System for imaging lesions aligning tissue surface
Inventors
Shachaf, Catherine M. • SHACHAF, Amit
Assignees
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Publication Number
US-11744510-B2
Publication Date
2023-09-05
Expiration Date
Abstract
Methods, compositions and systems are provided for the imaging of cavity/tissue lesions, including without limitation cavity/tissue malignant lesions, e.g. cancers of the skin, mouth, colon, digestive system cervix, bladder, lung, etc.
Core Innovation
The invention describes a system and methods for imaging an area of interest on a surface of an individual that includes a lesion, using both a visible image and a fluorescent image. An imaging device is configured to capture a fluorescent image in a fluorescent mode through a fluorescent light filter and to obtain features of the lesion by combining the visible image and the fluorescent image. A fluorescent fiducial is configured to be applied onto the area of interest to support the fluorescent imaging and feature extraction.
The fluorescent fiducial includes a base that is not visible in a predetermined emission spectra when exposed to light in a predetermined excitation spectra. The fiducial further includes a fluorescent calibration mark with a predetermined calibration brightness in the predetermined emission spectra, a fluorescent focus mark with sharply defined borders adapted for use by an autofocus mechanism of an integrated optical system, and a pair of measurement marks with predetermined spacing for lesion sizing. The fiducial also includes a fluorescent alignment mark that is visible in both visible light and the predetermined emission spectra and is not circularly symmetric, enabling overlay between visible and fluorescent images, as well as a direction mark adapted to identify at least one anatomical term of location for the individual.
The imaging system uses the fluorescent fiducial to provide calibration, autofocus, alignment, and measurement support during imaging and analysis. The integrated imaging device captures both visible and fluorescence images, and the lesion features are obtained by combining the visible image and the fluorescent image. The document additionally describes automated image analysis in which overlay/alignment and calibrated intensity comparisons can be used for lesion probability scoring, with the system configured to support differentiation of visible and fluorescence information and extraction of image features for classification.
Claims Coverage
Independent claim clm-00001 defines an imaging system with an imaging device configured for visible-plus-fluorescent capture and a fluorescent fiducial having specifically constrained spectral visibility, calibration brightness, autofocus, measurement spacing, alignment characteristics, and anatomical direction marking. The dependent claim set refines the fiducial-based system with additional lesion/biotag targeting and quantitative measurement workflow elements.
Fluorescent filter imaging with visible-fluorescent lesion feature combination
An imaging device comprising a fluorescent light filter configured to image an area of interest comprising a first area and a second area on a surface of an individual, wherein the first area comprises a lesion; configured to capture a fluorescent image of the area of interest in a fluorescent mode; and configured to obtain features of the lesion by combining a visible image and the fluorescent image.
Fluorescent fiducial base with predetermined emission non-visibility and structured fluorescent marks
A fluorescent fiducial comprising a base that is not visible in a predetermined emission spectra when exposed to light in a predetermined excitation spectra; a fluorescent calibration mark with a predetermined calibration brightness in the predetermined emission spectra; a fluorescent focus mark with sharply defined borders adapted for use by an autofocus mechanism of an integrated optical system; a pair of measurement marks with predetermined spacing; a fluorescent alignment mark visible in both visible light and in the predetermined emission spectra when exposed to the predetermined excitation spectra and not circularly symmetric; and a direction mark adapted to identify at least one anatomical term of location for the individual.
Biotag binding to tumor-cell and tumor-macroenvironment regions
The biotag is configured to bind to two specified regions, with the first region containing tumor cells and the second region containing a tumor macroenvironment.
Biotag fluorescence dye conjugating with cancer-sensitive biological entities
The biotag includes a first fluorescence dye that can conjugate with one or more cancer-sensitive biological entities selected from protein, RNA, and DNA.
Biotag includes Cy5.5 as a detectable marker
The biotag includes Cy5.5 as a detectable marker.
Auto-exposure calibrated measurement of biotag quantity with numerical output to a medical service
The calibrated exposure marks on the fluorescent fiducial are used in an auto-exposure imaging mode to automatically numerically measure a quantity of the biotag in an area of interest and to provide the resulting numerical measurement to a medical service alongside an image from first and second imaging sequences.
Specific binding partner size constraint as polypeptide under 10,000 daltons
A binding partner specifically binds to a targeted molecule of interest in a suspected cancerous or pre-cancerous lesion, where the binding partner is a polypeptide of less than 10,000 daltons.
The claim coverage centers on an imaging device that captures visible and fluorescence images and obtains lesion features by combining them, supported by a fluorescent fiducial with predetermined spectral visibility/non-visibility, calibration brightness for measurement, focus marks for autofocus, measurement marks with predetermined spacing, non-circularly symmetric alignment marks for overlay, and a direction mark for anatomical location. Dependent refinements specify biotag binding regions and biotag fluorophore/entity conjugation options, include Cy5.5, add an auto-exposure calibrated numerical measurement workflow for biotag quantity, and constrain a binding partner as a polypeptide of less than 10,000 daltons.
Stated Advantages
Enables obtaining lesion features by combining a visible image and the fluorescent image.
Provides calibration brightness for fluorescence-based imaging support via the fluorescent calibration mark.
Supports autofocus using a fluorescent focus mark with sharply defined borders adapted for an autofocus mechanism of an integrated optical system.
Supports lesion sizing using a pair of measurement marks with predetermined spacing.
Supports overlay/alignment between visible light and fluorescence using a fluorescent alignment mark visible in both modes and not circularly symmetric.
Supports anatomical location identification using a direction mark adapted to identify at least one anatomical term of location for the individual.
Enables auto-exposure numerical measurement of a quantity of the biotag and delivery of the resulting numerical measurement to a medical service alongside images.
Documented Applications
Imaging cavity/tissue lesions on a surface of an individual, including melanoma and other skin/cavity cancers, using a detectably labeled biotag and combining visible and fluorescent images.
Quantitative lesion-related assessment using calibrated intensity comparisons for tumor probability scoring based on captured visible and fluorescence images.
Automated image analysis involving overlay/alignment and calibrated intensity comparisons, including differentiation between visible and fluorescence information and automated feature extraction/classification.
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