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Introduction to CTIIP

Imaging-based cancer research is in the beginning phase of an integrative-biology revolution. It is now feasible to extract large sets of quantitative image features relevant to cancer prognosis or treatment across three complementary research domains: in vivo clinical imaging, pre-clinical imaging, and digital pathology. These high-dimensional image feature sets can be used to infer clinical phenotypes or correlate with gene–protein signatures. This type of analysis, however, requires large volumes of data.

To serve the need for research across domains, the National Cancer Institute Clinical and Translational Imaging Informatics Project (NCI CTIIP) team is developing and deploying a set of open source software tools that supports a comprehensive and reusable exploration and fusion of imaging, clinical, and molecular data. The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA) projects have created a rich multi-domain data set. This data set, however, is in an infrastructure that provides limited query capability for identifying cases based on all of the available data types. (For example...?)

The CTIIP team will therefore develop a unified query interface to facilitate cross-disciplinary analysis. This infrastructure would then be applied to clinical/co-clinical settings, using data collected for this purpose, and provide a common platform and data engine for the hosting of “pilot challenges.” These pilot challenge projects will proactively facilitate biological and clinical research across three NCI divisions. The algorithms used in the pilot challenges will be shared with the community via an open-source software clearinghouse.

The approach taken to development in this project emphasizes modular semantic interoperability and open source tooling, making it immediately valuable to scientists with NCI funded research networks in the three research domains, as well as the national and international research communities, and providing a framework for enhanced adoption of these methods by biologists in the larger genomics/proteomic communities.

Most importantly, the common informatics infrastructure will provide researchers with analysis tools they can use to directly mine data from multiple high-volume information repositories, creating a foundation for research and decision support systems to better diagnose and treat patients with cancer.

The following table presents the data that the CTIIP team is integrating through various means. This integration relies on the expansion of software features and on the application of data standards, as described in subsequent sections of this document.

DomainData Set
Clinical ImagingThe Cancer Genome Atlas (TCGA) clinical and molecular data
 The Cancer Imaging Archive (TCIA) in-vivo imaging data
Pre-clinicalSmall animal models
Digital PathologycaMicroscope

The sub-projects, along with the solutions they provide, are discussed in this guide and listed below.

Sub-Project NameSolution it Provides
Digital Pathology and Integrated Query SystemAddress the interoperability of digital pathology data, improve integration and analytic capabilities between TCIA and TCGA, and raise the level of interoperability to create the foundation required for pilot demonstration projects in each of the targeted research domains: clinical imaging, pre-clinical imaging, and digital pathology imaging.
DICOM Standards for Small Animal Imaging; Use of Informatics for Co-clinical TrialsAddress the need for standards in pre-clinical imaging and test the informatics created in the Digital Pathology and Integrated Query System sub-project for decision support in co-clinical trials.
Pilot ChallengesChallenges will be designed to develop knowledge extraction tools and compare decision support systems for the three research domains, which will now be represented as a set of integrated data from TCIA and TCGA. The intent is not to specifically implement a rigorous “Grand Challenge,” but rather to develop pilot challenge projects. These would use limited data sets for proof-of-concept, and test the informatics infrastructure needed for such “Grand Challenges” that would later be scaled up and supported by extramural initiatives.

The Importance of Data Standards to Integrative Queries

Informatics helps us communicate. It can help us better treat our patients.

This common infrastructure depends on data interoperability, which is greatly aided by adherence to data standards. While standards such as Annotation and Image Markup (AIM) and Digital Imaging and Communications in Medicine (DICOM) exist, vendors of data viewers and other tools required for the analysis of imaging data have not widely adopted them. Digital pathology, unlike its more mature radiographic counterpart, has yet to standardize on a single storage and transport media. The result of this lack of uniformly accepted standards is that outside a given laboratory of small collaborative groups, the integration of pathology data with radiographic, genomic, and proteomic data is all but impossible. The lack of standards in pre-clinical and pathology prevents the ability to share and leverage data across studies and institutions.

Furthermore, because each pathology-imaging vendor produces its own image management systems, these systems are also, by extension, proprietary and not standardized. The result is that images produced on different systems cannot be analyzed via the same mechanisms.

In addition, no standard currently exists for markup and annotations on images.

Within these three research domains, only one, clinical imaging, has made some progress in terms of establishing a framework and standards for informatics solutions. For pre-clinical imaging and digital pathology, there are no such standards that allow for the seamless viewing, integration, and analysis of disparate data sets to produce integrated views of the data, quantitative analysis, data integration, and research or clinical decision support systems.

