Computerized screening devices and performance assessment: development of a policy towards automation. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The extension of automation to the diagnostic assessment of clinical materials raises issues of professional responsibility, on the part of both the medical professional and designer of the device. The International Academy of Cytology (IAC) and other professional cytology societies should develop a policy towards automation in the diagnostic assessment of clinical cytologic materials. CONSENSUS POSITION: The following summarizes the discussion of the initial position statement at the International Expert Conference on Diagnostic Cytology Towards the 21st Century, Hawaii, June 1997. 1. The professional in charge of a clinical cytopathology laboratory continues to bear the ultimate medical responsibility for diagnostic decisions made at the facility, whether automated devices are involved or not. 2. The introduction of automated procedures into clinical cytology should under no circumstances lead to a lowering of standards of performance. A prime objective of any guidelines should be to ensure that an automated procedure, in principle, does not expose any patient to new risks, nor should it increase already-existing, inherent risks. 3. Automated devices should provide capabilities for the medical professional to conduct periodic tests of the appropriate performance of the device. 4. Supervisory personnel should continue visual quality control screening of a certain percentage of slides dismissed at primary screening as within normal limits (WNL), even when automated procedures are employed in the laboratory. 5. Specifications for the design of primary screening devices for the detection of cervical cancer issued by the IAC in 1984 were reaffirmed. 6. The setting of numeric performance criteria is the proper charge of regulatory agencies, which also have the power of enforcement. 7. Human expert verification of results represents the "gold standard" at this time. Performance characteristics of computerized cytology devices should be determined by adherence to defined and well-considered protocols. Manufacturers should not claim a new standard of care; this is the responsibility of the medical community and professional groups. 8. Cytology professionals should support the development of procedures that bring about an improvement in diagnostic decision making. Advances in technology should be adopted if they can help solve problems in clinical cytology. The introduction of automated procedures into diagnostic decision making should take place strictly under the supervision and with the active participation and critical evaluation by the professional cytology community. ONGOING ISSUES: Guidelines should be developed for the communication of technical information about the performance of automated screening devices by the IAC to governmental agencies and national societies. Also, guidelines are necessary for the official communication of IAC concerns to industry, medicolegal entities and the media. Procedures and guidelines for the evaluation of studies pertaining to the performance of automated devices, performance metrics and definitions for evaluation criteria should be established.

Digital imagery/telecytology. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Optical digital imaging and its related technologies have applications in cytopathology that encompass training and education, image analysis, diagnosis, report documentation and archiving, and telecommunications. Telecytology involves the use of telecommunications to transmit cytology images for the purposes of diagnosis, consultation or education. This working paper provides a mainly informational overview of optical digital imaging and summarizes current technologic resources and applications and some of the ethical and legal implications of the use of these new technologies in cytopathology. CONSENSUS POSITION: Computer hardware standards for optical digital imagery will continue to be driven mainly by commercial interests and nonmedical imperatives, but professional organizations can play a valuable role in developing recommendations or standards for digital image sampling, documentation, archiving, authenticity safeguards and teleconsultation protocols; in addressing patient confidentiality and ethical, legal and informed consent issues; and in providing support for quality assurance and standardization of digital image-based testing. There is some evidence that high levels of accuracy for telepathology diagnosis can be achieved using existing dynamic systems, which may also be applicable to telecytology consultation. Static systems for both telepathology and telecytology, which have the advantage of considerably lower cost, appear to have lower levels of accuracy. Laboratories that maintain digital image databases should adopt practices and protocols that ensure patient confidentiality. Individuals participating in telecommunication of digital images for diagnosis should be properly qualified, meet licensing requirements and use procedures that protect patient confidentiality. Such individuals should be cognizant of the limitations of the technology and employ quality assurance practices that ensure the validity and accuracy of each consultation. Even in an informal teleconsultation setting one should define the extent of participation and be mindful of potential malpractice liability. ONGOING ISSUES: Digital imagery applications will continue to present new opportunities and challenges. Position papers such as this are directed toward assisting the profession to stay informed and in control of these applications in the laboratory. Telecytology is an area in particular need of studies of good quality to provide data on factors affecting accuracy. New technologic approaches to addressing the issue of selective sampling in static image consultation are needed. The use of artificial intelligence software as an adjunct to enhance the accuracy and reproducibility of cytologic diagnosis of digital images in routine and consultation settings deserves to be pursued. Other telecytology-related issues that require clarification and the adoption of workable guidelines include interstate licensure and protocols to define malpractice liability.

Quantitative DNA ploidy analysis of breast carcinoma: a study of the effects of joint photographer experts group (JPEG) compression on DNA ploidy images.

Telepathology usage in the past has typically been a qualitative procedure rather than a quantitative measurement. DNA ploidy using image analysis has been favorably compared to DNA ploidy analysis by flow cytometry in numerous publications. A step from DNA ploidy analysis using conventional image analysis to DNA ploidy analysis using stored images allows DNA ploidy analysis by image cytometry to become a powerful tool in telepathology. Remote DNA ploidy analysis using stored images has an impact on the field of pathology, as not every hospital or laboratory can afford to perform this type of specialized testing. However, images have large data files and require lengthy transmission times over communication systems to other computers. Joint Photographer Experts Group (JPEG) compression is a computer algorithm that allows the file size of an image to be reduced in order to decrease transmission times to another computer. A study was initiated to investigate the effects of JPEG compression on images of Feulgen stained breast tumor touch preps and the resulting DNA ploidy histograms.

