Archive for Digital Pathology

Improving Efficiency in Stereology

In biomedical research, it is essential to gain accurate knowledge about cells, tissues or organs. To this point, a standard procedure is to use histological sections and microscopy. However, when analyzing 2D sections it is extremely important to realize that structures image seen in the microscope or on a whole slide image does not directly represent what was present in the living tissue.

Stereology provides efficient practical techniques for obtaining 3D quantities from 2D sections – such as cell number and volume. The methods are statistically proven and the study is consequently unbiased by design – i.e. there are no assumptions, models or correction factors involved.

The use of stereology is often avoided because of how time consuming it can be. However, a recent publication highlights how productivity can be improved greatly using digital pathology and Visiopharm’s stereology solutions- the Autodisector and Proportionator.  Compared to traditional stereology methods, the Proportionator was 50% to 90% more time efficient than systematic, uniform random sampling. The time efficiency of the Autodisector on virtual slides was 60% to 100% better than the disector on tissue slides. The publication was released in the Journal of Microscopy.  Access is available through Wiley Online Library, download it here.

Abstract

Cell counting in stereology is time-consuming. The proportionator is a new stereological sampling method combining automatic image analysis and non-uniform sampling. The autodisector on virtual slides combines automatic generation of disector pairs with the use of digital images. The aim of the study was to investigate the time efficiency of the proportionator and the autodisector on virtual slides compared with traditional methods in a practical application, namely the estimation of osteoclast numbers in paws from mice with experimental arthritis and control mice. Tissue slides were scanned in a digital slide scanner and the autodisector was applied on the obtained virtual tissue slides. Every slide was partitioned into fields of view, and cells were counted in all of them. Based on the original exhaustive data set comprising 100% of fields of view and covering the total section area, a proportionator sampling and a systematic, uniform random sampling were simulated. We found that the proportionator was 50% to 90% more time efficient than systematic, uniform random sampling. The time efficiency of the autodisector on virtual slides was 60% to 100% better than the disector on tissue slides. We conclude that both the proportionator and the autodisector on virtual slides may improve efficiency of cell counting in stereology.

To learn more about Visiopharm stereology solutions and schedule a demonstration click here.

Insight into Islet Pathology in Type 2 Diabetes

New Webinar

Quantitative Analysis of Pancreas Immunostaining – Insight into Islet Pathology in Type 2 Diabetes

Speaker: Rebecca Hull, PhD, University of Washington

Thursday, April 18, 2013

9 AM PST/ 12 PM EST / 6 PM CET

Register at:  https://www1.gotomeeting.com/register/329213176

Abstract

Type 2 diabetes is characterized by loss of ?-cell mass and function. Islet amyloid deposition occurs in the vast majority subjects with type 2 diabetes. The extent of islet amyloid deposition is associated with decreased islet ?-cell area and increased ?-cell apoptosis, suggesting that islet amyloid contributes to ?-cell loss. To better understand the detrimental effects of amyloid deposition in islets, we developed a transgenic mouse model that expresses the human, amyloidogenic form of islet amyloid polypeptide (hIAPP) in its ? cells. In vivo studies demonstrated that increased dietary fat intake increases islet amyloid deposition in these mice, resulting in ?-cell loss. Anti-diabetic therapies, including rosiglitazone and metformin are highly effective in inhibiting islet amyloid deposition and its detrimental effects on the ? cell. Islet transplantation is another setting in which amyloid deposition likely has detrimental effects. Indeed, transplantation of hIAPP transgenic islets into diabetic mice results in amyloid deposition, leading to increased ?-cell apoptosis, with no corresponding increase in ?-cell replication and ultimately leading to ?-cell loss. Amyloid deposition can also be induced in isolated islets from these mice, with culture at elevated glucose levels. This in vitro model has allowed us to demonstrate roles for oxidative stress and JNK signaling, but not ER stress, in mediating amyloid-induced ?-cell apoptosis. Recently, we have been working to identify strategies to inhibit islet amyloid deposition, with the goal of developing novel therapeutic strategies to limit amyloid-induced ?-cell loss in diabetes.

