THESIS
2022
1 online resource (xiv, 141 pages) : illustrations (some color)
Abstract
Histopathology remains the gold standard for surgical margin assessment. However,
routine pathological examination based on formalin-fixed and paraffin-embedded tissues is
laborious and time-consuming, failing to guide surgeons intraoperatively. Thus, rapid and high-resolution
imaging with minimal tissue preparation has long been a challenging and yet captivating
medical pursuit. In this thesis, we propose several imaging techniques that enable rapid, label-free,
and non-destructive imaging of freshly-excised and unprocessed tissues, holding great promise to
streamline the current practice of surgical pathology. Specifically, computational high-throughput
autofluorescence microscopy by pattern illumination (CHAMP) can bypass the resolution
constraint set by the system numerical aperture...[
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Histopathology remains the gold standard for surgical margin assessment. However,
routine pathological examination based on formalin-fixed and paraffin-embedded tissues is
laborious and time-consuming, failing to guide surgeons intraoperatively. Thus, rapid and high-resolution
imaging with minimal tissue preparation has long been a challenging and yet captivating
medical pursuit. In this thesis, we propose several imaging techniques that enable rapid, label-free,
and non-destructive imaging of freshly-excised and unprocessed tissues, holding great promise to
streamline the current practice of surgical pathology. Specifically, computational high-throughput
autofluorescence microscopy by pattern illumination (CHAMP) can bypass the resolution
constraint set by the system numerical aperture with the assistance of computational microscopy,
achieving high-throughput and label-free imaging of thick and unprocessed tissues at an imaging
speed of 1 mm
2/s with 1.1-μm lateral resolution. In addition, microscopy with ultraviolet single-plane
illumination (MUSI) further extends the system depth-of-field to ~200 μm with an improved
axial resolution of ~3 μm, achieving highly encouraging results in the diagnosis of different
subtypes of human lung adenocarcinomas. Furthermore, with the combination of block-face
imaging and serial microtome sectioning, the proposed microtomy-assisted autofluorescence
tomography (MATE) enables label-free three-dimensional (3D) imaging of paraffin-embedded
whole organs at an acquisition speed of 0.25 cm
3/s with a voxel resolution of 1.2 × 1.2 × 10 μm
3,
facilitating comprehensive pathological analysis to study the disease heterogeneity in 3D. Finally, wide-field fluorescence-based histological imaging with High-and-Low-frequency microscopy
(HiLo) can reveal highly-specific cellular contents at an unprecedented high acquisition speed of
5 cm
2/min, providing sufficient sampling of large-scale resection margins with a surface area of
dozens of square centimeters. In conclusion, in this thesis, we have proposed four promising and
transformative imaging techniques (i.e., CHAMP, MUSI, MATE, and HiLo) to revolutionize the
current practice of surgical pathology, greatly facilitating the clinical translations of modern optical
microscopy for biomedical imaging applications.
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