Methods and devices for diagnosis of blood vessel blockage or hemorrhage

• US 11,006,932 B2
• Filed: 03/14/2014
• Issued: 05/18/2021
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Hoelscher, Thilo, Voie, Arne
• Primary Examiner(s): Bui Pho, Pascal M
• Assistant Examiner(s): Yang, Yi-Shan
• Application Number:
  US14/776,664
• Publication Number:
  US 20160030009A1
• Time in Patent Office: 2,622 Days
• Field of Search: None
• CPC Class Codes: A61B 8/0808 for diagnosis of the brain
• CPC Class Codes: A61B 8/0891 for diagnosis of blood vessels
• CPC Class Codes: A61B 8/4477 using several separate ultrasound transducers or probes
• CPC Class Codes: A61B 8/481 involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream analysis of echo signal exploiting properties of a contrast enhancer in devices for short-range imaging with acoustic waves G01S7/52039
• CPC Class Codes: A61B 8/5223 for extracting a diagnostic or physiological parameter from medical diagnostic data for algorithms to analyse biomedical images G06T7/0012
• CPC Class Codes: A61B 8/56 Details of data transmission or power supply
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment

Abstract

A method of diagnosing the occurrence or non-occurrence of a blood vessel blockage or hemorrhage comprises non-invasively applying ultrasound to a location on a patient'"'"'s body, where the ultrasound is applied in an alternating and pulsed fashion, administering acoustic amplifiers to the patient, monitoring a feedback acoustic response signal of the acoustic amplifiers triggered by the ultrasound, and determining a diagnosis based at least in part on a relationship between an acoustic response signature of the acoustic response signal and a baseline acoustic response signature.

Claims

1. A method comprising:

applying, to at least one transducer, an ultrasound signal to cause the at least one transducer to transmit ultrasound to a location on a patient'"'"'s body;

administering acoustic amplifiers intravenously to the patient, the acoustic amplifiers including microbubbles, the microbubbles including a shell filled with a gas such that the microbubbles are stabilized to pass through lungs of the patient;

monitoring a feedback acoustic response signal from the at least one transducer to receive data indicative of an acoustic response of the acoustic amplifiers triggered by the ultrasound;

controlling a power of the ultrasound such that acoustic response signals representing at least subharmonics or ultra-harmonics, or both, are measured in the monitored feedback acoustic signal;

and

differentiating between an occurrence of a hemorrhagic stroke and an ischemic stroke, and an absence of the hemorrhagic stroke or the ischemic stroke based at least in part on a relationship between an acoustic response signature of the feedback acoustic response signal and a baseline acoustic response signature,

wherein the differentiating further comprises

determining that the hemorrhagic stroke has occurred if the acoustic response signature including the measured sub-harmonics or ultra-harmonics or both, exhibits a diminished signal amplitude in comparison to the baseline acoustic response signature,

determining that the ischemic stroke has occurred if the acoustic response signature including the measured sub-harmonics or ultra-harmonics or both, exhibits signal exhaustion or no signal in comparison to the baseline acoustic response signature, and

determining that the absence of the hemorrhagic stroke or the ischemic stroke has occurred if the acoustic response signature exhibits a common acoustic response signal in both brain hemispheres,

wherein the baseline acoustic response signature corresponds to an unaffected brain hemisphere or a known normal acoustic response signature.

2. The method of claim 1, wherein the at least one transducer includes a plurality of transducers and the ultrasound signal is applied in an alternating pattern and pulsed fashion.

3. The method of claim 2, wherein the at least one transducer comprises a first transducer and a second transducer and applying the ultrasound signal comprises:

applying a first pulse of ultrasound during a first On-time period with the first transducer; and

applying a second pulse of ultrasound during a second On-time period with the second transducer, the second On-time period being outside of the first On-time period.

4. The method of claim 3, wherein the monitoring comprises:

receiving a first feedback acoustic response signal from the first transducer during the second On-time period; and

receiving a second feedback acoustic response signal from the second transducer during the first On-time period.

5. The method of claim 1, wherein the ultrasound signal is applied to a patient'"'"'s skull, and the method further comprising diagnosing at least one of presence of the hemorrhagic stroke and presence of the ischemic stroke based at least in part on the relationship between the acoustic response signature and the baseline acoustic response signature.

6. The method of claim 5, wherein, the at least one transducer comprises two transducers and the baseline acoustic response signature comprises at least one of a known normal acoustic response signature, and an acoustic response signature corresponding to an unaffected hemisphere, wherein the baseline acoustic response signature is obtained from one of the two transducers.

7. The method of claim 1, wherein applying the ultrasound signal comprises applying the ultrasound signal in accordance with at least one of patient age, patient race, and patient gender.

