Biomedical subjects

Ray Freeman

Publications and source records attributed to Ray Freeman.

5 recordsLinked to original sources

PubMed2003

Frequency-domain Hadamard spectroscopy.

A new technique is proposed for multichannel excitation and detection of NMR signals in the frequency domain, an alternative to the widely used pulse-excited Fourier transform method. An extensive array of N radiofrequency irradiation channels covers the spectrum of interest. A selective radiofrequency pulse sequence is applied to each channel, generating a steady-state NMR response acquired one-point-at-a-time in the intervals between pulses. The excitation pattern is repeated N times, phase-encoded according to a Hadamard matrix, and the corresponding N composite responses are decoded by reference to the same matrix. This multiplex technique offers the same sensitivity advantage as conventional Fourier transform spectroscopy. The irradiation pattern may be tailored to concentrate on interesting spectral regions, to facilitate homonuclear double resonance, or to avoid exciting strong solvent peaks. As no free induction decay is involved, the new method avoids problems of pulse breakthrough or lineshape distortion by premature termination of the time-domain signal.

Fourier Analysis↗

PubMed2003

Two-dimensional Hadamard spectroscopy.

Direct frequency-domain excitation of NMR with an array of different radiofrequencies has been used to speed up two-dimensional NMR experiments by a large factor. Multiplex excitation in the F(1) frequency dimension is restricted to the signal-bearing regions and is encoded according to a Hadamard matrix of dimension N by N, where N is a relatively small number. The detected signals are decoded by reference to the same Hadamard matrix. Alternatively a phase-encoding scheme can be employed. Two-dimensional correlation experiments (COSY and TOCSY) and cross-relaxation measurements (NOESY) implemented on proton systems can be completed in less than a minute in cases where the intrinsic sensitivity is sufficiently high that prolonged multiscan averaging is not required. The results are presented in the form of a high-resolution contour diagram similar to the familiar two-dimensional spectra obtained by Fourier transform methods. Experiments on strychnine demonstrate more than two orders of magnitude improvement in speed compared with the traditional methods.

Algorithms↗

PubMed2003

Fast multi-dimensional Hadamard spectroscopy.

Multi-dimensional NMR spectroscopy can be speeded up by large factors by replacing the time-domain evolution dimensions by direct irradiation at signal-bearing sites with a frequency-domain multiplex scheme. There is no loss in sensitivity per unit time. The excitation and transfer operations are encoded according to Hadamard matrices and the detected NMR signals are decoded by reference to the same matrices. Most traditional multi-dimensional NMR pulse sequences can be readily converted into this new Hadamard mode. Three-dimensional TOCSY-HSQC experiments on strychnine at 700 MHz bear out these ideas, indicating that the measurement time can be reduced by as much as three orders of magnitude in favorable cases.

Algorithms↗

PubMed2003

Fast multi-dimensional NMR of proteins.

Three-dimensional HNCO and HNCA subspectra from a small protein (agitoxin, 4 kDa, enriched in carbon-13 and nitrogen-15), have been obtained by direct frequency-domain excitation of selected carbon and nitrogen sites. This new technique applies an array of several simultaneous soft radiofrequency spin-inversion pulses, encoded (on or off) according to nested Hadamard matrices, and the resulting responses are extracted by reference to the same matrices. This not only simplifies the spectra but, by avoiding extensive sampling in the traditional evolution dimensions, affords a speed advantage of more than two orders of magnitude.

Amino Acid Sequence↗

PubMed2003

New methods for fast multidimensional NMR.

Considerable excitement has been aroused by recent new methods for speeding up multidimensional NMR experiments by radically modifying the normal time-domain sampling protocols. These new schemes include the filter diagonalization method, GFT-NMR, the single-scan two-dimensional technique, Hadamard spectroscopy, and a proposal based on projection-reconstruction of three-dimensional spectra. All these methods deliver appreciable improvements in the speed of data acquisition and show promise for speeding up multidimensional NMR of proteins. This perspective aims to describe these important new procedures in simple terms and to comment on their advantages and possible limitations.

Magnetic Resonance Spectroscopy↗