IP Library Granted Patent US 12,232,858
Granted Patent B2
US 12,232,858 · App. 18/127,538 · Granted Feb 25, 2025

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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 12,232,858
App. No.
18/127,538
Granted
Feb 25, 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 (374)

1. An apparatus for electron paramagnetic resonance oxygen imaging (EPROI) of a volume of animal tissue in vivo, 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 transmit RF pulses that generate an excitation magnetic field in the volume of animal tissue in response to an applied electrical signal; and

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 and wherein the set of transmit coils and the set of receive coils are high-isolation coils configured to reduce the reception of the transmitted RF pulses by the receive coils;

a pulsed-RF driver circuit, operatively coupled to the set of transmit coils, that drives a plurality of pulse sets, wherein each pulse set has a plurality of successive transmitted pulses, including a first pulse having a plurality of cycles of RF, followed by a first delay and thereafter by a second pulse that includes a plurality of cycles of RF; and

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 pulses are of magnitudes and durations configured to measure an electron T 1e spin-lattice relaxation in the volume of tissue in order to measure oxygen in the volume of tissue.

2. The apparatus of claim 1 , wherein for different ones of the plurality of pulse sets:

the second transmit pulses have RF cycles that are shifted in phase by a selected different amount (by about either 0 degrees, 90 degrees, 180 degrees or 270 degrees for different ones of the plurality of pulse sets) relative to the first pulse.

3. The apparatus of claim 1 , wherein each pulse set includes the first pulse, followed by the first delay and thereafter by the second pulse, wherein the second pulse is followed by a second delay and thereafter by a third pulse that includes a plurality of cycles of RF.

4. The apparatus of claim 3 , wherein for different ones of the plurality of pulse sets, the second transmit pulses have RF cycles that are shifted in phase by a selected different amount (by about either 0 degrees, 90 degrees, 180 degrees or 270 degrees) relative to the first pulse, and the third pulses have RF cycles that are shifted in phase by a selected different amount (by about either 0 degrees, 90 degrees, 180 degrees or 270 degrees) relative to the first pulse.

5. The apparatus of claim 3 , wherein for each of the plurality of pulse sets, the first, second and third transmit pulses form an inversion recovery with electron-spin echo detection (IRESE) sequence.

6. The apparatus of claim 3 , wherein for each of the plurality of pulse sets,

the first, second and third transmit pulses form an inversion recovery with electron-spin echo detection (IRESE) sequence having a π-pulse as the first pulse, a T delay as the first delay, a π/2-pulse as the second pulse, a τ delay as the second delay, a π-pulse as the third pulse, wherein the first, second and third pulses are each about 35 ns in duration,

wherein the π/2 pulse rotates a magnetization π/2 radians and the π-pulses rotate a magnetization π radians,

wherein τ=630 ns,

wherein T has a value in a range of about 500 ns to about 16,000 ns, and

wherein the cycles of RF have a frequency of about 250 MHz.

7. The apparatus of claim 3 , wherein for each of the plurality of pulse sets,

the first, second and third transmit pulses form an inversion recovery with electron-spin echo detection (IRESE) sequence having a π-pulse as the first pulse, a T delay as the first delay, a π/2-pulse as the second pulse, a τ delay as the second delay, a π-pulse as the third pulse, a τ delay as a third delay, wherein the first, second and third pulses are each about 35 ns in duration,

wherein the π/2 pulse rotates a magnetization π/2 radians and the π-pulses rotate a magnetization π radians,

wherein τ=630 ns,

wherein T has a value in a range of about 500 ns to about 16,000 ns,

wherein the cycles of RF have a frequency of about 250 MHz,

wherein the plurality of pulse sets about 7520 acquisitions

wherein about 7520 acquisitions are acquired per value of T and include phase cycling,

wherein eight T values that are approximately logarithmically spaced between one-half microseconds (0.5 μs) and sixteen microseconds (16 μs) are used,

wherein T LF R =25 μs, and

wherein the phase cycling includes values selected from rows of the following table:

Detection

Detection

First

First

Second

Second

Third

Third

channel Re

channel Im

pulse

delay

pulse

delay

pulse

delay

(real)

