Bronchial denervation using integrated a-mode signal for optimization of ultrasound treatment

Abstract

Apparatus and methods for deactivating bronchial nerves extending along a bronchial branch of a mammalian subject to treat asthma and related conditions. An ultrasonic transducer (11) is inserted into the bronchus as, for example, by advancing the distal end of a catheter (10) bearing the transducer into the bronchial section to be treated. The ultrasonic transducer emits focused ultrasound so as to heat tissues throughout circular impact volume (13) as, for example, at least about 1 cm3 encompassing the bronchus to a temperature sufficient to inactivate nerve conduction but insufficient to cause rapid ablation or necrosis of the tissues. The treatment can be performed without locating or focusing on individual bronchial nerves.

1 . A method for treating adverse respiratory symptoms in a mammalian subject, comprising:
 inserting an ultrasound transducer into a bronchial tree of the mammalian subject; and   operating an actuator or control unit, electrically connected to the ultrasound transducer, to energize the ultrasound transducer to emit a short pulse at a sub-therapeutic level;   receiving via the ultrasound transducer an ultrasound echo from organic tissues of the mammalian subject in response to the short pulse, the ultrasound echo being a volume-integrated A-mode signal;   operating the actuator or control unit to process the volume integrated A-mode signal, which represents an accumulated intensity of the circumferential ultrasound echoes;   analyzing the volume integrated A-mode signal to determine locations of bronchial cartilage rings; and   activating the ultrasound transducer to transmit ultrasound therapeutic waveform energy between adjacent ones of the bronchial cartilage rings.   
     
     
         2 . The method of  claim 1 , further comprising moving the ultrasound transducer to position same adjacent a space or gap between the adjacent ones of the bronchial cartilage rings prior to the activating of the ultrasound transducer to transmit the ultrasound therapeutic waveform energy. 
     
     
         3 . The method of  claim 1  wherein the ultrasound transducer includes multiple separately activatable transducer elements, the activating of the ultrasound transducer includes energizing the separately activatable transducer elements to direct the ultrasound therapeutic waveform energy between the adjacent ones of the bronchial cartilage rings 
     
     
         4 . The method of  claim 1 , further comprising analyzing the volume integrated A-mode signal to detect presence of air pockets or trapped air between balloon and bronchus, the activating of the ultrasound transducer to transmit ultrasound therapeutic waveform energy being carried out only when analyzing of the volume integrated A-mode signal reveals an absence of air, thereby ensuring complete circumferential coupling. 
     
     
         5 . The method of  claim 1 , further comprising operating the actuator or control unit to process the electrical signal to measure time delay of the ultrasound echo waveform relative to a time of emission of the short pulse to determine diameter of a bronchial section to be treated, wherein the activating of the ultrasound transducer to transmit ultrasound therapeutic waveform energy includes activating the ultrasound transducer at an acoustic power level in accordance with the determined size of the bronchial section. 
     
     
         6 . The method of  claim 1  wherein the activating of the ultrasound transducer includes transmitting an amount of ultrasound therapeutic waveform energy into an impact volume circumferentially surrounding a bronchial section, in an amount therapeutically effective to inactivate conduction of all the bronchial nerves in the impact volume. 
     
     
         7 . The method of  claim 1 , wherein for an impact volume of approximately 1 cm 3 , the ultrasound therapeutic waveform energy is transmitted at an acoustic power level of approximately 10 to approximately 50 watts for approximately 10 to approximately 20 seconds to provide an absorbed dose of approximately 100 to approximately 1000 joules throughout the impact volume. 
     
     
         8 . The method of  claim 1 , wherein the ultrasound therapeutic waveform energy is transmitted so as to maintain the temperature of a bronchial wall section surrounding the ultrasound transducer below 65° C. while heating bronchial nerves in a circumferential impact volume about the bronchial wall section to above 42° C. 
     
     
         9 . The method of  claim 1 , wherein the inserting of the ultrasound transducer into the bronchial tree is performed through a working channel of a bronchoscope under visual guidance, or through a steerable sheath, or with a steerable ultrasound catheter through an oral intubating device, or under optical imaging guidance with an optical fiber inserted through the central lumen of the steerable ultrasound treatment catheter, or without a sheath or bronchoscope, directly through an oral intubation device with a steerable ultrasound catheter with a distance scale marking for monitoring degree of insertion after conducting a CT, MRI procedure to ascertain distance along a bronchial tree to the bronchial section. 
     
     
         10 . The method of  claim 1 , further comprising:
 inserting an air filled balloon into the esophagus of the patient;   monitoring the volume integrated A-mode signal;   advancing the treatment catheter distally in extreme cases beyond the first bifurcation until an esophageal signal caused by the air filled balloon inside the esophagus is diminished, thereby enabling prevention of peri esophageal nerve damage; and   circulating a cooling fluid through the balloon, displacing the air, and thereby reducing peri-esophageal nerve damage.   
     
     
         11 . The method of  claim 1 , wherein the ultrasound transducer is mounted to a distal end of a catheter, the inserting of the ultrasound transducer into the bronchial tree includes inserting the catheter so that the ultrasound transducer is placed at a desired operating position determined at least in part based on a bending radius of a distal catheter portion monitored via strain gages. 
     
     
         12 . The method of  claim 1 , whereas the desired catheter position is determined by monitoring the diameters of trachea and bifurcated bronchi. 
     
     
         13 . Apparatus for inactivating bronchial nerve conduction in a mammalian subject, comprising:
 an ultrasound transducer adapted for insertion into a bronchial tree of the mammalian subject and for emitting ultrasound energy; and   an actuator or control unit electrically connected to the ultrasound transducer, the actuator or control unit being configured to activate the ultrasound transducer to emit a short pulse at a sub-therapeutic level, the ultrasound transducer being operatively connected to the actuator or control unit for receiving an electrically encoded volume-integrated A-mode signal or accumulated intensity of ultrasound echoes from organic tissues of the mammalian subject, the actuator or control unit being further configured to process the volume integrated A-mode signal.   
     
     
         14 . The apparatus of  claim 13  wherein the actuator or control unit is additionally configured to analyze the volume integrated A-mode signal to distinguish a relative minimum of the volume integrated A-mode signal with respect to degree of insertion of the ultrasound transducer in the bronchial tree, thereby enabling positioning of the ultrasound transducer to transmit therapeutically effective focused ultrasound energy into a treatment or impact volume between bronchial cartilage rings. 
     
     
         15 . The apparatus of  claim 14  wherein the actuator or control unit is configured to measure time delay of the volume integrated A-mode signal and therewith determine size of a bronchial section, the actuator or control unit being also configured to control the ultrasound transducer to vary the amount of the therapeutically effective focused ultrasound energy in accordance with the determined size of the bronchial section. 
     
     
         16 . The apparatus of  claim 13  wherein the ultrasound transducer includes a longitudinal array of separately activatable transducer elements and the actuator or control unit is configured to energize the separately activatable transducer elements in a sequence to direct the ultrasound therapeutic waveform energy between the adjacent ones of the bronchial cartilage rings. 
     
     
         17 . The apparatus of  claim 13  wherein the actuator or control unit is configured to analyze the volume integrated A-mode signal to facilitate complete circumferential coupling. 
     
     
         18 . The apparatus of  claim 13  wherein the ultrasound transducer is provided on a steerable ultrasound catheter with a distance scale marking for monitoring degree of insertion after conducting a CT, MRI procedure to ascertain distance along a bronchial tree to a bronchial section. 
     
     
         19 . The apparatus of  claim 13  wherein the ultrasound transducer is provided on a catheter with strain gages. 
     
     
         20 - 55 . (canceled)