Newsletter A meeting with ... Research teams from the University Hospital of Quebec-University Laval & the Quebec University lnstitute ofCardiology and Pneumology. Here, digital pathology supports research activities in oncology for the development of new clinical applications.

The city of Quebec has two major university-based hea lthcare institutions associate d with the Laval University: th e University Hospital of Quebec-University Laval (CHU ("Centre Hospitalie r Universitaire" or University Hospital) of Quebec-UL) and th e Quebec University ln stitute of Cardiology an d Pneumology ("Institut Universitaire de Card iologie et de Pneumologie de Québec" or IUCPQ).

The University Hospital of Quebec-UL is one of the three leading University Hospita ls in Canada: it contribut es to numerous projects in the fields of hea lthcare, science and knowledge-sharing. Based in five hosp itals (the Hôtel-Dieu de Quebec, CHUL, Saint Francis of Assisi, Saint-Sacreme nt and the Hôpital d e l'En fan t-Jésus), the staff teams of the University Hospita l, representing over 15,000 employees, focus th e ir efforts on the delivery of healthcare and services for the benefit of patients. ln terms of hea lthcare, the University Hosp ital has 1,800 beds for the in-patient accommodation of 67,000 pati ents each year. lt is recognized as a centre of excellence for oncology in Easte rn Canada. The researc h centr e of the University Hospit al of Quebec-UL ("Centr e de Recherche du Centre Hosp italier Universitaire" or CRCHU ofQu ebec-U L) involves 2,500 researchers, students and research professionals condu cting research on a var iety of tapies, including nephrolo gy and endocr inolo gy, conditions of the immune system and infectious diseases, regenerative med icine, neuro scie nces, reprodu ction, maternity and in fant health , public health and the optimization of hea lthc are, and oncology. The IUCPQ is an ultra-specialized ho spital centre devoted ta prevention, treatment, teaching and research in the fields of card iovasc ular and respiratory d iseases, and conditi ons associated wi th obesity. The research centr e of the IUCPQ [CRIUCPQ] is a facility of wor ldw ide reno wn, where 400 researchers and researc h professionals wor k each day on th e understanding and exp lanatio n ofthese conditions, in the interests of improv ing their treatment.

A joint project

At a very ear ly stage, th e University Hospita l of Quebec-UL, enco ura ged by patho logist and researcher Dr Bernard Têtu, identified the potential benefits or digita l path ology in a number of areas: the esta blishm ent o r a remote frozen tissue examination nctwork on th e LAVAL integrated uni versity healt hcare ne twork, the eval uat ion of an in-house digital pathology solution for th e interpretation of biopsi es, and the development of digita l imagi ng for educatio nal purposes. ln 20 12, rcsearch teams at the CRCHU ofQucbec-UL and the CRIUCPQ cxpr essed th e need for an effect ive quantification so luti on for slides marked-up by irnmunohi stoche mical stai nin g and digitized on th e Hamamatsu digitizer. Further ta the initiat ive launched by Dr B. Têtu and Dr Y. Fradet, uro- oncol ogist and researcher, a numb er of teams met with a view ta secu rin g the necessa ry budget for the acquis ition of the CaloPix Resea rch solution. Accor din gly, the re searc h tea ms of Doctors B. Têtu, Y. Frad et , L. Lacombe and C. Diori a or th e CRCHU of Quebec-UL and of Dr P. Joub ert, pathologist and researcher at th e CRIUCPQ, we nt on ta pro cure th e Calop ix Researc h so lution. This solution was dep loyed in 2014 within an IT infrastructure which permits networked operations . As Dr A. Bergeron, associate professor, emph asizes: " A(ter a number o( evaluations, we opted for the CaloPix Research solution produced by TRIBVN Healthcare, which features an effective quantification performance, a network installation capabi/ity and a good cost/bcncfit ratio."

