Automated Tissue Image Systems
Encyclopedia
Automated tissue image analysis is a process by which computer-controlled automatic test equipment
Automatic test equipment
Automatic or Automated Test Equipment is any apparatus that performs tests on a device, known as the Device Under Test , using automation to quickly perform measurements and evaluate the test results...

 to evaluate tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...

 samples, using computations to derive quantitative measurements from an image to avoid subjective errors.

In a typical application, automated tissue image analysis could be used to measure the aggregate activity of cancer cell
Cancer cell
Cancer cells are cells that grow and divide at an unregulated, quickened pace. Although cancer cells can be quite common in a person they are only malignant when the other cells fail to recognize and/or destroy them. In the past a common belief was that cancer cells failed to be recognized and...

s in a biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

 of a cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

ous tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 taken from a patient. In breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

 patients, for example, automated tissue image analysis may be used to test for high levels of proteins known to be present in more aggressive forms of breast cancers.

Applications

Automated tissue imaging analysis can significantly reduce uncertainty in characterizing tumors compared to evaluations done by histologists, or improve the prediction rate of recurrence of some cancers. As it is a digital system, suitable for networking, it also facilitates cooperative efforts between distant sites. Systems for automatically analyzing tissue samples also reduce costs and save time.

High-performance CCD cameras
Charge-coupled device
A charge-coupled device is a device for the movement of electrical charge, usually from within the device to an area where the charge can be manipulated, for example conversion into a digital value. This is achieved by "shifting" the signals between stages within the device one at a time...

 are used for acquiring the digital images. Coupled with advanced widefield microscope
Fluorescence microscope
A fluorescence microscope is an optical microscope used to study properties of organic or inorganic substances using the phenomena of fluorescence and phosphorescence instead of, or in addition to, reflection and absorption...

s and various algorithms for image restoration, this approach can provide better results than confocal techniques at comparable speeds and lower costs.

Processes

The United States Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 classifies these systems as medical device
Medical device
A medical device is a product which is used for medical purposes in patients, in diagnosis, therapy or surgery . Whereas medicinal products achieve their principal action by pharmacological, metabolic or immunological means. Medical devices act by other means like physical, mechanical, thermal,...

s, under the general instrumentation category of automatic test equipment
Automatic test equipment
Automatic or Automated Test Equipment is any apparatus that performs tests on a device, known as the Device Under Test , using automation to quickly perform measurements and evaluate the test results...

.

ATIS have seven basic processes (sample preparation, image acquisition, image analysis, results reporting, data storage, network communication, and self-system diagnostics) and realization of these functions highly accurate hardware and well-integrated, complex, and expensive software.

Preparation

Specimen preparation is critical for evaluating the tumor in the automated system. In the first part of the preparation process the biopsied tissue is cut to an appropriate size (typically 4 mm), fixed in buffered formalin, dehydrated in ethanol-xylene
Xylene
Xylene encompasses three isomers of dimethylbenzene. The isomers are distinguished by the designations ortho- , meta- , and para- , which specify to which carbon atoms the two methyl groups are attached...

, embedded in paraffin
Paraffin
In chemistry, paraffin is a term that can be used synonymously with "alkane", indicating hydrocarbons with the general formula CnH2n+2. Paraffin wax refers to a mixture of alkanes that falls within the 20 ≤ n ≤ 40 range; they are found in the solid state at room temperature and begin to enter the...

, thin section
Thin section
In optical mineralogy and petrography, a thin section is a laboratory preparation of a rock, mineral, soil, pottery, bones, or even metal sample for use with a polarizing petrographic microscope, electron microscope and electron microprobe. A thin sliver of rock is cut from the sample with a...

ed typically to 4 um slices, then moutned onto at least two barcode
Barcode
A barcode is an optical machine-readable representation of data, which shows data about the object to which it attaches. Originally barcodes represented data by varying the widths and spacings of parallel lines, and may be referred to as linear or 1 dimensional . Later they evolved into rectangles,...

d slides (a control
Scientific control
Scientific control allows for comparisons of concepts. It is a part of the scientific method. Scientific control is often used in discussion of natural experiments. For instance, during drug testing, scientists will try to control two groups to keep them as identical and normal as possible, then...

 and a test). Next the paraffin is removed from the tissue, the tissue is rehydrated, then stained. Any inconsistency in these procedures from case to case may result in uncertainties in the outcome of the analysis. These potential and irreducible inconsistencies in analysis results motivated the development of Automated Tissue Image Systems.

Acquisition

Digital micrographs are acquired of the stained specimen on the glass slide. The images are taken by a set of charge-coupled devices (CCD).

Analysis

Image analysis involves complex computer algorithms which identify and characterize cellular color, shape, and quantity of the tissue sample using image pattern recognition technology based on vector quantization
Vector quantization
Vector quantization is a classical quantization technique from signal processing which allows the modeling of probability density functions by the distribution of prototype vectors. It was originally used for data compression. It works by dividing a large set of points into groups having...

. Vector representations of objects in the image, as opposed to bitmap representations, have superior zoom-in ability. Once the sample image has been acquired and resident in the computer's random access memory as a large array of 0's and 1's, a programmer knowledgeable in cellular architecture can develop deterministic algorithms applied to the entire memory space to detect cell patterns from previously defined cellular structures and formations known to be significant.

The aggregate algorithm outcome is a set of measurements that is far superior to any human sensitivity to intensity or luminance
Luminance
Luminance is a photometric measure of the luminous intensity per unit area of light travelling in a given direction. It describes the amount of light that passes through or is emitted from a particular area, and falls within a given solid angle. The SI unit for luminance is candela per square...

 and color hue, while at the same time improving test consistency from eyeball to eyeball.

Reporting

The systems have the capability of presenting the resulting data in text and graphically, including on high definition monitors, to the system user. Computer printers, as relatively low image resolution devices, are used mostly to present final pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....

 reports that could include text and graphics.

Storage

Storage of the acquired data (graphical digital slide files and text data) involves saving system information in a data storage device
Data storage device
thumb|200px|right|A reel-to-reel tape recorder .The magnetic tape is a data storage medium. The recorder is data storage equipment using a portable medium to store the data....

 system having at least convenient retrieval, and file management capabilities.

Medical imaging industry standards includes the Picture Archiving and Communication Systems (PACS
PACS
PACS is an acronym with several meanings:*Pacte civil de solidarité, a form of civil union in France*Palo Alto Chinese School, Palo Alto, Calif.*Partial Anterior Circulation Stroke Syndrome, the symptoms of a type of an ischemic stroke...

), of European origin, which are image and information management solutions in computer networks that allow hospitals and clinics to acquire, distribute and archive medical images and diagnostic reports across the enterprise. Another standard of European origin is the Data and Picture Archiving and Communication System (DPACS). Although medical images can be stored in various formats, a common format has been Digital Imaging and Communications in Medicine (DICOM).
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