OCT imaging system and method for long-term cerebral blood flow detection

Abstract

The invention discloses an OCT (Optical Coherence Tomography) imaging system and method for long-term cerebral blood flow detection, and relates to the field of OCT imaging, the OCT imaging system comprises an intracerebral implantation module and an extracerebral scanning module, and the intracerebral implantation module and the extracerebral scanning module are subjected to non-contact optical coupling through an air gap; the intracerebral implantation module is used as a low-cost consumable to be implanted into the brain in advance, and the intracerebral implantation module comprises a guide sleeve and a GRIN lens; the extra-brain scanning module is used for being reused as high-value equipment, the extra-brain scanning module comprises an OCT objective lens and a correction lens group, and the correction lens group is used for eliminating mixed aberration introduced by a GRIN lens and an air gap and conducting pre-compensation on aberration of a whole light path. According to the OCT imaging system and method for long-term cerebral blood flow detection, high-resolution imaging, deep brain region observation and repeatable imaging are achieved, and the optimal imaging effect is achieved through Zemax simulation optimization.

Description

Technical Field

[0001] This invention relates to the field of OCT imaging, and in particular to an OCT imaging system and method for long-term cerebral blood flow detection. Background Technology

[0002] Currently, cerebrovascular imaging technologies (such as two-photon microscopy and laser speckle imaging) are mainly limited to observation of the surface of the cerebral cortex. Although traditional OCT (optical coherence tomography) technology has the advantage of being non-invasive, it faces severe optical limitations in deep brain tissue imaging: (1) It cannot achieve long-term in situ monitoring: the integrated probe is large, heavy and complex in wiring, and cannot be left in the head of a conscious and freely moving mouse for a long time. Once removed, it cannot be guaranteed to return to the same micrometer-level observation point when reinserted, which makes it impossible to continuously track the course of chronic diseases such as Alzheimer's disease (AD) for several weeks to several months; (2) The equipment cost is high and the throughput is low: since the GRIN lens is integrated with expensive scanning and detection components (galvanometer, fiber optic coupler, etc.), each implant is extremely expensive. In the experiment, it is impossible to achieve high-throughput rotational observation of "one scanning system corresponding to multiple implanted mice"; (3) There are serious aberrations in the separate imaging: If the scanning optical path is simply separated from the implanted lens, due to the introduction of the air gap and the presence of the brain window coverslip, the beam will produce serious spherical aberration and dispersion before entering the GRIN lens. Existing commercial OCT objectives cannot match this non-contact complex optical path, resulting in a sharp drop in imaging resolution (usually only reaching tens of micrometers), and the capillaries (<10μm) cannot be seen clearly; (4) The docking operation is difficult: General optical docking requires micrometer-level coaxial accuracy. In live animal experiments, due to the micro-movements caused by breathing and heartbeat, it is extremely difficult for ordinary optical systems to achieve fast and stable alignment.

[0003] The following specific parameter limitations exist in existing traditional OCT technology when performing deep brain tissue imaging: (1) Imaging depth limit (X): Due to the high scattering characteristics of brain tissue, the effective imaging depth of traditional OCT is usually ≤1.0, which cannot reach deep brain structures such as the hippocampus (located about 1.0-1.5 mm below the cortex); (2) Lateral resolution bottleneck (Y): As the imaging depth increases, the scattering of the beam in the tissue causes the focal spot to diffuse. When the depth exceeds 0.5 mm, the lateral resolution of traditional OCT usually degrades to >15-20 μm, making it difficult to distinguish small capillaries (usually <10 μm); (3) Contradiction between depth of focus (DOF) and resolution (Z): Traditional lenses are limited by the physical constraints of high numerical aperture (NA) and depth of focus, and their depth of focus is usually only 0.1-0.2 mm. To improve resolution, the depth of focus will be further shortened, making it impossible to achieve clear full-layer imaging in thick brain tissue (such as the hippocampus); (4) Aberration problems of implantable probes: Although the introduction of GRIN lenses can extend the depth, the current simple "fiber + GRIN" docking method will produce severe spherical aberration and field curvature under non-contact (air gap) conditions, resulting in a sharp drop in resolution at the edge of the field of view. Summary of the Invention

[0004] The purpose of this invention is to provide an OCT imaging system and method for long-term cerebral blood flow detection, thereby solving the problems mentioned in the background art.

