CORRECTION METHOD FOR MAGNETIC RESONANCE T1-MAPPING OF VISCERAL ORGANS IN THE PRESENCE OF ELEVATED IRON AND ELEVATED FAT LEVELS, AND IN THE PRESENCE OF OFF-RESONANCE FREQUENCIES

Abstract

The present disclosure generally relates to medical imaging and, more particularly, relates to systems, apparatus and methods for performing processing of relaxation data obtained by magnetic resonance (MR) T1-mapping of the liver or other visceral organs in the presence of elevated iron and elevated fat levels, and in the presence of off-resonance frequencies in the MR system. The processing results in corrected values of T1 relaxation times of extracellular liquid of the mapped visceral organ that would have been measured if iron content had been at normal levels, if there had been zero fat in the mapped visceral organ and/or there had been zero off-resonance frequencies in the MR system.

Claims

1. A method for processing magnetic resonance (MR) relaxometry data of a visceral tissue of a subject, the method comprising: a) obtaining a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid from a bSSFP signal provided by a T1 mapping method using a MR system; b) determining measurements for the fat content of the subject's visceral tissue, the iron content of the subject's visceral tissue and the off-resonance frequencies of the MR system; c) simulating bSSFP signals from the T1 mapping method of the subject's visceral tissue for extracellular fluid for the determined fat content, iron content and off-resonance frequencies; d) comparing the bSSFP signal provided by the T1 mapping method of the subject's visceral tissue of Step (a) to the simulated bSSFP signals of the subject's visceral tissue for extracellular fluid of Step (c); and e) determining, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

2. A method of claim 1, comprising the steps: c) simulating bSSFP signals from the T1 mapping method of the subject's visceral tissue for different fractions of extracellular fluid for the determined fat content, iron content and off-resonance frequencies; d) comparing the bSSFP signal of the subject's visceral tissue of Step (a) to the simulated bSSFP signals of the subject's visceral tissue for extracellular fluid of Step (c), and determining from said comparison the extracellular fluid fraction value used in the simulation that produces the bSSFP signal in the presence of the determined fat content, iron content and off-resonance frequencies; and e) determining, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction determined in Step (d) based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

3. A method for processing magnetic resonance (MR) relaxometry data of a visceral tissue of a subject, comprising: a) obtaining a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid from a bSSFP signal provided by a T1 mapping method using a MR system; b) determining measurements for the fat content of the subject's visceral tissue, the iron content of the subject's visceral tissue and the off-resonance frequencies of the MR system; c) comparing the bSSFP signal from the T1 mapping method of the subject's visceral tissue of Step (a) to simulated bSSFP signals of the subject's visceral tissue for extracellular fluid for the determined fat content, iron content and off-resonance frequencies; and d) determining, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

4. A method of claim 3, comprising the steps: c) comparing the bSSFP signal from the T1 mapping method of the subject's visceral tissue of Step (a) to simulated bSSFP signals of the subject's visceral tissue for different fractions of extracellular fluid for the determined fat content, iron content and off-resonance frequencies, and determining from said comparison the extracellular fluid fraction value used in the simulation which produces the bSSFP signal in the presence of the determined fat content, iron content and off-resonance frequencies; and d) determining, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction value determined in Step (c) based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

5. A method for processing magnetic resonance (MR) relaxometry data of a visceral tissue of a subject, the method comprising: a) obtaining a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid using a MR system; b) determining measurements for the fat content of the subject's visceral tissue, the iron content of the subject's visceral tissue and the off-resonance frequencies of the MR system; c) simulating a T1 measurement of the subject's visceral tissue for extracellular fluid for the determined fat content, iron content and off-resonance frequencies; d) comparing the T1 measurement of the subject's visceral tissue of Step (a) to the simulated T1 measurement of the subject's visceral tissue for extracellular fluid of Step (c); and e) determining, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

