Long afterglow imaging system and method based on ultrasonic frequency resonance amplification
By designing a fluorophore-matrix composite structure to achieve ultrasonic frequency resonance amplification, the problem of low energy conversion efficiency in ultrasound-induced afterglow imaging was solved, resulting in a significant enhancement of afterglow brightness and improvement in deep tissue imaging.
Patent Information
- Application Number
- CN202610034373.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-01-12
- Publication Date
- 2026-02-13
AI Technical Summary
Existing ultrasound-induced afterglow imaging technology suffers from low energy conversion efficiency and insufficient afterglow brightness, which limits imaging sensitivity and application depth.
By designing a fluorophore-matrix composite structure, a precise match between the ultrasonic excitation frequency and the inherent vibration frequency of the composite material is achieved. Acoustic resonance is then used to efficiently convert acoustic energy into chemical energy and amplify it into a persistent optical afterglow signal.
It achieves an order-of-magnitude enhancement in afterglow brightness, improves the imaging signal-to-noise ratio, significantly enhances the imaging capability of deep tissues, and increases signal strength by at least 10 times, preferably by more than 20 times.
Smart Images
Figure CN121512460A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of medical imaging and nanomaterial technology, more particularly, to a long afterglow imaging system and method based on ultrasonic frequency resonance amplification. BACKGROUND
[0002] Long afterglow imaging technology has great potential in the biomedical field due to its advantages such as no need for real-time excitation light, effective suppression of tissue autofluorescence, high signal-to-noise ratio, etc. However, existing technologies mainly rely on optical (such as ultraviolet, visible light) or high-energy radiation (such as X-rays) excitation, which has inherent limitations such as limited tissue penetration depth, potential light damage or radiation hazards, etc.
[0003] In recent years, ultrasonic-induced afterglow has been proposed as a non-invasive and deep-penetration alternative, which usually indirectly triggers afterglow luminescence through ultrasonic-triggered sonochemical processes (such as reactive oxygen species generation). However, due to the dependence of traditional sonochemical processes on random molecular collisions, ultrasonic energy cannot be effectively directed and amplified, resulting in generally low energy conversion efficiency of existing ultrasonic-induced afterglow systems, insufficient afterglow brightness, and constraints on imaging sensitivity and application depth. SUMMARY
[0004] To solve the above technical problems, the present application provides a long afterglow imaging system and method based on ultrasonic frequency resonance amplification, which realizes precise matching of ultrasonic excitation frequency and inherent vibration frequency of the composite material by carefully designing the composite structure of fluorophore-matrix, thereby efficiently converting acoustic energy into chemical energy and ultimately amplifying it into persistent optical afterglow signals.
[0005] The technical solutions provided by the present application are as follows: In a first aspect, the present application provides a long afterglow imaging system based on ultrasonic frequency resonance amplification, comprising a resonance response unit and a frequency matching excitation unit. The resonance response unit comprises composite nanoparticles formed by carbon nanodots and amphiphilic block copolymers in a predetermined mass ratio, and the acoustic resonance frequency of the composite nanoparticles matches the target ultrasonic frequency. The frequency matching excitation unit is used to emit ultrasonic waves matching the acoustic resonance frequency of the resonance response unit, to excite the composite nanoparticles to produce long afterglow emission amplified by resonance.
[0006] In one possible implementation, the predetermined mass ratio of the carbon nanodots and the amphiphilic block copolymer is 1:(25-500).
[0007] In one possible implementation, different preset mass ratios correspond to different characteristic sizes of the composite nanomaterials; the acoustic resonance frequency of the composite nanomaterials is inversely proportional to the characteristic size of the composite nanomaterials.
[0008] In one possible implementation, the amphiphilic block copolymer is Pluronic F127, and the optimal mass ratio between the carbon nanodots and Pluronic F127 is 1:83, and the acoustic resonance frequency is 1 MHz.
