Tag Archive for Publications

Improving Efficiency in Stereology

April 15, 2013 Digital Pathology, Publications, Stereology Comments Off

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.

January Publications with Visiopharm Software

February 20, 2013 Image Analysis, Publications, Stereology Comments Off

Below is a list of 16 new publications that use Visiopharm software released in January and so far in February. These publications have been added to our website collection of over 450 publications written since 2010.

Image Analysis

1. Draganovic, V., van der Goot, A., Boom, R. & Jonkers, J. Wheat gluten in extruded fish feed: effects on morphology and on physical and functional properties Aquaculture Nutrition, 2013 , pp. n/a-n/a  DOI URL
2. Marshall, S.A., McClain, J.A., Kelso, M.L., Hopkins, D.M., Pauly, J.R. & Nixon, K. Microglial activation is not equivalent to neuroinflammation in alcohol-induced neurodegeneration: The importance of microglia phenotype. Neurobiol Dis, Department of Pharmaceutical Sciences, The University of Kentucky, Lexington, KY 40536-0596, USA., 2013 DOI URL
3. Park, S.-H., Chen, W.-C., Hoffman, C., Marsh, L.M., West, J. & Grunig, G. Modification of hemodynamic and immune responses to exposure with a weak antigen by the expression of a hypomorphic BMPR2 gene. PLoS One, Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, United States of America., 2013 , Vol. 8 (1) , pp. e55180 DOI URL

Stereology

1. Babiker, H., Ding, M. & Overgaard, S. Demineralized bone matrix and human cancellous bone enhance fixation of porous-coated titanium implants in sheep. J Tissue Eng Regen Med, Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. 2013 DOI URL
2. Barckman, J., Baas, J., Sørensen, M., Bechtold, J.E. & Soballe, K. Periosteal augmentation of allograft bone and its effect on implant fixation – an experimental study on 12 dogs(). Open Orthop J, Orthopaedic Research Laboratory, Aarhus University Hospital, Denmark., 2013 , Vol. 7 , pp. 18-24 DOI URL

3. Cerezuela, R., Fumanal, M., Tapia-Paniagua, S.T., Meseguer, J., Moriñigo, M.Á. & Esteban, M.Á. Changes in intestinal morphology and microbiota caused by dietary administration of inulin and Bacillus subtilis in gilthead sea bream (Sparus aurata L.) specimens. Fish Shellfish Immunol, Fish Innate Immune System Group, Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain., 2013 DOI URL
4.Glerup, S., Lume, M., Olsen, D., Nyengaard, J.R., Vaegter, C.B., Gustafsen, C., Christensen, E.I., Kjolby, M., Hay-Schmidt, A., Bender, D., Madsen, P., Saarma, M., Nykjaer, A. & Petersen, C.M. SorLA Controls Neurotrophic Activity by Sorting of GDNF and Its Receptors GFR?1 and RET. Cell Rep, MIND Centre, Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark. 2013 , Vol. 3 (1) , pp. 186-199 DOI URL

5. Hayes, D.M., Deeny, M.A., Shaner, C.A. & Nixon, K. Determining the Threshold for Alcohol-Induced Brain Damage: New Evidence with Gliosis Markers. Alcohol Clin Exp Res, Department of Pharmaceutical Sciences , College of Pharmacy, University of Kentucky, Lexington, Kentucky., 2013 DOI URL

6. Kadkhodaei, B., Alvarsson, A., Schintu, N., Ramsköld, D., Volakakis, N., Joodmardi, E., Yoshitake, T., Kehr, J., Decressac, M., Björklund, A., Sandberg, R., Svenningsson, P. & Perlmann, T. Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons. Proc Natl Acad Sci U S A, Ludwig Institute for Cancer Research Ltd, Stockholm Branch, SE-17177 Stockholm, Sweden., 2013 , Vol. 110 (6) , pp. 2360-2365 DOI URL

7. Linares, E., Seixas, L.V., Dos Prazeres, J.N., Ladd, F.V.L., Ladd, A.A.B.L., Coppi, A.A. & Augusto, O. Tempol Moderately Extends Survival in a hSOD1(G93A) ALS Rat Model by Inhibiting Neuronal Cell Loss, Oxidative Damage and Levels of Non-Native hSOD1(G93A) Forms. PLoS One, Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil., 2013 , Vol. 8 (2) , pp. e55868 DOI URL

