IP Library › Granted Patent US 12,440,119
Granted Patent B2
US 12,440,119 · App. 19/059,955 · Granted Oct 14, 2025

Stimulated-echo imaging for EPRI

Inventors: Howard J. Halpern (Chicago, IL); Boris Epel (Chicago, IL)
A61B5/055G01R33/341G01R33/3607G01R33/3621G01R33/60G01V3/104
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Quick Facts
Patent No.
US 12,440,119
App. No.
19/059,955
Granted
Oct 14, 2025
Kind
B2
Abstract

An apparatus and method for improved S/N measurements useful for electron paramagnetic resonance imaging in situ and in vivo, using high-isolation transmit/receive surface coils and temporally spaced pulses of RF energy (e.g., in some embodiments, a RF pi pulse) having an amplitude sufficient to rotate the magnetization by 180 degrees followed after varied delays, by a second RF pulse having an amplitude half that of the initial pulse to rotate the magnetization by, e.g., 90 degrees (a pi/2 pulse), to the plane orthogonal to the static field where it evolves for a short time. Then a third RF pi pulse sufficient to rotate the magnetization by, e.g., 180 degrees, forms an echo (in some embodiments, the second and third pulses are from the same signal as the first pulse but are phase shifted by 0, 90, 180, or 270 degrees to reduce signal artifact), to image human body.

Claims (1052)

1. An apparatus for stimulated-echo (SE) electron paramagnetic resonance imaging (EPRI) of a volume of animal tissue in vivo in an animal, the apparatus comprising:

a magnetic-field generator configured to generate a substantially static magnetic field in the volume of animal tissue;

a set of transmit coils, wherein the set of transmit coils generates an excitation magnetic field in the volume of animal tissue in response to an applied electrical signal;

a set of receive coils, wherein the set of receive coils generates a sensed electrical signal in response to a sensed magnetic field in the volume of animal tissue, wherein the set of receive coils is configured to detect electron paramagnetic resonance signals in the volume of animal tissue;

a pulsed-RF driver circuit, operatively coupled to an RF signal source and to the set of transmit coils, that drives a plurality of pulse sets, each pulse set including: a first π/2 pulse that includes a plurality of cycles of RF, followed by a fixed amount of time τ and then a second π/2 pulse that includes a plurality of cycles of RF followed by a waiting time T and thereafter a third π/2 pulse that includes a plurality of cycles of RF in the direction generally orthogonal to the substantially static magnetic field in the volume of animal tissue from a surface of the animal next to the volume of animal tissue;

an RF receiver circuit operatively coupled to the set of receive coils to receive the sensed electrical signal from the set of receive coils and to generate a received electrical signal, wherein the transmitted pulse sets are of magnitudes and durations configured such that after the first two π/2 pulses the magnetization is stored along the longitudinal z-axis where it remains during the waiting time T, wherein the waiting time T is varied allowing the magnetization to decay with T 1e and wherein the third π/2 pulse rotates the z-component back into the transverse xy-plane where it gives rise to a stimulated echo at the fixed amount of time τ after the third π/2 pulse to measure electron T 1e spin-lattice relaxation information from the volume of tissue in order to measure oxygen in the volume of tissue; and

an image-generation unit operatively coupled to the RF receiver circuit and configured to process the received electrical signal and to generate image data based on the received electrical signal.

2. The apparatus of claim 1 , wherein the set of transmit coils and the set of receive coils are oriented relative to one another such that the sensed electrical signal has little or no component directly due to the excitation magnetic field.

3. The apparatus of claim 1 , wherein the set of transmit coils are surface transmit coils.

4. The apparatus of claim 1 , wherein the set of receive coils are surface receive coils.

5. The apparatus of claim 1 , wherein the set of transmit coils are surface transmit coils, wherein the set of receive coils are surface receive coils, and wherein the set of transmit coils and the set of receive coils are oriented relative to one another such that the sensed electrical signal has little or no component directly due to the excitation magnetic field.

6. The apparatus of claim 1 , wherein the plurality of cycles of the second pulse are obtained from the RF signal source as are those of the first pulse but are phase shifted by respect to each other by 0, 90, 180, or 270 degrees to reduce signal artifact.

