Fig. 1.
Biological processes proposed to be involved in therapeutic-induced changes in tumor ADC values along with a pictorial description of the fDM analytical process. (A) A schematic representation of the dynamic biological processes associated with changes (increase or decrease) in tumor water diffusion values. Tumor cells within an image voxel have several fates during treatment. Cells can be resistant to therapy (unaltered ADC, green) or can undergo necrosis initiated by a transient cell swelling (decreased ADC, blue). Cell enlargement (swelling) can also be associated with mitotic catastrophe or a reduction in tumor blood flow resulting in focal ischemia/hypoxia (decreased ADC, blue). These processes can eventually progress to cell lysis and necrosis (increased ADC, red). Cells can also undergo apoptosis involving cell shrinkage and blebbing followed by phagocytosis (increased ADC, red). (B) The concept that necrotic or cystic regions of a tumor can undergo drainage (displacement) of water as cells move into the region resulting in a drop in diffusion values (decreased ADC, blue) is summarized. (C) Diffusion MRI data undergo digital image postprocessing and analysis that involves coregistration of images before and during treatment. Data are used to generate a three-color overlay representing regions in which tumor ADC values are unchanged (green voxels), significantly increased (red voxels), or significantly decreased (blue voxels). This data can also be presented in a scatter plot and percentages assigned to the three defined ADC regions, allowing quantitative assessment of overall changes in tumor ADC values.