For b-SSFP fMRI with adequate resolution and coverage, fast 3D acquisition techniques were combined with the two-acquisition method (9
) for whole-brain coverage. The corresponding SNR and specific absorption rate (SAR) were also calculated for comparison with the conventional methods.
b-SSFP acquisition involves short TR, typically a few milliseconds to at most tens of milliseconds. Such short TR allows 3D imaging compatibility. Furthermore, in the presence of blood flow and motion, 3D volumetric acquisitions provide a much more stable steady-state compared to the 2D acquisitions which will inevitably have blood flowing in and out of the thin slice while the location of the slice also changes with motion. 2D multi-slice acquisitions can also lead to additional overhead in scan time to move in and out of steady-state for each slice. Therefore, 3D volumetric acquisition is a natural choice to obtain proper contrast and efficient spatial coverage for b-SSFP fMRI acquisitions.
For 3D acquisitions, the most straightforward strategy is to use 3D Cartesian (3DFT) trajectories (). Because the TRs are short, the acquisition time using 3DFT is feasible for a relatively low-resolution and small-volume coverage. However, to obtain high-resolution acquisitions with practical volume coverage, an alternative acquisition strategy is necessary. To achieve such a goal, we chose interleaved stack-of-EPI and interleaved stack-of-spiral acquisitions ().
Figure 3 3D k-space trajectories and scan time for b-SSFP fMRI. (a) Any 3D imaging trajectories can be incorporated into a b-SSFP acquisition including simple 3DFT readout. To allow fast acquisitions for high spatial and temporal resolution, stack-of-EPI (b) and (more ...)
To compare the efficiency of different acquisition strategies, scan times were compared in . The comparison was performed for two different cases with different coverage and resolution (see legends to for further details). The first case was for whole-brain coverage and the second case was for high-resolution acquisition of a small volume of interest. Scan time was calculated as a function of TR. The choice of TR can potentially determine the spatial scale sensitivity as well as the overall functional contrast. Therefore, the comparison is valid only for identical TRs.
Functional brain imaging studies often target a specific brain area such as the primary visual cortex. In such cases, it is only necessary to image a localized region of the brain. To cover a certain localized region using passband b-SSFP fMRI methods, one simply needs to select the region of interest, shim around that region and then perform the acquisition. To fine tune the volume of interest, phase-cycling angles can also be adjusted to shift the passband region of the b-SSFP response. Due to the relatively large volume coverage provided by the large flat portion of the b-SSFP off-resonance profile, a single acquisition is often sufficient for targeted region-of-interest scans.
However, when whole-brain coverage is required, two acquisitions with different phase-cycling angles (28
) can be combined (see ). With two acquisitions at a 180° phase-cycling angle and a 0° phase-cycling angle, the entire off-resonance spectrum can be covered with the passband region of at least one of the two acquisitions (9
). To avoid mixing contrast from the passband region and the transition-band region, a maximal intensity projection (MIP) method was chosen for the combination. The passband (flat) portion of the b-SSFP off-resonance spectrum has a higher signal level. Therefore by selecting pixels from the image that have higher signal intensity, the passband acquired portion can be selected. The pixel selection was performed with the temporally averaged image from the whole fMRI acquisition so that each pixel is selected from one phase-cycling angle image throughout the time series. The MIP selection was then low-pass filtered to generate a selection mask that has a more continuous region unaffected by noise.
Figure 4 Two-acquisition method for passband b-SSFP fMRI. (a) By combining the 180° phase-cycled image and the 0° phase-cycled image, the passband of the two acquisitions cover the entire off-resonance spectrum. (b) The two images are combined (more ...)
It is important to note that while the two-acquisition method can cover the whole brain with just two acquisitions, in some cases, it may not be possible to repeat two identical exams. For example, the novelty of stimuli may be crucial for the experimental design. To avoid such problems, alternating between the two steady-states can be a useful approach. However, there will be scan time overhead during the transition, which will limit the temporal resolution.
When imaging at the given field strength and RF coil, the SNR associated with thermal noise is proportional to the following parameters where f (ρ, T1, T2) is the pulse sequence dependent function that determines the signal amplitude.
For acquisitions with the same spatial and temporal resolution, the voxel size is constant while the total readout and the function f depend on the pulse sequence. The total readout interval is dependent on the readout duty cycle defined as the ratio of the readout time per each TR. For GRE-BOLD imaging, the readout duty cycle is between 0.01 to 0.02 (TR = 1.5 – 3 s, readout duration of 100 ms). Passband b-SSFP imaging has higher readout duty cycle in the range of 0.2 to 0.8 (TR = 5 – 20 ms, readout duration of 2 – 16 ms). When TR is kept constant, the signal intensity (f) is higher in the case of b-SSFP imaging compared to GRE. However, since typical functional acquisitions for GRE-BOLD involve longer TR than that involved in b-SSFP imaging, f is usually larger in the case of GRE-BOLD. In the gray matter, f is typically 3 – 5 times larger in GRE-BOLD compared to b-SSFP imaging. Overall, the thermal noise SNR for passband b-SSFP is approximately 2 – 27 times higher than that of GRE-BOLD. This analysis is neglecting physiological noise. When the physiological noise is the dominant source of noise, such improvements in SNR will not be apparent. However, for high-resolution scans, the thermal noise is expected to be an increasingly dominant source of noise. For example, for the 1 × 1 × 1 mm3 resolution protocol described in the visual field mapping experiment, the expected b-SSFP acquisition SNR is 4.018 times larger compared to that of GRE-BOLD.
