonly employed in MRI for T 1 -weighted contrast and relaxation measurements. In the brain, it is often assumed that adiabatic pulses saturate the nonaqueous magnetization. We investigated this assumption using solid-state NMR to monitor the nonaqueous signal directly following adiabatic inversion and compared this with signals following hard and soft inversion pulses. The effects of the different preparations on relaxation dynamics were explored. Inversion recovery experiments were performed on ex vivo bovine and porcine brains using 360-MHz (8.4 T) and 200-MHz (4.7 T) NMR spectrometers, respectively, using broadband rectangular, adiabatic, and sinc inversion pulses as well as a long rectangular saturation pulse. Analogous human brain MRI experiments were performed at 3 T using single-slice echo-planar imaging. Relaxation data were fitted by mono- and biexponential decay models. Further fitting analysis was performed using only two inversion delay times. Adiabatic and sinc inversion left much of the nonaqueous magnetization along B 0 and resulted in biexponential relaxation. Saturation of both aqueous and nonaqueous magnetization components led to effectively monoexponential T 1 relaxation. Typical adiabatic inversion pulses do not, as has been widely assumed, saturate the nonaqueous proton magnetization in white matter. Unequal magnetization states in aqueous and nonaqueous 1 H reservoirs prepared by soft and adiabatic pulses result in biexponential T 1 relaxation. Both pools must be prepared in the same magnetization state (e.g., saturated or inverted) in order to observe consistent monoexponential relaxation.

Quantification of NAD+ in human brain with 1 H MR spectroscopy at 3 T: Comparison of three localization techniques with different handling of water magnetization.

PURPOSE: The detection of nicotinamide-adenine-dinucleotide (NAD+ ) is challenging using standard 1 H MR spectroscopy, because it is of low concentration and affected by polarization-exchange with water. Therefore, this study compares three techniques to access NAD+ quantification at 3 T-one with and two without water presaturation. METHODS: A large brain volume in 10 healthy subjects was investigated with three techniques: semi-LASER with water-saturation (WS) (TE = 35 ms), semi-LASER with metabolite-cycling (MC) (TE = 35 ms), and the non-water-excitation (nWE) technique 2D ISIS-localization with chemical-shift-selective excitation (2D I-CSE) (TE = 10.2 ms). Spectra were quantified with optimized modeling in FiTAID. RESULTS: NAD+ could be well quantified in cohort-average spectra with all techniques. Obtained apparent NAD+ tissue contents are all lower than expected from literature confirming restricted visibility by 1 H MRS. The estimated value from WS-MRS (58 µM) was considerably lower than those obtained with non-WS techniques (146 µM for MC-semi-LASER and 125 µM for 2D I-CSE). The nWE technique with shortest TE gave largest NAD+ signals but suffered from overlap with large amide signals. MC-semi-LASER yielded best estimation precision as reflected in relative Cramer-Rao bounds (14%, 21 µM/146 µM) and also best robustness as judged by the coefficient-of-variance over the cohort (11%, 10 µM/146 µM). The MR-visibility turned out as 16% with WS and 41% with MC. CONCLUSION: Three methods to assess NAD+ in human brain at 3 T have been compared. NAD+ could be detected with a visibility of ∼41% for the MC method. This may open a new window for the observation of pathological changes in the clinical research setting.

Non-water-excitation MR spectroscopy techniques to explore exchanging protons in human brain at 3 T.

PURPOSE: To develop localization sequences for in vivo MR spectroscopy (MRS) on clinical scanners of 3 T to record spectra that are not influenced by magnetization transfer from water. METHODS: Image-selected in vivo spectroscopy (ISIS) localization and chemical-shift-selective excitation (termed I-CSE) was combined in two ways: first, full ISIS localization plus a frequency-selective spin-echo and second, two-dimensional (2D) ISIS plus a frequency-selective excitation and slice-selective refocusing. The techniques were evaluated at 3 T in phantoms and human subjects in comparison to standard techniques with water presaturation or metabolite-cycling. ISIS included gradient-modulated offset-independent adiabatic (GOIA)-type adiabatic inversion pulses; echo times were 8-10 ms. RESULTS: The novel 2D and 3D I-CSE methods yield upfield spectra that are comparable to those from standard MRS, except for shorter echo times and a limited frequency range. On the downfield/high-frequency side, they yield much more signal for exchangeable protons when compared to MRS with water presaturation or metabolite-cycling and longer echo times. CONCLUSION: Novel non-water-excitation MRS sequences offer substantial benefits for the detection of metabolite signals that are otherwise suppressed by saturation transfer from water. Avoiding water saturation and using very short echo times allows direct observation of faster exchanging moieties than was previously possible at 3 T and additionally makes the methods less susceptible to fast T2 relaxation.

Understanding the mechanism of proteasome 20S core particle gating.

The 20S core particle proteasome is a molecular machine playing an important role in cellular function by degrading protein substrates that no longer are required or that have become damaged. Regulation of proteasome activity occurs, in part, through a gating mechanism controlling the sizes of pores at the top and bottom ends of the symmetric proteasome barrel and restricting access to catalytic sites sequestered in the lumen of the structure. Although atomic resolution models of both open and closed states of the proteasome have been elucidated, the mechanism by which gates exchange between these states remains to be understood. Here, this is investigated by using magnetization transfer NMR spectroscopy focusing on the 20S proteasome core particle from Thermoplasma acidophilum. We show from viscosity-dependent proteasome gating kinetics that frictional forces originating from random solvent motions are critical for driving the gating process. Notably, a small effective hydrodynamic radius (EHR; <4Å) is obtained, providing a picture in which gate exchange proceeds through many steps involving only very small segment sizes. A small EHR further suggests that the kinetics of gate interconversion will not be affected appreciably by large viscogens, such as macromolecules found in the cell, so long as they are inert. Indeed, measurements in cell lysate reveal that the gate interconversion rate decreases only slightly, demonstrating that controlled studies in vitro provide an excellent starting point for understanding regulation of 20S core particle function in complex, biologically relevant environments.

Detection of intermolecular homonuclear dipolar coupling in organic rich shale by transverse relaxation exchange.

The mechanism behind surface relaxivity within organic porosity in shales has been an unanswered question. Here, we present results that confirm the existence of intermolecular homonuclear dipolar coupling between solid and liquid phases in sedimentary organic matter. Transverse magnetization exchange measurements were performed on an organic-rich shale saturated with liquid hydrocarbon. Liquid and solid constituents were identified through both sample resaturation and through their T1/T2 ratios. Extensive cross peaks are observed in the T2-T2 exchange spectra between the solid and liquid constituents, indicating an exchange of magnetization between the two phases. This result cannot arise from physical molecular diffusion, and the dissolution energies are too high for chemical exchange, such that the magnetization exchange must arise from intermolecular homonuclear dipolar coupling. These results both confirm a possible source of surface relaxivity in organic matter and emphasize caution in the use of standard porous media interpretations of relaxation results in shales because of coupling between different magnetization environments.