Miniaturized bimodal imaging device

Abstract

The invention provides a miniaturized bimodal imaging device, the miniaturized bimodal imaging device comprises an imaging window and an imaging device, the imaging window is configured to be fixed in a target imaging area, and the imaging window is provided with a photoacoustic transparent window; the imaging device is fixedly connected with the imaging window and comprises a fluorescence microscopic device and an ultrasonic transduction device; the fluorescence microscopic device comprises an exciting light emitting unit and a fluorescence receiving unit, the exciting light emitting unit is configured to be used for emitting exciting light to the target imaging area, and the fluorescence receiving unit is configured to be used for receiving a fluorescence signal returned by the target imaging area through the opto-acoustic transparent window; and the ultrasonic transduction device is configured to be at least used for receiving an ultrasonic signal returned by the target imaging area through the opto-acoustic transparent window. The miniaturized bimodal imaging equipment can realize ultrasonic imaging and fluorescence imaging on a small animal at the same time, so that bimodal imaging of the freely moving small animal is realized.

Description

Technical Field

[0001] This application relates to the field of biomedical imaging, and particularly to a miniaturized dual-modal imaging device. Background Art

[0002] Currently, rodent models (especially mice) have become irreplaceable research carriers due to the high conservation of their brain structures with humans, mature gene manipulation techniques, and rich disease models.

[0003] In neuroscience, there is an indirect coupling relationship between cerebral hemodynamics and neural activity. Therefore, achieving real-time observation of hemodynamics across the whole brain in non-anesthetized, freely moving mice is of great significance for deeply revealing the spatio-temporal dynamic mechanisms and functional associations of neural circuits. It can not only be closer to the real physiological state but also provide valuable experimental evidence and theoretical support for exploring brain functions, the pathological mechanisms of brain diseases, and the relationship between neural signals and hemodynamic coupling.

[0004] In the field of neuroscience research, common imaging methods include single-photon fluorescence microscopy and functional ultrasound imaging, etc. Single-photon fluorescence microscopy and functional ultrasound imaging are two mainstream imaging methods, which are respectively used for monitoring cell-level activities and hemodynamics. Single-photon fluorescence microscopy is known for its high sensitivity and subcellular resolution, and it is particularly outstanding in the study of cortical nerves in freely moving mice. However, the imaging depth of this technology is limited, and it can only obtain cell activity information in the cerebral cortex area, which limits its wide application in whole-brain research. In contrast, functional ultrasound imaging has the advantages of non-invasiveness, real-time performance, and excellent deep tissue penetration ability, and has obvious advantages in the research of deep brain regions. It can not only provide structural information of deep brain regions and whole-brain hemodynamic data but also indirectly reflect the neuronal activities in deep brain regions through blood volume changes. However, compared with fluorescence imaging, the resolution of ultrasound imaging is lower, and the device volume is larger. The weight of its probe and the design of multi-channel signal transmission lines limit the flexibility of the device, making it difficult to be applied to freely moving small animal models. Summary of the Invention

[0005] In view of this, the embodiments of this application are committed to providing a miniaturized dual-modal imaging device to solve the problem of difficult high-density miniaturization in existing miniaturized dual-modal imaging devices.

[0006] The first aspect of this application provides a miniaturized dual-modal imaging device, including:

[0007] An imaging window, which is configured to be fixed to the target imaging area, and the imaging window is provided with a photoacoustic transparent window;

[0008] An imaging device, which is fixedly connected to the imaging window and includes a fluorescence microscopy device and an ultrasonic transducer device;

[0009] The fluorescence microscopy device includes an excitation light emitting unit and a fluorescence receiving unit. The excitation light emitting unit is configured to emit excitation light to a target imaging area, and the fluorescence receiving unit is configured to receive the fluorescence signal returned from the target imaging area through the photoacoustic transparent window;

[0010] The ultrasonic transducer device is configured to at least receive the ultrasonic signal returned from the target imaging area through the photoacoustic transparent window.

[0011] In an embodiment of the present application, the imaging window includes a fixed form and a photoacoustic transparent isolation film;

[0012] The fixed form is annular to enclose the photoacoustic transparent window, and the fixed form is provided with a mounting surface, which is configured to fit the outer contour of the target imaging area;

[0013] The photoacoustic transparent isolation film is fixedly arranged on the fixed form and covers the corresponding area of the photoacoustic transparent window, so that the excitation light, fluorescence signal and ultrasonic signal can penetrate the photoacoustic transparent isolation film;

[0014] The fixed form and the photoacoustic transparent isolation film are configured to form a closed chamber with the target imaging area.

[0015] In an embodiment of the present application, the fixed form includes a fixed part and a form part fixedly connected to each other. The fixed part is provided with the mounting surface, the form part is located at one end of the fixed part away from the target imaging area, and the photoacoustic transparent isolation film is configured to be fixedly arranged on the form part.

[0016] In an embodiment of the present application, the imaging device further includes a mounting base and a mounting bracket;

[0017] The mounting bracket is fixedly arranged on the housing of the fluorescence microscopy device, and the ultrasonic transducer device is fixedly arranged on the mounting bracket. The mounting base is configured to be fixedly connected to the imaging window on the side of the imaging window away from the target imaging area. A base window for the excitation light and the fluorescence signal of the fluorescence microscopy device to pass through is provided on the mounting base, and the objective lens of the fluorescence microscopy device is arranged in the base window.

[0018] In one embodiment of the present application, the ultrasonic transducer device includes at least one ultrasonic transducer assembly. The ultrasonic transducer assembly includes an ultrasonic transducer probe and a probe fixture. The ultrasonic transducer probe is fixedly arranged on the probe fixture; the probe fixture is arranged on the mounting bracket.

[0019] In one embodiment of the present application, the probe fixture is movably arranged on the mounting bracket.

[0020] In one embodiment of the present application, the mounting bracket is provided with mounting holes extending in a first direction;

[0021] The probe fixture is provided with fixing holes extending in a second direction;

[0022] The ultrasonic transducer device further includes a fixing member, which is configured to penetrate through the mounting hole and the fixing hole to fixedly arrange the probe fixture and the ultrasonic transducer probe on the mounting bracket, and the position of the fixing member in the mounting hole, the position of the fixing member in the fixing hole, and the included angle between the first direction and the second direction are adjustable.

