This morning Leica announced the release of a new image analysis application desgined to integrate with their portfolio of the SCN400 scanner and Ariol technology.  Was able to get a sneak peek at this application recently and was impressed with ease of use and accuracy embedded within a complete digital pathology solution from scanning to archiving to viewing to image analysis.  

As frequent readers know, I consider image analysis a significant component of digital pathology.  The technology takes pathology to a place we have not enjoyed with conventional microscopy and often single stains on a single slides, usually immunohistochemistry-only or flourescent-stain alone.  

While effective, it limits interpretation largely to tumor biology rather than cellular biology. Image analysis allows for deconvoluting multiplex staining to ask very specific questions about particular cellular phenotypes rather than tumor phenotypes, and in return, answer some specific questions related to celliular behavior, clinical prognosis & enhance biomarker development and drug discovery.

Lessons learned from the HER2 experience, related therapy and known issues with processing, staining and interpretation I think have shown the need for image analysis for improved accuracy, consistency and reproducibility.

Wetzlar, Germany, March 30, 2012—Leica Microsystems announces the release of Tissue IA 2.0, high performance image analysis for discovery research. Combining fluorescence and brightfield analysis capabilities in a single platform, with precision cell modelling, Tissue IA 2.0 offers a superior solution for IHC biomarker quantification. Tissue IA 2.0 joins the Total Digital Pathology portfolio from Leica, providing streamlined end-to-end excellence in capture, management and analysis of digital pathology images.

A major challenge in research today is retrieval of quantitative, reproducible data from tissue-based IHC studies. Tissue IA 2.0 provides expert tools for researchers to extract the most from their studies. Powerful color separation and multi-marker colocalization functionality provides advanced insight and unbiased measurement of multiple antigen immunostaining in brightfield or fluorescent samples. Sophisticated cell modelling accurately detects and quantifies differential expression of staining in cellular compartments, providing detailed insight into cytoplasmic, membrane and nuclear biomarker localization.

The advanced dual staining capabilities in Tissue IA 2.0 enable researchers to identify cell cohorts at the molecular level.  Use one marker to identify a population of interest and then quantify expression of a second, providing exceptional analysis performance and greater understanding of a user’s slides.  Algorithms are easily adjusted and optimized for different markers, tissue and protocols giving a flexible platform for drug discovery applications. 

Easy to deploy and easy to use, the Tissue IA web-accessible interface means that users can take their analysis with them wherever they go. With high throughput batch analysis capacity, Tissue IA 2.0 will process whole slides, regions of interest or tissue microarray cores, and automatically integrate analysis results with a user’s slides. A built-in upload interface facilitating integration of algorithms from 3rd party software solutions, gives greater flexibility to further expand analysis options.

Dr. Donal O’Shea, Head of Digital Pathology in Leica Microsystems, says:

“Mulitplexing is of growing importance in translational research and tools to help quantify the expression and location of multiple biomarkers concurrently in tissue are a real requirement.  TissueIA 2.0 delivers for the user through offering chromogenic and fluorescence quantification and co-localization, cell based histoscoring on multi-compartmental IHC staining and the power to include and exclude cell populations based on biomarker expression.  In conjunction with our SCN400 F and Ariol platforms, this further expands our Digital Pathology portfolio for the life science and clinical researcher and demonstrates our ongoing commitment to this area.”

Tissue IA 2.0, with its powerful, streamlined analysis, is the ideal choice for biomarker discovery and translational research. Its unique combination of flexibility, automation and ease-of-use make it an unparalleled tool for digital pathology research. To learn more about Tissue IA 2.0, please visit http://www.leica-microsystems.com/products/digital-pathology/analyze/details/product/tissue-ia/

Leica Microsystems will be at the American Association for Cancer Research Annual Meeting 2012, March 31 – April 4, Chicago, IL. Visit Leica at booth 4103 to experience our new image analysis solution for Digital Pathology.

*For research use only. Not for use in diagnostic procedures.