CBIIT has worked extensively for several years in the area of data standards for both clinical research and healthcare, working with the community and Standards Development Organizations (SDOs), such as the Clinical Data Interchange Standards Consortium (CDISC), Health Level 7 (HL7) and the International Organization for Standardization (ISO). From that work, EVS and caDSR is harmonized with the BRIDG, SDTM, and HL7 RIM models. Standardized Case Report Forms (CRFs), including those for imaging, have also been created. The CBIIT project work provides the bioinformatics foundation for semantic interoperability in digital pathology and co-clinical trials integrated with clinical and patient demographic data and data contained in TCIA / TCGA.

Digital Pathology and Integrated Query System

This sub-project addresses the lack of uniformly accepted standards within digital pathology and the simultaneous need for integration of pathology data with radiographic, genomic, and proteomic data.

Creating an open-source digital pathology image server that can host and serve digital pathology images for any of the major vendors without recoding, facilitating the integration of pathology data with radiographic, genomic, and proteomic data.

Establishing an informatics and IT infrastructure to implement pilot challenges for clinical and pre-clinical studies that integrate the genomics, diagnostic imaging, and digital pathology domains.

Project 1: Integrated Query System for Existing TCGA Data

1)      AIM 1 - Integrated query system for existing TCGA data (including improved pathology systems)

a)       Histopathology

i)       Incorporate Openslide with caMicrosocope enabling  caMicrosocope to directly serve whole slide pathology images from the majority of digital pathology vendors.

ii)      Incorporate support for basic image analysis algorithms into caMicroscope.

iii)     Standards-based image annotation utilizing the Annotation Image Markup (AIM) standard.

b)       Integrative Queries

i)       Programmatic Access to Data to TCGA-related image data.

ii)      Extend software to support data mashups between image-derived information from TCIA and clinical and molecular metadata from TCGA.

 

Integrative Query System

Look at Ulli's PPT

Extend software to support data mashups between image-derived information from TCIA and clinical and molecular metadata from TCGA.

Integrative Queries

Programmatic Access to Data to TCGA-related image data.

Extend software to support data mashups between image-derived information from TCIA and clinical and molecular metadata from TCGA.

What the data is used for

Relate data from TCIA, caMicroscope, animal model

genomics, animal

how do we make a decision on a firm diagnosis?

Get queries and relate it to the human data and vice versa

System should integrate clinical data (from TCGA), preclinical data (comes from UC Davis)

Use case: Breast cancer has biomarkers (progesterone status, etc.). One question to ask is "if the estrogen status is negative in humans, what does the pathology look like?" Then compare this to mice. Is the model we have a good model for the human condition?

If you treat a mouse model that has an ER negative status with a certain drug, what is the outcome? Then see this in humans.

We are setting up the data structure so when that is done, we'll be able to see what use cases are possible.

To make data comparable, we must collect it in a structured fashion. Common Data Elements for TCGA.

We are pulling data out of caDSR (ER negative and positive, other common data elements) and we are asking Bob Cardiff's team to ask the same questions so that we can compare human and mouse data.

We are exploring the standardization of informatics. Use all the tools we have to create standard informatics to compare patient to animal data. We are using the available standards: DICOM, AIM, micro AIM. Fundamental to integrative queries.

If you did an integrative query, how would you do it? Data calls to do different integrative queries. How would you use sufficient standard data. Come out with information that will allow you to make a decision. Pilot challenges to compare the decision support systems for three domains.

We need a clear explanation of how to do this.

Data mashups that allow us to

Explain our complicated project in a simple manner so they understand why we are doing and what we are doing.

Pathology problems:1.  proprietary data formats that cannot be displayed and manipulated in the same tools. Solution is to integrate caMicroscope with OpenSlide (allows us to read prop. formats without converting images). Makes a large number of image formats accessible. 2. no standard for markups and annotations. So we're creating microAIM.

Challenges

Solutions

The first step towards the goal of image data integration is the creation of an image server that can host and serve digital pathology images for any of the major vendors without recoding, which often introduces additional compression artifacts. This image server will be caMicroscope, with its functionality expanded by the OpenSlide library.

