Systems and methods for blood-brain barrier opening and cavitation imaging using a diagnostic imaging array
Inventors
Konofagou, Elisa E. • Burgess, Mark • Ji, Robin • Batts, Alec J.
Assignees
Columbia University in the City of New York
Publication Number
US-12369880-B2
Publication Date
2025-07-29
Expiration Date
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Abstract
The present subject matter relates to techniques for simultaneous blood-brain barrier opening and cavitation imaging. The disclosed system can include a transducer and a processor. The transducer can be configured to generate a plurality of focused transmits and simultaneously obtain a plurality of power cavitation images. The processor can be configured to control a parameter of the focused transmits, acquire the power cavitation images between each focused transmit, and generate a cavitation map based on the power cavitation images.
Core Innovation
The disclosed subject matter provides techniques for simultaneous blood-brain barrier opening and cavitation imaging using a single diagnostic transducer and a processor. The transducer is configured to generate a plurality of focused transmits and simultaneously obtain a plurality of power cavitation images, and the processor is configured to control a parameter of the focused transmits, acquire the power cavitation images between each focused transmit, and generate a cavitation map based on the power cavitation images.
The background identifies limitations of certain focused-ultrasound systems that require custom-built geometrically focused transducers with a fixed focal point or very complex multi-element arrays, can have limited focusing capabilities, be expensive or cumbersome, can require MRI guidance, and can target a single location at a time requiring physical translation or microbubble reinjection; additionally such transducers can provide insufficient spatial information of microbubble cavitation. The disclosed subject matter addresses the need for an improved ultrasound technique that can utilize diagnostic ultrasound systems for simultaneous blood-brain barrier opening and cavitation imaging.
Claims Coverage
Two independent claims are present: a system claim and a method claim. The main inventive features relate to (1) use of a single diagnostic/therapeutic transducer to transmit focused pulses and obtain power cavitation images between transmits, and (2) processor-mediated control of transmit parameters and generation of cavitation maps.
Transducer generates a plurality of focused transmits
A transducer configured to generate a plurality of focused transmits as part of a system for simultaneous blood-brain barrier opening and cavitation imaging, as stated in the system claim.
Transducer obtains power cavitation images between focused transmits
A transducer configured to obtain a plurality of power cavitation images corresponding to detection of microbubble cavitation in response to the focused transmits, with at least one power cavitation image obtained between successive focused transmits, as recited in the system claim.
Single diagnostic transducer configured for theranostic use
The transducer is specified as a single diagnostic transducer that is configured to obtain at least one power cavitation image between successive focused transmits, enabling combined therapeutic and imaging functionality in one transducer, as stated in the system claim.
Processor controls transmit parameters and acquires images
A processor configured to control a parameter of the plurality of focused transmits and to acquire the obtained plurality of power cavitation images, as recited in the system claim.
Processor generates a cavitation map based on acquired images
A processor configured to generate a cavitation map based on the obtained plurality of power cavitation images, the cavitation map signifying the location of microbubble cavitation within target tissue, as recited in the system claim.
Processor performs beamforming and spatiotemporal filtering
A processor configured to perform beamforming on acquired images, accumulate beamformed images, and spatiotemporally filter the beamformed images using a singular value decomposition filter, as recited in the system claim.
Simultaneous generation of focused transmits and acquisition of cavitation images using one transducer
A method comprising generating a plurality of focused transmits using a single therapeutic transducer configured to obtain at least one power cavitation image between each focused transmit, and simultaneously obtaining a plurality of power cavitation images corresponding to detection of microbubble cavitation in response to the focused transmits, as recited in the method claim.
Generating a cavitation map from power cavitation images
A method step of generating a cavitation map based on the obtained power cavitation images, as recited in the method claim.
The independent system claim centers on a single diagnostic transducer that both transmits focused ultrasound and obtains power cavitation images between transmits, together with a processor that controls transmit parameters and generates cavitation maps; the independent method claim centers on generating focused transmits with a single therapeutic transducer while obtaining power cavitation images between transmits and generating a cavitation map from those images.
Stated Advantages
Enables simultaneous blood-brain barrier opening and cavitation imaging using a single diagnostic/theranostic transducer.
Allows estimation of the size of the focus in the imaging plane using power cavitation images.
Permits targeting of multiple areas by adjusting transmit parameters without physical translation of the transducer and can allow multiple targets with a single injection of microbubbles.
Provides spatial cavitation maps that localize microbubble cavitation and correlate with contrast-enhanced MRI and hydrophone measurements for localization and monitoring.
Demonstrated feasibility for transcranial blood-brain barrier opening and cavitation monitoring in animal models and applicability to human and/or animal subjects.
Documented Applications
Noninvasive delivery of drugs to the central nervous system via focused-ultrasound mediated blood-brain barrier opening.
Simultaneous blood-brain barrier opening and cavitation imaging using a single diagnostic transducer for localization and monitoring of microbubble cavitation.
Transcranial blood-brain barrier opening and cavitation monitoring demonstrated in mice and non-human primates.
Use of cavitation maps to localize blood-brain barrier opening in vivo and comparison/correlation with contrast-enhanced MRI.
Potential clinical application including neuronavigation-guided focused-ultrasound induced blood-brain barrier opening outside the magnetic bore to treat Alzheimer’s disease patients (AD patients) as described.
Targeting of various tissues including brain, muscle, tendons, ligaments, skin, vessels, artery, arterial tissue, and renal tissue, as explicitly listed for target tissue.
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