Dataset Information

Manganese Dynamics in Mouse Brain After Systemic MnCl₂ Administration for Activation-Induced Manganese-Enhanced MRI.

ABSTRACT: Activation-induced manganese-enhanced MRI (AIM-MRI) is an attractive tool for non-invasively mapping whole brain activities. Manganese ions (Mn²⁺) enter and accumulate in active neurons via calcium channels. Mn²⁺ shortens the longitudinal relaxation time (T1) of H⁺, and the longitudinal relaxation rate R1 (1/T1) is proportional to Mn²⁺ concentration. Thus, AIM-MRI can map neural activities throughout the brain by assessing the R1 map. However, AIM-MRI is still not widely used, partially due to insufficient information regarding Mn²⁺ dynamics in the brain. To resolve this issue, we conducted a longitudinal study looking at manganese dynamics after systemic administration of MnCl₂ by AIM-MRI with quantitative analysis. In the ventricle, Mn²⁺ increased rapidly within 1 h, remained high for 3 h, and returned to near control levels by 24 h after administration. Microdialysis showed that extracellular Mn returned to control levels by 4 h after administration, indicating a high concentration of extracellular Mn²⁺ lasts at least about 3 h after administration. In the brain parenchyma, Mn²⁺ increased slowly, peaked 24-48 h after administration, and returned to control level by 5 days after a single administration and by 2 weeks after a double administration with a 24-h interval. These time courses suggest that AIM-MRI records neural activity 1-3 h after MnCl₂ administration, an appropriate timing of the MRI scan is in the range of 24-48 h following systemic administration, and at least an interval of 5 days or a couple of weeks for single or double administrations, respectively, is needed for a repeat AIM-MRI experiment.

SUBMITTER: Tanihira H

PROVIDER: S-EPMC8722453 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Manganese Dynamics in Mouse Brain After Systemic MnCl2 Administration for Activation-Induced Manganese-Enhanced MRI.

Tanihira Hiroki H Fujiwara Tomonori T Kikuta Satomi S Homma Noriyasu N Osanai Makoto M

Frontiers in neural circuits 20211220

Activation-induced manganese-enhanced MRI (AIM-MRI) is an attractive tool for non-invasively mapping whole brain activities. Manganese ions (Mn2+) enter and accumulate in active neurons via calcium channels. Mn2+ shortens the longitudinal relaxation time (T1) of H+, and the longitudinal relaxation rate R1 (1/T1) is proportional to Mn2+ concentration. Thus, AIM-MRI can map neural activities throughout the brain by assessing the R1 map. However, AIM-MRI ...[more]

