1. Advanced NMR techniques
By Group 4

2. Diffusion-Ordered NMR Spectroscopy
Pure Shift NMR ●
Diffusion-Ordered NMR Spectroscopy ●
Multivariate Processing Method ●
Suppression of J modulation ●
Suppression of T1 Noise in 2D-NMR by Reference Deconvolution ●
Magnetic resonance imaging (MRI) ●

3. Pure Shift NMR

4. Pure Shift NMR

5. Pure shift NMR methods Zangger-Sterk methods Band-selective methods
PSYCHE
BIRD, and its use in pure shift NMR
and pattern recognition
Constant-time evolution
Diagonal-suppressed 2D experiments
J-scaling
Measuring couplings to selected signals
2D J spectra, absorption-mode signals in 2D J spectra,

6. J. Chem. Phys. 64, 4229 (1976)

7. An active spin refocusing element placed at the start of the spin echo in a 2D J experiment yields an edited but conventional J-spectrum
Placing the ASR element at the end of the echo yields a J spectrum with multiplet tilts in the opposite direction
J. Magn. Reson. 189, 293 (2007)

8. 4-androstene-3,17-trione
Signal extraction algorithms are designed to give perfect results but can lead to overconfident interpretation of data
J. Magn. Reson. A 109, 103 (1994)

9. Z-filtered 2D J Spectrum
Conventional 1H spectrum
Reconstructed pure shift spectrum
J. Magn. Reson. 201, 18 (2009)

10. Diffusion-Ordered NMR Spectroscopy

11. Problem:

12. Diffusion-Ordered Spectroscopy
Solution:
Diffusion-Ordered Spectroscopy
(DOSY) allows the NMR signals of different species to be separated according to diffusion coefficient, and hence according to size.

13. Diffusion-ordered spectroscopy (DOSY) seeks to separate the NMR signals of different species according to their diffusion coefficient. A series of spin echo spectra is measured with different pulsed field gradient strengths, and the signal decays are analysed to extract a set of diffusion coefficients with which to synthesise the diffusion domain of a DOSY spectrum.

14. Multivariate Processing Method

15. Multivariate Processing Method
Stout beer
Intact living cell
●Too complex to analyze
●Tedious and costly separation and purification methods, such as chromatography
A wide variety of multidimensional methods are available
Combining TOCSY methods with automated analysis
Limited by the problem of spectral overlap

16. For spectra that are highly overlapped but have few components:
multivariate data analysis methods：
All signals of a given species show the same diffusional behavior
● well-separated diffusion coefficients
● the number of individual components is small
● not of very different concentration
Diffusion-Ordered Spectroscopy (DOSY) experiments

17. exploit more types of behavior to discriminate between species●
reduce the number of signals excited in a given acquisition to reduce the number of different species involved ●
TOCSY-t1 encoding :label using the evolution and mixing period of a conventional 2D experiment (e.g., COSY, NOESY, or TOCSY) before the selective TOCSY step give each spin system a characteristic (and complicated) t1 dependence
Relaxation encoding
the REST (relaxation-encoded selective
TOCSY) family of experiments, in which a combination of selective excitation and isotropic mixing is used to label each spin in a given system with the same relaxation weighting

18. SCALPEL
Spectral Component Acquisition by Localized PARAFAC Extraction of Linear components

19. Suppression of J modulation

20. samples contain a previous solvent. Normal WATERGATE
Promblem:
samples contain a previous solvent.
Normal WATERGATE
(WATER-suppression by GrAdient-Tailored Excitation):
employs relatively short,  
not very frequency-selective, 
a wide excitation minimum around the water signal
--20% of the spectrum signal reduction ● ● ●

21. By using the “perfect echo” (PE).
How to solve it ?
By using the “perfect echo” (PE).
It refocuses both shift and J couplings
By placing a spin echo and quadrature 90° pulse in front of a WATERGATE scheme to “prefocus” under the J coupling 

22. For example: semi-skimmed milk
protons in sugars signals are close to the water signal;
require narrow bandwidth selective pulses in the WATER
-GATE blocks.
 Spectra of semi-skimmed (1.7% fat) milk recorded using (a) conventional WATERGATE, (b) PE-WATERGATE, (c) WATERGATE with excitation sculpting, and (d) PE-WATERGATE with excitation sculpting, all using 10.5 ms rectangular 90° selective pulses. Calculated excitation profiles are overlaid.

23. Advantages of PE-WATERGATE
 run in a routine fashion with similar settings to a typical WATERGATE.
easier to analyse and interpret
cleaner results
 particularly useful when signals of interest lie close to the solvent signal.
Reference: Ralph W. Adams, a Chloe M. Holroyd, a Juan A. Aguilar, et al. ‘‘Perfecting’’ WATERGATE: clean proton NMR spectra from aqueous solution[J]. Chem. Commun., 2013, 49, ;

24. Suppression of T1 Noise in 2D-NMR by Reference Deconvolution

25. t1 noise: random or semi-random spurious streaks in 2D NMR spectrum.
Left: raw spectrum, signal-to-noise ratio 2600:1;
Right: reference deconvoluted, signal-to-noise ratio :1
zoom in
t1 noise: random or semi-random spurious streaks in 2D NMR spectrum.
500MHz COSY spectra of a tetracyclic orthoamide in deuteriochloroform.
Left: raw spectrum; Right: deconvolution using the TMS signal
From Journal of Magnetic Resonance, Series A, 101(3)

26. Reference Deconvolution The convolution process
A model of degradation/restoration process
The convolution process
The deconvolution process
g(x,y) = h(x,y)*f(x,y) + η(x,y)
r(x,y) = h(x,y)*fr(x,y) + η(x,y)
r(x,y), g(x,y), fr(x,y) h(x,y) f(x,y)

27. Magnetic resonance imaging (MRI)

28. As well as providing the most important structural tool in modern chemistry, magnetic resonance provides the basis of one of the most powerful imaging techniques available to medicine.

29. Magnetic resonance imaging (MRI)-based techniques have emerged as the preferred technique for the diagnostic evaluation of the small intestine, particularly in the adult population. The lack of ionising radiation makes MRI ideal for use in younger patients or in cases that require repeated follow-up investigations.
Enterography examinations are more acceptable to patients and may provide similar diagnostic accuracy compared to intubation methods.

30. A significant disadvantage of these sequences is the black boundary artefact along the bowel wall (Fig 1).
Figure 1. MRE examinations in a 36-year-old male patient. (a) Coronal true-FISP image shows black-boundary artefact adjacent to bowel wall(arrows). This artefact can obscure early mural changes. (b) Coronal true-FISP image with fat suppression reduces the artefact. High signal is seenparallel to the lumen consistent with a linear ulcer (arrow).

31. In a study comparing validated with matched surgical samples, the sensitivity and specificity of high-resolution MRE in the detection of superficial and deep ulcers was increased (69-99% and 94-99%, respectively) compared to standard imaging.
Figure 2. High resolution true-FISP images from MRE examinations in recurrent disease. (a) Quiescent CD is seen as a halo sign with hypointense
submucosal layer. (b) Early recurrent mucosal inflammation presents initially as thickening of the mucosal layer (arrow). (c) Progression of
mucosal thickening and isointense finger like projections in the submucosal (arrow). (d) At more advanced inflammation, the entire submucosa
becomes iso- or hyperintense (arrow). Recurrence seen in (b) and (c) are unlikely to be detected on MEGS assessment.

32. Thanks for listening！