7. The apparatus of claim 1 , wherein the plurality of cycles of the third pulse are obtained from the RF signal source as are those of the first pulse but are phase shifted by respect to each other by 0, 90, 180, or 270 degrees to reduce signal artifact.

8. The apparatus of claim 1 , wherein the plurality of cycles of the second pulse are obtained from the RF signal source as are those of the first pulse but are phase shifted by respect to each other by 0, 90, 180, or 270 degrees to reduce signal artifact, and wherein the plurality of cycles of the third pulse are obtained from the RF signal source as are those of the first pulse but are phase shifted by respect to each other by 0, 90, 180, or 270 degrees to reduce signal artifact.

9. The apparatus of claim 1 , wherein the plurality of cycles of the first pulse, the second pulse and the third pulse are obtained as follows:

First

First

Second

Second

N

pulse

delay

pulse

delay

1

  0.5X

630 ns

  0.5X

VD

2

  0.5X

630 ns

  0.5X

VD

3

  0.5X

630 ns

  0.5X

VD

4

  0.5X

630 ns

  0.5X

VD

5

  0.5X

630 ns

−0.5X

VD

6

  0.5X

630 ns

−0.5X

VD

7

  0.5X

630 ns

−0.5X

VD

8

  0.5X

630 ns

−0.5X

VD

9

−0.5X

630 ns

  0.5X

VD

10

−0.5X

630 ns

  0.5X

VD

11

−0.5X

630 ns

  0.5X

VD

12

−0.5X

630 ns

  0.5X

VD

13

−0.5X

630 ns

−0.5X

VD

14

−0.5X

630 ns

−0.5X

VD

15

−0.5X

630 ns

−0.5X

VD

16

−0.5X

630 ns

−0.5X

VD

17

−0.5Y

630 ns

  0.5X

VD

18

−0.5Y

630 ns

  0.5X

VD

19

−0.5Y

630 ns

  0.5X

VD

20

−0.5Y

630 ns

  0.5X

VD

21

−0.5Y

630 ns

−0.5X

VD

22

−0.5Y

630 ns

−0.5X

VD

23

−0.5Y

630 ns

−0.5X

VD

24

−0.5Y

630 ns

−0.5X

VD

25

  0.5Y

630 ns

  0.5X

VD

26

  0.5Y

630 ns

  0.5X

VD

27

  0.5Y

630 ns

  0.5X

VD

28

  0.5Y

630 ns

  0.5X

VD

29

  0.5Y

630 ns

−0.5X

VD

30

  0.5Y

630 ns

−0.5X

VD

31

  0.5Y

630 ns

−0.5X

VD

32

  0.5Y

630 ns

−0.5X

VD

Detection

Detection

Third

Third

channel

channel

N

pulse

delay

Re

Im

1

  0.5X

630 ns

  A

  B

2

−0.5X

630 ns

−A

−B

3

  0.5Y

630 ns

−B

  A

4

−0.5Y

630 ns

  B

−A

5

  0.5X

630 ns

−A

−B

6

−0.5X

630 ns

  A

  B

7

  0.5Y

630 ns

  B

−A

8

−0.5Y

630 ns

−B

  A

9

  0.5X

630 ns

−A

−B

10

−0.5X

630 ns

  A

  B

11

  0.5Y

630 ns

  B

−A

12

−0.5Y

630 ns

−B

  A

13

  0.5X

630 ns

  A

  B

14

−0.5X

630 ns

−A

−B

15

  0.5Y

630 ns

−B

  A

16

−0.5Y

630 ns

  B

−A

17

  0.5X

630 ns

  B

−A

18

−0.5X

630 ns

−B

  A

19

  0.5Y

630 ns

  A

  B

20

−0.5Y

630 ns

−A

−B

21

  0.5X

630 ns

−B

  A

22

−0.5X

630 ns

  B

−A

23

  0.5Y

630 ns

−A

−B

24

−0.5Y

630 ns

  A

  B

25

  0.5X

630 ns

−B

  A

26

−0.5X

630 ns

  B

−A

27

  0.5Y

630 ns

−A

−B

28

−0.5Y

630 ns

  A

  B

29

  0.5X

630 ns

  B

−A

30

−0.5X

630 ns

−B

  A

31

  0.5Y

630 ns

  A

  B

32

−0.5Y

630 ns

−A

 −B.

