WO2018047999A1

WO2018047999A1 - Otoscope capable of simultaneously achieving multiple types of imaging by non-invasive method

Info

Publication number: WO2018047999A1
Application number: PCT/KR2016/010253
Authority: WO
Inventors: 송경애; 유단친
Original assignee: 주식회사 현주인테크
Priority date: 2016-09-07
Filing date: 2016-09-12
Publication date: 2018-03-15
Also published as: KR101931751B1; KR20180027975A

Abstract

The present invention relates to an otoscope capable of simultaneously achieving multiple types of imaging by a non-invasive method. The present invention can not only simultaneously obtain a low-resolution tomographic image of the deep middle ear and/or a confocal high-resolution image of the proximal middle ear, but can also obtain a white-light image and/or a narrow-band image of the surface of the eardrum. Therefore, from the pathological viewpoint of the middle ear, it is possible to diagnose and assess the middle ear in a non-invasive manner without biopsy.

Description

Otoscope that allows multiple simultaneous imaging by non-invasive methods

The present invention relates to an otoscope capable of a plurality of simultaneous imaging by a non-invasive method, and can not only simultaneously obtain a low-resolution middle tomographic image and / or confocal high-resolution image of the middle ear layer, but also white light And / or narrowband images of the tympanic surface can be obtained, and from a pathological perspective of the middle ear, a noninvasive, nonbiopsy diagnostic evaluation is possible.

Otitis media (OM) is a middle ear infection often caused by the growth of bacteria between the tympanic membrane (TM) and the inner ear. Infants often develop middle ear infections due to an upper respiratory tract infection or an allergic reaction to food or environmental allergens.

Otitis media is characterized by symptoms, duration, otoscopic observations, physical diagnosis, and the like. The most common form is acute otitis media (AOM), a rapid rapid-onset infection with one or more symptoms. In this case, doctors use pneumatic otoscopy, which can usually detect abnormal aspects of the tympanic membrane, such as tympanic bulging, opacity, exudation, and reduced mobility.

Most non-purulent otitis media are treated within one or two weeks, sometimes with antibiotics. Recurrent acute otitis media and exudative otitis media (OM) are considered chronic otitis media (chronic OM). These diseases often cause long-term or permanent damage to the ear and can lead to hearing loss and speech delay if not well managed in children.

Exudative otitis media can usually be identified through pneumatic otoscope, but may also be supplemented by tympanometry and / or acoustic reflectometry. Exudative otitis media can also be directly identified by the presence of fluid in the external auditory canal following tympanocentesis or tympanic membrane perforation.

The important thing is to distinguish exudative otitis media from acute otitis media. Exudative otitis media is more common than acute otitis media. Exudative otitis media may be accompanied by bacterial pulmonary tuberculosis infection and become a pre-symptom of or develop acute otitis media.

Diagnosis of acute otitis media is often due to uncertainty, especially in infants and children. In other words, in the case of otitis media otitis media, when an exudative otitis media is considered uncertain, it may be mistakenly diagnosed as acute otitis media. In this case, there is a problem in that antibiotics are prescribed unnecessarily.

The clinician says that in children, discomfort in the middle ear due to dysfunction of the Eustachian tube and constriction of the tympanic membrane, or when acute pulmonary tuberculosis is accompanied by chronic premature middle effusion (MEE) Efforts should be made to prevent false-positive diagnosis.

The need for preventing such false diagnosis stems from the high demand for additional quantitative data that can help determine optimal treatment plans and enable more effective management of these common set diseases.

Recent clinical studies have produced strong evidence of the agreement between chronic otitis media and the presence of a bacterial biofilm on the back of the tympanic membrane. Biofilms are complex self-assembled habitats of many species of microorganisms (eg bacteria, fungi, viruses, etc.) and co-proliferate within cohesive biopolymer bases.

