In vitro experimental study of the relationship between the apparent diffusion coefficient and changes in cellularity and cell morphology

Abstract

Abstract. Diffusion-weighted magnetic resonance imaging (MRI) is frequently used clinically, and is available for the whole-body screening for tumors. The exact mechanism by which the apparent diffusion coefficient (ADC) value decreases in tumorous tissue remains unclear, although various theories have been proposed, including intracellular and extracellular factor theories. It is impossible to distinguish each factor in the intracellular and extracellular spaces as the source of MR signal generation by means of conventional comparison between MR images and pathological specimens. Other factors which have been reported to affect ADC include cellularity and cellular edema of human tissues, and temperature of phantoms at the time of measurement. We employed a new technique that enables cellular MR imaging using a newly developed bio-phantom containing a living culture tumor cell line, Jurkat-N1. We investigated possible reasons for observed decreases in ADC values for tumors, and we considered the contribution of both the intracellular and extracellular space to such a decrease. The ADC values of the bio-phantom increased with increasing heat exposure from 27 to 45˚C. ADC values also increased after the destruction by sonication of tumor cell membranes. ADC values decreased as cellularity increased in the bio-phantom. ADC values decreased due to cellular edema caused by a low salt concentration in the bio-phantom. Changes in pressure in the bio-phantom had no effect on the observed ADC values. We calculated both the intracellular ADC and extracellular ADC values using the ADC values, cellularity, and cellular volume of Jurkat-N1 cells in the bio-phantom. The extracellular ADC values in the bio-phantom were estimated to be lower than the ADC value of distilled water. These results indicate that not only intracellular ADC values, but also extracellular ADC values contribute to the determination of the ADC values of bio-phantoms. This is the first report to have examined the contribution of intracellular and extracellular space on the ADC values of bio-phantoms containing cultured tumor cells.

Which Parameter Influences Local Disease-Free Survival after Radiation Therapy Due to Osteolytic Metastasis? A Retrospective Study with Pre- and Post-Radiation Therapy MRI including Diffusion-Weighted Images

“…ADC is inversely correlated with tissue cellularity [ 25 ]. Increased ADC values indicate an increase in extracellular water content and loss of cell membrane integrity, whereas decreased ADC values represent a decrease in extracellular water or increase in cell number or size [ 26 ].…”

Simplified perfusion fraction from diffusion-weighted imaging in preoperative prediction of IDH1 mutation in WHO grade II–III gliomas: comparison with dynamic contrast-enhanced and intravoxel incoherent motion MRI

“…Diffusion-related parameters, including ADC and D values, were significantly lower in WHO grade III gliomas; this result is in line with those of previous studies. 19,35 It is now well established that ADC is strongly correlated with cellularity and the nuclear cytoplasmic ratio in tumor tissue [36][37][38] , both of which are important criteria in the histopathological grading of gliomas.…”

Target Heterogeneity in Oncology: The Best Predictor for Differential Response to Radioligand Therapy in Neuroendocrine Tumors and Prostate Cancer

“…Indeed, the diffusivity of water molecules is restricted in environments of high cellularity because this cellularity reduces the ratio of extracellular to intracellular space in a given area of tissue [ 67 ]. Studies conducted in vitro and in animal models show that the ADC is inversely correlated with tumor cellularity [ 68 , 69 ]. A quantitative assessment could be easily performed using the apparent diffusion coefficient (ADC) measuring signal attenuation being influenced by microscopic motion, including molecular diffusion of water as well as blood microcirculation.…”