Apparatus, system, method and computer-readable medium for isolating chemical exchange saturation transfer contrast from magnetization transfer asymmetry under two-frequency RF irradiation

1. A non-transitory computer-readable medium having stored thereon computer-executable instructions for isolating a chemical exchange saturation transfer (CEST), wherein, when a computer hardware arrangement executes the instructions, the computer arrangement is configured to perform procedures comprising:

determining a first frequency based on a resonance frequency of a CEST agent and a second frequency that is outside a typical range of chemical shifts for observed nuclear spins;

determining at least one of a main solvent or a medium for a sample;

causing an irradiation on the sample with both the first and second frequencies using a magnetic resonance (MR) apparatus;

receiving first data based on a first residual polarization of the irradiation of the sample with both the first and second frequencies;

determining third and fourth frequencies that are located symmetrically to the first and second frequencies, respectively, based on a resonance frequency of the at least one of the main solvent or the medium, wherein the at least one of the main solvent or the medium includes a molecule with an exchangeable nuclei;

causing an irradiation of the sample with both the third and fourth frequencies using the MR apparatus;

receiving second data based on a second residual polarization of the irradiation of the sample with both the third and fourth frequencies; and

determining third data related to a CEST contrast by subtracting the first data from the second data.

2. The computer-readable medium of claim 1 , wherein the second frequency is more than about 5 parts per million away from the at least one of the main solvent or the medium.

3. The computer-readable medium of claim 1 , wherein the second frequency causes magnetization transfer (MT) effects such that spins causing MT experience substantially simultaneous saturation by two frequencies.

4. The computer-readable medium of claim 3 , wherein the MT effects are uniform over a frequency range.

5. The computer-readable medium of claim 4 , wherein MT effects are used as an image contrast mechanism.

6. The computer-readable medium of claim 5 , wherein the image contrast mechanism is robust against B0 and B1 inhomogeneities.

7. The computer-readable medium of claim 1 , wherein the third and fourth frequencies are located substantially away from the first and second frequencies.

8. The computer-readable medium of claim 7 , wherein the third and fourth frequencies are within a range of a spectrum of spins causing MT effects such that the spins experience substantially simultaneous saturation by the third and fourth frequencies.

9. The computer-readable medium of claim 1 , wherein the subtracting of the first data from the second data reduces or eliminates a contribution of one of at least a direct solvent or medium saturation due to a pair-wise symmetric configuration.

10. The computer-readable medium of claim 1 , wherein subtracting eliminates an MT contribution.

11. The computer-readable medium of claim 1 , further comprising:

determining at least one further frequency;

receiving further data based on at least one further residual polarization of at least one further irradiation of the sample with the at least one further frequency; and

refining the CEST contrast by separating different exchange mechanisms.

12. The computer-readable medium of claim 1 , wherein the at least one of the main solvent or the medium is at least one of water or alcohol.

13. A non-transitory computer-readable medium having stored thereon computer-executable instructions for removing Magnetization (MT) asymmetry and correcting magnetic field (B0) inhomogeneity, wherein, when a computer hardware arrangement executes the instructions, the computer arrangement is configured to perform procedures comprising:

determining a first frequency based on a resonance frequency of a chemical exchange saturation transfer (CEST) agent and a second frequency that is outside a typical range of chemical shifts for observed nuclear spins;

causing an irradiation on a sample with (i) a fourth frequency corresponding to a difference f d between the first frequency and the second frequency, and (ii) a third frequency, equal to a half sum f 0 of the first frequency and the second frequency using a magnetic resonance apparatus;

receiving first data based on a irradiation of the sample; and

determining second data based on a residual polarization of the first data.

14. The computer-readable medium of claim 13 , wherein values of the third and fourth frequency values are measured with respect to at least one of a solvent or a medium nuclear spin resonance frequency.

15. The computer-readable medium of claim 13 , further comprising:

modifying f 0 to a new value f1 within about −f d and f d ;

receiving third data based on at least one further simultaneous irradiation with frequencies based on f1; and

generating visual information associated with the residual polarization against f 0 .

16. The computer-readable medium of claim 15 , further comprising constructing a B0 map.

17. The computer-readable medium of claim 16 , further comprising identifying two local minima on a plot corresponding to direct saturation of at least one of a main solvent or a medium nuclear spin resonance frequency, and averaging two frequencies respectively at the two local minima.

18. The computer-readable medium of claim 17 , further comprising quantifying a precision estimate for at least one of the main solvent or the medium nuclear spin resonance frequency as f d minus an average of the two frequencies respectively at the two local minima.

19. The computer-readable medium of claim 18 , further comprising correcting a CEST contrast, including shifting the plot by the average of the two frequencies respectively at the two local minima to center on zero.

20. A method for isolating a chemical exchange saturation transfer (CEST):

determining a first frequency based on a resonance frequency of a CEST agent and a second frequency that is outside a typical range of chemical shifts for observed nuclear spins;

determining at least one of a main solvent or a medium for a sample;

irradiating the sample with both the first and second frequencies using a magnetic resonance (MR) apparatus;

receiving first data based on a first residual polarization of the irradiation of the sample with both the first and second frequencies;

determining third and fourth frequencies that are located symmetrically to the first and second frequencies, respectively, based on a resonance frequency of the at least one of the main solvent or the medium, wherein the at least one of the main solvent or the medium includes a molecule with an exchangeable nuclei;

irradiating the sample with both the third and fourth frequencies using the MR apparatus receiving second data based on a second residual polarization of the irradiation of the sample with both the third and fourth frequencies; and

using a computer hardware arrangement, determining third data related to a CEST contrast by subtracting the first data from the second data.

