Microvascular Specificity of Spin Echo BOLD fMRI: Impact of EPI Echo Train Length.

A spatially specific fMRI acquisition requires specificity to the microvasculature that serves active neuronal sites. Macrovascular contributions will reduce the microvascular specificity but can be reduced by using spin echo (SE) sequences that use a π pulse to refocus static field inhomogeneities near large veins. The microvascular specificity of a SE-echo planar imaging (SE-EPI) scan depends on the echo train length (ETL)-duration, but the dependence is not well-characterized in humans at 7T. To determine how microvascular-specific SE-EPI BOLD is in humans at 7T, we developed a Monte Carlo voxel model that computes the signal of a proton ensemble residing in a vasculature subjected to a SE-EPI pulse sequence. We characterized the ETL-duration dependence of the microvascular specificity by simulating the BOLD signal as a function of ETL, the range adhering to experimentally realistic readouts. We performed a validation experiment for our simulation observations, in which we acquired a set of SE-EPI BOLD time series with varying ETL during a hyperoxic gas challenge. Both our simulations and measurements show an increase in macrovascular contamination as a function of ETL, with an increase of 30% according to our simulation and 60% according to our validation experiment between the shortest and longest ETL durations (23.1 - 49.7 ms). We conclude that the microvascular specificity decreases heavily with increasing ETL-durations. We recommend reducing the ETL-duration as much as possible to minimize macrovascular contamination in SE-EPI BOLD experiments. We additionally recommend scanning at high resolutions to minimize partial volume effects with CSF. CSF voxels show a large BOLD response, which can be attributed to both the presence of large veins (high blood volume) and molecular oxygen-induced -shortening (significant in a hyperoxia experiment). The magnified BOLD signal in a GM-CSF partial volume voxel reduces the desired microvascular specificity and, therefore, will hinder the interpretation of functional MRI activation patterns.