In a method for ex vivo evaluation of tissue response, a target biological sample is placed in a chamber of a sample holder. Biodynamic imaging (BDI) is performed on the sample to extract BDI data of the entire sample, optical coherence imaging (OCI) data is generated from the BDI data; and then motility contrast imaging (MCI) data is generated from the OCI data. The MCI data is used to select an area of the ex vivo sample having the highest normalized standard deviation (NSD) value, indicative of a region of desirable responsiveness to a stimuli. The sample is subjected to a perturbation or external condition and an MCI analysis is performed on the selected area to determine the tissue response to the perturbation or external condition. In one aspect, the selected area or region of interest is obtained using a gradient descent method.