6. A method of claim 5, comprising the steps: c) simulating T1 measurements of the subject's visceral tissue for different fractions of extracellular fluid for the determined fat content, iron content and off-resonance frequencies; d) comparing the T1 measurement of the subject's visceral tissue of Step (a) to the simulated T1 measurements of the subject's visceral tissue for extracellular fluid of Step (c), and determining from said comparison the extracellular fluid fraction value used in the simulation that produces the measured T1 relaxometry data in the presence of the determined fat content, iron content and off-resonance frequencies; and e) determining, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction value determined in Step (d) based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

7. A method for processing magnetic resonance (MR) relaxometry data of a visceral tissue of a subject, comprising: a) obtaining a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid using a MR system; b) determining measurements for the fat content of the subject's visceral tissue, the iron content of the subject's visceral tissue and the off-resonance frequencies of the MR system; c) comparing the T1 measurement of the subject's visceral tissue of Step (a) to a simulated T1 measurement of the subject's visceral tissue for extracellular fluid for the determined fat content, iron content and off-resonance frequencies; and d) determining, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

8. A method as claimed in claim 7, the method comprising the steps: c) comparing the T1 measurement of the subject's visceral tissue of Step (a) to simulated T1 measurements of the subject's visceral tissue for different fractions of extracellular fluid for the determined fat content, iron content and off-resonance frequencies, and determining from said comparison the extracellular fluid fraction value used in the simulation which produces the measured T1 relaxometry data in the presence of the determined fat content, iron content and off-resonance frequencies; and d) determining, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction value determined in Step (c) based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

9. A method for processing magnetic resonance (MR) relaxometry data of a visceral tissue of a subject, the method comprising: a) obtaining a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid from a bSSFP signal provided by a T1 mapping method using a MR system; b) determining a measurement for the iron content of the subject's visceral tissue; c) simulating bSSFP signals from the T1 mapping method of the subject's visceral tissue for extracellular fluid for the determined iron content; d) comparing the bSSFP signal provided by the T1 mapping method of the subject's visceral tissue of Step (a) to the simulated bSSFP signals of the subject's visceral tissue for extracellular fluid of Step (c); and e) determining, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on a normal iron content for the subject's visceral tissue.

10. A method of claim 9, comprising the steps: c) simulating bSSFP signals from the T1 mapping method of the subject's visceral tissue for different fractions of extracellular fluid for the determined iron content; d) comparing the bSSFP signal of the subject's visceral tissue of Step (a) to the simulated bSSFP signals of the subject's visceral tissue for extracellular fluid of Step (c), and determining from said comparison the extracellular fluid fraction value used in the simulation that produces the bSSFP signal in the presence of the determined iron content; and e) determining, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction determined in Step (d) based on a normal iron content for the subject's visceral tissue.

11. A method for processing magnetic resonance (MR) relaxometry data of a visceral tissue of a subject, comprising: a) obtaining a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid from a bSSFP signal provided by a T1 mapping method using a MR system; b) determining a measurement for the iron content of the subject's visceral tissue; c) comparing the bSSFP signal from the T1 mapping method of the subject's visceral tissue of Step (a) to simulated bSSFP signals of the subject's visceral tissue for extracellular fluid for the determined iron content; and d) determining, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on a normal iron content for the subject's visceral tissue.

12. A method of claim 11, comprising the steps: c) comparing the bSSFP signal from the T1 mapping method of the subject's visceral tissue of Step (a) to simulated bSSFP signals of the subject's visceral tissue for different fractions of extracellular fluid for the determined iron content, and determining from said comparison the extracellular fluid fraction value used in the simulation which produces the bSSFP signal in the presence of the determined iron content; and d) determining, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction value determined in Step (c) based on a normal iron content for the subject's visceral tissue.

13. The method of claim any one of the preceding claims, wherein the MR relaxometry data is obtained by use of a medical imaging device including a magnetic resonance (MR) scanner and wherein the device is used to measure one or more characteristic relaxation times in a tissue in the visceral tissue.

