Systems and methods to target blood vessel adventitia with transcutaneous focused ultrasound

Abstract

Systems and methods for maintaining the alignment of a therapeutic ultrasound applicator to a target site are described. Overlapping ultrasound signals are sent to a target tissue site and the echo detected. An algorithm is described for detecting tissue movement relative to the applicator based on comparison of the echo with a previously stored echo.

1 . A method of applying therapeutic energy to a target region comprising a blood vessel, the method comprising:
 emitting first ultrasonic pulses from at least three ultrasound transducers to tissue at a target point within the target region, wherein the target point comprises the adventitia of a blood vessel;   detecting first ultrasonic echoes from the blood vessel with the ultrasound transducers;   emitting second ultrasonic pulses from the ultrasound transducers;   detecting second ultrasonic echoes from the blood vessel with the ultrasound transducers;   comparing the first and second ultrasonic echoes to determine time shifts or phase differences between the first and second ultrasonic echoes;   determining the amount of relative tissue movement using the time shifts or phase differences and pre-determined unit vectors of each ultrasound transducer;   adjusting a focus of a therapeutic ultrasound applicator based at least in part on the determined amount of relative tissue movement to keep the target point within the focus of the therapeutic applicator; and   emitting a dose of therapeutic ultrasonic energy from the therapeutic ultrasound applicator such that the target point is exposed to the dose.   
     
     
         2 . The method of  claim 1 , wherein determining the amount of relative tissue movement comprises executing a recursive algorithm. 
     
     
         3 . The method of  claim 1 , wherein the predetermined unit vectors are determined experimentally. 
     
     
         4 . The method of  claim 1 , wherein the therapeutic applicator comprises at least one of the ultrasound transducers. 
     
     
         5 . A method of applying focused ultrasound therapeutic energy, the method comprising:
 emitting a first ultrasonic pulse from a first ultrasound transducer through skin tissue to a target point within a target region, wherein the target point comprises the adventitia of a blood vessel, the first ultrasound transducer comprising an array of at least one therapeutic piezoelectric element;   detecting a first ultrasonic echo from the blood vessel at one of the therapeutic piezoelectric elements of the first ultrasound transducer;   emitting a second ultrasonic pulse from the first ultrasound transducer;   detecting a second ultrasonic echo from the blood vessel at one of the therapeutic piezoelectric elements of the first ultrasound transducer;   comparing the first and second echoes to determine time shifts or phase differences between the detected echoes;   determining the position of the target point relative to the focus of the therapy using the time shifts or phase differences;   adjusting a focus of a therapeutic ultrasound applicator based at least in part on the determined position to keep the target point within the focus of the therapeutic applicator; and   emitting a dose of therapeutic ultrasonic energy from the therapeutic ultrasound applicator such that the target point is exposed to the dose.   
     
     
         6 . The method of  claim 5 , further comprising detecting the ultrasonic echoes with at least one additional ultrasound transducer. 
     
     
         7 . The method of  claim 6  wherein the additional ultrasound transducer does not contribute to therapy. 
     
     
         8 . The method of  claim 6  wherein the additional ultrasound transducer is placed on the perimeter of the annular array. 
     
     
         9 . The method of  claim 5 , further comprising detecting the amount of relative tissue motion between the first and second echoes. 
     
     
         10 . A method of applying therapeutic energy to a target region comprising a blood vessel, the method comprising:
 emitting an ultrasonic pulse from a first ultrasound transducer to tissue at a target point within the target region, wherein the target point comprises the adventitia of a blood vessel;   detecting a first ultrasonic echo from the target point;   comparing the first echo to a previously recorded echo to determine time shifts or phase differences between the detected echoes and the previously recorded echoes;   determining the amount of relative tissue movement using the time shifts or phase differences and pre-determined unit vectors of each ultrasound transducer;   adjusting a focus of a therapeutic ultrasound applicator based at least in part on the determined amount of relative tissue movement to keep the target point within the focus of the therapeutic applicator; and   emitting a dose of therapeutic ultrasonic energy from the therapeutic ultrasound applicator such that the target point is exposed to the dose.   
     
     
         11 . The method of  claim 10 , further comprising detecting the ultrasonic echo with at least one additional ultrasound transducer. 
     
     
         12 . The method of  claim 10 , wherein determining the amount of relative tissue movement comprises executing a recursive algorithm. 
     
     
         13 . The method of  claim 10 , wherein the predetermined unit vectors are determined experimentally. 
     
     
         14 . The method of  claim 10 , wherein the therapeutic applicator comprises the first ultrasound transducer. 
     
     
         15 . The method of  claim 10 , wherein the first ultrasound transducer comprises a piezoelectric element adapted exclusively to transmit imaging ultrasonic pulses.