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

Abstract

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 T 2 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 T 2 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.

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

“…If small subpopulations of necrosis are present, changes in the overall necrosis may be small and would show little to no change in the mean tumor ADC (9). Given that previous studies have also had difficulty in identifying regions of mixed viability (9, 10, 14), an MS approach aimed at subdividing individual tissue regions, specifically viable tissue, is needed.…”

“…Spectroscopic ADCs or mean ADC calculations based on total tumor volume do not assess tissue heterogeneity, and therefore mask the complex tissue response. Helmer et al (10) attempted to address this issue of heterogeneity by analyzing tissue that was either clearly viable or clearly necrotic, as determined from H&E‐stained sections. Tissue that contained a mixture of viable cells and acellular regions was excluded from analysis.…”

Multispectral quantification of tissue types in a RIF‐1 tumor model with histological validation. Part I

“…Over the past decade, diffusion imaging has emerged as a powerful contrast mechanism for characterizing tissue in both experimental tumor models (17–20) and the clinical setting (21, 22). Measurement of exogenous water diffusion based on the random translational motion of molecules due to thermal energy permits differentiation between viable and necrotic tissue based on changes in cellular density.…”

“…In that study the degree of correlation was dependent on the size of the necrotic region. Helmer et al (19) reported a correlation between ADC values and the necrotic fraction in an RIF‐1 tumor model; however, they considered only tissue regions that were clearly viable or clearly necrotic. Regions of mixed tissue were excluded from further analysis.…”

Predicting and monitoring response to chemotherapy by 1,3‐bis(2‐chloroethyl)‐1‐nitrosourea in subcutaneously implanted 9L glioma using the apparent diffusion coefficient of water and 23Na MRI

“…Three histology slices (one each from the anterior, middle, and posterior regions of each tumor) were compared with water ADC maps and 23 Na MRI. The histological regions with low cell density that contained relatively few intact nuclei and liquefied/caseous material were designated as "necrotic" (15,16). These regions could be differentiated from regions of higher cell density ("viable" regions) on lower-resolution images.…”