Digital Pathology Blog

Year in Review

2010, in a word, was about change.  Personally, my family and I moved from Mayo Clinic in cold and snowy Rochester, MN to private practice in slight less cold and snowy Charlotte, NC. So far the move and new opportunities have exceeded our personal and professional expectations.  My many thanks to the readers and sponsors for your continued support, ideas, comments and criticisms.

The anatomic pathology and digital pathology market also saw many changes, particularly within the last few months of this year, namely, Ventana's acquisition of BioImagene , GE's acquisition of Clarient, Sonic's acquisition of CBL Path and Philips, Omnyx and Leica having a greater presence in the digital pathology space.  About this time last year Danaher made an offer to acquire Genetix which earlier acquired SlidePath and is the parent company of Leica Microsystems.  That deal closed in March of this year.  Most recently CRI's acquisition by Caliper Life Sciences was announced in the world of optical imaging technologies.

The arrival of the large healthcare companies with digital pathology products (Philips and Omnyx) was expected and we have seen hints of their efforts for some time before nearing production mode for distribution.  Leica's offerings were also present but on a smaller scale as they have ramped up production as well going into 2011.  By all accounts, the introduction of the large healthcare technology and last of the traditional microscope companies into the the digital pathology space shows maturation of the technology and the value these companies see in the digital pathology market. 

The acquisition of Clarient is interesting on several fronts.  Does GE have intentions of becoming a pathology services provider and stepping out beyond providing technology?  Will it do the same with its greater presence and bigger market with radiology imaging than currently exists with molecular diagnostics and the hopes of personalized medicine?  And where does these leave Omnyx?  Arguably it will make it more difficult for them to sell to other large reference laboratories if they view Clarient, A GE Healthcare Company and Omnyx as a GE Company.  Clearly Omnyx and Philips both need and will have a place in large reference laboratories and large academic/university medical centers given their high volume, high throughput scanning and respective emphasis on workflow and PACS-enabled viewing. Does a company like Philips benefit from the GE-Clarient deal?  Will GE keep Clarient? For how long?

CBL Path's acquisition by Sonic Healthcare, the large international laboratory services company gives Sonic another US laboratory, a presence in New York state and molecular pathology. 

Perhaps most interesting to goings on in digital pathology is the sale of BioImagene to Ventana, a company Roche paid close to $4 billion about 3 years ago.  It was not a secret when Siemens invested in BioImagene and brought in Ajit Singh, PhD, that his job was to get BioImagene sold.  What does it mean for the industry now? Historically, BioImagene was very aggressive with their pricing models and placed numerous systems.  Despite that, it is unlikely they ever generated more than $10 million a year in revenue. 

Ventana now has an offering in digital pathology to sell with their suite of stainers and stains that their competitors do not have.  Ventana customers can now have a complete end-to-end solution from staining to scanning with image analysis algorithms optimized for their stains. 

Leica of course produces microscopes, routine stainers and coverslippers and could perhaps develop an end-to-end solution from H&E to coverslip to scanner with their own image management and analysis in conjunction with SlidePath as both companies are owned by the same parent company.  This may also offer Leica a competive advantage offer Philips and Omnyx who do not have a similar presence in anatomic pathology laboratories.

With talk of "lot of money on the sidelines", talk of billion dollar IPOs in the offering for 2011 according to the Wall Street Journal, signs of economic rebound, as well as changes in healthcare it will be interesting to see what the next year brings for digital pathology vendors and consumers.

Any predictions? 

Tissue-based proteomics meets digital pathology

Expression Pathology and Flagship Biosciences recently announced a services alliance in tissue-based proteomics, combining digital pathology with mass-spec FFPE tissue proteomics. While this collaboration is oriented towards research and companion diagnostics development, mass spec is making rapid inroads in all areas of clinical applications, including tissue. The ability to run protein expression in FFPE instead of fresh tissue is a major enhancement on the road to clinical adoption. Mass spec offers the ability to better characterize post-translational modifications of proteins and various isoforms, high levels of multiplexing, and the avoidance of dependence on a given target epitope or antibody for test results. It does require up to 30,000 cells for protein expression measurements, meaning approximately 2 mm x 4 mm of 10 micron thick tissue sample. Up until now, one of the most manual steps has been the selection of tissue for the microdissection, an obvious application where digital pathology and histology pattern recognition can have advantages. The Mayo Clinic licenses Expression Pathology's approach in the diagnosis and classification of amyloidosis in routine biopsy specimen. A number of large reference laboratories are systematically transitioning their small molecular analysis platforms from the traditional ELISAs that require antibodies to mass spec. 