14. The method of any one of claims 5 to 8, wherein the visceral tissue is measured for extracelluar fluid using T1 mapping.

15. The method of any one of claim 1-4, 9-12 or 14, wherein the T1 mapping is performed using a modified Look Locker inversion (MOLLI) recovery pulse sequence or a shortened modified Look Locker inversion recovery (Sh-MOLLI) sequence.

16. The method of any one of claim 1 to 8 or 14, wherein the measurement for fat content of the subject's visceral tissue is obtained by .sup.1H MR spectroscopy.

17. The method of any one of the preceding claims, wherein the visceral tissue is measured for iron content using one or more of T2 mapping, T2* mapping, magnetic resonance spectroscopy, or measuring one or more blood biomarkers.

18. The method of any one of claim 1 to 8, 14 or 16, wherein the simulation includes determining a predicted T1 measurement for extracellular fluid for the determined fat content, iron content and off-resonance frequencies.

19. The method of any one of claim 1 to 8, 14, 16 or 18, wherein the simulation includes the impact of fat content, iron content and off-resonance frequencies in the visceral tissue on both the intra- and extracellular relaxation times in a multi-compartment model of various fractions of extracellular fluid in the visceral tissue.

20. The method of claim 19, wherein the multi-compartment model has the following compartments: (i) an extracellular blood compartment; (ii) an extracellular interstitial fluid compartment, (iii) an intracellular liquid pool compartment; (iv) an intracellular semi-solid pool compartment; and (v) an intracellular lipid (fat) compartment.

21. The method of any one of claim 1 to 8, 14, 16 or 18-20, wherein the simulation includes the impact of fat content, iron content and off-resonance frequencies on both the intra- and extracellular fluid relaxation times and simulating a predicted measurement of the visceral tissue for various fractions of extracellular fluid in combination with a simulation of an imaging sequence.

22. The method of any one of the preceding claims, wherein the simulation involves a Bloch equation simulation, with or without exchange between intra- and extra-cellular fluid compartments, and with or without magnetisation transfer effects.

23. The method of any one of claims 1 to 22, wherein the visceral tissue is liver, kidney, spleen or heart, preferably liver.

24. The method of any one of claims 1 to 23 which is computer-implemented.

25. A system or apparatus comprising at least one computing device and at least one application executable in the at least one computing device, the at least one application comprising logic that: a) obtains a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid from a bSSFP signal provided by a T1 mapping method using a MR system; b) measures the fat content of the subject's visceral tissue, the iron content of the subject's visceral tissue, and the off-resonance frequencies of the MR system; c) simulates bSSFP signals from the T1 mapping method of the subject's visceral tissue for extracellular fluid for the determined fat content, iron content and off-resonance frequencies; d) compares the bSSFP signal provided by the T1 mapping method of the subject's visceral tissue of Step (a) to the simulated bSSFP signals of the subject's visceral tissue for extracellular fluid of Step (c); and e) determines, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

26. The system or apparatus of claim 25, the at least one application comprising logic that: c) simulates bSSFP signals from the T1 mapping method of the subject's visceral tissue for different fractions of extracellular fluid for the determined fat content, iron content and off-resonance frequencies; d) compares the bSSFP signal of the subject's visceral tissue of Step (a) to the simulated bSSFP signals of the subject's visceral tissue for extracellular fluid of Step (c), and determines from said comparison the extracellular fluid fraction value used in the simulation that produces the bSSFP signal in the presence of the determined fat content, iron content and off-resonance frequencies; and e) determines, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction determined in Step (d) based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

27. A system or apparatus comprising at least one computing device and at least one application executable in the at least one computing device, the at least one application comprising logic that: a) obtains a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid from a bSSFP signal provided by a T1 mapping method using a MR system; b) measures the fat content of the subject's visceral tissue, the iron content of the subject's visceral tissue and the off-resonance frequencies of the MR system; c) compares the bSSFP signal from the T1 mapping method of the subject's visceral tissue of Step (a) to simulated bSSFP signals of the subject's visceral tissue for extracellular fluid for the determined fat content, iron content and off-resonance frequencies; and d) determines, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