[0009] In one possible implementation, the ultrasonic frequency of the ultrasonic wave emitted by the frequency-matched excitation unit is 0.2 MHz to 15 MHz.
[0010] In one possible implementation, for the composite nanoparticles formed by the carbon nanodots and Pluronic F127 in an optimal mass ratio of 1:83, the matched ultrasonic frequency is 0.5 MHz to 2 MHz.
[0011] In a second aspect, the present application provides a use of the long-afterglow imaging system according to any one of the first aspect in the preparation of a medical imaging preparation or device for deep tissue optical imaging, tumor diagnosis, image-guided surgery, or monitoring of a treatment process.
[0012] In a third aspect, the present application provides a long-afterglow imaging method based on ultrasonic frequency resonance amplification, comprising: applying the resonance response unit according to any one of the first aspect to a target region; using a frequency-matched excitation unit to irradiate the target region with ultrasonic waves matched in frequency with the resonance frequency of the resonance response unit; after stopping the ultrasonic irradiation, detecting a long-afterglow optical signal generated by the resonance amplification effect to obtain an image of the target region.
[0013] Compared with the prior art, the technical solution provided by the present application has the following beneficial effects: The present application first proposes and constructs a long-afterglow imaging system based on ultrasonic frequency resonance amplification effect. The system realizes precise matching of the ultrasonic excitation frequency and the inherent vibration frequency of the composite material by carefully designing the composite structure of the fluorophore-matrix, thereby efficiently converting acoustic energy into chemical energy (reactive oxygen) and finally amplifying it into a persistent optical afterglow signal. Through frequency matching, the afterglow brightness is enhanced by orders of magnitude, solving the core problem of weak ultrasonic-induced afterglow signal. The size-frequency relationship disclosed provides a universal theoretical framework for rationally designing ultrasonic response probes with different resonance frequencies. BRIEF DESCRIPTION OF DRAWINGS
[0014] Figure 1This is a schematic diagram comparing the afterglow performance of different fluorophore matrices at non-resonance and resonance frequencies in this application.
[0015] Figure 2 This is a schematic diagram of the ultrasonic-induced afterglow performance characterization results of carbon nanodot-based resonant response units (p-CDs), including power, time, frequency dependence, and decay curves.
[0016] Figure 3 This is a schematic diagram of transmission electron microscopy images showing the morphological evolution of composite materials under different composition ratios.
[0017] Figure 4 The diagram illustrates the inverse monotonic law based on the analysis results of the relationship between the size of composite materials and the ultrasonic resonance frequency in finite element simulation.
[0018] Figure 5 This is a schematic diagram comparing the tissue penetration depth of the resonance amplification system and the photoexcitation system.
[0019] Figure 6 This is a schematic diagram demonstrating the application of in vivo tumor ultrasound resonance afterglow imaging and image-guided tumor resection based on the system of this application.
[0020] Figure 7 A flowchart of a long-persistence imaging method based on ultrasonic frequency resonance amplification provided in this application. Detailed Implementation
[0021] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the embodiments of this application. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application.
[0022] Acoustic resonance, a classic physical phenomenon, can maximize energy absorption and enhance the local field when the frequency of an external sound wave matches the natural frequency of the system. However, this principle has not yet been systematically explored and applied in the field of ultrasound-induced afterglow imaging. To overcome the problems of low energy conversion efficiency and insufficient signal strength in existing ultrasound-induced afterglow technologies, this application proposes and constructs for the first time a long-persistence imaging system based on the ultrasonic frequency resonance amplification effect. The size-frequency resonance selection law in the ultrasound-induced afterglow system is revealed, and based on this law, a nanoprobe with resonant response is constructed, namely the long-persistence imaging system described in this application.
[0023] The technical solutions provided in this application will now be described in detail through specific embodiments.
[0024] Example 1
[0025] The long afterglow imaging system based on ultrasonic frequency resonance amplification provided by the embodiment one of the application comprises a resonance response unit p-CDs and a frequency matching excitation unit.
