Image microarrays (IMA): Digital pathology's missing tool

Abstract

Introduction: The increasing availability of whole slide imaging (WSI) data sets (digital slides) from glass slides offers new opportunities for the development of computer-aided diagnostic (CAD) algorithms. With the all-digital pathology workflow that these data sets will enable in the near future, literally millions of digital slides will be generated and stored. Consequently, the field in general and pathologists, specifically, will need tools to help extract actionable information from this new and vast collective repository.

Methods: To address this limitation, we designed and implemented a tool (dCORE) to enable the systematic capture of image tiles with constrained size and resolution that contain desired histopathologic features.

Results: In this communication, we describe a user-friendly tool that will enable pathologists to mine digital slides archives to create image microarrays (IMAs). IMAs are to digital slides as tissue microarrays (TMAs) are to cell blocks. Thus, a single digital slide could be transformed into an array of hundreds to thousands of high quality digital images, with each containing key diagnostic morphologies and appropriate controls. Current manual digital image cut-and-paste methods that allow for the creation of a grid of images (such as an IMA) of matching resolutions are tedious.

Conclusion: The ability to create IMAs representing hundreds to thousands of vetted morphologic features has numerous applications in education, proficiency testing, consensus case review, and research. Lastly, in a manner analogous to the way conventional TMA technology has significantly accelerated in situ studies of tissue specimens use of IMAs has similar potential to significantly accelerate CAD algorithm development.

Keywords: IMA; SIVQ; TMA; WSI.

Figure 1

Screen capture of the IMA tool: Depicted is a representative screen capture of the user interface of the IMA tool. Files are loaded in the directory in the left hand panel. The matrix of cells in the middle represents the array. Images are loaded into the array by clicking on the file name in the directory, followed by clicking on the desired cell. The top and right-hand columns are where labels can be included.

Figure 2

Screen capture of the dCORE tool: Depicted is a representative screen capture of the dCORE user interface. Images are loaded into the directory in the center right. Images can be panned using the upper left viewing window. Features can be cropped by altering the size of the viewing window. Clicking on the “save picture” button on the right hand panel saves the image displayed in the viewing window

Figure 3

Malignant pleural effusion of a patient with lung adenocarcinoma. A cell block of a pleural effusion from a patient with metastatic lung adenocarcinoma was stained with H and E. Multiple images representative of different fields of view were taken using the camera on the Arcturus XT^™ LCM stage. The slide was not coverslipped and was coated with xylene. The images were then “autocorrected” using Microsoft Picture Manager. dCORE was used to capture representative malignant and benign features, which were then loaded into IMA to create the image array shown here.

Figure 4

SIVQ analysis of the pleural effusion IMA. The top panel was loaded into SIVQ. A vector was selected from a tumor cell and was then used to search the image. A heatmap corresponding to the quality of matches is displayed in the lower panel.

Figure 5

An IMA was created from the University of Michigan, Department of Pathology WSI library: Various tumors were used to create this digital slide IMA

Figure 6

A representative “key” to the IMA in Figure 5: The IMA tool has a feature that will export the file names of the images from the corresponding IMA, thus creating an Excel file which serves as a key to the IMA.

Figure 7

Prostate IMA: A digital slide of a prostate cancer tissue section was used by dCORE to capture various malignant and benign morphologic features, as described in the right hand column of the text. Various magnifications were taken of these features, displayed in the top row of the text