Specific Absorption Rate
SAR can be compared based on the RF energy deposition for each imaging method. Simple calculations can provide comparisons for GRE-BOLD, SE-BOLD and b-SSFP fMRI methods.
For GRE-BOLD and SE-BOLD, imaging is typically done with the multi-slice acquisition scheme. With the multi-slice approach, while the TR for each slice is long, the RF energy is deposited in the whole imaging volume every time an RF pulse is played out for each slice excitation. Therefore, the difference in RF energy deposition for GRE-BOLD, SE-BOLD and passband b-SSFP fMRI methods can be calculated by calculating the difference in RF power deposition per TR times the difference in number of interleaves used for the in-plane encoding. This is assuming the same number of slices is being encoded for all three methods.
As for the RF power deposition per TR, GRE-BOLD typically uses 30o - 90° flip angles; SE-BOLD involves a 90° and a 180° pulse while passband b-SSFP method can be used with a 30° - 60° flip angle pulse. Since the GRE or SE-BOLD acquisitions are usually performed in 1 – 2 shots, while the passband b-SSFP method requires 10 – 20 shots for each phase encoding location, the difference is 5 – 20 times more RF pulses for passband b-SSFP methods. Overall, the SE-BOLD method has 5 – 45 times higher SAR compared to GRE-BOLD and the passband b-SSFP method has 0.56 – 80 times SAR compared to the GRE-BOLD method. The passband b-SSFP fMRI method has a number of parameters that can be quite flexibly selected so that a comparable SAR can be achieved as GRE-BOLD if needed. For example, in the case of the whole-brain coverage protocol used for the breath-holding experiments described later, compared to the GRE-BOLD, SAR of passband SSFP fMRI is only 1.54 times higher while the SAR of SE-BOLD is 8.27 times higher.
Functional MRI Studies
Several experiments were performed to demonstrate the viability and unique capabilities of passband b-SSFP based functional imaging (). All experiments were conducted using a GE 3 T Excite system with a maximum gradient of 40 mT/m and maximum slew rate of 150 T/m/s. A total of 15 normal healthy volunteers participated in the study with the approval of the Stanford University institutional review board (13 males, 2 females; 23 – 55 years old). Subjects were individually recruited for a single session. Some subjects participated in more than one session but no subject participated in all the different types of studies. All the results presented in this study were obtained with spiral acquisitions for both the GRE-BOLD and passband b-SSFP fMRI studies. For all experiments, 4 dummy acquisitions were used. In the case of passband b-SSFP acquisitions, 4 dummy acquisitions, which included more than 1000 dummy TRs, were used to make sure steady-state was reached before the actual fMRI scans. The flip angles for GRE-BOLD acquisitions were 70°, and for passband b-SSFP acquisitions 30° (other than for the hemodynamic response function measurements with varying flip angles). The GRE-BOLD acquisitions all had a TE of 30 ms and the passband b-SSFP acquisitions all had minimum TE. The minimum TE depends on the slice-select z-gradient rewinder duration and the z-phase encoding gradient duration. Therefore, the thinner the slab and the higher the z-resolution, the minimum TE becomes longer except for the 0.9 × 0.9 × 0.9 mm3 resolution retinotopy experiment where the minimum TE was further reduced by combining the slice select gradient rewinder and the phase encode gradient. summarizes the different functional paradigms and the corresponding imaging volumes used for our experimental studies.
Experiments conducted using passband b-SSFP fMRI.
Breath-holding experiments were designed to demonstrate the capability of passband b-SSFP fMRI for distortion-free full-brain coverage. Hypercapnia induced by breath-holding increases cerebral blood flow (CBF), resulting in increased oxygenation across the entire brain (29
). Breath-holding is thus a simple and robust method to elucidate the extent to which a particular functional imaging technique can measure the degree of oxygenation saturation across the whole brain. In this study, to compare the effectiveness of the full-brain coverage, breath-holding experiments were conducted with GRE-BOLD and passband b-SSFP fMRI in the same subjects within the same imaging session lasting for less than 30 minutes. GRE-BOLD technique was chosen for comparisons since it is the most widely accepted method for functional brain imaging.
The GRE-BOLD and passband b-SSFP fMRI experiments were conducted with identical spatial and temporal resolution. The spatial resolution was 2 × 2 × 5 mm3 and the temporal resolution was 3 s. For GRE-BOLD, 22 × 22 cm2 field-of-view (FOV) spirals with 2 interleaves were used with a 20-slice acquisition. For passband b-SSFP, the FOV was chosen to be 22 × 22 × 12 cm3 covering the whole cerebral cortex (see ). The passband 3D b-SSFP acquisitions involved 14-interleave spirals and 24 kz phase encoding locations. The temporal resolution of the fMRI acquisition was 3 s with a TR of 1.5 s for GRE-BOLD (two-shot spiral) and 8.928 ms for passband b-SSFP. For passband b-SSFP acquisitions, TE was 1.632 ms and the readout duration per TR was 3.392 ms. For the passband b-SSFP acquisitions, a 180° phase-cycling and a 0° phase-cycling acquisitions were combined with MIP as described in the two-acquisition method section.