The microstructure of the biofilm was found to be very heterogeneous in composition and composition, including cell distribution, cell aggregation, structural voids, and fluid channels. Within biofilms, microorganisms may be protected from harsh environments, such as exposure to antibiotics or disinfectant treatments, to increase resistance periodically, and may allow for recurrence or perpetuation of infectious diseases.

Major bacteria that cause otitis media include Streptococcus pneumoniae, Moraxella catarrhalis, and non-encapsulated Haemophilus influenza.

As optical coherence tomography (OCT) combined with otoscope, conventional systems have been used as additional equipment to diagnose and quantify otitis media (Kim et al. US2014 / 0012141 A1).

While the standard otoscope focused on illumination and enlargement of the tympanic surface, it was relatively ineffective in displaying the structure of the middle ear, and it was more difficult to identify the middle ear structure, especially when the eardrum was no longer transparent due to disease. Therefore, the invasion process should be performed, in which case there is a problem that adversely affects the eardrum.

OCT can obtain high resolution images for depth range, has imaging capability, and has various applications in diagnosing the middle ear, and can detect and quantify the middle ear biofilm. In addition, micro-resolution allows OCT to image the microstructure of biofilms, including the dynamics of biofilm formation.

However, the diagnostic evaluation is performed not only by otoscopic visual analysis but also by tomographic examination of the gross morphological features, and thus, clinical doubt is high. Such stratification using only morphology is not constant, and there is a problem that confusion occurs by generating various diagnostic results, thus limiting the biochemical understanding of defining diseases. As a result, the patient will receive excessive levels of treatment in the worst case, adversely affecting the body.

On the other hand, non-invasive detection of the middle ear environment using molecular biological methods, such as the Raman spectroscopic (RS) detection platform, provides fundamental physiology that makes it possible to predict not only the state of the body but also future behavior. Get to know.

In addition to morphological analysis as well as chemical analysis of the pathology of the middle ear, it is disclosed in US2016 / 0007840A1. This detection system is based on molecular biological data collection to analyze vibrational modes that provide a "fingerprint" of pathological physiological conditions. Because of the molecular biological specificity of these technologies, spectral data not only enables better objective detection and grading than now, but also provides a new way to identify cell types within tissues. However, such a device has a low positional accuracy and there is a problem that high uncertainty and diversity exist in diagnosis because it is impossible to properly designate a diagnosis range due to lack of structural information inside the middle ear.

The present invention has been made to solve the above problems, the present invention relates to a combination structure in the otoscope for using Raman Spectroscopy (RS) and OCT, to establish a complementary relationship between the RS and OCT, By providing images and correlating them with the biochemical data of the middle ear, the goal is to help determine the optimal treatment strategy and thus to significantly improve the accuracy of the examination.

It is another object of the present invention to more effectively manage a common set of diseases from the accuracy of such examinations.

It is another object of the present invention to simultaneously aggregate OCT dose measurement data and biochemical Raman spectrum maps over a large area of a sample, and to improve synergy between the two devices using the aggregated data.

In addition, another object of the present invention is to enable a wider range of biomedical applications by combining them compared to the areas where RS and OCT technologies are applicable respectively.

In addition, the present invention guides the construction of a combined RS-OCT system to obtain a Raman spectrum in a small (<100 μm) region of irregular tissue by using the OCT, and by using the RS of the ambiguous structure in the OCT image It is another object to specify the biochemical composition.

In addition, the present invention is not only able to image the signal obtained from the otoscope using CCD, but also to distribute the appropriately to the RS and OCT to obtain the necessary biometric information in another object.

In order to achieve the above object, the present invention is inserted into the ear canal, the insertion tube is disposed an optical channel for optical signal transmission; A knob positioned at the rear of the insertion tube, supporting the optical channel, and having a luminaire coupled thereto; A housing located at a rear side of the knob and including a reflection mirror reflecting an optical signal received from the white light image channel; And

A camera module positioned below the housing and receiving an optical signal reflected from the reflection mirror; And the optical signal is transmitted to the Raman spectroscopy (RS) and the optical coherence tomography apparatus (OCT) by the optical fiber, the otoscope capable of a plurality of simultaneous imaging by a non-invasive method. To provide.

