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Second Harmonic Optical Coherence Tomography

详细技术说明

Optical coherence tomography (OCT) is an emerging imaging technology that provides in-vivo high-resolution, cross-sectional images of biological tissues. Using coherence gating technique, OCT is capable of detecting the backscattered light from highly scattering tissues at depths of 2-3 mm. OCT imaging contrast originates from the inhomogeneities of sample scattering properties that are linearly dependent on sample refractive indices. In many instances such as pathological processes in tissue, changes in sample linear scattering properties are small and difficult to measure. For example, many cancers originate in the epithelium that has a thickness suitable for OCT imaging, but in their early stages when these cancers are developing through cell dysplasia, changes in tissue morphology and refractive index between normal and diseased tissues are very small and difficult to detect. Therefore, to meet the challenges found in OCT clinical applications, imaging contrast enhancement is very important. In recent years, many OCT contrast enhancement methods have been developed. These techniques include Doppler OCT, polarization sensitive OCT, spectroscopic OCT, pump-probe techniques, and using contrast agents for OCT. More recently, applying nonlinear optical effects of second harmonic generation (SHG) and coherent anti-Stokes Raman scattering for OCT contrast enhancement have also been demonstrated. SHG is a powerful contrast mechanism in nonlinear optical microscopy. SHG signals provide unique information regarding sample structure symmetry because the signals strongly depend on the orientation, polarization and local symmetry properties of chiral molecules. SHG enables direct imaging of anisotropic biological structures, such as membranes, structure proteins, and microtubule ensembles. Besides successfully producing high-resolution and highly contrasting images of tissue morphology, recently SHG microscopy has also been applied to study dynamics in tissue physiology, such as monitoring collagen modification in tumors growing, and optically recording the action potentials change in neuron cells. SHG is emerging as a powerful nonlinear optical imaging modality for cell biology and biophysics. We have developed a noninvasive optical tomography technique of second harmonic optical coherence tomography and experimentally demonstrated the feasibility of using this technique to image biological samples. Compared with conventional OCT performed at fundamental wavelength, SH-OCT offers enhanced molecular contrast and spatial resolution. It is also an improvement over existing second harmonic scanning microscopy technology as the intrinsic coherence gating mechanism enables the detection and discrimination of second harmonic signals generated at deeper locations. The enhanced molecular contrast of SH-OCT extends conventional OCT's capability for detecting small changes in molecular structure. Second harmonic-OCT is promising for the diagnosis of cancers and other diseases at an early stage when changes in tissue and molecular structure are small. More details can be found in patent no. 7,256,894.

*Abstract

The invention is an apparatus and method for second harmonic optical coherence tomography of a sample comprising a laser coupled to an interferometer which has a reference arm and in a sample arm. A nonlinear crystal in the reference arm generates a second harmonic reference signal. The sample typically backscatters some second harmonic light into the sample arm. A broadband beam splitter optically coupled to the reference arm and sample arm combines the signals from the reference arm and sample arm into interference fringes and a dichroic beam splitter splits the interference fringes into a fundamental and second harmonic interference signal. A detector is optically coupled to the dichroic beam splitter detects interference fringes from which both an OCT and second harmonic OCT image can be constructed using a conventional data processor.

*IP Issue Date

Aug 14, 2007

*Principal Investigation

Name: Yi Jiang

Department:

Name: Zhongping Chen

Department:

附加资料

Patent Number: US7256894B2
Application Number: US2004970485A
Inventor: Chen, Zhongping | Jang, Yi
Priority Date: 20 Oct 2003
Priority Number: US7256894B2
Application Date: 20 Oct 2004
Publication Date: 14 Aug 2007
IPC Current: G01B000902 | A61B000500 | G01N002147 | G01N002165
US Class: 356497 | 356489
Assignee Applicant: The Regents of the University of California
Title: Method and apparatus for performing second harmonic optical coherence tomography
Usefulness: Method and apparatus for performing second harmonic optical coherence tomography
Summary: Used for imaging a sample e.g. biological tissue.
Novelty: Harmonic optical coherence tomography apparatus for imaging biological tissue, has dichroic beam splitter splitting interference fringes into fundamental and harmonic interference signal, and detector detecting fringes

主要类别

生物医学

细分类别

医学影像

申请号码

7256894

其他

Tech ID/UC Case

23006/2004-181-0

Related Cases

2004-181-0

国家/地区

美国