Quantitative NumART 2 * mapping in functional MRI studies at 1.5 T Gisela E. Hagberg a,b,* , Marta Bianciardi a,b , Fabiana Patria a , Iole Indovina a,b a Laboratory of Functional Neuroimaging, Fondazione Santa Lucia IRCCS, Rome, Italy b Enrico Fermi Centre, Rome, Italy Received 15 August 2003; received in revised form 22 August 2003; accepted 23 August 2003 Abstract Quantitative mapping of the effective transverse relaxation time, T 2 * and proton density was performed in a motor activation functional MRI (fMRI) study using multi-echo, echo planar imaging (EPI) and NumART 2 * (Numerical Algorithm for Real time T 2 *). Comparisons between NumART 2 * and conventional single echo EPI with an echo time of 64 ms were performed for five healthy participants examined twice. Simulations were also performed to address specific issues associated with the two techniques, such as echo time-dependent signal variation. While the single echo contrast varied with the baseline T 2 * value, relative changes in T 2 * remained unaffected. Statistical analysis of the T 2 * maps yielded fMRI activation patterns with an improved statistical detection relative to conventional EPI but with less activated voxels, suggesting that NumART 2 * has superior spatial specificity. Two effects, inflow and dephasing, that may explain this finding were investigated. Particularly, a statistically significant increase in proton density was found in a brain area that was detected as activated by conventional EPI but not by NumART 2 * while no such changes were observed in brain areas that showed stimulus correlated signal changes on T 2 * maps. © 2003 Elsevier Inc. All rights reserved. Keywords: Functional MRI (fMRI); Quantitative; Effective transverse relaxation; T 2 * 1. Introduction The ideal acquisition technique for functional magnetic resonance imaging studies (fMRI) should comprise a num- ber of desirable features. First of all, it must be fast enough to consent whole brain coverage within a couple of seconds. A high contrast to noise ratio and high spatial specificity should also be guaranteed in order to obtain reproducible activation patterns. The most widely used acquisition scheme in fMRI is gradient echo, echo planar imaging (EPI), with which activation-induced changes in the effec- tive transverse relaxation time (T 2 *) are detected at a fixed echo time (TE). The TE is generally adjusted close to the resting tissue T 2 * so as to produce maximal blood oxygen- ation dependent (BOLD) contrast [1,2]. EPI is a fast tech- nique, and images of the whole brain can be obtained in less than 3 s. Extensive use of BOLD-EPI during the last 5-10 years have suggested its robustness for a large variety of fMRI studies, stretching from studies of primary brain func- tion—may it be sensory or motor—to higher order cogni- tion. Nevertheless, the contrast to noise in single echo EPI inherently depends on the relation between the chosen TE and the T 2 *-value of the resting brain, that may vary be- tween 50-100 ms dependent on the brain area [3]. This echo time dependence may cause variation in activation patterns and detectability, as has been shown in a number of previ- ous fMRI studies [4,5]. Moreover, findings of activations that extend over large brain areas, perhaps even enclosing areas remote from the primary area of activation, may rise some doubts regarding the spatial specificity of the single echo EPI approach. Indeed, it is well-known that signal changes in BOLD images may extend beyond the paren- chymal capillaries in the immediate vicinity of active neu- rons, and manifest itself in remote draining vessels. The origin of this effect is linked with the gradient echo EPI technique itself that does not discern between vessels of different size, unlike spin echo methods [6]. In addition, signal contributions by inflowing spins that have a different T 1 saturation than the surrounding tissue may also have an impact on the extent of the activation pattern. A potential remedy for inflow effects is the application of dual-echo methods that encompass the acquisition of two images at different echo times in a single shot [7]. * Corresponding author. Tel.: +39-06-5150-1349; fax: +39-06-5150- 1213. E-mail address: g.hagberg@hsantalucia.it (G. Hagberg). Magnetic Resonance Imaging 21 (2003) 1241–1249 0730-725X/03/$ – see front matter © 2003 Elsevier Inc. All rights reserved. doi:10.1016/j.mri.2003.09.003