Everyday use

At present, regu lar users of CaloPix are therefo re concentrated in the hosp itals of Hôte l-Dieu de Quebec, Saint-Sacrement, the University Hospital of Quebcc-UL and th e IUCPQ. The regular use of CaloPix permit s the identification of tissues and regions of intere st, and the sub seq uent quantification of tumoral biomarkers present on slides. The so lution is capab le of processing large quant ities of slides, de livering bath efficiency and reproducibîlity. The re lîability of quantitative results is enha n ced, and res ea rchers benefit from time-saving . According to Michèle Orain,

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Research Assistant in Oncopathology: " CaloPix is a pathological image analysis tool with a unique potential for research teams working in a clinical environment, allowing them to independently explore sol ution s for the analysis of speci m ens which combine high levels of accessibility with the guaranteed delivery of results which are more than satisfactory, in term s of quality. Add to this the consistent speed and reliability of TRJBVN Healthcare, in terms of responsiveness , attentiveness and results, in response to our requirements for the refinementofalgorithms. "

The objective of th ese research operations is to add ress specific clini cal issues, and to plot th e route from observations in the laboratory to clinicat app licatio ns whic h might ultirnate ly be impleme nted in the hospital env ironm en t for the impro vement of patient care. Dr. Joubert, anatomopathologist , shared hi s views as follows: " Issues associated with the evaluation o( biomarkers in thoracic oncology are key, particularly since tlie emergence of increasingly targeted treatments, and the development of immunotherapy and associated companion tests, often based upon immunohistochemistry CaloPix permits the reliable reading of large series of slides and the production of robust quantitative data in s upport of our work. "

A flexible tool

At pre sent, various works are in preparation or have bee n published w hich use CaloPix for th e quantification of histo logical and associated morphological data, specifica lly: • Th e quantific a tion of reactive stroma! cells having an impact upon

prognostics for cancers o f the breast, ovary and prostate. • Th e analysis and quantification of diagno stic and progn ostic

markers in breast ca ncer. • Evalu ation of var iou s biomarkers whic h are capa ble of pr edicti ng

the de ve lopment of cancers or thei r response to treatment in uro­o ncolo gy ( cancers of the prostate, bladdcr and kidncy

• Characteristic analysis of tumoral a nt igens and the development of new imrnunotherapeutic approache s to urologic al cancers.

• Ident ificat ion a nd quantification of biomarkers for the potential prediction of th e development or response to treatment of certa in pu lmonary neoplasms wi th limited chara cte rizat io n

• Eva luation of immuno therapy mark ers associated wit h pulmonary ade no carc inom as, neuroendocrine pulmonary tumours and thymomas.

Potential for developrnent

As dig ital so lu t ions are increasi ngly integrated in clini ca l pathology and rc sca rch work, CaloPix offcrs a bcncficial so lution for th e robus t and object ive quant ification of biomarkers in the field of onco logy. Moreove1: the ve rsat ility of CaloPix in the eva luation of tissues, and of hi stochemical and immunohistochemical stai ning, pro vid es a glim pse of a hu ge potential to meet the needs of researchers in a number of fields. Research cen t res in th e Region of Quebec have already had an involvement with this tool for a number of yea rs, and are working in collaborat ion with the TRIBVN Healthcare team in the interests of th e ongoing improv ement of the potential capabilities and th e perform a nce of the CaloPix so lu t ion.

• Dr. Alain BERGERON Associate professor , CRCHU

• Mich èle ORAIN Research Assistant in Oncopathology , CRCHU & CRIUCPQ

• Dr. Philippe JOUBERT Anatomopathologist, IUCPQ

• Progno stic significanc e ofTJMP -2, MMP-2, and MMP-9 on high-gr ade serous ovarian carcinoma using digital image analysis . Hu man Pat hology, 2015. P. Desmeules, D. Trud el, S. Turcotte, J.Sirois, M.Plante, J. Grégoire, M-C. Renaud, M. Orain, B. Têtu, 1. Bairati.

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• Histo logical and Urodynamic Effects of Auto logous Stromal Vascular Fraction Extracted from Fat Tissue with Minimal Ex Vivo Manipulation in a Porcine Mode/ oflntrinsic Sphincter Deficiency . The Journa l ofUro logy, 2016. R. Boissierc, J. Magalona, F.Sabatiera, J. Verane, L. Giraudoe, S. Giusianoc, S. Garciac, F. Dignat-Georgeh, L.Arnaudh, G. Magalonc, ... , E. Lecheva llierc, S.

• Calreticulin Expression in Human Non- Sma ll Cell Lung Cancers Correlates with Increa se d Accumulation of Antitumor Immune Cells and Favorable Prognosis. Cancer Research, 2016. J. Fucikova, E. Becht. K. lribarren, j. Goc, R. Remark, O. Oamotte, M. Alifano, P. Devi, J. Biton, C. Germain, A. Lupo, WH. Fridman, ... , M-C. Dieu-Nosjean.