  • caMicroscope is a digital pathology viewer provides researchers with an HTML5-based web client that can be used to view a digitized pathology image at full resolution. While it is standards-based, implementing both the Annotation and Image Markup (AIM) and Digital Imaging and Communications in Medicine (DICOM) standards, it supports limited formats adopted by whole-slide vendors.
  • OpenSlide is a C library that can read whole-slide images in many common formats adopted by whole-slide vendors.

This project is also proposing a standard for markup and annotations called microAIM.

This infrastructure can be expanded to include more data types and additional integration, which will provide analytic and decision support to researchers, who can then pursue a broader set of novel community research projects.

Small Animal/Co-clinical Improved DICOM Compliance and Data Integration

The impact on integrative research projects such as co-clinical trials would be to give researchers the ability to directly compare data from pre-clinical animal models with real-time clinical data.

Developing DICOM standards for small animal imaging and identify co-clinical datasets to test the integration of TCIA and TCGA for this data.

TCGA Infrastructure Applied to Co-Clinical

1)      AIM 2 - TCGA infrastructure ported to/applied to co-clinical setting 

a)       Pilot improve small-animal DICOM compliance

b)       Identify co-clinical pilot data set and populate integrated ‘omics/imaging infrastructure.

Co-clinical and animal model images: most imaging machines for animal model imaging do not follow the DICOM standard. We developed a supplement to the DICOM standard to accommodate small animal imaging (standard out for balloting). We want to include co-clinical/animal model data in the integrative queries. For this new standard to be used, equipment manufacturers would need to incorporate this standard when they develop machines/software.

Challenges

Solutions

DICOM Working Group 30

Challenges

Solutions

Pilot Challenges

1)      AIM 3 - “Pilot Challenges” to compare the decision support systems for three imaging research domains: Clinical Imaging, Pre-clinical Imaging, and Digital Pathology.

a)       Leverage and extend the above platform and data systems to validate and share algorithms, support precision medicine and clinical decision making tools, including correlation of imaging phenotypes with genomics signatures. The aims are fashioned as four complementary “Pilot Challenges”.

i)       Clinical Imaging: QIN image data for several modalities/organ systems are already hosted on TCIA. Pilot challenge projects are being explored for X-ray CT, DWI MRI and PET CT similar to the HUBzero pilot CT challenge project.

ii)      Pre-clinical / Co-clinical Imaging leveraging the Mouse Models of Human Cancer Consortium (MHHCC) Glioblastoma co-clinical trials with associated ’omics data sets from the Human Brain Consortium. This proof of concept will focus on bringing together ‘omics and imaging data into a single platform.

iii)     Digital Pathology clinical support. Leveraging Aims1-3 develop open source image analysis algorithms which complement ‘omics data sets and provide additional decision support.

iv)     Enable community sharing of algorithms on a software clearinghouse platform such as HubZero.

Three pilot challenges–pathology, radiology, co-clinical.

Medical Image Computational and computer-assisted Intervention: MICCAI

Interventions in tumors, cardiology, etc that are image-based

Mass General will guide the pilots

Ground truth: find the compatibility of the informatics that we need to run pilots. Take images out of TCIA, CGA, clinical data and compare them.

Jasharee doing MICCAI Challenge in Munich. Segmentation of nuclear imaging in pathology. Combined radiology and pathology classification.

Want to be able to say that these informatics allow us to compare the pathology, rad, co-clinical findings.

Document the approach, technology, application to do a MICCAI challenge the way Jaysharee does it. See their order of march.

Challenges: read one-page document. We want to use pathology images in the challenges. The tool used to display the markup and annotations (for the pathology images) is caMicroscope. There will be a challenge in which animal model data will be used. Give people images they have never seen before and develop algorithms (like to circle all the nuclei). Ground truth decided by a pathologist and a radiologist. The algorithm that comes closest to ground truth is the winner.

Challenge Management System, MedICI

Jaysharee's program: Medical Imaging Challenge Infrastructure: MedICI

  1. Based on open-source CodaLab
  2. ePAD (created by Daniel Rubin's group at Stanford): tool for annotating images, creates AIM images
  3. caMicroscope

http://miccai.cloudapp.net:8000/competitions/28

  1. Competition #1: MICCAI challenge has a training phase where they train their algorithms. A test phase where they run their algorithms on images they have never seen before. They are compared to the ground truth that is determined beforehand. caMicroscope is used to see what is there before and to visualize the results. Overlap/completeness match determines the winner.
  2. Competition #2: They are given slides.

From PPT: Use titles of slides

Setting up a competition by an organizer. Organizer creates competition bundle.

