Extravascular proton-density changes as a non-BOLD component of contrast in fMRI of the human spinal cord

The fractional signal intensity change (Delta S/S) observed during activation in T(2)-weighted fMRI of the spinal cord has previously been shown to depend linearly on the echo time (TE) but to have a positive value of roughly 2.5% extrapolated to zero TE. In this study we investigated the origin of this finding by measuring the Delta S/S in spinal fMRI with very short TEs. Our results demonstrate that the Delta S/S does not approach zero, but has a value as high as 3.3% at TE = 11 ms. At TEs > 33 ms we observed the linear relationship between Delta S/S and TE as in previous studies. These data demonstrate that there is a non-BOLD contribution to signal changes observed in spinal fMRI. We hypothesize that this contribution is a local proton density increase due to increased water exudation from capillaries with increased blood flow during neuronal activation, and term this effect "signal enhancement by extravascular protons" (SEEP).