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Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI).

ABSTRACT: Dynamic manganese-enhanced magnetic resonance imaging (MEMRI) detects neuronal activity based on the passage of Mn(2+) into active neurons. Because this mechanism is independent of any hemodynamic response, it is potentially ideal for pharmacological studies and was applied to investigate the acute CNS effects of cocaine in the rat. Dose-dependent, region-specific MEMRI signals were seen mostly in cortical and subcortical mesocorticolimbic structures. To verify the spatial accuracy and physiological mechanisms of MEMRI, neuronal activation following electrical forepaw stimulation revealed somatotopic signal enhancement in the primary and secondary somatosensory cortices, which was blocked by diltiazem, a Ca2+ channel antagonist. These data suggest that MEMRI may serve as a tool for investigating the effects of pharmacological agents and opens an application of MRI to study CNS drug effects at a systems level.

SUBMITTER: Lu H

PROVIDER: S-EPMC1892936 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI).

Lu Hanbing H Xi Zheng-Xiong ZX Gitajn Leah L Rea William W Yang Yihong Y Stein Elliot A EA

Proceedings of the National Academy of Sciences of the United States of America 20070207 7

Dynamic manganese-enhanced magnetic resonance imaging (MEMRI) detects neuronal activity based on the passage of Mn(2+) into active neurons. Because this mechanism is independent of any hemodynamic response, it is potentially ideal for pharmacological studies and was applied to investigate the acute CNS effects of cocaine in the rat. Dose-dependent, region-specific MEMRI signals were seen mostly in cortical and subcortical mesocorticolimbic structures. To verify the spatial accuracy and physiolog ...[more]

PMID: 17287361

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Project description:BackgroundTakotsubo syndrome is an acute cardiac emergency characterized by transient left ventricular systolic dysfunction typically following a stressful event. Despite its rapidly rising incidence, its pathophysiology remains poorly understood. Takotsubo syndrome may pass unrecognized, especially if timely diagnostic imaging is not performed. Defective myocardial calcium homeostasis is a central cause of contractile dysfunction and has not been explored in takotsubo syndrome. We aimed to investigate myocardial calcium handling using manganese-enhanced magnetic resonance imaging during the acute and recovery phases of takotsubo syndrome.MethodsTwenty patients with takotsubo syndrome (63±12 years of age; 90% female) and 20 volunteers matched on age, sex, and cardiovascular risk factors (59±11 years of age; 70% female) were recruited from the Edinburgh Heart Centre between March 2020 and October 2021. Patients underwent gadolinium and manganese-enhanced magnetic resonance imaging during index hospitalization with repeat manganese-enhanced magnetic resonance imaging performed after at least 3 months.ResultsCompared with matched control volunteers, patients had a reduced left ventricular ejection fraction (51±11 versus 67±8%; P<0.001), increased left ventricular mass (86±11 versus 57±14 g/m2; P<0.001), and, in affected myocardial segments, elevated native T1 (1358±49 versus 1211±28 ms; P<0.001) and T2 (60±7 versus 38±3 ms; P<0.0001) values at their index presentation. During manganese-enhanced imaging, kinetic modeling demonstrated a substantial reduction in myocardial manganese uptake (5.1±0.5 versus 8.2±1.1 mL/[100 g of tissue ·min], respectively; P<0.0001), consistent with markedly abnormal myocardial calcium handling. After recovery, left ejection fraction, left ventricular mass, and T2 values were comparable with those of matched control volunteers. Despite this, native and postmanganese T1 and myocardial manganese uptake remained abnormal compared with matched control volunteers (6.6±0.5 versus 8.2±1.1 mL/[100 g of tissue ·min]; P<0.0001).ConclusionsIn patients with takotsubo syndrome, there is a profound perturbation of myocardial manganese uptake, which is most marked in the acute phase but persists for at least 3 months despite apparent restoration of normal left ventricular ejection fraction and resolution of myocardial edema, suggesting abnormal myocardial calcium handling may be implicated in the pathophysiology of takotsubo syndrome. Manganese-enhanced magnetic resonance imaging has major potential to assist in the diagnosis, characterization, and risk stratification of patients with takotsubo syndrome.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT04623788.

Project description:Magnetic resonance imaging (MRI) allows obtaining anatomical and functional information of the brain in the same subject at different times. Manganese-enhanced MRI (MEMRI) uses manganese ions to identify brain activity, although in high doses it might produce neurotoxic effects. Our aims were to identify a manganese dose that does not affect motivated behaviors such as sexual behavior, running wheel and the rotarod test. The second goal was to determine the optimal dose of chloride manganese (MnCl2) that will allow us to evaluate activation of brain regions after females mated controlling (pacing) the sexual interaction. To achieve that, two experiments were performed. In experiment 1 we evaluated the effects of two doses of MnCl2, 8 and 16 mg/kg. Subjects were injected with one of the doses of MnCl2 24 hours before the test on sessions 1, 5 and 10 and immediately thereafter scanned. Female sexual behavior, running wheel and the rotarod were evaluated once a week for 10 weeks. In experiment 2 we followed a similar procedure, but females paced the sexual interaction once a week for 10 weeks and were injected with one of the doses of MnCl2 24 hours before the test and immediately thereafter scanned on sessions 1, 5 and 10. The results of experiment 1 show that neither dose of MnCl2 induces alterations on sexual behavior, running wheel and rotarod. Experiment 2 demonstrated that MEMRI allow us to detect activation of different brain regions after sexual behavior, including the olfactory bulb (OB), the bed nucleus of the stria terminalis (BNST), the amygdala (AMG), the medial preoptic area (MPOA), the ventromedial hypothalamus (VMH), the nucleus accumbens (NAcc), the striatum (STR) and the hippocampus (Hipp) allowing the identification of changes in brain circuits activated by sexual behavior. The socio sexual circuit showed a higher signal intensity on session 5 than the reward circuit and the control groups indicating that even with sexual experience the activation of the reward circuit requires the activation of the socio sexual circuit. Our study demonstrates that MEMRI can be used repeatedly in the same subject to evaluate the activation of brain circuits after motivated behaviors and how can this activation change with experience.

Dataset Information

Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI).

Publications

Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI).

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