Digital Pathology Blog

Aperio Introduces Industry's First Digital IHC Solution With Integrated Image Analysis for Quantification of Breast Cancer

In yet another step towards full adoption of digital pathology in the clinical workspace Aperio recently announced a complete solution for reading and IHC stains with integrated reporting for a wide variety of tissue types and stains.  

Pathologists now can read and report digital slides with added ease of reporting in the same application.  Adoption has been occurring in niches and this is another barrier to entry that has been crossed - the ability to interpret and report in a more functional clinical workflow.  The added advantage of "real-time onsite image analysis" provides another deliverable over "analog pathology".

Abbreviated press release:

Slides to Reports in Less Than 30 Minutes

Aperio Technologies, Inc., (Aperio), a global leader in digital pathology for the healthcare and life sciences industry, is pleased to announce the launch of a digital pathology solution for Immunohistochemistry (IHC) designed specifically for the clinical market. Aperio’s digital IHC solution is the only commercially available FDA-cleared system allowing pathologists to run quantitative IHC image analysis while reading slides on a computer monitor.

A digital IHC system significantly streamlines clinical workflow. By using a single system to read digital IHC slides, perform quantitative image analysis, and create professional reports, pathologists can provide faster turn-around times, more informed decision-making, and accurate and consistent test results.

Eric F. Glassy, MD, medical director at Pathology Inc., stated, "After switching to Aperio's digital IHC solution from a different computer-assisted technology, we immediately experienced improved efficiency. More importantly, the interpretation algorithms offer far more control and accuracy, and the reporting capability is superior. We especially appreciate the ability to link thumb nail images on the PDF file to the actual whole slide images. The power and flexibility are simply remarkable."

The digital IHC system includes FDA-cleared algorithms for HER2, ER and PR stained breast specimens for diagnosing digital slides for clinical use in pathology. In addition, the system comes with a suite of image analysis algorithms that can be tuned for different tissue types (e.g. breast, colon, prostate), stains (e.g. HER2, ER, PR, Ki-67, P53, EGFR), reagents (e.g. Dako, Ventana) or to correlate algorithm results with other test methods (e.g. FISH, CISH).

“An integrated system is key to providing an efficient workflow for pathologists, and a major advantage over add-on image analysis systems,” said Dirk Soenksen, CEO of Aperio. “Pathologists can now use Aperio’s sophisticated cell-based image analysis capabilities with the click of a button while reading a slide.”

BioImagene Develops Companion Algorithms (TM) to Further Enable Personalized Medicine

This morning BioImagene annouced the use of companion algorithms.  What I think we are seeing in digital pathology is less talk and interest in hardware and more interest with software whether it be image analysis, algorithms for detection/diagnosis or software to help meet the demands of personalized medicine. 

While the actual scanning is not trivial and much effort has been put in to this to provide adequate solutions for clinical use, the value of the whole slide rests not only with being able to view this locally or remotely but use the digital data set to enhance what may not be possible or feasible with the "raw" glass alone.  I gather we will see more applications like this in the near future. 

Full press release below.

SUNNYVALE, Calif.--June 29, 2009  -- (BUSINESS WIRE)--BioImagene, the leading provider of innovative digital pathology solutions, announced today that the company is advancing its goal of bridging personalized medicine and the clinical practice of pathology by providing Companion Algorithms (TM). These specialized algorithms, which BioImagene develops for use with its Virtuoso (TM) suite of web-based software, aid pathologists in the quantitative assessment of specialized diagnostic tests used to determine patient suitability for specific cancer therapies. As pharmaceutical companies work to develop companion diagnostics to individualize therapy for cancer patients, Companion Algorithms further enable pathologists to correctly identify and accurately measure specific biomarkers used to determine appropriate treatment options for patients.

“Companion diagnostics will play an increasing role in cancer care as physicians strive to provide the therapies that are most likely to be advantageous to individual patients,” said Keith J. Kaplan, M.D., Mayo Clinic. “Companion Algorithms bring personalized medicine one step closer to reality and can help the pathologist provide the most actionable information to the oncologist.”