The optical channel for transmitting the optical signal is a Raman spectroscope-optical coherence tomography (RS-OCT) scanning probe and a white light image channel arranged independently of each other in parallel with each other, and the knob includes an adjustable lens and the RS- The first optical fiber is connected to the opposite end of the inner ear direction of the OCT scanning probe to transmit an optical signal to the RS and the OCT or to transmit the optical signal from the RS and the OCT to the RS-OCT scanning probe.

The signal transmitted from the first optical fiber is reflected and transmitted by a dichroic mirror, and the reflected signal and the transmitted signal are preferably transmitted to RS and OCT or OCT and RS, respectively.

It is preferable that a collimation lens is further provided between the white light image channel and the reflection mirror.

The RS-OCT scanning probe includes a lead-zirconium titanate including a tube and probe optical fibers embedded in the tube and having two pairs of electrodes generally having a cylindrical shape and axially penetrating the electrodes. PZT) scanning probe, and a gradient index objective lens installed at the inner ear end of the tube and transferring the pattern formed by the probe optical fiber to the inner ear.

The lighting means preferably includes an embedded LED and a second optical fiber having one end connected to the LED and the other end connected to the insertion tube.

The optical channel is preferably an optical relay provided with a lens at both ends of the channel.

A first optical fiber for transmitting an optical signal to Raman spectroscopy (RS) and an optical coherence tomography (OCT) device, and a second optical fiber for connecting the luminaire and the insertion tube, wherein the housing includes the optical relay A first reflection mirror for sending an optical signal transmitted through the camera module; A second reflection mirror that transmits or reflects the optical signal transmitted through the optical relay to the first reflection mirror; And a third reflection mirror for receiving the optical signal reflected from the second reflection mirror and transferring the optical signal to the first optical fiber.

According to the present invention as described above, by combining the white light imaging device, Raman Spectroscopy (RS) and OCT into a single device, by establishing a complementary relationship, by providing an image of the structure and interconnected with the biochemical data of the middle ear It can be helpful in determining the optimal treatment strategy, and therefore an effect is expected to greatly improve the accuracy of the examination.

In addition, the present invention is expected to have an effect of more effectively managing a common set of diseases from the accuracy of such examination.

In addition, the present invention is expected to combine the OCT dose measurement data and biochemical Raman spectrum maps over a large area of the sample at the same time, and to use the aggregated data to improve the synergy between the two devices.

In addition, the present invention is expected to have an action effect to greatly widen the range of biomedical applications by combining them compared to the areas where the respective RS and OCT technologies were applicable.

In addition, the present invention guides the construction of a combined RS-OCT system to obtain a Raman spectrum in a small (<100 μm) region of irregular tissue by using the OCT, and by using the RS of the ambiguous structure in the OCT image An effect is expected to characterize the biochemical composition.

In addition, the present invention is expected not only to image the signal obtained from the otoscope by using the CCD, it is expected that the effect that can be obtained in a variety of biological information by appropriately distributed to RS and OCT.

In addition, the present invention can further reduce the thickness of the element to be inserted in the otoscope, it is expected that the effect that can be extended to the age range that can be applied to the otoscope infants.

In addition, the present invention is expected to have an effect of enabling the accurate examination of the disease or condition to the inner middle ear region of the tympanic membrane, which is not observed by the naked eye.

1 is a schematic diagram of a white light-RS-OCT system having a combined white light image channel, an RS-OCT channel and a modeled scanning optics according to an embodiment of the invention.

2 is a schematic diagram of a white light-RS-OCT system having a separate white light image channel, an RS-OCT channel, and a modeled scanning optics according to another embodiment of the present invention.

3 is a perspective view showing a modeled RS-OCT scanning probe according to an embodiment of the present invention and a cross-sectional view showing an operating state.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings and preferred embodiments.

