Robert C. Leif

DICOM-compatible format for analytical cytology data that can be expressed in XML

Flow cytometry data can be directly mapped to the Digital Imaging and Communications in Medicine, DICOM standard. A preliminary mapping of list-mode data to the DICOM Waveform information Object will be presented. This mapping encompasses both flow and image list-mode data. Since list- mode data is also produced by digital slide microscopy, which has already been standardized under DICOM, both branches of Analytical Cytology can be united under the DICOM standard. This will result in the functionality of the present International Society for Analytical Cytology Flow Cytometry Standard, FCS, being significantly extended and the elimination of the previously reported FCS design deficiencies. Thus, the present Flow Cytometry Standard can and should be replaced by a Digital Imaging and Communications in Medicine, DICOM, standard. Expression of Analytical Cytology data in any other format, such as XML, can be made interoperable with DICOM by employing the DICOM data types. A fragment of an XML Schema has been created, which demonstrates the feasibility of expressing DICOM data types in XML syntax. The extension of DICOM to include Flow Cytometry will have the benefits of 1) retiring the present FCS, 2) providing a standard that is ubiquitous, internationally accepted, and backed by the medical profession, and 3) inter-operating with the existing medical informatics infrastructure.

Evolution of flow cytometry standard, FCS3.0, into a DICOM-compatible format

The International Society for Analytical Cytology, ISAC, has developed a flow cytometry standard (FCS) to permit data interchange, ISAC will soon replace FCS 2.0 with FCS 3.0. Unfortunately, the proposed FCS 3.0 is still fraught with problems, which are of sufficient magnitude as to warrant its early replacement. The most reasonable replacement is as a supplement to the digital imaging and communications in medicine, DICOM 3.0, standard. The recent digital microscopy extension of DICOM can be extended and modified to include flow cytometry data. DICOM includes: image graphics objects, specifications for describing: studies, reports, the acquisition of the data and the individuals involved, physician, patient, etc. Storing the present FCS data in a database, which has already been accomplished with the QC tracker software, will facilitate the transition of FCS to DICOM.

Optimizing the luminescence of lanthanide(III) macrocyclic complexes for the detection of anti-5BrdU

A Eu(III)-macrocycle-mono-isothiocyanate, Quantum Dye®, has been coupled to a monoclonal antibody against 5BrdU. Since Quantum Dyes do not undergo concentration quenching, the coupling conditions were optimized to achieve the maximum number of Eu(III) macrocycles bound to the antiBrdU, without decrease in solubility or loss of antigen-binding ability. In order to optimize the coupling conditions, a colorimetric method for the quantitation of the Eu(III)- macrocycle-mono-isothio-cyanate has been developed. A simple mixture composed of an ethanolic solution and a Gd(III)- containing aqueous solution is now used to provide lanthanide enhanced luminescence, LEL. Under LEL conditions, the specific binding of Eu(III) macrocycles to apoptotic cells has been observed in both aqueous and mounted slide preparations. A comparison between measurements of the same LEL model system, obtained in both time-gated luminescence and standard fluorescence modes, has demonstrated that time- gating significantly improves the signal to noise ratio.

Increasing the luminescence of lanthanide(III) macrocyclic complexes by the use of polymers and lanthanide enhanced luminescence

A Eu (III)-macrocycle-isothiocyanate, Quantum DyeTM, has been reacted with lysine homo- and hetero-peptides to give polymers with multiple luminescent side chains. Contrary to the concentration quenching that occurs with conventional organic fluorophores, the attachment of multiple Quantum Dyes to a polymer results in a concomitant increase in luminescence. The emission intensity of the peptide-bound Quantum Dye units is approximately linearly related to their number. The attachment of peptides containing multiple lanthanide (III) macrocycles to analyte-binding species is facilitated by employing solid-phase technology. Bead-bound peptides are first labeled with multiple Quantum Dye units, then conjugated to an antibody, and finally released from the bead by specific cleavage with Proteinase K unedr physiological conditions. Since the luminescence of lanthanide(III) macrocycles is enhanced by the presence of GD(III) or Y(III) ions in a micellar system, a significant increase in signal can be achieved by attaching a polymer labeled with multiple Quantum Dye units to an analyte- binding species, such as a monoclonal antibody, or by taking advantage of the luminescence enhancing effects of Gd(III) or Y(III), or by both approaches concomitantly. A comparison between the integrated intensity and lifetime measurements of the Eu(III)-macrocycle under a variety of conditions show that the signal increase caused by Gd(III) can not be explained solely by the increase in lifetime, and must result in significant part from an energy transfer process invloving donors not directly bound to the Eu(III).© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

