Mapping iso-orientation columns by contrast agent-enhanced functional magnetic resonance imaging: reproducibility, specificity, and evaluation by optical imaging of intrinsic signal.

Activation resembling ocular dominance or orientation columns has been mapped with high-resolution functional magnetic resonance imaging (fMRI). However, the neuronal interpretation of these functional maps is unclear because of the poor sensitivity of fMRI, unknown point spread function (PSF), and lack of comparison with independent techniques. Here we show that cerebral blood volume (CBV)-weighted fMRI with a blood plasma contrast agent (monocrystalline iron oxide nanoparticles), in combination with continuous temporally encoded stimulation, can map columnar neuronal activity in the cat primary visual cortex with high sensitivity, selectivity, and reproducibility. We examined hemodynamic response PSF by comparing these CBV-based signals with oxygen metabolism-based negative blood oxygenation level-dependent signals. A significant positive correlation exists between CBV- and metabolism-based iso-orientation maps, suggesting that the hemodynamic PSF is narrower than intercolumn distances. We also compared CBV-based fMRI with optical intrinsic signal (OIS) imaging, a technique that identifies sites of increased neuronal activity, to investigate neuronal correlation. Iso-orientation maps obtained by fMRI and OIS were well matched, indicating that areas of the highest orientation-selective CBV signals correspond to sites of increased neural activity. Using CBV-based fMRI, we successfully mapped orientation-selective functional architecture in the medial bank of the visual cortex, an area inaccessible to OIS imaging. Thus, we conclude that contrast agent-based fMRI, in combination with continuous temporally encoded stimulation, is a highly sensitive technique capable of mapping neural activity at the resolution of functional columns without depth limitation.