Estimation of laminar BOLD activation profiles using deconvolution with a physiological point spread function.

BACKGROUND: The specificity of gradient echo (GE)-BOLD laminar fMRI activation profiles is degraded by intracortical veins that drain blood from lower to upper cortical layers, propagating activation signal in the same direction. This work describes an approach to obtain layer specific profiles by deconvolving the measured profiles with a physiological Point Spread Function (PSF). NEW METHOD: It is shown that the PSF can be characterised by a TE-dependent peak to tail (p2t) value that is independent of cortical depth and can be estimated by simulation. An experimental estimation of individual p2t values and the sensitivity of the deconvolved profiles to variations in p2t is obtained using laminar data measured with a multi-echo 3D-FLASH sequence. These profiles are echo time dependent, but the underlying neuronal response is the same, allowing a data-based estimation of the PSF. RESULTS: The deconvolved profiles are highly similar to the gold-standard obtained from extremely high resolution 3D-EPI data, for a range of p2t values of 5-9, which covers both the empirically determined value (6.8) and the value obtained by simulation (6.3). -Comparison with Existing Method(s) Corrected profiles show a flatter shape across the cortex and a high level of similarity with the gold-standard, defined as a subset of profiles that are unaffected by intracortical veins. CONCLUSIONS: We conclude that deconvolution is a robust approach for removing the effect of signal propagation through intracortical veins. This makes it possible to obtain profiles with high laminar specificity while benefitting from the higher efficiency of GE-BOLD sequences.

An in-vivo study of BOLD laminar responses as a function of echo time and static magnetic field strength.

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.

A cortical vascular model for examining the specificity of the laminar BOLD signal.

Blood oxygenation level dependent (BOLD) functional MRI has been used for inferring layer specific activation in humans. However, intracortical veins perpendicular to the cortical surface are suspected to degrade the laminar specificity as they drain blood from the microvasculature and BOLD signal is carried over from lower to upper cortical layers on its way to the pial surface. In this work, a vascular model of the cortex is developed to investigate the laminar specificity of the BOLD signal for Spin Echo (SE) and Gradient Echo (GE) following the integrative model presented by Uludag et al. (2009). The results of the simulation show that the laminar point spread function (PSF) of the BOLD signal presents similar features across all layers. The PSF for SE is highly localised whereas for GE there is a flat tail running to the pial surface, with amplitude less than a quarter of the response from the layer itself. Consequently the GE response at any layer will also contain a contribution accumulated from all lower layers.

Imaging the role of toll-like receptor 4 on cell proliferation and inflammation after cerebral ischemia by positron emission tomography.

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'-deoxy-3'-[(18)F]fluorothymidine and [(11)C]PK11195 at 2, 7, and 14 days following cerebral ischemia in TLR4(+/+)and TLR4(-/-)mice. MRI showed similar infarction volumes in both groups. Despite this, positron emission tomography with 3'-deoxy-3'-[(18)F]fluorothymidine and [(11)C]PK11195 evidenced an increase of neurogenesis and a decrease of inflammation in TLR4(-/-)mice after ischemia. These results evidence the versatility of neuroimaging techniques to monitor the role of toll-like receptor 4 after cerebral ischemia.

Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI.

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.

In vivo imaging of dopaminergic neurotransmission after transient focal ischemia in rats.

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.