DEVICE AND METHOD FOR IN VIVO DETECTION OF CLOTS WITHIN CIRCULATORY VESSELS

• US 20120065490A1
• Filed: 10/05/2011
• Published: 03/15/2012
• Est. Priority Date: 12/13/2007
• Status: Active Grant

• Current Assignee: Bioventures, LLC
• Original Assignee: The Board of Trustees of the University of Arkansas (University of Arkansas System)
• Inventors: Zharov, Vladimir Pavlovich, Galanzha, Ekaterina
• Granted Patent: US 9,451,884 B2
• Time in Patent Office: Days
• US Class Current: 600/407
• CPC Class Codes: A61B 18/1815 using microwaves
• CPC Class Codes: A61B 18/20 using laser
• CPC Class Codes: A61B 18/245 for removing obstructions in blood vessels or calculi
• CPC Class Codes: A61B 2018/0041 Removal of thrombosis
• CPC Class Codes: A61B 2018/00577 Ablation
• CPC Class Codes: A61B 2018/0088 Vibration
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/0095 by applying light and detecting acoustic waves, i.e. photoacoustic measurements
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/14535 for measuring haematocrit
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/412 Detecting or monitoring sepsis
• CPC Class Codes: A61B 5/415 the glands, e.g. tonsils, adenoids or thymus
• CPC Class Codes: A61B 5/416 the spleen
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/7282 Event detection, e.g. detecting unique waveforms indicative of a medical condition A61B5/4094, A61B5/4818, A61B5/349, A61B5/0823 take precedence
• CPC Class Codes: A61B 5/7405 using sound
• CPC Class Codes: A61B 5/742 using visual displays A61B5/339 takes precedence
• CPC Class Codes: A61B 5/7455 characterised by tactile indication, e.g. vibration or electrical stimulation
• CPC Class Codes: A61B 5/746 : Alarms related to a physiological condition, e.g. details of setting alarm thresholds or avoiding false alarms alarms per se G08B
• CPC Class Codes: A61B 8/06 : Measuring blood flow measuring volume flow in general G01F, e.g. G01F1/66, G01F1/72; measuring speed of fluids in general G01P5/00
• CPC Class Codes: A61B 8/08 : Detecting organic movements or changes, e.g. tumours, cysts, swellings A61B8/02 - A61B8/06 take precedence
• 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: A61K 49/22 : Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
• CPC Class Codes: B03C 1/288 : disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 1/30 : Combinations with other devices, not otherwise provided for
• CPC Class Codes: B03C 2201/06 : Ionising electrode being a needle
• CPC Class Codes: B03C 2201/26 : for use in medical applications
• CPC Class Codes: G01N 15/1425 : using an analyser being characterised by its control arrangement
• CPC Class Codes: G01N 15/1434 : Optical arrangements
• CPC Class Codes: G01N 15/147 : the analysis being performed on a sample stream
• CPC Class Codes: G01N 2015/1477 : Multiparameters
• CPC Class Codes: G01N 21/1702 : with opto-acoustic detection, e.g. for gases or analysing solids
• CPC Class Codes: G01N 2201/0221 : Portable; cableless; compact; hand-held
• CPC Class Codes: G01N 29/2418 : using optoacoustic interaction with the material, e.g. laser radiation, photoacoustics photoacoustic cells G01N21/1702; measuring characteristics of vibrations by using radiation-sensitive means G01H9/00; acousto-optical conversion techniques for short-range imaging G01S15/8965; sound-producing devices using laser bundle G10K15/046
• CPC Class Codes: G01N 29/4427 : with stored values, e.g. threshold values

Abstract

A device and method of using the device to detect the presence and composition of clots and other target objects in a circulatory vessel of a living subject is described. In particular, devices and methods of detecting the presence and composition of clots and other target objects in a circulatory vessel of a living subject using in vivo photoacoustic flow cytometry techniques is described.

Claims

1. A method for detecting a clot property within a circulatory vessel of a living organism, the method comprising:

pulsing a clot within the circulatory vessel with at least one pulse of laser energy at a first pulse wavelength, wherein the first pulse wavelength induces a photoacoustic signal from the clot that is lower in magnitude than the photoacoustic signal induced from surrounding red blood cells;

obtaining a photoacoustic pattern emitted by the clot induced by the at least one pulse of laser energy, wherein the photoacoustic pattern comprises at least one photoacoustic signal;

analyzing the photoacoustic pattern to calculate at least one characteristic of the photoacoustic pattern; and

comparing the at least one characteristic of the photoacoustic pattern to a set of calibration patterns to determine one or more clot properties.

2. The method of claim 1, wherein the one or more clot properties are chosen from a presence of a clot, a clot size, a clot composition, a clot speed through the circulatory vessel, and any combination thereof.