News Establishment of a centre of excellence for digital pathology

TRIBVN Healthcare and th e University Hospital of Montrea l are invo lved in a strategic partnersh ip for the creation of a centre of exce llence for digital pathology. The objective is the deve lopment of digital pathology within the pathology depa rtment. The deployment of digital patho logy in everyday practice is considered as essential to the improvement of diagnostic pa ti ent care. The pa rtnership th us estab lished will involve the procurement of Hamamatsu high-capac ity slide sca nn ers and th e impleme ntation of the CaloPix imaging solution produced by TRIBVN Hea lthcare, connected to the LMS system of th e laboratory. This so lut ion will prov ide pract itioners with rapid and easy access to ail their images, from a ny work station within the establish ment. Practitione rs will then be ab le ta view, a nnot:ate, inter pret and share their slides wit h complete secur ity, in a network ing a rrange ment. The effectiveness an d speed of the workflow is thus enhanced, and communica ti ons are improved. Finally, the partnership also incorporates a researc h dime nsion. Th e image analysis algorithms developed by TRIBVN Healthca re will be made availab le to pa th ologists and researchers at th e University Hos pita l of Montrea l. A number of projects for quan tifica tion and clinical validation are pla nned under the terms of this par tnership, in the interests of their general application in th e diagnostic cha in.

Digital pathology supports the reorganization of laboratories

TRIBVN Healthcare and the Civil Hospices of Lyon have been collabora ting for over 15 years on the develop ment of digital imag ing in the patho logy and bio logy depart ments of the Univers ity Hospita l. ln conjuncti on with the reorganization of labora tories and th e constit ution of a n innovative ce nt re for bio -patho logy on two sepa rate geog raphical sites, the Civil Hos pices of Lyon have pursued the fu rther developmen t of digital imagi ng. Spec ifically, the objective is th e further opti m ization of the laboratory work flow, in order to improve th e manageme nt of images and thus th e productivity of services. In order to enhance comm un ications be tween sites, TRIBVN Healt hca re has therefo re imple mented a n image management system using a centralized data base which is connected to the laboratory ma nagement system. ln ad ditio n ta macroscopy, the solution now incorporates tools for remote frozen tiss u e exami nations and high-capac ity scanni ng. The Civil Hospices of Lyon now enjoy access to an enhanced a nd ha rmo nized informa tion system for an urban context, which is conduc ive to the opti mi:zation of the working capac ities of laborator ies.

Calendar We attended the followin

• 09 & 10 junc 2016 AF H Congress - Pa ri s

• 13 oct. 2016 Belgian Week of Pathology - Gand

Come a nd m ee t us :

• 07 to 10 nov. 2016 Carrefour Pathologie - Pa ri s

• 01 & 02 dcc. 2016 Digital Pathology Congress - London

• Product focus

TeleSlide 4.0: A new ergonomies  Apre-premier presentation of the latest version of TeleSlide MultiMedia will take place at the "Carrefour Pathologie 2016" pathology conference. Version 4.0 of the software has been ent irely redesigned to provide users with state-of-the-art ergonomie features which are appropriate to their practices.

The design of visual and graphie elements has been reviewed in the interests of enhancing the dynamic presentation of the platform. Graphies, illustrat ions and colours are now more harmonious and aesthetically pleasing, thus enhancing the user-friendliness of TeleSlide Mult iMedia. The structure of pages has been simplified in the interests of easier and more intuitive navigation . The user is easily guided through the platform, and can now enjoy faster access ta the desired content. Moreover; in order to make navigation clearer still, the various functionalities availab le are now presented to users in accordance with their profile and their access entitlements to the various workshops. ln this way, the user can enjoy direct access ta the relevant content.

The major changes : • Optimization of the navigation and easier access to information • Reduction and simp lification of tabs and buttons • Harmonization of the terms used within the application • Customizing of the questionnaires layout

ln addition ta its ent irely new des ign, TeleSlide MultiMed ia 4.0 also incorporates functional improvements, including the automatic logging of data entries dur ing the comp letion of the vot ing form, the simplification of navigation from one case to another, the creation of links to a specific zone of the slide, or the direct integration of the viewer in the TeleSlide webpage .

