Unleashing the power of steady-state high-resolution NMR: Methods, Molecules, Metabolism

2026-07-22

Pulsed Fourier-transform (FT) has reigned supreme in nuclear magnetic resonance (NMR) for over 50 years, standing at the core of numerous analytical, pharmaceutical, materials, biophysical and medical applications. However, if spectral information is not a must, FT NMR is not necessarily the optimal way for maximizing sensitivity: when, as often happens, spin relaxation times are long and T1≈T2, steady-state free-precession (SSFP) experiments can provide a higher sensitivity per unit time. SSFP NMR applies a train of closely spaced pulses and works only at suitable offsets, and has therefore been assumed impractical when seeking high resolution among multiple chemical sites. We have recently found a way to break this limitation, enabling SSFP-based schemes to resolve multiple sharp peaks spread over arbitrarily large bandwidths. We have also devised routes that can incorporate J-driven polarization transfers onto these sequences. On the basis of such findings, we propose here a series of SSFP-based developments, that in numerous heteronuclear NMR applications should provide sensitivities exceeding by sizable margins those afforded by FT NMR. SteadyNMR presents preliminary experiments and calculations substantiating such claim (see below an example on a mix of aromatic hydrocarbons in chloroform), and builds on them to: devise optimal spectral reconstruction algorithms translating SSFP’s enhancements into high-resolution methods opening new frontiers in chemical and biomolecular research; exploit these methods potential to monitor dynamics on thermal and on hyperpolarized samples; develop new families of metabolic 13C spectroscopic imaging experiments that are both 1H- and SSFP-enhanced, serving as basis for potentially superior ways of detecting cancer and metabolic abnormalities on widely available MRI platforms; combine these and other principles into new approaches complementing –and eventually improving– existing FT-based 2D NMR schemes.

Israel

2025-10-01