[0023] In one embodiment of the present application, the ultrasonic transducer device includes two ultrasonic transducer assemblies, and the two ultrasonic transducer assemblies are respectively arranged on both sides of the fluorescence microscopy device.

[0024] In one embodiment of the present application, the ultrasonic transducer device further includes a flexible signal connection part and a communication cable, and each ultrasonic transducer probe is electrically connected to the communication cable through the flexible signal connection part.

[0025] In one embodiment of the present application, the ultrasonic transducer device is configured to send ultrasonic waves to a target imaging area and receive ultrasonic signals returned by the target imaging area through a photoacoustic transparent window.

[0026] During the use of the miniaturized dual-modal imaging device according to the embodiment of the present application, after the miniaturized dual-modal imaging device according to the embodiment of the present application is fixedly arranged on the head of a small animal, the small animal can move freely without anesthetizing or fixing the mouse; during the automatic movement of the small animal, in the miniaturized dual-modal imaging device according to the embodiment of the present application, by using a photoacoustic transparent window, a fluorescence microscopy device and an ultrasonic transducer device that can simultaneously transmit optical signals and acoustic signals in fluorescence imaging and ultrasonic imaging, ultrasonic imaging and fluorescence imaging can be simultaneously realized on the small animal, so as to realize dual-modal imaging of a freely moving small animal.

[0027] The miniaturized dual-modal imaging device according to the embodiments of the present application can simultaneously acquire cortical neuron activity information, biplane brain structure information, hemodynamic information, and functional response information of deep brain regions of small animals, facilitating the establishment of the connection between large-area neuron activity and hemodynamics, deep brain and cortical functions, providing a new technical means for the visual detection of neurovascular coupling, the analysis of functional connections between deep brain and cortex, and the research of cerebrovascular diseases, and also providing stronger technical support for the research of brain function and brain network, promoting the development of multi-dimensional brain science research.

[0028] During the use of the miniaturized dual-modal imaging device according to the embodiments of the present application, small animals can move freely without being anesthetized or fixed; the miniaturized dual-modal imaging device according to the embodiments of the present application can effectively avoid the interference of anesthesia and restraint of small animals in existing imaging devices on experimental results, and the obtained imaging results can comprehensively reflect the neuron activity of small animals. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 Shows the overall structural schematic diagram of the miniaturized dual-modal imaging device of the present application.

[0030] Figure 2 Shows the exploded structural schematic diagram of the miniaturized dual-modal imaging device of the present application.

[0031] Figure 3 Shows the structural schematic diagram of the imaging window of the miniaturized dual-modal imaging device of the present application combined with the skull of a small animal.

[0032] Figure 4 Shows the structural schematic diagram of the fixing part of the miniaturized dual-modal imaging device of the present application combined with the skull of a small animal.

[0033] Figure 5 Shows the cross-sectional schematic diagram of the window part of the miniaturized dual-modal imaging device of the present application.

[0034] Figure 6 Shows the schematic diagram of the fixed window of the miniaturized dual-modal imaging device of the present application combined with the skull of a small animal.

[0035] Figure 7 Shows the structural schematic diagram of the ultrasonic transducer assembly of the present application.

[0036] Figure 8 Shows another structural schematic diagram of the ultrasonic transducer assembly of the present application.

[0037] Reference Signs:

[0038] 10. Imaging window; 11. Photoacoustic transparent window; 12. Photoacoustic transparent isolation film; 13. Fixed form; 131. Fixed part; 1311. Fixed arm; 132. Form part; 1321. First cover; 1322. Second cover; 1323. Clamping groove; 1324. Clamping part; 133. Installation surface; 20. Imaging device; 21. Fluorescence microscopy device; 211. Objective lens; 212. Detector; 220. Ultrasonic transducer device; 22. Ultrasonic transducer assembly; 221. Ultrasonic transducer probe; 222. Probe fixture; 223. Flexible signal connection part; 2231. Shield ground; 2232. Signal ground; 2233. Signal line; 224. Communication cable; 2241. Coaxial cable; 23. Installation base; 24. Installation bracket. Detailed implementation

[0039] The following will clearly and completely describe the technical solutions in the embodiments of the present application with reference to the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of the present application.

[0040] It should be noted that: unless otherwise specifically stated, the relative arrangements, numerical expressions and values of the components and steps described in these embodiments do not limit the scope of the present application. In all the examples shown and discussed here, any specific value should be construed as merely exemplary, rather than as a limitation. Therefore, other examples of the exemplary embodiments may have different values.

[0041] Many specific details are set forth in the following description in order to provide a thorough understanding of the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar generalizations without departing from the connotation of the present application. Therefore, the present application is not limited by the specific implementations disclosed below. Technologies, methods and devices known to those of ordinary skill in the relevant fields may not be discussed in detail, but should be regarded as part of the specification when appropriate.

[0042] The terms used in one or more embodiments of the present application are only for the purpose of describing specific embodiments, and are not intended to limit one or more embodiments of the present application. The singular forms "a", "" and "the" used in one or more embodiments of the present application and the appended claims are also intended to include the plural forms, unless the context clearly indicates otherwise. It should also be understood that the term " / and" used in one or more embodiments of the present application refers to and includes any or all possible combinations of one or more of the associated listed items.

[0043] It should be understood that although the terms first, second, etc. may be used in one or more embodiments of the present application to describe various information, such information should not be limited to these terms. These terms are only used to distinguish information of the same type from each other. For example, without departing from the scope of one or more embodiments of the present application, the first may also be referred to as the second, and similarly, the second may also be referred to as the first. Depending on the context, the word "if" as used herein may be interpreted as "when" or "while" or "in response to a determination". In this article, "upper", "lower", "front", "rear", "left", "right", etc. are only used to represent the relative positional relationship between relevant parts, rather than defining the absolute positions of these relevant parts. In this article, "equal", "same", etc. are not strict mathematical and / or geometric limitations, and also include the allowable errors that can be understood by those skilled in the art and are allowed in manufacturing or using, etc. Unless otherwise specified, the numerical ranges in this article include not only the entire range within its two endpoints, but also several sub-ranges included therein.

[0044] As Figures 1 to 8 shown, an embodiment of the present application provides a miniaturized dual-modal imaging device, which is mainly used for small animals such as mice. When using this miniaturized dual-modal imaging device, it is necessary to wear and fix the miniaturized dual-modal imaging device on the head of a small animal, so as to realize brain ultrasound imaging and brain fluorescence imaging of the small animal.

