METHOD FOR LONGITUDINAL RELAXATION TIME MEASUREMENT IN INHOMOGENEOUS FIELDS

Abstract

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

Claims

1. A method for longitudinal relaxation time in inhomogeneous fields, the method comprising: (a) Put the sample into an NMR tube, and place the tube into the magnetic resonance spectrometer; (b) Run the spectrometer operation software on the console computer, and use the conventional 1D proton pulse sequence acquiring a 1D proton spectrum to gain the distribution of spectral peaks and the spectral width, then tune the probe; (c) Calibrate the length of the non-selective /2 RF pulse along with the length and power of the solvent-selective (/2).sup.I RF pulse; (d) Load the pulse sequence into the spectrometer console, and activate the modules for inversion recovery, spatial encoding, intermolecular double-quantum coherence signal selection and spatial decoding; (e) Set up the parameters of pulse sequence, check the setup and start data acquisition; (f) Once spectral data acquisition is done, apply 2D data reconstruction, 2D spectrum shearing and accumulated projection to the raw data, thus get a set of 1D spectra with high-resolution chemical shift information and the spectral amplitudes are modulated by the inversion recovery time; (g) Fitting the amplitude variation curve for each peak to obtain the longitudinal relaxation time.

2. The method of claim 1, wherein step (b) the conventional proton pulse sequence comprises a non-selective /2 RF pulse. The acknowledge of peak distribution and spectral width can be gained from the 1D proton spectrum acquired with the conventional 1D proton pulse sequence. Set the RF pulse transmit offset to the center of the solvent peak.

3. The method of claim 1, wherein step (c) the calibration of the length of the non-selective /2 RF pulse is carried out by measuring the duration of RF pulse to flip the magnetization from longitudinal direction onto the transverse plane; and transform the pulse shape in the conventional proton pulse sequence to Gaussian to calibrate the length and power of the solvent-selective (/2).sup.I RF pulse.

4. The method of claim 1, wherein step (d) the inversion recovery module comprises a solvent-selective ().sup.I RF pulse, a non-selective RF pulse and an inversion recovery delay .

5. The method of claim 1, wherein step (d) the spatial encoding module comprises two identical chirp adiabatic RF pulses and a pair of dipolar gradients.

6. The method of claim 1, wherein step (d) the intermolecular double-quantum coherence signal selection module comprises a gradient G.sub.1, a solvent-selective (/2).sup.I RF pulse, a gradient G.sub.2 and a spin echo --; 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 which are applied in the acquisition period.

7. The method of claim 1, wherein step (e) the parameters of pulse sequence comprise the length of the non-selective /2 RF pulse, the length and sweep bandwidth of chirp adiabatic pulses, the strength of encoding gradient G.sub.e, the length and strength of the gradients G.sub.1 and G.sub.2, the length and of power of the solvent-selective (/2).sup.I RF pulse, the power of solvent-selective ().sup.I RF pulse, the echo delay , the acquisition points np1 in the spatial decoding module, the number of repetition times N.sub.a of the spatial decoding module, the strength of decoding gradient G.sub.a, repetition delay TR, and the inversion recovery delay .

8. The method of claim 1, wherein step (e) the parameters of pulse sequence comprise a set of varied inversion recovery delays.

9. The method of claim 1, wherein step (f) when the data acquisition is completed, the raw data of each ultrafast 2D spectrum are reconstructed to a 2D matrix with the size of np1*N.sub.a, and the 2D spectrum is gained after FFT; rotate each 2D spectrum 45 counter-clockwise and make accumulated projection along the spatial encoding dimension, thus a set of high-resolution 1D spectra are attained, measure the amplitude of each peak and then normalize, set the amplitudes of the data points before the minimum amplitude to be negative, and plot the curves in which the amplitudes of peaks vary with the inversion recovery delay .

10. The method of claim 1, wherein step (g) the amplitude vs. curves plotted in step (f) are fitted with the function y=abexp(x/T.sub.1) in a computer, where the variable x is the inversion recovery time and the function value y is the amplitude of each peak. The values of a, b and T.sub.1 are obtained with a three-parameter fitting, and T.sub.1 is the longitudinal relaxation time of protons in the peak.

11. The method of claim 1, wherein the sample for the demonstration of the method is 1.0 M 1-butanol aqueous solution in which 1-butanol serve as solute and water serves as solvent.

12. The method of claim 1, wherein the pulse sequence for longitudinal relaxation time measurement comprises the modules for inversion recovery, spatial encoding, intermolecular double-quantum coherence signal selection and spatial decoding.