DICOM-compatible format for analytical cytology data

The addition of a list mode data type to the Digital Imaging and Communications in Medicine standard, DICOM will enhance the storage and transmission of digital microscopy data and extend DICOM to include flow cytometry data. This would permit the present International Society for analytical Cytology Flow Cytometry Standard to be retired. DICOM includes: image graphics objects, specifications for describing: studies, reports, the acquisition of the data, work list management, and the individuals involved (physician, patient, etc.) The glossary of terms (objects) suitable for use with DICOM has been extended to include the collaborative effort of Logical Observation Identifier Names and Codes (LOINC) and Systematized Nomenclature of Human and Veterinary Medicine (SNOMED) to create a consistent, unambiguous clinical reference terminology. It also appears that DICOM will be a significant part of the Common Object Request Broker Architecture, CORBA.

Creation of a laboratory instrument quality monitoring system with AdaSAGE

Two existing Ada tools AdaSAGE and AYACC were combined to produce a system that parses International Society for Analytical Cytology, ISAC, Flow Cytometry Standard 2.0 files and stores the data in AdaSAGE tables. There are significant differences in the way manufacturers interpret and conform to Flow Cytometry Standard 2.0. AdaSAGE is employed to analyze and plot the data from multiple experiments. This data is used to assess the stability of flow cytometers. The initial release will be for DOS. The utilization of AdaSAGE, which is a flexible database tool, will facilitate subsequent development of other products. The software engineer, whose previous professional experience was with C and C++, had very few problems with Ada syntax. The interface to the compiler and other tools was immature compared to those available for C++. The DOS text based user interface environment provided by AdaSAGE limited the functionality of the user interface. However, the present DOS 386 program can be directly ported to the newly released version of AdaSAGE for Microsoft Windows 95. Adas strong type checking and package structure have significantly facilitated the development of the product.

The development of software in the Ada language for a mid-range hematology analyzer

“... an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which...(2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals... (3) intended to affect the structure or any function of the body of man or other animals.”

SIGAda 2001 workshop, "creating a symbiotic relationship between XML and Ada"

The purpose of the workshop was to organize the Ada community to take advantage of the opportunity to create Ada applications that are operating systems independent because they are based on a web technology, XML, Extensible Markup Language. The commercial use of the Internet is the driving force behind XML. Four elements of XML, which together are sufficient to build a web application, and all employ the same syntax were described. These are XML; its schema; the Extensible Stylesheet Language, XSL; and the XML mechanism for forms, XForms. XML concerns the data objects that are included on the web page and their order of presentation. The schema contains the information on the types and objects for XML. Schemas are roughly equivalent to an Ada specification without the subprograms.Fortunately, the programing language that has the best fit with XML is Ada. XML has visibility and scoping rules, which are similar to Ada. XML has strong typing and has single inheritance similar to Ada. A mutually beneficial symbiosis requires the creation of applications in Ada that use and support XML, as well as, the use of XML to create Ada environments including XML based tools. These applications include: automated translation of Ada data types and objects in a specification to an XML schema; and conversely, automated translation of the data types and elements in an XML Schema to an Ada specification.

SIGAda 99, workshop: how do we expedite the commercial use of Ada?

The focus of this Workshop, which occurred on October 20, 1999, was on extending the use of Ada into the commercial off-the-shelf (COTS) domain. The goal of this Workshop is to determine what should we do to both make Ada the dominant language for COTS and profit by doing so? The contents of Sections 2. Red Hat, Where the Money Went, a Case Summary and 3. How to Commercialize Ada and Profit have been updated.

Ada in embedded boards for scientific and medical instruments

1. ABSTRACT The combination of Adas new class-wide programming with tagged types, generics, and representation clauses for both enumerated and record types greatly facilitates low level programing. A generic board register class was extended to represent the specific hardware and provide high level abstractions for reading and changing the states of the hardware registers. Subprograms included in this generic board register class include functions and procedures which address these registers by name and employ high-level syntax for bit manipulation. The use of these objects derived from the register class permits the development of easily understood, maintainable software for computer boards which control and acquire data from devices including scientific and medical instruments. A software library providing these and other relevant functionalities and an application with a commercial 100 megahertz scaler board for a PC will be described.