About our Speaker

Rebecca Hull-newDr. Rebecca L. Hull received her PhD in Biochemistry from the University of Nottingham, and undertook her postdoctoral training at the University of Washington prior to joining the faculty there.  Her research focuses on the mechanisms of pancreatic islet b-cell failure in type 2 diabetes. Dr. Hull is currently a Research Associate Professor in the Division of Metabolism, Endocrinology and Nutrition at the Veterans Affairs Puget Sound Health Care System and University of Washington School of Medicine.  She is Associate Director of the University of Washington Diabetes Research Center’s Cellular and Molecular Imaging Core and is an editorial board member for the Journal of Histochemistry and Cytochemistry. She has extensive expertise in specimen collection and immunostaining in pancreas, cultured islets and islet transplant grafts from humans and rodents.  She has expertise in morphometric analysis and has used these data to obtain sensitive measures of beta-cell mass, replication and apoptosis, and amyloid deposition for many of her studies.

 

Quantitative Digital Pathology in Action at USCAP 2013

Image analysis is of course not a new concept. Pathologists analyze glass slides (and maybe whole slide images) every day with their eyes for routine diagnosis. Pathologists who have research responsibilities probably use or have used image analysis software at some point to extract information from digital images. Yet the methods used to analyze are not always optimal; especially when review of hundreds or thousands of slides are required, or when what is trying to be found with the human eye is difficult.

Today everyone is being challenged to do more with less, faster, while not sacrificing quality. This is one of the many reasons that the popularity and use of digital pathology continues to grow. However so much of the focus of digital pathology is on slide scanning when it should be on obtaining meaningful information from whole slide images with quantitative digital pathology.

When I was consulting, I saw that approximately 50% of digital pathology users purchased an analysis software package or module for use with WSI; and if analysis software was purchased an even lower percent actually used it.

But why even buy a whole slide scanner if you are not going to do something useful with the meaningful data that is generated.

There are a few areas in digital pathology where quantitative information may not be needed, however the majority of applications would greatly benefit from integrating quantitative results with digital pathology. So why do so many still not use quantitative digital pathology? Here are some of the most common reasons:

  • It is too expensive! I have no money left after the scanner.
  • My application is very challenging. What if it does not work?
  • It’s too complicated and I do not have a MATLAB programming background.

I understand why adopters have these concerns; many software solutions on the market are very expensive, carry a lot of risk, and require expert knowledge to run. However at Visiopharm we have done a lot to address each of these barriers with our flexible platform options of cloud (SaaS) and/or deployed, and our Application Protocol Packages (APPs). APPs provide all current and potential customers with the ability to try our software on their application before purchase. Also APPs are load-and-go protocols so there is minimal learning required and no need for programming experience. You just open the APP, load your slides, and press go!

With regard to cost, we recognize that sometimes budgets will get cut or allocated toward other purchases. That is why we also have pay-as-you-go options for our both our cloud and deployed software solutions. But remember my quote above– why buy the scanner if you have no plans to do anything with all the meaningful data generated.

Quantitative digital pathology will provide you the results you need to justify the value of digital pathology and the slide scanner. So don’t cut the software out just remember to plan and budget for it.

Come see Visiopharm’s Quantitative Digital Pathology software in action at USCAP 2013. Our solutions will be on display and available for demonstrations at the booths of our authorized distributors. Come visit with us at:

You can also e-mail us to schedule a one-on-one meeting with a Visiopharm team member. We would welcome the opportunity to meet you and answer any of your questions!

 

DPA Member Spotlight Features Amanda Lowe

Thank you to the Digital Pathology Association for featuring me in their Member Spotlight series.  Below is our interview.

DPA Staff: What path has your career taken that has led you to digital pathology?

Lowe: My first job in the digital pathology industry was at Bacus Laboratories in 2004. As I interviewed for the sales manager position, my interviewer explained the fundamentals of scanning a glass slide, sharing the image via the internet, and how a computer could function as the microscope. I thought to myself, this technology just makes sense! The DPA shares my passion for a future with digital pathology. My involvement with the DPA provides a platform to give back to our community, and educate the research and healthcare markets on the numerous benefits of digital pathology.