8. Mateus-Pinheiro, A., Pinto, L., Bessa, J.M., Morais, M., Alves, N.D., Monteiro, S., Patrício, P., Almeida, O.F.X. & Sousa, N. Sustained remission from depressive-like behavior depends on hippocampal neurogenesis. Transl Psychiatry, ICVS/3B’s-PT Government Associate Laboratory, Guimarães, Portugal., 2013 , Vol. 3 , pp. e210 DOI URL

9. Park, Y.M., Lee, W.T., Bokara, K.K., Seo, S.K., Park, S.H., Kim, J.H., Yenari, M.A., Park, K.A. & Lee, J.E. The Multifaceted Effects of Agmatine on Functional Recovery after Spinal Cord Injury through Modulations of BMP-2/4/7 Expressions in Neurons and Glial Cells. PLoS One, Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea ; BK 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea., 2013 , Vol. 8 (1) , pp. e53911 DOI URL

10. Podolin, P.L., Foley, J.P., Carpenter, D.C., Bolognese, B.J., Logan, G.A., Long, 3rd, E., Harrison, O.J. & Walsh, P.T. T cell depletion protects against alveolar destruction due to chronic cigarette smoke exposure in mice. Am J Physiol Lung Cell Mol Physiol, 1GlaxoSmithKline., 2013 DOI URL

11. Shynlova, O., Nedd-Roderique, T., Li, Y., Dorogin, A., Nguyen, T. & Lye, S.J.  Infiltration of myeloid cells into decidua is a critical early event in the labour cascade and post-partum uterine remodelling. J Cell Mol Med, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, M5G 1X5., 2013 DOI URL

12. Vonder Haar, C., Friend, D.M., Mudd, D.B. & Smith, J.S. Successive bilateral frontal controlled cortical impact injuries show behavioral savings. Behav Brain Res, Restorative Neuroscience Laboratory, Center for Integrated Research in Cognitive and Neural Sciences, Department of Psychology, Southern Illinois University, Carbondale, IL, USA., 2013 , Vol. 240 , pp. 153-159  DOI URL

13. Wittwer, T., Madershahian, N., Rahmanian, P., Choi, Y.-H., Neef, K., Frank, K., Müller-Ehmsen, J., Ochs, M., Mühlfeld, C. & Wahlers, T. Surfactant application in experimental lung transplantation. J Heart Lung Transplant, Department of Cardiothoracic Surgery, Heart Center., 2013 DOI URL

New Publications with Visiopharm Software

January 16, 2013 Digital Pathology, Image Analysis, Publications, Stereology Comments Off

Below is a list of new publications that use Visiopharm software released in November and December. These 16 publications have been added to our website collection of over 450 publications written since 2010.

Image Analysis

1.      Fristrup, N., Birkenkamp-Demtröder, K., Reinert, T., Sanchez-Carbayo, M., Segersten, U., Malmström, P.-U., Palou, J., Alvarez-Múgica, M., Pan, C.-C., Ulhøi, B.P., Borre, M., Orntoft, T.F. & Dyrskjøt, L. Multicenter Validation of Cyclin D1, MCM7, TRIM29, and UBE2C as Prognostic Protein Markers in Non-Muscle Invasive Bladder Cancer. Am J Pathol, 2012 DOI URL 

2.      Nielsen, P.S., Riber-Hansen, R., Jensen, T.O., Schmidt, H. & Steiniche, T. Proliferation indices of phosphohistone H3 and Ki67: strong prognostic markers in a consecutive cohort with stage I/II melanoma. Mod Pathol, 2012  DOI URL 

3.      Ramos, H.J., Lanteri, M.C., Blahnik, G., Negash, A., Suthar, M.S., Brassil, M.M., Sodhi, K., Treuting, P.M., Busch, M.P., Norris, P.J. & Gale, Jr., M. IL-1-beta Signaling Promotes CNS-Intrinsic Immune Control of West Nile Virus Infection PLoS Pathog., Public Library of Science, 2012 , Vol. 8 (11) , pp. e1003039  DOI URL 