[0045] As Figure 1 and Figure 2 shown, the miniaturized dual-modal imaging device includes an imaging window 10 and an imaging device 20. The imaging window 10 is configured to be fixed to the target imaging area. In the case of applying to the head of a small animal, the target imaging area is the head of the small animal. The imaging window 10 can play a role in fixing to the target imaging area and protecting the tissues of the target imaging area.

[0046] Among them, in order to ensure that fluorescence imaging and photoacoustic imaging can be performed, the imaging window 10 is provided with a photoacoustic transparent window 11, and the photoacoustic transparent window 11 is used to transmit the optical signal and acoustic signal in fluorescence imaging and ultrasonic imaging.

[0047] As Figure 1 and Figure 2 shown, the imaging device 20 is fixedly connected to the imaging window 10 and includes a fluorescence microscopy device 21 and an ultrasonic transducer device 220; the fluorescence microscopy device 21 includes an excitation light emission unit and a fluorescence reception unit. The excitation light emission unit is configured to emit excitation light to the target imaging area, and the fluorescence reception unit is configured to receive the fluorescence signal returned from the target imaging area through the photoacoustic transparent window 11; the ultrasonic transducer device 220 is configured to at least receive the ultrasonic signal returned from the target imaging area through the photoacoustic transparent window 11.

[0048] Therefore, during the operation of the miniaturized dual-modal imaging device according to the embodiments of the present application, the excitation light emitting unit of the fluorescence microscopy device 21 can emit excitation light to the target imaging area. After the fluorescent markers in the tissue of the target imaging area receive the excitation light, fluorescent signals will be generated. The fluorescence receiving unit is used to receive the fluorescent signals returned from the target imaging area through the photoacoustic transparent window 11, so as to obtain the fluorescence imaging result of the target imaging area. That is, the miniaturized dual-modal imaging device according to the embodiments of the present application can perform fluorescence imaging using the fluorescence microscopy device 21; the ultrasonic transducer device 220 can at least be used to receive the ultrasonic signals returned from the target imaging area through the photoacoustic transparent window 11. Therefore, the miniaturized dual-modal imaging device according to the embodiments of the present application performs ultrasonic imaging using the ultrasonic signals received by the ultrasonic transducer device 220.

[0049] Specifically, the excitation light emitting unit of the fluorescence microscopy device 21 may include devices such as a light source, a filter, a dichroic mirror, etc. The fluorescence receiving unit may include devices such as an objective lens 211, a blocking filter, and a detector 212. The detector 212 is used to convert the received fluorescent signals into electrical signals and then output the corresponding fluorescent images.

[0050] It can be understood that in an embodiment of the present application, the ultrasonic transducer device 220 is configured to send ultrasonic waves to the target imaging area and receive the ultrasonic signals returned from the target imaging area through the photoacoustic transparent window 11. That is, during the conventional ultrasonic imaging process, the ultrasonic transducer device 220 can send ultrasonic waves to the target imaging area. After the ultrasonic waves are emitted to the tissue of the target imaging area, returned ultrasonic signals will be generated. The ultrasonic transducer device 220 can receive the ultrasonic signals returned from the target imaging area through the photoacoustic transparent window 11, so as to perform ultrasonic imaging.

[0051] In another embodiment of the present application, the ultrasonic transducer device 220 of the embodiments of the present application can also perform photoacoustic imaging; that is, when the excitation light emitting unit of the fluorescence microscopy device 21 or other excitation light emitting units can emit the excitation light required for photoacoustic imaging to the target imaging area, after the tissue of the target imaging area absorbs the excitation light, the temperature will rise, and then thermoelastic expansion will occur, thereby generating a pressure wave. This pressure wave is an ultrasonic signal and can contain information about the light absorption of each part of the tissue in the target imaging area. The ultrasonic transducer device 220 can receive the ultrasonic signals returned from the target imaging area through the photoacoustic transparent window 11, so as to achieve photoacoustic imaging.

[0052] It can be understood that during the use of the miniaturized dual-modal imaging device according to the embodiments of the present application, after the miniaturized dual-modal imaging device according to the embodiments of the present application is fixedly arranged on the head of a small animal, the small animal can move freely without the need to anesthetize or fix the mouse; during the automatic movement of the small animal, in the miniaturized dual-modal imaging device according to the embodiments of the present application, by using the photoacoustic transparent window 11, the fluorescence microscopy device 21 and the ultrasonic transducer device 220 that can simultaneously transmit the optical signal and the acoustic signal in fluorescence imaging and ultrasonic imaging, ultrasonic imaging and fluorescence imaging can be simultaneously realized on the small animal, so as to realize the dual-modal imaging of the freely moving small animal.

[0053] Specifically, fluorescence imaging and ultrasonic imaging can obtain biological information in different dimensions, and the miniaturized dual-modal imaging device according to the embodiments of the present application can give full play to the complementary advantages of the two technologies that can obtain biological information in different dimensions. Single-photon fluorescence imaging provides high-resolution cellular-level information in the cerebral cortex area, while ultrasonic imaging provides information on the tissue structure of the deep brain region, whole-brain hemodynamics, and deep neuronal activities.

[0054] Therefore, the miniaturized dual-modal imaging device according to the embodiments of the present application can simultaneously obtain the cortical neuron activity information, bi-planar brain structure information, hemodynamic information, and deep brain region functional response information of small animals, which is convenient for establishing the connection between large-area neuron activities and hemodynamics, deep brain and cortical functions, provides a new technical means for the visual detection of neurovascular coupling, the analysis of functional connections between the deep brain and the cortex, and the research of cerebrovascular diseases, also provides a stronger technical support for the research of brain function and brain network, and promotes the development of multi-dimensional brain science research.

[0055] It can be understood that the onset and recovery processes of brain function and brain diseases are closely related to the activity states of experimental subjects such as anesthesia or restraint. Research shows that anesthetics may affect the contraction and relaxation of cerebral microvessels, neuronal activity, and neurovascular coupling function, while the fixation operation may trigger the anxiety and panic emotions of experimental subjects, thereby interfering with the authenticity of neuronal activities.