Ajit Singh, Ph.D., chief executive officer of BioImagene, commented: “The Human Genome Project opened the doors to research in the field of biomarkers and cancer diagnostics; however, challenges still exist in using biomarkers to identify subpopulations of patients that are likely to respond favorably to targeted treatments. Providing pathologists with Companion Algorithms will ultimately move our industry closer to the goal of personalized medicine.”

BioImagene’s Companion Algorithms can be used by pathologists to aid in the interpretation of digitized images of cancer diagnostic tests including immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Digitized images can be generated by one of BioImagene’s iScan slide scanning systems, such as Coreo, Concerto, or Solo. In February 2009, BioImagene received clearance from the U.S. Food and Drug Administration (FDA) for use of one of its Companion Algorithms in the company’s PATHIAM™ IVD Imaging Software for HER2/neuimmunohistochemistry tests. The iScan Coreo and associated software are used to detect and provide a quantitative measurement of HER2/neu, a protein measured in breast cancer patients to determine their candidacy for treatment with the Genentech drug Herceptin (TM).

“The Herceptest, the first FDA-approved companion diagnostic, is used to identify the subset of breast cancer patients who over-express the HER2/neu protein and will therefore have a high probability of responding to Herceptin,” said Robert Monroe, M.D., Ph.D., chief medical officer of BioImagene. “BioImagene’s FDA-cleared HER2/neu Companion Algorithm improves the accuracy and reproducibility of Herceptest interpretation. BioImagene offers additional Companion Algorithms for breast cancer and is committed to developing new Companion Algorithms for other companion diagnostic tests used in prostate, colon, lung and other cancers.”

 

July 9-10 GTCBio Rediscovering Biomarkers, San Diego

Courtesy of Definiens:
Definiens Cordially Invites You to:
GTCBio's Third Annual Rediscovering Biomarkers
July 9-10, San Diego
Definiens will be demonstrating the Definiens XD image analysis platform for image analysis of cells, tissues, and non-invasive images.
Additionally, Peter Duncan, Director of Marketing and Business Development, Definiens, will be presenting:
Standardizing Image Analysis of Biomarkers Across the Biomedical Continuum
The talk will highlight a “game changing” image analysis software platform, Definiens XD. Definiens XD facilitates image analysis of complex images, from any source, in any dimension; allowing for the first time, a standardized platform for image analysis of biomarkers across the biomedical continuum.
Topics covered include:
• Image analysis of cell-based assays • Image analysis of biomarkers in heterogeneous tumor tissue • Image analysis in non-invasive imaging
If you are interested in attending, please contact us and we will provide a $500 voucher towards the conference registration.
See you at the conference!

Moffitt Cancer Center to Utilize Definiens Technology in Prognostic Research for Lung Cancer