[0026] The resonance response unit p-CDs comprises composite nanoparticles formed by carbon nanodots and amphiphilic block copolymer according to a preset mass ratio.
[0027] Specifically, in the embodiment of the application, carbon nanodots are used as a sonosensitizer and a light center, embedded into a three-dimensional gel network matrix formed by amphiphilic block copolymer to form a composite nanostructure. By adjusting the mass ratio of carbon nanodots to the amphiphilic block copolymer matrix, the overall size and mechanical modulus of the composite material can be accurately controlled, so as to set its inherent acoustic resonance frequency. The acoustic resonance frequency of the prepared composite nanoparticles is matched with the target ultrasonic frequency.
[0028] The frequency matching excitation unit is specifically used for providing ultrasonic radiation. The working frequency is selected and matched according to the inherent acoustic resonance frequency of the resonance response unit, so as to emit ultrasonic waves matched with the inherent acoustic resonance frequency of the resonance response unit. When the excitation frequency and the acoustic resonance frequency are matched, the system occurs acoustic resonance, which excites the composite nanoparticles to generate long afterglow emission through resonance amplification, so as to realize localized and efficient deposition and amplification of ultrasonic energy.
[0029] Preferably, the ultrasonic frequency generated by the frequency matching excitation unit is 0.2 MHz to 15 MHz.
[0030] Compared with the prior art, the technical scheme provided by the embodiment one of the application has the following beneficial effects: The application first systematically applies the principle of acoustic resonance to ultrasonic-induced afterglow imaging, realizes the paradigm shift from random acoustic chemistry to directional acoustic energy amplification. Through frequency matching, the afterglow brightness is enhanced by orders of magnitude, which solves the core problem of weak ultrasonic-induced afterglow signal. Combined with the deep penetration characteristics of ultrasonic and the high signal-to-noise ratio output of resonance enhancement, high-quality optical imaging of deep tissues is realized. Compared with non-matched frequency or traditional non-resonance system, the imaging quality is improved by at least 10 times, and preferably more than 20 times.
[0031] Embodiment two
[0032] In the embodiment of the application, a series of composite nanoparticles (p-CDs) with the mass ratio of CDs to F127 being 1:500, 1:167, 1:83 and 1:25 are prepared by emulsification-solvent evaporation method using plant-derived carbon nanodots CDs and Pluronic F127 as raw materials. The initial afterglow intensity is measured under the excitation of 1 MHz ultrasonic (2 W / cm², 2 minutes).
[0033] FIG. 8 shows the schematic diagram of the comparison of the afterglow performance of different fluorophore matrixes provided in Example 2 of the present application at non-resonance and resonance frequencies. Figure 1 As shown in FIG. 8, the preset mass ratio of carbon nanodots and amphiphilic block copolymer can be adjusted in the range of 1:25 to 1:500. When the above-mentioned amphiphilic block copolymer is Pluronic F127, and the mass ratio of CDs to F127 is 1:83, the above-mentioned composite nanomaterial forms a micron-sized three-dimensional gel network structure, and the matching ultrasonic frequency is 0.5 MHz to 2 MHz, and the optimal ultrasonic resonance frequency is about 1 MHz. At this time, the afterglow intensity reaches the peak value, and is 51 times higher than that of other ratios and the original material, indicating that this ratio is the optimal resonance composition of the system. Figure 1 Example 3
[0034] In the examples of the present application, the optimal composition p-CDs prepared in Example 2 above are respectively subjected to ultrasonic excitation at 1 MHz and 3 MHz, and the afterglow imaging is obtained to verify the frequency matching and resonance amplification effect.
[0035] FIG. 9 shows the ultrasonic-induced afterglow performance characterization results of the carbon nanodot-based resonance response unit (p-CDs) provided in Example 3 of the present application, including power, time, frequency dependence and decay curve.
