Histotripsy Bubble Clouds From Very Short Pulses for Sub-Diffraction Lesions
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Solution Overview
Problem
Conventional ultrasound therapies face limitations in generating small, precise lesions due to the diffraction limit, which restricts lesion size to around one wavelength, and require higher frequencies that reduce tissue penetration and increase thermal complications.
Innovation Solution
A method using ultrasound pulses with a peak negative pressure exceeding an intrinsic threshold to generate bubble clouds without shock-scattering, allowing for controlled lesion formation below the diffraction limit by adjusting the amplitude of the pulse to control bubble cloud size.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional ultrasound therapies use higher frequencies to generate smaller lesions, then lesion size precision is improved, but tissue penetration depth deteriorates and thermal complications increase
Solution Approach 1:
The patent changes the fundamental parameter of lesion generation from frequency-dependent thermal/coagulative processes to pressure-dependent mechanical cavitation. By using peak negative pressure exceeding an intrinsic threshold (e.g., >28 MPa), the system generates bubble clouds that create lesions independent of ultrasound frequency, thereby achieving small precise lesions while maintaining deep tissue penetration without thermal complications
Solution Approach 2:
The patent replaces thermal/chemical mechanisms with mechanical cavitation mechanisms. Instead of using high-frequency ultrasound to generate heat for coagulative necrosis, the system uses short pulses with peak negative pressure exceeding an intrinsic threshold to generate bubble clouds that mechanically fractionate tissue, eliminating thermal complications while achieving precise lesion formation
2Manufacturing precision
If conventional ultrasound therapies use tighter focal zones to reduce lesion size, then lesion precision is improved, but diffraction limit prevents smaller lesions
Solution Approach 1:
The patent changes the controlling parameter for lesion size from focal zone diameter (limited by diffraction) to bubble cloud size (controlled by pulse amplitude). By adjusting the amplitude of short ultrasound pulses to exceed an intrinsic threshold, the system generates bubble clouds of controllable size that are not constrained by the diffraction limit, enabling precise control of lesion dimensions
Solution Approach 2:
The patent transitions from two-dimensional focal zone control (lateral and axial dimensions constrained by diffraction) to three-dimensional bubble cloud control through pressure amplitude modulation. The bubble cloud formation adds a pressure dimension to lesion size control, allowing independent adjustment of lesion volume without being bound by focal zone geometry
3Quantity of substance
If conventional Histotripsy uses longer pulses (3-10 cycles) with shock-scattering mechanism, then bubble cloud generation is achieved, but lesion control precision deteriorates
Solution Approach 1:
The patent uses short periodic ultrasound pulses (e.g., single cycle or fewer than 3 cycles) with peak negative pressure exceeding an intrinsic threshold to generate bubble clouds. This periodic action with limited cycles prevents the elongated bubble cloud formation seen in conventional multi-cycle treatments, achieving dense localized bubble clouds with superior lesion control precision
Solution Approach 2:
The patent extracts the essential cavitation-inducing portion of the ultrasound pulse (the peak negative pressure half-cycle exceeding the intrinsic threshold) while removing the subsequent cycles that cause shock-scattering and elongated bubble cloud formation. This extraction of the critical pressure event enables precise lesion control while maintaining effective bubble cloud generation
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables precise and controlled lesion generation with smaller diameters than the diffraction limit, improving penetration depth, reducing thermal complications, and minimizing aberrations, particularly through complex tissues like bone and ribs.
Implementation Method 1
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
Implementation Method 2
The vigorous expansion and collapse of these microbubbles mechanically homogenizes cells and tissue structures within the focal volume
Implementation Method 3
Histotripsy, or pulsed ultrasound cavitation therapy, is a technology where extremely short, intense bursts of acoustic energy induce controlled cavitation (microbubble formation) within the focal volume
Data Source
AI summary
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.