About Leica Microsystems

Leica Microsystems is a leading global designer and producer of innovative, high-tech, precision optical systems for the analysis of microstructures. It is one of the market leaders in each of its business areas: Microscopy, Confocal Laser Scanning Microscopy with corresponding Imaging Systems, Specimen Preparation, and Medical Equipment. The company manufactures a broad range of products for numerous applications requiring microscopic imaging, measurement, and analysis. It also offers system solutions for life science including biotechnology and medicine, research and development of raw materials, and industrial quality assurance. The company is represented in over 100 countries with 16 manufacturing facilities in 9 countries, sales and service organizations in 19 countries and an international network of dealers. The global management is headquartered in Wetzlar, Germany.

If you had any doubts whether the various types of social media (e.g., Twitter, Facebook) were here to stay, take a look at a recent news article concerning a new hire the University of Michigan (see: University of Michigan social media director hired at $100K per year):

via labsoftnews.typepad.com

One of my all-time heroes as a child was Albert Einstein.  Regarded as one of the greatest minds of the 20th century if not civilization itself, he had an incredible personal story, professional triumphs and personal tragedies.  I used a quote of his to begin my essay for medical school: "“Imagination is more important than knowledge. For knowledge is limited to all we now know and understand, while imagination embraces the entire world, and all there ever will be to know and understand.”

There are dozens of other great quotes attributed to him, including "We can't solve problems by using the same kind of thinking we used when we created them" or "Logic will get you from A to B.  Imagination will take you everywhere".

Perhaps my favorite one is attributed to Einstein while helping a group of school-aged children with their math studies: "Do not worry about your difficulties with mathematicss; I can assure you mine are much worse".

Over 10 years ago a book was published entitled Driving Mr. Albert written in first person with someone who drove across America with Einstein's brain and the pathologist who for years had kept it in formalin. In addition for the trip, he talks about the problems associated with keeping wet tissue and the pathologists' problems, issues, paranoias and difficulties for doing so for decades.

Einstein died in 1955 at Princeton University due to a ruptured aortic aneurysm.  At the time he became ill he was offered surgery by a Dr. Nissen (I gather of Nissen fundoplication) to repair the aneurysm.  He refused.  The treatment offered to him at that time was a vascular graft, still experimental at the time, but an improvement over the standard therapy in early studies.  The other treatment was wrapping the aneurysm in saran wrap.  Grafts are standard of care today unless interventional radiology does it less invasively today by other means.

Anyways, looks like a trip to Britain is order as sections of the much talked about brain of Einstein will be on public display, news to me thanks to The Pathology Blawg.  Read more here.

Once again, Ole Eichorn, Aperio's Chief Technology Officer and The Daily Scan blogger put together a nice photo montage with captions and highlights from this years USCAP meeting exhibit floor.  In addition to showcasing Aperio's booth and products, Ole highlights many other companies, their products and how many other vendors are using digital pathology or services that tie into digital pathology.

Aperio also released their ePathViewer for iPad last week.  Was able to get a sneak peak at this from some Aperio folks earlier this month and is a must have for whole slide afficiendos. Reviewed some Juan Rosai collection slides as well as some SecondSlide cases with the app and despite a slow network the image refresh rate (and quality) were excellent (pre getting my iPad3 with HD display).

Below the screen shot below on the App Store you can also see other iPad viewers for viewing other whole slide images from Leica, Motic, Objective Pathology & large medical images with cool names like WholeSlide, iPathology and SlidePath.

Is was not so long ago that digital pathology relied upon being tethered to a desktop PC with enough RAM and bandwidth to view the images.  

No more.  Digital pathology is mobile!

The days of being tethered to your histology laboratory, your microscope and your laboratory information system (thanks to web-based LISs) are over.  

Next-generation Pathology

Pathology faces increasing competition from the modern methods of molecular biology. Genomics and proteomics promise to provide unbiased, quantitative data revealing insights into origin and progression of disease. Will pathology need to change in order to defend its territory? Quite certainly. Should pathologists forget what they have learned over the centuries? I don’t think so.

