In vivo device and method for skin fillers

Abstract

The application provides a skin filler in-vivo detection device and method, relates to the technical field of skin and subcutaneous tissue detection, and comprises a light source and a spectrometer module, a probe area, the light source and the spectrometer module are used for providing OCT broadband interference light and Raman excitation light, and receiving and processing OCT interference signals and Raman scattering signals; the probe area is integrated, and the probe area is provided with optical beam combining and separating elements, a two-dimensional scanning galvanometer and a scanning lens; the application breaks through the limitation of traditional evaluation means, realizes real-time monitoring in situ in the human body, adopts full-optical non-invasive design, the probe can be directly attached to the human skin, through coaxial dual-mode light paths, long-period longitudinal follow-up of the same part of the human body is carried out under the premise of non-invasion and non-radiation, the most real in-vivo metabolism data of the human body is acquired, and the problems that the traditional animal model data is greatly different from the human body and the human face cannot be destructively biopsied are solved.

Description

Technical Field

[0001] This invention relates to the field of skin and subcutaneous tissue testing technology, and more particularly to a device and method for in vivo testing of dermal fillers. Background Technology

[0002] With the rapid development of the medical aesthetics industry, various dermal fillers such as hyaluronic acid, recombinant collagen, and polylactic acid are widely used in facial rejuvenation, mesotherapy, and other minimally invasive injection procedures. Currently, clinical and research evaluations of the safety, in vivo degradation patterns, and biocompatibility of dermal fillers mainly rely on medical ultrasound equipment and single-modal OCT imaging equipment, which have been applied to some extent in skin analysis.

[0003] In existing detection technologies, medical ultrasound equipment has low spatial resolution and cannot identify chemical components, only able to locate and characterize but not monitor the microscopic distribution of fillers; single-modal OCT equipment, although having micron-level resolution, cannot distinguish between fillers with similar optical scattering characteristics and host tissue, nor can it track the biochemical state of materials; Raman spectroscopy can detect material properties and is used to detect the epidermal penetration of cosmetics, but its penetration depth is low and cannot detect signals at deeper levels. Spatial offset Raman has a deep penetration depth, but the hardware and OCT are not co-located, the optical path is not coaxial, and there are cumbersome post-calibration problems; a few OCT-Raman combined devices use free-space optical path superposition, resulting in serious axial color difference, leading to misalignment of structure and component detection, which cannot meet the clinical needs for non-invasive, accurate, and deep detection. Therefore, this invention proposes an in vivo detection device and method for dermal fillers to solve the problems existing in the prior art. Summary of the Invention

[0004] To address the aforementioned issues, this invention proposes an in vivo detection device and method for dermal fillers, overcoming the limitations of traditional evaluation methods and achieving true in-situ real-time monitoring of the human body. Employing a fully optical, non-invasive design, the probe can be directly attached to human skin. Through a coaxial dual-mode optical path, long-term longitudinal follow-up of the same human body site is conducted non-invasively and without radiation, obtaining the most accurate in vivo metabolic data. This solves the problems of significant differences between traditional animal model data and human data, and the inability to perform destructive biopsies on the human face.

[0005] To achieve the objectives of this invention, the invention is implemented through the following technical solution: a skin filler in vivo detection device, comprising a light source and spectrometer module and a probe area, wherein the light source and spectrometer module is used to provide OCT broadband interference light and Raman excitation light, and to receive and process OCT interference signals and Raman scattering signals;

[0006] The probe area is integrated and includes optical beam combining and separating elements, a two-dimensional scanning galvanometer, and a scanning lens. The OCT broadband interference light and the Raman excitation / collection light are coaxially measured within the probe area, sharing a common scanning lens. This is used for non-invasive structural imaging and chemical composition detection of skin tissue and its internal fillers. The two-dimensional scanning galvanometer can drive the Raman excitation beam to form a ring excitation spot, achieving in-situ excitation or dynamic ring scanning excitation.

[0007] Further improvements are made in the following aspects: the light source and spectral detection module include an OCT light source, a monochromatic Raman excitation light source, an OCT detection module, and a Raman spectrometer; the OCT light source can be a low-coherence broadband light source or a swept-frequency light source, used to generate OCT detection light; when using a low-coherence broadband light source, its center wavelength is preferably 800–1310 nm, and its bandwidth is preferably 50–150 nm; when using a swept-frequency light source, its center wavelength is preferably 800–1310 nm, and its scanning wavelength range is preferably 50–150 nm; the monochromatic Raman excitation light source is a semiconductor laser light source, with a wavelength preferably 532–1064 nm, more preferably 785 nm, and an output power adjustment range of 5–100 nm. mW; the OCT detection module can be an OCT detector or a photodetector, used to process OCT interference signals; when frequency domain OCT is used, the OCT detection module is an OCT detector; when frequency-sweep OCT is used, the OCT detection module is a balanced photodetector or other photodetector; the Raman spectrometer is used to process Raman scattering signals, and the spectral range is preferably 200–3000 cm⁻¹. -1 It can also perform baseline correction, characteristic peak extraction, and spectral analysis.