[0056] Since during the use of the miniaturized dual-modal imaging device according to the embodiments of the present application, the small animal can move freely without the need to anesthetize or fix the small animal; the miniaturized dual-modal imaging device according to the embodiments of the present application can effectively avoid the interference of the anesthesia and restraint of small animals in the existing imaging device 20 on the experimental results, and the obtained imaging results can comprehensively reflect the neuronal activity of small animals.

[0057] Specifically, such as Figure 3As shown, in an embodiment of the present application, the imaging window 10 includes a fixed form 13 and a photoacoustic transparent isolation film 12; the fixed form 13 is annular to enclose a photoacoustic transparent window 11, and the fixed form 13 is provided with a mounting surface 133, and the mounting surface 133 is configured to fit the outer contour of the target imaging area; the photoacoustic transparent isolation film 12 is fixedly arranged on the fixed form 13 and covers the corresponding area of the photoacoustic transparent window 11 to enable the excitation light, fluorescence signal and ultrasonic signal to penetrate the photoacoustic transparent isolation film 12; the fixed form 13 and the photoacoustic transparent isolation film 12 are configured to form a closed chamber with the target imaging area.

[0058] That is, during the use of the miniaturized dual-modal imaging device in the embodiment of the present application, the mounting surface 133 of the fixed form 13 can fit the outer contour of the target imaging area, and the shape of the mounting surface 133 can be scanned and customized according to the skull model of small animals to ensure that the mounting surface 133 of the fixed form 13 can fit the outer contour of the skull of small animals. It can be understood that for the same kind of small animals, the shapes of their skull outer contours are usually relatively consistent. Therefore, for the same kind of small animals, after one-time scanning and customization, the fixed form 13 with the same shape can be used in subsequent experiments.

[0059] Since the photoacoustic transparent isolation film 12 is fixedly arranged on the fixed form 13 and covers the corresponding area of the photoacoustic transparent window 11, in this way, during the working process of the miniaturized dual-modal imaging device in the embodiment of the present application, the excitation light emitted by the fluorescence microscopy device 21, the fluorescence signal returned from the target imaging area, the ultrasonic wave emitted by the ultrasonic transducer device 220 and the ultrasonic signal returned from the target imaging area can all be transmitted through the photoacoustic transparent isolation film 12, and there will be no excessive loss during the process of passing through the photoacoustic transparent isolation film 12.

[0060] Among them, the fixed form 13 and the photoacoustic transparent isolation film 12 are used to form a closed chamber with the target imaging area. During the working process of the miniaturized dual-modal imaging device in the embodiment of the present application, the closed chamber formed by the fixed form 13 and the photoacoustic transparent isolation film 12 and the target imaging area can be filled with transparent cerebrospinal fluid and all air can be discharged, so as to facilitate the transmission of ultrasonic signals.

[0061] Further, as Figure 3 and Figure 6As shown, in an embodiment of the present application, the photoacoustic transparent isolation film 12 is configured to be attached to at least a part of the target imaging area. During the operation of the miniaturized dual-modal imaging device according to the embodiment of the present application, the photoacoustic transparent isolation film 12 is attached to at least a part of the target imaging area, that is, the photoacoustic transparent isolation film 12 can flatten the protruding brain tissue after the small animal's craniotomy, facilitating the maintenance of the intracranial pressure of the small animal; the photoacoustic transparent isolation film 12 can also play a role in protecting the protruding brain tissue after the small animal's craniotomy. Moreover, since the photoacoustic transparent isolation film 12 is attached to at least a part of the target imaging area, it can also ensure that the fluorescence microscopy device 21 has a flat imaging plane, thereby improving the imaging quality of the fluorescence microscopy device 21.

[0062] In an embodiment of the present application, the photoacoustic transparent isolation film 12 is configured to have an acoustic impedance range of 0.8 MRayl to 3 MRayl and a light transmittance greater than 90%. Since the acoustic impedance range of the photoacoustic transparent isolation film 12 is 0.8 MRayl to 3 MRayl, which is relatively close to the acoustic impedance of brain tissue and cerebrospinal fluid, it has good ultrasonic compatibility, can effectively reduce the reflection of ultrasonic signals when the ultrasonic wave passes through the interface between the photoacoustic transparent isolation film 12 and the photoacoustic transparent isolation film 12, and effectively reduce the loss of ultrasonic signals; since the light transmittance of the photoacoustic transparent isolation film 12 is greater than 90%, it can effectively ensure the transmittance of the excitation light and the fluorescence signal, and reduce the loss when the excitation light and the fluorescence signal pass through the photoacoustic transparent isolation film 12.

[0063] Furthermore, in an embodiment of the present application, the photoacoustic transparent isolation film 12 is constructed of one of thermoplastic polyurethane elastomer (TPU), polydimethylsiloxane (PMDS), and poly-4-methyl-1-pentene (TPX). Among them, the thermoplastic polyurethane elastomer (TPU) has an acoustic impedance range of 1.65 - 2.63 MRayl, a light transmittance greater than 91%, and has a certain elasticity. Compared with the prior art solution of setting optical glass in the target imaging area, the acoustic impedance of the thermoplastic polyurethane elastomer is more adaptable to cerebrospinal fluid, can greatly reduce the reflection of ultrasonic signals, thereby effectively reducing the loss of ultrasonic signals, and can also effectively reduce the reflection artifacts of the obtained ultrasonic imaging results, thereby improving the signal-to-noise ratio and contrast of the ultrasonic imaging results. It can also effectively ensure the transmittance of the excitation light and the fluorescence signal, and reduce the loss when the excitation light and the fluorescence signal pass through. Moreover, the thermoplastic polyurethane elastomer (TPU) has excellent elasticity, tensile resistance, and wear resistance, which can better protect the brain tissue and effectively extend the service life of the photoacoustic transparent isolation film 12.

[0064] Similarly, the acoustic impedance range of polydimethylsiloxane (PMDS) is 0.97 - 1.0 MRayl, and the light transmittance is greater than 95%; compared with thermoplastic polyurethane elastomer (TPU), the wear resistance and rigidity of polydimethylsiloxane (PMDS) are slightly worse, and the protection and flattening effect on the brain tissue of small animals are slightly worse.

[0065] The acoustic impedance range of poly(4-methyl-1-pentene) (TPX) is 1.66 - 1.85 MRayl, and the light transmittance range is 93% - 95%. Compared with thermoplastic polyurethane elastomer (TPU), the acoustic impedance of poly(4-methyl-1-pentene) (TPX) is more suitable for cerebrospinal fluid, and the light transmittance is also higher, and the wear resistance and rigidity are also better.

