METHOD AND APPARATUS FOR IMAGING UNSECTIONED TISSUE SPECIMENS
First Claim
1. An apparatus for real-time optical imaging of a tissue specimen, the apparatus comprising:
- a primary imaging system configured to use an illumination source to acquire images of a tissue specimen through one or more spectrally separated channels, at least one of the one or more spectrally separated channels is configured to detect a range of wavelengths distinct from the range of wavelengths of the illumination source, the primary imaging system being an inverted microscope having a frame acquisition rate and configured to perform optical depth sectioning, the primary image system being configured to acquire a sequence of images;
an auxiliary imaging system, wherein the auxiliary imaging system is configured to acquire an auxiliary image of the tissue specimen, wherein the area of the auxiliary image is greater than the area of each image of the sequence of images acquired by the primary imaging system;
a specimen holder having a transparent window therewithin, the specimen holder being disposed in a specimen plane at a focal plane of the primary imaging system, the specimen holder being configured to hold the tissue specimen on the transparent window, the specimen holder comprising one or more position sensors, wherein the specimen holder is configured to be translatable in the specimen plane, the one or more position sensors being configured to measure a specimen holder position, and wherein the specimen holder is configured to be translatable to a focal plane of the auxiliary imaging system;
wherein the primary imaging system and the auxiliary imaging system are both disposed on the same side of the specimen plane, the apparatus further comprising;
a user input device configured to accept user input, wherein the specimen holder is configured to translate in response to the user input in real-time;
a processing unit in electrical communication with the primary imaging system, the auxiliary imaging system, and the position sensors, wherein the processing unit is configured to execute a sequence of instructions on the sequence of images acquired by the primary imaging system, the auxiliary image, and at least one specimen holder position to generate a composite representation of the tissue specimen that includes a representation of cell nuclei in the specimen; and
a display device in electrical communication with the processing unit, the display device being configured to display the composite representation of the tissue specimen in real-time.
1 Assignment
0 Petitions
Accused Products
Abstract
An apparatus and method for real-time optical imaging of a tissue specimen. The apparatus comprises a primary imaging system configured to use an illumination source to acquire images of a tissue specimen through one or more spectrally separated channels, and configured to perform optical depth sectioning; an auxiliary imaging system, configured to acquire an auxiliary image of the tissue specimen; a specimen holder having a transparent window therewithin, window, the specimen holder comprising one or more position sensors, wherein the specimen holder is configured to be translatable in the specimen plane; a user input device configured to accept user input, wherein the specimen holder is configured to translate in response to the user input in real-time; a processing unit configured to execute a sequence of instructions on the sequence of images acquired by the primary imaging system, the auxiliary image, and at least one specimen holder position to generate a composite representation of the tissue specimen that includes a representation of cell nuclei in the specimen; and a display device configured to display the composite representation of the tissue specimen in real-time.
-
Citations
62 Claims
-
1. An apparatus for real-time optical imaging of a tissue specimen, the apparatus comprising:
-
a primary imaging system configured to use an illumination source to acquire images of a tissue specimen through one or more spectrally separated channels, at least one of the one or more spectrally separated channels is configured to detect a range of wavelengths distinct from the range of wavelengths of the illumination source, the primary imaging system being an inverted microscope having a frame acquisition rate and configured to perform optical depth sectioning, the primary image system being configured to acquire a sequence of images; an auxiliary imaging system, wherein the auxiliary imaging system is configured to acquire an auxiliary image of the tissue specimen, wherein the area of the auxiliary image is greater than the area of each image of the sequence of images acquired by the primary imaging system; a specimen holder having a transparent window therewithin, the specimen holder being disposed in a specimen plane at a focal plane of the primary imaging system, the specimen holder being configured to hold the tissue specimen on the transparent window, the specimen holder comprising one or more position sensors, wherein the specimen holder is configured to be translatable in the specimen plane, the one or more position sensors being configured to measure a specimen holder position, and wherein the specimen holder is configured to be translatable to a focal plane of the auxiliary imaging system; wherein the primary imaging system and the auxiliary imaging system are both disposed on the same side of the specimen plane, the apparatus further comprising; a user input device configured to accept user input, wherein the specimen holder is configured to translate in response to the user input in real-time; a processing unit in electrical communication with the primary imaging system, the auxiliary imaging system, and the position sensors, wherein the processing unit is configured to execute a sequence of instructions on the sequence of images acquired by the primary imaging system, the auxiliary image, and at least one specimen holder position to generate a composite representation of the tissue specimen that includes a representation of cell nuclei in the specimen; and a display device in electrical communication with the processing unit, the display device being configured to display the composite representation of the tissue specimen in real-time. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60)
-
-
28. A method of real-time optical imaging of a tissue specimen comprising the steps of:
-