[0008] Further improvements are made in the following aspects: The optical beam combining and separating elements include an optical fiber coupler, a collimating lens, a dichroic mirror 1, a dichroic mirror 2, a first reflecting mirror, and a focusing lens; the optical fiber coupler is used to split the broadband beam emitted by the OCT light source into a reference beam and a sample beam. The reference beam is collimated by the collimating lens and then incident on the reference arm reflecting mirror, returning to the optical fiber coupler along the original path; the dichroic mirror 1 is used to combine the OCT sample beam and the Raman excitation beam. The OCT sample beam is transmitted through the dichroic mirror 1, and the Raman excitation beam is reflected by the first reflecting mirror and then reflected at the dichroic mirror 1, coaxially coinciding with the OCT sample beam; the dichroic mirror 2 is used to separate the OCT signal echo and the Raman scattering signal. The OCT signal echo is transmitted through the dichroic mirror 2, and the Raman scattering light is reflected at the dichroic mirror 2.

[0009] A further improvement lies in that: the two-dimensional scanning galvanometer is connected to a control system, and the control system applies sinusoidal alternating current control signals with a phase difference to the X-axis and Y-axis of the two-dimensional scanning galvanometer to drive the Raman excitation beam to deflect rapidly in a circular motion in the focal area of the skin to be measured, forming an annular excitation spot; the diameter of the annular excitation spot can be adjusted according to the objective lens field of view and the galvanometer control signal.

[0010] A further improvement lies in that: the core diameter of the collection optical fiber of the Raman spectrometer is conjugate to the static geometric center origin directly below the scanning lens, and the Raman collection optical path does not pass through the two-dimensional scanning galvanometer, which is used for physically shielding the strong backscattering and fluorescence interference of the epidermis; the collection optical fiber is connected to a focusing lens, and the focusing lens is used to couple the Raman scattered light into the collection optical fiber.

[0011] A further improvement lies in that: no dedicated dispersion compensation lens is provided in the probe area, and the OCT detection light and the Raman excitation light are transmitted through a common optical path and then acted on the detection area by the scanning module; by adjusting the annular scanning diameter of the inverse spatial offset Raman, the effective sampling depth of the Raman signal can be changed, so as to realize the selective Raman detection of target areas with different buried depths and match the structural depth information obtained by OCT; the scanning lens is preferably an achromatic lens group to improve the transmission and focusing performance of light beams with different wavelengths in the probe area. Adjust the scanning diameter, where d1 < d2 < d3. The smaller the diameter, the shallower the source of the scattered photons collected, and the larger the diameter, the deeper the source of the scattered photons collected.

[0012] A further improvement lies in that: in the optical path structure of the present invention, the dichroic mirror is arranged behind the scanning galvanometer and in front of the focusing lens. After the excitation light is deflected by the scanning galvanometer, its incident direction changes with the scanning state of the galvanometer, and different-diameter annular excitation positions are formed on the sample surface under the action of the focusing lens, so as to realize the scanning illumination of different lateral offset positions. Correspondingly, the Raman scattered photons generated inside the sample are scattered multiple times and then propagate to the central area of the sample surface, and are collected by the focusing lens and returned along a fixed collection optical path. Since the dichroic mirror is located behind the scanning galvanometer, the returned Raman collection light no longer passes through the deflection process that changes with the scanning of the galvanometer before entering the spectral splitting path, so its collection angle and collection direction do not change with the scanning state of the galvanometer and always remain consistent. Based on this structure, while changing the annular diameter of the excitation light, a stable Raman signal collection geometric relationship can be maintained, thereby effectively improving the consistency, stability and comparability of signal collection under different sampling depth conditions, and facilitating the detection purpose of obtaining information of different depth layers by adjusting the spatial offset amount of the excitation spot.

[0013] The method for in-vivo detection of skin fillers includes the following steps:

[0014] S1: Start the light source and spectrometer module, preheat, and adjust the parameters to ensure that the OCT light source, monochromatic Raman excitation source, OCT detector, and Raman spectrometer are working stably.

[0015] S2: Place the probe on the area of ​​the skin filler to be tested, use the OCT preview function to locate the detection area, and ensure that the scanning lens is focused on the depth of the filler;

[0016] S3: The broadband beam emitted by the OCT light source is split into a reference beam and a sample beam by the fiber optic coupler. The reference beam is reflected back to the fiber optic coupler after passing through the collimating lens and the reference arm mirror. The sample beam is focused on the skin tissue and filler area to be tested by passing through the collimating lens, dichroic mirror 1, two-dimensional scanning galvanometer, dichroic mirror 2, and scanning lens.

[0017] S4: The Raman excitation beam emitted by the monochromatic Raman excitation source is collimated by the collimating lens and reflected by the first reflecting mirror. It then illuminates the dichroic mirror 1 and is reflected, coaxially coinciding with the OCT sample beam and focusing together on the area to be measured. The two-dimensional scanning galvanometer is controlled to select the in-situ excitation mode or the ring scanning excitation mode to excite the filler.

