Virtual histological staining of unlabeled autopsy tissue
Yuzhu Li Nir Pillar Jingxi Li Tairan Liu Di Wu Songyu Sun Guangdong Ma Kevin de Haan Luzhe Huang Sepehr Hamidi Anatoly Urisman Tal Keidar Haran William Dean Wallace Jonathan E. Zuckerman Aydogan Ozcan
Histological examination is a crucial step in an autopsy; however, the
traditional histochemical staining of post-mortem samples faces multiple
challenges, including the inferior staining quality due to autolysis caused by
delayed fixation of cadaver tissue, as well as the resource-intensive nature of
chemical staining procedures covering large tissue areas, which demand
substantial labor, cost, and time. These challenges can become more pronounced
during global health crises when the availability of histopathology services is
limited, resulting in further delays in tissue fixation and more severe
staining artifacts. Here, we report the first demonstration of virtual staining
of autopsy tissue and show that a trained neural network can rapidly transform
autofluorescence images of label-free autopsy tissue sections into brightfield
equivalent images that match hematoxylin and eosin (H&E) stained versions of
the same samples, eliminating autolysis-induced severe staining artifacts
inherent in traditional histochemical staining of autopsied tissue. Our virtual
H&E model was trained using >0.7 TB of image data and a data-efficient
collaboration scheme that integrates the virtual staining network with an image
registration network. The trained model effectively accentuated nuclear,
cytoplasmic and extracellular features in new autopsy tissue samples that
experienced severe autolysis, such as COVID-19 samples never seen before, where
the traditional histochemical staining failed to provide consistent staining
quality. This virtual autopsy staining technique can also be extended to
necrotic tissue, and can rapidly and cost-effectively generate artifact-free
H&E stains despite severe autolysis and cell death, also reducing labor, cost
and infrastructure requirements associated with the standard histochemical
staining.