EEG-Guided Ultrasound BBB Opening Verification During Sonication
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Solution Overview
Problem
Existing methods for opening the blood-brain barrier (BBB) using focused ultrasound face challenges in verifying the successful opening due to the complex anatomy of the skull and brain, and existing techniques like mannitol injection risk global BBB opening and are not precise.
Innovation Solution
Utilizing physiologic signals, particularly EEG signals, to monitor and control the ultrasound-based BBB opening procedure, allowing for real-time verification of BBB opening by analyzing changes in EEG patterns indicative of BBB permeability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If focused ultrasound is used to open the BBB, then the ability to deliver drugs to brain tissue is improved, but the difficulty of verifying successful opening increases due to skull and brain anatomy
Solution Approach 1:
The patent employs real-time feedback through physiologic signal monitoring (EEG, ECG, EMG) during focused ultrasound treatment. The system continuously acquires baseline signals before treatment and compares them against signals during sonication to detect changes indicating BBB opening, providing immediate feedback on treatment efficacy without requiring post-procedure verification methods
Solution Approach 2:
The patent uses physiologic signals as intermediary indicators to indirectly assess BBB opening status. Rather than directly imaging or measuring BBB permeability changes, the system monitors physiological responses (brain electrical activity, cardiac signals, muscle activity) that serve as proxies for successful barrier disruption, enabling verification without direct measurement of the barrier itself
2Manufacturing precision
If mannitol injection is used to open the BBB, then BBB permeability is increased, but global BBB opening occurs which is not precise and may cause harmful effects
Solution Approach 1:
The patent achieves localized BBB opening by using focused ultrasound to target specific brain regions. The ultrasound energy is concentrated at a precise focal point within the brain, causing BBB disruption only in the targeted area rather than globally. This is accomplished through phase-array transducer technology that can dynamically focus and steer the ultrasound beam to the desired location
Solution Approach 2:
The patent replaces the chemical mechanism of mannitol injection with a mechanical/physical mechanism using focused ultrasound. Instead of using osmotic pressure from mannitol to disrupt the BBB throughout the brain, the system uses mechanical ultrasound waves to directly open the barrier at the focal point, eliminating the need for chemical agents and their associated side effects
3Reliability
If ultrasound sonication time is extended to ensure BBB opening, then permeability increases, but the risk of vascular damage increases
Solution Approach 1:
The patent uses real-time physiologic signal feedback to monitor BBB opening status during sonication. When the system detects signal changes indicating successful barrier disruption, it automatically terminates or adjusts the ultrasound exposure, preventing excessive sonication time that could cause vascular damage. This feedback-controlled approach ensures adequate but not excessive treatment duration
Solution Approach 2:
The patent employs dynamic adjustment of ultrasound parameters during treatment based on real-time monitoring. The system can modify sonication power, duration, and pulse patterns in response to physiologic signal changes, allowing optimization of BBB opening while minimizing vascular damage risk. This dynamic control enables adaptation to individual patient responses rather than using fixed treatment protocols
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 safe control of the BBB opening process, optimizing sonication time, and ensuring targeted BBB permeability without causing vascular damage, thereby enhancing the safety and efficacy of drug delivery and liquid biopsy procedures.
Implementation Method 1
Focused ultrasound can be used to safely open or increase the permeability the blood-brain barrier (BBB) temporarily
Implementation Method 2
The processor circuitry is configured to control the ultrasound-based BBB opening procedure as a result of the physiologic signals
Implementation Method 3
obtain a physiologic signal, such as an electroencephalography (EEG) signal
Data Source
AI summary
Examples are directed to devices, methods, and systems for determining opening or increased permeability of a blood-brain barrier (BBB) of a patient. An example device comprises memory circuitry that stores a set of non-transitory instructions, and processor circuitry coupled to the memory circuitry and configured to execute the instructions to determine opening or increased permeability of a BBB of a patient during an ultrasound-based BBB opening procedure using physiologic signals obtained from the patient.