[0018] S5: Collect OCT signal echo and Raman scattering signal: The OCT signal echo returns along the original path, interferes with the reference beam, and is guided to the OCT detector for processing to obtain a three-dimensional structural image of the filler; the Raman scattered light returns along the original scanning optical path, is reflected by the dichroic mirror 2, and is coupled to the collecting fiber by the focusing lens, and is sent to the Raman spectrometer for processing to obtain the chemical composition information of the filler;

[0019] S6: Fusion analysis of OCT structural images and Raman spectral data to complete in vivo detection of dermal fillers, and long-term follow-up detection can be performed as needed.

[0020] A further improvement is made in S4, where, in the annular scanning excitation mode, the scanning frequency of the two-dimensional scanning galvanometer and the diameter of the annular excitation spot are adjusted by the control system, and appropriate scanning parameters are selected based on the injection depth and distribution density of the filler.

[0021] Further improvements are made in S5: the three-dimensional structural image of the filler obtained after processing by the OCT detector; the characteristic chemical bonds of the filler are accurately identified after processing by the Raman spectrometer, the degradation rate and cross-linking degree of the filler are quantitatively evaluated, and early inflammatory responses are warned by capturing abnormal lipid / protein ratios.

[0022] A further improvement is made in S6, where, during long-term follow-up testing, tests are conducted at different time points after filler injection under the same testing parameters. The OCT structural images and Raman spectral data at each time point are compared to analyze the in vivo degradation pattern and biocompatibility of the filler, and foreign body rejection or inflammatory reactions are detected in a timely manner.

[0023] The beneficial effects of this invention are as follows:

[0024] 1. This invention breaks through the limitations of traditional evaluation methods, realizing true in-situ real-time monitoring of the human body. It adopts a fully optical non-invasive design, and the probe can be directly attached to the human skin. Through a coaxial dual-mode optical path, it can perform long-term longitudinal follow-up on the same part of the human body without invasiveness or radiation, and obtain the most realistic in vivo metabolic data. It solves the problems of large differences between traditional animal model data and human data and the inability to perform destructive biopsy on the human face.

[0025] 2. This invention breaks through the resolution bottleneck of ultrasound imaging, achieving micron-level fine distribution analysis. It integrates OCT technology and utilizes the interference principle of near-infrared broadband light to increase the spatial resolution to the micron level of 1~10μm. Compared with high-frequency skin ultrasound at the level of hundreds of micrometers, it can clearly present the three-dimensional microscopic distribution morphology, diffusion boundary and internal microporous structure of fillers in the dermis and subcutaneous tissue, solving the defect that ultrasound cannot distinguish the microscopic interweaving state of fillers and surrounding tissue collagen fiber network.

[0026] 3. This invention fills the gap in chemical composition and inflammation monitoring, realizes structure-biochemical dual-dimensional diagnosis, integrates Raman spectroscopy optical path, and utilizes the "molecular fingerprint" characteristics of Raman spectroscopy to accurately identify the characteristic chemical bonds of macromolecular materials. It can not only see the structure of fillers through OCT, but also identify the components through Raman spectroscopy. It can quantitatively assess the degradation rate of collagen and the cross-linking and breakage of hyaluronic acid in real time, and provide early warning of early inflammatory reactions caused by injection, thus solving the problem that simple morphological imaging cannot provide chemical molecular information.

[0027] 4. This invention utilizes mirror-driven inverse spatial offset Raman to overcome the challenge of deep-layer detection. By reusing a two-dimensional scanning mirror and applying a sinusoidal AC control signal with a phase difference, the Raman excitation beam is driven to deflect rapidly in a circular motion to form a ring-shaped excitation spot. This significantly reduces the local optical power density and increases the total injected optical power while adhering to tissue MPE and thermal damage thresholds. Combined with center point signal collection, it avoids epidermal fluorescence interference and achieves millimeter-level subcutaneous depth detection. This solves the problems of shallow penetration and skin burns caused by blindly increasing power in traditional confocal Raman. Attached Figure Description

[0028] Figure 1 This is a diagram illustrating the composition of the present invention;

[0029] Figure 2This is a schematic diagram of the skin after PLLA injection measured using OCT according to the present invention;

[0030] Figure 3 This is a schematic diagram of different dermal fillers measured by Raman spectroscopy according to the present invention;

[0031] Figure 4 This is a schematic diagram of the Raman spectroscopy measurement of the skin after injection according to the present invention;

[0032] Figure 5 This is a schematic diagram of the scattered photons collected by the present invention;

[0033] Figure 6 This is a schematic diagram of the optical path structure of the present invention. Detailed Implementation

[0034] To enhance understanding of the present invention, the present invention will be further described in detail below with reference to embodiments. These embodiments are only used to explain the present invention and do not constitute a limitation on the scope of protection of the present invention.

[0035] Example 1

[0036] To verify the feasibility of the in vivo detection technology route for dermal fillers described in this invention, basic experiments based on optical coherence tomography (OCT) and Raman spectroscopy were conducted to verify the visualization capability of the morphological distribution of dermal fillers in skin tissue and the identification capability of their chemical components.

