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 × 10 –5 cm 2 /s, T 2 = 36–45 ms; and ADC f = 2.2–2.8 × 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 (Δ) for Δ < 100 ms, and increased at longer Δ. 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. © 2001 Wiley‐Liss, Inc.