Regional specificity of manganese accumulation and clearance in the mouse brain: implications for manganese-enhanced MRI.

Manganese-enhanced MRI has recently become a valuable tool for the assessment of in vivo functional cerebral activity in animal models. As a result of the toxicity of manganese at higher dosages, fractionated application schemes have been proposed to reduce the toxic side effects by using lower concentrations per injection. Here, we present data on regional-specific manganese accumulation during a fractionated application scheme over 8 days of 30 mg/kg MnCl2 , as well as on the clearance of manganese chloride over the course of several weeks after the termination of the whole application protocol supplying an accumulative dose of 240 mg/kg MnCl2 . Our data show most rapid accumulation in the superior and inferior colliculi, amygdala, bed nucleus of the stria terminalis, cornu ammonis of the hippocampus and globus pallidus. The data suggest that no ceiling effects occur in any region using the proposed application protocol. Therefore, a comparison of basal neuronal activity differences in different animal groups based on locally specific manganese accumulation is possible using fractionated application. Half-life times of manganese clearance varied between 5 and 7 days, and were longest in the periaqueductal gray, amygdala and entorhinal cortex. As the hippocampal formation shows one of the highest T1 -weighted signal intensities after manganese application, and manganese-induced memory impairment has been suggested, we assessed hippocampus-dependent learning as well as possible manganese-induced atrophy of the hippocampal volume. No interference of manganese application on learning was detected after 4 days of Mn(2+) application or 2 weeks after the application protocol. In addition, no volumetric changes induced by manganese application were found for the hippocampus at any of the measured time points. For longitudinal measurements (i.e. repeated manganese applications), a minimum of at least 8 weeks should be considered using the proposed protocol to allow for sufficient clearance of the paramagnetic ion from cerebral tissue.

The influence of moderate hypercapnia on neural activity in the anesthetized nonhuman primate.

Hypercapnia is often used as vasodilatory challenge in clinical applications and basic research. In functional magnetic resonance imaging (fMRI), elevated CO(2) is applied to derive stimulus-induced changes in the cerebral rate of oxygen consumption (CMRO(2)) by measuring cerebral blood flow and blood-oxygenation-level-dependent (BOLD) signal. Such methods, however, assume that hypercapnia has no direct effect on CMRO(2). In this study, we used combined intracortical recordings and fMRI in the visual cortex of anesthetized macaque monkeys to show that spontaneous neuronal activity is in fact significantly reduced by moderate hypercapnia. As expected, measurement of cerebral blood volume using an exogenous contrast agent and of BOLD signal showed that both are increased during hypercapnia. In contrast to this, spontaneous fluctuations of local field potentials in the beta and gamma frequency range as well as multiunit activity are reduced by approximately 15% during inhalation of 6% CO(2) (pCO(2) = 56 mmHg). A strong tendency toward a reduction of neuronal activity was also found at CO(2) inhalation of 3% (pCO(2) = 45 mmHg). This suggests that CMRO(2) might be reduced during hypercapnia and caution must be exercised when hypercapnia is applied to calibrate the BOLD signal.

Magnetic spin imaging under ambient conditions with sub-cellular resolution.

The detection of small numbers of magnetic spins is a significant challenge in the life, physical and chemical sciences, especially when room temperature operation is required. Here we show that a proximal nitrogen-vacancy spin ensemble serves as a high precision sensing and imaging array. Monitoring its longitudinal relaxation enables sensing of freely diffusing, unperturbed magnetic ions and molecules in a microfluidic device without applying external magnetic fields. Multiplexed charge-coupled device acquisition and an optimized detection scheme permits direct spin noise imaging of magnetically labelled cellular structures under ambient conditions. Within 20 s we achieve spatial resolutions below 500 nm and experimental sensitivities down to 1,000 statistically polarized spins, of which only 32 ions contribute to a net magnetization. The results mark a major step towards versatile sub-cellular magnetic imaging and real-time spin sensing under physiological conditions providing a minimally invasive tool to monitor ion channels or haemoglobin trafficking inside live cells.

Optical detection of a single rare-earth ion in a crystal.

Rare-earth-doped laser materials show strong prospects for quantum information storage and processing, as well as for biological imaging, due to their high-Q 4f↔4f optical transitions. However, the inability to optically detect single rare-earth dopants has prevented these materials from reaching their full potential. Here we detect a single photostable Pr(3+) ion in yttrium aluminium garnet nanocrystals with high contrast photon antibunching by using optical upconversion of the excited state population of the 4f↔4f optical transition into ultraviolet fluorescence. We also demonstrate on-demand creation of Pr(3+) ions in a bulk yttrium aluminium garnet crystal by patterned ion implantation. Finally, we show generation of local nanophotonic structures and cell death due to photochemical effects caused by upconverted ultraviolet fluorescence of praseodymium-doped yttrium aluminium garnet in the surrounding environment. Our study demonstrates versatile use of rare-earth atomic-size ultraviolet emitters for nanoengineering and biotechnological applications.