Revisiting aliasing noise to build more robust sparsity in nonuniform sampling 2D-NMR

A continuing priority is to better understand and resolve the barriers to using nonuniform sampling (NUS) in challenging small molecule 2D NMR with subsampling of the Nyquist grid (a.k.a. coverage) below 50%. Possible causes for artifacts, often termed sampling noise, in 1D-NUS of 2D-NMR are revisited here, where weak aliasing artifacts are a growing concern as NUS becomes sparser. As NUS schedules become sparser, repeat sequences are shown to occur in the dense sampling regions early in the sampling schedule, causing aliasing artifacts in resulting spectra. An intuitive screening approach that detects patterns in sampling schedules based on a convolutional filter was implemented. Sampling schedules that have low proportions of repeat sequences show significantly reduced artifacts. Another route to remediate early repeat sequences is a short period of uniform sampling at the beginning of the schedule, which also leads to a significant suppression of unwanted sampling noise. Combining the repeat sequence filter with a survey of HSQC and LR-HSQMBC experiments, it is shown that very short initial uniform regions of about 2%-4% of the sampling space can ameliorate repeat sequences in sparser NUS and lead to robust spectral reconstructions by iterative soft thresholding (IST), even when the point spread function is unchanged. Using the principles developed here, a suite of 'one-click' schedules was developed for broader use.

Automated summary

Resolving the barriers to using nonuniform sampling (NUS) in challenging small molecule 2D NMR, especially when the subsampled coverage is below 50%, is a continuing priority. The presence of repeat sequences in the dense sampling regions during the early stages of NUS schedules leads to aliasing artifacts in resulting spectra. By implementing a repeat sequence filter and incorporating a short period of uniform sampling at the beginning of the schedule, it is possible to significantly reduce sampling noise and improve the robustness of spectral reconstructions.