[0036] As shown in FIG. 9, the signal intensity under 1 MHz excitation is 29 times that under 3 MHz. Combined with the morphology analysis of FIG. 8 and the finite element simulation of FIG. 7, it is confirmed that the 1 MHz ultrasonic and the 1:83 p-CDs gel network have frequency resonance, thereby realizing efficient energy conversion and signal amplification. Figure 2 Figure 2 Example 4 Figure 3 Figure 4 In Example 4 of the present application, the p-CDs aqueous solution of the optimal composition is placed below the ex vivo chicken breast tissue, and the tissue thickness is 0.5 cm to 3.0 cm. The matching ultrasonic (1 MHz) or red light (660 nm) is respectively used for excitation above. As shown in FIG. 10, the afterglow signal detection penetrating the tissue shows that the ultrasonic resonance afterglow can still maintain a clear and distinguishable signal at a thickness of 2.5 cm. While the light-excited afterglow signal is close to the background at 2.0 cm, and the penetration depth of the traditional fluorescence imaging is less than 1.0 cm. This example directly demonstrates the significant advantage of the long afterglow imaging system provided in the present application in deep tissue imaging.
[0037] Example 5
[0038] In Example 5 of the present application, the p-CDs aqueous solution of the optimal composition is placed below the ex vivo chicken breast tissue, and the tissue thickness is 0.5 cm to 3.0 cm. The matching ultrasonic (1 MHz) or red light (660 nm) is respectively used for excitation above. As shown in FIG. 10, the afterglow signal detection penetrating the tissue shows that the ultrasonic resonance afterglow can still maintain a clear and distinguishable signal at a thickness of 2.5 cm. While the light-excited afterglow signal is close to the background at 2.0 cm, and the penetration depth of the traditional fluorescence imaging is less than 1.0 cm. This example directly demonstrates the significant advantage of the long afterglow imaging system provided in the present application in deep tissue imaging. Figure 5 Example 5
[0039] In Example 5 of the present application, the p-CDs aqueous solution of the optimal composition is placed below the ex vivo chicken breast tissue, and the tissue thickness is 0.5 cm to 3.0 cm. The matching ultrasonic (1 MHz) or red light (660 nm) is respectively used for excitation above. As shown in FIG. 10, the afterglow signal detection penetrating the tissue shows that the ultrasonic resonance afterglow can still maintain a clear and distinguishable signal at a thickness of 2.5 cm. While the light-excited afterglow signal is close to the background at 2.0 cm, and the penetration depth of the traditional fluorescence imaging is less than 1.0 cm. This example directly demonstrates the significant advantage of the long afterglow imaging system provided in the present application in deep tissue imaging.
[0040] Intratumorally inject p-CDs in a mouse model carrying subcutaneous tumors. Apply 1 MHz ultrasound pulses (2 minutes) to the tumor site for excitation. After excitation, use the afterglow signal for long-time imaging without using any real-time excitation light source. As shown in FIG. 7, after a single ultrasound excitation, the tumor site can generate a high signal-to-noise ratio (SNR > 11.5) afterglow signal that lasts more than 60 minutes. Using this continuously emitted afterglow as a navigation light, surgeons successfully achieved precise identification of the tumor boundary and complete resection, without the need for additional illumination or imaging equipment during surgery. Figure 6
[0041] Example Six
[0042] The embodiments of the present application provide a long afterglow imaging method of ultrasound frequency resonance amplification. As shown in FIG. 1, the specific implementation steps of the above method include: Figure 7 Step 101, apply the resonance response unit as described in any one of embodiments one to three to the target area.
[0043] Step 102, use a frequency-matched excitation unit to irradiate the target area with ultrasound waves that match the resonance frequency of the above-mentioned resonance response unit.
[0044] Step 103, after stopping the ultrasound irradiation, detect the long afterglow optical signal generated by the resonance amplification effect to obtain an image of the target area.