Radiology versus pathology: Not more quantitative, just more digital

Steve Potts, of Flagship Biosciences, a digital pathology services company, submitted the following blog comparing the perceptions of radiology with pathology.

At a molecular imaging meeting earlier this year, Flagship presented pharma regulatory compliance for digital pathology. Our talk was the only one on pathology. The others were all various presentations on the different modalities of radiology imaging applied to clinical trials -- X-ray, MRIs, microCT scans, PET scans, CAT scans, dog scans, and so on :)

 

A radiologist told me several years ago, "Pathology is where you see the details of real biology -- the highest resolution look at the local disease state." And yet why does the average person on the street know what an MRI is, what a CAT scan, what an X-ray is, and yet has never heard of an IHC, or much less an H&E? Not only much greater awareness among the general public, but there is also a perception that radiology is a quantitative science. It is not.

 

How many pattern recognition programs exist in the daily radiology workflow? How much quantitation occurs by the computer in radiology? Nothing wrong with this, but most clinical diagnoses in radiology are a trained professional making qualitative judgments on a computer screen. The three-dimensional nature of tissue heterogeneity makes quantitative evaluation in radiology as difficult as it is in pathology. Regarding pharmaceutical companion diagnostics development, standard radiology imaging approachs in clinical trials involve agreement on a study design with manual tiered scoring, similar in many ways to qualitative pathology approaches. Once could argue radiology is less quantitative than pathology if one considers the progress made in breast cancer HER2/ER/PR quantitative IHC clearances. There has been a noticable decrease in the volume of CAD (computer-aided diagnosis) messaging at this year's RSNA tradeshow, the number one show for the medical radiology technology community.

 

Radiology isn't more quantitative, it is just more digital.

 

Imagine two presenters, one using a blackboard and the other powerpoint. Which one seems more modern, more professional? Or two people writing a manuscript -- which appears better, the neat word document or the pages of legal pad scribbles? The irony is that no cute powerpoint presentation beats that one professor you had (maybe the teacher in high school or college who first got you interested in science -- it only takes one) who used every portion of the blackboard, and left you hanging on every word.

 

Similar in manuscripts. At Flagship we have been digging back through a century of histopathology literature looking for special stains to use in our new multiplexing IHC technology to help the computer identify subanatomic organelles. The quality of the manuscripts of some of the pioneering work in histology stains from decades ago is remarkable. Careful, detailed pen and ink drawings of which stains work best in which substructures. Thoughtful, comprehensive staining recipes from the days when quality beat quantity in publications. Biology rationales behind non-specific staining artifacts in other substructures, from the era of pen and ink drawings. But while digital does not mean better, it certainly appears more quantitative to the outsider.

 

Radiology isn't waiting for pathology to go digital. From their perspective, it is just one more digital mode to integrate with better resolution than they had before.

 

The topic of the RSNA meeting this year is instructive -- personalized medicine. The next time I go to a "molecular imaging" conference, I want people to think pathology first, and radiology second.

 

Radiology is not more quantitative than pathology, it is just more digital.

 

Tissue-based Companion Diagnostics Alliance Formed to Address Quantitative IHC Needs in Europe

Flagstaff, AZ (PRWEB) December 22, 2010

Flagship Biosciences LLC, a quantitative pathology company and HistologiX, a GLP accredited CRO today announced a joint partnership to provide histology services and tissue-based companion diagnostics development to European pharmaceutical clients.

Tissue-based diagnostics is a major component in most oncology portfolios for companion diagnostics, and depends on tissue procurement, outstanding immunohistochemistry practices, image analysis, and board-certified pathologist review. The nature of most oncology clinical trials are global, so shipping glass slides and adequately supervising the histology and pathology can be a difficult logistics challenge.