The present invention relates to a wideband imaging otoscope having a plurality of modes, which not only can simultaneously obtain a low-resolution tomographic image of a middle ear and / or a confocal high-resolution image of a middle ear proximal tomography, as well as white light and / or tympanic membrane. Narrow-band images of the surface can be obtained and, therefore, from a pathology perspective of the middle ear, non-invasive, non-biopsy diagnostic evaluation is possible. In addition, the Raman spectroscopic detection mode enables biochemical analysis of the middle ear and enables cell type recognition in tissue without staining.

The otoscope according to the present invention is composed of two optical channels, which are a non-flowing wide image channel and a focusable scanning confocal image channel. The wide image channel includes an embedded white and / or narrow color LED array and a pair of CMOS camera sensors used for wideband white light and narrowband filtered images. The adjustable scanning confocal channel includes a built-in MEMS scanner and a focus adjustable lens system for adjusting the position of the focus relative to other wavelengths.

Most approaches to combining white images, RS and OCT into a single instrument combine sampling and light scanning while maintaining their function as an independent detector. The advantage of this white light-RS-OCT system is that it uses independent detection arms to position the hardware so that each technology can be optimized and operated independently.

Advantages of conventional RS-OCT scanning and sampling optics can be used to induce Raman spectrum acquisition for small areas of irregular tissue (<100 μm) using OCT, and biochemistry for obscure structures in OCT images using RS The enemy composition can be specified.

The main objectives in the design of a white light-RS-OCT combination system are the selection of the appropriate light source and light scanner, and the selection of a suitable detector architecture.

In order to understand the white light-RS-OCT system in combination with conventional scanning and sampling optics, the first consideration is to select the light source so that the Raman scattering spectrum and the OCT bandwidth do not overlap on the spectrum. For tissue RS, results have been reported ranging from ultraviolet to infrared wavelength range of 1064 nm.

Typically, a light source in the near infrared region is preferred because tissue autofluorescence is reduced. However, Raman scattering intensity and detector response also usually decrease with longer wavelengths. A wavelength stabilized 785 nm diode laser was employed as the Raman source, providing a “fingerprint” region for organic molecules of relative wavenumbers of 815 to 930 nm, ie 500 to 2000 cm −1. The SLD (Superluminescent Diode) source for the OCT was chosen to have an optical 3dB bandwidth of 80nm and a maximum spectral width of about 1250-1370nm at the center, so that no overlap occurred in combination with the RS system.

In order to combine the two types of RS-OCT into one channel, a double-clad optical fiber (first optical fiber) for single mode of 1250 to 1600 nm and multi-mode operation of 400 to 2200 nm was used.

White light-RS-OCT system 100 according to an embodiment of the present invention is shown in FIG. The laser beams output from the Raman spectroscope (RS, 150) and the optical coherence tomography (OCT) 170 modules are provided by the first optical fiber 140, which is a double clad, via a dichroic mirror 161. Combined into one beam (optical signal). Thereafter, the combined beam is irradiated in parallel by the collimating lens 127 coated with a wavelength band of 750 ~ 1350nm, and through the third reflecting mirror 125 and the first reflecting mirror 129 which are scanning mirrors, In the present invention, the third reflecting mirror 125 may be a galvanometer mirror pair or MEMS mirror having a low height, and the beam may be shaken on two planes. That is, one beam is shaken in a specific path on one plane, another beam is shaken in a specific path on another plane, and the two beams are shaken in different paths.

The output beam is then focused on the tympanic membrane 11 by the optical relay 111. In order to view the entire area of the tympanic membrane 11, the scanning area (Field-of-Scanning) is adjusted to 7 mm x 7 mm. On the other hand, in order to more easily approach the proximal end of the tympanic membrane 11 through the ear canal, the thickness of the insertion portion 110 of the otoscope 100 is manufactured to have a diameter of 3.6 mm and a length of 50 mm. Thus, if not an adult, it is possible to insert the otoscope 100 into the ear canal.

