REPOSITORY
THE NICOLAUS COPERNICUS UNIVERSITY
IN TORUŃ
is an institutional repository of Nicolaus Copernicus University in Toruń. The task of the Repository is to promote scientific achievements and research conducted at NCU and to support teaching.
Recent Submissions
Wide-field quantitative micro-elastography of freshly excised human prostate
(Optica Publishing Group, 2025-06) Tamborski, Szymon; Skrok, Marta K.; Hepburn, Matt S.; Maniewski, Mateusz; Zdrenka, Marek; Kowalewski, Adam; Szylberg, Łukasz; Kennedy, Brendan F.
Prostate cancer is a significant global health issue. To advance diagnostic and treatment procedures, such as image-guided needle biopsy, optical imaging methods offering high spatial resolution have been proposed. Optical coherence tomography (OCT) allows for detailed visualization of prostate microarchitecture in three dimensions; however, it does not reliably differentiate tumors from surrounding healthy tissue. In this study, we use wide-field quantitative micro-elastography (QME) to image the micro-scale mechanical properties of freshly excised human prostate to provide additional contrast of tumor, which is known to exhibit increased stiffness. In our approach, we generate volumetric OCT, strain, and elasticity images over a field-of-view (x × y × z) of 46 × 46 × 1 mm3. We validate the contrast obtained in our images through co-registration with standard histology images.
Imaging of prostate micro-architecture using three-dimensional wide-field optical coherence tomography
(Optica Publishing Group, 2024) Skrok, Marta K.; Tamborski, Szymon; Hepburn, Matt S.; Fang, Qi; Maniewski, Mateusz; Zdrenka, Marek; Szkulmowski, Maciej; Kowalewski, Adam; Szylberg, Łukasz; Kennedy, Brendan F.
Prostate cancer is a global health issue that requires new diagnostic methods to provide accurate and precise visualization of prostate tissue on the micro-scale. Such methods have the potential to improve nerve-sparing surgery and to provide image guidance during prostate biopsy. In this feasibility study, we assess the potential of en face three-dimensional wide-field optical coherence tomography (OCT), covering a volumetric imaging field-of-view up to 46 × 46 × 1 mm3, to visualize micro-architecture in 18 freshly excised human prostate specimens. In each case, validation of contrast in OCT images is provided by co-registered wide-field histology images. Using this co-registration, we demonstrate that OCT can distinguish between healthy and cancerous glands at different stages, as well as visualize micro-architecture in the prostate, such as epineurium and perineurium in nerves and the tunica intima and tunica media in blood vessels.
A novel stress sensor enables accurate estimation of microscale tissue mechanics in quantitative micro-elastography
(AIP Publishing, 2024-09) Metzner, Kai L.; Fang, Qi; Sanderson, Rowan W.; Yeow, Yen L.; Green, Celia; Abdul-Aziz, Farah; Hamzah, Juliana; Mowla, Alireza; Kennedy, Brendan F.
Quantitative micro-elastography (QME) is a compression-based optical coherence elastography technique enabling the estimation of tissue mechanical properties on the micro-scale. QME utilizes a compliant layer as an optical stress sensor, placed between an imaging window and tissue, providing quantitative estimation of elasticity. However, the implementation of the layer is challenging and introduces
unpredictable friction conditions at the contact boundaries, deteriorating the accuracy and reliability of elasticity estimation. This has largely limited the use of QME to ex vivo studies and is a barrier to clinical translation. In this work, we present a novel implementation by affixing the stress sensing layer to the imaging window and optimizing the layer thickness, enhancing the practical use of QME for
in vivo applications by eliminating the requirement for manual placement of the layer, and significantly reducing variations in the friction conditions, leading to substantial improvement in the accuracy and repeatability of elasticity estimation. We performed a systematic validation of the integrated layer, demonstrating >30% improvement in sensitivity and the ability to provide mechanical contrast in a
mechanically heterogeneous phantom. In addition, we demonstrate the ability to obtain accurate estimation of elasticity (<6% error compared to <14% achieved using existing QME) in homogeneous phantoms with mechanical properties ranging from 40 to 130 kPa. Furthermore, we show the integrated layer to be more robust, exhibiting increased temporal stability, as well as improved conformity to
variations in sample surface topography, allowing for accurate estimation of elasticity over acquisition times 3 longer than current methods. Finally, when applied to ex vivo human breast tissue, we demonstrate the ability to distinguish between healthy and diseased tissue features, such as stroma and cancer, confirmed by co-registered histology, showcasing the potential for routine use in biomedical applications.
Full-field optical coherence microscopy enables high-resolution label-free imaging of the dynamics of live mouse oocytes and early embryos
(Springer Nature, 2024) Morawiec, Seweryn; Ajduk, Anna; Stremplewski, Patrycjusz; Kennedy, Brendan F.; Szkulmowski, Maciej
High quality label-free imaging of oocytes and early embryos is essential for accurate assessment of their developmental potential, a key element of assisted reproduction procedures. To achieve this goal, we propose full-field optical coherence microscopy (FF-OCM), constructed as a compact module fully integrated with a commercial wide-field fluorescence microscope. Our system achieves optical sectioning in wide-field, high in-plane resolution of 0.5 µm, and high sensitivity to backscattered light. To demonstrate its imaging capabilities, we study live mouse oocytes and embryos at all important stages of meiotic maturation and early embryogenesis. Our system enables visualization of intracellular structures, which are not visible in common bright-field microscopy, i.e., internal structure of nuclear apparatus, cytoskeletal filaments, cellular cortex, cytoplasmic protrusions, or zona pellucida features. Additionally, we visualize and quantify intracellular dynamics like cytoplasmic stirring motion, nuclear envelope fluctuations and nucleolus mobility. Altogether, we demonstrate that FF-OCM is a powerful tool for research in developmental biology that also holds great potential for non-invasive time-lapse monitoring of oocyte and embryo quality in assisted reproduction.
Multimodal mechano-microscopy reveals mechanical phenotypes of breast cancer spheroids in three dimensions
(AIP Publishing, 2024-09) Mowla, Alireza; Hepburn, Matt S.; Li, Jiayue; Vahala, Danielle; Amos, Sebastian E.; Hirvonen, Liisa M.; Sanderson, Rowan W.; Wijesinghe, Philip; Maher, Samuel; Choi, Yu Suk; Kennedy, Brendan F.
Cancer cell invasion relies on an equilibrium between cell deformability and the biophysical constraints imposed by the extracellular matrix (ECM). However, there is little consensus on the nature of the local biomechanical alterations in cancer cell dissemination in the context of three-dimensional (3D) tumor microenvironments (TMEs). While the shortcomings of two-dimensional (2D) models in replicating in situ cell behavior are well known, 3D TME models remain underutilized because contemporary mechanical quantification tools are limited to surface measurements. Here, we overcome this major challenge by quantifying local mechanics of cancer cell spheroids in 3D TMEs. We achieve this using multimodal mechano-microscopy, integrating optical coherence microscopy-based elasticity imaging with confocal fluorescence microscopy. We observe that non-metastatic cancer spheroids show no invasion while showing increased peripheral cell elasticity in both stiff and soft environments. Metastatic cancer spheroids, however, show ECM-mediated softening in a stiff microenvironment and, in a soft environment, initiate cell invasion with peripheral softening associated with early metastatic dissemination. This exemplar of live-cell 3D mechanotyping supports that invasion increases cell deformability in a 3D context, illustrating the power of multimodal mechano-microscopy for quantitative mechanobiology in situ.