Dedicated sequences for auditory fMRI

Summary of Chapter 5: Results - Continuous EPI: The aim of the work presented in this chapter was to characterize the spatial and temporal imaging characteristics of the Continuous EPI sequence compared to the standard (conventional) EPI sequence, and to compare and optimize its performance in relation to conventional EPI for the use in auditory fMRI experiments. Characterization Two characteristic image artifacts which appear in the Continuous EPI sequence were identified and characterized. One, based on the irregular echo spacing of the readout train, results in a multiple ghosting artifact, which is hardly noticeable under practical conditions. The other, resulting from gradient shape imperfections in the water excitation slice select gradients, leads to an intensity modulation over multi-slice images and can be corrected by a system-specific bias on the second of the two slice selection gradients. Further, the fat suppression using these water selective binomial pulses was shown to be equally effective when applied to conventional and Continuous EPI sequences. For fMRI applications, the temporal signal stability of a sequence is a crucial factor influencing the detection efficiency of functional activation. Based on histograms of the voxel-wise relative standard deviation, the temporal stability of Continuous EPI could be shown to be equal to that of matched conventional EPI sequences at 1.5, 3 and 7 T. Finally, based on sequence sound recordings, the use of “soft”, sinusoidally shaped gradient ramps (which occupy a large part of the gradient duration) are beneficial for the suppression of the pulsating sound component. fMRI experiments The second part of this chapter consisted in the results of seven auditory fMRI experiments in which conventional and Continuous EPI sequences were compared. In the first experiment, a 5 min pulsed sine tone block design experiment of four volunteers measured on the 1.5T Sonata system, consistently showed a larger BOLD response amplitude for the Continuous EPI sequence in all subjects, on average by 40%. The second experiment was a single volunteer 3 min proof-of-concept experiment of an interesting extension of the Continuous EPI, the auditory stimulation evoked by the periodic re-introduction of the pulsating gradient sound component. The third through fifth experiments compared the BOLD response amplitude using conventional and Continuous EPI at 1.5, 3 and 7T field strength using a pulsed sine tone stimulus of three different frequencies, which were presented in a pseudo-randomized order over a total duration of 15 min. While in the 7T experiment, a single run on one volunteer showed a 50% increased BOLD response amplitude for Continuous EPI for two of the stimulation frequencies, but no difference for the third, the predictive power of this result was severely limited by the measurement of only one single session. At 3 T, four volunteers were measured in two sessions per subject. In both sessions both a conventional and a Continuous EPI run was measured, with the order of those runs interchanged for the second session. While the inter-session and inter-individual differences were larger than the difference between sequences, the average BOLD response was greater for the Continuous EPI sequence at all three frequencies by 12 to 25%. At 1.5 T, the observed difference between sequences was even smaller, after complications (RF artifacts and the exclusion of one subject) in the first trial, a second trial on 6 volunteers (again measured in two sessions with interchanged sequence order) gave average improvements for Continuous over conventional EPI of only 3 to 11%, with even larger inter-individual and inter-session differences. These large variations were also reflected by the failure to observe consistently high significance levels in the activation patterns of the individual runs. While some of the variance may be explained by the lower contrast to noise level at 1.5T and the lower statistical power of the short stimulation epochs (compared to fMRI experiment 1), a part of the more unusual activation patterns could also be traced back to subject motion (both stimulus-correlated and uncorrelated motion was observed). The last two experiments aimed at exploring some of the sequence parameters in the Continuous EPI sequence that could be expected to influence the acoustic performance as well as testing some of the assumptions that had been used in its implementation. Both experiments, even though measuring 6 and 8 volunteers, respectively, were plagued by insufficient statistical power due to the even more extreme variance between sessions and subjects. They both used 16 s epoch block designs which are known to yield optimum statistical power [169, chapter 1]. Especially with the clear effect seen in the block design fMRI experiment 1 in mind, these experiment could have been expected to yield statistically significant results. Different factors could have contributed to the failure to do so. On the one hand, rather long sessions of around 45min were used (compared to about 25 min in exp. 1). Although in these experiments an attempt was made to control subject attention by simultaneously projecting a cartoon movie, varying attention levels could be a part of the problem (or the distraction by the movie itself). On the other hand, the backwardspeech stimulus which was used here might not have been an ideal stimulus even though it resulted in consistent activation patterns of high statistical significance. As a third factor, the scanner system itself might have had some unexpected influence on the sequence differences measured in these experiment (and the preceding experiment 4). Compared to the Sonata system, the Avanto system used here is much better damped acoustically (an important selling point, and easily detectable when listening to the same sequence on both scanners). Here, it could be suspected that the general increase in acoustic contrast between stimulus and scanner sound might have reduced the difference in activation measured with Continuous versus conventional EPI sequences, even though the trends from a volume graded acoustic stimulation experiment do not support (nor contradict) this, and stimulus volume is known to have no direct influence on BOLD response amplitude ([117]). Of the non-significant trends found in these experiment, maybe the most robust one is that of both sequences resulting in the same BOLD response amplitude in a visual task (something that has been shown clearly for the original implementation of Continuous EPI [152]). Another trend, reproducible between the two experiments, was that of an increase in BOLD response for increasing fundamental frequency of the Continuous EPI sequence sound beyond the psycho-acoustically motivated “critical point” of about 30 Hz. However, for the highest frequency setting of 110 Hz measured in experiment 7, very low response amplitudes were measured. Summary of Chapter 8: Results - BURST: In the course of the present work, the steady state behavior of gradient echo BURST (URGE) was examined in detail. An approximate relation for the optimal flip angle and the achievable signal amplitude could be given and compared to more exact numerical simulations and phantom measurements. Also, the size of the spoiler gradient necessary to obtain efficient dephasing of remaining transverse magnetization has been determined to be at least as large as the encoding gradient. As an alternative, gradient spoiling along a different gradient axis has been proposed and found to be beneficial in practical situations. An URGE-EVI sequence was implemented on two clinical 1.5T and 3T systems using the above findings. Sound levels during scanning were only 6 dB(A) above the ambient noise level, compared to about 30-35 dB(A) for EPI sequences. Temporal signal stability was found to be reduced, compared to the standard EPI sequence at 3 T, but still in a range where reliable BOLD fMRI measurements should be possible. Also, the signal to noise ratio was found to be comparable to an EPI sequence with similar parameters (which were certainly not optimal for the EPI). In an fMRI experiment combining auditory stimulation with a simultaneous finger-tapping task, the BOLD sensitivity of the URGE sequence was established, as highly significant activation was found in the expected location for the motor cortex and the supplementary motor area. However, this experiment has failed to show activation in the expected location of the primary auditory cortex. This was very likely a result of pronounced distortion and signal drop-out artifacts present in the functional image volumes. As currently implemented, the usefulness of URGE-EVI for auditory fMRI is therefore seen to be severely limited. The main obstacles are pronounced distortion artifacts similar to those expected for a relatively lowbandwidth EVI sequence and signal drop-outs due to the rather large voxel size. For the currently used 3D segmented phase encoding scheme and given the limitations imposed by the gradient hardware – and especially by a cumbersome limitation in the scanner’s current image reconstruction software – these issues are not easy to resolve. The removal of that software limitation in the upcoming version opens prospects of making higher temporal and spatial resolution possible, especially in combination with parallel imaging techniques. This might also reduce the signal drop-out artifacts. While the distortion artifacts might be relieved by using 3D phase encoding scheme using only 2D segments (a stack-of-EPI trajectory), such schemes (which multiply refocus the echoes of a BURST excitation) can be expected to give rise to ghosting artifacts based on phase or magnitude errors in the individual echoes.