DPA Staff: How has digital pathology directly affected your business?

Lowe: I just accepted a new position as the Director of Marketing, in the Americas, with Visiopharm. Visiopharm has been in the stereology and image analysis business for over 11 years; our business has grown significantly with the evolution of digital pathology. Image analysis software can be time consuming and manual, but Visiopharm’s software partnered with whole slide images (WSI) creates a whole new standard of quality, automation, and analytics. Valuable data is extracted from the scanned glass slides; this data provides essential information to support diagnostics and research in a timely fashion.

DPA Staff: How do you foresee learning more about digital pathology impacting the healthcare and diagnostics industries?

Lowe: Digital pathology will become the new gold standard; it will promote better patient care, streamline laboratory workflow, improve communication between pathologists and other physicians, and provide tools for the research and biopharma community to uncover new discoveries in medicine. Pathology cannot continue to function the way it has for the last 150 years, we need this digital revolution.

DPA Staff: In your opinion, what benefits does the DPA provide to its members?

Lowe: The DPA is an educational resource for the healthcare and research industries to learn more about digital pathology. It also provides a community of likeminded individuals who believe in and are passionate about digital pathology. The DPA and its members want to make a difference and support worldwide adoption of digital pathology.

Webinar on Progression Markers in Non-Muscle Invasive Bladder Cancer

appicon-10012On February 28, 2013 at 9 AM EST / 3 PM CET Visiopharm will host a webinar titled “Progression Markers in Non-Muscle Invasive Bladder Cancer” presented by Dr. Niels Fristrup from Aarhus University Hospital, Denmark.   This webinar coordinates with Visiopharm’s Cancer Research APPs for Bladder Cancer.  Our current six Bladder Cancer APPs include:

Register Now

 

Abstract

Transcripts from the four genes encoding cyclin D1, MCM7, TRIM29, and UBE2C have previously been included in gene expression signatures for outcome prediction in stage Ta/T1 urothelial carcinomas. Here, we investigated the prognostic value of the protein expressions in patients with stage Ta/T1 urothelial carcinomas. We used four different tissue microarrays with a total of 859 Ta/T1 urothelial carcinomas from Danish, Swedish, Spanish, and Taiwanese patient cohorts with long-term follow-up. Protein expression was measured by immunohistochemistry, and antibody specificity was validated by Western blotting.We found the expression of cyclin D1, MCM7, TRIM29, and UBE2C to be significantly associated with progression to muscle-invasive bladder cancer (log-rank test; p<0.001) in the Danish training cohort (n=283). Multivariate Cox regression analysis identified cyclin D1 (p=0.003), TRIM29 (p=0.001), and UBE2C (p<0.001) as independent prognostic markers. The prognostic value of the four proteins was validated in a joint validation cohort from Sweden, Spain, and Taiwan (n=576). We applied computer-assisted image analysis of the prognostic markers and produced results comparable to those obtained by manual scoring. Finally, a four-protein maximum-likelihood classifier was trained on the Danish training cohort; and applied to the validation cohort. The four protein markers may help optimize treatment of patients with Ta/T1 bladder cancer. Additional prospective studies are needed for further validation of their clinical relevance.

php27Gd9LAMAbout our Speaker

Niels Fristrup was educated as medical doctor from the University of Aarhus in 2010. His research started in 2008, primarily concerning prognostic protein markers in non-muscle invasive bladder cancer, now also focusing on predictive markers of Bacillus Calmette Guérin (BCG) treatment response. In his research Niels works to correlate advanced molecular analyses of cancer tissues from patients suffering from bladder cancer with extensive long-term follow-up of large patient cohorts. The goal is to create new, precise ways of identifying the aggressiveness of the cancers as early as possible, or the responsiveness towards BCG immunotherapy. This resarch could potentially lead to a more precise prognostication, again leading towards personalized medicine; the right treatment for each patient. Niels publication list encompasses 10 peer-reviewed articles in renowned journals as The American Journal of Pathology, Oncogene, and Cancer Research.

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