Optical coherence tomography technology based on interferometer principle
Optical Coherence Tomography (OCT) is a low-loss, high-resolution, non-invasive medical and imaging technology developed in the early 1990s. Its principle is similar to ultrasound imaging, except that it uses light instead of sound.
Optical coherence tomography technology uses the basic principle of weak coherent light interferometer to detect back reflection or several scattering signals of incident weak coherent light at different depth levels of biological tissue. Through scanning, two-dimensional or three-dimensional structural images of biological tissue can be obtained. .
Compared with some other imaging technologies, such as ultrasound imaging, magnetic resonance imaging (MRI), X-ray computed tomography (CT), etc., OCT technology has relatively higher resolution (several microns). At the same time, it is similar to confocal imaging. Compared with ultra-high resolution technologies such as micro and multi-photon microscopy, OCT technology has greater tomographic capabilities. It can be said that OCT technology fills the gap between these two types of imaging technologies.
The structure and basic principles of optical coherence tomography
Optical coherence tomography is based on the principle of interferometer. It uses near-infrared weak coherent light to illuminate the tissue to be measured, and generates interference based on the coherence of the light. It uses superheterodyne detection technology to measure the intensity of the reflected light, which is used to image the superficial layer of the tissue. . The OCT system is composed of a low-coherence light source, a fiber-optic Michelson interferometer, and a photoelectric detection system.
The core of OCT is the fiber optic Michelson interferometer. The light emitted by the low-coherence light source Superluminescence Diode (SLD) is coupled into the single-mode fiber and is divided equally into two paths by the 2×2 fiber coupler. One path is the reference light collimated by the lens and returned from the plane reflector. ;The other path is the sampling beam focused on the sample under test through the lens.
The reference light returned by the reflector and the backscattered light of the sample under test merge on the detector. When the optical path difference between the two is within the coherence length of the light source, interference occurs, and the detector output signal reflects the backscattered light of the medium. scattering intensity.
Scanning the mirror and recording its spatial position allows the reference light to interfere with backscattered light from different depths within the medium. According to the position of the mirror and the corresponding interference signal intensity, the measurement data at different depths (z direction) of the sample are obtained. Combined with the scanning of the sampling beam in the xy plane, the results are processed by a computer to obtain the three-dimensional structural information of the sample.
Development of OCT imaging technology
With the widespread application of ultrasonic examination in the field of ophthalmology, people hope to develop a higher-resolution detection method. The emergence of ultrasonic biological microscopy (UBM) meets this requirement to a certain extent. It can perform high-resolution imaging of the anterior segment by using higher frequency sound waves. However, due to the rapid attenuation of high-frequency sound waves in biological tissues, its detection depth is subject to certain limitations. If light waves are used instead of sound waves, can their defects be compensated?
In 1987, Takada et al. developed an optical low-coherence interferometry method, which was developed into a method for high-resolution optical measurement with the support of fiber optics and optoelectronic components; Youngquist et al. developed an optical coherence reflectometer, whose light source is A superluminescent diode coupled directly to an optical fiber. One arm of the instrument contains the reference mirror, while the optical fiber in the other arm is connected to a camera-like device. These have laid the theoretical and technical basis for the emergence of OCT.
In 1991, David Huang, a Chinese scientist at MIT, and others used the developed OCT to measure isolated retinas and coronary arteries. Because OCT has unprecedented high resolution, similar to optical biopsy, it was quickly developed for the measurement and imaging of biological tissues.
Due to the optical characteristics of the eye, OCT technology has developed fastest in clinical ophthalmology. Before 1995, Huang and other scientists used OCT to measure and image tissues such as the retina, cornea, anterior chamber, and iris of the human eye in vitro and in vivo, and continued to improve OCT technology. After several years of improvement, the OCT system was further improved and developed into a clinically practical detection tool, a commercial instrument was made, and its superiority in fundus and retinal imaging was finally determined. In 1995, OCT began to be officially used in ophthalmology clinical practice.
In 1997, OCT was gradually used in dermatology, gastrointestinal tract, urinary system and cardiovascular examinations. Esophageal, gastrointestinal, urological OCT and cardiovascular OCT are all invasive examinations, similar to endoscopes and catheters, but they have higher resolution and can observe ultrastructure. Skin OCT is a contact examination and can also observe ultrastructure.
