The development and validation of the Virtual Tissue Matrix, a software application that facilitates the review of tissue microarrays on line.
BACKGROUND
The Tissue Microarray (TMA) facilitates high-throughput analysis of hundreds of tissue specimens simultaneously. However, bottlenecks in the storage and manipulation of the data generated from TMA reviews have become apparent. A number of software applications have been developed to assist in image and data management; however no solution currently facilitates the easy online review, scoring and subsequent storage of images and data associated with TMA experimentation.


RESULTS
This paper describes the design, development and validation of the Virtual Tissue Matrix (VTM). Through an intuitive HTML driven user interface, the VTM provides digital/virtual slide based images of each TMA core and a means to record observations on each TMA spot. Data generated from a TMA review is stored in an associated relational database, which facilitates the use of flexible scoring forms. The system allows multiple users to record their interpretation of each TMA spot for any parameters assessed. Images generated for the VTM were captured using a standard background lighting intensity and corrective algorithms were applied to each image to eliminate any background lighting hue inconsistencies or vignetting. Validation of the VTM involved examination of inter-and intra-observer variability between microscope and digital TMA reviews. Six bladder TMAs were immunohistochemically stained for E-Cadherin, beta-Catenin and PhosphoMet and were assessed by two reviewers for the amount of core and tumour present, the amount and intensity of membrane, cytoplasmic and nuclear staining.


CONCLUSIONS
Results show that digital VTM images are representative of the original tissue viewed with a microscope. There were equivalent levels of inter-and intra-observer agreement for five out of the eight parameters assessed. Results also suggest that digital reviews may correct potential problems experienced when reviewing TMAs using a microscope, for example, removal of background lighting variance and tint, and potential disorientation of the reviewer, which may have resulted in the discrepancies evident in the remaining three parameters.
Conway
Catherine M
CM
Medical Informatics Group, School of Biotechnology, Dublin City University, Dublin, Ireland. catherine.conway3@mail.dcu.ie
O'Shea
Deirdre
D
O'Brien
Sallyann
S
Lawler
Darragh K
DK
Dodrill
Graham D
GD
O'Grady
Anthony
A
Barrett
Helen
H
Gulmann
Christian
C
O'Driscoll
Lorraine
L
Gallagher
William M
WM
Kay
Elaine W
EW
O'Shea
Daniel G
DG
D000465:Algorithms; D019544:Equipment Failure Analysis / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D009862:Online Systems; D011786:Quality Control; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012984:Software; D012985:Software Design; D012986:Software Validation; D046888:Tissue Array Analysis / Q000295:instrumentation* / Q000379:methods*; D014584:User-Computer Interface