Digital pathology and quantitative IHC offers the ability for the image analysis and pathology review to be conducted remotely, and centralizes all data in a trial into a single location. Flagship Biosciences is teaming with Histologix to offer this service to European pharmaceutical clients. The histology and slide scanning will be conducted by Histologix in the UK. The slides are then uploaded to a Flagship digital pathology secure server, where image analysis provides quantitation and pathology review can be conducted virtually. Geography is then removed as a major logistics challenge, and the pathology analysis becomes both quantitative and can be reviewed by an expert pathologist in a study and effectively communicated to pharmaceutical clients.

"Image analysis and quantitative IHC is a growing opportunity in oncology drug development, from early stage research through clinical trials," said David Fairley, Managing Director of Histologix, and a veteran in the management of tissue-based regulated diagnostic testing. "Our partnership with Flagship Biosciences gives our clients virtual access, a centralized and standardized approach to slide review, and a quantitative scoring approach that assists with pathology reads."

"It is clear than in most companion diagnostics programs, a 510k or PMA will be required for approval," said Dr. Holger Lange, Chief Technology Officer of Flagship Biosciences, and who is based in Germany. "We are working to define a regulatory approach that will meet the needs of both US and European diagnostics approvals process in tissue. Flagship needed an expert partner in tissue handling and IHC methodology in Europe, as image analysis results are dependent on outstanding histology practices."

"The tissue-based companion diagnostics programs that are under development at pharmaceutical companies are far more complex than the currently approved biomarkers for breast cancer," said Dr. David Young, President of Flagship Biosciences, and a well-recognized leader in tissue-based companion diagnostics development. "Histologix brings outstanding talent and experience in tissue procurement, histology and immunohistochemistry procedures, and GLP and regulatory expertise. This competency allows Flagship to build quantitative IHC techniques for European clients on a strong GLP histology foundation."

Flagship Biosciences LLC, with a datacenter in Flagstaff, Arizona and a Boston digital pathology office, is a pathologist-owned company that delivers quantitative pathology to pharmaceutical and medical device clients.

HistologiX Ltd is a rapidly growing GLP accredited Contract Research Organisation (CRO) providing commercial services to the Pharmaceutical, Biotechnology and Academic/Healthcare industries in Histology, Immunohistochemistry (IHC), Human Tissue Procurement, Clinical Trials, Molecular Biology and Advisory Consultancy. The Company was formed in 2005 by individuals with extensive experience in regulatory and non-regulatory diagnostic and clinical histology as well as IHC.

For the original version on PRWeb visit: www.prweb.com/releases/prweb2010/12/prweb4919964.htm

Webinar Reminder For Definiens Developer XD

Image Analysis Strategies for Challenging Biomedical Images using Definiens Developer XD™

Join us for a webinar:  Image Analysis Strategies for Challenging Biomedical Images using Definiens Developer XD™

Learn image analysis strategies from the pros at Definiens using Definiens Developer XD on the following examples:

• The Rolling Ball Method for Correcting Heterogeneous Backgrounds in Fluorescently Stained Golgi Cells
• Three Dimensional Analysis of Dendritic Spines
• Classifying Tumor vs. Non-Tumor and Tumor Morphology in Non-Small Cell Lung Cancer

Speakers: 

Peter Duncan - Director, Marketing and Business Development
Dr. Thomas Mrowiec - Consultant, Professional Services
Dr. Florian Leiss - Trainer and Marketing Specialist

 

Title:		Image Analysis Strategies for Challenging Biomedical Images using Definiens Developer XD™
Date:		Wednesday, December 22, 2010
Time:		11:00 AM - 12:00 PM EST / 4:00 PM - 5:00 PM GMT

 

After registering you will receive a confirmation email containing information about joining the Webinar.

 

System Requirements PC-based attendees Required: Windows® 7, Vista, XP or 2003 Server

Macintosh®-based attendees Required: Mac OS® X 10.4.11 (Tiger®) or newer

 

Space is limited. Reserve your Webinar seat now at: https://www2.gotomeeting.com/register/227449746

 

Simple answer to Send My Slides Back Now!