28. The system or apparatus of claim 27, the at least one application comprising logic that: c) compares the bSSFP signal from the T1 mapping method of the subject's visceral tissue of Step (a) to simulated bSSFP signals of the subject's visceral tissue for different fractions of extracellular fluid for the determined fat content, iron content and off-resonance frequencies, and determines from said comparison the extracellular fluid fraction value used in the simulation which produces the bSSFP signal in the presence of the determined fat content, iron content and off-resonance frequencies; and d) determines, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction value determined in Step (c) based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

29. A system or apparatus comprising at least one computing device and at least one application executable in the at least one computing device, the at least one application comprising logic that: a) obtains a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid using a MR system; b) measures the fat content of the subject's visceral tissue, the iron content of the subject's visceral tissue, and the off-resonance frequencies of the MR system; c) simulates a T1 measurement of the subject's visceral tissue for extracellular fluid for the determined fat content, iron content and off-resonance frequencies; d) compares the T1 measurement of the subject's visceral tissue of Step (a) to the simulated T1 measurement of the subject's visceral tissue for extracellular fluid of Step (c); and e) determines, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

30. The system or apparatus of claim 29, the at least one application comprising logic that: c) simulates T1 measurements of the subject's visceral tissue for different fractions of extracellular fluid for the determined fat content, iron content and off-resonance frequencies; d) compares the T1 measurement of the subject's visceral tissue of Step (a) to the simulated T1 measurements of the subject's visceral tissue for extracellular fluid of Step (c), and determines from said comparison the extracellular fluid fraction value used in the simulation that produces the measured T1 relaxometry data in the presence of the determined fat content, iron content and off-resonance frequencies; and e) determines, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction value determined in Step (d) based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

31. A system or apparatus comprising at least one computing device and at least one application executable in the at least one computing device, the at least one application comprising logic that: a) obtains a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid using a MR system; b) measures the fat content of the subject's visceral tissue, the iron content of the subject's visceral tissue, and the off-resonance frequencies of the MR system; c) compares the T1 measurement of the subject's visceral tissue of Step (a) to a simulated T1 measurement of the subject's visceral tissue for extracellular fluid for the determined fat content, iron content and off-resonance frequencies; and d) determines, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

32. The system or apparatus of claim 31, the at least one application comprising logic that: c) compares the T1 measurement of the subject's visceral tissue of Step (a) to simulated T1 measurements of the subject's visceral tissue for different fractions of extracellular fluid for the determined fat content, iron content and off-resonance frequencies, and determines from said comparison the extracellular fluid fraction value used in the simulation which produces the measured T1 relaxometry data in the presence of the determined fat content, iron content and off-resonance frequencies; and d) determines, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction value determined in Step (c) based on zero fat content and a normal iron content, and preferably zero off-resonance frequency, for the subject's visceral tissue.

33. A system or apparatus comprising at least one computing device and at least one application executable in the at least one computing device, the at least one application comprising logic that: a) obtains a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid from a bSSFP signal provided by a T1 mapping method using a MR system; b) measures the iron content of the subject's visceral tissue; c) simulates bSSFP signals from the T1 mapping method of the subject's visceral tissue for extracellular fluid for the determined iron content; d) compares the bSSFP signal provided by the T1 mapping method of the subject's visceral tissue of Step (a) to the simulated bSSFP signals of the subject's visceral tissue for extracellular fluid of Step (c); and e) determines, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on a normal iron content for the subject's visceral tissue.

34. The system or apparatus of claim 33, the at least one application comprising logic that: c) simulates bSSFP signals from the T1 mapping method of the subject's visceral tissue for different fractions of extracellular fluid for the determined iron content; d) compares the bSSFP signal of the subject's visceral tissue of Step (a) to the simulated bSSFP signals of the subject's visceral tissue for extracellular fluid of Step (c), and determines from said comparison the extracellular fluid fraction value used in the simulation that produces the bSSFP signal in the presence of the determined iron content; and e) determines, from said comparison Step (d), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction determined in Step (d) based on a normal iron content for the subject's visceral tissue.