Stereology

1.      Berger, T., Conley, A.J., Van Klompenberg, M., Roser, J.F. & Hovey, R.C. Increased testicular Sertoli cell population induced by an estrogen receptor antagonist. Mol Cell Endocrinol, 2012  DOI URL 

2.      Bradner, J.M., Suragh, T.A., Wilson, W.W., Lazo, C.R., Stout, K.A., Kim, H.M., Wang, M.Z., Walker, D.I., Pennell, K.D., Richardson, J.R., Miller, G.W. & Caudle, W.M. Exposure to the Polybrominated Diphenyl Ether Mixture DE-71 Damages the Nigrostriatal Dopamine System: Role of Dopamine Handling in Neurotoxicity.  Exp Neurol, 2012  DOI URL 

3.      Brüel, A., Vegger, J.B., Raffalt, A.C., Andersen, J.E.T. & Thomsen, J.S. PTH (1-34), but not strontium ranelate counteract loss of trabecular thickness and bone strength in disuse osteopenic rats. Bone, 2012 , Vol. 53 (1) , pp. 51-58 DOI URL 

4.      Bursa?, B.N., Djordjevic, A.D., Vasiljevi?, A.D., Milutinovi?, D.D.V., Veli?kovi?, N.A., Nestorovi?, N.M. & Mati?, G.M. Fructose consumption enhances glucocorticoid action in rat visceral adipose tissue. J Nutr Biochem, 2012 DOI URL 

5.      Darsalia, V., Ortsäter, H., Olverling, A., Darlöf, E., Wolbert, P., Nyström, T., Klein, T., Sjöholm, A. & Patrone, C. The DPP-4 Inhibitor Linagliptin Counteracts Stroke in the Normal and Diabetic Mouse Brain: A Comparison With Glimepiride. Diabetes, 2012 DOI URL 

6.      Keller, K.K., Thomsen, J.S., Stengaard-Pedersen, K., Dagnæs-Hansen, F., Nyengaard, J.R. & Hauge, E.-M. Bone Formation and Resorption Are Both Increased in Experimental Autoimmune Arthritis PLoS ONE, Public Library of Science, 2012 , Vol. 7 (12) , pp. e53034 DOI URL 

7.      Shynlova, O., Nedd-Roderique, T., Li, Y., Dorogin, A. & Lye, S.J. Myometrial immune cells contribute to term parturition, preterm labour and post-partum involution in mice.J Cell Mol Med, 2012 DOI URL 

8.      Vasilescu, D.M., Klinge, C., Knudsen, L., Yin, L., Wang, G., Weibel, E.R., Ochs, M. & Hoffman, E.A. Stereological Assessment of Mouse Lung Parenchyma via Non-destructive Multi-scale Micro CT Imaging validated by Light Microscopic Histology. J Appl Physiol, 2012 DOI URL 

9.      Verina, T., Schneider, J.S. & Guilarte, T.R. Manganese exposure induces ?-synuclein aggregation in the frontal cortex of non-human primates. Toxicol Lett, 2012  DOI URL 

10.   Dmytriyeva, O., Pankratova, S., Owczarek, S., Sonn, K., Soroka, V., Ridley, C.M., Marsolais, A., Lopez-Hoyos, M., Ambartsumian, N., Lukanidin, E., Bock, E., Berezin, V. & Kiryushko, D. The metastasis-promoting S100A4 protein confers neuroprotection in brain injury. Nat Commun, 2012 , Vol. 3 , pp. 1197 DOI URL 

11.   Gottliebsen, M., Rahbek, O., Poulsen, H.D. & Møller-Madsen, B. Similar growth plate morphology in stapling and tension band plating hemiepiphysiodesis: A porcine experimental histomorphometric study. J Orthop Res, 2012  DOI URL 

12.   Shin, J.Y., Ahn, Y.-H., Paik, M.-J., Park, H.J., Sohn, Y.H. & Lee, P.H. Elevated homocysteine by levodopa is detrimental to neurogenesis in parkinsonian model. PLoS One, 2012 , Vol. 7 (11) , pp. e50496 DOI URL 