Dr. Thomas Wheeler entered the following blog (below) on Medscape about a week ago.  There is a simple solution to all of this that negates time, cost and risk for both referring and consulting pathologist/institution.  The answer of course in two words is digital pathology. Particularly with the ever increasing power of cloud computing.  Simply, the referring institution scans and uploads the slides, regardless of patient, physician or pathologist request for consultation or second opinion.  The referring pathologist uses the cloud to review the slides, render his or her report and complete the case.  This negates the need for referring hospital to package, send, check receipt of delivery and record receipt of slides upon return and account for any loss or damage upon return.  The consulting hospital is also spared the need to take receipt of case, inventory contents, accession and maintain slides in original number and condition.  Both sides are spared the cost and resources to maintain either send outs or consults.  A record of slide(s) reviewed is kept and data with regards to images reviewed can be maintained.  Perhaps most importantly, unlike the courier model, both the referring and consulting pathologist have a mechanism to look at the same slide(s) at the same time.

If the case requires additional immunohistochemical stains, these too may be done by referring hospital and later uploaded for review thus negating need to send tissue blocks and allowing referring hospital to capture the TC with potentially less delay than sending the block which would add another day on top of the time to do the stain(s).  This of course will not work depending on size and skill of referring laboratory but the model works the same when possible and requires courier if necessary. 

Lastly, cases of interest for potential further study or teaching are maintained where several participants can have access while maintaining access and patient privacy. No slides leave the originating department.

For reference labs this is common practice - that is hosting images for review by others.  It negates need to overnight slides when technical services are required and provides a shared image for both the reference lab and the client if discussion or repeat testing is needed.

More labs can and should do this on both ends of the slide consult model.  Why is this not more common?

Several reasons, among them -- cost of scanners, resources to scan and upload slides and maintain control and access, consultants reluctant to adopt digital pathology and/or referring pathologist reluctant to adopt, receiving pathologist may want to do his/her "own stains" and well-established processes in place that facilitate courier models in nearly every laboratory/hospital.  The first is really the still remaining barrier for some labs, the others are largely psychological and technical which requires a culture of change and degree of trust to allow for this kind of slide exchange.

Courtesy of Dr. Thomas Wheeler via Medscape (registration required):

Now more than ever, patients seek definitive treatment for cancer or other serious conditions at a major medical center, one different from the institution where the diagnosis is made.  This necessitates transfer of medical records, radiology reports and yes -- the pathology report and associated microscopic slides.  Typically, the slides are reviewed at the final institution where a pathology report on the referred slides is generated.  In most cases the original laboratory requests that the slides be returned along with a copy of the new pathology report.  Problems arise at this juncture.  The new institution may retain the slides or fail to return them in a timely fashion.

Case law is fairly clear that the original slides and blocks are the work product for the originating laboratory, a fact that can be construed to mean ownership.  Therefore, the original laboratory has the legal right to request/demand return of their slides.  After all, they are required to keep these slides for purposes of accreditation and by statute.

So why would the final institution want to keep the slides?  There are several reasons – teaching, clinical research, saving the expense of the return and medicolegal issues.  The first two are relatively straightforward, especially in institutions that have a pathology residency program and an active clinically-oriented research program.  The expense of returning the slides, even by standard mail, is not trivial when multiplied by hundreds or thousands of times over the course of a year.

See full blog post @ Medscape 

New! FREE White Paper on Vaginitis Diagnosis: An Opportunity to Improve Patient Care

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Published statistics indicate that, each year, there are more than 10 million visits to ob-gyn and primary care physicians because of vaginitis. Since this health condition could be caused by a number of different infectious agents, physicians—and their clinical laboratories—must often perform multiple diagnostic tests.

 

That takes time, often doesn’t deliver a definitive diagnosis if the right infectious agent assays were not requested, and can frustrate both physician and patient. Clinical laboratory testing plays a crucial diagnostic role in healthcare in the United States. That’s good news for pathologists, laboratory directors, and laboratory scientists. With the advancements in technology, laboratory test results are helping physicians make earlier and more accurate diagnoses. Numerous new diagnostic tests are available in the clinical marketplace.