The OCT initially used in clinical practice was OCT1, which consisted of a console and a power table. The console includes an OCT computer, OCT monitor, control panel and monitor screen; the power stage includes a fundus observation system and an interference light control system. Since the console and the power stage are relatively independent devices and are connected by wires, the instrument is larger and takes up more space.
The analysis program of OCT1 is divided into image processing and image measurement. Image processing includes image standardization, image calibration, image calibration and standardization, image Gaussian smoothing, and image median smoothing; there are few image measurement procedures, only retinal thickness measurement and retinal nerve fiber layer thickness measurement. However, since OCT1 had fewer scanning programs and analysis programs, it was quickly replaced by OCT2.
OCT2 is formed by software upgrade based on OCT1. There are also some instruments that combine the console and the power stage into one to form an OCT2 instrument. This instrument reduces the image monitor and can observe the OCT image and monitor the patient's scanning site on the same computer screen, but the operation is the same as that of the OCT1 Similar, manual operation on the control panel.
The emergence of OCT3 in 2002 marked a new stage for OCT technology. In addition to the more friendly operation interface of OCT3, all operations can be completed on the computer with the mouse, and its scanning and analysis procedures are becoming more and more perfect. More importantly, the resolution of OCT3 is higher, with an axial resolution of ≤10 μm and a lateral resolution of 20 μm. The number of axial samples acquired by OCT3 increased from the original 128 to 768 in one A-scan, so the points of OCT3 increased from the original 131,072 to 786,432, and the hierarchical structure of the scanned tissue cross-sectional image constructed was clearer.
Types of OCT imaging techniques
In terms of OCT technical means, depending on the type of detection signal, there are two main OCT technical means: time domain OCT (Time Domain OCT, TD-OCT) and frequency domain OCT (Fourier Domain OCT, FD-OCT).
Time domain OCT technology
The principle diagram of time domain OCT technology is as follows:
Optical coherence tomography systems combine the features of low-coherence interference and confocal microscopy measurements. The light source selected for the system is a broadband light source, and superradiant light-emitting diodes (SLD) are commonly used. The light emitted by the light source passes through the 2×2 coupler and is irradiated to the sample and reference mirror respectively through the sample arm and the reference arm. The reflected light in the two optical paths merges in the coupler, and the optical path difference between the two arms can only be within a coherent length. An interference signal occurs. At the same time, because the sample arm of the system is a confocal microscope system, the beam returned at the focus of the detection beam has the strongest signal, which can eliminate the influence of scattered light from the sample outside the focus. This is one of the reasons why OCT can perform high-performance imaging. The interference signal is output to the detector. The intensity of the signal corresponds to the reflection intensity of the sample. After processing by the demodulation circuit, it is finally collected by the acquisition card and sent to the computer for grayscale imaging.
The main purpose of OCT imaging is to obtain the reflectance distribution at different depths of the sample. If the reflectivity at the reference mirror is constant, then due to the inhomogeneity of the sample structure, the intensity of the light scattered back from different depths of the sample is different. Therefore, when the light from the two arms meets, the interference signal generated when the light from the two arms meets will contain the intensity of the different depths of the sample. Light reflectance information. It can be seen from the low coherence of the broadband light source that the OCT interferometer can obtain a narrow coherence length, ensuring that the imaging resolution of axial scanning is at the micron level. For a narrow-band light source, as shown in Figure a, due to its long coherence length, interference fringe changes can be output within a considerable optical path difference range. Such interference fringe contrast has almost nothing to do with the change in optical path difference between the two arms. If the position of the zero-order fringe cannot be determined, the equal optical path point cannot be found, and the function of precise positioning is lost. For a broadband light source, as shown in Figure b, only when the optical path difference between the two arms is within this short coherence length, the detector can detect the contrast change of the interference fringe. Moreover, the maximum contrast corresponds to the equal optical path point. As the optical path difference increases, the contrast decreases rapidly, so it has good tomographic positioning accuracy. Therefore, the reflective scanning mirror of the reference arm can be moved to find the equilibrium point after the change. By measuring the displacement of the reflective scanning mirror before and after the change, the corresponding change in the length of the optical fiber sensor can be measured.