13. The method of claim 1, wherein the data processing comprises: (a) The raw data of each ultrafast 2D spectrum are reconstructed to a 2D matrix with the size of np1*N.sub.a, and the 2D spectrum is gained after FFT; rotate each 2D spectrum 45 counter-clockwise and make accumulated projection along the spatial encoding dimension, thus a set of high-resolution 1D spectra are attained, assign the spectral peaks to their proton groups according to the chemical shifts. (b) The absolute amplitude of the butanol-H2 varies with the inversion recovery delay . Measure the amplitude of each peak. (c) Normalize the amplitude with reference to the amplitude of the peak when is 32 s, and plot the curves of amplitude vs. . (d) As the 2D spectra are displayed in absolute value mode, set the amplitudes of the data points before the minimum amplitude to be negative, and plot the curves in which amplitudes of peaks vary with the inversion recovery delay . (e) The amplitude vs. A curves are fitted with the function y=abexp(x/T.sub.1) in a computer, where the variable x is the inversion recovery delay and the function value y is the amplitude of peak. The values of a, b and T.sub.1 are obtained with a three-parameter fitting, and T.sub.1 is the longitudinal relaxation time of protons in the peak. The T.sub.1 values of 1-butanol protons (H2, H3, H4, H5) are 2.73, 2.77, 3.08 and 3.18 s, respectively.

14. The method of claim 2, wherein step (d) the spatial encoding module comprises two identical chirp adiabatic RF pulses and a pair of dipolar gradients.

15. The method of claim 3, wherein step (d) the spatial encoding module comprises two identical chirp adiabatic RF pulses and a pair of dipolar gradients.

16. The method of claim 4, wherein step (d) the spatial encoding module comprises two identical chirp adiabatic RF pulses and a pair of dipolar gradients.

17. The method of claim 2, wherein step (d) the intermolecular double-quantum coherence signal selection module comprises a gradient G1, a solvent-selective (/2)I RF pulse, a gradient G2 and a spin echo --; where the area ratio of gradients G1 and G2 is 1:(2); the spatial decoding module comprises a pair of dipolar gradients which are applied in the acquisition period.

18. The method of claim 3, wherein step (d) the intermolecular double-quantum coherence signal selection module comprises a gradient G1, a solvent-selective (/2)I RF pulse, a gradient G2 and a spin echo --; where the area ratio of gradients G1 and G2 is 1:(2); the spatial decoding module comprises a pair of dipolar gradients which are applied in the acquisition period.

19. The method of claim 4, wherein step (d) the intermolecular double-quantum coherence signal selection module comprises a gradient G1, a solvent-selective (/2)I RF pulse, a gradient G2 and a spin echo --; where the area ratio of gradients G1 and G2 is 1:(2); the spatial decoding module comprises a pair of dipolar gradients which are applied in the acquisition period.

20. The method of claim 11, wherein the pulse sequence for longitudinal relaxation time measurement comprises the modules for inversion recovery, spatial encoding, intermolecular double-quantum coherence signal selection and spatial decoding.

21. The method of claim 1, wherein the data processing comprises: (a) The raw data of each ultrafast 2D spectrum are reconstructed to a 2D matrix with the size of np1*Na, and the 2D spectrum is gained after FFT; rotate each 2D spectrum 45 counter-clockwise and make accumulated projection along the spatial encoding dimension, thus a set of high-resolution 1D spectra are attained, assign the spectral peaks to their proton groups according to the chemical shifts. (b) The absolute amplitude of the butanol-H2 varies with the inversion recovery delay . Measure the amplitude of each peak. (c) Normalize the amplitude with reference to the amplitude of the peak when is 32 s, and plot the curves of amplitude vs. . (d) As the 2D spectra are displayed in absolute value mode, set the amplitudes of the data points before the minimum amplitude to be negative, and plot the curves in which amplitudes of peaks vary with the inversion recovery delay . (e) The amplitude vs. curves are fitted with the function y=abexp(x/T1) in a computer, where the variable x is the inversion recovery delay and the function value y is the amplitude of peak. The values of a, b and T1 are obtained with a three-parameter fitting, and T1 is the longitudinal relaxation time of protons in the peak. The T1 values of 1-butanol protons (H2, H3, H4, H5) are 2.73, 2.77, 3.08 and 3.18 s, respectively.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0020] FIG. 1 is a diagram of the pulse sequence used for the measurement of longitudinal relaxation time in inhomogeneous fields.

[0021] FIG. 2 is a 1D spectrum of 1-butanol solution acquired using the conventional 1D proton pulse sequence in an inhomogeneous field which imposed 100 Hz line broadening on peaks. The structure of 1-butanol is given at the upper right, in which proton groups are labelled by numbers.

[0022] FIG. 3 is the high-resolution 1D spectrum obtained by rotating and projecting the 2D spectrum acquired using the pulse sequence in the present invention. The inversion recovery time is 32 s.

[0023] FIG. 4 is the variation of absolute amplitude of butanol-H2 peak detected by the present invention.

