Spin-echo MRI underestimates functional changes in microvascular cerebral blood plasma volume using exogenous contrast agent.

While most functional MRI studies using exogenous contrast agent employ gradient-echo (GE) signal, spin echo (SE) imaging would represent an attractive alternative if its detection power were more comparable with GE imaging. This study demonstrates that SE methods systematically underestimate functional changes in microvascular cerebral blood plasma volume (CBV), so that SE detection power in brain tissue cannot match that provided by GE signal. Empirically, the in vivo response of SE-CBV was about 40% smaller than that of GE-CBV in rat brain at low basal values of CBV, a result that is consistent with physics predictions under the simplifying assumption of uniform vessel dilation. However, increasing values of basal CBV were associated with monotonically increasing mean vessel sizes and monotonically decreasing GE to SE ratios of functional changes in CBV (fCBV). This result suggests the presence of large but weakly reactive conduit vessels at high basal values of CBV. Hence, we conclude that GE imaging is the method of choice for functional MRI (fMRI) using exogenous contrast agent in most cases, although SE methods may represent a more spatially linear representation of underlying neural activity that becomes most apparent in regions with high basal CBV, such as the cortical surface.

Characterization of event-related designs using BOLD and IRON fMRI.

Despite many desirable characteristics, event-related (ER) stimulus designs for BOLD and IRON suffer from low detection power relative to block designs because the hemodynamic impulse response function (IRF) acts as a low-pass filter on neural activation to attenuate the size of differential responses to alternate stimuli. While the use of exogenous contrast agent (IRON technique) provides an alternative fMRI method in animal models to improve sensitivity and spatial localization, the inherently slower hemodynamic IRF causes IRON detection efficiency to decrease faster than BOLD efficiency as the interstimulus interval (ISI) is shortened. Using simulations based upon assumptions of stimulus-response linearity and experimental data obtained in awake, non-human primates, this study compared detection efficiencies for fixed, random and semi-random ISI distributions for BOLD and IRON techniques. A larger relative gain in detection efficiency at short ISI was obtained by randomized designs using IRON contrast relative to BOLD contrast due to the slower IRF of the IRON method. To quantify tradeoffs between detection efficiency and the predictability of stimulus presentation, the Shannon entropy was introduced as an objective measure of predictability. Small amounts of entropy can be traded for large gains in efficiency, particularly for the IRON method.

Repeated fMRI using iron oxide contrast agent in awake, behaving macaques at 3 Tesla.

Iron oxide contrast agents have been employed extensively in anesthetized rodents to enhance fMRI sensitivity and to study the physiology of cerebral blood volume (CBV) in relation to blood oxygen level-dependent (BOLD) signal following neuronal activation. This study quantified the advantages of exogenous agent for repeated neuroimaging in awake, nonhuman primates using a clinical 3 Tesla scanner. A monocrystalline iron oxide nanoparticle (MION) solution was injected at iron doses of 8 to 10 mg/kg in two macaque monkeys. Adverse behavioral effects due to contrast agent were not observed in either monkey using cumulative doses in excess of 60 mg/kg. Relative to BOLD imaging at 3 Tesla, MION increased functional sensitivity by an average factor of 3 across the brain for a stimulus of long duration. Rapid stimulus presentation attenuated MION signal changes more than BOLD signal changes, due to the slower time constant of the blood volume response relative to BOLD signal. Overall, the contrast agent produced a dramatic improvement in functional brain imaging results in the awake, behaving primate at this field strength. (c) 2002 Elsevier Science (USA).