Method for longitudinal relaxation time measurement in inhomogeneous fields

Abstract

A protocol to determine chemical shift-specific Ti constants in inhomogeneous magnetic fields is provided. Based on intermolecular double-quantum coherences and spatial encoding techniques, the method can resolve overlapped NMR spectral peaks in inhomogeneous magnetic fields acquired using conventional methods. With inversion recovery involved, the amplitude of spectral peak will be modulated by inversion recovery time. After fitting the spectral peak amplitude variation curve, the corresponding longitudinal relaxation time can be achieved. With the measured T.sub.1 values in inhomogeneous magnetic fields, insights into chemical exchange rates, signal optimization, and data quantitation can be obtained.

Claims

1. A method for measuring longitudinal relaxation time of protons in inhomogeneous magnetic fields, the method comprising: (a) putting a sample to be tested into a nuclear magnetic resonance (NMR) tube, and placing the NMR tube into an NMR spectrometer; (b) acquiring a proton NMR spectrum using a one-dimensional (1D) proton NMR pulse sequence to gain a distribution of spectral peaks and a spectral width of the sample to be tested, and then tuning a probe of the NMR spectrometer; (c) measuring a length of a non-selective π/2 radio-frequency (RF) pulse along with a length and a power of a solvent-selective (π/2).sup.I RF pulse; (d) loading a designed pulse sequence into the NMR spectrometer comprising an inversion recovery module, the non-selective π/2 RF pulse, two spatial encoding modules, an intermolecular double-quantum coherence signal selection module, and a spatial decoding module; (e) setting up parameters of the designed pulse sequence, and then using the designed pulse sequence to acquire a set of spectral data of the sample to be tested; (f) processing the set of spectral data to obtain a set of 1D spectra with chemical shift information and spectral peak amplitudes modulated by an inversion recovery time; (g) measuring absolute amplitudes of each of solute spectral peaks under different inversion recovery times and then normalizing, setting the absolute amplitudes before a minimum amplitude to be negative, and plotting variation curves of the absolute amplitudes with the inversion recovery time for each of the solute spectral peaks; and (i) fitting the variation curves to obtain the longitudinal relaxation time of the protons.

2. The method of claim 1, wherein: measuring the length of the non-selective π/2 RF pulse comprises measuring a duration of a non-selective RF pulse to flip proton magnetization from a longitudinal direction onto a transverse plane, and measuring the length and the power of the solvent-selective (π/2).sup.I RF pulse comprises measuring a duration and a power of the solvent-selective (π/2).sup.I RF pulse to flip solvent proton magnetization from the longitudinal direction onto the transverse plane.

3. The method of claim 1, wherein the inversion recovery module comprises a solvent-selective (π).sup.I RF pulse, a non-selective π RF pulse, and the inversion recovery time.

4. The method of claim 1, wherein each of the two spatial encoding modules comprises two identical adiabatic chirp RF pulses and a pair of first dipolar gradients.

5. The method of claim 1, wherein: the intermolecular double-quantum coherence signal selection module comprises a first gradient, the solvent-selective (π/2).sup.I RF pulse, a second gradient, and a spin echo unit, and an area ratio of the first gradient and the second gradient is 1:(−2).

6. The method of claim 1, wherein the parameters of the designed pulse sequence comprise the length of the non-selective π/2 RF pulse, a length of a non-selective π RF pulse of the inversion recovery module, a length and a sweep bandwidth of two identical adiabatic chirp RF pulses of each of the two spatial encoding modules, a strength of a pair of first dipolar gradients of each of the two spatial encoding modules, a length and a strength of a first gradient and a second gradient of the intermolecular double-quantum coherence signal selection module, the length and the power of the solvent-selective (π/2).sup.I RF pulse, a length and a power of a solvent-selective (π).sup.I RF pulse of the inversion recovery module, echo delay, acquisition points in the spatial decoding module, a number of repetition times of the spatial decoding module, a strength of a pair of second dipolar gradients of the spatial decoding module, repetition time, and the inversion recovery time.