The subjects were instructed to inhale and hold their breath when the screen showed a small red box in the middle of the visual field and to breathe normally when the box turned green. Breath holding and normal breathing were alternated in 15 s intervals for 255 s starting and ending with a normal breathing period.
Full-Field Flashing Visual Checkerboard Experiment
As an initial attempt to demonstrate the passband b-SSFP fMRIs capability to generate oxygenation contrast following stimulus-induced neuronal activation, simple on/off full visual-field flashing checkerboard experiments were performed. The flashing checkerboard on and off blocks were in 15 s intervals for a total duration of 2 min.
The FOV of the acquisition was 22 × 22 × 3 cm3 and the resolution was 2 × 2 × 2 mm3 to cover the visual cortex (see ). The 3D spiral acquisition consisted of 16 interleaved spirals and 16 kz phase encodes. The temporal resolution was 2 s with a TR of 8 ms and TE of 2.104 ms. The readout duration was 3.344 ms per TR. While a single acquisition was sufficient to cover the visual cortex, the two-acquisition scheme was chosen to demonstrate how distortion and signal-dropout free functional images can be obtained using two acquisitions.
Hemodymamic Response Function Measurement
For the comparison of the hemodynamic response functions (HRF) derived from passband and GRE-BOLD images, respectively, a full-visual field flashing checkerboard with a 3 s impulse duration was used. The impulse was repeated every 30 s for repeated measurements. The measurement was repeated 6 times every 30 s at each trial over 2 trials (12 measurements total). We averaged the signal across all voxels in the primary visual cortex (V1) (see ). V1 was identified using standard visual field mapping methodology (30
) in previous scanning sessions with an identical stimulus setup. An oblique volume through the visual cortex was selected for both acquisitions. The passband b-SSFP acquisition FOV was 22 × 22 × 6 cm3
and the spatial resolution was 2 × 2 × 3 mm3
. 3D spiral acquisitions used 14 interleaves with 12 phase encoding locations in kz
, a TR
of 8.928 ms, TE
of 1.952 ms, and a readout duration of 3.392 ms per TR
. In order to show the flip angle dependency in passband fMRI, the flip angle was varied from 20o to 70° in 10° steps. GRE-BOLD images were acquired with a 22-cm FOV and 3.4 × 3.4 × 5 mm3
resolution. Temporal resolution was 1.5 s for both acquisitions.
Visual Field Mapping
High-resolution visual field mapping (30
) was performed to demonstrate the high-resolution imaging capability of the passband b-SSFP fMRI. Visual field mapping was chosen since it produces extra temporal phase information that can be used to verify the passband b-SSFP fMRI techniques capability to accurately track the time course of the oxygenation signal. Visual field mapping experiments involved a stimulus with a contrast pattern comprising a rotating wedge (90°) that slowly rotated around fixation, completing a cycle in 42 sec. The wedge rotated around 6 times (total duration 4 min 12 s).
Two different experiments were conducted for the high-resolution visual field mapping. For both experiments, the FOV was 8 × 8 × 1 cm3 covering the primary visual cortex (see ). The temporal resolution was 3.5 s. One experiment had a spatial resolution of 1 × 1 × 1 mm3 with a TR of 10.936 ms and a TE of 2.460 ms. The readout duration was 3.104 ms. The 3D spirals had 16 interleaves with 20 kz phase encodes. The data were averaged from 6 runs. The other experiment had a spatial resolution of 0.9 × 0.9 × 0.9 mm3 with a TR of 11.364 ms and a TE of 1.616 ms. The readout duration was 4.128 ms. The 3D spirals were designed to have 14 interleaves and 22 phase encoding in kz. For this experiment, the data were averaged from 4 runs.
Functional Data Analysis
The acquired 4D functional data set was reconstructed with a gridding reconstruction (32
). Using FSL (33
), hypercapnia and the full field visual stimulation data were analyzed with a high-pass filter cutoff of 30 s, MCFLIRT motion correction and BET brain extraction. Cluster thresholding was used with z threshold of 2.3 and cluster p threshold of 0.05. Custom software (VISTA, see http://white.stanford.edu/software
) was used for the hemodynamic response function measurements and the visual field map analysis. For the analysis using VISTA, no corrections other than high-pass filtering were used. For the hemodynamic response function measurements, the primary visual cortex V1 was first identified. Then, the signal was averaged over the selected region. The visual field map data was coherence thresholded (34
) and overlaid onto T1
anatomical images and/or color coded on a flattened cortical surface. The coherence threshold was 0.3 for the 1 mm isotropic image acquisition and 0.5 for the 0.9 mm isotropic acquisition.