Comparison of tissue occupancy functional contrasts for 3D turbo-spin-echo acquisition

Introduction: Functional vascular occupancy imaging has demonstrated task correlated MR signal changes using inversion recovery (IR) prepared images, where the inversion time (TI) has been chosen to selectively null blood (vascular space occupancy – VASO, (Lu et al., 2003)), grey matter (VASO by tissue suppression – VAST (Wu et al., 2008)), or CSF (VASO-FLAIR (Donahue et al., 2006)). Weakness of these approaches are that functional responses may not be due to volume changes in a single tissue compartment, and that the underlying imaging sequence may be sensitive to other mechanisms (e.g. BOLD) (Donahue et al., 2006). Our purpose was to compare the functional responses from different vascular space occupancy preparations of a short TE turbo-spin echo (TSE) sequence. Methods: Eight healthy subjects were scanned at 3T after providing informed consent. The task consisted of self-paced, left-hand finger tapping. Four variants of vascular occupancy fMRI were tested: VASO (TI = 646ms), VAST (TI = 578ms), VASO-FLAIR (TI = 781ms) and nonInVASO (no inversion pulse VASO), all based on a 3D TSE acquisition (TE/TR 8.4ms/2.4s, 4 shots, time per volume 9.6s, 1.5x1.5x1.5mm, 8 slices, FOV 222x60x12mm, 180° refocusing pulses, ant/post sat bands). Task blocks were 48s long, and each run consisted of 45 volumes, with the sequence order varied between subjects. These scans were centered on the focus of BOLD response in/adjacent to the right hand knob detected with an EPI acquisition (TE/TR 30ms/3s, 3x3x3mm, 42 slices) performed during execution of the same task (30 second blocks, 70 volumes). Whole-brain T2, 3D T1, and nonInVASO images were also obtained. GLM analysis (1.5mm FWHM smoothing, high pass filter cut-off 100s, default gamma-variate hrf, GRF-based voxel-wise corrected p<0.05) was per formed following motion correction and ICA denoising (4 components) using fsl (v 5.0.1). Due to slight rotations during acquisition, only 6 slices were retained for analysis. Results: Despite operator confirmation of task performance, one subject showed minimal BOLD and no significant vascular occupancy responses, and was therefore excluded from analysis. In the other subjects, VASO, VAST and VASO-FLAIR showed nearly identical patterns and locations of activity (Figure 1) and no significant differences in the grey matter (GM), white matter, CSF distribution of activated voxels. The nonInVASO scans showed smaller volumes of activity. GM was the predominant site of response for all scans. VAST yielded the highest % signal changes; VASO yielded the highest z-score followed closely by VASO-FLAIR; and these all had signal changes negatively correlated with the task. The nonInVASO responses correlated positively with the task and were the smallest % signal change and maximum z-scores roughly one-third lower than VASO. Significant oppositely-signed responses (i.e. positive of VASO, VAST and VASO-FLAIR, negative for nonInVASO) were not observed.Conclusions: Our results suggest that VASO, VAST and VASO-FLAIR are sensitive to volume changes in the same tissue compartment. VAST yielded the highest % signal changes due mainly to the smallest baseline signal but this did not result in greater sensitivity to activation as indicated by maximum z-scores. The negative VAST response however, suggests that the inversion was not fully optimized to grey matter but could reflect T2 blurring of white matter signal. VASO was the most sensitive to activation followed closely by VASO-FLAIR. Similarly located activations were seen with nonInVASO, but with smaller spatial extents and lower sensitivity. The implications and operative mechanism for the nonInVASO functional contrast remain to be established. Possible mechanisms include BOLD contrast (through T2 sensitivity or blurring by the long TSE echo train), vascular space occupancy changes coupled with inherent blood-tissue contrast, diffusion, or changes within the tissue compartment as proposed for SEEP - signal enhancement by extravascular protons (Stroman et al, 2003).