35. A system or apparatus comprising at least one computing device and at least one application executable in the at least one computing device, the at least one application comprising logic that: a) obtains a measurement of T1 relaxometry data of a subject's visceral tissue for extracellular fluid from a bSSFP signal provided by a T1 mapping method using a MR system; b) measures the iron content of the subject's visceral tissue; c) compares the bSSFP signal from the T1 mapping method of the subject's visceral tissue of Step (a) to simulated bSSFP signals of the subject's visceral tissue for extracellular fluid for the determined iron content; and d) determines, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for extracellular fluid based on a normal iron content for the subject's visceral tissue.

36. The system or apparatus of claim 35, the at least one application comprising logic that: c) compares the bSSFP signal from the T1 mapping method of the subject's visceral tissue of Step (a) to simulated bSSFP signals of the subject's visceral tissue for different fractions of extracellular fluid for the determined iron content, and determines from said comparison the extracellular fluid fraction value used in the simulation which produces the bSSFP signal in the presence of the determined iron content; and d) determines, from said comparison Step (c), a corrected value of T1 for the subject's visceral tissue for the extracellular fluid fraction value determined in Step (c) based on a normal iron content for the subject's visceral tissue.

37. The system or apparatus of any one of claims 25 to 36, wherein the logic further determines from said measurements and comparison the presence or absence of visceral tissue fibrosis or inflammation.

38. The system or apparatus of any one of claims 25 to 36, wherein the MR relaxometry data is obtained by use of a medical imaging device including a magnetic resonance (MR) scanner and the device is used to measure one or more characteristic relaxation time or times in tissue in the visceral tissue.

39. The system or apparatus of any one of claims 29 to 32, wherein the visceral tissue is measured for extracellular fluid using T1 mapping.

40. The system or apparatus of any one of claim 25-28, 33-36 or 39, wherein the T1 mapping is performed using a modified Look Locker inversion (MOLLI) recovery pulse sequence or a shortened modified Look Locker inversion recovery (Sh-MOLLI) sequence.

41. The system or apparatus of any one of claims 25-33, wherein the measurement for fat content of the subject's visceral tissue is obtained by .sup.1H MR spectroscopy.

42. The system or apparatus of any one of claims 25-41, wherein the visceral tissue is measured for iron content using one or more of T2 mapping, T2* mapping, magnetic resonance spectroscopy, or measuring one or more blood biomarkers.

43. The system or apparatus of any one of claims 25-32, wherein the simulation includes determining a predicted T1 measurement for extracellular fluid for the determined fat content, iron content and off-resonance frequencies.

44. The system or apparatus of any one of claim 25-32 or 43, wherein the simulation includes the impact of fat content, iron content and off-resonance frequencies in the visceral tissue on both the intra- and extracellular relaxation times in a multi-compartment model of various fractions of extracellular fluid in the visceral tissue.

45. The system or apparatus of claim 44, wherein the multi-compartment model has the following compartments: (i) an extracellular blood compartment; (ii) an extracellular interstitial fluid compartment, (iii) an intracellular liquid pool compartment; (iv) an intracellular semi-solid pool compartment; and (v) an intracellular lipid (fat) compartment.

46. The system or apparatus of any one of claim 25-32 or 43-45, wherein the simulation includes the impact of fat content, iron content and off-resonance frequencies on both the intra- and extracellular fluid relaxation times and simulating a predicted measurement of the visceral tissue for various fractions of extracellular fluid in combination with a simulation of an imaging sequence.

47. The system or apparatus of any one of claims 25 to 46, wherein the simulation involves a Bloch equation simulation or a Bloch-McConnell equation simulation, with or without exchange between intra- and extra-cellular fluid compartments, and with or without magnetisation transfer effects.

