Switchable Photoacoustic Probes for Deep-Tissue Background Suppression
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Solution Overview
Problem
Existing photoacoustic imaging techniques face challenges with strong light scattering in tissue, leading to a tradeoff between spatial resolution and penetration depth, and suffer from background signals from endogenous biomolecules like hemoglobin, which hamper accurate spectral unmixing, especially at depths beyond the optical diffusion limit.
Innovation Solution
Employing reversibly-switchable photoacoustic probes, such as bacterial phytochrome BphP1, that can switch between high and low absorbance states, allowing for differential PA imaging by subtracting PA signals obtained in different states to isolate probe signals from background noise.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional photoacoustic imaging is used, then optical absorption contrast can be detected, but strong light scattering in tissue leads to a tradeoff between spatial resolution and penetration depth
Solution Approach 1:
The patent employs reversibly-switchable probes that change their optical absorption parameters in response to light stimulation. By switching the probes between different absorption states, the system can differentiate probe signals from background signals even at deep tissue depths, effectively resolving the tradeoff between spatial resolution and penetration depth through parameter modulation rather than physical separation.
2Loss of information
If conventional PA imaging is used to detect optical absorption contrast, then molecular imaging information can be obtained, but strong background signals from endogenous biomolecules like hemoglobin hamper accurate spectral unmixing
Solution Approach 1:
The patent applies preliminary action by stimulating the reversibly-switchable probes with specific wavelength light before the main imaging measurement. This preliminary stimulation switches the probes to a known state, allowing the subsequent imaging signal to be differentially processed and separated from background signals through knowledge of the probe's switched state, thereby preserving molecular imaging information while improving spectral unmixing accuracy.
Solution Approach 2:
The system uses feedback by monitoring the state of reversibly-switchable probes and adjusting the imaging acquisition accordingly. The probe switching state provides feedback information that is used to differentiate probe signals from background signals during image reconstruction, enabling accurate spectral unmixing even in the presence of strong endogenous biomolecule signals.
3Adaptability or versatility
If GFP-like fluorescent proteins are used as probes, then genetic encoding is achieved, but they lack strong optical absorption at wavelengths beyond 610 nm and are prone to photobleaching
Solution Approach 1:
The patent replaces GFP-like proteins with reversibly-switchable probes such as bacterial phytochromes that have fundamentally different optical absorption parameters. These probes exhibit strong absorption at wavelengths beyond 610 nm (including near-infrared wavelengths) and possess reversible photoswitching capability instead of photobleaching, thereby maintaining genetic encoding versatility while dramatically improving optical absorption strength and photostability through parameter changes in the probe molecules themselves.
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
Enhances image resolution and sensitivity by significantly reducing background noise, enabling high-resolution imaging of deep-tissue structures with improved spatial and axial resolution, particularly suitable for molecular imaging.
Implementation Method 1
Photoacoustic (PA) tomography (PAT), on the other hand, breaks the depth and resolution limitations of pure optical imaging by acoustically detecting optical absorption contrast. In PAT, light-induced ultrasound waves are detected outside tissue to form an image that maps the original optical energy deposition inside the tissue.
Implementation Method 2
Employing reversibly-switchable photoacoustic probes, such as bacterial phytochrome BphP1, that can switch between high and low absorbance states
Data Source
AI summary
Reversibly switchable photoacoustic tomography (RS-PAT), a photoacoustic technique with enhanced sensitivity and resolution, is disclosed. RS-PAT utilizes a subtractive process for the formation of a photoacoustic image of a region containing a plurality of switchable photoacoustic probes. In various aspects, the photoacoustic detection in RS-PAT imaging occurs minimally twice: a first image obtained when the photoacoustic probe is in active (absorbing or ON) state and a second image obtained when the photoacoustic probe is in an inactive (less-absorbing or OFF) state. Subtraction of the second image from the first image is used to obtain the RS-PAT image.