Abstract
Kidneys, like other organs, have an inherent capacity to recover from acute injury; however, severe or
recurrent injury can result in chronic kidney disease (CKD), the sequelae of which result in 82,000 deaths
annually in the US alone. Regardless of the etiology of the initial injury, the common final pathway leading to-
end stage renal disease is closely connected to fibrosis (excess or aberrant collagen distribution), one of the
most important determinants of renal disease severity and prognosis. Histology is the gold standard for
evaluation, typically using histochemical stains such as trichrome and PAS that highlight the presence of
collagens and basement membrane, respectively. Nevertheless, these stains are not completely specific, can
be technically challenging to perform well and reproducibly, and thus contribute to interobserver variability and
a concomitant decrease in diagnostic precision. Moreover, they also require the preparation of extra slides and
additional staining procedures, and thus increase cost and can prolong the diagnostic process.
We propose to optimize, deploy, and test a new kind of microscope, DUET (DUal mode Emission and
Transmission microscopy), developed at UC Davis, that will be a low-cost and very rapid solution for detection
and digital characterization of the presence and distribution of collagen and other macromolecules, directly
from standard formalin-fixed, paraffin-embedded hematoxylin and eosin-stained slides. Specifically, we will
finalize the design of the hardware and software components of the instrument itself, validate imaging
performance against standard histology and immunohistochemical stains for collagen and other components,
and with the assistance of scientists at our partnering institutions (John Hopkins University and University of
Buffalo) develop robust tools for analysis and quantitation of fibrosis. DUET instrument hardware will be shared
with JHU to ensure that the methods are technically reproducible across multiple sites.
The application leverages the expertise across three institutions in optics, biomedical engineering, renal
pathology and novel artificial intelligence approaches. The goal of the project is development and validation of
DUET, which promises to be a robust, inexpensive, and practical approach for the rapid and accurate
evaluation of fibrosis, extensible to other renal pathologies, and indeed across other organs systems, with
significant positive impact on disease research, clinical practice, and patient outcomes.