21. The method of claim 20 , wherein the at least one of the main solvent or the medium is at least one of water or alcohol.

22. A system for substantially isolating a chemical exchange saturation transfer (CEST), comprising:

a hardware processing arrangement configured to:

determine a first frequency based on a resonance frequency of a CEST agent and a second frequency that is outside a typical range of chemical shifts for observed nuclear spins;

determine at least one of a main solvent or a medium for a sample;

cause an irradiation of the sample with both the first and second frequencies using a magnetic resonance (MR) apparatus;

receive first data based on a first residual polarization of the irradiation of the sample with both the first and second frequencies;

determine third and fourth frequencies that are located symmetrically to the first and second frequencies, respectively, based on a resonance frequency of the at least one of the main solvent or the medium, wherein the at least one of the main solvent or the medium includes a molecule with an exchangeable nuclei;

causing an irradiation of the sample with both the third and fourth frequencies using the MR apparatus;

receive second data based on a second residual polarization of the irradiation of the sample with both the third and fourth frequencies; and

determine third data related to a CEST contrast by subtracting the first data from the second data.

23. The system of claim 22 , wherein the at least one of the main solvent or the medium is at least one of water or alcohol.

24. A non-transitory computer-readable medium having stored thereon computer-executable instructions for isolating a first transfer in a first frequency spectrum from a second transfer in a second frequency spectrum, wherein, when a computer hardware arrangement executes the instructions, the computer arrangement is configured to perform procedures comprising:

determining a first frequency based on a resonance frequency of a chemical exchange saturation CEST agent and a second frequency that is outside a typical range of chemical shifts for observed nuclear spins;

determining at least one of a main solvent or a medium for a sample;

causing a substantially-simultaneous irradiation of the sample with both the first and second frequencies using a magnetic resonance (MR) apparatus;

receiving first data based on a first residual polarization of the substantially-simultaneous irradiation of the sample with both the first and second frequencies;

determining third and fourth frequencies based on the first and second frequencies and a resonance frequency of the at least one of the main solvent or the medium, wherein the at least one of the main solvent or the medium includes a molecule with an exchangeable nuclei;

causing an irradiation on the sample with both the third and fourth frequencies using the MR apparatus;

receiving second data based on a second residual polarization of the irradiation of the sample with both the third and fourth frequencies; and

determining third data related to substantially isolating the first transfer in the first frequency spectrum from a second transfer in a second frequency spectrum by subtracting the first data from the second data, wherein the subtraction approximately eliminates the second transfer contribution because the substantially simultaneous two-frequency irradiation makes the MT effects uniform.

25. The computer-readable medium of claim 24 , wherein the first transfer is based on a first transfer mechanism and is at least one of (i) CEST in the case of chemical exchange, or (ii) Nuclear Overhauser Effect (“NOE”) in the case of through-space magnetization transfer to a small mobile molecule.

26. The computer-readable medium of claim 25 , wherein the second transfer is based on a second transfer mechanism where a second frequency spectrum is broader than a first frequency spectrum and is broadened by dipolar coupling including at least one of (i) magnetization transfer (MT) in the case of exchange with a bound state to a macromolecule, or (ii) magnetization transfer through space to bound moieties on the macromolecule.

27. The computer-readable medium of claim 24 , wherein the first frequency is further based on a resonance frequency of the first transfer mechanism.

28. The computer-readable medium of claim 24 , wherein the second frequency is more than about 5 parts per million away from the at least one of the main solvent or the medium.

29. The computer-readable medium of claim 24 , wherein the second frequency causes the second transfer mechanism, such that spins causing the second transfer experience substantially simultaneous saturation by two frequencies.

30. The computer-readable medium of claim 24 , wherein the third and fourth frequencies are located substantially away from the first and second frequencies.

31. The computer-readable medium of claim 24 , wherein the third and fourth frequencies are within a range of a spectrum of spins causing the second transfer mechanism, such that those spins experience substantially simultaneous saturation by the third and fourth frequencies.

32. The computer-readable medium of claim 24 , wherein the subtraction approximately eliminates a contribution of direct solvent or medium saturation, due to a pair-wise symmetric configuration.

33. The computer-readable medium of claim 24 , wherein the at least one of the main solvent or the medium is at least one of water or alcohol.

34. A non-transitory computer-readable medium having stored thereon computer-executable instructions for isolating a chemical exchange saturation transfer (CEST), wherein, when a computer hardware arrangement executes the instructions, the computer arrangement is configured to perform procedures comprising:

determining first and second frequencies wherein the second frequency causes magnetization transfer (MT) effects such that spins causing MT experience substantially simultaneous saturation by two frequencies;

causing a simultaneous irradiation of a sample with both the first and second frequencies using a magnetic resonance (MR) apparatus;

receiving first data based on a first residual polarization of the simultaneous irradiation of the sample with both the first and second frequencies;

determining third and fourth frequencies based on the first and second frequencies;

causing an irradiation of the sample with both the third and fourth frequencies using the MR apparatus;

receiving second data based on a second residual polarization of the irradiation of the sample with the third and fourth frequencies; and

determining third data related to a chemical exchange saturation transfer contrast based on the first data and the second data.

35. The computer-readable medium of claim 34 , wherein the MT effects are uniform over a frequency range.

36. The computer-readable medium of claim 35 , wherein the MT effects are used as an image contrast mechanism.

37. The computer-readable medium of claim 36 , wherein the image contrast mechanism is robust against B0 and B1 inhomogeneities.