[0037] In this embodiment, a spectral OCT system with a center wavelength of 1310 nm was used to perform tomographic imaging of the injected skin area, and a Raman spectroscopy system with an excitation wavelength of 785 nm was used to acquire spectra of different dermal filler samples. The samples tested included ex vivo dermal filler samples and in vivo samples after injection into skin tissue. The dermal fillers included hyaluronic acid (HA) fillers, poly-L-lactic acid (PLLA) fillers, and calcium hydroxyapatite (CaHA) fillers.

[0038] 1. OCT in vivo morphological examination

[0039] The 1310 nm spectral domain OCT system was used to scan and image the skin area injected with dermal filler. The results showed that the filler and skin tissue in the injection area exhibited different scattering characteristics in the OCT images.

[0040] like Figure 2 As shown, after hyaluronic acid fillers are injected into the skin, obvious low-scattering regions can be observed in OCT images. Hyaluronic acid appears as a relatively continuous low-scattering dark area in the image, while the skin exhibits a high-scattering signal. After injection, the hyaluronic acid is squeezed into the skin, forming discrete dark areas.

[0041] The above results demonstrate that OCT detection can non-invasively characterize the spatial distribution, depth, and local morphological features of injected dermal fillers, and can distinguish hyaluronic acid carrier regions, thus providing a basis for subsequent chemical component identification.

[0042] 2. In vitro Raman spectroscopy detection of different dermal fillers

[0043] Different types of dermal fillers were analyzed using a 785 nm Raman spectroscopy system. Raman spectral signals were acquired, and the resulting spectra were preprocessed. The preprocessing may include one or more of baseline correction, smoothing, and normalization.

[0044] like Figure 3 As shown, different dermal fillers exhibit distinguishable Raman characteristic spectra. Hyaluronic acid fillers, PLLA fillers, and CaHA fillers each have their own corresponding characteristic peak positions and relative peak intensity distributions, indicating that different types of dermal fillers have significant differences in Raman spectral dimensions.

[0045] The above results demonstrate that Raman spectroscopy can be used to identify the chemical composition of different types of dermal fillers, and a corresponding characteristic spectral database can be established based on this, providing a basis for material identification and comparative analysis in subsequent in vivo testing.

[0046] 3. In vivo Raman spectroscopy detection after dermal filler injection

[0047] Building upon in vitro detection, in vivo Raman spectroscopy was further performed on different dermal fillers injected into skin tissue. During the detection process, 785 nm excitation light was applied to the corresponding area of ​​the skin surface, and Raman scattering signals from the injection site were collected.

[0048] like Figure 4 As shown, although the in vivo Raman spectra of different dermal fillers injected into the skin are affected by the background signal of the skin tissue and scattering attenuation, characteristic peaks related to the corresponding fillers can still be identified after preprocessing. The in vivo spectra of different types of fillers generally correspond to their in vitro spectra.

[0049] The above results demonstrate that the characteristic Raman signals of dermal fillers can still be detected and identified after they are injected into the skin tissue, thus proving the feasibility of in vivo Raman detection of dermal fillers.

[0050] 4. Explanation of the feasibility of the technical solution of the present invention

[0051] The experimental results above show that OCT detection can locate the morphological distribution of dermal fillers after injection, while Raman spectroscopy can distinguish the chemical components of different types of dermal fillers. Therefore, the combined detection technology based on "OCT localization + Raman recognition" can achieve in vivo detection of dermal fillers.

[0052] The experimental results obtained in this embodiment demonstrate that the location and chemical characteristics of dermal fillers in skin tissue can be acquired optically, indicating the feasibility of the combined detection scheme described in this invention. Based on these fundamental verification results, and combined with the Raman detection structure design disclosed in this invention, effective detection and identification of deep dermal fillers can be further achieved.

[0053] Therefore, this embodiment verifies the rationality of the technical route of the present invention from two aspects: morphological characterization and chemical feature recognition, and provides experimental basis for the implementation of the device and method of the present invention.

[0054] Example 2

[0055] according to Figure 1 , 2 As shown in Figures 3, 4, 5, and 6, this embodiment proposes an in vivo detection device and method for dermal fillers, the specific structure of which is as follows:

[0056] The light source and spectrometer module includes an OCT light source, a monochromatic Raman excitation source, an OCT detection module, and a Raman spectrometer. The OCT light source uses a broadband light source with a center wavelength of 1310 nm and a bandwidth of 100 nm to generate broadband OCT interference light. The monochromatic Raman excitation source uses a 785 nm semiconductor laser with an adjustable output power range of 10~100 mW. The OCT detection module has a spectral resolution of 0.1 nm, and the Raman spectrometer has a spectral range of 200~3000 cm⁻¹. -1 These are used to process OCT interference signals and Raman scattering signals respectively;

[0057] The probe area is a highly integrated structure, internally equipped with an optical fiber coupler, a collimating lens, a dichroic mirror 1, a dichroic mirror 2, a first reflecting mirror, a two-dimensional scanning galvanometer, a scanning lens, and a focusing lens. The optical fiber coupler is used to split the broadband beam emitted by the OCT light source into a reference beam and a sample beam. The reference beam is collimated by the collimating lens and then incident on the reference arm reflecting mirror, returning along the original path to the optical fiber coupler. The sample beam is introduced into the probe area through an optical fiber, converted into a parallel beam by the collimating lens, horizontally transmitted through the dichroic mirror 1, incident on the two-dimensional scanning galvanometer, deflected by the galvanometer, passed downward through the dichroic mirror 2, and then focused by the scanning lens onto the skin tissue and filler area to be tested.