10. An apparatus for stimulated-echo electron paramagnetic resonance imaging (EPRI) of a volume of animal tissue in vivo in an animal, the apparatus comprising: means for generating a substantially static magnetic field in the volume of animal tissue; means for generating an excitation magnetic field in the volume of animal tissue by driving a set of transmit coils with a plurality of RF-signal pulse sets, each pulse set including: a first π/2 pulse that includes a plurality of cycles of RF, followed by a fixed amount of time τ and then a second π/2 pulse that includes a plurality of cycles of RF followed by a waiting time T and thereafter a third π/2 pulse that includes a plurality of cycles of RF in the direction generally orthogonal to the substantially static magnetic field in the volume of animal tissue from a surface of the animal next to the volume of animal tissue; means for generating a sensed electrical signal from a set of receive coils in response to a sensed magnetic field in the volume of animal tissue, wherein the set of receive coils is configured to detect electron paramagnetic resonance signals in the volume of animal tissue; means for receiving the sensed electrical signal from the set of surface receive coils and generating a received electrical signal, wherein the transmitted pulse sets are of magnitudes and durations configured such that after the first two π/2 pulses the magnetization is stored along the longitudinal z-axis where it remains during the waiting time T, wherein the waiting time T is varied allowing the magnetization to decay with T 1e and wherein the third π/2 pulse rotates the z-component back into the transverse xy-plane where it gives rise to a stimulated echo at the fixed amount of time τ after the third pulse to measure electron T 1e spin-lattice relaxation information from the volume of tissue in order to measure oxygen in the volume of tissue; and means for processing the received electrical signal and generating image data based on the received electrical signal.

11. The apparatus of claim 10 , wherein the set of transmit coils and the set of receive coils are oriented relative to one another such that the sensed electrical signal has little or no component directly due to the excitation magnetic field.

12. The apparatus of claim 10 , wherein the plurality of cycles of the third pulse are obtained from the RF signal source as are those of the first pulse but are phase shifted by respect to each other by 0, 90, 180, or 270 degrees to reduce signal artifact.

13. The apparatus of claim 10 , wherein the plurality of cycles of the second pulse are obtained from the RF signal source as are those of the first pulse but are phase shifted by respect to each other by 0, 90, 180, or 270 degrees to reduce signal artifact, and wherein the plurality of cycles of the third pulse are obtained from the RF signal source as are those of the first pulse but are phase shifted by respect to each other by 0, 90, 180, or 270 degrees to reduce signal artifact.

14. The apparatus of claim 10 , wherein the plurality of cycles of the first pulse, the second pulse and the third pulse are obtained as follows:

