Acceleration of natural-abundance solid-state MAS NMR measurements on bone by paramagnetic relaxation from gadolinium-DTPA

Reducing the data collection time without affecting the signal intensity and spectral resolution is one of the major challenges for the widespread application of multidimensional nuclear magnetic resonance (NMR) spectroscopy, especially in experiments conducted on complex heterogeneous biological systems such as bone. In most of these experiments, the NMR data collection time is ultimately governed by the proton spin-lattice relaxation times (T₁). For over two decades, gadolinium(III)-DTPA (Gd-DTPA, DTPA = Diethylene triamine pentaacetic acid) has been one of the most widely used contrast-enhancement agents in magnetic resonance imaging (MRI). In this study, we demonstrate that Gd-DTPA can also be effectively used to enhance the longitudinal relaxation rates of protons in solid-state NMR experiments conducted on bone without significant line-broadening and chemical-shift-perturbation side effects. Using bovine cortical bone samples incubated in different concentrations of Gd-DTPA complex, the ¹H T₁ values were calculated from data collected by ¹H spin-inversion recovery method detected in natural-abundance ¹³C cross-polarization magic angle spinning (CPMAS) NMR experiments. Our results reveal that the ¹H T₁ values can be successfully reduced by a factor of 3.5 using as low as 10 mM Gd-DTPA without reducing the spectral resolution and thus enabling faster data acquisition of the ¹³C CPMAS spectra. These results obtained from ¹³C-detected CPMAS experiments were further confirmed using ¹H-detected ultrafast MAS experiments on Gd-DTPA doped bone samples. This approach considerably improves the signal-to-noise ratio per unit time of NMR experiments applied to bone samples by reducing the experimental time required to acquire the same number of scans.