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Manganese imaging with positron emission tomography, autoradiography, and magnetic resonance Topping, Geoffrey John
Manganese is a magnetic resonance imaging (MRI) contrast agent for small animals that can provide a blood-flow-independent measure of neuronal activation. Established Mn MRI methods have limited ability to measure concentrations of Mn or details of its distribution in vivo, which limits their experimental power. Positron emission tomography (PET) can measure quantitative distributions in vivo in small animals of positron-emitting radionuclides such as Mn-52, although has poorer spatial resolution than MRI. Autoradiography (AR) can also measure quantitative distributions of Mn-52, in ex vivo brain tissue, with spatial resolution similar to MRI. This work has three primary goals: to develop and characterize Mn-52 as a radionuclide for PET in phantoms and in small animals, to develop a quantitative MRI method for measuring Mn concentration in the brain of small animals, and to validate the MRI results by comparisons with AR and PET. Mn-52 was produced by proton irradiation of natural Cr foil, isolated by column chromatography, and used as a PET tracer for the first time in phantoms and in vivo in rats. Mn-52 phantom image quality metrics were similar to F-18, an established PET radionuclide. After systemic administration in rats, Mn-52 accumulation was seen in bones, but little was seen in the brain, due to the blood-brain barrier. Direct injection into the lateral ventricle effectively delivers Mn-52 throughout the rat brain. Mn-52 AR images were acquired and used for comparison with MRI. MRI R1 relaxation rate maps of rat brain were acquired using a radiofrequency field strength independent inversion recovery Look-Locker sequence, and used to generate relaxation rate change and Mn concentration maps after Mn administration. These maps showed excellent quantitative agreement with PET and AR images of the same animal, confirming that MR R1 change accurately measures Mn concentration in rat brain in the range 0 to 0.1 mM, in the absence of other sources of R1 change. However, at some point above this concentration, measured R1 becomes inaccurate. Accordingly, Mn concentration mapping with MRI is a potentially useful tool to improve the experimental power of Mn-uptake imaging to assess neuronal activation.
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