Severe Transient Hypoglycemia Causes Reversible Change in the Apparent Diffusion Coefficient of Water

Abstract

Background and Purpose The aim of this study was to determine the effects of temporary severe hypoglycemia on the apparent diffusion coefficient (ADC) acquired by diffusion-weighted MRI of brain water with the use of serial multislice ADC mapping in rats. Severe hypoglycemia reduces the extracellular space volume, as does ischemia. Demonstrating a reduction of ADC with hypoglycemia should increase our understanding of the mechanisms underlying ADC changes in ischemia and other conditions. Methods Fasted rats were given regular insulin (15 IU/kg IP). Rats were subjected to 15 minutes (n=5) and 50 minutes (n=5) of temporary severe hypoglycemia, causing a transiently isoelectric electroencephalogram (EEG). ADC mapping was performed every 30 seconds beginning at the onset of isoelectricity for 8.5 minutes. ADC maps were also obtained later during the isoelectric EEG period and 10, 20, 30, and 40 minutes after glucose infusion. Control images were obtained from a separate group of animals suffering cardiac arrest (n=5). Results Abnormal ADC values were not observed before the onset of cerebral isoelectricity, except for isolated areas in the cortex and periventricular regions. Cortical ADC values globally declined at the onset of EEG isoelectricity. The ADC decline spread to subcortical regions within a few minutes. During the isoelectric period, significant declines of ADC values (27% to 45%) occurred in the entire brain. Glucose infusion normalized most of the ADC changes, even after a 50-minute period of isoelectricity. Conclusions ADC mapping during hypoglycemia clearly demonstrates changes likely related to energy depletion. Most of these ADC declines were reversible. Hypoglycemia is a condition known to be associated with shrinkage of the extracellular space. These observations support the hypothesis that ADC reductions observed in ischemia are also related to shifts of water from the extracellular to the intracellular compartment.