Noninvasive monitoringn of CCl4 induced acute and chronic liver damage in rat by single quantum and triple quantum filtered 23Na magnetic resonance imaging

Abstract

In present study, single quantum (SQ) and triple quantum filtered (TQF) 23Na magnetic resonance imaging (MRI) was used to monitor the severity and progression of CCl4 induced acute and chronic liver damage in rat model. SQ 23Na MRI was proposed to measure the 23Na signal intensity (SI) of total tissue sodium ions, and TQF 23Na MRI was proposed to measure the SI of intracellular sodium ions. In addition, shift reagent aided 23Na and 31P magnetic resonance spectroscopy (MRS) was used to measure in vivo intracellular sodium concentration ([Na+i]), total tissue sodium concentration ([Na+t]) and relative extracellular space (rECS) of liver in the same model. In acute high dose CCl4 intoxication, 24 hours after single dose of CCl4 in 5ml per kg body weight of mixture of CCl4 and oil in 1:1 ratio, SQ 23Na SI increased by 83% and TQF 23Na SI increased by 174% compared to the baseline level. According to SR-aided 23Na and 31P MRS, [Na+i] increased by 188% and [Na+t] increased by 43%. In addition, there was significant decrease in cellular energetic level, represented by ATP/Pi ratio. Histology examination showed pronounced inflammatory response in centrilobular regions, with neutrophiles infiltration, fatty accumulation and swollen hepatocytes. In chronic 8-week experiment, chronic damage was induced by biweekly administration of CCl4 in a dosage of 0.5 ml per kg body weight. From week 1 to week 6, SQ 23Na SI remained relatively constant, and then increased by 15% from week 6 to week 8. TQF 23Na SI progressively increased from week 1 to week 8, totally by 56%. Both SQ and TQF 23Na SI showed significant difference between treated group and control at every week. SR-aided 23Na and 31P MRS experiment showed that, at the end of 8-week CCl4 intoxication, both [Na+t] and rECS were higher than control, by 49% and 47% respectively; however, there was no significant difference for [Na+i] between two groups. Histology examination showed excessive deposition of extracellular matrix. In conclusion, SQ and TQF 23Na MRI appears valuable in the functional assessment of liver in noninvasive approach, and could be a promising diagnostic modality for liver diseases in clinical area.