Since the light source is a low-coherence broadband light source, its coherence length is extremely short. Only when the optical path difference between the reference arm and the measurement arm is within a coherence length of the light source, the backscattered light and the reference light will interfere, and the maximum coherent intensity will occur when the optical path difference is close to zero. Therefore, as the reference mirror moves axially, the layer in the sample that is equal to the optical path can be selected for imaging, while the information from other layers will be filtered out, thus achieving tomographic imaging.
Shown here is the result of a longitudinal scan of a simple tissue. This sample structure is composed of two layers, with refractive index n1 and n2 respectively, which are different from the refractive index n of air. In the sample arm, reflections occur at the interface between two media with different refractive indexes. As the reference arm's mirror scans, two interference signals are seen at the output of the detector. The first interference signal corresponds to the interface between air and tissue layer 1, and the second interference signal corresponds to the interface between tissue layer 1 and tissue layer 2. By demodulating at the carrier frequency, the light intensity of the original interference signal can be obtained. A three-dimensional image of the sample can be obtained by moving the sample arm along the X and Y directions of the sample surface.
Frequency domain OCT technology
Frequency-domain OCT has gradually replaced time-domain OCT in recent years. The important reason is that it does not require optical path scanning in the reference arm and directly acquires longitudinal scans in one go. In this way, the imaging speed of the frequency domain OCT system will be greatly improved. Time domain OCT collects the intensity signal that changes with the optical path of the reference arm, and each longitudinal scanning time is equal to the time of one cycle of the optical path change of the reference arm. The reference arm of frequency domain OCT does not need to scan. It collects the interference spectrum signal in the depth direction at a certain lateral position at one time, that is, the frequency domain signal. The time domain signal in the depth direction is encoded in this spectrum. Each longitudinal scan actually corresponds to an interference spectrum, and the time domain signal can be recovered by performing Fourier transform on the spectrum. Frequency domain OCT saves the time of deep scanning in traditional time domain OCT and greatly improves the imaging acquisition speed.
There are currently two main methods for obtaining interference spectra, one is based on a spectrometer, and the other is based on a swept frequency light source. The former is called spectral frequency domain OCT (SD-OCT), and the latter is called swept frequency OCT (SS-OCT).
SD-OCT uses a spectrometer based on gratings and lenses to separate and focus the interference signal onto a linear array charge-coupled device (CCD) to obtain the interference spectrum.
SS-OCT uses a swept frequency light source whose output wavelength scans at high speed over time, and then records the signal of each wavelength through the detector to obtain the interference spectrum.
Application of optical coherence tomography technology
Early OCT was mostly used in ophthalmology because the eye is a relatively light-transmitting medium. With the continuous development of OCT technology, OCT has gradually found many applications in other tissues with poor light transmittance and strong scattering. In the past decade or so, OCT has been combined with fiber optic technology and endoscopic technology, and its application has expanded to many fields such as the gastrointestinal tract, skin, lungs, kidneys, and cardiovascular systems.
Applications in ophthalmology
The first clinical application area of OCT technology was ophthalmology. Due to the low coherence of the broadband light source, OCT has excellent optical sectioning capabilities and can achieve high-resolution tomographic imaging of subsurfaces. Its detection depth far exceeds that of traditional confocal microscopes, and is especially suitable for imaging research on eye tissue. It can provide retinal cross-sectional structural images that cannot be provided by traditional ophthalmic non-destructive diagnostic technology. It can not only clearly display the subtle structure and pathological changes of the retina, but also observe and make quantitative analysis. Its research in ophthalmic diagnosis is OCT Biology It is one of the key directions in the development of medical applications and has made a significant contribution to the diagnosis of ophthalmic diseases. It has now become a powerful diagnostic tool for retinal diseases and glaucoma.
As the performance of OCT improves, it can be predicted that OCT will have a more profound impact on ophthalmology, thereby improving the sensitivity and specificity of early diagnosis of disease and changing the ability to monitor disease progression. OCT plays an increasingly important role in understanding the structure and function of the retina, explaining the pathogenesis of retinal diseases, determining new treatment options, and monitoring the effects of disease treatment. Currently, OCT is mainly used clinically for early diagnosis and postoperative follow-up of glaucoma, macular degeneration, vitreoretinal diseases, and subretinal neovascularization.
Applications in dermatology
OCT technology has achieved the purpose of human skin imaging. High-resolution OCT can detect the epidermis, dermis, appendages and blood vessels of healthy human skin. Welzel et al. realized human skin imaging with an OCT system. The wavelength of the imaging system is 830nm, the depth resolution is 15μm, the detection depth is 0.5~1.5mm, and the imaging time is 10~40s. The axial resolution can also be depicted by Wang et al.