[0005] To achieve the above objectives, the present invention provides an OCT imaging system for long-term cerebral blood flow detection, comprising an intracerebral implantation module and an extracerebral scanning module, wherein the intracerebral implantation module and the extracerebral scanning module are non-contact optically coupled through an air gap. The intracranial implantation module is used as a low-cost consumable for pre-implantation into the brain, and the intracranial implantation module includes a guide cannula and a GRIN lens. The extracranial scanning module is designed for reuse as a high-value device. The extracranial scanning module includes an OCT objective lens and a corrective lens group. The corrective lens group is used to eliminate mixed aberrations introduced by the GRIN lens and air gap, and to pre-compensate aberrations throughout the optical path.

[0006] Preferably, the corrective lens group is disposed between the OCT objective lens and the GRIN lens, and is composed of a lens unit having five optical surfaces.

[0007] Preferably, the system parameters of each optical surface of the corrective lens group are obtained through ZEMAX simulation optimization.

[0008] Preferably, the five optical surfaces correspond to Surface2-6, and their specific parameters are as follows: Optical surface Surface2: radius of curvature of 9.554mm, thickness of 1.000mm, material of H-ZK20 S glass, and net aperture of 1.205mm; Optical surface Surface3: radius of curvature -14.034mm, thickness 4.000mm, net aperture 1.205mm; Optical surface Surface4: radius of curvature 2.992mm, thickness 1.000mm, material is BAK5 S glass, net diameter 0.954mm; Optical surface Surface5: radius of curvature 8.499mm, thickness 3.000mm, net aperture 0.817mm; Surface6 optical surface: radius of curvature of 0.579mm, thickness of 3.000mm, material of BK7 glass, and net diameter of 0.390mm.

[0009] Preferably, the GRIN lens is an SLW-1.8 self-focusing lens, and the GRIN lens has a pitch of 0.39 and a length L of 3.57 mm.

[0010] Preferably, the system parameters of each optical surface of the GRIN lens are obtained through ZEMAX simulation optimization.

[0011] Preferably, the GRIN lens includes optical surfaces Surface7-8, with specific parameters as follows: Optical surface Surface7: aperture type is gradient 9, radius of curvature is infinite, thickness is 3.570mm, material is SLW-1.8 glass, and net diameter is 0.900mm; Optical surface Surface8: The aperture type is a standard surface, the radius of curvature is infinite, the thickness is 2.000mm, and the net aperture is 0.900mm.

[0012] Preferably, the GRIN lens extends the physical imaging focal plane to a depth greater than 3 mm below the skin.

[0013] A method for an OCT imaging system for long-term cerebral blood flow detection includes the following steps: S1. Implantation: The cannula containing the GRIN lens is implanted above CA1 in the hippocampus to establish a long-term observation window; S2. Coarse alignment: During the experiment, adjust the position of the extracerebral part so that its optical axis is aligned with the center of the implanted cannula; S3. Imaging: After being shaped by the corrective lens group, the OCT beam enters the GRIN lens with a pre-compensated wavefront, forming a diffraction-limited focus in the deep brain layer to achieve microvascular imaging with a resolution better than 10μm.

[0014] Therefore, the present invention employs the above-mentioned OCT imaging system and method for long-term cerebral blood flow detection, which has the following beneficial effects: (1) This invention achieves high-resolution imaging with a lateral resolution of less than 10 μm through aberration correction, enabling long-term in vivo imaging of the deep brain region of the mouse hippocampus (1 mm below the cortex). The implanted cannula ensures repeated operation for several months or even a year, allowing for repeated imaging. Furthermore, the parameters are optimized through Zemax simulation optimization, achieving the best imaging effect.

[0015] (2) This invention solves the problem of shallow penetration depth in traditional optical imaging technology, overcomes the limitation of imaging depth, effectively eliminates the aberration of Green lens implantation through external brain correction lens, eliminates the influence of aberration, significantly improves the imaging field of view and resolution, and improves imaging quality.

[0016] (3) This invention provides an important tool for the study of neurodegenerative diseases such as Alzheimer's disease. It can monitor changes in brain microvessels over a long period of time, study disease progression, and provide technical support for the development and efficacy evaluation of drugs for neurological diseases.