Rapid, Accurate Image Analysis of Lung Nodules to Support the Development of Stratification Models for Patient Treatment As part of the research engagement, Moffitt scientists will also explore Definiens TissueMap and Definiens Developer for tissue-based image analysis. Definiens versatile portfolio spans clinical imaging and tissue imaging, supporting potential development of translational cancer research models. Munich, Germany and Tampa, FL, US – May 20, 2009 – Definiens, the number one Enterprise Image Intelligence® company, today announced that Moffitt Cancer Center will utilize Definiens technology in the analysis of lung cancer CT images for the purpose of developing more accurate prognosis and prediction models for response to specific lung cancer therapies. Image features extracted with Definiens technology will be compared to disease outcomes, as well as gene expression data available through Total Cancer CareTM, Moffitt’s comprehensive approach to cancer that enables researchers and caregivers to identify and meet all the needs of a patient and their family during the patient’s lifetime and for future generations. Moffitt is part of an elite group of National Cancer Institute (NCI) Comprehensive Cancer Centers focusing on the development of early stage translational research models. The Center will employ a lung tumor analysis research application developed by Definiens to rapidly and accurately identify, segment and analyze lung tumors from CT and PET/CT fused images. The application will also allow the researchers to measure lung nodule volume, surface-to-volume, attenuation gradient at the edges, shape features, texture and homogeneity measures, as well as tracking tumors’ volumetric changes over time. “At Moffitt, we are enthusiastic about deploying these cutting-edge tools to support our researchers with their critical work,” said Robert J. Gillies, Ph.D., Vice-Chair Radiology and Director of the Experimental Imaging Program at Moffitt. “We anticipate that the Definiens platform will streamline the analysis of hundreds, if not thousands, of CT and PET images. These numbers are necessary in order to develop more robust patient stratification models.” Following the release of the pioneering Definiens LymphExpert application for the analysis of lymph nodes, Definiens is developing image analysis applications for a variety of cancer types, addressing lung and liver tumors as next steps. All Definiens medical imaging applications are built upon the company’s proprietary Definiens Cognition Network Technology, an image analysis technology that examines objects in relation to one another and emulates human cognitive processes to extract intelligence from images. “We are excited to support Moffitt’s groundbreaking research into cancer therapies and personalized cancer care,” said Frank-P. Klein, Vice President, Medical Imaging at Definiens. “This project provides further confirmation that Definiens’ unique technology can address the most challenging image analysis tasks facing researchers for a variety of cancer types.” As part of the research engagement, Moffitt scientists will also explore Definiens TissueMap and Definiens Developer for tissue-based image analysis. Definiens versatile portfolio spans clinical imaging and tissue imaging, supporting potential development of translational cancer research models. Definiens in Medical Imaging By automating image analysis, Definiens supports healthcare providers in analyzing and interpreting vast numbers of digital images accurately and consistently. Definiens improves the analysis of tissue samples and non-invasive imaging, enabling translational medicine - from early diagnosis to personalized treatment. About Definiens Definiens is the number one Enterprise Image Intelligence® company for analyzing and interpreting images on every scale, from microscopic cell structures to satellite images. The Definiens Cognition Network Technology®, developed by Nobel Laureate Prof. Gerd Binnig and his team, is an advanced and robust context-based technology designed to fulfill the image analysis requirements of the Medical, Life Science, and Earth Science markets. The technology is modeled on the powerful human cognitive perception processes to extract intelligence from images. Definiens provides organizations with faster image analysis results, allowing deeper insights enabling better business decisions. The company is headquartered in Munich, Germany and has offices in the United States. Further information is available at www.definiens.com. Definiens, Definiens Cellenger, Definiens Cognition Network Technology, Definiens eCognition, Enterprise Image Intelligence and Understanding Images are trademarks or registered trademarks of Definiens.

BioImagene Launches New Ki-67 Algorithm For Prostate Image Analysis

From Medical News Today.  Time will tell if this is a useful marker in the clinical setting in prostate cancer.  What I find most interesting about the press release is the statement about expected "launch of a series of additional algorithms to serve the pathology and research communities".

"BioImagene, the leading provider of innovative digital pathology solutions announced the launch of a new Ki-67 prostate image analysis algorithm. The algorithm, which is part of Virtuoso TM, a comprehensive suite of web-based software applications for digital pathology, is used to detect and provide quantitative measurement of the protein biomarker Ki-67.

According to the Journal of Clinical Oncology, Cancer Research and other clinical journals, Ki-67 immunohistochemistry may be a valuable predictor of biochemical relapse and distant metastasis after prostatectomy and radiation therapy. Prostate cancer continues to be the most prevalent cancer in men, according to the American Cancer Society.

"The launch of the Ki-67 algorithm that can be used in a research setting illustrates the potential impact digital pathology can have on the practice of medicine," commented Dr. Ajit Singh, CEO BioImagene. "In the coming months, we expect to launch a series of additional algorithms to serve the pathology and research communities."