[0045] Compared with the prior art, the technical scheme provided by the embodiments of the present application has the following beneficial effects: In view of the problems of low energy conversion efficiency and insufficient signal strength of the existing ultrasound-induced afterglow imaging technology, the present application first proposes and constructs a composite probe system composed of carbon nanodots and an amphiphilic polymer matrix, and by accurately controlling the composition and microstructure of the composite material, the characteristic size is resonantly matched with a specific ultrasound frequency.
[0046] When the external excitation ultrasound frequency matches the inherent resonance frequency, the system undergoes acoustic resonance, realizing the localized and efficient aggregation and amplification of ultrasound energy, thereby significantly enhancing the sonochemical process (such as active oxygen generation) and finally converting into a high-intensity, long-lifetime optical afterglow signal. This resonance amplification effect makes the afterglow brightness increase by up to 51 times, and after a single short-time ultrasound excitation, a near-infrared afterglow can be generated for more than 240 minutes, and a tissue penetration depth of up to 2.5 centimeters is achieved, with a signal-to-noise ratio significantly better than traditional imaging methods.
[0047] The present application discloses the inverse resonance law between the size of the material and the ultrasound frequency, providing a new paradigm for designing high-performance ultrasound response probes, which has important application value in the fields of deep tumor high-contrast imaging, image-guided precise surgery, and long-term in vivo monitoring.
[0048] While embodiments of the present application have been shown and described, it is to be understood that the embodiments described are merely divergences and modifications and not limitations of the scope of the application, which is defined by the appended claims and their equivalents.
Claims
1. A long-persistence imaging system with ultrasonic frequency resonant amplification, characterized in that, Includes resonant response units and frequency matching excitation units; The resonant response unit includes composite nanoparticles formed by carbon nanodots and amphiphilic block copolymers in a preset mass ratio, wherein the acoustic resonance frequency of the composite nanoparticles matches the target ultrasonic frequency. The frequency matching excitation unit is used to emit ultrasonic waves that match the acoustic resonance frequency of the resonance response unit, thereby exciting the composite nanoparticles to produce a long afterglow emission amplified by resonance.
2. The long-persistence imaging system with ultrasonic frequency resonant amplification according to claim 1, characterized in that, The preset mass ratio of the carbon nanodots to the amphiphilic block copolymer is 1:(25-500).
3. The long-persistence imaging system with ultrasonic frequency resonant amplification according to claim 1, characterized in that, Different preset mass ratios correspond to the formation of composite nanomaterials with different feature sizes; the acoustic resonance frequency of the composite nanomaterial is inversely proportional to the feature size of the composite nanomaterial.
4. The long-persistence imaging system with ultrasonic frequency resonant amplification according to claim 1, characterized in that, The amphiphilic block copolymer is Pluronic F127, and the optimal mass ratio between the carbon nanodots and Pluronic F127 is 1:83, corresponding to an acoustic resonance frequency of 1MHz.
5. The long-persistence imaging system with ultrasonic frequency resonant amplification according to claim 1, characterized in that, The frequency matching excitation unit emits ultrasonic waves at frequencies ranging from 0.2 MHz to 15 MHz.
6. The long-persistence imaging system with ultrasonic frequency resonant amplification according to claim 4, characterized in that, For composite nanoparticles formed from the carbon nanodots and Pluronic F127 at an optimal mass ratio of 1:83, the matched ultrasonic frequency is 0.5 MHz to 2 MHz.
7. The use of a long-persistence imaging system as described in any one of claims 1 to 6 in the preparation of medical imaging agents or devices for deep tissue optical imaging, tumor diagnosis, image-guided surgery, or monitoring of treatment processes.
8. A long-persistence imaging method with super-frequency resonant amplification, characterized in that, include: Apply the resonant response unit as described in any one of claims 1 to 6 to the target region; The target area is irradiated with an ultrasonic wave that matches the resonant frequency of the resonant response unit using a frequency-matched excitation unit. After the ultrasonic radiation is stopped, the long-persistent optical signal generated by the resonant amplification effect is detected to obtain an image of the target area.