IP Library Granted Patent US 10,001,536
Granted Patent B2
US 10,001,536 · App. 14/705,898 · Granted Jun 19, 2018

System and method for measuring pH using magnetic resonance

Inventor: Phillip Zhe Sun (Waltham, MA)
Assignee: The General Hospital Corporation
G01R33/4804G01R33/483G01R33/4828G01R33/5601G01R33/5608G01R33/5605
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Quick Facts
Patent No.
US 10,001,536
App. No.
14/705,898
Granted
Jun 19, 2018
Kind
B2
Abstract

Systems and methods for indicating pH in a subject using a magnetic resonance imaging (MRI) system are provided. The method includes selecting a contrast agent, generating a chemical exchange saturation transfer (CEST) pulse sequence, performing the pulse sequence with the saturating pulse at a first power level, and performing the pulse sequence again with the saturating pulse at a power level different from the first power level. The method also includes generating values indicating pH of the subject, and generating a report indicating the pH using those values.

Claims (372)

1. A method for assessing pH in a subject using a magnetic resonance imaging (MRI) system, comprising:

a) generating, using the MRI system, a chemical exchange saturation transfer (CEST) pulse sequence comprising a saturating magnetic field used to saturate protons of the subject by irradiating the subject with the field, wherein the field has a frequency offset from a Lamar frequency of water protons, and the frequency offset is related to a contrast agent associated with the subject;

b) performing the pulse sequence wherein the saturating magnetic field is at a first radio-frequency (RF) power level (ω 11 ) and a first set of MR signals of the subject are acquired;

c) performing the pulse sequence wherein the saturating magnetic field is at a second RF power level (ω 12 ) different from ω 11 and a second set of MR signals are acquired;

d) generating first inverse CEST ratio and a second inverse CEST ratio of the subject using the first and the second set of MR signals; and

e) generating a report indicating pH using the values based on a labile proton exchange rate, where the labile proton exchange rate is derived using RF-power based inverse CEST ratio (PRICESTR) between the first inverse CEST ratio and the second inverse CEST ratio.

2. The method as recited in claim 1 , wherein the sequence generated in a) comprises:

a first subpart including irradiating protons in the subject at a first frequency offset (Δω) equal to a chemical shift difference between a proton exchange site of the contrast agent and the Lamar frequency, and acquiring labeled MR signals (I label );

a second subpart including irradiating the protons at a second frequency offset (−Δω) that is opposite of the first frequency offset, and acquiring reference MR signals (I ref ); and

a third subpart including turning off saturating magnetic field, and acquiring control MR signals I 0 .

3. The method as recited in claim 2 , wherein step e) includes:

calculating an inverse CEST ratio (CESTR ind ) as CESTR ind =I 0 /I label −I 0 /I ref using each of the first and the second set of MR signals to generate the first inverse CEST ratio CESTR ind (ω 11 ) for the first set of MR signals and the second inverse CEST ratio CESTR ind (ω 12 ) for the second set of MR signals;

calculating the PRICESTR as a ratio of CESTR ind (ω 11 ) and CESTR ind (ω 12 );

deriving the labile proton exchange rate based on the PRICESTR using a preset equation; and

deriving the values indicating the pH based on the labile proton exchange rate.

4. The method as recited in claim 3 , wherein the preset equation is:

k

sw

=

R

2

s

2

+

4

ω

11

2

·

ω

12

2

·

1

-

PRICESTR

ω

12

2

·

PRICESTR

-

ω

11

2

-

R

2

s

2

,

where k sw is the labile proton exchange rate and R 2s is a transverse relaxation rate of a solute.

5. The method as recited in claim 4 , wherein a labile proton ratio is derived as:

f

r

=

R

1

w

·

(

ω

1

2

+

k

sw

(

k

sw

+

R

2

s

)

)

k

sw

·

ω

1

2

·

CESTR

ind

(

ω

1

)

,

where ω 1 denotes the first RF power level ω 11 or the second RF power level ω 12 , θ=atan(ω 1 /Δω), and R 1w is a longitudinal relaxation rate of water.