13.   Wilson, D.W., Oslund, K.L., Lyons, B., Foreman, O., Burzenski, L., Svenson, K.L., Chase, T.H. & Shultz, L.D. Inflammatory Dilated Cardiomyopathy in Abcg5-deficient Mice. Toxicol Pathol, 2012 DOI URL 

The Digital Transformation of Pathology

September 16, 2010 Digital Pathology, Pathology, Publications, Transformation Comments Off

After my article last month, Advance offered me the opportunity to write a web article to compliment their vendor roundtable article.  Below is the article.

The Digital Transformation of Pathology

by Amanda Lowe

When does the future become a reality?

Imagine your digital future. You walk into your office, and on the desk is a computer; your microscope is covered and untouched; on the shelves are books and journals, and nothing is on the floor. Paper and glass do not cover every inch of your office. Gone are the numerous external hard drives filled with countless images. All that remains is you, your knowledge and a computer.

This computer is your diagnostic workstation, customized to you and providing you with resources to improve diagnostic outcomes, advise on treatments and monitor patient response to those treatments. Digital pathology will enable and frame our digital future. However, forging this vision has not been easy, and realization of the vision is a constant work in progress.

History
In the 1990s, the first robotic microscope was controlled over the Internet by Ronald S. Weinstein, MD,1 and the first slide scanner was invented to measure preinvasive cancer by James W. Bacus, MD, and his son Jim V. Bacus Jr.2 At about the same time, Dirk G. Soenksen, founder of Aperio, was imagining a world where microscopists looked at computer monitors rather than microscopes.3 These four inventors established the foundation for our digital future. As visionaries and advocates, they have brought digital pathology to life.

Resistant to Change

Ask around and the consensus is that digital pathology is our future. However, the timeline of when our future becomes a reality is widely debated. The digital pathology industry, pathology organizations and consumer crusaders have worked hard over the past 15 years to educate the market on the benefits of digital pathology, yet they are often met with a fierce resistance to change. The resistance is often driven by fear–not of change but of being changed.

No one pathologist, department or company can be forced to adopt and learn something new. Therefore, we must continue to educate and create an understanding of the tangible advantages, which instills a desire to change. Change is hard, but if we overestimate the importance of pathology’s capabilities today, we will underestimate the significance of what the field could become tomorrow.

Tangible Advantages

Digital pathology can reduce subjectivity, increase diagnostic confidence and ensure diagnoses are reproducible–all important advantages, especially when incidences of misdiagnosis have been publicized lately and the practice of pathology and laboratory medicine scrutinized. It is well-known that risk for human error in slide preparation and patient identification is greatly reduced when the histology process is bar coded.

A 2009 publication in the American Journal of Clinical Pathology about the Henry Ford Health System surgical pathology lab highlights a 62% reduction in the overall misidentification case rate.3 Add digital pathology to the picture, and you will enable scanning of glass slides, software (instead of technicians) correlating patient data and whole slide images, and electronic delivery of patient information and slides to the pathologist. Risk of error will continue to drop while powerful tools will support the pathologist throughout the diagnostic process.

Have a difficult case? No problem. The pathologist can simply assign the case or send an e-mail request to a specialized pathologist for a second opinion. This digital consultation process, often described as telepathology, is more secure and eliminates the risk of patient slides being lost or damaged, decreases the turnaround time to hours rather than days and reduces subjectivity while controlling costs. Still want more diagnostic support? Search the digital pathology slide database to review relevant clinical slides, quickly retrieve historical patient data, perform image analysis to obtain quantitative support, or easily set up a tumor board with physicians to illustrate the patient case and create a forum to discuss the next step or design a treatment plan.

All the tangible advantages described above can be done today and are being done, although the process is not perfect. Yet to achieve perfection you must find imperfections and then take time to transform those imperfections for the better.

Transformation

Government demands and consumer expectations are growing for transparency in medicine, improvements in patient safety and identification, electronic medical records and more personalized treatment plans. At the same time, the perception of laboratory medicine and pathology needs to improve, especially given its essential and significant role in patient care.