The position of the focal point of the RS-OCT system is adjustable inside the optical relay 111, at which time it is adjusted by a convertible lens provided in the knob 120. The light signal scattered from the intratympanic tissue is condensed by the same optical focus and reincident to the first optical fiber 140. The signal is then processed by separate RS 150 and OCT module 170.

A white optical image channel having a bandwidth of 400 to 700 nm is combined with the RS-OCT scanning channel via the optical relay 111 in the insertion unit 110 of the otoscope to realize the full color image. That is, the two channels overlap. Subsequently, light is irradiated toward the tympanic membrane 11 through the second optical fiber 115 by the embedded LED array 113 serving as a lighting means, and the reflected optical signal is a white light image signal by the dichroic mirror 121. Separated from the RS-OCT scanning channel, the separated optical signal is transmitted to the CMOS camera sensor 135. The position on the axis of the tympanic image can be adjusted by the focus lens 131.

In order to satisfy the conditions of the filed-of-scanning of the RS-OCT system and the field-of-view for the white light image, the optical relay 111 in the insertion unit 110 is provided with a plurality of lenses. It is composed. The optical elements of the optical relay 111 have an antireflective coating for wavelengths of 800 to 1550 nm and have an average loss rate of less than 1% over the entire bandwidth.

White light-RS-OCT system according to another embodiment of the present invention is shown in Figures 2 and 3.

In this embodiment, the white light image channel and the RS-OCT combination channel are separated, and the RS-OCT scanning system is positioned at the distal end of the insertion path. This eliminates the excess and complexity of the optical elements.

According to another embodiment of the present invention, a white light-RS-OCT system with separate channels and a simplified scanning probe is shown schematically in FIG. 2.

The cross-sectional area of the insert 110 is kept as small as possible, less than 3.6mm. In addition, the white light image channel in the insertion portion is composed of a white light image fiber 119 having 30,000 pixels and a gradient index objective lens 121.

Thereafter, the irradiated image (pattern) is collimated by the collimating lens (focal lens) 131 and irradiated by the camera sensor 135. The RS-OCT scanning probe 117 can be moved from side to side with respect to the otoscope axis, and the RS-OCT scanning probe 117 is moved to the front of the end of the otoscope by the knob 120 which can adjust the focus. The focus can be adjusted by allowing it to be configured. At this time, the movement of the RS-OCT scanning probe 117 is due to the conventional mechanism (mechanism) for converting the rotational movement into a linear movement. That is, when the knob 120 is rotated clockwise or counterclockwise, the RS-OCT scanning probe 117 moves left or right with respect to the direction of the eardrum, thereby allowing perspective to be adjusted.

By such an otoscope system, it is possible to adjust the working distance of the RS-OCT scanning probe 117 at a narrower ear canal than the embodiment of FIG. 1, and in particular, a high numerical aperture index objective (see FIG. 3). 180) can be produced to have a high resolution.

3 is a perspective view and a cross-sectional view illustrating an operation of the RS-OCT scanning probe according to an embodiment of the present invention.

As shown, the simplified RS-OCT scanning probe 117 performs scanning by supporting the distal end of the first optical fiber 140 in a simplified operating system. Here, the system may be a small-diameter lead-zirconium titanate (PZT) scanning probe or a MEMS scanning probe having the same size, and the two probes may have a fixed gradient index at the end of the first optical fiber 140. The objective lens 180 has a function of operating on two different axes in front.

The probe 117 is embedded in a thin walled hypodermic injection tube 147 having a total diameter of about 2.6 mm. The probe 117 is configured such that two pairs of piezoelectric elements 141 form a cylindrical shape as a whole, and an electrode 143 is provided at one end of the piezoelectric element to connect a wire 145 to each other. The element 141 is shaped such that a hole is formed at the center thereof, and the first optical fiber 140 penetrates the hole at the center thereof.

When an amplitude modulated sine wave having a phase difference of 90 ° is applied to the two pairs of piezoelectric elements 141, the two pairs of piezoelectric elements 141 operate in a spiral pattern according to the amplitude modulated sine wave, and the first optical fiber 140 also works in conjunction with the same pattern, and the OCT and the RS receives the pattern to obtain 3D and 2D data, respectively.