(imaginary)

X

T

0.5X

630 ns

 X

630 ns

 A

 B

X

T

0.5X

630 ns

−X

630 ns

 A

 B

X

T

0.5X

630 ns

 Y

630 ns

−A

−B

X

T

0.5X

630 ns

−Y

630 ns

−A

−B

X

T

−0.5X

630 ns

 X

630 ns

−A

−B

X

T

−0.5X

630 ns

−X

630 ns

−A

−B

X

T

−0.5X

630 ns

 Y

630 ns

 A

 B

X

T

−0.5X

630 ns

−Y

630 ns

 A

 B

X

T

0.5Y

630 ns

 X

630 ns

 B

−A

X

T

0.5Y

630 ns

−X

630 ns

 B

−A

X

T

0.5Y

630 ns

 Y

630 ns

−B

 A

X

T

0.5Y

630 ns

−Y

630 ns

−B

 A

X

T

−0.5Y

630 ns

 X

630 ns

−B

 A

X

T

−0.5Y

630 ns

−X

630 ns

−B

 A

X

T

−0.5Y

630 ns

 Y

630 ns

 B

−A

X

T

−0.5Y

630 ns

−Y

630 ns

 B

 −A.

8. The apparatus of claim 3 , wherein the substantially static magnetic field in the volume of animal tissue is generally orthogonal to both the excitation magnetic field and to the sensed magnetic field in the volume of animal tissue; and wherein the apparatus further comprises:

a digital-signal processor (DSP) unit operatively coupled to the RF receiver circuit and configured to process the received electrical signal and to generate image data;

a storage unit operatively coupled to the DSP unit to receive and store the image data; and

a display unit operatively coupled to the storage unit to receive and display the image data.

9. The apparatus of claim 2 , further comprising:

a digital-signal processor (DSP) unit operatively coupled to the RF receiver circuit and configured to process the received electrical signal and to generate image data; and

a display unit operatively coupled to receive and display the image data.

10. An apparatus for electron paramagnetic resonance oxygen imaging (EPROI) 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 a plurality of pulse sets, wherein the means for generating each one of the plurality of pulse sets includes:

means for generating a first RF excitation magnetic field pulse having a plurality of RF cycles in a first 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 delaying for a first delay time after the first RF excitation magnetic field pulse,

means for generating a second RF excitation magnetic field pulse having a plurality of RF in the first direction generally orthogonal to the substantially static magnetic field,

means for sensing an RF spin-relaxation signal, and

means for generating a received electrical signal based on the sensed RF signal;

wherein the first and second RF excitation magnetic field pulses are of magnitudes and durations configured to measure T 1e spin-lattice relaxation response in the volume of tissue in order to measure oxygen in the volume of tissue; and

means for generating an EPROI image of the in vivo animal tissue using the T 1e response.

11. The apparatus of claim 10 , wherein for different ones of the plurality of pulse sets:

the second transmit pulses have RF cycles that are shifted in phase by a selected different amount (by about either 0 degrees, 90 degrees, 180 degrees or 270 degrees for different ones of the plurality of pulse sets) relative to the first pulse.

12. The apparatus of claim 10 , further comprising:

means for delaying for a second delay time after the second RF excitation magnetic field pulse;

means for generating a third RF excitation magnetic field pulse having a plurality of RF in the first direction generally orthogonal to the substantially static magnetic field.

13. The apparatus of claim 12 , wherein for different ones of the plurality of pulse sets:

the second transmit pulses have RF cycles that are shifted in phase by a selected different amount (by about either 0 degrees, 90 degrees, 180 degrees or 270 degrees for different ones of the plurality of pulse sets) relative to the first pulse, and

the third transmit pulses have RF cycles that are shifted in phase by a selected different amount (by about either 0 degrees, 90 degrees, 180 degrees or 270 degrees) relative to the first pulse.

14. The apparatus of claim 12 , wherein for each of the plurality of pulse sets:

the first transmit pulse is a pi pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin by pi radians;

the second transmit pulse is a pi/2 pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin 1/2 pi radians; and

the third transmit pulse is a pi pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin pi radians.

