T1ρ contrast in functional magnetic resonance imaging

The most frequently used sequence in functional MRI (fMRI) studies, gradient-echo (GE) echo-planar imaging (EPI), is particularly sensitive to changes in the oxygenation state of hemoglobin, commonly referred to as blood oxygenation level-dependent (BOLD) contrast (1). BOLD contrast results from a complex interaction of physiologic changes, including changes in cerebral blood flow, cerebral blood volume (CBV), and the cerebral metabolic rate of oxygen consumption (2). Recently introduced functional sequences detect neural activity by directly or indirectly measuring these or other physiologic changes (3–6). Generally, these sequences allow for quantitation of physiologic parameters or more accurate localization of neuronal activity, but are less sensitive in detecting activation than conventional BOLD fMRI. An alternative method for detecting neural activity using MRI is via changes in T1ρ, the spin–lattice relaxation time in the rotating frame. T1ρ is sensitive to physical processes with correlation times (τc) close to the reciprocal of the applied spin-locking frequency (typically on the order of several milliseconds). Processes with relevant τc include dipolar fields created by slowly tumbling molecules (7), the diffusion of spins through susceptibility gradients (8), and chemical exchange processes (9). The potential of spin-locking to reveal functional changes in the brain lies in the fact that the T1ρ of blood increases with increasing hemoglobin oxygen saturation and is longer than the T1ρ of brain tissue, which is reported to be insensitive to changes in blood-induced susceptibility gradients (10). T1ρ preweighting can be prepended to a GE EPI sequence with the resultant signal (assuming a 90° flip angle) taking the form S(TR,TSL,TE)∝∑ixi(1−e−TR/T1i)e−TSL/Tρie−TE/T2*i [1] where x is the volume fraction of the ith compartment (e.g., gray matter, blood, CSF), TR is the repetition time, TSL is the duration of the spin-lock pulse, TE is the echo time of the gradient echo, and T1ρ is the relaxation in the rotating frame for a given spin-locking frequency. In the brain, blood and tissue compose the largest fractions of activated voxels. At 3 T, T1 is longer, and T2* is shorter, in blood compared to brain tissue. Consequently, local increases in blood volume fraction due to neural activation (reported to be on the order of 20–40% (11–13)) generate negative contrast in conventionally weighted MRI, according to the T1 and T2* terms of Eq. [1]. This contrast subtracts from any positive BOLD contrast caused by blood saturation effects on T2*. Like T1, T1ρ is longer in blood than it is brain tissue (~110 ms versus ~75 at 3 T). However, because T1ρ decay acts like T2* in Eq. [1], increases in CBV will cause overall parenchymal (perfused tissue: tissue + blood) T1ρ to increase and thus create positive contrast to neural activation. Because the positive T1ρ (spin-lock) contrast due to increased CBV adds to positive T2* BOLD (EPI) contrast, a sequence that derives functional contrast from both T1ρ and T2* contrast may have certain advantages over a traditional EPI sequence. A major distinction between T1ρ and T2* contrast is a markedly different sensitivity to static susceptibility gradients. The lengthy echo times used in the traditional EPI sequences, required to produce adequate T2* BOLD contrast, result in significant signal loss in areas with large static susceptibility gradients due to intravoxel dephasing (14). A variety of methods have been implemented to reduce susceptibility-induced signal losses in EPI data, including static gradient shimming (15), modified pulse sequences (16–18), and susceptibility matching (19). In practice, however, appreciable signal losses remain in EPI data, and fMRI sensitivity in brain regions near tissue–air boundaries is adversely affected. In contrast, T1ρ is not very sensitive to static susceptibility gradients. Spin-locking acts on the transverse magnetization in a manner analogous to a Carr–Purcell echo train (20) with a very short interecho interval, equal to the reciprocal of the spin-locking frequency. Therefore, static susceptibility effects are efficiently refocused, or “spin-locked”, and T1ρ contrast can be obtained with little static susceptibility-induced signal loss. This work presents fMRI results at 3 T using a T1ρ-modified EPI sequence to measure activation in the visual cortex. This new sequence produces a positive CBV-based contrast, augments BOLD contrast, and reduces static susceptibility-induced signal loss while maintaining high detection sensitivity. A model is presented that estimates the CBV and blood oxygenation contributions to the T1ρ contrast, and the model predictions are compared to the experimental results from the visual fMRI study.