Detecting metastatic potential of cancer through longitudinal vasculature imaging of biomaterial scaffold using non-invasive in vivo photoacoustic microscopy and optical coherence tomography.

Abstract

Metastasis represents a stage in which the therapeutic objective changes from curing disease to prolonging survival, as detection typically occurs at advanced stages. Technologies for the early identification of disease would enable treatment at a lower disease burden and heterogeneity. Herein, we investigate the vascular dynamics within a synthetic metastatic niche as a potential marker of disease progression. Methods: The synthetic metastatic niche consists of a biomaterial scaffold implanted subcutaneously, which supports the formation of a vascularized tissue that recruits immune cells due to the foreign body response that then leads to tumor cell recruitment. This defined site is analyzed with multi-modal imaging techniques, including photoacoustic microscopy (PAM) and optical coherence tomography (OCT), to monitor the changes in vasculature of the niche as a measure of metastatic progression. We investigated angiogenesis for three triple-negative breast cancer models (4T1, 4T07, and 67NR cell lines) with distinct metastatic capabilities. Results: Longitudinal imaging with PAM and OCT offered high-resolution, 3D views of vascular morphology, revealing accelerated and disorganized vascular reorganization with metastases, in contrast to the stable vessels observed in the control and non-metastatic model. Quantitative image analysis of vascular parameters, such as vessel area density, vessel mean tortuosity, and total vessel length substantiated these observations, with significant differences in vascular metrics emerging as early as 8 days post tumor-inoculation in metastatic models. Conclusions: This study identifies the potential for longitudinal monitoring of vascular remodeling at a subcutaneous site for assessing metastatic progression in triple-negative breast cancer.