Challenges are emerging with regard to the pre-clinical, regulatory assessment of display systems used for viewing and interpreting medical images. This article discusses those, and also the types of evidence that might be relevant to the evaluation of mobile image-viewing devices, true-color devices with applications in digital microscopy, and 3-D medical displays as discussed in Part 1.
by Aldo Badano, Wei-Chung Cheng, Brendan J. O'Leary, and Kyle J. Myers
DISPLAY SYSTEMS are important elements of imaging systems. They represent the last component in the chain that readers (radiologists, physicians, or technicians) use to make a determination regarding a patient's condition based on imaging data. In this context, a display system consists of all the hardware and software that determine the quality of the luminance output in the screen for a given image, including pre-processing operations on the data, the environment in which the device is operated, and device-user interactions.
Since the introduction of digital technologies for the image capture, processing, archiving, and transmission of medical images, display systems have been evolving technologically from bulky cathode-ray tubes with mono-chrome screens and poor spatial resolution to the current generation of liquid-crystal displays (LCDs) with increased image contrast and sharpness. This technological revolution has required the medical imaging community, including regulators, to adopt new assessment methodologies.
First, there is a need to characterize display image-quality issues that emerging technologies bring to the fore. In addition, it is occasionally useful to remove particular testing procedures because they have become obsolete due to technological advances. Today, we are seeing the transition from analog to digital in many areas of medicine, including tissue microscopy, pathology, and visible light-imaging modalities such as colposcopy (a gynecological diagnostic procedure). Medical displays need to be capable of providing stable and reproducible image quality that is appropriate for the application. For a display device to be marketed in the U.S. as part of a medical device, the manufacturer (or sponsor) needs to secure the FDA's approval or clearance. The regulatory pathways for medical display systems, briefly summarized in the following section, aim to promote public health and innovation by providing practical approaches for demonstrating safety and effectiveness.
Regulatory efforts are concentrated in two areas: pre-market and post-market. Pre-market refers to new products and technologies that have not yet been commercialized, for which evidence is gathered in support of a sponsor submission. The post-market area refers to issues that arise from the usage of the device after introduction into the market. In this article, we focus our analysis on pre-market topics since they relate to the introduction of new technologies.
The safety and effectiveness criteria for medical display systems are based on the clinical performance of the device and the potential for misdiagnosis due to pitfalls in the device design. Generally speaking, a device can be defined as safe if its use does not cause illness or injury. In terms of display performance, an effectiveness concern could be the use of a device that does not convey the image data to the user in a proper way due to, for instance, additional spatial noise resulting from variations in pixel gains or unwanted reflections of ambient light that mask lesions and significantly affect the outcome of the diagnostic test.
The FDA uses a three-tier classification system to categorize medical devices based on risk. Devices are classified as Class I, II, or III, from lowest to highest risk, with the class level determining the degree of regulatory oversight required. Currently, stand-alone display systems (referred to as "accessories" to complete imaging systems) fall under Class II based on moderate risk. For these systems, established testing methods provide adequate evidence of risk mitigation. These devices typically require 510(k) pre-market notification prior to marketing based on device-specific requirements described in Refs. 1 and 2.
This article describes the current challenges faced by both industry and regulators in the pre-clinical assessment of medical imaging display devices. In this context, it may be useful to provide a technical framework for future guidelines or guidance documents. From the perspective of the regulatory evaluation of displays, there is sometimes a trade-off between the need for sufficient evidence that allows performance comparisons with previously cleared devices already in the marketplace and the need of to establish additional benchmarks for next-generation devices designed to improve performance in areas where current devices are weak.
Efforts to document pre-clinical performance serve two purposes. First, comprehensive and appropriate pre-clinical testing of devices can minimize the need for more burdensome clinical evidence in support of the sponsor's claim. Second, the pre-clinical evidence sets quantifiable and reproducible performance levels that are benchmarks for new technology. A discussion of the least-burdensome requirements for regulatory review has to be framed by an analysis of the relevance of each test with respect to the clinical tasks to be performed with the device.
Evidence Supporting a Submission
It is useful to define three types of pre-clinical evidence to be considered while evaluating medical display devices: (a) description of the hardware components of the display system, (b) pre-clinical performance tests that relate to the quality of the image display, and (c) supplemental characterization tests. Supplemental information on physical characteristics can be used to provide additional evidence in support of a particular display feature or to minimize the need for more comprehensive clinical evidence.
Technological Characteristics of the Display System. The list provided in this section might serve as a template for the description of the software and hardware components of the display system. Some technological descriptors of the display device (e.g., an LCD panel with a TFT active-matrix array with fluorescent backlight) are also included to facilitate comparisons with previously cleared devices. Some of these components might not be present in all medical display products.
The most relevant characteristics to describe include:
• Technology: Description of the technological characteristics of the display device (e.g., LCD panel with TFT active-matrix array with fluorescent backlight).
• Screen size: Physical size of the viewable area in diagonal and aspect ratio.
• Emissive phosphor type (CRT only): Description of the type of cathodo-luminescent phosphor material used in the cathode-ray tube (CRT) and its principal characteristics if not a known phosphor.
• Backlight type (transmissive displays only): Detailed description of the backlight type and, if substantially different from predicate devices, main properties including temporal and spectral characterization.
• Pixel array, pitch, subpixel pattern: Description of the pixel array including pixel size, pixel pitch, and subpixel pattern (e.g., chevron, RGBW).
• Subpixel driving (spatial and temporal dithering): Are the subpixels used to improve gray-scale or temporal resolution?
• Video bandwidth: Capabilities of the information transfer pipeline between the image source and the digital driving levels in all associated components including the CPU, the GPU, and the connectors.