[0058] The Raman excitation beam is introduced into the probe area via an optical fiber, collimated by a collimating lens, and then deflected to the right by the first reflecting mirror to illuminate dichroic mirror 1. Reflection occurs at dichroic mirror 1, and the beam coaxially coincides with the OCT sample beam path. The combined dual-mode beam is then incident on the two-dimensional scanning galvanometer, dichroic mirror 2, and scanning lens, illuminating the tissue to be tested. The two-dimensional scanning galvanometer is connected to a control system that can apply mutually orthogonal sinusoidal AC control signals with a phase difference to its X and Y axes, driving the Raman excitation beam to deflect rapidly in a circular motion in the focal region of the skin to be tested, forming a ring-shaped excitation spot. The ring diameter is adjustable from 50 to 500 μm, and the scanning frequency is 1 to 10 kHz.

[0059] Signal Echo and Separation Collection Process: The OCT structural signal light backscattered from the tissue returns along the original path, passes through the scanning lens and galvanometer, and is transmitted through the dichroic mirror 1. It is then coupled back to the fiber coupler by the collimating lens and interferes with the light returning from the reference arm. The interference signal is guided to the OCT detection module for processing to obtain a three-dimensional structural image of the skin and filler with a spatial resolution better than 10 μm and an imaging depth of up to 2 mm. The Raman scattered light (Stokes frequency shift light) generated by the tissue returns along the original scanning optical path and is reflected at the dichroic mirror 2. It is then coupled into the collecting fiber by the focusing lens and transported to the Raman spectrometer for chemical spectrum analysis. The core diameter of the collecting fiber of the Raman spectrometer is conjugate to the static geometric center origin directly below the scanning lens, which can effectively shield the strong backscattering and fluorescence interference from the epidermis.

[0060] The detection method of this embodiment includes the following steps:

[0061] Debug the testing device by starting the OCT light source, monochromatic Raman excitation source, OCT detection module, and Raman spectrometer, and preheating for 10 minutes to ensure stable operation of each component; adjust the output power of the Raman excitation source to 50mW, set the scanning frequency of the two-dimensional scanning galvanometer to 5kHz, and set the diameter of the annular excitation spot to 100μm.

[0062] The probe is placed in close contact with the light spot and focused on the area of ​​skin to be tested (such as the injection site of facial hyaluronic acid injection), ensuring that the probe is in close contact with the skin without pressure damage.

[0063] The broadband beam emitted by the OCT light source enters the fiber coupler and is split into a reference beam and a sample beam. The reference beam is collimated by the collimating lens and then incident on the reference arm reflector, returning to the fiber coupler along the original path. The sample beam is introduced into the probe area through the fiber and passes sequentially through the collimating lens, dichroic mirror 1, two-dimensional scanning galvanometer, dichroic mirror 2, and scanning lens, focusing on the filler area of ​​the dermal layer of the skin.

[0064] The 785nm laser emitted by the monochromatic Raman excitation source is introduced into the probe area through an optical fiber. After being collimated by a collimating lens, it is reflected by the first reflecting mirror to the dichroic mirror 1. After reflection, it is coaxial with the OCT sample beam and focused on the area to be measured. The control system controls the two-dimensional scanning galvanometer to drive the Raman excitation beam to deflect at high speed in a circular manner, forming a ring-shaped excitation spot to dynamically excite the filler.

[0065] The OCT signal echo returns along the original path, interferes with the reference beam, and is then processed by the OCT detection module to generate a three-dimensional structural image of the filler in the dermis. The distribution morphology, diffusion boundary, and internal micropores of the water-light injection droplets can be clearly observed. The Raman scattered light is reflected by the dichroic mirror 2 and coupled to the collecting fiber by the focusing lens, and then sent to the Raman spectrometer to analyze and obtain the characteristic Raman peaks of the filler, accurately identifying the type of filler (such as hyaluronic acid).

[0066] After the test is completed, all light sources and spectrometers are turned off, the probes are cleaned and disinfected, and the test data is saved for subsequent analysis and follow-up.

[0067] Validation data: The device described in this embodiment was used to perform in vivo testing on the skin of 10 mouse subjects who received hyaluronic acid injections. OCT imaging clearly distinguished droplets larger than 10 μm in diameter; Raman spectroscopy accurately identified the characteristic Raman peak of hyaluronic acid (1640 cm⁻¹). -1 The deep detection depth can reach 1~2mm, which can effectively track the degradation of hyaluronic acid 1~6 months after injection.