[0066] Further, as Figure 3 shown, in an embodiment of the present application, the fixed window 13 includes a fixed part 131 and a window part 132 fixedly connected to each other. The fixed part 131 is provided with an installation surface 133. The window part 132 is located at one end of the fixed part 131 away from the target imaging area. The photoacoustic transparent isolation film 12 is configured to be fixedly arranged on the window part 132.

[0067] In this way, during the installation of the miniaturized dual-modal imaging device in the embodiment of the present application, the photoacoustic transparent isolation film 12 can be first fixedly arranged on the window part 132, and then the fixed part 131 can be fixedly installed on the skull of the small animal. After craniotomy on the small animal, after adding cerebrospinal fluid to the brain tissue of the small animal to discharge all the air, the window part 132 with the photoacoustic transparent isolation film 12 is fixedly arranged on the fixed part 131, thereby completing the installation of the photoacoustic transparent isolation film 12.

[0068] The embodiment of the present application can effectively avoid introducing air between the photoacoustic transparent isolation film 12 and the brain tissue, thereby avoiding the influence of the air between the photoacoustic transparent isolation film 12 and the brain tissue on the normal transmission of ultrasonic signals; compared with the solution of directly fixedly arranging the photoacoustic transparent isolation film 12 on the target imaging area of the small animal, the embodiment of the present application fixedly arranges the photoacoustic transparent isolation film 12 on the window part 132, which can ensure the flatness of the photoacoustic transparent isolation film 12 and avoid the occurrence of defocus in some areas, and improve the imaging quality of the fluorescence microscopy device 21.

[0069] Moreover, compared with the situation of directly bonding the photoacoustic transparent isolation film 12 to the small animal with glue, the embodiment of the present application can effectively avoid the situation of glue entering the brain tissue of the small animal and avoid the glue damaging the brain tissue of the small animal. It can be understood that the installation surface 133 between the fixed part 131 and the window part 132 can be a plane, so as to facilitate the window part 132 to be fixedly arranged on the fixed part 131. The upper surface of the headgear is a plane, providing a flat platform for the bonding of the cranial window body.

[0070] As Figure 3 and Figure 5 shown, in an embodiment of the present application, the window part 132 includes a first cover body 1321 and a second cover body 1322. Both the first cover body 1321 and the second cover body 1322 are annular, and a matching clamping structure is provided between the first cover body 1321 and the second cover body 1322 to sandwich the photoacoustic transparent isolation film 12 between the first cover body 1321 and the second cover body 1322.

[0071] Since both the first cover body 1321 and the second cover body 1322 are annular, and a matching clamping structure is provided between the first cover body 1321 and the second cover body 1322, the photoacoustic transparent isolation film 12 can be effectively fixed and clamped between the first cover body 1321 and the second cover body 1322, preventing the photoacoustic transparent isolation film 12 from sliding relative to the first cover body 1321 and the second cover body 1322.

[0072] Moreover, during the process of sandwiching the photoacoustic transparent isolation film 12 between the first cover body 1321 and the second cover body 1322, the photoacoustic transparent isolation film 12 can be effectively pre-stretched, so as to ensure that the whole photoacoustic transparent isolation film 12 is relatively flat. When the imaging window 10 is fixed in the target imaging area and at least part of the photoacoustic transparent isolation film 12 fits with the target imaging area, the tissue surface of the target detection area can be kept basically flat and not easily wrinkled, so that the cerebral cortex tissue of the small animal is laid flat on the focal plane of the fluorescence microscope device 21, ensuring the focusing accuracy of the fluorescence microscope device 21 in the whole target detection area and effectively improving the imaging quality of the fluorescence microscope device 21 and the ultrasonic imaging device 20. Specifically, as Figure 3 shown, in an embodiment of the present application, the bottom surface of the second cover body 1322 is fixedly connected to the fixing part 131; the part of the photoacoustic transparent isolation film 12 located inside the photoacoustic transparent window 11 is flush with the bottom surface of the second cover body 1322. That is, after the first cover body 1321, the photoacoustic transparent isolation film 12 and the second cover body 1322 of the window part 132 are fixed, the bottom surface of the second cover body 1322 can be fixedly connected to the fixing part 131, thereby fixedly connecting the window part 132 and the fixing part 131 together. Since the part of the photoacoustic transparent isolation film 12 located inside the photoacoustic transparent window 11 is flush with the bottom surface of the second cover body 1322, after the window part 132 is fixedly connected to the fixing part 131, it is convenient for the edge of the photoacoustic transparent isolation film 12 to fit or be fixedly connected to the fixing part 131, and the part located inside the photoacoustic transparent window 11 fits with at least part of the target imaging area.

[0073] Specifically, as Figure 5As shown, in an embodiment of the present application, the first cover 1321 is provided with a clamping groove 1323, and the second cover 1322 is provided with a clamping portion 1324 adapted to the clamping groove 1323, and the side wall of the clamping groove 1323 is configured to extend to the bottom surface of the first cover 1321 adjacent to the fixing portion 131.

[0074] That is, when the photoacoustic transparent isolation film 12 is clamped between the clamping groove 1323 of the first cover 1321 and the clamping portion 1324, the fixing and flattening of the photoacoustic transparent isolation film 12 can be realized by using the clamping groove 1323 and the clamping portion 1324.

[0075] Since the side wall of the clamping groove 1323 extends to the bottom surface of the first cover 1321 adjacent to the fixing portion 131, the portion of the photoacoustic transparent isolation film 12 located within the photoacoustic transparent window 11 can be flush with the bottom surface of the second cover 1322. It can be understood that the shapes of the clamping groove 1323 and the clamping portion 1324 can be selected according to needs, as long as it is ensured that the photoacoustic transparent isolation film 12 can be clamped between the first cover 1321 and the second cover 1322 and is not likely to slide relative to the first cover 1321 and the second cover 1322.

[0076] Specifically, taking the imaging window 10 in the miniaturized dual-modal imaging device of the embodiment of the present application installed in the brain of a small animal as an example, the installation steps of the imaging window 10 will be described.