Telepathology: frozen section diagnosis at a distance.

Telepathology may be used to provide a frozen section service to hospitals without a department or institute of pathology. We have developed a telepathology system using the commercially available Integrated Services Digital Network (ISDN). The main software and hardware elements of our system are: Apple Macintosh workstations, a program for simultaneous transfer of image, voice and data, and a data bank for storage of patients' data and microscopic images. A picture instrument manager (PIM) makes remote control of microscopes or other instruments possible. The system connects the Department of Pathology of the University of Basel with the Regional Hospital of Samedan, 250 km away, and the Regional Hospital of Burgdorf, 100 km away. During a period of 20 months, frozen sections with the hospitals in Samedan and Burgdorf were performed in 53 patients. Between 54 and 58 s were required for the transfer of a diagnostic 8-bit grey level image containing 341 +/- 26.1 (standard error) kbytes (n = 13) or a diagnostic 24-bit colour image containing 165 +/- 16.9 kbytes (n = 40). Frozen section diagnosis was completed in 20-40 min. True-positive diagnoses of malignant tumours were achieved in 85.7% of cases (sensitivity = 0.857). No false-positive diagnosis was made. In 3 of the 53 cases telepathological diagnosis was not possible for technical reasons.

Quantitative DNA analysis: a comparison of conventional DNA ploidy analysis and teleploidy.

JPEG compression can be used on images for DNA ploidy analysis if careful consideration is given to the level of compression used for file storage. The amount of JPEG compression possible may vary depending on the type of tissue analyzed, however, a compromise may be reached for all types of tissue. JPEG compression should not go over a level of 70 for DNA analysis as this would result in possibly erroneous IOD calculation and erroneous DNA ploidy analysis. Also, the resulting file quality is so poor that even visual analysis is not possible. With careful training of personnel in cell selection, remote DNA ploidy analysis would be an effective tool for standardization and quality control in the pathology laboratory. By using remote DNA ploidy analysis, it is possible for hospitals to consolidate their workload, and make DNA ploidy analysis by image cytometry a cost effective test in the laboratory. Proficiency testing would also become possible as all laboratories performing DNA ploidy analysis would receive the same fields of view for testing. DNA ploidy analysis by image cytometry using stored images could be a versatile tool for the telepathology community.

Non-distorted assemblage of the digital images of adjacent fields in histological sections.

In the following article a method is described for the distortion-free reassemblage of adjacent digitised microscopic images of histological sections. The correct positioning of the microscopic specimen is achieved via a computer-controlled scanning stage. During an internal calibration step the correction function for the image distortions and the parameters of the transformation scanning-stage-to image-coordinate system are determined. In the subsequent application phase the new positions the scanning stage has to move to can now be computed in such a way that the distortion-corrected digitised images of the section parts under consideration neatly fit together to one composite image.

Segmentation of microscopic cell scenes.

Different methods for the automated segmentation of microscopic cell scenes are presented with examples. The techniques discussed include edge detection by thresholding, "blob" detection by split-and-merge algorithm, global thresholding using gray-level histograms, hierarchic thresholding using color information, global thresholding using two-dimensional histograms and segmentation by "blob" labeling. Methods are more robust against insignificant changes in the scene and perform more reliably as more a priori knowledge about the scene is incorporated in the segmentation algorithm. The inclusion of both photometric and geometric a priori knowledge can result in a high level of correct segmentations, the cost of which is increased computation time.

Measurement of the optical thickness of transparent tissue layers.

The method of Duc de Chaulnes was employed to determine the mechanical and optical thickness, as well as the refractive index, of transparent tissue layers in living specimens. To this end the reproducible accuracy of the method and its dependence on the adjustment in focusing and on the numerical aperture of the objective was evaluated on test specimens using the procedures of transmitted light, phase-contrast (PC), and differential interference contrast (DIC) microscopy. The best working conditions were then applied to the actual measurements.

Analysis of the wall permeability of blood vessels in the rat mesentery.

The transport of fluorescent tracer molecules of various molecular weights (MW 340-300,000) within the blood vessels and through the vessel walls into the perivascular tissue of the rat mesentery was studied microscopically. Using a highly sensitive TV-tube the fluorescence intensities were transformed into video signals and recorded for subsequent analysis. The results show that small molecules, such as the water-soluble dye fluorescein-sodium ( F1Na ) (MW 340) can pass through the wall of all blood vessels with minimal delay, whereas the passage of large molecules, such as the serum proteins (MW greater than 60,000), depends very strongly on the diameter of the vessels and on the medium in which the mesentery is embedded during the observation. In this respect, no difference was registered between vessels of the arterial and of the venous part of the microcirculation. The large serum protein molecules moved through the blood vessel walls at specific leakage points. The small dye molecules, however, traversed the wall uniformly along the entire length of the blood vessel. The small-molecule behavior could be described by a passive diffusion model with a cylindrical diffusion source.