applying one or more fluorescent contrast agents to a tissue specimen, wherein at least one of the one or more fluorescent contrast agents is a nuclear contrast agent; providing an apparatus, comprising; a primary imaging system configured to use an illumination source to acquire images of a tissue specimen through one or more spectrally separated channels, at least one of the one or more spectrally separated channels is configured to detect a range of wavelengths distinct from the wavelength of the illumination source, the primary imaging system being an inverted microscope having a frame acquisition rate and configured to perform optical depth sectioning, the primary image system being configured to acquire a sequence of images; an auxiliary imaging system, wherein the auxiliary imaging system is configured to acquire an auxiliary image of the tissue specimen, wherein the area of the auxiliary image is greater than the area of each image of the sequence of images acquired by the primary imaging system; a specimen holder having a transparent window therewithin, the specimen holder disposed in a specimen plane at a focal plane of the primary imaging system, the specimen holder being configured to hold the tissue specimen on the transparent window, the specimen holder comprising one or more position sensors, wherein the specimen holder is configured to be translatable in the specimen plane, the one or more position sensors being configured to measure a specimen holder position, and wherein the specimen holder is configured to be translatable to the focal plane of the auxiliary imaging system; wherein the primary imaging system and the auxiliary imaging system are both disposed on the same side of the specimen plane, the apparatus further comprising; a user input device configured to accept user input, wherein the specimen holder is configured to translate in response to the user input in real-time; a processing unit in electrical communication with the primary imaging system, the auxiliary imaging system, and the position sensors, wherein the processing unit is configured to execute a sequence of instructions on the sequence of images acquired by the primary imaging system, the auxiliary image, and at least one specimen holder position to form a representation of cell nuclei and to generate a composite representation of the tissue specimen; and a display device in electrical communication with the processing unit, the display device being configured to display the composite representation of the tissue specimen in real-time, situating the tissue specimen in the specimen holder; positioning the specimen holder at the focal plane of the auxiliary imaging system; causing the auxiliary imaging system to acquire the auxiliary image; positioning the specimen holder at the focal plane of the primary imaging system; causing the primary imaging system to acquire the sequence of images; causing a processing unit to detect cell nuclei within the tissue specimen and to generate a composite representation of the tissue specimen; causing the display device to display the composite representation of the tissue specimen in real-time; and causing the specimen holder to translate in the specimen plane using the user input device. - View Dependent Claims (29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 61, 62)
inserting the transparent window back into the specimen holder.
-
-
35. The method of claim 28, wherein the specimen holder includes a specimen divider configured to separate two or more tissue specimens.
-
36. The method of claim 28, wherein the specimen holder includes a lid, the method further including covering the tissue specimen with the lid.
-
37. The method of claim 40, wherein the lid includes a specimen guide, the method further including compressing the tissue specimen against the transparent window using the specimen guide.
-
38. The method of claim 28, further including identifying surgical inks, sutures, or exogenous markings on the tissue specimen created during a medical procedure using the auxiliary image.
-
39. The method of claim 38, further including measuring the distance between a selected location in any one of the sequence of images acquired by the primary imaging system and the surgical inks, sutures or exogenous markings on the tissue specimen using the representation of the auxiliary image.
-
40. The method of claim 38, further including illuminating the tissue specimen with a narrow band illumination and identifying surgical inks, sutures, or exogenous markings from known absorption spectra.
-
41. The method of claim 38, further including trans-illuminating the tissue specimen with the illumination source and identifying surgical inks, sutures, or exogenous markings.
-
42. The method of claim 28, further including causing the processing unit to record at least one of:
- the sequence of images acquired by the primary imaging system, the specimen holder position, the auxiliary image, or the composite representation.
-
43. The method of claim 28, further including:
causing the graphics processing unit to execute computer executable instructions for a series of parallel processing operations on the sequence of images.
-
44. The method of claim 43, wherein the graphics processing unit includes computer executable instructions for a series of parallel processing operations for virtual transillumination microscopy processing.
-
45. The method of claim 28, further including causing the processing unit to generate the composite representation of the tissue specimen, said composite representation comprising, for each image from the sequence of images acquired by the primary imaging system:
-
a representation of the image from the sequence of images; and a representation of the auxiliary image with a subregion of the auxiliary image indicating the location on the specimen holder where the image from the sequence of images was acquired, wherein the subregion of the auxiliary image is computed using one or more specimen holder positions.
-
-
61. The method of claim 28, wherein the composite representation comprises, for at least one image in the sequence of images acquired by the primary imaging system:
-
a representation of the image indicating two or more fiducial marks; a representation of the auxiliary image; and a representation of a distance between the two or more fiducial marks.
-
-
62. The method of claim 28, wherein the processing unit is configured to generate a first and a second composite representations, wherein:
-
the first composite representation comprises; a representation of a first image from the sequence of images acquired by the primary imaging system, the representation of the first image indicating a first fiducial mark, recorded in response to user input; and a representation of the auxiliary image; the second composite representation comprises; a representation of a second image from the sequence of images acquired by the primary imaging system, the representation of the second image indicating a second fiducial mark, recorded in response to user input; and a representation of the auxiliary image; and a representation of a distance between the first and the second fiducial marks.
-
-
46. A histological specimen cassette apparatus comprising:
-
an open-end receptacle, including a bottom wall and a specimen retaining structure; a specimen cover, configured to close the open-end receptacle; a specimen cover connector, configured to connect the open-end receptacle and the specimen cover; a transparent window; a transparent window connector, configured to connect the bottom wall or the specimen cover and the transparent window; a plurality of perforations in one or more of the open-end receptacle, the transparent window or the specimen cover. - View Dependent Claims (47, 48, 49)
-
Specification