[0077] During the installation of the imaging window 10 in the miniaturized dual-modal imaging device of the embodiment of the present application, the installation of the window portion 132 can be carried out first. The specific steps are to drop an appropriate amount of adhesive such as glue into the clamping groove 1323 provided on the first cover 1321, and then place the cut photoacoustic transparent isolation film 12 on the first cover 1321, and then buckle the clamping portion 1324 of the second cover 1322 into the clamping groove 1323 of the first cover, so as to fix and clamp the photoacoustic transparent isolation film 12 between the first cover 1321 and the second cover 1322, and realize the uniform stretching of the photoacoustic transparent isolation film 12 to improve the flatness of the photoacoustic transparent isolation film 12.

[0078] Then, the installation of the fixing part 131 is carried out. The specific steps are as follows: First, anesthetize the small animal and place it on the operating platform. Cut off the skin at the skull of the small animal, remove the tissues near the installation position, then absorb the moisture on the skull surface to keep the bonding surface dry. Then, use adhesives such as dental cement and instant glue to bond the fixing part 131 to the mouse skull; after the adhesive cures, make a craniotomy at the center position of the fixing part 131, and then evenly apply a layer of waterproof glue outside the fixing part 131, so as to form a concave area at the center position of the fixing part 131, and then drop artificial cerebrospinal fluid into this area; bond the sterilized window part 132 to the fixing part 131, and the waterproof glue can seal the bonding area between the fixing part 131 and the window part 132 to prevent air from entering; then add a layer of photocuring resin glue outside the fixed window 13 for sealing to avoid the situation that the fixed window 13 falls off due to the movement of the mouse during the curing process of the waterproof glue.

[0079] In another embodiment of the present application, in the miniaturized dual-modal imaging device of the present application embodiment, the fixed window 13 may include a first split body and a second split body. The first split body is provided with an installation surface 133. Both the first split body and the second split body are annular, and a matching clamping structure is provided between the first split body and the second split body to clamp the photoacoustic transparent isolation film 12 between the first split body and the second split body.

[0080] As Figure 4 shown, in an embodiment of the present application, fixing arms 1311 may be provided at both ends of the fixing part 131, so as to fix the position of the small animal in special scenarios.

[0081] As Figure 1 and Figure 2 shown, in the miniaturized dual-modal imaging device of the present application embodiment, the imaging device 20 further includes an installation base 23 and an installation bracket 24; the installation bracket 24 is fixedly arranged on the housing of the fluorescence microscopy device 21, and the ultrasonic transducer device 220 is fixedly arranged on the installation bracket 24. The installation base 23 is configured to be fixedly connected to the imaging window 10 on the side of the imaging window 10 away from the target imaging area. A base window through which the excitation light and fluorescence signal of the fluorescence microscopy device 21 can pass is provided on the installation base 23, and the objective lens 211 of the fluorescence microscopy device 21 is arranged in the base window.

[0082] In this way, during the installation process of the miniaturized dual-modal imaging device of the present application embodiment, after the objective lens 211 of the fluorescence microscopy device 21 is arranged in the base window of the installation base 23, then the installation base 23 and the imaging window 10 are fixed to each other, the housing of the fluorescence microscopy device 21 is fixedly arranged on the installation base 23, and then the ultrasonic transducer device 220 is fixedly arranged on the installation bracket 24.

[0083] Since the mounting base 23 is provided with a base window through which the excitation light and fluorescence signal of the fluorescence microscopy device 21 can pass, the base window can allow the excitation light and fluorescence signal of the fluorescence microscopy device 21 to pass through; specifically, since the objective lens 211 of the fluorescence microscopy device 21 is disposed within the base window, the height of the mounting base 23 can be adjusted according to the focal length of the fluorescence microscopy device 21, and the size of the base window matches the objective lens 211 of the fluorescence microscopy device 21.

[0084] To facilitate the transmission of the ultrasonic signal, after determining the imaging position and bonding and fixing the mounting base 23 on the imaging window 10, ultrasonic coupling agent can be evenly added into the base window of the mounting base 23. The ultrasonic coupling agent can completely fill the optical path of the fluorescence microscopy device 21, thereby avoiding affecting the imaging quality of the fluorescence microscopy device 21; then, after combining the mounting bracket 24, the fluorescence microscopy device 21 and the ultrasonic imaging device 20, they are mounted on the mounting base 23.

[0085] By providing the mounting base 23, it is convenient for the staff to disassemble and assemble the fluorescence microscopy device 21 and the ultrasonic imaging device 20 without changing the imaging position, which is beneficial to long-term multiple observations of the same research object.

[0086] Specifically, as Figure 1 shown, in an embodiment of the present application, the ultrasonic transducer device 220 includes at least one ultrasonic transducer assembly 22. The ultrasonic transducer assembly 22 includes an ultrasonic transducer probe 221 and a probe fixture 222. The ultrasonic transducer probe 221 is fixedly disposed on the probe fixture 222; the probe fixture 222 is disposed on the mounting bracket 24. Specifically, a plurality of linearly arranged ultrasonic transducer units can be provided on the ultrasonic transducer probe 221, and the plurality of ultrasonic transducer units can form a one-dimensional ultrasonic transducer array. The probe fixture 222 can effectively fix the ultrasonic transducer probe 221 on the mounting bracket 24, so that the ultrasonic transducer probe 221 can face the photoacoustic transparent window 11 and the target imaging area, thereby being used to emit ultrasonic signals to the target imaging area and receive the ultrasonic signals returned from the target imaging area through the photoacoustic transparent window 11. Specifically, the mounting bracket 24 extends two cantilevers with slots on both sides as the fixing positions of the probe fixture 222.

[0087] As Figure 1 and Figure 2 shown, in an embodiment of the present application, the probe fixture 222 includes two parts of left and right structures. The front end of the probe fixture 222 fixes the ultrasonic transducer probe 221, and the probe fixture 222 is connected and fixed by buckles arranged up and down, which can effectively reduce the mass.

[0088] Specifically, the mounting base 23 and the imaging window 10 can be bonded by an adhesive such as a photo-curing resin adhesive, or can be fixedly connected by mechanical means such as screws, or structures such as snap fits or magnetic attractions can be adopted to achieve rapid assembly and disassembly between the mounting base 23 and the imaging window 10.

