# Enhanced Sensitivity and Resolution in Biomolecular CEST NMR Experiments Using the Extended Hadamard Encoding Scheme

## TL;DR

This paper introduces an improved method for CEST NMR experiments that reduces artifacts and improves sensitivity using an extended Hadamard encoding scheme.

## Contribution

The novel extended Hadamard Transform (eHT) scheme eliminates artifacts in CEST NMR while maintaining sensitivity gains.

## Key findings

- Classical Hadamard encoding in CEST NMR leads to strong artifacts due to chemical exchange effects.
- The extended Hadamard Transform (eHT) eliminates these artifacts while preserving sensitivity enhancements.
- eHT CEST outperforms other accelerated CEST NMR methods in terms of artifact-free performance.

## Abstract

By untangling information
using deterministic frequency-domain
linear combinations, the Hadamard Transform (HT) offers a robust way
to extract spectral information. Hadamard-based encoding schemes can
shorten the acquisition times of nuclear magnetic resonance (NMR)
experiments, and lead to substantial sensitivity gains/unit time.
However, the presence of spin–spin couplings, spin–spin
cross-relaxation, or other mechanisms that break simple one-to-one
relationships between a peak intensity and its frequency-domain position
can complicate this approach. A case where manipulations at a given
peak frequency position may affect the intensity of other peaks in
the spectra arises in chemical exchange. Thus, in frequency-domain
NMR experiments such as chemical exchange saturation transfer (CEST),
saturation at one frequency position may bring about significant intensity
changes at another frequency. This study shows that when based on
classical frequency-domain Hadamard encodings, strong artifacts will
then arise in NMR CEST experiments. The origin of these artifacts
is explained and a way to eliminate them while preserving HT’s
desirable characteristics is proposed, utilizing an extended HT (eHT)
scheme. CEST NMR experiments performed and processed using the eHT
are shown to be free from artifacts, while leveraging Hadamard’s
sensitivity-enhanced performance over step-by-step frequency-domain
implementations. Good performance is also observed when eHT CEST is
compared against other accelerated versions of protein CEST NMR. A
summary of the features and potential opened by these new experiments
is provided.