By Nicholas Borgert

 Applied Imaging Corp’s Ariol automated imaging and image analysis system.

With today’s clinical labs challenged to streamline their workflow, enhance test throughput, and cut turnaround times, the Ariol® image-analysis system from Applied Imaging Corporation is grabbing plenty of interest. Company officials believe Ariol can improve many applications, including cancer diagnostics, at a time when so many of the recent innovations in treatments are costly, present a toxic risk to patients, and promise only modest improvements in survival rates.

Ariol is a high-throughput automated imaging and image-analysis system for the analysis of cell and tissue biomarkers on microscopic slides in the clinical laboratory. It is also used in clinical research, including translational research and biopharma. Ariol adds flexibility and customization. Its goal is not to remove or diminish human control but to provide automation that will enhance manual analysis. A fully programmable joystick and a series of interfaces enable operators to interact and work with the images. High-definition camera and displays ensure superior image quality.

The Ariol’s capability also encompasses bar coding for identifying each specific slide and relating information to a predetermined set of procedures that enable a slide to be consistently analyzed. Also, the system generates full-color reports with selected images, including relevant data and diagnostic comments. Another benefit: Ariol is network-friendly.

The high level of automation and quantitative analysis reduces hands-on time, improves throughput in the laboratory, and pushes productivity higher. Specifically, the Ariol system enhances productivity by providing walkaway analysis of up to 50 bar-coded slides. The automated system scans the slides to produce a high-resolution electronic slide image, and identifies user-defined fields and features of interest on each slide. Then, after analyzing those features for details, the system electronically archives the information and displays selected images of the results on a computer screen for easy review and further study. By indexing each of these features electronically, Ariol enables the operator to automatically return to any specific feature on any particular slide for a more detailed review.

An emerging Ariol application is tissue microarrays (TMAs). These allow researchers to examine hundreds of small tissue samples on a single glass slide. Currently, TMAs are used for research, yet they are already being integrated for clinical purposes by early adopters of this methodology. Because of the difficulty in managing data sets, automated TMA scanning and image analysis will be of paramount importance.

What impact will improving automated image analysis have on the world of the clinical laboratory? The answer, says one Applied Imaging Corporation professional, is substantial. As technical product manager for the pathology market, Iqbal Habib coordinates the marketing of Applied Imaging’s automated scanning and image-analysis systems within the clinical laboratory, translational research, and biopharma.

 The Ariol slide loader.

Providing Increased Productivity, Accuracy, And Objectivity
For today’s clinical laboratories, the focus is on enhancing productivity without compromising accuracy and objectivity in slide analysis. The recent explosion of new immunological and DNA-based biomarkers creates enormous opportunities in the area of targeted therapeutics. Despite this fact, advances in these assays have created a challenge for the laboratory technologist on whose deductive insights these tests rely. The pressure to analyze an ever-growing number of slides and tests has been made more complex by the requirements for quantitative multi-spectral analysis of a wide variety of chromogenic and fluorescent markers.

Fortunately, advances in digital imaging and image analysis offer a solution that can help clinical labs objectively analyze specimens and generate quantifiable results. Ariol can be programmed to interpret images and identify the subtlest variations in color as well as intensity. This makes the system ideal for multi-spectral quantitative analysis. In addition, Ariol provides a degree of consistency, impartiality, and objectivity to aid the human eye, an important benefit at a time when technologists are managing and processing ever-growing volumes of images and data at incredible speeds. Breadth of capability is another feature that distinguishes the Ariol system, according to Bill Cook, senior director of strategy and business development for Applied Imaging and CTC Inc.

“The Ariol platform is equally useful for analyzing samples in brightfield mode and fluorescence mode,” Cook says. “It offers value and efficiency, both as a discovery tool for studies of protein and nucleic acid expression and as a validated clinical system.

“Because the software that drives the system can be trained by the operator to recognize specific patterns and features, the Ariol system is a valuable tool in new biomarker applications. That dual capability has fed the Ariol system’s popularity in recent years among clinical researchers as well as drug-discovery and pharmaceutical-development groups,” Cook says.

For clinical lab applications, Ariol has received US Food and Drug Administration (FDA) clearance as an aid to pathologists in the detection, classification, and counting of cells of interest—those of a particular color, intensity, size, pattern, and shape. Applied Imaging has received additional FDA 510(k) clearances for specific applications, including the breast cancer tumor assessment estrogen receptor, progesterone receptor, and HER2 immunohistochemistry and HER2 using the fluorescent in situ hybridization technique.

Circulating Tumor Cell Technology
In 2004, Applied Imaging formed a separate company, CTC Inc, and charged it with developing new products with the capability of accurately detecting, quantifying, and characterizing tumor cells that circulate in the bloodstreams of cancer patients. Analyzing circulating tumor cells (CTCs) in the bloodstreams of cancer patients is an important advancement. Traditional imaging and blood tests lack the sensitivity and specificity to provide physicians with the critical information they need to make accurate and timely analyses of cancer status.

The initial clinical application will be for breast cancer. Today the clinical laboratory assesses the level of MUC1 in the blood of breast-cancer patients by using either CA15.31 or 27.29 immunoassays. However, the limitations of these tests in sensitivity to earlier recurrence of disease and specificity to cancer are widely known, truncating their clinical usefulness.

On the other hand, the potential for CTCs to improve patient care is nearly unlimited. The number of cells shed from primary and metastatic tumors and found circulating in patients’ blood has already been correlated to the extent of the disease2 and may be a valuable tool in assessing the progression and regression of disease, and therefore in improving patient care.

But counting cells is just the beginning. Each cell contains unique protein and nucleic acid signatures, which can provide critical information about the status of the disease. “The capabilities of the Ariol system offer the potential to interrogate identified cells of interest and, consequently, may provide additional insight into the best initial therapy choice or changes in therapeutic regimen over time,” Cook says.

From its base in San Jose, Calif, Applied Imaging has grown into a leading provider of automated imaging and image-analysis systems. To date, the company has installed more than 4,000 of its imaging and image-analysis systems in more than 1,000 laboratories representing in excess of 60 countries. Its fluorescence and brightfield microscopy brands include Ariol, SPOT™, and CytoVision® product lines.

Nicholas Borgert is a contributing writer for Clinical Lab Products.

1. Bast RC Jr. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1865–78.
2. Cristofanilli M. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–91.