3. The method of claim 2, wherein the clot composition is chosen from one or more cell types incorporated into the clot, a relative amount of the one or more cell types incorporated into the clot, and combinations thereof, wherein the one or more cell types are chosen from a platelet, a white blood cell, a red blood cell, and a circulating tumor cell.

4. The method of claim 1, wherein the first pulse wavelength ranges from about 500 nm to about 600 nm.

5. The method of claim 2, wherein the photoacoustic pattern comprises a series of photoacoustic signals induced by a series of consecutive laser pulses at the first pulse wavelength.

6. The method of claim 5, wherein the photoacoustic pattern comprises a negative contrast dip.

7. The method of claim 6, wherein the set of calibration patterns comprise a group of one or more calibration photoacoustic patterns previously measured for a group of clots with known clot properties, wherein each calibration photoacoustic pattern comprises a characteristic chosen from a width of a negative contrast dip, a magnitude of the negative contrast dip, a shape of the negative contrast dip, and combinations thereof.

8. The method of claim 1, further comprising:

pulsing the clot within the circulatory vessel with at least one additional pulse of laser energy at a second pulse wavelength;

obtaining a second photoacoustic pattern emitted by the clot induced by the at least one additional pulse of laser energy, wherein the second photoacoustic pattern comprises at least one additional photoacoustic signal;

analyzing the second photoacoustic pattern to calculate at least one additional characteristic of the second photoacoustic pattern; and

comparing the first photoacoustic pattern and the second photoacoustic pattern to the set of calibration patterns to determine the one or more clot properties.

9. The method of claim 8, wherein the first pulse wavelength ranges from about 400 nm to about 500 nm.

10. A device for the continuous monitoring of a circulatory vessel of a living organism, comprising:

an in vivo flow cytometer, wherein the in vivo flow cytometer comprises

a pulsed laser for pulsing a clot within the circulatory vessel with at least one pulse of laser energy at a pulse wavelength ranging between about 500 nm and about 600 nm; and

an ultrasound transducer for receiving a photoacoustic signal emitted by a clot in response to the at least one pulse of laser energy;

a clot monitoring system for analyzing a photoacoustic pattern comprising at least one photoacoustic signal and producing a detection signal if the photoacoustic pattern indicates a clot; and

an alarm system for providing an alarm signal to the living organism in response to a detection signal produced by the clot monitoring system.

11. The device of claim 10, wherein the device is secured to an appendage of the living organism, wherein the appendage is chosen from an arm, a leg, a finger, a toe, a neck, and a head.

12. The device of claim 10, wherein the alarm signal comprises an intermittent or continuous indication to the living organism chosen from a visual display, an audible sound, a vibration, a signal to summon medical assistance, and any combination thereof.

13. The device of claim 12, wherein the signal to summon medical assistance is a wireless signal chosen from a Bluetooth signal, a cellular signal, a wireless internet signal, and a radio signal.

14. The device of claim 10, wherein the device further comprises a clot treatment system for initiating a clot treatment in response to a detection signal, wherein the clot treatment is chosen from administration of anti-clotting medication and pulsing the clot with a high-intensity laser pulse at a laser fluence sufficient to ablate the clot.

15. The device of claim 13, wherein the high-intensity laser pulse is delivered at a second wavelength, wherein the clot has a high energy absorbancy for the second wavelength.

16. The device of claim 14, wherein the second wavelength ranges from about 400 nm to about 500 nm.

17. A wearable device for the continuous monitoring of a circulatory vessel of a living organism, comprising:

an in vivo flow cytometer, wherein the in vivo flow cytometer comprises

a pulsed laser for pulsing a clot within the circulatory vessel with at least one pulse of laser energy at a pulse wavelength ranging from about 500 nm to about 600 nm; and

an ultrasound transducer for receiving a photoacoustic signal emitted by a clot in response to the at least one pulse of laser energy;

a clot monitoring system for analyzing a photoacoustic pattern comprising at least one photoacoustic signal and producing a detection signal if the photoacoustic pattern indicates a clot;

an alarm system for providing an alarm signal to the living organism in response to a detection signal produced by the clot monitoring system; and

a power source for providing power to the in vivo flow cytometer, the clot monitoring system, and the alarm system;

wherein the device is secured to an appendage of the living organism chosen from an arm, a leg, a finger, a toe, a neck, and a head.

18. The device of claim 17, wherein the alarm signal comprises an intermittent or continuous indication to the living organism chosen from a visual display, an audible sound, a vibration, a signal to summon medical assistance, and any combination thereof.

19. The device of claim 18, wherein the signal to summon medical assistance is a wireless signal chosen from a Bluetooth signal, a cellular signal, a wireless internet signal, and a radio signal.

20. The device of claim 17, wherein the device is a portable and self-contained device.