[0068] Example 3

[0069] according to Figure 1 , 2 As shown in Figures 3, 4, 5, and 6, this embodiment proposes an in vivo detection device and method for dermal fillers. Based on Embodiment 2, some structures are optimized, making it suitable for long-term in vivo monitoring of polylactic acid (PLLA) fillers. The specific structure is as follows:

[0070] In the light source and spectrometer module, the OCT light source uses a broadband light source with a center wavelength of 1310nm and a bandwidth of 150nm, which further improves the lateral resolution of OCT imaging; the monochromatic Raman excitation light source uses a 785nm semiconductor laser with an adjustable output power range of 5~80mW, which is compatible with the Raman excitation characteristics of PLLA; the spectral resolution of the OCT detection module is improved to 0.1nm, and the Raman spectrometer adds a baseline correction function, which can effectively suppress the interference of autofluorescence in biological tissues.

[0071] Within the probe area, a dispersion compensation lens is added between the dichroic mirror 1 and the two-dimensional scanning galvanometer to compensate for the slight axial chromatic aberration caused by the wavelength difference between the OCT broadband light and the Raman excitation light, ensuring the spatial registration accuracy of OCT structural imaging and Raman component detection. The scanning lens is an achromatic cemented doublet lens group, composed of a low-dispersion positive lens and a high-dispersion negative lens, to further optimize the chromatic aberration correction effect and improve imaging clarity. Referring to the existing achromatic lens design concept, it ensures that the focusing accuracy of beams of different wavelengths is consistent.

[0072] The control system of the two-dimensional scanning galvanometer has been enhanced with a scanning mode switching function, which can flexibly switch between in-situ excitation mode and ring scanning excitation mode according to the detection requirements. The adjustable range of the spot diameter in the ring scanning mode has been expanded to 30~300μm, and the adjustable range of the scanning frequency is 0.5~15kHz, which is suitable for the detection of PLLA microspheres with different depths and distribution densities. At the same time, a transparent protective cover is added to the front end of the probe to prevent the probe from directly contacting the skin and causing contamination. The protective cover is made of high-transmittance optical material and does not affect the beam transmission.

[0073] In the signal collection section, a deep-cooled detector is used for Raman collection to further improve the collection efficiency of deep Raman signals. A filter is added between the focusing lens and the collecting fiber to filter stray light and further improve the purity of the Raman signal. The OCT detection module is connected to the Raman spectrometer with a data processing terminal, which can realize the synchronous display, fusion analysis and long-term storage of dual-modal data, which is convenient for subsequent longitudinal follow-up comparison.

[0074] The detection method in this embodiment, for long-term monitoring of PLLA filler injections 1 to 12 months after injection, includes the following steps:

[0075] Preparation before testing: Debug the testing device, start each component to preheat for 15 minutes, adjust the output power of the Raman excitation source to 30mW according to the injection depth of PLLA filler (1~3mm), select the ring scanning mode for the two-dimensional scanning galvanometer, set the spot diameter to 150μm, and set the scanning frequency to 8kHz; adjust the dispersion compensation lens to ensure the spatial registration accuracy between the OCT and Raman optical paths.

[0076] Locating the detection area: Using the preview function of the data processing terminal, move the probe and focus the scanning lens on the PLLA filler injection area to ensure that the initial distribution state of the filler microspheres can be clearly seen in the OCT imaging.

[0077] OCT optical path operation: The 1310nm broadband beam emitted by the OCT light source is split by the fiber coupler. The reference beam returns through the collimating lens and the reference arm mirror. The sample beam is focused on the subcutaneous PLLA filler area through the collimating lens, dichroic mirror 1, dispersion compensation lens, two-dimensional scanning galvanometer, dichroic mirror 2, and scanning lens inside the probe. The backscattered OCT signal light from the tissue returns along the original path and interferes with the reference beam. It is then processed by the OCT detection module to generate a three-dimensional structural image of the PLLA microspheres with a lateral resolution of 10μm. The dispersion state, particle size (10~100μm), and interweaving with the surrounding collagen fibers of the PLLA microspheres can be clearly observed.

[0078] Raman optical path operation: The 785nm Raman excitation beam is introduced into the probe through an optical fiber, collimated by a collimating lens, reflected by the first reflecting mirror, and reflected by dichroic mirror 1. It is then coaxial with the OCT sample beam and focused on the PLLA filler region. The two-dimensional scanning galvanometer drives the Raman excitation beam to perform a high-speed circular scan, reducing the local optical power density and avoiding thermal damage to the skin. The Raman scattered light generated by the PLLA microspheres is reflected by dichroic mirror 2, filtered by a filter, and coupled by a focusing lens before entering the collecting optical fiber and being transported to the Raman spectrometer for processing.

[0079] Data Processing and Analysis: The data processing terminal simultaneously receives OCT structural data and Raman spectral data, fusing them to generate a two-dimensional "structure-composition" image; and analyzes the characteristic peaks of the Raman spectrum (the characteristic peak of PLLA is 875 cm⁻¹). -1 1450cm -1 The system accurately identifies PLLA components and quantifies their degradation level; it also tracks the particle size changes, dispersion uniformity, and integration with surrounding tissues of PLLA microspheres using OCT images.

