Comparison of quantitative T2 and ADC mapping in the assessment of 3-nitropropionic acid-induced neurotoxicity in rats

To assess the relative performance of MRI T-2 relaxation and ADC mapping as potential biomarkers of neurotoxicity, a model of 3-nitropropionic acid (NP)-induced neurodegeneration in rats was employed. Male Sprague-Dawley rats received NP (N = 20,16-20 mg/kg, ip or sc) or saline (N = 6, 2 ml/kg, ip) daily for 3 days. MRI was performed using a 7 Tsystem employing quantitative 12 and ADC mapping based on spin echo pulse sequence. All maps were skull stripped and co-registered and the changes were quantified using baseline subtraction and anatomical segmentation. Following the in vivo portion of the study, rat brains were histologically examined. Four NP-treated rats were considered responders based on their MRI and histology data. T-2 values always increased in the presence of toxicity, while ADC changes were bidirectional, decreasing in some lesion areas and increasing in others. In contrast to T-2 in some cases, ADC did not change. The effect sizes of T-2 and ADC signals suggestive of neurotoxicity were 2.64 and 1.66, respectively, and the variability of averaged T-2 values among anatomical regions was consistently lower than that for ADC. The histopathology data confirmed the presence of neurotoxicity, however, a more detailed assessment of the correlation of MRI with histology is needed. T-2 mapping provides more sensitive and specific information than ADC about changes in the rat brain thought to be associated with neurotoxicity due to a higher signal-to-noise ratio, better resolution, and unidirectional changes, and presents a better opportunity for biomarker development. (C) 2018 Published by Elsevier B.V.