Combined reflectance confocal microscopy-optical coherence tomography system for imaging of biological tissue

Inventors

Iftimia, Nicusor V.Mujat, MirceaFerguson, R. DanielPatel, Ankit H.Rajadhyaksha, Milind

Assignees

Physical Sciences IncMemorial Sloan Kettering Cancer Center

Publication Number

US-9655521-B2

Publication Date

2017-05-23

Expiration Date

2033-01-31

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Abstract

A dual-modality apparatus for imaging of biological tissue includes a reflectance confocal microscopy (RCM) imaging apparatus and an optical coherence tomography (OCT) imaging apparatus. A first optical component reflects a first beam of light provided by a RCM imaging apparatus towards a sample and passes a second beam of light provided by an OCT imaging apparatus towards the sample, such that the first and second beam of lights share at least a portion of an imaging path.

Core Innovation

The invention provides a dual-modality imaging apparatus and methods for imaging biological tissue by combining Reflectance Confocal Microscopy (RCM) and Optical Coherence Tomography (OCT) within a single system. The apparatus includes an RCM imaging apparatus with an RCM source and an OCT imaging apparatus with an OCT source. A dichroic mirror reflects a beam from the RCM source and passes a beam from the OCT source, enabling both beams to share at least a portion of an imaging path and to interact with the sample.

The problem addressed by this invention is that existing imaging technologies such as RCM or OCT, when used alone, are insufficient for providing both detailed cellular imaging and deep tissue structural information. RCM offers high-resolution en face images with limited depth and can struggle with reliably locating and delineating the dermo-epidermal junction (DEJ), which is clinically significant for cancer and burn assessment. OCT allows imaging of deeper tissue layers and structural features like the DEJ but lacks sub-cellular resolution necessary for early diagnosis.

By integrating RCM and OCT into a single probe and optical system, the invention enables synchronized, co-registered, and real-time acquisition of both imaging modalities. Key optical components—such as a dichroic mirror and an imaging objective with an adjustable numerical aperture—allow optimized performance for high-resolution surface imaging (via RCM) and deep tissue penetration (via OCT). This combined approach delivers comprehensive morphological and functional information about biological samples, supporting more effective diagnosis and monitoring of tissue conditions.

Claims Coverage

The patent has four independent claims, each introducing unique inventive features centered on combining RCM and OCT imaging through shared optical components and simultaneous imaging.

Dual-modality imaging apparatus with dichroic mirror and shared imaging objective

The apparatus comprises: - A reflectance confocal microscopy (RCM) imaging apparatus with an RCM source. - An optical coherence tomography (OCT) imaging apparatus with an OCT source. - A dichroic mirror configured to: - Reflect an RCM light beam toward a sample and pass an OCT light beam toward the sample, allowing both beams to share at least a portion of an imaging path. - Reflect returning RCM light from the sample to the RCM imaging apparatus. - Pass returning OCT light from the sample to the OCT imaging apparatus. - An imaging objective with a numerical aperture: - Fully utilized in the RCM mode for high-resolution imaging. - Underutilized in the OCT mode (using 6.7%–10.7% of the NA) to allow imaging depths of greater than one millimeter. - Co-registration and simultaneous acquisition and display of RCM and OCT images.

Method for simultaneous acquisition and display of RCM and OCT images via shared optical path

- Providing first and second light signals from an RCM source and an OCT source, respectively. - Delivering both signals via a common optical path that includes an imaging objective with a numerical aperture, fully utilized by the RCM and underutilized by the OCT to permit deep imaging. - Detecting return signals from the sample with corresponding imagers. - Generating RCM and OCT images based on the detected signals. - Enabling simultaneous acquisition and display of both image types.

Method combining RCM and polarization sensitive OCT optical paths via dichroic mirror and imaging objective

- Combining the optical paths of the RCM imager and a polarization sensitive OCT imager using a dichroic mirror and imaging objective (NA 0.8 to 1.0). - Underutilizing the objective's numerical aperture for OCT to achieve depth over one millimeter, while fully utilizing it for RCM. - Detecting and generating spatially co-registered RCM and OCT images, displayed simultaneously.

Method for imaging with common optical path for RCM and polarization sensitive OCT with co-registered and simultaneous display

- Delivering RCM and polarization sensitive OCT light beams to a sample via a common optical path including an objective with NA 0.8 to 1.0. - Underutilizing the NA for OCT (using 6.7%–10.7% of NA for depth), fully utilizing it for RCM. - Receiving and processing respective signals to generate RCM and OCT images. - Co-registering and/or displaying the images simultaneously.

The inventive features collectively enable a dual-modality system that integrates RCM and OCT imaging through shared optics, permitting high-resolution, deep, and co-registered imaging of biological tissue with simultaneous display.

Stated Advantages

Provides reliable assessment of tissue viability.

Enables enhanced diagnosis of skin and oral tissue conditions.

Achieves real-time, noninvasive, and three-dimensional quantitative assessment of biological tissue.

Improves assessment of morphological, structural, and functional parameters such as microstructure, blood perfusion, and birefringence.

Utilizes a single imaging probe for both RCM and OCT modalities.

Allows co-registration and substantially simultaneous or real-time display of RCM and OCT images.

Provides comprehensive and complementary data sets via noninvasive imaging.

Enables an imaging objective that operates at two different wavelengths and supports both imaging modalities.

Combines optical paths of RCM and OCT beams for efficient imaging setup.

Permits full utilization of numerical aperture for high-resolution RCM and underutilization for deep OCT imaging.

Enables detection of the dermo-epidermal junction and both structural and functional imaging data.

Documented Applications

Diagnosis of skin cancers and oral cancers.

Assessment and diagnosis of skin and/or oral burns.

Noninvasive screening and diagnosis of cancers and/or burns, minimizing need for biopsy.

Efficient and reliable assessment of epithelial lesions.

Monitoring therapy outcomes for tissue conditions.

Imaging human skin to visualize epidermal and dermal layers, dermo-epidermal junction, and collagen integrity.

Staging and detection of oral or skin lesions by providing cellular and structural tissue details.

Testing and imaging of skin tissue constructs, such as EpiDermFT™, for biomedical research.

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