Quantitative Imaging Informatics for Cancer Research.

PURPOSE: We summarize Quantitative Imaging Informatics for Cancer Research (QIICR; U24 CA180918), one of the first projects funded by the National Cancer Institute (NCI) Informatics Technology for Cancer Research program. METHODS: QIICR was motivated by the 3 use cases from the NCI Quantitative Imaging Network. 3D Slicer was selected as the platform for implementation of open-source quantitative imaging (QI) tools. Digital Imaging and Communications in Medicine (DICOM) was chosen for standardization of QI analysis outputs. Support of improved integration with community repositories focused on The Cancer Imaging Archive (TCIA). Priorities included improved capabilities of the standard, toolkits and tools, reference datasets, collaborations, and training and outreach. RESULTS: Fourteen new tools to support head and neck cancer, glioblastoma, and prostate cancer QI research were introduced and downloaded over 100,000 times. DICOM was amended, with over 40 correction proposals addressing QI needs. Reference implementations of the standard in a popular toolkit and standalone tools were introduced. Eight datasets exemplifying the application of the standard and tools were contributed. An open demonstration/connectathon was organized, attracting the participation of academic groups and commercial vendors. Integration of tools with TCIA was improved by implementing programmatic communication interface and by refining best practices for QI analysis results curation. CONCLUSION: Tools, capabilities of the DICOM standard, and datasets we introduced found adoption and utility within the cancer imaging community. A collaborative approach is critical to addressing challenges in imaging informatics at the national and international levels. Numerous challenges remain in establishing and maintaining the infrastructure of analysis tools and standardized datasets for the imaging community. Ideas and technology developed by the QIICR project are contributing to the NCI Imaging Data Commons currently being developed.

Reversible anonymization of DICOM images using automatically generated policies.

Many real-world applications in the area of medical imaging like case study databases require separation of identifying (IDATA) and non-identifying (MDATA) data, specifically those offering Internet-based data access. These kinds of projects also must provide a role-based access system, controlling, how patient data must be organized and how it can be accessed. On DICOM image level, different image types support different kind of information, intermixing IDATA and MDATA in a single object. To separate them, it is possible to reversibly anonymize DICOM objects by substituting IDATA by a unique anonymous token. In case that later an authenticated user needs full access to an image, this token can be used for re-linking formerly separated IDATA and MDATA, thus resulting in a dynamically generated, exact copy of the original image. The approach described in this paper is based on the automatic generation of anonymization policies from the DICOM standard text, providing specific support for all kinds of DICOM images. The policies are executed by a newly developed framework based on the DICOM toolkit DCMTK and offer a reliable approach to reversible anonymization. The implementation is evaluated in a German BMBF-supported expert network in the area of skeletal dysplasias, SKELNET, but may generally be applicable to related projects, enormously improving quality and integrity of diagnostics in a field focused on images. It performs effectively and efficiently on real-world test images from the project and other kind of DICOM images.

dcmqi: An Open Source Library for Standardized Communication of Quantitative Image Analysis Results Using DICOM.

Quantitative analysis of clinical image data is an active area of research that holds promise for precision medicine, early assessment of treatment response, and objective characterization of the disease. Interoperability, data sharing, and the ability to mine the resulting data are of increasing importance, given the explosive growth in the number of quantitative analysis methods being proposed. The Digital Imaging and Communications in Medicine (DICOM) standard is widely adopted for image and metadata in radiology. dcmqi (DICOM for Quantitative Imaging) is a free, open source library that implements conversion of the data stored in commonly used research formats into the standard DICOM representation. dcmqi source code is distributed under BSD-style license. It is freely available as a precompiled binary package for every major operating system, as a Docker image, and as an extension to 3D Slicer. Installation and usage instructions are provided in the GitHub repository at https://github.com/qiicr/dcmqi Cancer Res; 77(21); e87-90. ©2017 AACR.

DICOM for quantitative imaging biomarker development: a standards based approach to sharing clinical data and structured PET/CT analysis results in head and neck cancer research.

