Aditya N Bade1, Biyun Zhou2, JoEllyn McMillan1, Prabagaran Narayanasamy3, Ram Veerubhotla1, Howard E Gendelman1, Michael D Boska4, Yutong Liu5. 1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, United States. 2. Department of Anesthesiology, Tongji Medical College, Huanzhong University of Science and Technology, China. 3. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, United States; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, United States. 4. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, United States; Department of Radiology, University of Nebraska Medical Center, Omaha, NE, 68198-1045, United States. 5. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, United States; Department of Radiology, University of Nebraska Medical Center, Omaha, NE, 68198-1045, United States. Electronic address: yutongliu@unmc.edu.
Abstract
BACKGROUND: Manganese (Mn(2+))-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn(2+) is relatively long with a half-life (t1/2) of 51-74 days causing a slow decline of MRI signal enhancement following Mn(2+) administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months. This is because residual Mn(2+) from preceding administrations can confound the interpretation of imaging results. We investigated whether the Mn(2+) enhancement decline could be accelerated thus enabling repeated MEMRI, and as a consequence broadens the utility of MEMRI tests. NEW METHODS: We investigated whether N-acetyl-para-aminosalicylic acid (AcPAS), a chelator of Mn(2+), could affect the decline of Mn(2+) induced MRI enhancement in brain. RESULTS AND CONCLUSION: Two-week treatment with AcPAS (200mg/kg/dose×3 daily) accelerated the decline of Mn(2+) induced enhancement in MRI. In the whole brain on average the enhancement declined from 100% to 17% in AcPAS treated mice, while in PBS controls the decline is from 100% to 27%. We posit that AcPAS could enhance MEMRI utility for evaluating brain biology in small animals. COMPARISON WITH EXISTING METHODS: To the best of our knowledge, no method exists to accelerate the decline of the Mn(2+) induced MRI enhancement for repeated MEMRI tests.
BACKGROUND:Manganese (Mn(2+))-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn(2+) is relatively long with a half-life (t1/2) of 51-74 days causing a slow decline of MRI signal enhancement following Mn(2+) administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months. This is because residual Mn(2+) from preceding administrations can confound the interpretation of imaging results. We investigated whether the Mn(2+) enhancement decline could be accelerated thus enabling repeated MEMRI, and as a consequence broadens the utility of MEMRI tests. NEW METHODS: We investigated whether N-acetyl-para-aminosalicylic acid (AcPAS), a chelator of Mn(2+), could affect the decline of Mn(2+) induced MRI enhancement in brain. RESULTS AND CONCLUSION: Two-week treatment with AcPAS (200mg/kg/dose×3 daily) accelerated the decline of Mn(2+) induced enhancement in MRI. In the whole brain on average the enhancement declined from 100% to 17% in AcPAS treated mice, while in PBS controls the decline is from 100% to 27%. We posit that AcPAS could enhance MEMRI utility for evaluating brain biology in small animals. COMPARISON WITH EXISTING METHODS: To the best of our knowledge, no method exists to accelerate the decline of the Mn(2+) induced MRI enhancement for repeated MEMRI tests.
Authors: Helene Benveniste; Yu Ma; Jasbeer Dhawan; Andrew Gifford; S David Smith; Igor Feinstein; Congwu Du; Samuel C Grant; Patrick R Hof Journal: Ann N Y Acad Sci Date: 2007-02 Impact factor: 5.691
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