8. A system, comprising:

two ultrasound transducer elements configured to provide ultrasound to a patient;

a power and control module (PCM) device communicatively coupled to the two ultrasound transducer elements and configured to;

control an application of the ultrasound to trigger an acoustic response from acoustic amplifiers infused into the patient, the acoustic amplifiers including microbubbles, the microbubbles including a shell filled with a gas such that the microbubbles are stabilized to pass through lungs of the patient; and

monitor a feedback acoustic response signal from the two ultrasound transducer elements to receive data indicative of the acoustic response, and wherein a power of the applied ultrasound is controlled such that acoustic response signals representing at least sub-harmonics or ultra-harmonics, or both, are measured in the monitored feedback acoustic response signal; and

use an acoustic response signature of the feedback acoustic response signal to enable a diagnosis based at least in part on a relationship between the acoustic response signature and a baseline acoustic response signature, the diagnosis including differentiating between an occurrence of a hemorrhagic stroke, an ischemic stroke and an absence of the hemorrhagic stroke or ischemic stroke,

wherein the differentiating further comprises

determining that the hemorrhagic stroke has occurred if the acoustic response signature including the measured sub-harmonics or ultra-harmonics, or both, exhibits a diminished signal amplitude in comparison to the baseline acoustic response signature,

determining that the ischemic stroke has occurred if the acoustic response signature including the measured sub-harmonics or ultraharmonics, or both, exhibits signal exhaustion or no signal in comparison to the baseline acoustic response signature, and

determining that the absence of the hemorrhagic stroke or the ischemic stroke has occurred if the acoustic response signature exhibits a common acoustic response signal in both brain hemispheres,

wherein the baseline acoustic response signature correspond to an unaffected brain hemisphere or a known normal acoustic response signature.

9. The apparatus of claim 8, wherein the PCM device is communicatively coupled wirelessly to the two ultrasound transducer elements.

10. The apparatus of claim 8, wherein the PCM device is further configured to allow selection of a manual control mode or an automatic control mode for controlling the application of the ultrasound.

11. The apparatus of claim 8, wherein the two ultrasound transducer elements are configured to provide the ultrasound to a patient'"'"'s skull, and the PCM device is further configured to diagnose at least one of presence of the hemorrhagic stroke and presence of the ischemic stroke based at least in part on the relationship between the acoustic response signature and the baseline acoustic response signature.

12. The apparatus of claim 11, wherein, the baseline acoustic response signature comprises at least one of a known normal acoustic response signature, and an acoustic response signature corresponding to an unaffected hemisphere, wherein the baseline acoustic response signature is obtained from one of the two ultrasound transducer elements.

13. An apparatus comprising:

a processor;

a non-transitory memory storing program code, the program code for causing the processor to;

apply, to at least one transducer, an ultrasound signal to cause the at least one transducer to transmit ultrasound to a location on a patient'"'"'s body, the ultrasound signal to trigger an acoustic response of acoustic amplifiers infused into the patient, the acoustic amplifiers including microbubbles, the microbubbles including a shell filled with a gas such that the microbubbles are stabilized to pass through lungs of the patient;

monitor a feedback acoustic response signal from the at least one transducer to receive data indicative of the acoustic response of the acoustic amplifiers, and wherein a power of the applied ultrasound is controlled such that acoustic response signals representing at least sub-harmonics or ultra-harmonics, or both, are measured in the monitored feedback acoustic response signal; and

differentiate between an occurrence of a hemorrhagic stroke, an ischemic stroke and an absence of the hemorrhagic stroke or ischemic stroke based at least in part on a relationship between an acoustic response signature of the feedback acoustic response signal and a baseline acoustic response signature,

wherein the differentiate includes

determining that the hemorrhagic stroke has occurred if the acoustic response signature including the measured sub-harmonics or ultra-harmonics, or both, exhibits a diminished signal amplitude in comparison to the baseline acoustic response signature, determining that the ischemic stroke has occurred if the acoustic response signature including the measured sub-harmonics or ultra-harmonics, or both, exhibits signal exhaustion or no signal in comparison to the baseline acoustic response signature, and

determining that the absence of the hemorrhagic stroke or the ischemic stroke has occurred if the acoustic response signature exhibits a common acoustic response signal in both brain hemispheres,

wherein the baseline acoustic response signature corresponds to an unaffected brain hemisphere or a known normal acoustic response signature.

14. The apparatus of claim 13, wherein the at least one transducer includes a plurality of transducers and the program code causes the processor to apply the ultrasound signal in an alternating pattern and pulsed fashion.

15. The apparatus of claim 14, wherein the at least one transducer comprises a first transducer and a second transducer and the program code causes the processor to:

apply a first pulse of ultrasound during a first On-time period with the first transducer; and

apply a second pulse of ultrasound during a second On-time period with the second transducer, the second On-time period being outside of the first On-time period.

16. The apparatus of claim 15, wherein the program code causes the processor to:

receive a first feedback acoustic response signal from the first transducer during the second On-time period; and

receive a second feedback acoustic response signal from the second transducer during the first On-time period.

17. The apparatus of claim 13, wherein the at least one transducer includes two ultrasound transducer elements that are configured to transmit the ultrasound to a patient'"'"'s skull, and the program code causes the processor to diagnose at least one of presence of a stroke, presence of the hemorrhagic stroke and presence of the ischemic stroke based at least in part on the relationship between the acoustic response signature and the baseline acoustic response signature.

18. The apparatus of claim 17, wherein, the at least one transducer comprises two transducers and the baseline acoustic response signature comprises at least one of a known normal acoustic response signature, and an acoustic response signature corresponding to an unaffected hemisphere, wherein the baseline acoustic response signature is obtained from one of the two transducers.