48. The system or apparatus of any one of claims 25 to 47, wherein the visceral tissue is liver, kidney, spleen or heart, preferably liver.

49. A system or apparatus comprising at least one computing device and at least one application executable in the at least one computing device, the at least one application comprising logic that performs the method of any one of claims 1-24.

50. A carrier bearing software comprising instructions for configuring a processor to carry out the steps of the method of any one of claims 1 to 24.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0313] Many aspects of the disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present disclosure.

[0314] Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views.

[0315] FIG. 1 schematically depicts the changes in the three cellular components of an exemplary model of the current invention: extracellular fluid (ECF) fraction (which increases as cells die), iron overload (iron is primarily stored intracellularly) and fat fraction (fat droplets are stored inside hepatocytes).

[0316] FIGS. 2A and 2B depict flow charts for non-limiting embodiments for performing magnetic (MR) methods as disclosed herein.

[0317] FIG. 3 is a schematic block diagram of an apparatus in which embodiments of the present method disclosed herein may be implemented.

[0318] FIG. 4: Measured and fat-corrected shMOLLI T1 values in phantoms. The figure shows correlation between spectroscopically measured T1 of the water in phantoms (using STEAM) and shMOLLI T1 of phantoms before and after applying fat correction. Besides the increase in R.sup.2, a reduction of the variation of measurements can also be noticed after correction for fat. The dashed line represents the line of identity. Individual symbol sizes are proportional to the amount of fat in each phantom (0%, 5%, 10%, 20% and 30%).

[0319] FIG. 5: Iron-corrected and fat-, iron- and frequency-corrected shMOLLI T1 values. The figure shows correlation between spectroscopically-measured T1 of the water in the liver of participants and shMOLLI T1 of the liver of participants before and after applying the fat correction. Fat-, iron- and frequency-correction reduces the variability of shMOLLI T1 values and also increases their correlation coefficient with spectroscopically-measured T1 of water in the liver. The dashed line represents the line of identity. Individual symbol sizes are proportional to the amount of fat in each subject's liver (range: 1.5% to 20.3%).

EXAMPLES

[0320] The present invention is further illustrated by the following Examples, in which parts and percentages are by weight and degrees are Celsius, unless otherwise stated. It should be understood that these Examples, while indicating preferred embodiments of the invention, are given by way of illustration only. From the above discussion and these Examples, one skilled in the art can ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Thus, various modifications of the invention in addition to those shown and described herein will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

Example 1: Validation of the MOLLI T1 Correction Method

[0321] Phantom Study

[0322] Water and peanut oil emulsions with varying peanut oil concentrations (0%, 5%, 10%, 20% and 30%) were fixed in 2% agar gel, as described in [1]. Three batches of phantoms were built (i.e. a total of 15 phantoms) in order to reflect different T1s of the water component, by adding 0.45 mM, 0.73 mM and 1.61 mM of NiCl.sub.2 to the water-oil emulsion.

[0323] The phantoms were then scanned using a Siemens 3T Trio Tim imager (Siemens Healthcare, Erlangen, Germany). T2* values and static field inhomogeneities were determined from multiple-echo gradient recalled echo (GRE) images; T1 maps were collected using the shortened modified Look-Locker inversion recovery sequence (ShMOLLI) [2]; and fat fraction was determined from stimulated echo acquisition mode (STEAM) [3] single voxel magnetic resonance spectroscopy (MRS). An additional STEAM MRS sequence involving multiple repetition (TR) and multiple echo times (TR) [4] was used to quantify the T1 and T2 of the water component. The multiple-TR, multiple-TE STEAM sequence was also used to characterise the T1 and T2 values of individual fat peaks in a pure peanut oil phantom.

[0324] Phantom Model

[0325] Phantoms were described using a two-compartment model, comprising a water and a fat compartment. The overall measured balanced steady-state free precession (bSSFP) signal arose as the weighted sum of the individual bSSFP signals from each component. The weighting reflected the fat fraction of the phantom.

