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Disease Diagnosis by High-Throughput Scanning of Cell Morphologies

IP.com Disclosure Number: IPCOM000132445D
Original Publication Date: 2005-Dec-16
Included in the Prior Art Database: 2005-Dec-16
Document File: 3 page(s) / 80K

Publishing Venue

IBM

Abstract

This invention combines the use of (1) three-dimensional high-throughput microscopy of cells derived from living organisms with (2) computer storage of the resulting image data and with (3) computer algorithms for identifying the cells based on a set of morphological descriptors. The descriptors may include simultaneously size, two-dimensional or three-dimensional shape, color, and surface texture. These are compared against a database of previously identified features, which may be continuously trained and updated. The invention forms an architecture for performing health assessment and disease diagnosis by measuring the concentrations of healthy cells and identifying abnormal ones over a wide range of concentrations and cell types.

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Disease Diagnosis by High-Throughput Scanning of Cell Morphologies

Main Idea

The diagnosis of disease states based on patent phenotype, including characteristics at the cellular and molecular level, is often difficult because (1) each disease presents different symptoms, biomarkers, etc. that make it necessary to devise diagnostic tests separately for each disease, and (2) the disease must often progress considerably before it causes the sizeable phenotypic changes that can be detected using blood tests, radiography, body temperature, etc. For example, in the diagnosis of cancer, it is often necessary for the disease to progress until it can be detected by the shape and size of malignant tissue growths. In a very few specialized cases, such as the prostate-specific antigen blood test for prostatic cancer, more sensitive tests are available, but these have been developed only with great difficulty, and often require that the disease develop to an unacceptable extent before they become effective. Therefore there is always a need for diagnostic tests that can be applied to a wide range of disease states, and that are sensitive enough to detect the disease in its early stages. This disclosure describes a new approach for overcoming these limitations in disease diagnosis.

Many, if not all, diseases cause changes in the concentrations of certain cells, or the occurrence of new types of cells, in the blood and lymph. These abnormal cells can generally be identified under a microscope, based on their sizes, shapes, or colors. An extreme example is sickle-cell anemia, in which red blood cells change from being roughly oval to a elongated and pointed shape. This is shown in the figure, which contains a micrograph of normal red blood cells on the left, and those from an affected individual on the right.

This invention describes a novel high-throughput procedure of diagnosing disease based on microscopy combined with the computational recognition of abnormal cell types. Specifically it employs two new existing technologies in a novel way.

The first is the development of high-throughput three-dimensional microscopy. Three-dimensional microscopy involves interfacing a microscope to a computer, which controls the focus. For a clinical sample, the computer automatically focuses the microscope in a series of parallel planes perpendicular to the line of sight, in order to image all the cells in the sample regardless of their positions or orientations, and also to characterize the images in three dimensions. These images are recorded, generally by a video camera, and then stored for later analysis. A second computer records the identities and controls the positions of the samples. The process is completely automated, and can be repeated several times per second. This high-throughput autofocus technology has been recently developed, principally

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by Q3DM (for quantitative 3-dimension...