[0089] Furthermore, as Figure 1 shown, in an embodiment of the present application, the probe fixture 222 is movably arranged on the mounting bracket 24. Since the probe fixture 222 is movably arranged on the mounting bracket 24, by adjusting the position of the probe fixture 222 arranged on the mounting bracket 24, the orientation of the ultrasonic transducer probe 221 and / or the distance from the target imaging area can be adjusted, so that the ultrasonic transducer probe 221 can emit ultrasonic signals to the required area in the target imaging area as needed and receive the ultrasonic signals returned by the required area in the target imaging area through the photoacoustic transparent window 11, thereby meeting the imaging requirements.

[0090] Specifically, in an embodiment of the present application, the mounting bracket 24 is provided with mounting holes extending in a first direction; the probe fixture 222 is provided with fixing holes extending in a second direction; the ultrasonic transducer device 220 further includes a fixing member configured to penetrate through the mounting holes and the fixing holes to fixedly arrange the probe fixture 222 and the ultrasonic transducer probe 221 on the mounting bracket 24, and the position of the fixing member in the mounting holes, the position of the fixing member in the fixing holes, and the angle between the first direction and the second direction are adjustable. Specifically, the fixing member can be a screw-nut mechanism or other fixing mechanisms, which are not limited herein.

[0091] Since the mounting holes on the mounting bracket 24 extend in the first direction and the fixing holes on the probe fixture 222 extend in the second direction, the position of the fixing member in the mounting holes, the position of the fixing member in the fixing holes, and the angle between the first direction and the second direction are adjustable.

[0092] In this way, the orientation angle of the ultrasonic transducer probe 221 can be adjusted by adjusting the angle between the first direction and the second direction as needed; the position of the ultrasonic transducer probe 221 in the first direction can be adjusted by adjusting the position of the fixing member in the mounting holes, and the position of the ultrasonic transducer probe 221 in the second direction can be adjusted by adjusting the position of the fixing member in the fixing holes; in this way, the ultrasonic transducer probe 221 can have three degrees of freedom relative to the mounting bracket 24, including one rotational degree of freedom and two translational degrees of freedom, which can facilitate the flexible adjustment of the orientation position of the ultrasonic transducer probe 221 and the distance from the target imaging area as needed, so as to obtain corresponding ultrasonic imaging results as needed.

[0093] As Figure 1As shown, in one embodiment of the present application, the ultrasonic transducer device 220 includes two ultrasonic transducer components 22, and the two ultrasonic transducer components 22 are respectively arranged on both sides of the fluorescence microscopy device 21. In this way, dual-plane ultrasonic imaging can be effectively achieved, thereby effectively improving the ultrasonic imaging efficiency.

[0094] It can be understood that in other embodiments of the present application, more ultrasonic transducer components 22 can be arranged around the fluorescence microscopy device 21; and the ultrasonic transducer probe 221 can also be changed to a phased array or a planar array probe according to needs, which is convenient for the miniaturized dual-modal imaging device in the embodiments of the present application to perform three-dimensional ultrasonic imaging.

[0095] As Figure 7 and Figure 8 As shown, in one embodiment of the present application, the ultrasonic transducer device 220 further includes a flexible signal connection part 223 and a communication cable 224, and each ultrasonic transducer probe 221 is electrically connected to the communication cable 224 through the flexible signal connection part 223.

[0096] Specifically, in the embodiment in Figure 7 , in the case where two ultrasonic transducer components 22 are provided, the two ultrasonic transducer components 22 can be respectively electrically connected to the same communication cable 224 through the flexible signal connection part 223. In another embodiment of the present application, they can also be separately electrically connected to a communication cable 224, and there is no limitation here.

[0097] Since each ultrasonic transducer probe 221 is electrically connected to the communication cable 224 through the flexible signal connection part 223, the communication cable 224 can be connected to various signal processing devices, and the signal processing device can process the received signals to obtain ultrasonic imaging results.

[0098] It can be understood that when the ultrasonic transducer probe 221 is directly electrically connected to related devices through the communication cable 224, when the number of ultrasonic transducer units of the ultrasonic transducer probe 221 increases, the increase in the number of coaxial lines 2241 in the communication cable 224 will cause an increase in the wire diameter and hardness of the communication cable 224, thereby greatly reducing flexibility. When worn on the head of a small animal, the free movement of the research object is severely restricted, thus affecting the experimental results.

[0099] Therefore, in the miniaturized dual-modal imaging device of the embodiments of the present application, each ultrasonic transducer probe 221 is electrically connected to the communication cable 224 through the flexible signal connection part 223. The flexible signal connection part 223 will greatly reduce the stiffness of torsion and bending, thereby improving the movement flexibility when a small animal wears the miniaturized dual-modal imaging device of the embodiments of the present application. The flexible signal connection part 223 can be a multi-layer flexible printed circuit board (FPC) structure.

[0100] Specifically, the width of the flexible signal connection part 223 can be reduced to 4 mm, thereby further reducing the stiffness of torsion and bending. As Figure 8 shown, both the upper and lower surfaces of the flexible signal connection part 223 are covered with a shielding ground 2231, which is connected to the shielding ground 2231 of the coaxial cable 2241 through the coaxial cable welding area, so as to wrap all the signal lines 2233 of the ultrasonic transducer unit to reduce the interference of external electromagnetic signals on the ultrasonic signals; the signal lines 2233 of the signal lines 2233 of the ultrasonic transducer unit and the signal ground 2232 are led out to the surface layer of the coaxial cable welding area through vias, facilitating welding with each coaxial cable 2241 in the communication cable 224.

[0101] In a specific embodiment of the present application, the photoacoustic transparent window 11 can be controlled within 9 mm × 10 mm, and the entire miniaturized dual-modal imaging device can effectively achieve dual-modal imaging of the brains of small animals; the two ultrasonic transducer assemblies 22 are compactly located in front of and behind the objective lens 211 of the fluorescence microscopy device 21, and the two ultrasonic transducer probes 221 and the objective lens 211 of the fluorescence microscopy device 21 are controlled within the range of 9 mm * 10 mm, making full use of the space within the photoacoustic transparent window 11. The element width of the ultrasonic transducer probe 221 is 0.08 mm, the element spacing is 0.02 mm, the main axis aperture is 6.38 mm, with a total of 64 elements, and the total width is only 8.4 mm, which is comparable to the size of the mouse brain; the size of the objective lens 211 of the fluorescence microscopy device 21 is less than 4.5 mm × 4.5 mm. By arranging the two ultrasonic transducer probes 221 and the objective lens 211 of the fluorescence microscopy device 21 longitudinally and placing them in the front and back positions of the fluorescence microscopy device 21 respectively, the mutual interference of dual-modal imaging is avoided, and the occupied space of the entire imaging structure is controlled within 9 mm × 10 mm, which enables the miniaturized dual-modal imaging device to be installed on the head of a small animal.