 

However, few of these assays possess the right combination of increased sensitivity, reasonable test cost, and the ability to significantly contribute to clinical care. The Dark Report is happy to offer our readers a chance to download our recently published FREE White Paper “Vaginitis Diagnosis: An Opportunity to Improve Patient Care” at absolutely no charge. This free download will provide readers with a detailed overview of current legal challenges that your lab may encounter in the near future.

 

Pathologists and clinical laboratory scientists recognize how important it is that new diagnostic assays fit the following criteria:

• Improved sensitivity and specificity over existing lab testing technologies.
• Faster turnaround time to a complete result.
• Specimen collection methods that are easier to use, safer to transport, and/or have a longer shelf life.
• Easier for the laboratory to perform, preferably with automation available.

Whenever all of these criteria are met, it presents clinical laboratories with the opportunity to hit a “diagnostic home run” with referring physicians. An example would the diagnosis of vaginitis. Currently there are several tests available for the detection of the causative agents for vaginitis, but few tests are available for the simultaneous detection of these causative agents from one collected specimen. Such a test would be of significant benefit to the clinician and patient, as multiple specimens would not have to be collected.

Every pathologist and laboratory scientist should evaluate this assay and review the clinical guidelines that call for its use in diagnostic and treatment decisions for vaginitis. This white paper is a good starting point. It has been organized to provide an accurate and broad overview of this subject.

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Here is just some of what you will take away...

1. The role of microscopy and culture.
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3. DNA Probe Technology
4. For more about Implementing DNA Probe Technology in the Lab, please CLICK HERE

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Table of Contents

Preface - Page 3  

Chapter 1. Abstract — Page 5  

Chapter 2. Background— Page 6  

Chapter 3. The Three Common Underlying Causes of Vaginitis — Page 8  

Chapter 4. Diagnosis of Vaginitis: Current Practice — Page 10  

Chapter 5. DNA Probe Technology Opens the Door to Improved Vaginitis Care — Page 12  

Chapter 6. Implications for Patient Care — Page 14  

Chapter 7. Implications for the Laboratory — Page 15  

Chapter 8. Assessing the Opportunity — Page 17

Chapter 9. Implementing DNA Probe Technology in the Lab — Page 21

Chapter 10. Marketing New Vaginitis Testing Capabilities — Page 22  

Chapter 11. The BD Affirm VPIII Microbial Identification System at Work — Page 23

Chapter 12. Conclusion — Page 26

Appendices A-1 About Andrea J. Linscott, PhD — Page 30

A-2 About BD — Page 31

A-3 About DARK DAILY — Page 32

A-4 About The Dark Intelligence Group, Inc., and The Dark Report— Page 33

A-5 About Executive War College on Laboratory and Pathology Management — Page 34

A-6 About Lena Chow — Page 36 Terms of Use — Page 40

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Image Analysis Strategies for Challenging Biomedical Images using Definiens Developer XD™

Join us for a webinar: Image Analysis Strategies for Challenging Biomedical Images using Definiens Developer XD™

Register Here:

Learn image analysis strategies from the pros at Definiens using Definiens Developer XD on the following examples:

• The Rolling Ball Method for Correcting Heterogeneous Backgrounds in Fluorescently Stained Golgi Cells
• Three Dimensional Analysis of Dendritic Spines
• Classifying Tumor vs. Non-Tumor and Tumor Morphology in Non-Small Cell Lung Cancer

Speakers:

Peter Duncan – Director, Marketing and Business Development
Dr. Thomas Mrowiec – Consultant, Professional Services
Dr. Florian Leiss – Trainer and Marketing Specialist

Title: Image Analysis Strategies for Challenging Biomedical Images using Definiens Developer XD™

Date: Wednesday, December 22, 2010

Time: 11:00 AM – 12:00 PM EST / 4:00 PM – 5:00 PM GMT

After registering you will receive a confirmation email containing information about joining the Webinar.

System Requirements:

PC-based attendees

Required: Windows® 7, Vista, XP or 2003 Server

Macintosh®-based attendees

Required: Mac OS® X 10.4.11 (Tiger®) or newer

Space is limited.