[0017] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of brain tissue implantation in an embodiment of an OCT imaging system and method for long-term cerebral blood flow detection according to the present invention; Figure 2 This is a diagram of the integrated optical system of the corrective lens group and the GRIN lens in an embodiment of the OCT imaging system and method for long-term cerebral blood flow detection according to the present invention. Figure 3 This is a curve showing the relationship between corrected interstitial distance and lateral resolution in an embodiment of an OCT imaging system and method for long-term cerebral blood flow detection according to the present invention. Figure 4 This is the imaging effect after adding a corrective lens group in an embodiment of the OCT imaging system and method for long-term cerebral blood flow detection of the present invention; Figure 5 This is a schematic diagram of the process after adding a corrective lens group in an embodiment of the OCT imaging system and method for long-term cerebral blood flow detection according to the present invention; Figure reference numerals: 101, intracranial implantation module; 102, guide cannula; 103, GRIN lens; 104, sealing coverslip; 201, extracranial scanning module; 202, OCT objective lens; 203, corrective lens group. Detailed Implementation

[0019] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments.

[0020] Unless otherwise defined, the technical or scientific terms used in this invention shall have the ordinary meaning understood by one of ordinary skill in the art to which this invention pertains. The terms "first," "second," and similar terms used in this invention do not indicate any order, quantity, or importance, but are merely used to distinguish different components. Terms such as "comprising" or "including" mean that the element or object preceding the word encompasses the elements or objects listed following the word and their equivalents, without excluding other elements or objects. Terms such as "connected" or "linked" are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect. Terms such as "upper," "lower," "left," and "right" are used only to indicate relative positional relationships; when the absolute position of the described object changes, the relative positional relationship may also change accordingly.

[0021] Example Please see Figures 1-5 This invention provides an OCT imaging system for long-term cerebral blood flow detection. The system is physically divided into two independent modules, such as... Figure 1 As shown, it includes: Intracerebral implantation module 101: includes a guide cannula 102, a Green GRIN lens 103 and a sealing coverslip 104, which are pre-implanted into the CA1 region of the mouse hippocampus as a low-cost consumable.

[0022] Extracranial scanning module 201: includes OCT objective lens 202 and specially designed 5-piece corrective lens group 203, which can be reused as a high-value device.

[0023] The two are optically coupled non-contactly through an air gap, and the aberrations of the entire optical path are pre-compensated by the extracranial corrective lens group 203.

[0024] In order to eliminate the mixed aberrations introduced by the GRIN lens 103 and the air gap, a specific corrective lens group 203 is designed in this embodiment, which is located between the OCT objective lens 202 and the GRIN lens 103.

[0025] The corrective lens assembly consists of lens units corresponding to five optical surfaces (Surface 2-6), which cooperate with the rear GRIN lens (Surface 7-8). Specific design parameters are shown in Tables 1 and 2 below (unit: mm): Table 1 Parameters of the Correcting Lens Group

[0026] Table 2 GRIN Lens Parameters

[0027] The parameters mentioned above are all optimal embodiments optimized by ZEMAX simulation. The specific material combination (H-ZK20, BAK5, BK7) is matched with the GRIN lens of SLW-1.8 material, which can eliminate chromatic aberration and advanced spherical aberration under broadband light sources to the greatest extent.

[0028] like Figure 2 As shown, this is an embodiment. Figure 1 The diagram shows an integrated optical schematic of the corrective lens group and the GRIN lens. In the diagram, 0-1 represent various surfaces, where 0 is the object plane at infinity, 1 is the aperture stop, 2-6 correspond to the photometric diagram of the corrective lens group, 7-8 correspond to the photometric diagram of the corrective lens group, and 9 is the image plane.

[0029] like Figure 3 As shown, the quantitative relationship between the GRIN lens pitch (P) and the system's lateral resolution, obtained through Zemax simulation, is illustrated. Wherein: Horizontal axis: Represents the pitch P of the GRIN lens, ranging from 0.25 to 0.50.

[0030] Vertical axis: Represents the horizontal resolution of the system (the smaller the value, the higher the resolution and the clearer the image), in micrometers (μm).

[0031] Curve trend: As the pitch increases from 0.25, the resolution value gradually decreases (performance improves); it reaches an extreme point at around P=0.40, and then the resolution value rebounds (performance declines).

[0032] Optimal operating point (marked with a red square): In this embodiment, P=0.39 is selected as the design operating point. At this point, the system's lateral resolution is better than 10μm (shown in the light blue area in the figure), meeting the imaging requirements for microvascular details. Furthermore, 0.39 is chosen instead of 0.40 or higher to ensure high resolution while maintaining sufficient depth of focus and working distance, avoiding shallow imaging depth due to excessively large pitch. This data fully demonstrates the scientific validity and technical advantages of the parameter selection in this scheme.

