Exogenous contrast agent improves sensitivity of gradient‐echo functional magnetic resonance imaging at 9.4 T

Abstract

Relative to common clinical magnetic field strengths, higher fields benefit functional brain imaging both by providing additional signal for high-resolution applications and by improving the sensitivity of endogenous contrast due to the blood oxygen level dependent (BOLD) mechanism, which has limited detection power at low magnetic fields relative to the use of exogenous contrast agent. This study evaluates the utility of iron oxide contrast agent for gradient echo functional MRI at 9.4 T in rodents using cocaine and methylphenidate as stimuli. Relative to the BOLD method, the use of high iron doses and short echo times provided a roughly twofold global increase in functional sensitivity, while also suppressing large vessel signal and reducing susceptibility artifacts. MRI is widely used to assess brain function in humans and animals due to a powerful combination of capabilities, including high spatiotemporal resolution, volumetric coverage, and the potential for noninvasive, longitudinal studies. Many of the target applications for fMRI in animal models are inherently challenging in terms of sensitivity. For instance, functional signals often are attenuated in disease or recovery states, such as the evolution of neuronal plasticity during recovery from stroke (1-3). Pharmacological stimuli can produce widespread, graded, dosedependent changes in local brain function; low-field blood oxygen level dependent (BOLD) signal is simply inadequate for detecting changes in many brain regions without averaging results from a very large number of animals (4,5).High magnetic field strengths provide numerous advantages for fMRI, as well as challenges (6). Sample polarization increases with magnetic field, providing additional signal that can be traded for higher spatial resolution. Functional changes in the BOLD relaxation rate also increase with field strength (7), making BOLD detection power more competitive with that provided by an exogenous agent (8). Moreover, paramagnetic deoxyhemoglobin shortens blood relaxation times at high field strengths, which should decrease spatially nonspecific signal associated with draining vessels. However, the time scale for relaxation of transverse magnetization using gradient echoes (T 2 *) becomes progressively shorter and more heterogeneous, especially in regions near magnetic susceptibility interfaces that arise at air-tissue and bone-tissue interfaces. Signal dropout and image distortion reduce some of the theoretical advantages of BOLD fMRI at high fields by forcing a choice between increased image artifacts or the reduced sensitivity that accompanies short gradient echo times or spin echo methods.Because of the limitations of BOLD sensitivity, many fMRI applications in animal models have employed exogenous contrast agents (1-3,9 -11), which experimentally have been shown to markedly improve fMRI sensitivity at magnetic field strengths up to 4.7 T (4,5,8,12-14). The use of exogenous agents with very long blood half lives for fMRI has been termed IRON fMRI (5), to denote the increas...

Polymer-Coated Superparamagnetic Iron Oxide Nanoparticles as T 2 Contrast Agent for MRI and their Uptake in Liver

“…At 7 T, 15-20 mg Fe/kg ultrasmall superparamagnetic iron oxides improve functional contrast-to-noise ratio (CNR) by 70% in rats compared with BOLD contrast [38]. Mandeville et al [39] reported that CNR in CBVweighted fMRI with 28 mgFe/kg improved twofold compared with BOLD upon pharmacological stimulation with cocaine. Even in humans, relatively high dosages of ultrasmall superparamagnetic iron oxides of 7 mgFe/kg have been used in fMRI acquisitions [40].…”

Real-time electrochemical monitoring of brain tissue oxygen: A surrogate for functional magnetic resonance imaging in rodents

“…The CBV fMRI measurements were obtained using a long half-life iron oxide contrast agent (ferumoxtran-10; Sinerem ® , Guerbet, France) to label the blood pool (Mandeville et al, 2004). A moderate increase (ca.…”

Inhibition of stimulated dopamine release and hemodynamic response in the brain through electrical stimulation of rat forepaw

“…fMRI MR images were acquired repeatedly using a gradient echo EPI sequence with the IRON (Increased Relaxivity for Optimized Neuroimaging) technique [6,21] to assess relative cerebral blood volume (rCBV) changes. Since the rCBV measurement is insensitive to the magnetic field strength [21], data were acquired using both 4.7T and 9.4T MRI scanners (Bruker, Billerica, MA). Basic EPI parameters were: 16 segmentations, TR/TE of 625ms/6ms (a 10s/ volume temporal resolution), in-plane resolution of 0.2345mm × 0.2345mm, and 20 contiguous coronal slices, each 1 mm thick.…”

“…Maps of rCBV responses were calculated on a pixel-by-pixel basis as described in [6,21]. The rCBV effect induced by AMPH and EA were characterized by two gamma functions (t*exp (-t/τ)) using general linear model (GLM), with time constant τ representing the peak time of the gamma curve.…”