6. The method as recited in claim 5 , further comprising:

deriving a concentration based on the labile proton ratio.

7. The method as recited in claim 2 , wherein step e) includes:

calculating a CEST ratio (CESTR) as CESTER=(I ref −I label )/I 0 using each of the first and the second set of MR signals to generate a CESTR(ω 11 ) for the first set of MR signals and a CESTR(ω 12 ) for the second set of MR signals;

calculating an RF-power based CEST ratio (rCESTR) as a ratio of CESTR(ω 11 ) and CESTR(ω 12 );

deriving a labile proton exchange rate based on the rCESTR using a second preset equation; and

deriving the values indicating the pH based on the labile proton exchange rate.

8. The method as recited in claim 7 , wherein the second preset equation is:

k

sw

=

R

2

s

2

+

4

(

w

12

2

-

w

11

2

(

(

1

-

σ

)

w

12

(

1

-

σ

)

w

11

)

·

w

12

2

w

11

2

·

rCESTR

-

1

-

w

11

2

)

-

R

2

s

2

,

where k sw is the labile proton exchange rate and R 2s is a transverse relaxation rate of a solute, and (1−σ) indicates a spillover factor.

9. The method as recited in claim 7 , wherein the first and the second RF power levels ω 11 and ω 12 are optimized by maximizing a relative contrast-to-noise ratio (rCNR), where

rCNR

=

CNR

SNR

I

0

,

CNR is a contrast-to-noise ratio of the rCESTR, SNR I 0 is a signal-to-noise ratio of the control MR signals I 0 .

10. The method as recited in claim 7 , wherein

the contrast agent has two or more exchangeable sites;

a frequency offset of the pulse sequence applied in step b) correspond to a chemical shift of a first exchangeable site or a first chosen offset;

a frequency offset of the pulse sequence applied in step c) correspond to a chemical shift of a second exchangeable site or a second chosen offset.

11. A magnetic resonance imaging (MRI) system, comprising:

a magnet system configured to generate a polarizing magnetic field about at least a portion of a subject arranged in the MRI system;

a magnetic gradient system including a plurality of magnetic gradient coils configured to apply at least one magnetic gradient field to the polarizing magnetic field;

a radio frequency (RF) system configured to apply an RF field to the subject and to receive magnetic resonance (MR) signals therefrom;

a computer system programmed to:

a) generate, using the MRI system, a chemical exchange saturation transfer (CEST) pulse sequence comprising a saturating magnetic field used to saturate protons of the subject by irradiating the subject with the field, wherein the field has a frequency offset from a Lamar frequency of water protons, and the frequency offset is related to a contrast agent associated with the subject;

b) perform the pulse sequence wherein the saturating magnetic field is at a first radio-frequency (RF) power level (ω 11 ) and a first set of MR signals of the subject are acquired;

c) perform the pulse sequence wherein the saturating magnetic field is at a second RF power level (ω 12 ) different from ω 11 and a second set of MR signals are acquired;

d) generate first inverse CEST ratio and a second inverse CEST ratio of the subject using the first and the second set of MR signals; and

e) generate a report indicating pH using the values based on a labile proton exchange rate, where the labile proton exchange rate is derived using RF-power based inverse CEST ratio (PRICESTR) between the first inverse CEST ratio and the second inverse CEST ratio.

12. The system as recited in claim 11 , wherein the sequence generated in a) comprises:

a first subpart including irradiating protons in the subject at a first frequency offset (Δω) equal to a chemical shift difference between a proton exchange site of the contrast agent and the Lamar frequency, and acquiring labeled MR signals (I label );

a second subpart including irradiating the protons at a second frequency offset (−Δω) that is opposite of the first frequency offset, and acquiring reference MR signals (I ref ); and

a third subpart including turning off the saturating magnetic field and acquiring control MR signals I 0 .