[0033] like Figure 4 As shown, this is the imaging effect after adding the corrective lens group. Through aberration correction, a lateral resolution of less than 10μm is achieved.

[0034] Therefore, the present invention, through the aforementioned split-type optical imaging system, can achieve: Breakthrough in depth (X): By using an implanted GRIN lens (Length = 3.57mm) as a relay optical path, the physical imaging focal plane is directly extended to a depth >3mm below the cortex, breaking through the 1mm depth limit caused by tissue scattering.

[0035] Optimization for resolution (Y): The wavefront error introduced by the air gap was compensated by combining external H-ZK20 and BAK5 glass. Simulation data show that this design compresses the root mean square radius of the system's point spread function (PSF) to within the Airy disk, achieving a diffraction-limited resolution of <10 μm.

[0036] Regarding the balance of depth of focus (Z): By optimizing the pitch of the GRIN lens (Pitch = 0.39), sufficient depth of focus is maintained while ensuring high resolution (<10μm), thus resolving the contradiction between high resolution and large depth of focus.

[0037] This invention also provides a method for an OCT imaging system used for long-term cerebral blood flow detection, such as... Figure 5 As shown, it includes the following steps: S1. Implantation: A cannula containing a GRIN lens (3.57 mm long) was implanted above CA1 in the hippocampus of mice to establish a long-term observation window.

[0038] S2. Coarse Alignment: During the experiment, adjust the position of the extracerebral portion to align its optical axis with the center of the implanted cannula. Thanks to the large entrance pupil design of the corrective lens assembly, the system allows for a radial deviation of ±0.2mm and an angular deviation of ±2°.

[0039] S3. Imaging: After being shaped by the corrective lens group, the OCT beam enters the GRIN lens with a pre-compensated wavefront, forming a diffraction-limited focus in the deep brain layer to achieve microvascular imaging with a resolution better than 10μm.

[0040] Experiments have verified that this method has the following advantages: (1) Imaging performance when the probe beam deviates from the axis of the GRIN lens: In practice, when the external brain scanning module undergoes horizontal displacement (e.g., 0.2 mm) relative to the implanted module, the imaging range will geometrically shift accordingly. Without the corrective design of this invention, the beam will pass through the GRIN lens along an asymmetric path, exciting severe third-order coma. This will result in a severely asymmetric point spread function (PSF), causing image "tailing," a sudden deterioration in resolution from 5 μm to over 30 μm, and uneven brightness at image edges due to vignetting.

[0041] By employing the 5-element corrective lens assembly of this invention, the system can accommodate off-axis light rays due to its large entrance pupil design and refractive index matching of the specific material (H-ZK20). At this time, although the center of the imaging field of view undergoes physical displacement (i.e., the position of the seen image changes), the imaging quality (aberration) of each point within the image is still controlled within the diffraction limit. This means that although the blood vessels seen by the user are "off-center," they are still "clear," which is crucial for locating target blood vessels. See Table 3 below: Table 3. Resolution differences between the present invention and conventional solutions when the axis is deviated.

[0042] (2) Optical performance under "Tilt" conditions: When there is an angular deviation in the incident beam (e.g., 2°), traditional coupling methods will cause the imaging focal plane to be non-parallel to the cross-section of the biological tissue, resulting in one side of the imaging range being in focus while the other side is blurred (out of focus). At the same time, the angular deviation will introduce significant astigmatism, causing the microvessels to appear elliptical in cross-section, making it impossible to accurately measure the diameter.

[0043] The corrective lens assembly of this invention constructs a flat image plane by optimizing the field curvature characteristics of the BK7 lens (surface 6). When a 2° tilt occurs, the reverse field curvature generated by the lens assembly can effectively offset the defocus difference caused by the tilt, ensuring consistent sharpness across the entire imaging range. At this time, astigmatism is suppressed to within 0.5 wavelengths, guaranteeing accurate reproduction of microvascular morphology. (See Table 4 below.) Table 4. Resolution differences between the present invention and conventional solutions when there is an angle deviation.