[0024] FIG. 5 shows the variation curves of absolute amplitude of each peak with the increase of the inversion recovery delay .

[0025] FIG. 6 shows the variation curves of amplitude of each peak with the increase of the inversion recovery delay , in which the amplitudes of the data points before the minimum amplitude are set to be negative with reference to the fully relaxed data points.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] Embodiments of the present invention are illustrated in further detail below as examples to explain the object, technical solution and advantages thereof.

[0027] 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.

[0028] The pulse sequence for the measurement of longitudinal relaxation time (as shown in FIG. 1), comprises the modules for inversion recovery, spatial encoding, intermolecular double-quantum coherence signal selection and spatial decoding. The inversion recovery module comprises a solvent-selective ().sup.I pulse, a non-selective pulse and an inversion recovery delay . The spatial encoding module comprises two identical chirp adiabatic pulses and a pair of dipolar gradients. The intermolecular double-quantum coherence signal selection module comprises a gradient G.sub.1, a solvent-selective (/2).sup.I RF pulse, a gradient G.sub.2 and a spin echo --, 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 which are applied in the acquisition period.

[0029] The present invention is a method for the measurement of longitudinal relaxation time in inhomogeneous fields, wherein the steps include:

[0030] (a) Sample injection: inject some 1-butanol aqueous solution (about 0.6 mL) into a 5 mm NMR tube, then place the tube into the NMR spectrometer.

[0031] (b) Calibrate the length and power of RF pulses: use the 1D proton pulse sequence to measure the length of the non-selective /2 pulse, which is 15 s, and observe the distribution of peaks and the spectral width, then set the RF pulse transmit offset to the center of water peak (as shown in FIG. 2). The length of the Gaussian-shaped solvent-selective (/2).sup.I RF pulse is measured to be 5 ms, and the power is 19 dB. Set the length of the solvent-selective ().sup.I RF pulse as 5 ms and the power as 25 dB.

[0032] (c) Import the pulse sequence of the present invention: load the pulse sequence (as shown in FIG. 1) into the spectrometer console; activate the modules for inversion recovery, spatial encoding, intermolecular double-quantum coherence signal selection and spatial decoding.

[0033] (d) Set up the parameters of pulse sequence and start data acquisition as follows: create the chirp pulses using Pbox subroutine libraries, where the duration of each chirp pulse is 10 ms, the sweep width of each chirp 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 duration of 1.5 ms, the strength of coherence selection gradient G.sub.2 is 20 G/cm with duration of 1.5 ms; the length of delay is 24 ms; the detection block repeated 180 times (N.sub.a=180); the number of data 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 was performed with 14 different inversion recovery delays (=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.

[0034] (e) The data were processed as follows: (I) the raw data of each ultrafast 2D spectrum are reconstructed to a 2D matrix with the size of np1*N.sub.a, and a 2D spectrum is gained after FFT; rotate each 2D spectrum 45 counter-clockwise and make accumulated projection along the spatial encoding dimension, thus a set of high-resolution 1D spectra are attained (as shown in FIG. 3), assign the spectral peaks to their protons according to the chemical shifts. (II) As displayed in FIG. 4, the absolute amplitude of the butanol-H2 varies with the inversion recovery delay . Measure the amplitude of each peak. (III) Normalize the amplitudes with reference to the amplitude of the peak when is 32 s, and obtain the variation curves of amplitudes with A, as shown in FIG. 5. (IV) As the 2D spectra are displayed in absolute value mode, the curves in FIG. 5 cannot represent the actual variation of amplitudes. Set the amplitudes of the data points before the minimum amplitude to be negative, and plot the variation curves of amplitudes with the inversion recovery delay , as displayed in FIG. 6. (V) The amplitude vs. A curves plotted in FIG. 6 are fitted with the function y=abexp(x/T.sub.1) in a computer, where the variable x is the inversion recovery time and the function value y is the amplitude of each peak. The values of a, b and T.sub.1 are obtained with a three-parameter fitting, and T.sub.1 is the longitudinal relaxation time of protons in the peak. The T.sub.1 values of 1-butanol protons (H2, H3, H4, H5) are 2.73, 2.77, 3.08 and 3.18 s, respectively.

[0035] In summary, the present invention provides a method for the measurement of proton longitudinal relaxation time in inhomogeneous 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 the chemical shift information. In conjunction with inversion recovery, the intensities of peaks vary with the inversion recovery delay, and the 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 the chemical exchange rates in inhomogeneous fields.

[0036] The present measurement method for longitudinal relaxation time of protons in inhomogeneous fields, can obtain longitudinal relaxation time in inhomogeneous fields, which can give insights into the dynamics of chemical shift exchange rates, and is of great significance to signal optimization and data quantification. It has wide application and good industrial practicability.