1. 0 October 23, 2009 Formal Oral Presentation: FDA Hematology and Pathology Devices Panel of the Medical Devices Advisory Committee

2. Introduction We thank you for the opportunity to cooperate with and assist the FDA in its efforts. The adoption of whole slide imaging as a new medium to complement the microscope medium will lead to substantial opportunities for improved diagnosis and patient care through: Increased, Accelerated and Standardized Consultation Online collaboration (one reference slide available to all) Access to complete information (Patient Info, Dicom, Gross, WS etc.) Access to quantitative analysis Workflow securisation Process standardization Access to reference archives / side by side comparison Auditable for quality control (HIPAA) 1

3. Introduction to Aurora Interactive Aurora is committed to facilitating and contributing to better patient outcomes by enabling efficient digital communications tools for health care practitioners Operating since 2002 Hardware and Analysis vendor neutral Focused on pathology 2.0 Creator of Web-based image viewer software that allows for rapid and efficient cross-platform digital communications (content enrichment, sharing and collaboration) -“Pixel-for-pixel” images -Non-compressed images -Non-converted images (native formats) 2

4. Introduction to Aurora Interactive 3 Light Source Image Processing Software Dig. Image Sensor Imaging Optics Mechanical Scanner Remote Display Local Display Storage Web Transmission 010100010001000100100 SCANNER

5. Technical Discussion - Compression Lossy and Lossless compression within the scanner to a regulated maximum is suitable for visual qualitative analysis but not for algorithm based digital analysis. The eye fuses adjacent pixels on computer monitor 4 UNCOMPRESSED COMPRESSED Suitable for visual and algorithmic analysis Suitable for visual only PIXELS

6. Technical Discussion – Compound Compression Compound compression is undesirable because: Potential problem if different tiles are compressed using different parameters Incremental application of compression will likely introduce additional error in practice Can lead to the loss of valuable information (that may be, or become, critical to a patient’s diagnosis) or may introduce false information (artifacts) 5

7. Technical Discussion – Compression Recommendation 1.Lossy or lossless compression should be allowed during image acquisition at levels depending on the use of the image (i.e. a maximum acceptable for visual analysis and no compression for algorithmic analysis) 2.Compound compression should never be allowed. 6

8. Technical Discussion – Conversion Conversion includes:  Retiling  Alteration of the dynamic range 7

9. Technical Discussion – Conversion / Retiling In order to retile you must decompress the image, apply the retiling and recompress the image which a form of compound compression. Furthermore, you are likely to introduce artifacts at the edge of the tiles. Since you have increased the number of edges you increase the amount of artifacts introduced. 8

10. Technical Discussion – Conversion / Alteration of the dynamic range One form of conversion is the alteration of the dynamic range. If at anytime this conversion is operated, it cannot be reversed within the system. 9 Scanner NetworkStorageViewerMonitor

11. Technical Discussion – Conversion Recommendation Post scanning conversion should not be allowed to avoid the unnecessary risk of irreversible information loss and/or the introduction of false information (artifacts) resulting from improper conversion and/or re- compression of the scanned image 10

12. Technical Discussion – Other One problem identified yesterday was the use of the 8bit RGB color standard in the context of the limited dynamic range. A possible solution may be using YCC encoding where Y is the luminance. By granting it its dedicated channel this color space may be more suited for digital pathology. To our knowledge Z-stack solutions are available in the market. 11