[0044] Therefore, this invention employs the aforementioned OCT imaging system and method for long-term cerebral blood flow detection, proposing and implementing an aberration correction mechanism based on a Green's lens aberration elimination method using extracorporeal corrective lenses. Parameter optimization is achieved through a Zemax simulation optimization technique, and an integrated system design combining the corrective lens group and the Green's lens is adopted to protect the specific lens formulation. The aberration correction lens group consists of multiple lenses, including lens units made of H-ZK20, BAK5, and BK7 glass materials, providing reverse compensation for the SLW-1.8 GRIN lens and its resulting chromatic aberration and spherical aberration. A large-tolerance optical path design is adopted; the numerical aperture and field stop configuration of this optical system have adaptive alignment tolerance, maintaining the predetermined imaging resolution even within a ±0.2mm radial deviation range between the extracorporeal module and the implanted module.

[0045] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. An OCT imaging system for long-term cerebral blood flow detection, characterized in that: It includes an intrabrain implantation module and an external brain scanning module, wherein the intrabrain implantation module and the external brain scanning module are optically coupled non-contactly through an air gap; The intracerebral implantation module is used as a low-cost consumable for pre-implantation into the brain, and the intracerebral implantation module includes a guide cannula and a GRIN lens. The extracranial scanning module is designed for reuse as a high-value device. The extracranial scanning module includes an OCT objective lens and a corrective lens group. The corrective lens group is used to eliminate mixed aberrations introduced by the GRIN lens and air gap, and to pre-compensate aberrations throughout the optical path.

2. The OCT imaging system for long-term cerebral blood flow detection according to claim 1, characterized in that: The corrective lens group is positioned between the OCT objective and the GRIN lens, and consists of a lens unit with five optical surfaces.

3. The OCT imaging system for long-term cerebral blood flow detection according to claim 2, characterized in that: The system parameters of each optical surface of the corrective lens group were obtained through ZEMAX simulation optimization.

4. The OCT imaging system for long-term cerebral blood flow detection according to claim 3, characterized in that, The five optical surfaces correspond to Surface2-6, and their specific parameters are as follows: Optical surface Surface2: radius of curvature of 9.554mm, thickness of 1.000mm, material of H-ZK20 S glass, and net aperture of 1.205mm; Optical surface Surface3: radius of curvature -14.034mm, thickness 4.000mm, net aperture 1.205mm; Optical surface Surface4: radius of curvature 2.992mm, thickness 1.000mm, material is BAK5 S glass, net diameter 0.954mm; Optical surface Surface5: radius of curvature 8.499mm, thickness 3.000mm, net diameter 0.817mm; Surface6 optical surface: radius of curvature of 0.579mm, thickness of 3.000mm, material of BK7 glass, and net diameter of 0.390mm.

5. An OCT imaging system for long-term cerebral blood flow detection according to claim 1, characterized in that: The GRIN lens is an SLW-1.8 self-focusing lens, and the pitch of the GRIN lens is 0.39 and the length L is 3.57mm.

6. An OCT imaging system for long-term cerebral blood flow detection according to claim 5, characterized in that: The system parameters of each optical surface of the GRIN lens were obtained through ZEMAX simulation optimization.

7. An OCT imaging system for long-term cerebral blood flow detection according to claim 6, characterized in that, The GRIN lens includes optical surfaces Surface7-8, with the following specific parameters: Optical surface Surface7: aperture type is gradient 9, radius of curvature is infinite, thickness is 3.570mm, material is SLW-1.8 glass, and net diameter is 0.900mm; Optical surface Surface8: The aperture type is a standard surface, the radius of curvature is infinite, the thickness is 2.000mm, and the net diameter is 0.900mm.

8. An OCT imaging system for long-term cerebral blood flow detection according to claim 1, characterized in that: The GRIN lens extends the physical imaging focal plane to a depth greater than 3 mm below the skin.

9. A method using an OCT imaging system for long-term cerebral blood flow detection according to any one of claims 1-8, characterized in that, Includes the following steps: S1. Implantation: The cannula containing the GRIN lens is implanted above CA1 in the hippocampus to establish a long-term observation window; S2. Coarse alignment: During the experiment, adjust the position of the extracerebral part so that its optical axis is aligned with the center of the implanted cannula; S3. Imaging: After being shaped by the corrective lens group, the OCT beam enters the GRIN lens with a pre-compensated wavefront, forming a diffraction-limited focus in the deep brain layer to achieve microvascular imaging with a resolution better than 10μm.

Images