[0080] Long-term follow-up: Tests were conducted under the same conditions at 1 month, 3 months, 6 months and 12 months after injection. The test data at each time point were compared to analyze the in vivo degradation pattern of PLLA filler and assess its biocompatibility. If an abnormal rate of decrease in Raman characteristic peak intensity was detected, or an abnormal spot appeared in the OCT image, an early warning of foreign body rejection or inflammatory reaction was given.

[0081] Validation data: Using the device of this embodiment, 8 subjects who were injected with PLLA filler were monitored for 12 months. OCT imaging could clearly track the entire process of PLLA microspheres from a dispersed state to gradual degradation and fusion with surrounding tissues. Raman spectroscopy could accurately capture the changes in the intensity of characteristic peaks during the degradation of PLLA. There were no adverse reactions such as skin damage or infection during the entire monitoring process, realizing non-invasive long-term follow-up of PLLA filler.

[0082] This invention breaks through the limitations of traditional evaluation methods, achieving true in-situ real-time monitoring of the human body. Employing a fully optical, non-invasive design, the probe can directly adhere to the human skin. Through a coaxial dual-modal optical path, it enables long-term longitudinal follow-up of the same body part without invasiveness or radiation, obtaining the most authentic in vivo metabolic data. This solves the problems of significant differences between traditional animal model data and human data, and the inability to perform destructive biopsies on the human face. This invention also overcomes the resolution bottleneck of ultrasound imaging, achieving micron-level fine distribution analysis. Integrating OCT technology and utilizing the interference principle of near-infrared broadband light, the spatial resolution leaps to the micron level of 1-10 μm. Compared to high-frequency skin ultrasound at the hundred-micron level, it can clearly present the three-dimensional microscopic distribution morphology, diffusion boundaries, and internal microporous structure of fillers in the dermis and subcutaneous tissue, overcoming the limitation of ultrasound in distinguishing the microscopic interweaving state of fillers and surrounding collagen fiber networks. This invention fills the gap in chemical composition and inflammation monitoring, achieving dual-dimensional structural-biochemical diagnosis. It integrates Raman spectroscopy, utilizing the "molecular fingerprint" characteristic of Raman spectroscopy to accurately identify characteristic chemical bonds in macromolecular materials. It not only allows for visualization of filler structures via OCT but also identifies components through Raman spectroscopy. It enables real-time quantitative assessment of collagen degradation rates and hyaluronic acid cross-linking breakage, providing early warning of injection-induced inflammatory reactions and solving the problem that morphological imaging alone cannot provide chemical molecular information. Furthermore, this invention utilizes mirror-driven inverse spatial shift Raman spectroscopy to overcome the challenge of deep-layer detection. By reusing a two-dimensional scanning mirror and applying a sinusoidal AC control signal with a phase difference, it drives the Raman excitation beam to deflect rapidly in a circular motion, forming a ring-shaped excitation spot. This significantly reduces local optical power density while increasing total injected optical power while adhering to tissue MPE and thermal damage thresholds. Combined with center-point signal collection, it avoids epidermal fluorescence interference, achieving millimeter-level subcutaneous depth detection. This solves the problems of shallow penetration and skin burns caused by blindly increasing power in traditional confocal Raman spectroscopy.

[0083] Compared with existing high-frequency ultrasound skin detection methods, this invention introduces an OCT detection module, which improves the imaging resolution of the microscopic morphological distribution of dermal fillers, facilitating the display of the filler's layered distribution, diffusion boundaries, and local structural features within skin tissue. This invention also incorporates a Raman spectroscopy detection module, enabling the identification of the chemical composition of different filler materials, thus achieving joint detection of structural and chemical information of dermal fillers. Furthermore, this invention preferably employs an inverse spatially offset Raman optical path structure, using a galvanometer to drive the excitation light to form a ring-shaped excitation region, combined with a central collection method. This helps reduce local optical power density, minimize surface fluorescence interference, and improve deep signal acquisition capabilities, thereby enhancing the detection effect of deep dermal fillers.

[0084] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A device for detecting dermal fillers in vivo, comprising a light source and spectrometer module, and a probe area, characterized in that: The light source and spectrometer module is used to provide OCT broadband interference light and Raman excitation light, and to receive and process OCT interference signals and Raman scattering signals; The probe area is integrated and includes optical beam combining and separating elements, a two-dimensional scanning galvanometer, and a scanning lens. The OCT broadband interference light and the Raman excitation / collection light are coaxially measured within the probe area, sharing a common scanning lens. This is used for non-invasive structural imaging and chemical composition detection of skin tissue and its internal fillers. The two-dimensional scanning galvanometer can drive the Raman excitation beam to form a ring excitation spot, achieving in-situ excitation or dynamic ring scanning excitation.

2. The in vivo detection device for dermal fillers according to claim 1, characterized in that: The light source and spectrometer module includes an OCT light source, a monochromatic Raman excitation light source, an OCT detector, and a Raman spectrometer; the light source is an OCT light source or a scanning light source; the monochromatic Raman excitation light source is a semiconductor laser; the OCT detector is a spectrometer or a photodetector; the Raman spectrometer is used to process Raman scattering signals to achieve baseline correction.

