Title:
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Whole slide analysis, intelligent search and integromics in digital pathology
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Digital pathology is now underpinning biomarker and drug discovery, clinical diagnosis
via companion diagnostics and provides valuable tools for the current move towards
providing personal stratified medicine. The potential digital pathology has for giving better
insight into many disease mechanisms is due to firstly it's digital (and therefore
linkable/indexable) nature, and secondly the sheer amount of data that can now be
generated by imaging hardware and image analysis methodologies. The work carried out in
this thesis was an examination of the current barriers to verifying and exploiting the large
amounts of information that is available via the use of digital pathology.
The large size of whole slide images generated in digital pathology means that lossy
image compression becomes a necessity due to storage limitations. Lossy image
compression however discards data in a non-linear transformation, e.g. JPEG image
compression, and therefore changes the values of pixels in the images. As image analysis
algorithms use these values to perform quantification and segmentation of regions within
the image, the first piece of this thesis examines the affect image compression has on
fundamental image calculations common in image analysis algorithms.
Tissue imagery data is complex but the' visual pathological information provided is the
basis of clinical diagnosis. These patterns are currently used to show the symptoms of
disease. This thesis details a system that can make this information easily searchable
using these patterns as the input criterion for the search. A system that may highlight tissue
with specific malignant morphological properties could clearly provide a valuable resource in
large clinical trials where manual analysis of specimens requires many work hours.
The imaging information provided by digital pathology is not independent from other
experimental and clinical data and the final piece of this thesis provides a framework for
connecting clinico-pathological, genetic and imaging information in an attempt to provide a
much more detailed and connected view of related diseases. This work highlights the
considerations necessary in designing studies employing image analysis and underpins the
future importance of digital pathology applications in modern tissue-based translational
research.
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