Multispectral tissue characterization in a RIF-1 tumor model: monitoring the ADC and T2 responses to single-dose radiotherapy. Part II.

A multispectral (MS) approach that combines apparent diffusion coefficient (ADC) and T(2) parameter maps with k-means (KM) clustering was employed to distinguish multiple compartments within viable tumor tissue (V1 and V2) and necrosis (N1 and N2) following single-dose (1000 cGy) radiotherapy in a radiation-induced fibrosarcoma (RIF-1) tumor model. The contributions of cell kill and tumor growth kinetics to the radiotherapy-induced response were investigated. A larger pretreatment V1 volume was correlated with decreased tumor growth delay (TGD) (r = 0.68) and cell kill (r = 0.71). There was no correlation for the pretreatment V2 volume. These results suggest that V1 tissue is well oxygenated and radiosensitive, whereas V2 tissue is hypoxic and therefore radioresistant. The relationship between an early ADC response and vasogenic edema and formation of necrosis was investigated. A trend for increased ADC was observed prior to an increase in the necrotic fraction (NF). Because there were no changes in T(2), these observations suggest that the early increase in ADC is more likely based on a slight reduction in cell density, rather than radiation-induced vasogenic edema. Quantitative assessments of individual tissue regions, tumor growth kinetics, and cell kill should provide a more accurate means of monitoring therapy in preclinical animal models because such assessments can minimize the issue of intertumor variability.