Compartmentation of intracellular water in multicellular tumor spheroids: diffusion and relaxation NMR

Diffusion and relaxation of water in C6 glioma and MLS human ovarian carcinoma spheroids were measured from 1D projections acquired using a 2D diffusion-relaxation correlation pulse sequence and processed by non-negative least-square (NNLS) analysis. Systematic underestimation of I(s) and ADC(s) were observed for I(s)/(I(s) + I(f)) < 0.001. In the presence of spheroids, two apparent diffusion coefficient (ADC) compartments were observed, where ADC(f), ADC(s), and I(f), I(s) are the respective ADCs and signal intensities of the fast and slow compartments. These compartments differed also in their T(2) relaxation (ADC(s) = 0.5-0.74 x 10(-5) cm(2)/s, T(2) = 36-45 ms; and ADC(f) = 2.2-2.8 x 10(-5) cm(2)/s, T(2) = 280-316 ms). The two ADC compartments and the slow T(2) compartment were consistent with slow exchange. The fast T(2) compartment showed a drift with diffusion weighting, suggesting that it represents water exchanging between compartments that differ in their ADC and T(2). Both ADC(s) and I(s) were markedly attenuated with increasing diffusion time (Delta) for Delta < 100 ms, and increased at longer Delta. These results are consistent with restricted diffusion and fast relaxation of intracellular water for short diffusion time (T(1)' = 46.6 ms), and with predominant extracellular contribution to ADC(s) at longer diffusion times. Magn Reson Med 46:68-77, 2001.