7. The method of claim 1, wherein: processing the set of spectral data comprises: rearranging each spectral data of the set of spectral data to a two-dimensional (2D) matrix having a first dimension np1 and a second dimension N.sub.a, fast Fourier transforming (FFT) the 2D matrix along the second dimension N.sub.a to obtain a 2D spectrum; rotating each 2D spectrum 45° counter-clockwise, making an accumulated projection along the first dimension np1 to produce the set of 1D spectra.

8. The method of claim 1, wherein: fitting the variation curves comprises fitting using a three-parameter function y=a−b×exp(−x/T.sub.1) in a computer to obtain values of a, b, and T.sub.1, where x is the inversion recovery time, y is the absolute amplitude of each of the spectral peaks at a corresponding inversion recovery time, and T.sub.1 is the longitudinal relaxation time of the protons.

9. The method according to claim 1, wherein the spatial decoding module comprises a pair of second dipolar gradients configured to be applied during acquiring the proton NMR spectrum.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is a diagram of the designed pulse sequence for proton longitudinal relaxation time measurement in inhomogeneous magnetic fields.

(2) FIG. 2 is a 1D spectrum of a 1-butanol aqueous solution acquired using a 1D proton pulse sequence in an inhomogeneous field which imposed 100 Hz line broadening on spectral peaks. The structure of 1-butanol is given at the upper right, in which proton groups are labelled by numbers.

(3) FIG. 3 is a high-resolution 1D spectrum obtained by rotating and projecting a 2D spectrum acquired using the designed pulse sequence in the present invention. The inversion recovery time is 32 s.

(4) FIG. 4 shows the variation of absolute amplitude of butanol-H2 spectral peak with inversion recovery time Δ detected by the present invention.

(5) FIG. 5 shows the variation curves of absolute amplitude of each solute spectral peak with inversion recovery time Δ.

(6) FIG. 6 shows the variation curves of amplitude of each solute spectral peak with inversion recovery time Δ, in which the amplitudes before the minimum amplitude are set to be negative.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

(7) Embodiments of the present invention are illustrated in further detail below as examples to explain the object, technical solution, and advantages thereof.

(8) The present invention can be implemented on any suitable equipment, and the preferred embodiment has been implemented on a Varian NMR System 500 MHz spectrometer (Varian, Palo Alto, Calif., USA). The sample is 1.0 M 1-butanol aqueous solution, in which 1-butanol serves as solute and water serves as solvent.

(9) The designed pulse sequence for the measurement of proton longitudinal relaxation time in inhomogeneous magnetic fields (as shown in FIG. 1) comprises an inversion recovery module, a non-selective π/2 RF pulse, two spatial encoding modules, an intermolecular double-quantum coherence signal selection module, and a spatial decoding module. The inversion recovery module comprises a solvent-selective (π).sup.I RF pulse, a non-selective π RF pulse, and an inversion recovery time Δ. The spatial encoding module comprises two identical adiabatic chirp RF pulses and a pair of dipolar gradients (G.sub.e and −G.sub.e). The intermolecular double-quantum coherence signal selection module comprises a gradient G.sub.1, a solvent-selective (π/2).sup.I RF pulse, a gradient G.sub.2, and a spin echo unit δ-π-δ, where the area ratio of gradients G.sub.1 and G.sub.2 is 1:(−2). The spatial decoding module comprises a pair of dipolar gradients (G.sub.a and −G.sub.a) which are applied in the acquisition period.

(10) The present invention is a method for the measurement of proton longitudinal relaxation time in inhomogeneous magnetic fields, and the longitudinal relaxation time of 1-butanol protons in an inhomogeneous field is obtained according to the procedure of the following steps (a) to (i).

(11) (a) Putting some 1-butanol aqueous solution (about 0.6 mL) into a 5 mm NMR (nuclear magnetic resonance) tube, and placing the NMR tube into the NMR spectrometer.

(12) (b) Acquiring a proton NMR spectrum of the solution using a one-dimensional (1D) proton pulse sequence to gain the distribution of spectral peaks and the spectral width of 1-butanol aqueous solution.

(13) (c) Tuning the probe of the NMR spectrometer.