3. The in vivo detection device for dermal fillers according to claim 2, characterized in that: The optical combining and separating elements include an optical fiber coupler, a collimating lens, a dichroic mirror 1, a dichroic mirror 2, a first reflecting mirror, and a focusing lens. The optical fiber coupler is used to split the broadband beam emitted by the OCT light source into a reference beam and a sample beam. The reference beam is collimated by the collimating lens and then incident on the reference arm reflecting mirror, returning to the optical fiber coupler along the original path. The dichroic mirror 1 is used to combine the OCT sample beam and the Raman excitation beam. The OCT sample beam is transmitted through the dichroic mirror 1, and the Raman excitation beam is reflected by the first reflecting mirror and then reflected at the dichroic mirror 1, coaxially coinciding with the OCT sample beam. The dichroic mirror 2 is used to separate the OCT signal echo and the Raman scattering signal. The OCT signal echo is transmitted through the dichroic mirror 2, and the Raman scattering light is reflected at the dichroic mirror 2.

4. The in vivo detection device for dermal fillers according to claim 3, characterized in that: The two-dimensional scanning galvanometer is connected to a control system. The control system applies sinusoidal AC control signals that are orthogonal to each other and have a phase difference to the X and Y axes of the two-dimensional scanning galvanometer, driving the Raman excitation beam to deflect rapidly in a circular manner in the focal region of the skin to be tested, forming an annular excitation spot. The diameter of the annular excitation spot is adjustable according to the objective lens field of view and the galvanometer deflection angle.

5. The in vivo detection device for dermal fillers according to claim 4, characterized in that: The core diameter of the collecting fiber of the Raman spectrometer is conjugate with the static geometric center origin directly below the scanning lens. The Raman collecting optical path does not pass through the two-dimensional scanning mirror, which is used for physical-level shielding of strong backscattering and fluorescence interference from the skin layer. The collecting fiber is connected to the focusing lens, which is used to couple Raman scattered light to the collecting fiber.

6. A method for detecting dermal fillers in vivo, using the dermal filler detection device described in claim 5, characterized in that, Includes the following steps: S1: Start the light source and spectrometer module, preheat, and adjust the parameters to ensure that the OCT light source, monochromatic Raman excitation source, OCT detector, and Raman spectrometer are working stably. S2: Place the probe on the area of ​​the skin filler to be tested, use the OCT preview function to locate the detection area, and ensure that the scanning lens is focused on the depth of the filler; S3: The broadband beam emitted by the OCT light source is split into a reference beam and a sample beam by the fiber optic coupler. The reference beam is reflected back to the fiber optic coupler after passing through the collimating lens and the reference arm mirror. The sample beam is focused on the skin tissue and filler area to be tested by passing through the collimating lens, dichroic mirror 1, two-dimensional scanning galvanometer, dichroic mirror 2, and scanning lens. S4: The Raman excitation beam emitted by the monochromatic Raman excitation source is collimated by the collimating lens and reflected by the first reflecting mirror. It then illuminates the dichroic mirror 1 and is reflected, coaxially coinciding with the OCT sample beam and focusing together on the area to be measured. The two-dimensional scanning galvanometer is controlled to select the in-situ excitation mode or the ring scanning excitation mode to excite the filler. S5: Collect OCT signal echo and Raman scattering signal: The OCT signal echo returns along the original path, interferes with the reference beam, and is guided to the OCT detector for processing to obtain a three-dimensional structural image of the filler; the Raman scattered light returns along the original scanning optical path, is reflected by the dichroic mirror 2, and is coupled to the collecting fiber by the focusing lens, and is sent to the Raman spectrometer for processing to obtain the chemical composition information of the filler; S6: Fusion analysis of OCT structural images and Raman spectral data to complete in vivo detection of dermal fillers, and long-term follow-up detection can be performed as needed.

7. The in vivo detection method for dermal fillers according to claim 6, characterized in that: In S4, under the ring scanning excitation mode, the scanning frequency of the two-dimensional scanning galvanometer and the diameter of the ring excitation spot are adjusted by the control system, and appropriate scanning parameters are selected according to the injection depth and distribution density of the filler.

8. The in vivo detection method for dermal fillers according to claim 6, characterized in that: In S5, the three-dimensional structural image of the filler obtained after processing by the OCT detector has an imaging depth of 1-3 mm; after processing by the Raman spectrometer, the characteristic chemical bonds of the filler are accurately identified, the degradation rate and cross-linking degree of the filler are quantitatively evaluated, and early inflammatory responses are warned by capturing abnormal lipid / protein ratios.

9. The in vivo detection method for dermal fillers according to claim 6, characterized in that: In S6, during long-term follow-up testing, under the same testing parameters, tests are conducted at different time points after the filler injection. The OCT structural images and Raman spectral data at each time point are compared to analyze the in vivo degradation pattern and biocompatibility of the filler, and foreign body rejection or inflammatory reactions are detected in a timely manner.

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