• On-screen user controls: Control knobs available for end users that relate to the display image quality (brightness and contrast controls, power saving options, etc.).
• Ambient light sensing: Method, instrumentation, and software tool description.
• Touch-screen technology: Method and functionality. Does it require calibration and periodic re-tuning?
• Luminance calibration tools: Description of the sensor hardware and associated software for performing luminance calibration. This also includes, if applicable, details about the user-level procedures, service-action tolerances, and centralized automatic calibration tools.
• Quality-control procedures: Frequency and nature of quality-control tests to be performed by the user and/or the hospital physicist with associated action limits. A detailed QC manual should be included for regulatory review.
Pre-Clinical Tests: This section presents a list of pre-clinical, or physical, measurements useful for defining the performance character-istics of a medical display product. For all of these tests, there exist several methodologies that have been described in the literature, in professional guidelines3 and recommendations,4 or in standards.5 The most relevant pre-clinical tests include:
• Maximum and minimum luminance (achievable and recommended): Measurements of the maximum and minimum luminance that the device outputs as used in the application under recommended conditions and the achievable values if the device is set to expand the range to the limit.
• Gray-scale resolution: Technique to convert image values to digital driving levels for achieving some degree of control over the transformation and measurements of the obtained 256 gray-scale resolution.
• Conformance to a gray-scale function (e.g., DICOM GSDF): Measurements of the intrinsic and calibrated mapping between image values and the luminance output following a target model response.
• Luminance at 30° and 45° in diagonal, horizontal, and vertical directions at center and edge spots: Measurements of the luminance response at off-normal viewing related to the target model for the luminance response.
• Geometrical distortion: Measurements of the geometrical distortion introduced by the display device.
• Luminance uniformity or Mura test: Measurements of the uniformity of the luminance across the display screen.
• Bidirectional reflection distribution function: Measurements of the reflection coefficients of the display device. Specular and diffuse coefficients can be used as surrogates for the full bidirectional reflection distribution function.
• Pixel fill factor: Measurements of the active pixel area typically referred to as the pixel fill factor. Since fill factor might vary with luminance, data at several points in the luminance range are indicated. Small fill factors add an unwanted, deterministic pattern to the image.
• Pixel defects (count and map): Measurements (counts) and location of pixel defects. This is typically provided as a tolerance limit. Pixel defects can interfere with the visibility of small details in medical images.
• Veiling glare or small-spot contrast: Measurements of the contrast obtained for small targets.
• Chromaticity at 5, 50, and 95% of maximum luminance and its variation across the screen or within screens for 205 multi-head displays: Measurements of the color at different luminance levels as indicated (at minimum) by the color coordinates in an appropriate units system (u'v', CIELAB) and its variability across points in the screen.
• Spatial resolution: Measurements of the transfer of information from the image data to the luminance fields at different spatial frequencies of interest or by reporting the modulation transfer function. Non-isotropic resolution properties need to be characterized properly by providing two-dimensional measurements or measurements along two axes.
• Spatial noise: Measurements of the spatial noise level as represented by the noise power spectrum using an appropriate ratio of camera and display pixels. Spatial noise and resolution (see previous item) affect the way images are presented to the viewer and can alter features that are relevant to the interpretation process of the physician or radiologist.
• Frame rate and temporal/spatial backlight modulation techniques: Measurements of the temporal and spatial modulation of the backlight component.
• Rise and fall time constants for 5–95% and 40–60% luminance transitions: Measurements of the temporal behavior of the display in responding to changes in image values from frame to frame. Since these transitions are typically not symmetric, rise and fall time constants are needed to characterize the system. Slow displays can alter details and contrast of the image when large image stacks are browsed or in video mode.
• Stability of luminance response with temperature and lifetime: Measurements of the change in luminance response with temperature and use time for a subset of the measured data in previous items.
Table 1 presents a general summary of how these tests might apply to products under different categories.
The table also includes a tentative list of pre-clinical tests that might be used in support of novel application areas such as three-dimensional breast imaging, true-color modalities, and mobile displays, which are reviewed in the companion article in this issue ofInformation Display.
Displays are integral parts of medical imaging systems. Their assessment and characterization need to balance the impact on public health with practical and meaningful approaches to demonstrate their safety and effectiveness. Creating an assessment framework upfront is especially important as displays continue to evolve extremely rapidly.
The mention of commercial products herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. This is a contribution of the Food and Drug Administration and is not subject to copyright.
1Guidance for the Submission of Premarket Notifications for Medical Image Management Devices, Tech. Rep. (November 2000);http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm073720.htm
2Guidance for Industry and FDA Staff: Class II Special Controls Guidance Document: Full Field Digital Mammography System, Technical Report (November 2010);http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm107552.htm
3E. Siegel, E. Krupinski, E. Samei, M. Flynn, K. Andriole, B. Erickson, J. Thomas, A. Badano, J. A. Seibert, and E. D. Pisano, "Digital mammography image quality: image display," J. Am. Coll. Radiol. 3 (8), 615–627 (2006).
4E. Samei, A. Badano, D. Chakraborty, K. Compton, C. Cornelius, K. Corrigan, M. J. Flynn, B. Hemminger, N. Hangiandreou, J. Johnson, M. Moxley, W. Pavlicek, H. Roehrig, L. Rutz, J. Shepard, R. Uzenoff, J. Wang, and C. Willis, "Assessment of display performance for medical imaging systems," Draft Report of the American Association of Physicists in Medicine (AAPM) Task Group 18, Technical Report, AAPM (October 2002).
5International Electrotechnical Commission, IEC62563-1. Medical electrical equipment - Medical image display systems – Part 1: Evaluation methods. •