Optical coherence tomography: an emerging technology for biomedical imaging and optical biopsy

Abstract

Optical coherence tomography (OCT) is an emerging technology for performing high-resolution cross-sectional imaging. OCT is analogous to ultrasound imaging, except that it uses light instead of sound. OCT can provide cross-sectional images of tissue structure on the micron scale in situ and in real time. Using OCT in combination with catheters and endoscopes enables high-resolution intraluminal imaging of organ systems. OCT can function as a type of optical biopsy and is a powerful imaging technology for medical diagnostics because unlike conventional histopathology which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time. OCT can be used where standard excisional biopsy is hazardous or impossible, to reduce sampling errors associated with excisional biopsy, and to guide interventional procedures. In this paper, we review OCT technology and describe its potential biomedical and clinical applications.

Figure 1

OCT performs imaging by measuring the echo time delay of reflected light using low-coherence interferometry. The system is based on a Michelson type interferometer. Reflections or backscattering from the object being imaged are correlated with light which travels a reference path.

Figure 2

Cross-sectional images are constructed by performing measurements of the echo time delay of light at different transverse positions. The result is a two-dimensional data set which represents the backscattering in a cross-sectional plane of the tissue. This data can be displayed as a gray scale or false color image.

Figure 3

Schematic of OCT instrument based on a fiber optic implementation of a Michaelson interferometer. One arm of the interferometer is interfaced to the measurement instrument and the other arm has a scanning delay line. The system shown is configured for high-speed catheter/endoscope-based imaging. The technology can be engineered into a compact and clinically viable form.

Figure 4

OCT image of the human retina papillary-macular axis in vivo illustrating the ability to discriminate structural morphology. The optic disk as well as several of the retinal layers are observed. The highly backscattering retinal nerve fiber layer (NFL) and choriocapillaris appear red in the false color image. From Ref. [5].

Figure 5

OCT image of atherosclerotic plaque in vitro and corresponding histology. The plaque is heavily calcified with a low lipid content. A thick intimal layer covers the plaque. The high resolution of OCT can resolve small structures such as the thin intimal layer which are associated with unstable plaques. From Ref. [11].

Figure 6

OCT image of cervix imaged in vitro showing the ability to differentiate architectural morphology (image size: 1.5 mm x 2 mm, resolution: 6 µm x 10 µm). The epithelial layer (e) of the ectocervix and the basal membrane (arrow) were clearly identified. From Ref. [26].

Figure 7

OCT image of the ectocervix in vitro. Deep endocervical glands (g), some of which developed into fluid filled cysts, were also visible and are a finding common in postmenopausal women. From Ref. [26].

Figure 8

Cervical disease imaged in vitro (image size: 3 mmx2 mm, resolution: 6 µm x 10 µm). (A) Carcinoma in situ is characterized by a thick, irregular epithelial layer in addition to thickening of the basement membrane (B). (C and E) Images of invasive carcinoma show a heterogeneous surface with the basement membrane no longer defined. Distinct backscattering patterns can be noted in cellular (C) and noncellular (N) regions. Images are correlated with histopathology. From Ref. [26].

Figure 9

OCT images of human gastrointestinal tissues and pathology in vitro showing the ability to differential epithelial structure and glandular organization. (A) normal human esophagus showing squamous epithelial structure, (B) normal colon with columnar epithelium and crypt structures, and (C) ampullar/carcinoma showing associated disruption of normal epithelial organization. The carcinoma is evident on the left of the image. The bar is 500 µm. From Ref. [14].

Figure 10

Photograph of prototype OCT catheter for transverse, intraluminal imaging. The catheter consists of a single mode optical fiber contained in a rotating cable with a distal lens and prism. The rotating elements are housed in a stationary, transparent plastic sheath. The beam is emitted and scanned in a radial direction. The diameter of the catheter is 2.9 For 1 mm.

Figure 11

OCT catheter/endoscope image in vivo of the esophagus of a New Zealand White Rabbit. The image is 512 pixels in circumference with 256 axial pixels and is acquired at four frames per second. The image clearly differentiates the layers of the esophagus including the mucosa, submucosa, inner muscularis, and outer muscularis. The bar is 500 µm. From Ref. [15].

Figure 12

OCT images of an anastomosis in a rabbit artery. The 1-mm-diameter rabbit artery was anastomosed with a continuous suture as seen in the digital image (F). Labeled lines in F indicate planes from which corresponding cross-sectional images were acquired. (A,D) Opposite ends of the anastomosis showing multilayered structure of the artery with a patent lumen. (B) Partially obstructed lumen and the presence of a thrombogenic flap. (C) Fully obstructed portion of the anastomosis site. Intraluminal features as seen in B and C are not observable from the en face microscope view. Three-dimensional projection shown in G can be arbitrary sectioned at any plane, such as the longitudinal section in E to show the obstruction. From Ref. [20].

Figure 13

Three-dimensional OCT projection image of a laser ablation crater. The lesion was produced by a 3-W, 10-s argon exposure of rat rectus abdominis muscle. The projection illustrates a central ablation crater and concentric zones of thermal injury. From Ref. [84].

Figure 14

En face images through ablation crater. En face sections in depth illustrate concentric zones of damage. Numbers refer to depth below surface. Bar represents 1 mm. From Ref. [84].

Figure 15

Real-time imaging of ablation. Series of OCT images taken at eight frames per second during argon laser exposure of in vitro muscle (beef). Exposure parameters include 1-W laser power, 0.8-mm spot diameter on tissue. Times indicated are seconds post-exposure. At 2.25 seconds, the formation of a blister at the surface can be seen. The blister explodes (2.5 seconds) and a crater develops (5 seconds).

Figure 16

Ultrahigh-resolution OCT images of a X. laevis (African frog) tadpole in vivo. The resolution is 1 µm axial by 3 µm transverse. The image is constructed by fusing multiple images with different focal positions (in analogy with C mode ultrasound) to overcome depth of field limitations associated with the fine transverse resolution. Cell membranes and individual cell nuclei are visible. From Ref. [36].