Reserve your Webinar seat now at:

https://www2.gotomeeting.com/register/227449746

The Transformation of Pathology

The College of American Pathologists has been active with several ideas concerning the transformation of our specialty with rapid growth of new technologies, disruptive technologies and changes in the healthcare system that will impact medicine.  One of the initiatives being discussed from CAP is increased direct dialogue by pathologists with patients.  True one-on-one meetings with patient's about their pathology and their particular disease and its biology to better inform and educate patients as an integral part of the care team beyond the pathology report.  

Dr. Jennifer Hunt at the Massachusetts General Hospital is leading the effort.  The below video is from the College's YouTube channel that has a few similar videos with more to come.  

If you are a pathologist, are you going to transform?  How do you feel about speaking directly with patients and their families?  

Clarient Launches Insight® Dx Mammostrat® Breast Cancer Recurrence

Test Novel Test Designed to Help Classify Risk of Recurrence of Breast Cancer, and Aid in Management of Therapy

ALISO VIEJO, Calif., Dec. 9, 2010 /PRNewswire/ -- Clarient, Inc. (Nasdaq: CLRT), a premier technology and services resource for pathologists, oncologists and the pharmaceutical industry, today announced the commercial launch of Mammostrat, a patented, novel test designed to help quantify the likelihood of recurrence of breast cancer following surgery and initial treatment. The Mammostrat test employs an optimal set of five biomarkers that are able to be identified visually on a patient's tumor specimen by using a well-established technology called immunohistochemistry. Those biomarkers are then analyzed using a mathematical algorithm to generate an assessment of risk for cancer recurrence. Mammostrat is well-validated, having been clinically studied on more than 3,000 women, as reported in multiple peer-reviewed journals, including Breast Cancer Research (Volume 12, 2010), Clinical Cancer Research (Volume 14, October 2006), and the Journal of Clinical Oncology (Volume 24, July 2008).

Data fromMammostrat trials have also been presented at national conferences, including the American Society of Clinical Oncology (ASCO) and the San Antonio Breast Cancer Symposium. By using the Mammostrat test pathologists, oncologists and patients can gain greater understanding of the aggressiveness of a patient's disease and guide clinical management. Mammostrat provides additional clinical information that cannot be obtained from routinely used prognostic factors. The Mammostrat test can be performed on small biopsy samples, and results are typically delivered in as little as 48-72 hours, thereby allowing more rapid treatment decisions. "Mammostrat can be an important tool for clinicians assessing the aggressiveness of their patient's breast cancer," said Clarient Vice Chairman and Chief Executive Officer Ron Andrews. "Mammostrat results can provide clinicians important information to help select the appropriate therapeutic management for each individual patient. For patients, Mammostrat offers the confidence that the decisions being made to manage their breast cancer are based on the clinical characteristics of their specific disease using the most current validated technology available." More than 210,000 women in the U.S. develop breast cancer each year.

Mammostrat test development was targeted to breast tumors which express estrogen receptor, the most commonly identified subtype of breast cancer representing about 75 percent of the women diagnosed each year. The standard of care for most of these patients includes surgery to remove the tumor, followed by anti-hormonal therapy (e.g. tamoxifen or aromatase inhibitors). Andrews continued, "Mammostrat fits well within the combined Clarient goals of bringing value to both the patient and to the healthcare system. The test provides validated information more rapidly than other tests currently available, which may allow for treatment to begin earlier in the course of the disease."

Clarient is currently in coverage determination discussions with both government and private insurance carriers. Patents covering the use of the Mammostrat test were granted in the U.S. and Europe in the summer of 2010. For more information on the Mammostrat test, please visit www.clarientinc.com/mammostrat.aspx.

 

About Clarient

Clarient combines innovative diagnostic technologies with world class pathology expertise to assess and characterize cancer. Clarient's mission is to become the leader in cancer diagnostics by dedicating itself to collaborative relationships with the healthcare community to translate cancer discovery and research into better patient care. Clarient's principal customers include pathologists, oncologists, hospitals, and biopharmaceutical companies. The rise of individualized medicine as the new direction in oncology has created the need for a centralized resource providing leading diagnostic technologies, such as flow cytometry and molecular testing. Clarient is that resource, having created a state-of-the-art commercial cancer laboratory providing the most advanced oncology testing and diagnostic services.