15. The apparatus of claim 12 , wherein for each of the plurality of pulse sets, the first, second and third transmit pulses form an inversion recovery with electron-spin echo detection (IRESE) sequence.

16. The apparatus of claim 12 , wherein for each of the plurality of pulse sets,

the first, second and third transmit pulses form an inversion recovery with electron-spin echo detection (IRESE) sequence having a π-pulse as the first pulse, a T delay as the first delay, a π/2-pulse as the second pulse, a τ delay as the second delay, a π-pulse as the third pulse, a τ delay as a third delay, wherein the first, second and third pulses are each about 35 ns in duration,

wherein the π/2 pulse rotates a magnetization π/2 radians and the π-pulses rotate a magnetization π radians,

wherein τ=630 ns,

wherein T has a value in a range of about 500 ns to about 16,000 ns,

wherein the cycles of RF have a frequency of about 250 MHz,

wherein the plurality of pulse sets apply a sixteen-step phase cycling,

wherein about 7520 acquisitions are acquired per value of T and include phase cycling,

wherein eight T values are approximately logarithmically spaced between one-half microseconds (0.5 μs) and sixteen microseconds (16 μs) are used,

wherein T LF R =25 μs, and

wherein the phase cycling uses values selected from rows of the following table:

Detection

Detection

First

First

Second

Second

Third

Third

channel Re

channel Im

pulse

delay

pulse

delay

pulse

delay

(real)

(imaginary)

X

T

0.5X

630 ns

 X

630 ns

 A

 B

X

T

0.5X

630 ns

−X

630 ns

 A

 B

X

T

0.5X

630 ns

 Y

630 ns

−A

−B

X

T

0.5X

630 ns

−Y

630 ns

−A

−B

X

T

−0.5X

630 ns

 X

630 ns

−A

−B

X

T

−0.5X

630 ns

−X

630 ns

−A

−B

X

T

−0.5X

630 ns

 Y

630 ns

 A

 B

X

T

−0.5X

630 ns

−Y

630 ns

 A

 B

X

T

0.5Y

630 ns

 X

630 ns

 B

−A

X

T

0.5Y

630 ns

−X

630 ns

 B

−A

X

T

0.5Y

630 ns

 Y

630 ns

−B

 A

X

T

0.5Y

630 ns

−Y

630 ns

−B

 A

X

T

−0.5Y

630 ns

 X

630 ns

−B

 A

X

T

−0.5Y

630 ns

−X

630 ns

−B

 A

X

T

−0.5Y

630 ns

 Y

630 ns

 B

−A

X

T

−0.5Y

630 ns

−Y

630 ns

 B

 −A.

17. The apparatus of claim 10 , wherein the means for generating an EPROI image includes:

digital-signal-processing means operatively coupled to process the received electrical signal and to generate image data;

storage means operatively coupled to receive and store the image data; and

display means operatively coupled to the storage means to receive and display the image data.

18. The apparatus of claim 2 , further comprising:

a digital-signal processor (DSP) unit operatively coupled to the RF receiver circuit and configured to process the received electrical signal and to generate image data; and

a storage unit operatively coupled to the DSP unit to receive and store the image data.

19. The apparatus of claim 2 , wherein each of the plurality of pulse sets further includes a third transmit pulse, and wherein for each of the plurality of pulse sets:

the first transmit pulse is a pi pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin by pi radians;

the second transmit pulse is a pi/2 pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin 1/2 pi radians; and

the third transmit pulse is a pi pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin pi radians.

20. The apparatus of claim 1 , wherein the transmitted RF pulses are of magnitudes and durations configured to measure an electron T 1e spin-lattice relaxation using a reporter molecule in the volume of tissue.

21. The apparatus of claim 10 , wherein the transmitted RF pulse sets are of magnitudes and durations configured to measure an electron T 1e spin-lattice relaxation using a reporter molecule in the volume of tissue.

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 (6)
Division 15213768 · Jul 19, 2016
Division 13032637 · Feb 22, 2011
Provisional Application 61445037 · Feb 21, 2011
Provisional Application 61356555 · Jun 18, 2010
Provisional Application 61306917 · Feb 22, 2010
Related Publication 20230240553A1 · Aug 3, 2023
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