In vitro assessment of factors affecting the apparent diffusion coefficient of Ramos cells using bio-phantoms

The roles of cell density, extracellular space, intracellular factors, and apoptosis induced by the molecularly targeted drug rituximab on the apparent diffusion coefficient (ADC) values were investigated using bio-phantoms. In these bio-phantoms, Ramos cells (a human Burkitt's lymphoma cell line) were encapsulated in gellan gum. The ADC values decreased linearly with the increase in cell density, and declined steeply when the extracellular space became less than 4 μm. The analysis of ADC values after destruction of the cellular membrane by sonication indicated that approximately 65% of the ADC values of normal cells originate from the cell structures made of membranes and that the remaining 35% originate from intracellular components. Microparticles, defined as particles smaller than the normal cells, increased in number after rituximab treatments, migrated to the extracellular space and significantly decreased the ADC values of bio-phantoms during apoptosis. An in vitro study using bio-phantoms was conducted to quantitatively clarify the roles of cellular factors and of extracellular space in determining the ADC values yielded by tumor cells and the mechanism by which apoptosis changes those values.