First

First

Second

Second

N

pulse

delay

pulse

delay

1

  0.5X

630 ns

  0.5X

VD

2

  0.5X

630 ns

  0.5X

VD

3

  0.5X

630 ns

  0.5X

VD

4

  0.5X

630 ns

  0.5X

VD

5

  0.5X

630 ns

−0.5X

VD

6

  0.5X

630 ns

−0.5X

VD

7

  0.5X

630 ns

−0.5X

VD

8

  0.5X

630 ns

−0.5X

VD

9

−0.5X

630 ns

  0.5X

VD

10

−0.5X

630 ns

  0.5X

VD

11

−0.5X

630 ns

  0.5X

VD

12

−0.5X

630 ns

  0.5X

VD

13

−0.5X

630 ns

−0.5X

VD

14

−0.5X

630 ns

−0.5X

VD

15

−0.5X

630 ns

−0.5X

VD

16

−0.5X

630 ns

−0.5X

VD

17

−0.5Y

630 ns

  0.5X

VD

18

−0.5Y

630 ns

  0.5X

VD

19

−0.5Y

630 ns

  0.5X

VD

20

−0.5Y

630 ns

  0.5X

VD

21

−0.5Y

630 ns

−0.5X

VD

22

−0.5Y

630 ns

−0.5X

VD

23

−0.5Y

630 ns

−0.5X

VD

24

−0.5Y

630 ns

−0.5X

VD

25

  0.5Y

630 ns

  0.5X

VD

26

  0.5Y

630 ns

  0.5X

VD

27

  0.5Y

630 ns

  0.5X

VD

28

  0.5Y

630 ns

  0.5X

VD

29

  0.5Y

630 ns

−0.5X

VD

30

  0.5Y

630 ns

−0.5X

VD

31

  0.5Y

630 as

−0.5X

V.D

32

  0.5Y

630 ns

−0.5X

VD

Detection

Detection

Third

Third

channel

channel

N

pulse

delay

Re

Im

1

  0.5X

630 ns

  A

  B

2

−0.5X

630 ns

−A

−B

3

  0.5Y

630 ns

−B

  A

4

−0.5Y

630 ns

  B

−A

5

  0.5X

630 ns

−A

−B

6

−0.5X

630 ns

  A

  B

7

  0.5Y

630 ns

  B

−A

8

−0.5Y

630 ns

−B

  A

9

  0.5X

630 ns

−A

−B

10

−0.5X

630 ns

  A

  B

11

  0.5Y

630 ns

  B

−A

12

−0.5Y

630 ns

−B

  A

13

  0.5X

630 ns

  A

  B

14

−0.5X

630 ns

−A

−B

15

  0.5Y

630 ns

−B

  A

16

−0.5Y

630 ns

  B

−A

17

  0.5X

630 ns

  B

−A

18

−0.5X

630 ns

−B

  A

19

  0.5Y

630 ns

  A

  B

20

−0.5Y

630 ns

−A

−B

21

  0.5X

630 ns

−B

  A

22

−0.5X

630 ns

  B

−A

23

  0.5Y

630 ns

−A

−B

24

−0.5Y

630 ns

  A

  B

25

  0.5X

630 ns

−B

  A

26

−0.5X

630 ns

  B

−A

27

  0.5Y

630 ns

−A

−B

28

−0.5Y

630 ns

  A

  B

29

  0.5X

630 ns

  B

−A

30

−0.5X

630 ns

−B

  A

31

  0.5Y

630 ns

  A

  B

32

−0.5Y

630 ns

−A

 −B.

15. A method for stimulated-echo electron paramagnetic resonance imaging (EPRI) of a volume of animal tissue in vivo in an animal, the method comprising:

generating a substantially static magnetic field in the volume of animal tissue;

generating an excitation magnetic field in the volume of animal tissue by driving a set of transmit coils with a plurality of RF-signal pulse sets, each pulse set including: a first π/2 pulse that includes a plurality of cycles of RF, followed by a fixed amount of time τ and then a second π/2 pulse that includes a plurality of cycles of RF followed by a waiting time T and thereafter a third π/2 pulse that includes a plurality of cycles of RF in the direction generally orthogonal to the substantially static magnetic field in the volume of animal tissue from a surface of the animal next to the volume of animal tissue;

generating a sensed electrical signal from a set of receive coils in response to a sensed magnetic field in the volume of animal tissue, wherein the set of receive coils is configured to detect electron paramagnetic resonance signals in the volume of animal tissue;

receiving the sensed electrical signal from the set of receive coils and generating a received electrical signal, wherein the transmitted pulse sets are of magnitudes and durations configured such that after the first two π/2 pulses the magnetization is stored along the longitudinal z-axis where it remains during the waiting time T, wherein the waiting time T is varied allowing the magnetization to decay with T 1e and wherein the third π/2 pulse rotates the z-component back into the transverse xy-plane where it gives rise to a stimulated echo at the fixed amount of time τ after the third pulse to measure electron T 1e spin-lattice relaxation information from the volume of tissue in order to measure oxygen in the volume of tissue; and

processing the received electrical signal and generating image data based on the received electrical signal.

16. The method of claim 15 , wherein the set of transmit coils and the set of receive coils are oriented relative to one another such that the sensed electrical signal has little or no component directly due to the excitation magnetic field.

17. The method of claim 15 , wherein the set of transmit coils are surface transmit coils.

18. The method of claim 15 , wherein the set of receive coils are surface receive coils.

19. The method of claim 15 , wherein the set of transmit coils are surface transmit coils, wherein the set of receive coils are surface receive coils, and wherein the set of transmit coils and the set of receive coils are oriented relative to one another such that the sensed electrical signal has little or no component directly due to the excitation magnetic field.