Can go to cancerimagingarchive.net and create shared lists. Shared lists are pulled into CodaLab. That is how they get the test and training data.

Next is to create ground truth.

Regions of interest in a tumor for annotations are necrosis, adema, and active cancer. Radiologists create the ground truth.

Once participants upload their results, they can see them in ePad.

Challenges

Solutions

Scenarios

Need to generate proper therapy for a patient. Look at in vivo imaging, radiology and pathology, run a gene panel to look for abnormal. Look at co-clinical trials (model of a tumor in a mouse that is similar to a human. Experiment therapies on mice.) Run an integrative query to develop a sophisticated diagnosis. Search big data.

Visual pathology integrative queries–Ashish at Emory. Imaging consistent with ground truth.

Need to explain how the challenge management system and integrative query system play together in a scientific scenario.

three tocs: one for challenge steps, one for int query sys. how well does it integrate; what are the common–how do we annotate the tumor in MedICI such that it is compatible with the annotations in the components of the integrative query system. What relationships can we find in the informatics in the animal and patient findings.

Most cancer diagnoses are made based on images. You have to see a tumor, or compare images of it over time, to determine its level of threat. Ultrasounds, MRIs, and X-rays are all common types of images that radiologists use to collect information about a patient and perhaps cause a doctor to recommend a biopsy. Once that section of the tumor is under the microscope, pathologists learn more about it. Radiologists and pathologists represent different scientific disciplines. To gather even more information, a doctor may order a genetic panel. If that panel shows that the patient has a genetic anomaly, the doctor or a geneticist may search for clinical trials that match it, or turn to therapies that researchers have already proven effective for this combination of tumor and genetic anomaly through recent advances in precision medicine.

Another way we learn about cancer in humans is through small animal research. Images from small animals allow detailed study of biological processes, disease progression, and response to therapy, with the potential to provide a natural bridge to human disease. Due to differences in how data is collected and stored about animals and humans, however, the bridge is man-made.

Each of these diagnostic images are at a different scale, from a different scientific discipline. A large-scale image like an X-ray may be almost life-size. Slices of tumors are smaller still and you must put them on a slide under a microscope to see them. Not surprisingly, each of these image types require specialized knowledge to create, handle, and interpret them. While complementary, each specialist comes from a different scientific discipline.

One promise of big data is that data mashups can integrate two or more data sets in a single interface so that doctors, pathologists, radiologists, and laboratory technicians can make connections that improve outcomes for patients. Such mashups require and await technical solutions in the areas of data standards and software development. A significant start to all of these technical solutions are the sub-projects of the National Cancer Institute Clinical and Translational Imaging Informatics Project (NCI CTIIP).

CTIIP Sub-Projects

As discussed so far, cancer research is needed across disciplines. To serve this need, the National Cancer Institute Clinical and Translational Imaging Informatics Project (NCI CTIIP) team plans to meet it by creating a data mashup interface, along with other software and standards, that accesses The Cancer Genome Atlas (TCGA) clinical and molecular data, The Cancer Imaging Archive (TCIA) in-vivo imaging data, caMicroscope pathology data, a pilot data set of animal model data, and relevant imaging annotation and markup data.

The common informatics infrastructure that will result from this project will provide researchers with analysis tools they can use to directly mine data from multiple high-volume information repositories, creating a foundation for research and decision support systems to better diagnose and treat patients with cancer.

CTIIP is composed of the following sub-projects. Each project is discussed on this page.

Sub-Project NameDescription
Digital PathologyAddresses the accessibility of digital pathology data through the integration of OpenSlide, improves tools for annotation and markup of pathology images through the development of microAIM (μ-AIM), and integrates analysis tools with caMicroscope. These developments increase the interoperability in each of the targeted research domains: clinical imaging, pre-clinical imaging, and digital pathology imaging.
Integrated Query SystemProvides a data mashup interface that accesses TCGA clinical and molecular data, TCIA in-vivo imaging data, caMicroscope pathology data, relevant imaging annotation and markup data, and a pilot data set of animal model data.
DICOM Standards for Small Animal Imaging; Use of Informatics for Co-clinical TrialsAddresses the need for standards in pre-clinical imaging and applies the informatics tools created by the Digital Pathology and Integrated Query System sub-projects to co-clinical trials.
Pilot ChallengesPilot challenges are a tool to find suitable image analysis algorithms. The pilot challenges would use limited data sets for proof-of-concept, and test the informatics infrastructure needed for more rigorous “Grand Challenges” that could later be scaled up and supported by extramural initiatives.