[0102] Moreover, in terms of quality control, in the miniaturized dual-modal imaging device of the embodiment of the present application, the mass of the ultrasonic transducer probe 221 is less than 0.3 g, and the mass of the fluorescence microscopy device 21 is also within 3.25 g; the probe fixture 222 can be made of resin material and assembled through a snap structure, and its mass is as light as 0.2 g. The total mass of the imaging device 20 in the miniaturized dual-modal imaging device of the embodiment of the present application is less than 4.25 g. The imaging window 10 is also processed with resin material, and the overall weight is less than 0.6 g. The total installation mass of the miniaturized dual-modal imaging device of the embodiment of the present application can be less than 4.85 g, and it can be worn on the head of a freely moving small animal for dual-modal real-time imaging.

[0103] The above are only the preferred embodiments of the present application and are not intended to limit the present application. Any modifications, equivalent replacements, etc. made within the spirit and principle of the present application shall be included within the protection scope of the present application.

[0104] The above are only the preferred embodiments of the present application and are not intended to limit the present application. Any modifications, equivalent replacements, etc. made within the spirit and principle of the present application shall be included within the protection scope of the present application.

[0105] Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The choice of terminology used herein is intended to best explain the principles of the embodiments, the practical application, or improvements made to the technology in the market, or to enable other ordinary skill in the art to understand the embodiments disclosed herein. The scope of the present application is defined by the appended claims.

Claims

1. A miniaturized dual-modal imaging device, characterized in that, Comprising: An imaging window (10), the imaging window (10) being configured to be fixed to a target imaging area, and the imaging window (10) being provided with a photoacoustic transparent window (11); An imaging device (20), the imaging device (20) being fixedly connected to the imaging window (10) and comprising a fluorescence microscopy device (21) and an ultrasonic transducer device (220); The fluorescence microscopy device (21) comprises an excitation light emitting unit and a fluorescence receiving unit, the excitation light emitting unit being configured to emit excitation light towards the target imaging area, and the fluorescence receiving unit being configured to receive the fluorescence signal returned from the target imaging area through the photoacoustic transparent window (11); The ultrasonic transducer device (220) is configured to at least receive the ultrasonic signal returned from the target imaging area through the photoacoustic transparent window (11).

2. The miniaturized dual-modal imaging device according to claim 1, wherein The imaging window (10) comprises a fixing form (13) and a photoacoustic transparent isolation film (12); The fixing form (13) is annular to enclose the photoacoustic transparent window (11), and the fixing form (13) is provided with a mounting surface (133), the mounting surface (133) being configured to fit the outer contour of the target imaging area; The photoacoustic transparent isolation film (12) is fixedly arranged on the fixing form (13) and covers the corresponding area of the photoacoustic transparent window (11) so that the excitation light, the fluorescence signal and the ultrasonic signal can penetrate the photoacoustic transparent isolation film (12); The fixing form (13) and the photoacoustic transparent isolation film (12) are configured to enclose a closed chamber with the target imaging area.

3. The miniaturized dual-modal imaging device according to claim 2, characterized in that, The fixing form (13) comprises a fixing part (131) and a form part (132) fixedly connected to each other, the fixing part (131) being provided with the mounting surface (133), the form part (132) being located at one end of the fixing part (131) away from the target imaging area, and the photoacoustic transparent isolation film (12) being configured to be fixedly arranged on the form part (132).

4. The miniaturized dual-modal imaging device according to claim 1, wherein The imaging device (20) further comprises a mounting base (23) and a mounting bracket (24); The mounting bracket (24) is fixedly arranged on the housing of the fluorescence microscopy device (21), and the ultrasonic transducer device (220) is fixedly arranged on the mounting bracket (24). The mounting base (23) is configured to be fixedly connected to the imaging window (10) on the side of the imaging window (10) away from the target imaging area. A base window for the excitation light and the fluorescence signal of the fluorescence microscopy device (21) to pass through is provided on the mounting base (23), and the objective lens (211) of the fluorescence microscopy device (21) is arranged in the base window.

5. The miniaturized dual-modal imaging device according to claim 4, characterized in that, The ultrasonic transducer device (220) includes at least one ultrasonic transducer assembly (22), and the ultrasonic transducer assembly (22) includes an ultrasonic transducer probe (221) and a probe fixture (222). The ultrasonic transducer probe (221) is fixedly arranged on the probe fixture (222); the probe fixture (222) is arranged on the mounting bracket (24).

6. The miniaturized dual-modal imaging device according to claim 5, characterized in that The probe fixture (222) is movably arranged on the mounting bracket (24).

7. The miniaturized dual-modal imaging device according to claim 6, wherein The mounting bracket (24) is provided with mounting holes extending in a first direction; The probe fixture (222) is provided with fixing holes extending in a second direction; The ultrasonic transducer device (220) further includes a fixing member, and the fixing member is configured to penetrate through the mounting holes and the fixing holes to fixedly arrange the probe fixture (222) and the ultrasonic transducer probe (221) on the mounting bracket (24), and the position of the fixing member in the mounting holes, the position of the fixing member in the fixing holes, and the included angle between the first direction and the second direction are adjustable.

8. The miniaturized dual-modal imaging device according to claim 5, wherein The ultrasonic transducer device (220) includes two ultrasonic transducer assemblies (22), and the two ultrasonic transducer assemblies (22) are respectively arranged on both sides of the fluorescence microscopy device (21).

9. The miniaturized dual-modal imaging device according to claim 5, wherein, The ultrasonic transducer device (220) further includes a flexible signal connection part (223) and a communication cable (224), and each ultrasonic transducer probe (221) is electrically connected to the communication cable (224) through the flexible signal connection part (223).

10. The miniaturized dual-modal imaging device according to any one of claims 1 to 9, characterized in that, The ultrasonic transducer device (220) is configured to send ultrasonic waves to a target imaging area and receive ultrasonic signals returned by the target imaging area through the photoacoustic transparent window (11).

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