20. The method of claim 15 , wherein the plurality of cycles of the second pulse are obtained from the RF signal source as are those of the first pulse but are phase shifted by respect to each other by 0, 90, 180, or 270 degrees to reduce signal artifact, and, wherein the plurality of cycles of the third pulse are obtained from the RF signal source as are those of the first pulse but are phase shifted by respect to each other by 0, 90, 180, or 270 degrees to reduce signal artifact.

21. The method of claim 15 , wherein the plurality of cycles of the first pulse, the second pulse and the third pulse are obtained as follows:

First

First

Second

Second

N

pulse

delay

pulse

delay

1

  0.5X

630 ns

  0.5X

VD

2

  0.5X

630 ns

  0.5X

VD

3

  0.5X

630 ns

  0.5X

VD

4

  0.5X

630 ns

  0.5X

VD

5

  0.5X

630 ns

−0.5X

VD

6

  0.5X

630 ns

−0.5X

VD

7

  0.5X

630 ns

−0.5X

VD

8

  0.5X

630 ns

−0.5X

VD

9

−0.5X

630 ns

  0.5X

VD

10

−0.5X

630 ns

  0.5X

VD

11

−0.5X

630 ns

  0.5X

VD

12

−0.5X

630 ns

  0.5X

VD

13

−0.5X

630 ns

−0.5X

VD

14

−0.5X

630 ns

−0.5X

VD

15

−0.5X

630 ns

−0.5X

VD

16

−0.5X

630 ns

−0.5X

VD

17

−0.5Y

630 ns

  0.5X

VD

18

−0.5Y

630 ns

  0.5X

VD

19

−0.5Y

630 ns

  0.5X

VD

20

−0.5Y

630 ns

  0.5X

VD

21

−0.5Y

630 ns

−0.5X

VD

22

−0.5Y

630 ns

−0.5X

VD

23

−0.5Y

630 ns

−0.5X

VD

24

−0.5Y

630 ns

−0.5X

VD

25

  0.5Y

630 ns

  0.5X

VD

26

  0.5Y

630 ns

  0.5X

VD

27

  0.5Y

630 ns

  0.5X

VD

28

  0.5Y

630 ns

  0.5X

VD

29

  0.5Y

630 ns

−0.5X

VD

30

  0.5Y

630 ns

−0.5X

VD

31

  0.5Y

630 ns

−0.5X

VD

32

  0.5Y

630 ns

−0.5X

VD

Detection

Detection

Third

Third

channel

channel

N

pulse

delay

Re

Im

1

  0.5X

630 ns

  A

  B

2

−0.5X

630 ns

−A

−B

3

  0.5Y

630 ns

−B

  A

4

−0.5Y

630 ns

  B

−A

5

  0.5X

630 ns

−A

−B

6

−0.5X

630 ns

  A

  B

7

  0.5Y

630 ns

  B

−A

8

−0.5Y

630 ns

−B

  A

9

  0.5X

630 ns

−A

−B

10

−0.5X

630 ns

  A

  B

11

  0.5Y

630 ns

  B

−A

12

−0.5Y

630 ns

−B

  A

13

  0.5X

630 ns

  A

  B

14

−0.5X

630 ns

−A

−B

15

  0.5Y

630 ns

−B

  A

16

−0.5Y

630 ns

  B

−A

17

  0.5X

630 ns

  B

−A

18

−0.5X

630 ns

−B

  A

19

  0.5Y

630 ns

  A

  B

20

−0.5Y

630 ns

−A

−B

21

  0.5X

630 ns

−B

  A

22

−0.5X

630 ns

  B

−A

23

  0.5Y

630 ns

−A

−B

24

−0.5Y

630 ns

  A

  B

25

  0.5X

630 ns

−B

  A

26

−0.5X

630 ns

  B

−A

27

  0.5Y

630 ns

−A

−B

28

−0.5Y

630 ns

  A

  B

29

  0.5X

630 ns

  B

−A

30

−0.5X

630 ns

−B

  A

31

  0.5Y

630 ns

  A

  B

32

−0.5Y

630 ns

−A

 −B.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 23, 2025
From: HALPERN, HOWARD J.; EPEL, BORIS M.
To: O2M TECHNOLOGIES, LLC
Reel/Frame 073307/0449 →
Continuity (2)
Division 18127538 · Mar 28, 2023
Related Publication 20250204804A1 · Jun 26, 2025
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