The Importance of Data Standards

NCI CBIIT has worked extensively for several years in the area of data standards for both clinical research and healthcare, working with the community and Standards Development Organizations (SDOs), such as the Clinical Data Interchange Standards Consortium (CDISC), Health Level 7 (HL7) and the International Organization for Standardization (ISO). From that work, Enterprise Vocabulary Services (EVS) and Cancer Data Standards Registry and Repository (caDSR) are harmonized with the Biomedical Research Integrated Domain Group (BRIDG), Study Data Tabulation Model (SDTM), and Health Level Seven® Reference Information Model HL7 RIM models. Standardized Case Report Forms (CRFs), including those for imaging, have also been created. The CBIIT project work provides the bioinformatics foundation for semantic interoperability in digital pathology and co-clinical trials integrated with clinical and patient demographic data and data contained in TCIA and TCGA.

The common infrastructure that will result from CTIIP and its sub-projects depends on data interoperability, which is greatly aided by adherence to data standards. While image data standards exist to support communicating image data in a common way, the data standards that do exist for image data are inconsistently adopted. One reason for the lack of uniform adoption is that vendors of image management tools required for the analysis of imaging data have created these tools so that they only accept proprietary data formats. Researchers then make sure their data can be interpreted by these tools. The result is that data produced on different systems cannot be analyzed by the same mechanisms.

Another challenge for CTIIP with its goal of integrating data from complimentary domains is the lack of a defined standard for co-clinical and digital pathology data. Without a data standard for these domains, it is very difficult to share and leverage such data across studies and institutions. As part of the CTIIP project, the team has extended the DICOM model to co-clinical and small animal imaging. The long-term goal is to generate DICOM-compliant images for small animal research.

Within the three research domains that CTIIP intends to make available for integrative queries, only one, clinical imaging, has made some progress in terms of establishing a framework and standards for informatics solutions. Those standards include Annotation and Image Markup (AIM), which allows researchers to standardize annotations and markup for radiology images, and Digital Imaging and Communications in Medicine (DICOM), which is a standard for handling, storing, printing, and transmitting information in medical imaging. For pre-clinical imaging and digital pathology, there are no such standards that allow for the seamless viewing, integration, and analysis of disparate data sets to produce integrated views of the data, quantitative analysis, data integration, and research or clinical decision support systems. The micro-Annotation and Image Markup (µAIM) model is currently in development to serve the unique needs of the pre-clinical domain.

The following table presents the data that the CTIIP team is integrating through various means. This integration relies on the expansion of software features and on the application of data standards, as described in subsequent sections of this document.

DomainData SetApplicable Standard
Molecular and Clinical DataThe Cancer Genome Atlas (TCGA) molecular and clinical dataN/A
Clinical ImagingThe Cancer Imaging Archive (TCIA) in vivo imaging dataDICOM
Pre-ClinicalSmall animal models

Supplement 187: Preclinical Small Animal Imaging Acquisition Context

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of the DICOM standard exists but has not yet been adopted.

Digital PathologycaMicroscope

DICOM is applicable but has not yet been adopted.

AllAnnotations and markup on imagesµAIM is in development.

Digital Pathology and Integrated Query System

One of the goals of this sub-project is to create a digital pathology image server that can accept whole slide images from multiple vendors and display them despite the proprietary formats they were created in. This is accomplished by integrating the OpenSlide

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libraries with caMicroscope.

Using this server, which is an extended version of caMicroscope, researchers can select data from different imaging data sets and use them in image algorithms. The first data sets that are being integrated on this image server are TCGA and TCIA.

TCGA finalized tissue collection with matched tumor and normal tissues from 11,000 patients, allowing for the comprehensive characterization of 33 cancer types and subtypes, including 10 rare cancers, and has provided this information to the research community. TCIA and the underlying National Biomedical Image Archive (NBIA) manage well-curated, publicly-available collections of medical image data. The linkages between TCGA and TCIA are valuable to researchers who want to study diagnostic images associated with the tissue samples sequenced by TCGA. TCIA currently supports over 40 active research groups including researchers who are exploiting these linkages.

Although TCGA and TCIA comprise a rich, complementary, multi-discipline data set, they are in an infrastructure that provides limited ability to query the data. Researchers want to query multiple databases at the same time to identify cases based on all available data types.

