No abstract

CD163 is a membrane receptor expressed by macrophage lineage. Studies performed in atherosclerosis have shown that CD163 expression is increased at inflammatory sites, pointing at the presence of intraplaque hemorrhagic sites or asymptomatic plaques. Hence, imaging of CD163 expressing macrophages is an interesting strategy in order to detect atherosclerotic plaques. We have prepared a targeted probe based on gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody for the specific detection of CD163 by MRI. Firstly, the specificity of the targeted probe was validated in vitro by incubation of the probe with CD163(+) or (−) macrophages. The probe was able to selectively detect CD163(+) macrophages both in human and murine cells. Subsequently, the targeted probe was injected in 16 weeks old apoE deficient mice developing atherosclerotic lesions and the pararenal abdominal aorta was imaged by MRI. The accumulation of probe in the site of interest increased over time and the signal intensity decreased significantly 48 hours after the injection. Hence, we have developed a highly sensitive targeted probe capable of detecting CD163-expressing macrophages that could provide useful information about the state of the atheromatous lesions.

The precise biologic mechanisms involved in functional recovery processes in response to stroke such as dopaminergic neurotransmission are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging and positron emission tomography (PET) with [(18)F]fluorodeoxyglucose ([(18)F]FDG) and [(11)C]raclopride at 1, 3, 7, 14, 21, and 28 days after middle cerebral artery occlusion in rats. In the ischemic territory, PET [(18)F]FDG showed a initial decrease in cerebral metabolism followed by a time-dependent recovery to quasi-normal values at day 14 after ischemia. The PET with [(11)C]raclopride, a ligand for dopamine D(2) receptor, showed a sustained binding during the first week after ischemia that declined dramatically from day 14 to day 28. Interestingly, a slight increase in [(11)C]raclopride binding was observed at days 1 to 3 followed by the uppermost binding at day 7 in the contralateral territory. Likewise, in vitro autoradiography using [(3)H]raclopride confirmed these in vivo results. Finally, the neurologic test showed major neurologic impairment at day 1 followed by a recovery of the cerebral function at day 28 after cerebral ischemia. Taken together, these results might suggest that dopamine D(2) receptor changes in the contralateral hemisphere could have a key role in functional recovery after cerebral ischemia.

Layer specific functional MRI requires high spatial resolution data. To compensate the associated poor signal to noise ratio it is common to integrate the signal from voxels at a given cortical depth. If the region is sufficiently large then physiological noise will be the dominant noise source. In this work, activation profiles in response to the same visual stimulus are compared at 1.5 T, 3 T and 7 T using a multi-echo, gradient echo (GE) FLASH sequence, with a 0.75 mm isotropic voxel size and the cortical integration approach. The results show that after integrating over a cortical volume of 40, 60 and 100 mm3 (at 7 T, 3 T, and 1.5 T, respectively), the signal is in the physiological noise dominated regime. The activation profiles obtained are similar for equivalent echo times. BOLD-like noise is found to be the dominant source of physiological noise. Consequently, the functional contrast to noise ratio is not strongly echo-time or field-strength dependent. We conclude that laminar GE-BOLD fMRI at lower field strengths is feasible but that larger patches of cortex will need to be examined, and that the acquisition efficiency is reduced.

The influence of toll-like receptor 4 on neurogenesis and inflammation has been scarcely explored so far by using neuroimaging techniques. For this purpose, we performed magnetic resonance imaging and positron emission tomography with 3 À/À mice after ischemia. These results evidence the versatility of neuroimaging techniques to monitor the role of toll-like receptor 4 after cerebral ischemia.