The launch of the Ki-67 algorithm adds to the company's growing offering of image analysis tools. BioImagene also has a PIN4 algorithm for prostate cancer research, and FDA cleared algorithms to assess HER2/neu immunohistochemistry status. The iScan Coreo and associated software are used to detect and provide a quantitative measurement of HER2/neu, a protein measured in breast cancer patients to determine their candidacy for treatment with the Genentech drug Herceptin™."

BioImagene Ushers in 2009 with Record Growth

Despite a volatile and difficult fourth quarter for the economy, BioImagene, recently announced a record 2008. The company saw a doubling of business volume compared to the previous year, with 50 scanners shipped in the in the fourth quarter alone. Pathologists worldwide scanned and analyzed 25,000 anatomic pathology slides using BioImagene systems during this quarter.

Several economists believe 2009 will continue to be a tough year economically before and my sense is that vendors in the clinical laboratory space and research arena remain optimistic that with some careful planning they can continue to meet their goals. 

My own institution has taken steps in terms of planned capital investments, research funding and recruitment of key personnel to meet our goals in this climate.  I gather other hospitals face similar pressures and new microscopes or whole slide scanning instruments will need strong justification for acquisition. 

Nonetheless, BioImagene was able to secure additional venture funding from Siemens Venture Capital, the successful establishment of a Global Customer Care Center and expansion into European markets before the market downturn in September and years' end. The company also added new reference laboratory customers, as well as hospital customers that are among the Best Cancer Hospitals as ranked by US News and World Reports. Agility Bio - a division of BioImagene Inc, entered into a partnership with Advinus Therapeutics, a TATA enterprise, to provide imaging services in conjunction with preclinical development services offered by Advinus.

Dr. Ajit Singh, CEO, BioImagene observed, “It has been an outstanding year for us and for digital pathology. The current economic climate does not appear to have dampened the demand for digital solutions for anatomic pathology. This bodes well for Digital Pathology as an industry, as well as the future of Personalized Medicine.” Dr. Singh had spoken recently at the California Society of Pathologists where he hailed Digital Pathology as “… the last missing link for enabling Personalized Medicine.”

Full press release

Aperio Receives Second FDA Clearance for Diagnosis of Digital Breast Cancer Slides

Aperio has recently received FDA clearance for interpretation of progesterone receptor to its already approved HER2 clearance for digital reads as well as image analysis applications for ER and PR.

Excellent news for signing out breast cancers with whole slide images on a computer monitor. 

The recent press release states: "Aperio has received its second FDA clearance from the U.S. Food and Drug Administration (FDA) for reading digital PR (Progesterone Receptor) slides from a computer monitor using its patented ScanScope® digital slide scanning system. Aperio previously received FDA clearance for the reading of digital HER2 slides from a computer monitor in December 2007.

The ScanScope System is intended for use as an aid to the pathologist in the detection and quantitative measurement of PR (Progesterone Receptor) by manual examination of the digital slide of formalin-fixed, paraffin-embedded normal and neoplastic tissue immunohistochemically stained for PR on a computer monitor. It is indicated for use as an aid in the management, prognosis, and prediction of therapy outcomes of breast cancer."

 Full press release

AgilityBio And Advinus Announce Partnership To Introduce Digital Pathology Services In Pre Clinical Research

In another sign of the pharma market for digital imaging, I came across this press release:

"AgilityBio, a division of BioImagene Inc, and Advinus Therapeutics, a TATA enterprise, announced a partnership that will enable providing imaging services in conjunction with preclinical development services offered by Advinus. This partnership will bring about a synergy between drug development at US based biotech and pharma industries and India's highly developed life sciences service industry. Advinus, a leading service provider of pre-clinical development services to the global Pharma and Biotech industry will combine its services with AgilityBio's imaging services that use BioImagene's cutting edge digital pathology solutions for cancer diagnosis and research."

Increased use of digital pathology and workflow solutions whether here or abroad in pharmaceutical R&D, toxicology or other life sciences markets will continue to help spur broad adoption within the clinical space.  I think those of us who are clinical practioners of medicine will learn much from this integration and the other one I posted earlier this week.  In particular, image analysis applications for cancer diagnostics and workflow management, first through LIMS, then LISs.