Background. Imaging biomarkers hold tremendous promise for precision medicine clinical applications. Development of such biomarkers relies heavily on image post-processing tools for automated image quantitation. Their deployment in the context of clinical research necessitates interoperability with the clinical systems. Comparison with the established outcomes and evaluation tasks motivate integration of the clinical and imaging data, and the use of standardized approaches to support annotation and sharing of the analysis results and semantics. We developed the methodology and tools to support these tasks in Positron Emission Tomography and Computed Tomography (PET/CT) quantitative imaging (QI) biomarker development applied to head and neck cancer (HNC) treatment response assessment, using the Digital Imaging and Communications in Medicine (DICOM(®)) international standard and free open-source software. Methods. Quantitative analysis of PET/CT imaging data collected on patients undergoing treatment for HNC was conducted. Processing steps included Standardized Uptake Value (SUV) normalization of the images, segmentation of the tumor using manual and semi-automatic approaches, automatic segmentation of the reference regions, and extraction of the volumetric segmentation-based measurements. Suitable components of the DICOM standard were identified to model the various types of data produced by the analysis. A developer toolkit of conversion routines and an Application Programming Interface (API) were contributed and applied to create a standards-based representation of the data. Results. DICOM Real World Value Mapping, Segmentation and Structured Reporting objects were utilized for standards-compliant representation of the PET/CT QI analysis results and relevant clinical data. A number of correction proposals to the standard were developed. The open-source DICOM toolkit (DCMTK) was improved to simplify the task of DICOM encoding by introducing new API abstractions. Conversion and visualization tools utilizing this toolkit were developed. The encoded objects were validated for consistency and interoperability. The resulting dataset was deposited in the QIN-HEADNECK collection of The Cancer Imaging Archive (TCIA). Supporting tools for data analysis and DICOM conversion were made available as free open-source software. Discussion. We presented a detailed investigation of the development and application of the DICOM model, as well as the supporting open-source tools and toolkits, to accommodate representation of the research data in QI biomarker development. We demonstrated that the DICOM standard can be used to represent the types of data relevant in HNC QI biomarker development, and encode their complex relationships. The resulting annotated objects are amenable to data mining applications, and are interoperable with a variety of systems that support the DICOM standard.

The control of source to sink carbon flux during tuber development in potato.

We have used top-down metabolic control analysis to investigate the control of carbon flux through potato (Solanum tuberosum) plants during tuberisation. The metabolism of the potato plant was divided into two blocks of reactions (the source and sink blocks) that communicate through the leaf apoplastic sucrose pool. Flux was measured as the transfer of 14 C from CO2 to the tuber. Flux and apoplastic sucrose concentration were varied either by changing the light intensity or using transgenic manipulations that specifically affect the source or sink blocks, and elasticity coefficients were measured. We have provided evidence in support of our assumption that apoplastic sucrose is the only communicating metabolite between the source and sink blocks. The elasticity coefficients were used to calculate the flux control coefficients of the source and sink blocks, which were 0.8 and 0.2, respectively. This work suggests that the best strategy for the manipulation of tuber yield in potato will involve increases in photosynthetic capacity, rather than sink metabolism.

Experiences with a workstation prototype for softcopy reading within the Bavarian mammography recertification program: workstations and education.

RATIONALE AND OBJECTIVES: In January 2002, the Bavarian Statutory Health Care Administration ("Kassenärztliche Vereinigung Bayerns", KVB) started a recertification program for quality assurance and quality improvement in mammography reading. MATERIALS AND METHODS: All accredited radiologists and gynecologists are asked to prove their qualification every 1-2 years. The recertification program requires the physicians to read 50 cases randomly selected from a larger collection of high-quality test cases. The portion of malignant and benign cases corresponds to the requirements of the German National Association of Statutory Health Insurance Physicians ("Kassenäztliche Bundesvereinig ung", KBV). In order to perform the recertification in a manageable manner a decentralized approach (test at different locations in parallel) was preferred over a centralized one. Therefore, the X-ray films were digitized and converted to DICOM Digital Mammography format to be read on a softcopy device. To verify the applicability of digitized mammograms for recertification purposes, a comparative study with 32 trained radiologists and gynecologists was performed. RESULTS: A system of two high-resolution/high-contrast monitors (2048 X 2560 pixels, > or = 350 cd/m2) in combination with a 5 mega-pixel dual-head graphics adapter with calibrated output was chosen for the mammography workstation. The software was implemented according to the particular requirements of this program. As a result, the comparative study showed that there was no significant difference in the error rate of the reported findings between conventional film and softcopy reading. CONCLUSION: The first intermediate results of this quality initiative are promising. As of 2003, the test is mandatory for all mammography-reading physicians in Bavaria.