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lntegra tion of the e-CaloPix viewer in the TeleSlide MultiMedia 4.0 use r inter face

TeleSlide MultiMedia 4.0 features significant advances. This new version is substantia lly distinguished from its predecessors by its new ergonomie features. ln addition to providing a new visual identity, whilst preserving the existing functionalities upon which its reputation is based, the software incorporates new fonctions, still with the aim of fulfilling the expectat ions of users. Our teams have worked in close collaborat ion with practit ioners, in order to provide a software which is tailored to the ir needs, and which is consistent with their everyday practices and requirements. TeleSlide MultiMed ia 4.0 has been designed with you in mind, and will secure the future development of digital pathology. By incorporat ing biopatho logical digita l imaging from the training stage onwards, TeleSlide MultiMedia encourages practit ioners to deve lop the practices of the future.

CaloPix 3.1.2: A diagnostic claim  Last [uly, TRIBVN Healt hcare announced the latest version of its dedicated CaloPix software for the managemen t and ana lysis of images, with a daim for diagnostic capability. CaloPix 3.1.2 is a vers ion designed for everyday use, includ ing in vitro diagnostic operat ions: faster; more ergonomie and validated for clinical use, CaloPix is now more than ever an essential tool for pathologists us ing digital microscopy. The software, which carries the CE ma rk and has been regis tered with the Health Canada agency, has bee n validated at the Gustave Roussy institute for the establishment of on-screen diagnosis in routine pathology. This allows daims made for the product to be extended to incorporate diagnostic app lication, and prov ides users with the assurance of a reliable and secure solution for their patients. This validation phase marks a major step in the transition of laboratories to the digital patho logy of the future .

For intensive everyday use, CaloPix version 3.1.2 features significant improvements, including:

• The rev ision of the display in the interest:s ofimproved fluidity. • The improvement of the navigation function in working lists, such as image folders, in the interests ofimproved product ivity. • The deve lopment of the "slide platform" mode for rapid and intelligent pre-load ing, thereby permitting the instantaneous viewing of the information sought.

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• The improvement of networking in data bases comprising tho usands of examinations and hundreds and tho usands of images.

CaloP ix vers ion 3.1.2 has been ent irely des igned and developed in 64 -bit mode, in order to permit the para llel execution of tasks and the effective allocat ion of memory on wo rk stations. Process execution times, and specifically image ana lysis times, have been halved: the quantification, segmentation and description of tissues and cells on ROAs or on whole slides have been signîficantly accelerated. Automatic learning tools are increasing in effectiveness, and are progress ively becomi ng indispe nsab le in the quantitat ive interpretat ion of t issues. The dedicated lmmuno suite for the quantification of biomarkers has been ent irely redesigned on the basis of these new concepts .

Finally, numerous functionalities have been expanded and addcd: notificat ion and management of errors, management of new formats, adaptation of display conditions for the var ious formats, display of images with associated captions, management ofSnomed CT and TNM coding systems, improvement of the e-Calopix full web viewer, etc.

Already deploycd on a numbe r of sites, CaloPix version 3.1.2 can provide the assura nce of innovation and success at your la bo ra tory.

Discover Immuno Object by Learning (IOBL), for even greater accuracy in the quantification of your immunohistochemical slides

Quantification of tumoral cells usi ng lmmu no Object by Learning

Imm uno Object by Learning perm its the identification and counting of marked-up cells on your irnmunoh istochemica l s lides in an accurate and effective manner. For nuclear, membrana l or cytoplasmic mark-up,the

TRIBVN Healthcare 39 rue Louveau - 92320 Chatillon - FRANCE

+33.1.55.58.05.20 www.tribvn- hc.com · www.teleslide.fr

algorithm identifies and counts positive and negative cells, and calculates a score.

This is a flexible and robust image analysis macro, based upon a lea rning algorithm.

lmmuno Object by Learning uses the CaloPix RFT classifier. This too l allows the algor ithm to use a learning base of cells, and to extract appropriate characteristics from this base for the effective segmentation of cells. A substantial learning base can be employed, tak ing account of the d iversity of tissues, thus permitting the algorithm to operate robustly and effectively over the full range of tissues and customary mark-ups in the Jaboratory. The Immuno Object by Learning macro features a simple and comprehensive interface, which permits the rapid defin ition of the correct learning mode ! and its serial application thereafter. It also incorporates advanced fonctions for colorimetric adjustment, intelligent sampling, quality contrai, etc ..

Using this macro, you can finally achieve the high-speed quantification of your Immuno slides.