[0326] The fat component was modelled with six spectral peaks, using the T1 and T2 values determined from the multiple-TR, multiple-TE STEAM MRS sequence. Several water signals were simulated for T1 values in the range of 500-1600 ms. Water T2 values were different for different concentrations of NiCl2 but remained constant between phantoms with different fat fractions at the same NiCl.sub.2 concentration. Each water signal was combined with the fat signal in a proportion corresponding to the fat fraction in each phantom. The simulated signal obtained this way was then fitted to the measured bSSFP signal. Equation (1) was used for fitting.

Smeas=aSsim(1)

[0327] S.sub.meas is the measured bSSFP signal, S.sub.sim is the simulated signal and a is a fitting parameter. Goodness of fit was evaluated using the R.sup.2 coefficient of determination. The water T1 corresponding to the signal with the highest R.sup.2 value was then used to simulate a pure water ShMOLLI T1 at 0 Hz off-resonance frequency, equivalent to the ShMOLLI T1 of the phantoms in the ideal case of no fat and no static field inhomogeneities.

[0328] Human Participant Study

[0329] N=20 patients (10 females, mean age 52 years) with various levels of hepatic lipid content and hepatic scarring were scanned using the same 3T scanner as mentioned in the phantom study section and the same measurements were performed as in the case of phantoms.

[0330] Liver Model

[0331] The model of the liver described by Tunnicliffe et al. [5] was extended with a further tissue compartment representing fat droplets in hepatocytes. Volume fractions of the liquid liver, semi-solid liver and extracellular fluid compartments were adjusted so that they reflected the fat fraction measured by 1H MRS. bSSFP signals corresponding to all fluid compartments and fat were simulated using Bloch equation simulations. The fat signal was modelled using six spectral peaks, as described by Hamilton et al. [6]. Due to the similarity between the spectrum of human adipose fat and the spectrum of peanut oil [7], the same individual T1 values were used as they were determined in a peanut oil sample. T2 values for three peaks were taken from the literature [8], while T2 values for the 2.75, 4.2 and 5.3 ppm peaks were considered to be equal to those corresponding to the same peaks of the peanut oil spectrum.

[0332] The overall simulated signal was obtained by combining the signals corresponding to fat, liquid liver compartment, semisolid liver compartment and the extracellular fluid compartment. T1 and T2 values of the liver components, other than fat were the same as in [5] and magnetisation transfer effects were considered between the semisolid and liquid compartments of the liver. The extracellular fluid volume fraction (ECVF) was varied between 0.25 and (0.9625fat fraction), where 0 corresponds to 0% ECVF, i.e. no extracellular fluid, only cells and 1 corresponds to 100% extracellular fluid and no cells. The ECVF corresponding to the signal which showed the highest level of similarity to the measured signal was used to simulate a signal with 0% fat fraction, no variation of the static field strength and at normal hepatic iron content (HIC) (HIC=1 mg/g dry weight). Similarity between signals was assessed by the R2 of fitting the simulated signal to the measured signal, as detailed in the phantom study section.

[0333] Results

[0334] In order to assess the validity of the correction, both measured and corrected ShMOLLI T1 values were plotted against water T1 values measured by the multiple-TR, multiple-TE STEAM MRS sequence. It is known that ShMOLLI T1 values underestimate real T1 values (2), therefore a linear relationship was expected to exist between STEAM T1s and corrected T1s, once the variability introduced by off-resonance frequencies and fat were removed.

[0335] The same relationship holds for corrected liver T1s as well, since all participants had normal or close to normal iron levels (HIC 1 mg/g dry weight), and so neither ShMOLLI nor STEAM T1s were reduced by iron. FIG. 4 and FIG. 5 show results of the correction and results of fitting to STEAM-measured T1 values. An increase in the R.sup.2 values, and thus an increase in the strength of the linear relationship, has been observed: 0.829 to 0.997 in case of the phantoms and 0.058 to 0.556 in case of human participants.

REFERENCES

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