(14) (d) Using the 1D proton pulse sequence to measure the length of non-selective π/2 pulse, which is 15 μs, and using a Gaussian-shaped RF pulse to measure the length and power of solvent-selective (π/2).sup.I RF pulse, which are 5 ms and 19 dB. Setting the length of solvent-selective (π).sup.I RF pulse as 5 ms and the power as 25 dB.

(15) (e) Loading the designed pulse sequence for proton longitudinal relaxation time measurement in inhomogeneous magnetic fields (as shown in FIG. 1) into the NMR spectrometer.

(16) (f) Setting up parameters of the designed pulse sequence and acquiring data as follows: the duration of each adiabatic chirp RF pulse is 10 ms, the sweep width of each adiabatic chirp RF pulse is 20 kHz; the strength of encoding gradients G.sub.e is 3.9 G/cm; the strength of coherence selection gradient G.sub.1 is 10 G/cm with a duration of 1.5 ms; the strength of coherence selection gradient G.sub.2 is −20 G/cm with a duration of 1.5 ms; the length of delay δ is 24 ms; the number of repetition times N.sub.a of the spatial decoding module is 180 (N.sub.a=180); the number of acquisition points (np1) is 75; the strength of decoding gradient G.sub.a is 5.9 G/cm; the repetition time TR is 20 s; the experiments were performed with fourteen different inversion recovery times (Δ=0.0625, 0.125, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 16, 32 s). There were fourteen 2D spectra recorded taking 7.5 min.

(17) (g) Processing the acquired data as follows: rearranging each spectral data to a 2D matrix with a size of np1×N.sub.a; fast Fourier transforming (FFT) the matrix along the dimension of N.sub.a to obtain a 2D spectrum; rotating each 2D spectrum 45° counter-clockwise and making an accumulated projection along the dimension of np1, thus producing a set of high-resolution 1D spectra (see FIG. 3 for an example); and assigning the spectral peaks to corresponding protons according to the chemical shifts. FIG. 4 displays the variation of the absolute amplitude of butanol-H2 spectral peak with the inversion recovery time Δ.

(18) (h) Measuring the absolute amplitudes of each butanol spectral peak under different inversion recovery time Δ, normalizing the amplitudes with reference to the absolute amplitude of the spectral peak when Δ is 32 s, and plotting the variation curves of absolute spectral peak amplitudes with Δ, as shown in FIG. 5. As the 2D spectra are displayed in absolute value mode, the curves in FIG. 5 cannot represent the actual variation of spectral peak amplitudes. Setting the spectral peak amplitudes before the minimum spectral peak amplitude to be negative, and plotting the variation curves of spectral peak amplitudes with the inversion recovery time Δ, as displayed in FIG. 6.

(19) (i) Fitting the variation curves of spectral peak amplitudes with inversion recovery time Δ plotted in FIG. 6 with the function y=a−b×exp(−x/T.sub.1) in a computer, where the variable x is the inversion recovery time Δ and the function value y is the amplitude of solute spectral peak. The values of a, b and T.sub.1 are obtained after fitting, and T.sub.1 is the longitudinal relaxation time of protons to be measured. The obtained T.sub.1 values of 1-butanol protons (H2, H3, H4, H5) are 2.73, 2.77, 3.08 and 3.18 s, respectively.

(20) In summary, the present invention provides a method for measurement of proton longitudinal relaxation time in inhomogeneous magnetic fields. With the advantage of intermolecular double-quantum coherence, the measurement method reduces the spectral line broadening and overlapping caused by the inhomogeneity of magnetic fields and retrieves chemical shift information. In conjunction with inversion recovery, spectral peak amplitude varies with inversion recovery time, and longitudinal relaxation time of protons can be figured out by numeric fitting. With the knowledge of longitudinal relaxation time measured by the present invention, strong signals could be suppressed and weak signals could be retrieved. Furthermore, the knowledge of longitudinal relaxation time can potentially provide insights into chemical exchange rates in inhomogeneous magnetic fields, and is of great significance to signal optimization and data quantification. It has wide application and good industrial practicability.