To address these limitations, the CTIIP team is developing an Integrated Query System to make it easier to analyze data from different research disciplines represented by TCGA, TCIA, and co-clinical/small animal model data. 

Digital Pathology

Digital pathology, unlike its more mature radiographic counterpart, has yet to standardize on a single storage and transport media. In addition, each pathology-imaging vendor produces its own image management system, making image analysis systems proprietary and not standardized. The result is that images produced on different systems cannot be viewed and analyzed via the same mechanisms. Not only does this lack of standards and the dominance of proprietary formats impact digital pathology, but it prevents digital pathology data from integrating with data from other disciplines.

The team is using OpenSlide, a vendor-neutral C library, to extend the software of caMicroscope, a digital pathology server. The extended software will support some of the common formats adopted by whole slide vendors as well as basic image analysis algorithms. With the incorporation of common whole slide formats, caMicroscope will be able to read whole slides without recoding, which often introduces additional compression artifacts.

Image markups and annotations also require standards so that they can be read by different imaging disciplines along with the rest of the image data. Support for the μ-AIM model will be added to caMicroscope so that researchers can include image annotation and markup features in digital pathology data.

caMicroscope slide with markupImage Added
caMicroscope Slide with Markup

With caMicroscope's support for basic image analysis algorithms, researchers can use this tool to enable analytic and decision support using digital pathology images.

Integrated Query System

The purpose of the integrative query component of CTIIP is to support data mashups between images, image-derived information, and clinical, pre-clinical, and genomic data. Co-clinical data and clinical data such as patient information and outcome will also be accessible through the Integrated Query System.

To make data accessible and comparable, it must first be collected in a structured fashion. For example, TCGA relies on Common Data Elements, which are the standard elements that structure TCGA data. Second, data comparisons require common data vocabularies. For example, when a tumor is described in a human or an animal, one of a discrete number of approved vocabulary options must be used to describe the tumor.

Data federation, a process whereby data is collected from different databases without ever copying or transferring the original data, is part of the new infrastructure. The software used to accomplish this data federation is Bindaas.  Bindaas is a middleware used to develop web services that allow data providers to share data, stored in databases, using a popular standard for developing web services called Representational State Transfer. Developers can use the REST interface with most modern languages to rapidly create and deploy applications that can consume data contained in the underlying database. Bindaas enables resource providers to rapidly generate APIs with only an understanding of the underlying data model. It is able to do so because it uses a declarative programming model that allows data providers to create REST APIs without having to write a single line of code. 

The Integrated Query System will access multiple data types in a federated fashion, meaning that the original data will reside in independent systems. The Integrated Query System will provide an interface  scientists can use to select the data types they want to combine, or "mash up," based on their own research questions.

The following table presents the data types and their sources that the Integrated Query System will make available.

Data Types in the Integrated Query SystemData Source
GenomicGoogle Genomics Cloud
ClinicalDownloaded from TCGA and stored in a customized database at Emory University
PreclinicalCustomized database at Emory University
Radiology Images (Human and Animal) TCIA
Radiology Image Annotation and MarkupAIM Data Service (AIME)
Pathology Images (Human and Animal) caMicroscope
Pathology Image Annotation and MarkupuAIM Data Service (uAIME)

The Integrated Query System, with its support for whole slides and data mashups of federated data, will act as a foundation for a broader set of novel community research projects.

DICOM Working Group 30

Since its first publication in 1993, DICOM has revolutionized the practice of radiology, allowing the replacement of X-ray film with a fully digital workflow. Each year, the standard is updated with formats for medical images that can be exchanged with the data and quality necessary for clinical use. (Source: http://dicom.nema.org/Dicom/about-DICOM.html)

As part of the Small Animal/Co-clinical Improved DICOM Compliance and Data Integration sub-project of CTIIP, the NCI supported the development of a DICOM supplement for small animal imaging. The group of people contributing to it, Working Group 30, completed Supplement 187: Preclinical Small Animal Imaging Acquisition Context

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, in 2015.

Supplement 187 Data Elements

Information about how a small animal image was acquired is relevant to the interpretation of the image and must be stored with it. While DICOM defines terminology applicable to other types of images, it does not include data elements associated with small animal image acquisition. The new Supplement 187, developed as part of the CTIIP project in 2015, defines terminology that is unique to small animal imaging. It includes the following templates that include terminology relevant to image acquisition.