Digital pathology supports this healthcare evolution and enables the digital transformation of pathology and laboratory medicine. Our transformation is not easy. The process is not perfect, but the benefits are powerful and will outweigh the fears. Do not resist the transformation, embrace it.

Click here read the vendor roundtable print article and web article.

ADVANCE Article: Putting the Digital Pieces Together

August 13, 2010 Data Storage, Digital Pathology, Image Analysis, IT, Laboratory Automation, LIS, Pathology, Publications One comment

Below is an article I wrote for ADVANCE for Laboratory Professionals, Perspectives In Pathology.

Putting the Digital Pieces Together

By Amanda Lowe

Digital pathology is often described as the scanning of a glass slide into a whole slide image; yet, it is much more. It is so much more, in fact, that pathologists and laboratory professionals find themselves puzzled with how it will affect their future. As technology progresses, we must start to understand how to put the pieces of it together—from acquisition to integration to data management and interpretation.

Acquisition

Acquisition of a whole slide image from a glass slide is done on a slide scanner, which creates the image necessary for interpretation. Important elements of slide preparation and patient information can make the acquisition process simple or complex.

Slide preparation is a crucial and often overlooked element of digital pathology. Pathologists can handle slide artifacts such as folds and air bubbles under a microscope; slide scanners are not always as forgiving. Also, staining has to be perfected, not only for scanning but for accurate interpretation and use with image analysis software. Poor staining can result in tissue not being scanned, inaccurate image analysis data—and in the worst case—a wrong diagnosis.

Traditionally, when glass slides are prepared, they are manually matched with the patient paperwork (including patient history, requisition and gross review), then delivered to the pathologist. With digital pathology, the process looks different. You now have whole slide images that need to be reconciled to the digital patient paperwork, then delivered to the pathologist. The only way to do this is with a laboratory information system (LIS), electronic medical record (EMR) integration, and bar codes. Bar codes will reduce human error, save time on the constant need for verification and re-checks, and improve quality assurance by tracking all specimens throughout the histology process.

Integration

The LIS and often the EMR need to share information with the digital pathology software to create a pathology picture archiving and communication system (PACS) that consolidates all patient paperwork, gross images and whole slide images for interpretation. This is the most important but also the most difficult piece for labs to handle. The process can be costly and require collaboration of two or more vendors, which can be a frustrating and hard process to manage. However, it can be accomplished with a plan, a budget and someone to manage the project.

Data Management

Many hospitals do not have adequate IT resources or the expertise to handle their already stressed storage demands. Yet these whole slide images have to be stored somewhere. Unfortunately, most IT departments do not understand the fundamentals of digital pathology. Pathology leaders and their lab personnel must improve communication with their IT departments and take an active role in educating IT on the realistic needs of the department now and over the next five years. Hospitals have to prepare for the increase in lab data and pathology images that will soon be their future.

To estimate your whole slide image storage needs, divide the number of surgical slides your lab generates per year by 3,500 to get an estimate of terabytes needed annually; 3,500 is the average number of whole slide images per one terabyte.

Healthcare providers are required to save medical records for a specified time; for most, this is a minimum of seven years. Security is not optional, and HIPAA mandates backup and disaster recovery plans for patient records, including all medical images. The specialty of pathology will not be an exception to the rule.

Interpretation

One goal of digital pathology is to enhance the sign-out process for pathologists. Pathologists should be able to sit down at a computer monitor to sign out digital cases retrieved from a pathology PACS system. Easy access to archived cases for disease progression or comparison, rapid case sharing and consultations, data mining for decision support and image analysis will all help improve the diagnostic process.

Powered by the rapid and endless growing portfolio of image analysis algorithms, pathology will transition from a qualitative to a quantitative discipline. Digital pathology partnered with image analysis will create the infrastructure necessary so pathologists can confidently determine the severity of a disease and predict responses to a target therapy.

Digital pathology streamlines laboratory workflow, enhances the sign-out process, and can improve diagnostic outcomes and treatment responses for patients while at the same time forge a new foundation for the use of pathology data to drive translational research and higher standards of care.

 
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