 

 

High throughput imaging speeds analysis of hormone receptors

Source: Baylor College of Medicine: Public Library of Science One (PLoS One), November 2008

A new high throughput microscopy technique enabled researchers at Baylor College of Medicine in Houston to analyse thousands of individual cells expressing androgen receptor, a finding that could herald new ways of evaluating the effect of drugs or other treatments on cells with normal or aberrant hormone receptors.

In a report in the current issue of Public Library of Science One (PLoS One), Dr. Michael Mancini and his collaborators reported a new, next generation high throughput image-based assay that helps determine the level and location of androgen receptor and its transcriptional activity on a cell-by-cell basis.

"This has application to personalised medicine," said Mancini, associate professor of molecular and cellular biology at BCM and director of its Integrated Microscopy Core. "For example, we could use the high throughput microscope and robust image analysis to determine which drug might be best to turn off or repair a mutated cell that is causing disease."

In this case, he and his colleagues analysed the androgen receptor, a molecule that binds the hormones testosterone or dihydrotestosterone and is responsible for regulating genes that give an organism or animal male characteristics.

"As our ability to image cells using high throughput microscopy got going faster and faster, we began to collect enormous amounts of functional data that was usually only accessible by separate (and slow) biochemical experiments. Our customized software approaches then allowed us two assemble the results into a more systems-level appreciation of the biology, linking together several functional characteristics of the androgen receptor," he said.

The high throughput technique, often called high content analysis, enables researchers to analyse effects on a cell-by-cell basis, taking into account the heterogeneity of the cells, he said. Before the development of new microscopes, he said, taking a few images an hour was a feat.

"Now we routinely take thousands of pictures a day," said Mancini.

Not only that, but scientists such as Adam Szafran, the M.D./Ph.D. student who is first author of this report, can essentially look at several elements of cellular response at the same time.

"We can study issues dealing with the cell cycle as it goes through its life," said Szafran. Previously, scientists had to manipulate cells to capture them at different points in their lives. The new imaging technology enables them to study the cell in a more natural form.

In the PLoS study, Szafran, Mancini and their colleagues were able to study the response of a particular androgen mutation to different ligands (molecules that can trigger binding to a particular protein).

"We could show how the receptor was defective in respect to the endogenous (or normally present) ligand. When we used a different ligand, we could rescue aspects of the receptor’s function," said Szafran.

One day, physicians could take the individual cells of a patient diagnosed with a disease and use the high throughput microscope to see how different drugs affect the mutated cells. The high speed approaches for androgen receptor studies are also being used to investigate basic science and personalised medicine possibilities in several other projects, including breast and prostate cancers, and adipose (fat cell) biology.

Role in HER2 in gastric cancer

Gastric cancer is the second leading cause of cancer mortality in the world and its management, especially in advanced stages, has evolved relatively little. In particular, no targeted modality has so far been incorporated to its treatment armamentarium. HER2 overexpression is increasingly recognized as a frequent molecular abnormality, driven as in breast cancer by gene amplification. There is mounting evidence of the role of HER2 overexpression in patients with gastric cancer, and it has been solidly correlated to poor outcomes and a more aggressive disease. Additionally, preclinical data are showing significant antitumor efficacy of anti-HER2 therapies (particularly monoclonal antibodies directed towards the protein) in in vitro and in vivo models of gastric cancer. As a result, several clinical trials are exploring in different settings and with diverse designs the potential of anti-HER2 therapies in gastric cancer patients.

A recent review from the Annals of Oncology discusses the issues with HER2 in gastric cancer. 

This is another example of a potential targeted therapy in the age of personalized, predictive and pre-emptive medicine and yet another role for the likely importance of image analysis in such cases.

Download her2_in_gastric_cancer_a_new_prognostic_factor_and_a_novel_therapeutic_target_annals_of_oncology.pdf