If a wave is applied at slightly different frequencies, the scanning pattern forms a Lissajou pattern according to the frame rate of the difference between the two driving frequencies (ratio of the rate at which successive images are taken or reproduced). do.

Although the present invention has been described in more detail with reference to the examples, the present invention is not necessarily limited to these embodiments, and various modifications can be made without departing from the spirit of the present invention. Therefore, the embodiments disclosed in the present invention are not intended to limit the technical idea of the present invention but to describe the present invention, and the scope of the technical idea of the present invention is not stabilized by these embodiments. The protection scope of the present invention should be interpreted by the following claims, and all technical ideas within the equivalent scope should be interpreted as being included in the scope of the present invention.

Claims

An insertion tube inserted into the ear canal and having an optical channel for transmitting an optical signal;

A knob positioned at the rear of the insertion tube, supporting the optical channel, and having a luminaire coupled thereto;

A housing located at a rear side of the knob and including a reflection mirror reflecting an optical signal received from the white light image channel; And

A camera module positioned below the housing and receiving an optical signal reflected from the reflection mirror;

It is configured to include,

The optical signal is transmitted to the Raman spectroscopy (RS) and optical coherence tomography (OCT) by the optical fiber, a plurality of simultaneous otoscope by non-invasive method.
The method of claim 1,

The optical channel for transmitting the optical signal is a Raman spectroscope-optical coherence tomography (RS-OCT) scanning probe and a white light image channel arranged side by side and independently of each other,

The knob has a built-in adjustable lens,

A non-invasive method characterized in that the first optical fiber is connected to the opposite end of the RS-OCT scanning probe, the optical fiber is transmitted to the RS and OCT or the optical signal from the RS and OCT to the RS-OCT scanning probe. Otoscope that allows multiple simultaneous imaging by means.
The method of claim 2,

The signal transmitted from the first optical fiber is reflected and transmitted by a dichroic mirror, and the reflected signal and the transmitted signal are transmitted to RS and OCT or OCT and RS, respectively, by a plurality of simultaneous invasive methods. Otoscope capable of imaging.
The method of claim 2,

An otoscope capable of a plurality of simultaneous imaging by a non-invasive method, characterized in that a collimating lens is further provided between the white light image channel and the reflection mirror.
The method of claim 2,

The RS-OCT scanning probe,

With the tube,

A lead-zirconium titanate (PZT) scanning probe embedded in the tube, the lead-zirconium titanate (PZT) scanning probe comprising a probe optical fiber axially penetrating the electrodes while the two pairs of electrodes are generally cylindrical in shape;

An otoscope having a plurality of simultaneous imaging by a non-invasive method, characterized in that it is installed at the inner end of the tube, and comprises a gradient index objective lens for transferring the pattern formed by the probe optical fiber to the inner ear. .
The method of claim 1,

The lighting means,

An otoscope capable of a plurality of simultaneous imaging by a non-invasive method comprising an embedded LED and a second optical fiber, one end of which is connected to the LED and the other end of which is connected to the insertion tube.
The method of claim 1,

The optical channel is an otoscope capable of a plurality of simultaneous imaging by a non-invasive method, characterized in that the optical relay is provided with a lens at both ends of the channel.
The method of claim 7, wherein

It comprises a first optical fiber for transmitting to the optical signal Raman spectroscopy (RS) and optical coherence tomography (OCT), and a second optical fiber connecting the luminaire and the insertion tube,

In the housing,

A first reflection mirror for sending an optical signal transmitted through the optical relay to the camera module;

A second reflection mirror that transmits or reflects the optical signal transmitted through the optical relay to the first reflection mirror; And

A third reflection mirror for receiving the optical signal reflected from the second reflection mirror and transferring the optical signal to the first optical fiber;

Otoscope capable of simultaneous imaging of a plurality by a non-invasive method characterized in that it comprises a.