Figure 3
Size heterogeneity in vitro and in vivo and size-dependent therapeutic response.
(a): In vivo nodule size heterogeneity from representative fluorescent microendoscope fields of xenograft implanatation of ovarian cancer cells, which resembles size distribution of the same cells grown in vitro. Endoscope fields are 800 μm in diameter. (b): A representation of our use of segmentation in 3D culture image data to identify individual nodules from the brightfield channel to generate a mask for computation of multiple readouts (shown in truncated form) for each individual nodule. In (c), viability-volume scatter plots output by qVISTA code showing the rescaled viability of each nodule with respect to its volume, for thousands of nodules in each treatment group, for each treatment. The vertical spread reflects dose response heterogeneity and for given a range of sizes. Probing size-dependent response in this manner reveals, for example, that the only nodules that are completely responsive to carboplatin are the smallest volume nodules while the largest remain weakly viable even at a 1000 μM (LD80) dose. Response to paclitaxel is the most homogeneous and size-independent of therapies evaluated. Etoposide-treated cultures exhibit a broad spread of viabilities over a broad spread of nodule sizes, while verteporfin-PDT treatment induces a pronounced bi-modal response with simultaneously emergent populations of small nodules (1–10 cells) that are almost completely viable and almost completely non-viable.
