Comparison of the return-to-the-origin probability and the apparent diffusion coefficient of water as indicators of necrosis in RIF-1 tumors.

Two model-independent measures of diffusion, the apparent diffusion coefficient (ADC) and return-to-the-origin probability enhancement (R) were compared for their ability to detect tissue necrosis in RIF-1 murine tumors. Both reflect the degree of restriction experienced by the endogenous water molecules; however, the ADC is calculated from the initial linear slope of the diffusion attenuation curve, while R is calculated from data that includes the non-monoexponential part of the curve. In spectroscopic studies (n 9), neither the ADC nor R showed a strong correlation with tumor volume. In imaging studies (n 14), ADC, R, and T2 were calculated on a pixel-by-pixel basis. There, the mean ADC and mean R for the entire imaging slice showed reasonable correlation with necrotic tumor fraction (r 2 0.679 and ‐ 0.665, respectively). The mean T2 value yielded a poor correlation (r 2 0.436). Regions-of-interest were chosen from areas identified as either necrotic or viable and the resulting sets of ADC and R-values were subjected to discriminant analysis to determine the identification error rate. The error was greater for R than for the ADC (P < 0.001). Therefore, in this application, the use of the non-monoexponential part of the diffusion attenuation curve does not provide additional identification power. Magn Reson Med 49:468 ‐ 478, 2003. © 2003 Wiley-Liss, Inc. The goal of this study was to compare the apparent diffusion coefficient (ADC) and the return-to-the-origin (RTO) probability (1) of endogenous water molecules for their ability to detect tumor necrosis and characterize the diffusion properties of tumor tissue. Both quantities are calculated from diffusion-weighted (DW) NMR data; however, the data used to calculate the ADC is a subset of that needed to calculate the RTO probability. The RTO probability is a model-independent measure that can be used to characterize the non-monoexponential shape of the diffusion attenuation curve of tissue water. It does not attempt to separate the effects of restrictions from those of diffusion within and between multiple compartments, but rather produces a single measure that characterizes the shape of the curve regardless of its origin. The relative weighting of highly restricted spins in the ADC and RTO probability are different, however. The ADC calculation weights signal from freely diffusing and highly restricted spins equally; however, since the ADC is calculated from the initial slope of the signal attenuation curve (at low applied gradient values), the majority of the signal attenuation arises from more freely diffusing spins. The RTO probability, on the other hand, more strongly weights the signal arising from the highly restricted molecules. The diffusion path of an in vivo water molecule is influenced by the presence of restrictions, such as cell membranes and organelles, and is therefore sensitive to changes in tissue organization, the water distribution between intra- and extracellular spaces, and membrane permeability. Because of this sensitivity, diffusion-weighted MRI has been shown to give good contrast between normal and ischemic tissue in cases of cerebral ischemia (2). Early studies of the diffusion-weighted imaging in tumors suggested that diffusion sensitization could be used to distinguish between tumors or cysts (3) or as an indicator of tumor tissue heterogeneity (4). The ADC has been shown to be sensitive to pathophysiological and structural changes in response to chemotherapy (5,6).