It could be claimed that the basic pathological methods have changed too little since the invention of the light microscope. However, the basic reason to look at histological samples didn’t change either. The morphological details of heterogeneous tissue provided invaluable information well before genes and proteins were discovered. And they continue doing so ever since.

Genes and proteins are essential components of the molecular magic that brings about tissue morphology (among other things). No biological science can afford ignoring all we have learned about them in the recent past. At the same time, genetic fingerprints and protein profiles are mostly obtained from blood or homogenized tissue samples that lack the spatial dimension histology is all about.

Tissue slides reveal the complex interplay between different cellular populations, their gene expression levels and metabolic status. They thus are a more comprehensive readout of molecular dynamics than any molecular technique alone could ever provide. Pathological scores, though, are necessarily less comprehensive. They aim at reducing complexity in order to increase consistency. They are so successful at achieving the former, that the quantitative requirements of modern science are hardly met. Yet they often fail to establish the latter as inter-observer variation remains high.

Next generation pathology will need to integrate molecular techniques into the traditional framework of histology: the morphological complexity of heterogeneous tissue. The required methods are well established and they are now transforming pathology. Immunohistochemistry combines molecular information on protein levels with spatial context. Novel methods based on in situ hybridization are reaching the maturity required to complement the histological toolbox. One by one, IHC stains put proteins into context. SISH, CISH, FISH et al. now do the same with genes. These advances open another dimension to the information that can be derived from histological samples. The spatial dimensions can be complemented with molecular ones. And the molecular information can be added to the information residing in tissue instead of competing with it.

As usual, the next generation comes along with novel toys. Automated image analysis is required to capture the quantitative readouts promised by the molecular advances. In order to go beyond genomics and proteomics, pathological knowledge will have to be accounted for and it is thus essential to make the novel approaches available to pathologists. To get from toys to tools, automated image analysis solutions need to be straightforward enough to be used routinely by pathologists. At the same time, they need to be flexible enough to robustly cope with the heterogeneity of histological samples.

Tissue proteomics and tissue genomics should be the pathologist’s reply to the molecular challenge they face.

For more information on this, check out Definiens Webinar series, including one this Thursday entitled "Quantitative Digital Pathology Out-of-the-Box: Definiens Tissue Studio Combines Flexibility and Ease-of-Use with High Productivity". Click here to register.

Thursday March 29th, 2012

CBLPath recently announced it is one of a select few labs within the United States to offer Vysis(R) ALK Break Apart fluorescence in situ hybridization (FISH) testing for non-small cell lung carcinoma (NSCLC). The Vysis ALK FISH test detects rearrangements in the ALK gene employing fluorescent probes to detect the presence or absence of specific DNA sequences.

Vysis ALK FISH is the only FDA-approved companion diagnostic for XALKORI(R) (crizotinib). XALKORI was recently approved under the FDA's priority review program for treatment of patients with late-stage NSCLC who have an abnormal ALK gene. XALKORI has been shown to inhibit the proliferation of ALK, thereby suppressing growth of NSCLC tumors.

"CBLPath is proud of the positive impact our work has on patients' lives," said Chief Medical Officer, Dr. Carlos D. Urmacher, FCAP, FASCP. "Keeping at the forefront of the latest technologies ensures our clients and their patients have access to the best therapies available. By receiving approval from New York State to run the Vysis ALK FISH test, we are able to help clinicians identify those patients who will benefit from treatment with XALKORI."

Non-small cell lung cancer is the most common type of lung cancer with approximately 170,000 new cases per year in the United States. Non-small cell lung cancer includes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. There are a variety of treatment options for NSCLC, and a patient's success with any treatment option is dependent upon their genetic profile. About 1-7% of patients with NSCLC possess the ALK gene abnormality. These patients are typically young and non-smokers. Patients with the ALK mutation respond favorably to treatment with XALKORI.

XALKORI is a registered trademark of Pfizer Inc. Vysis is a registered trademark of Abbott Laboratories.

Full press release.