  • Preclinical Small Animal Image Acquisition Context
    • Language of Content Item and Descendants
    • Observation Context
    • Biosafety Conditions
    • Animal Housing
    • Animal Feeding
    • Heating Conditions
    • Circadian Effects
    • Physiological Monitoring Performed During Procedure
    • Anesthesia
      • Medications and Mixture Medications
    • Medication, Substance, Environmental Exposure

Consult Supplement 187: Preclinical Small Animal Imaging Acquisition Context

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for details about each of these templates.

Pilot Challenges

Challenges are being increasingly viewed as a mechanism to foster advances in a number of fields, including healthcare and medicine. Large quantities of publicly available data, such as that in TCIA, and cultural changes in the openness of science have now made it possible to use these challenges, as well as crowdsourcing (enlisting the services of people via the Internet), to propel the field forward.

Some of the key advantages of challenges over conventional methods include 1) scientific rigor (sequestering the test data), 2) comparing methods on the same datasets with the same, agreed-upon metrics, 3) allowing computer scientists without access to medical data to test their methods on large clinical datasets, 4) making resources available, such as source code, and 5) bringing together diverse communities (that may traditionally not work together) of imaging and computer scientists, machine learning algorithm developers, software developers, clinicians, and biologists.  

As explained in the Challenge Management System Evaluation Report, challenge hosts and participants cannot do it alone. The computing resourcing needed to process these large datasets may be beyond what is available to individual participants. For the organizers, creating an infrastructure that is secure, robust, and scalable can require resources that are beyond the reach of many researchers. Additionally, imaging formats for pathology images can be proprietary and interoperability between formats can require additional software development efforts.

Over the last few years, Grand Challenges

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have become popular in several imaging-based research communities. A Grand Challenge is designed to validate and compare imaging analysis algorithms. The algorithms are applied to a single dataset and the results for each algorithm are compared against a previously-determined ground-truth dataset.

The Pilot Challenges sub-project of CTIIP will sponsor complementary Pilot Challenge projects. As opposed to a more rigorous Grand Challenge, each Pilot Challenge will involve data sets of reduced size and demonstrate the infrastructure as capable of running Grand Challenges in the future.

Challenges are often conducted in conjunction with scientific conferences. The following Pilot Challenges, supported by the CTIIP project and described in the following table, were part of the Computational Brain Tumor Cluster of Event (CBTC) 2015 which was held on October 9, 2015 in Munich, Germany, in conjunction with MICCAI 2015.

MICCAI 2015 ChallengesSample ImageDescription

Combined Radiology and Pathology Classification

 

Radiology or pathology image sampleImage Added

The datasets for this challenge are Radiology and Pathology images obtained from the same patients. Each case corresponds to a single patient. There is one Radiology image and one whole slide tissue image for each case. The training set contains a total of 32 cases: 16 cases that are classified by pathologists as Oligodendroglioma and 16 cases classified as Astrocytoma. The test set will have 20 cases. Please note that the number of cases in the test set may not be equally partitioned between the two sub-types. The whole slide tissue images are stored in Aperio SVS format. There are open source tools and libraries that can read these images: OpenSlide

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and Bio-Formats
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.

Segmentation of Nuclei in Pathology Images

 

Image tile from whole slide tissue imageImage Added

The goal of this challenge is to evaluate the performance of algorithms for detection and segmentation of nuclear material in a tissue image. Participants are asked to detect and segment all the nuclei in a given set of image tiles extracted from whole slide tissue images. The algorithm results will be compared with consensus pathologist-segmented sub-regions. Winners will be ranked based on their nuclei segmentation best matching the reference standards. The reference standard for the challenge will be pathologist-generated nuclear segmentation on select regions of TCGA Glioma whole slide images.

A team from Massachusetts General Hospital will guide the Pilot Challenges. They are using Medical Imaging Challenge Infrastructure (MedICI), a medical imaging challenge platform, to support the challenges. MedICI, in turn, uses the CodaLab framework, an open-source challenge platform developed by Microsoft Research and others in the medical imaging and machine learning communities. Because CodaLab does not have built-in imaging handling, display or annotation capabilities, the team is building on two application packages, ePad and caMicroscope, to provide those features. For example, once participants upload their results, they can see them in ePad.

Challenge participants receive test and training data by creating shared lists in TCIA, then pulling those into CodaLabDescribe each section separately and then see if we can merge the two to answer the scientific question.