OCT can be used for damage repair monitoring. Yeh et al. used OCT and multiphoton microscope (MPM) to monitor laser thermal damage and subsequent damage repair in a skin tissue simulation model. The isolated skin tissue simulation model consists of the dermis containing type 1 collagen, fibroblasts, and the epidermis with different keratinases. Non-invasive light imaging techniques were used as serial measurements of stromal damage and repair over time and compared with histopathological findings.
Applications in cardiovascular system
As a non-invasive detection technology for in vivo blood imaging, OCT has great value in biomedical research and clinical diagnosis. Optical Doppler tomography (ODT) combines a laser Doppler flowmeter with OCT, also known as Color Doppler optical coherence tomography (CDOCT), which can achieve High-resolution imaging and real-time detection of human blood flow. Chen et al. used ODT to obtain in vivo blood flow tomographic velocity imaging of the chorionic villi of chicken embryos and rodent mesentery in vivo, and monitored changes in hemodynamics and vascular structure after intervention with vasoactive drugs and photodynamic therapy. .
Application in interdisciplinary surgery
In interdisciplinary surgery, OCT can analyze the presence of cancer cells during surgery to remove tumors. Generally speaking, when surgeons remove tissue around a tumor, they always hope to remove all cancer cells. The removed tumor and surrounding tissue will be sent to the pathology laboratory for analysis for a week to prepare a written report after the operation. Since OCT images have the same resolution in histology/pathology applications, the OCT system in the operating room allows the surgeon to accurately know how much tissue needs to be removed and how much safety margin is left during the operation. This way, tissue that is not infected by cancer will not be mistakenly removed, thus saving the cost and pain of subsequent surgery. OCT technology allows doctors to see images in real time at histological resolution, allowing them to make better decisions during first-time surgical procedures to remove tumors.
There will be more medical applications using OCT technology in the future. For example, OCT can be used with biopsy to remove small tumors in their early stages. For patients suffering from breast cancer, OCT can be combined with vision and "intelligent" signal processing technology to guide the insertion of fine needles into precise tumor locations to identify suspected infected tissues and minimize the invasiveness of surgery. For patients with cardiovascular disease, OCT can be used with extremely small catheter stents to more accurately identify intravascular stents or detect plaque deposition. In these types of applications, advanced digital signal processing techniques not only achieve excellent image quality but also enable tissue classification.
Applications in non-medical fields
The original purpose of OCT research was for biomedical tomography, and medical applications still continue to dominate. In addition to its application in the medical field, with the development of OCT technology, OCT technology is advancing to other fields, especially in the field of industrial measurement, such as displacement sensors, thickness measurement of thin films, and measurement of other measured objects that can be converted into displacement.
Recently, low-coherence technology has emerged as a key technology for high-density data storage. OCT technology can also be used to measure residual porosity, fiber architecture, and structural integrity of highly scattering polymer molecules. It can also be used to measure the coating of materials. OCT technology can also be used in materials science. JPDunkers et al. used OCT technology to conduct non-destructive inspection of composite materials. M.Bashkansky et al. used the OCT system to detect ceramic materials and expanded the application scope of OCT technology. SRChinn et al. also studied the application of OCT in high-density data storage to achieve multi-layer optical storage and high detection sensitivity.
Future development trends of OCT technology
The future development trend of OCT can be roughly considered as the development from OCT for pure structural imaging to OCT for comprehensive imaging of function and structure. Usually the functional parameters of biological tissues begin to change before lesions occur. Therefore, functional parameters are very useful for early diagnosis of diseases. These functional parameters usually include blood flow velocity, oxygen pressure, tissue structure changes, birefringence properties, etc. Functional OCT provides more information by detecting these changes for functional imaging. Functional OCT technologies that have developed rapidly in recent years include: Doppler OCT, polarization-sensitive OCT, spectral OCT and dual-ray OCT.
As a novel imaging technology, optical coherence tomography can perform real-time, in-vivo, high-resolution tomographic imaging of the internal microstructure of living tissues. Compared with traditional imaging diagnostic methods, optical coherence tomography shows great superiority in medicine. It has great potential in disease diagnosis.
Review Editor: Huang Fei
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