Longitudinal characterisation of the tumour vascular response to radiotherapy is essential for understanding the role of oxygenation and microvascular disruption in response to therapy. Using multi-scale in vivo photoacoustic imaging (PAI), we assessed early response to two hypofractionated radiotherapy schemes in two human breast cancer models. Mesoscopic and multispectral tomographic photoacoustic imaging was performed 24h pre-, post-radiotherapy, and at endpoint. PAI biomarkers were validated ex vivo with multiplex immunofluorescence using a 20-plex panel developed specifically for vascular response assessment at sub-cellular resolution. PAI captured radiotherapy response, revealing the differential effect between radiotherapy schemes and models with different hypoxia phenotypes.
Longitudinal mesoscopic photoacoustic imaging of vascular networks requires accurate image co-registration to assess local changes in growing tumours, but remains challenging due to sparsity of data and scan-to-scan variability. Here, we compared a set of 5 curated co-registration methods applied to 49 pairs of vascular images of mouse ears and breast cancer xenografts. Images were segmented using a generative adversarial network and pairs of images and/or segmentations were fed into the 5 tested algorithms. We show the feasibility of co-registering vascular networks accurately using a range of quality metrics, taking a step towards longitudinal characterization of those complex structures.
Breast cancer and Glioblastoma brain cancer are aggressive malignancies with poor prognosis. In this study primary Glioblastoma and secondary breast cancer spheroids are formed and treated with the well-known Temozolomide and Doxorubicin chemotherapeutics, respectively. A custom multi-angle Light Sheet Fluorescence Microscope is employed for high resolution imaging of both cancer cell spheroids. Such a technique is successful in realizing pre-clinical drug screening, while enables the discrimination among physiologic tumor parameters. LSFM technique, parameters and method followed are also presented.
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