Bridging the integration gap between imaging and information systems: a uniform data concept for content-based image retrieval in computer-aided diagnosis.

It is widely accepted that content-based image retrieval (CBIR) can be extremely useful for computer-aided diagnosis (CAD). However, CBIR has not been established in clinical practice yet. As a widely unattended gap of integration, a unified data concept for CBIR-based CAD results and reporting is lacking. Picture archiving and communication systems and the workflow of radiologists must be considered for successful data integration to be achieved. We suggest that CBIR systems applied to CAD should integrate their results in a picture archiving and communication systems environment such as Digital Imaging and Communications in Medicine (DICOM) structured reporting documents. A sample DICOM structured reporting template adaptable to CBIR and an appropriate integration scheme is presented. The proposed CBIR data concept may foster the promulgation of CBIR systems in clinical environments and, thereby, improve the diagnostic process.

The expression of an extensin-like protein correlates with cellular tip growth in tomato.

Extensins are abundant proteins presumed to determine physical characteristics of the plant cell wall. We have cloned a cDNA encoding LeExt1 from a tomato (Lycopersicon esculentum Mill.) root hair cDNA library. The deduced sequence of the LeExt1 polypeptide defined a novel type of extensin-like proteins in tomato. Patterns of mRNA distribution indicated that expression of the LeExt1 gene was initiated in the root hair differentiation zone of the tomato rhizodermis. Cloning of the corresponding promoter and fusion to the -glucuronidase (GUS) reporter gene allowed detailed examination of LeExt1 expression in transgenic tomato plants. Evidence is presented for a direct correlation between LeExt1 expression and cellular tip growth. LeExt1/GUS expression was detectable in trichoblasts (=root hair-bearing cells), but not in atrichoblasts of the tomato rhizodermis. Both hair formation and LeExt1 expression was inducible by the plant hormone ethylene. Comparative analysis of the LeExt1/GUS expression was performed in transgenic tomato, potato (Solanum tuberosum), tobacco (Nicotiana tabacum), and Arabidopsis plants. In the apical/basal dimension, GUS staining was absent from the root cap and undifferentiated cells at the root tip in all species investigated. It was induced at the distal end of the differentiation zone and remained high proximally to the root/hypocotyl boundary. In the radial dimension, GUS expression was root hair specific in the solanaceous species. Whereas LeExt1 mRNA was exclusively detectable in the rhizodermis, root hair-specific expression correlated with GUS expression in germinating pollen tubes. This is correlative evidence for a role of LeExt1 in root hair tip growth [corrected].

Overexpression of the sucrose transporter SoSUT1 in potato results in alterations in leaf carbon partitioning and in tuber metabolism but has little impact on tuber morphology.

The aim of this work was to examine the consequences of the heterologous expression of a spinach ( Spinacia oleracea L.) sucrose transporter ( SoSUT1) in potato ( Solanum tuberosum L.). Many studies have indicated that reduction of the expression of this class of sucrose transporter has deleterious effects on plant growth and development; however, until now the possibility of improving plant performance by enhancing the expression of this sucrose transporter has not been reported. With this intention we constructed a chimeric construct in which SoSUT1 was cloned in-frame with the myc epitope. We confirmed that this construct, SoSUT1m, was able to mediate sucrose transport by expression in the yeast strain SUSY7. SoSUT1m was expressed in wild-type potato in the sense orientation under the control of the cauliflower mosaic virus 35S promoter to evaluate the effect of an increased constitutive expression of a class-I sucrose transporter. We confirmed that these plants displayed expression of SoSUT1 at both the transcript and protein level and that microsomal fragments isolated from selected lines had an increased sucrose uptake capacity. Analysis of metabolism of these lines indicated that the leaves were characterised by a reduced sucrose level yet exhibited little change in photosynthetic rate. Furthermore, despite the observed increase in sugar (and reduction in amino acid) levels within the tubers, there was little change in either starch content or tuber yield in the transformants. In summary, the genetic manipulation described in this paper resulted in a shift in carbon partitioning in both leaves and tubers and an increased sucrose uptake rate in plasma-membrane vesicles isolated from these lines, but had little impact on tuber metabolism or morphology.