13. The system as recited in claim 12 , wherein d) includes

calculating an inverse CEST ratio CESTR ind , as CESTR ind =I 0 /I label −I 0 /I ref using each of the first and the second set of MR signals to generate the first inverse CEST ratio CESTR ind (ω 11 ) for the first set of MR signals and the second inverse CEST ratio CESTR ind (ω 12 ) for the second set of MR signals;

calculating the PRICESTR as a ratio of CESTR ind (ω 11 ) and CESTR ind (ω 12 );

deriving the labile proton exchange rate based on the PRICESTR using a preset equation; and

deriving the values indicating the pH based on the labile proton exchange rate.

14. The system as recited in claim 13 , wherein the labile proton exchange rate in relation with the PRICESTR is characterized by the preset equation:

k

sw

=

R

2

s

2

+

4

ω

1

a

2

·

ω

1

b

2

·

1

-

PRICESTR

ω

1

b

2

·

PRICESTR

-

ω

1

a

2

-

R

2

s

2

,

where k sw is the labile proton exchange rate and R 2s is a transverse relaxation rate of a solute.

15. The system as recited in claim 14 , wherein a labile proton ratio is derived as:

f

r

=

R

1

w

·

(

ω

1

2

+

k

sw

(

k

sw

+

R

2

s

)

)

k

sw

·

ω

1

2

·

CESTR

ind

(

ω

1

)

,

where ω 1 denotes the first RF power level ω 11 or the second power level ω 12 , θ=atan(ω 1 /Δω), and R 1w is a longitudinal relaxation rate of water.

16. The system as recited in claim 15 , wherein a concentration is derived based on the labile proton ratio.

17. The system as recited in claim 12 , wherein d) includes

calculating a CEST ratio (CESTR) as CESTR=(I ref −I label )/I 0 using each of the first and the second set of MR signals to generate a CESTR(ω 11 ) for the first set of MR signals and a CESTR(ω 12 ) for the second set of MR signals;

calculating an RF-power based CEST ratio (rCESTR) as a ratio of CESTR(ω 11 ) and CESTR(ω 12 )

deriving a labile proton exchange rate based on the rCESTR using a second preset equation; and

deriving the values indicating the pH based on the labile proton exchange rate.

18. The system as recited in claim 17 , wherein the labile proton exchange rate in relation with the rCESTR is represented by the second preset equation:

k

sw

=

R

2

s

2

+

4

(

w

12

2

-

w

11

2

(

(

1

-

σ

)

w

12

(

1

-

σ

)

w

11

)

·

w

12

2

w

11

2

·

rCESTR

-

1

-

w

11

2

)

-

R

2

s

2

,

where k sw is the labile proton exchange rate and R 2s is a transverse relaxation rate of a solute, and (1−σ) indicates a spillover factor.

19. The system as recited in claim 17 , wherein the first and the second RF power levels ω 11 and ω 12 are optimized by maximizing a relative contrast-noise ratio (rCNR), where

rCNR

=

CNR

SNR

I

0

,

CNR is a contrast-to-noise ratio of the rCESTR, SNR I 0 is a signal-to-noise ratio of the control MR signals I 0 .

20. The system as recited in claim 17 , wherein

the contrast agent has two or more exchangeable sites;

a frequency offset of the pulse sequence applied in b) correspond to a chemical shift of a first exchangeable site or a first chosen offset;

a frequency offset of the pulse sequence applied in c) correspond to a chemical shift of a second exchangeable site or a second chosen offset.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 19, 2018
From: SUN, PHILLIP ZHE
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 045265/0225 →
Continuity (2)
Provisional Application 61988971 · May 6, 2014
Related Publication 20150323632A1 · Nov 12, 2015
Cited By (1)
US 12,186,104