Bubble-induced color doppler feedback during histotripsy

Abstract

A Histotripsy therapy system is provided that can include any number of features. In some embodiments, the system includes a high voltage power supply, a pulse generator electrically coupled to at least one signal switching amplifier, at least one matching network electrically coupled to the signal switching amplifier(s), and an ultrasound transducer having at least one transducer element. The Histotripsy therapy system can further include an ultrasound Doppler imaging system. The Doppler imaging system and the Histotripsy therapy system can be synchronized to enable color Doppler acquisition of the fractionation of tissue during Histotripsy therapy. Methods of use are also described.

What is claimed is: 
     
         1 . An ultrasound system configured to monitor bubble-induced color Doppler during Histotripsy treatment comprises:
 a ultrasound therapy transducer configured to transmit Histotripsy pulses into a treatment region including tissue, the Histotripsy pulses having a pulse length less than 50 μsec, a peak negative pressure greater than 10 MPa, and a duty cycle less than 5%;   an ultrasound Doppler imaging system configured to transmit ultrasound imaging pulses along the propagation direction of the Histotripsy pulses and generate color Doppler imaging of the treatment region from the transmitted ultrasound imaging pulses; and   a control system configured to synchronize transmission of the ultrasound imaging pulses with transmission of the Histotripsy pulses to monitor Histotripsy tissue fractionation in real-time with the Doppler imaging.   
     
     
         2 . The ultrasound system of  claim 1  wherein the control system is configured to set specific Doppler parameters to follow the tissue displacement using color Doppler. 
     
     
         3 . The ultrasound system of  claim 2  wherein the specific Doppler parameters are selected from the group consisting of a time delay between a Doppler pulse packet and the Histotripsy pulses, a pulse repetition frequency of the Doppler pulse packet, and a number of frames in the Doppler pulse packet. 
     
     
         4 . The ultrasound system of  claim 1  wherein the ultrasound therapy transducer includes a hole configured to house an ultrasound imaging transducer of the ultrasound Doppler imaging system so as to align the ultrasound imaging transducer along a propagation path of the Histotripsy pulses. 
     
     
         5 . The ultrasound system of  claim 1  wherein the control system is configured to synchronize transmission of the ultrasound imaging pulses with transmission of the Histotripsy pulses by sending a trigger signal from the control system to the ultrasound Doppler imaging system during the transmission of each Histotrispy pulse plus a pre-determined time delay. 
     
     
         6 . The ultrasound system of  claim 1  wherein a pulse repetition frequency (PRF) and a number of frames of Doppler imaging pulse packet are set by the ultrasound Doppler imaging system so color Doppler flow velocity increases as a degree of tissue fractionation generated by the Histotripsy pulses increases. 
     
     
         7 . The ultrasound system of  claim 1  wherein an expansion of a temporal profile of a color Doppler velocity increases as a degree of tissue fractionation generated by the Histotripsy pulses increases. 
     
     
         8 . The ultrasound system of  claim 1  wherein a rapid expansion of a temporal profile of a color Doppler velocity corresponds to microscopic cellular damage, while a slow expansion of the temporal profile of the color Doppler velocity corresponds to macroscopic tissue structural damage generated by the Histotripsy pulses. 
     
     
         9 . The ultrasound system of  claim 1  wherein a saturation or decrease of expansion of a temporal profile of a color Doppler velocity indicates complete homogenization and liquefaction of the tissue. 
     
     
         10 . The ultrasound system of  claim 1  wherein a PRF and number of frames of color Doppler pulse packet is controlled by the ultrasound Doppler imaging system such that a direction of a color Doppler flow changes from towards an imaging transducer to away from the imaging transducer when the tissue is sufficiently fractionated by the Histotripsy pulses. 
     
     
         11 . The ultrasound system of  claim 1  wherein a wall filter value can be set by the ultrasound Doppler imaging system such that a color Doppler flow map matches the treatment tissue region when it has been fractionated by the Histotripsy pulses. 
     
     
         12 . The ultrasound system of  claim 1 , wherein 2D or 3D images of the tissue can be reconstructed by scanning a focus of the ultrasound therapy transducer and collecting a color Doppler map at each position of the focus. 
     
     
         13 . The ultrasound system of  claim 1  wherein the Doppler imaging can be configured to monitor vessel function and cardiac function during the transmission of Histotripsy pulses. 
     
     
         14 . The ultrasound system of  claim 1  wherein the ultrasound Doppler imaging system can display different colors to distinguish tissue motion from blood flow. 
     
     
         15 . A method of monitoring Doppler-based feedback during Histotrispy treatment comprising the steps of:
 transmitting Histotripsy pulses into tissue having a pulse length less than 50 μsec, a peak negative pressure greater than 10 MPa, and a duty cycle less than 5% with an ultrasound therapy transducer;   obtaining color Doppler acquisition of the tissue during transmission of the Histotripsy pulses with an ultrasound imaging system; and   synchronizing the color Doppler acquisition with the transmission of Histotripsy pulses with a control system.   
     
     
         16 . The method of  claim 15  further comprising setting specific Doppler parameters to follow tissue displacement using color Doppler acquisition. 
     
     
         17 . The method of  claim 15  further comprising obtaining color Doppler acquisition along a propagation line of the Histotripsy pulses to measure tissue displacement of the tissue. 
     
     
         18 . The method of  claim 15  wherein the synchronizing step comprises sending a trigger signal to the ultrasound imaging system from the control system during the transmission of each Histotrispy pulse plus a pre-determined time delay. 
     
     
         19 . The method of  claim 15  further comprising setting a PRF and number of frames for color Doppler acquisition such that a color Doppler flow velocity increases with an increasing degree of tissue fractionation generated by the Histotripsy pulses. 
     
     
         20 . The method of  claim 15  further comprising setting a PRF and number of frames for color Doppler acquisition such that a direction of a color Doppler flow changes from towards the ultrasound imaging system to away from the ultrasound imaging system when the tissue is sufficiently fractionated by the Histotripsy pulses. 
     
     
         21 . The method of  claim 15  further comprising setting a wall filter value such that a color Doppler flow map matches a fractionated tissue region generated by the Histotripsy pulses. 
     
     
         22 . The method of  claim 15  further comprising reconstructing 2D or 3D Doppler imaging of a fractionated tissue by scanning a focus of the ultrasound therapy system and collecting a color Doppler map at a position of the focus. 
     
     
         23 . The method of  claim 15  further comprising monitoring vessel function and cardiac function during transmission of the Histotripsy pulses. 
     
     
         24 . The method of  claim 15  further comprising distinguishing tissue displacement from blood flow with the color Doppler acquisition. 
     
     
         25 . The method of  claim 15  wherein the color Doppler acquisition can be used to monitor and indicate microscopic cellular damage versus macroscopic tissue structure homogenization. 
     
     
         26 . The ultrasound system of  claim 4  wherein the hole is concentrically aligned within the ultrasound therapy transducer. 
     
     
         27 . The ultrasound system of  claim 4  wherein the hole is not concentrically aligned within the ultrasound therapy transducer.