University of Michigan

Histosonics, Inc.

Other

Charles A Cain

Zhen Xu

Adam D Maxwell

Hitinder S Gurm

J Brian Fowlkes

William W Roberts

Timothy L Hall

Thomas W Davison

Dejan Teofilovic

Kuang-Wei Lin

Russell Carl Jahnke

James A Bertolina

Jonathan Sukovich

Aditya S Pandey

Matthew N O'Donnell

Ryan M Miller

Michael Thomas Kusner, Jr

Simone Park

Adam Strickberger

S Adam Strickberger

Emad S Ebbini

Yohan Kim

Tzu-Yin Wang

Michael Thomas Kusner

Apparatus and methods are provided for applying ultrasound pulses into tissue or a medium in which the peak negative pressure (P−) of one or more negative half cycle(s) of the ultrasound pulses exceed(s) an intrinsic threshold of the tissue or medium, to directly form a dense bubble cloud in the tissue or medium without shock-scattering. In one embodiment, a microtripsy method of Histotripsy therapy comprises delivering an ultrasound pulse from an ultrasound therapy transducer into tissue, the ultrasound pulse having at least a portion of a peak negative pressure half-cycle that exceeds an intrinsic threshold in the tissue to produce a bubble cloud of at least one bubble in the tissue, and generating a lesion in the tissue with the bubble cloud. The intrinsic threshold can vary depending on the type of tissue to be treated. In some embodiments, the intrinsic threshold in tissue can range from 15-30 MPa.

Histotripsy using very short ultrasound pulses

Methods for performing non-invasive thrombolysis with ultrasound using, in some embodiments, one or more ultrasound transducers to focus or place a high intensity ultrasound beam onto a blood clot (thrombus) or other vascular inclusion or occlusion (e.g., clot in the dialysis graft, deep vein thrombosis, superficial vein thrombosis, arterial embolus, bypass graft thrombosis or embolization, pulmonary embolus) which would be ablated (eroded, mechanically fractionated, liquefied, or dissolved) by ultrasound energy. The process can employ one or more mechanisms, such as of cavitational, sonochemical, mechanical fractionation, or thermal processes depending on the acoustic parameters selected. This general process, including the examples of application set forth herein, is henceforth referred to as 'Thrombolysis.'

Histotripsy for thrombolysis

A histotripsy therapy system configured for the treatment of brain tissue is provided, which may include any number of features. In one embodiment, the system includes an ultrasound therapy transducer, a drainage catheter, and a plurality of piezoelectric sensors disposed in the drainage catheter. The ultrasound therapy is configured to transmit ultrasound pulses into the brain to generate cavitation that liquefies a target tissue in the brain. The drainage catheter is configured to detect the ultrasound pulses. An aberration correction algorithm can be executed by the system based on the ultrasound pulses measured by the drainage catheter to automatically correct for an aberration effect caused by the ultrasound pulses passing through a skullcap of the patient.

Histotripsy therapy systems and methods for the treatment of brain tissue

Apparatus and methods are provided for applying ultrasound pulses into tissue or a medium in which the peak negative pressure (P&#x2212;) of one or more negative half cycle(s) of the ultrasound pulses exceed(s) an intrinsic threshold of the tissue or medium, to directly form a dense bubble cloud in the tissue or medium without shock-scattering. In one embodiment, a microtripsy method of Histotripsy therapy comprises delivering an ultrasound pulse from an ultrasound therapy transducer into tissue, the ultrasound pulse having at least a portion of a peak negative pressure half-cycle that exceeds an intrinsic threshold in the tissue to produce a bubble cloud of at least one bubble in the tissue, and generating a lesion in the tissue with the bubble cloud. The intrinsic threshold can vary depending on the type of tissue to be treated. In some embodiments, the intrinsic threshold in tissue can range from 15-30 MPa.

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.

Bubble-induced color doppler feedback during histotripsy

Histotripsy using very short monopolar ultrasound pulses

A medical imaging and therapy device is provided that may include any of a number of features. The device may include a Histotripsy transducer, a generator and controller configured to deliver Histotripsy energy from the transducer to target tissue, and an imaging system. In some embodiments, a method of treating tissue with Histotripsy energy comprises positioning a focus of a histotripsy transducer on a target tissue, delivering histotripsy energy from the histotripsy transducer through a bone aberrator, forming a histotripsy bubble cloud on the focus, and preventing the formation of secondary histotripsy bubble clouds without implementing an aberration correction algorithm.

Lesion generation through bone using histotripsy therapy without aberration correction

A medical imaging and therapy device is provided that may include any of a number of features. One feature of the device is that it can image a target tissue volume and apply ultrasound energy to the target tissue volume. In some embodiments, the medical imaging and therapy device is configured controllably apply ultrasound energy into the prostate by maintaining a cavitational bubble cloud generated by an ultrasound therapy system within an image of the prostate generated by an imaging system. The medical imaging and therapy device can be used in therapeutic applications such as Histotripsy, Lithotripsy, and HIFU, for example. Methods associated with use of the medical imaging and therapy device are also covered.

Automated control of micromanipulator arm for histotripsy prostate therapy while imaging via ultrasound transducers in real time

A medical imaging and therapy device is provided that may include any of a number of features. One feature of the device is that it can deliver Lithotripsy therapy to a patient, so as to fractionate urinary stones. Another feature of the device is that it can deliver Histotripsy therapy to a patient, so as to erode urinary stones. In some embodiments, the medical imaging and therapy device is configured to target and track urinary stones in the patient during therapy. Methods associated with use of the medical imaging and therapy device are also covered.

Ultrasound lithotripsy and histotripsy for using controlled bubble cloud cavitation in fractionating urinary stones

Therapy methods using pulsed cavitational ultrasound therapy can include the subprocesses of initiation, maintenance, therapy, and feedback of the histotripsy process, which involves the creation and maintenance of ensembles of microbubbles and the use of feedback in order to optimize the process based on observed spatial-temporal bubble cloud dynamics. The methods provide for the subdivision or erosion of tissue, liquification of tissue, and/or the enhanced delivery of therapeutic agents. Various feedback mechanisms allow variation of ultrasound parameters and provide control over the pulsed cavitational process, permitting the process to be tuned for a number of applications. Such applications can include specific tissue erosion, bulk tissue homogenization, and delivery of therapeutic agents across barriers.

Pulsed cavitational ultrasound therapy

Growing community of inventors

Ann Arbor, MI, United States of America

Charles A Cain