PMID: 34987361

Similar Datasets

Project description:Life threatening fear after a single exposure evolves in a subset of vulnerable individuals to anxiety, which may persist for their lifetime. Yet neither the whole brain's response to innate acute fear nor how brain activity evolves over time is known. Sustained neuronal activity may be a factor in the development of a persistent fear response. We couple two experimental protocols to provoke acute fear leading to prolonged fear: Predator stress (PS), a naturalistic approach to induce fear in rodents; and Serotonin transporter knockout mouse (SERT-KO) that responds to PS with sustained defensive behavior. Behavior was monitored before, during and at short and long times after PS in wild type (WT) and SERT-KO mice. Both genotypes responded to PS with defensive behavior. SERT-KO retained defensive behavior for 23 days, while WT mice returned to baseline exploratory behavior by 9 days. Thus, differences in neural activity between WT and SERT-KO 9 days after PS identifies neural correlates of persistent defensive behavior, in mice. We used longitudinal manganese-enhanced magnetic resonance imaging (MEMRI) to identify brain-wide neural activity associated with different behaviors. Mn2+ accumulation in active neurons occurs in awake, behaving mice and is retrospectively imaged. Following the same two cohorts of mice, WT and SERT-KO, longitudinally allowed unbiased quantitative comparisons of brain-wide activity by statistical parametric mapping (SPM). During natural behavior in WT, only low levels of activity-induced Mn2+-accumulation were detected, while much more accumulation appeared immediately after PS in both WT and SERT-KO, and evolved at 9 days to a new activity pattern (p < 0.0001, uncorr., T = 5.4). Patterns of accumulation differed between genotypes, with more regions of the brain and larger volumes within regions involved in SERT-KO than WT. A new computational segmentation analysis, using our InVivo Atlas based on a manganese-enhanced MR image of a living mouse, revealed dynamic changes in the volume of significantly enhanced voxels within each segment that differed between genotypes across 45 of 87 segmented regions. At Day 9 after PS, the striatum and ventral pallidum were active in both genotypes but more so in the SERT-KO. SERT-KO also displayed sustained or increased volume of Mn2+ accumulations between Post-Fear and Day 9 in eight segments where activity was decreased or silenced in WT. C-fos staining, an alternative neural activity marker, of brains from the same mice fixed at conclusion of imaging sessions confirmed that MEMRI detected active neurons. Intensity measurements in 12 regions of interest (ROIs) supported the SPM results. Between group comparisons by SPM and of ROI measurements identified specific regions differing between time points and genotypes. We report brain-wide activity in response to a single exposure of acute fear, and, for the first time, its evolution to new activity patterns over time in individuals vulnerable to persistent fear. Our results show multiple regions with dynamic changes in neural activity and that the balance of activity between segments is disordered in the SERT-KO. Thus, longitudinal MEMRI represents a powerful approach to discover how brain-wide activity evolves from the natural state either after an experience or during a disease process.

Project description:ObjectiveIn a proof-of-concept study, to quantify myocardial viability in patients with acute myocardial infarction using manganese-enhanced MRI (MEMRI), a measure of intracellular calcium handling.MethodsHealthy volunteers (n=20) and patients with ST-elevation myocardial infarction (n=20) underwent late gadolinium enhancement (LGE) using gadobutrol and MEMRI using manganese dipyridoxyl diphosphate. Patients were scanned ≤7 days after reperfusion and rescanned after 3 months. Differential manganese uptake was described using a two-compartment model.ResultsAfter manganese administration, healthy control and remote non-infarcted myocardium showed a sustained 25% reduction in T1 values (mean reductions, 288±34 and 281±12 ms). Infarcted myocardium demonstrated less T1 shortening than healthy control or remote myocardium (1157±74 vs 859±36 and 835±28 ms; both p<0.0001) with intermediate T1 values (1007±31 ms) in peri-infarct regions. Compared with LGE, MEMRI was more sensitive in detecting dysfunctional myocardium (dysfunctional fraction 40.5±11.9 vs 34.9%±13.9%; p=0.02) and tracked more closely with abnormal wall motion (r2=0.72 vs 0.55; p<0.0001). Kinetic modelling showed reduced myocardial manganese influx between remote, peri-infarct and infarct regions, enabling absolute discrimination of infarcted myocardium. After 3 months, manganese uptake increased in peri-infarct regions (16.5±3.5 vs 22.8±3.5 mL/100 g/min, p<0.0001), but not the remote (23.3±2.8 vs 23.0±3.2 mL/100 g/min, p=0.8) or infarcted (11.5±3.7 vs 14.0±1.2 mL/100 g/min, p>0.1) myocardium.ConclusionsThrough visualisation of intracellular calcium handling, MEMRI accurately differentiates infarcted, stunned and viable myocardium, and correlates with myocardial dysfunction better than LGE. MEMRI holds major promise in directly assessing myocardial viability, function and calcium handling across a range of cardiac diseases.Trial registration numbersNCT03607669; EudraCT number 2016-003782-25.

Dataset Information

Manganese Dynamics in Mouse Brain After Systemic MnCl₂ Administration for Activation-Induced Manganese-Enhanced MRI.

Publications

Manganese Dynamics in Mouse Brain After Systemic MnCl<sub>2</sub> Administration for Activation-Induced Manganese-Enhanced MRI.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets