Open Implementation of DICOM for Whole-Slide Microscopic Imaging Sebastien´ Jodogne1, Eric´ Lenaerts1, Lara Marquet1, Charlotte Erpicum2, Roland Greimers2, Pierre Gillet, Roland Hustinx1 and Philippe Delvenne2 1Department of Medical Physics, 2Department of Pathology, University Hospital of Liege,` Avenue de l’Hopital,ˆ 4000 Liege,` Belgium http://www.chuliege.be/ Keywords: Whole-slide imaging, telepathology, DICOM. Abstract: This paper introduces an open implementation of DICOM for whole-slide microscopic imaging, following Supplement 145 of the DICOM standard. The software is divided into two parts: (a) a command-line tool to convert an whole-slide image to the DICOM format, and (b) a zero-footprint Web interface to display such DICOM images. The software architecture leverages the DICOM server Orthanc. The entire framework is available as free and open-source software. The existence of this software supports the development of digital pathology and telepathology in clinical environments, featuring a smooth integration with existing EHR and PACS solutions. 1 INTRODUCTION tanowitz, 2016). • Education and research: Telepathology is highly Anatomopathology plays important medical roles promising in medical education and clinical re- by detecting preneoplastic lesions and by giving a di- search. Currently, digital imaging starts to replace agnosis, prognosis and evaluation of therapeutic re- traditional glass slides and high quality micro- sponse based on visual observations of cellular or scopes to discuss interesting cases during lessons, tissue samples. Telepathology is an application of symposia and conferences. Telepathology facili- telemedicine that allows the practice of the anato- tates interactions between multiple users and al- mopathology over a long distance with the use of im- lows the consistency and longevity of imaged ma- ages in an electronic format rather than viewing glass terials (Maree´ et al., 2016). slides (Ling and Krishnappa, 2012). Telepathology is • Pathology archiving: The storage of histolog- potentially useful for several applications: ical slides is mandatory for a long period of • Intraoperative consultation: Intraoperative con- time. Since the virtual slide perfectly reproduces sultations are emergencies in anatomopathology the glass slide without any loss of information, since the purpose of this examination is to guide telepathology could enable the storage of images immediate surgical management. For such con- in an entirely electronic way. As a consequence, sultations, the results should be given within 30 the currently-used, costly physical archives could minutes (Ribback et al., 2014). Telepathology can become legacy systems in the future (Webster and be used in this context for obtaining consultation Dunstan, 2014). by a pathologist present in a remote physical lo- Telepathology requires microscopic images to be cation. put quickly and easily online, from a slide scanner • Secondary consultation from experts: Secondary onto a secured Web server. To this end, at least three consultation refers to situations where a primary technical difficulties must be overcome. diagnosis has been performed on the primary ma- Firstly, any pathology laboratory requires high terial and further opinion is needed. Telepathol- electronic storage capacities to store their whole-slide ogy is beneficial by accelerating the process and images, as the size of the latter may range from hun- by reducing the risks of material loss or break dreds of megabytes to hundreds of gigabytes, de- compared to postal services (Farahani and Pan- pending on the scanning objective and the tissue sec- tion. A typical, uncompressed whole-slide image of rity reasons: A telepathology viewer should there- 80,000×60,000 pixels acquired in 24-bit color (RGB) fore be able to run entirely inside a standard Web weights over 10GB (DICOM Standards Committee, browser, as such a browser is almost always installed Working Group 26, Pathology, 2010). Image com- by default on any computer. A Web application also pression (JPEG or JPEG 2000) can divide this size by has the advantage of being compatible with mobile a factor 10, but this still roughly corresponds to the devices. The OpenSlide software can already serve size of 3D medical images (e.g. computed tomogra- whole-slide images generated by commonplace scan- phy or magnetic resonance imaging). Storing and in- ners onto the Web (Goode et al., 2013). Similarly, dexing such a large amount of data on the long run is the Cytomine software builds upon the OpenSlide ex- obviously not compatible with the manual administra- perience to provide an advanced collaborative anal- tion of a filesystem: It implies the use of automated, ysis framework for research and education in digital scalable, enterprise-ready database systems similar to pathology (Maree´ et al., 2016). Unfortunately, nei- the PACS of the hospital (Picture Archiving and Com- ther of those platforms currently supports the DICOM munication System). standard that is mandatory for clinical workflow. The second technical difficulty is the lack of inter- The previous discussion calls for the engineer- operability between the proprietary ecosystems that ing of a framework built upon the DICOM standard are implemented by the manufacturers of slide scan- that would support the development of workflow for ners. A single hospital might host several scanners digital pathology and telepathology in clinical envi- from different manufacturers, making it hard to con- ronments, featuring a smooth integration with exist- solidate all the whole-slide images inside a central- ing hospital information systems (EHR and PACS). ized tool because of a large variety of file formats. For The needed software would be able to convert whole- the same reason, it is hard to link the EHR (Electronic slide images encoded using proprietary formats, to Health Record) of a patient to her anatomopathology a standard DICOM file in accordance with the “VL images. This lack of interoperability in the clinical Whole Slide Microscopy Image Information Object workflow is also an obstacle to the exchange of im- Definition (IOD)”, as specified in the “PS3.3: Infor- ages between hospitals, as well as to the use of stan- mation Object Definitions” part of the DICOM stan- dalone post-processing tools that are necessary for dard (NEMA — National Electrical Manufacturers big-data analysis, medical research or education. Association, 2016). It would then be able to for- A possible solution to this problem consists in ward the converted images to a generic PACS sys- taking advantage of the DICOM standard for medi- tem, while serving them directly over Internet, using cal imaging (NEMA — National Electrical Manufac- a zero-footprint Web client. turers Association, 2016). Indeed, in 2010, the DI- This paper introduces such an innovative frame- COM Committee defined a standard way of exchang- work and makes it available as free and open-source ing whole-slide microscopic imaging that is vendor- software to support the development of digital pathol- independent and that is fully compatible with exist- ogy and telepathology in hospitals. ing PACS systems (DICOM Standards Committee, Working Group 26, Pathology, 2010). Unfortunately, there is currently no open implementation of this re- cent standard, most probably because of the existence 2 SYSTEM AND METHODS of many patents (Cucoranu et al., 2014): As a con- sequence, even if any modern PACS can ingest such DICOM images, few will render them. There is also a According to the Introduction section, our soft- lack of sample files, which strongly calls for an open ware framework for digital pathology and telepathol- infrastructure to share knowledge about this complex ogy is divided into two separate components: standard, to the benefit of hospitals, manufacturers • A standalone command-line tool that takes as in- and researchers. put a non-DICOM whole-slide microscopic im- The third technical challenge for telepathology age, and that generates a compliant DICOM file. consists in serving the images over Internet. Be- cause of the size of whole-slide images, a raw transfer • A DICOM server that can easily publish such im- of the files would not be compatible with real-time ages on the Web. constraints or mobile applications. It is also highly desirable to avoid the installation of some heavy- This section will fully describe our technical solu- weight client software on the computers of an hos- tion, after an introduction to the DICOM file format pital, as this operation is often prevented for secu- for whole-slide microscopic imaging. Figure 1: Mapping a multi-resolution pyramid according to the DICOM standard (DICOM Standards Committee, Working Group 26, Pathology, 2010). Each level of the pyramid is a downscaled version of the whole-slide image, and is decomposed as a set of tiles. The tiles are encoded as separate frames of multi-frame DICOM instances (files). 2.1 DICOM FOR VISIBLE LIGHT The DICOM standard models the real world as WHOLE-SLIDE MICROSCOPIC follows: A given patient benefits during her life from a set of medical imaging studies. Each study is made IMAGES of a set of series. Each series is in turn a set of in- stances, the latter being a synonym for a DICOM file. Because images for digital pathology are very large A single DICOM instance can be multi-frame, mean- (possibly dozens of gigabytes), they most often can- ing it can store several independent images (provided not entirely fit inside the memory of a standard com- all of its individual frames