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To improve ultra-high field diffusion-weighted imaging (DWI) in the presence of inhomogeneous transmit B1 field by designing a novel semi-adiabatic single-refocused DWI technique.
A 180° slice-selective, adiabatic radiofrequency (RF) pulse of 4 ms duration was designed using the adiabatic Shinnar-Le Roux algorithm. A matched-phase slice-selective 90° RF pulse of 8 ms duration was designed to compensate the nonlinear phase of the adiabatic 180° RF pulse. The resulting RF pulse combination, Matched-phase Adiabatic Spin Echo (MASE), was integrated into a single-shot echo planar DWI sequence. The performance of this sequence was compared to single-refocused Stejskal-Tanner (ST), twice-refocused spin echo (TRSE) and twice-refocused adiabatic spin echo (TRASE) in simulations, phantoms and healthy volunteers at 7T.
In regions with inhomogeneous B1, MASE resulted in increased signal intensity compared to ST (up to 64 %). Moderate increase in specific absorption rate (35–39%) was observed for adiabatic RF pulses. MASE resulted in higher signal homogeneity at 7T, leading to improved visualization of measures derived from diffusion-weighted images such as white matter tractography and track density images.
Efficient adiabatic SLR pulses can be adapted to single-refocused DWI, leading to substantially improved signal uniformity when compared to conventional acquisitions.
7 Tesla (7T) MRI scanners have the potential to improve techniques such as diffusion-weighted imaging (DWI) by providing increased signal-to-noise ratio (SNR) when compared to 3T scanners. However several physical effects, including severe inhomogeneity of the static field (B0) and transmit radiofrequency (RF) field (B1) and decreased tissue T2 values, stand in the way of performing robust DWI acquisitions at 7T. B1 variations across the imaging volume lead to signal intensity artifacts that become more severe when using RF pulses with large flip angles, such as the 180° RF pulse used to generate a single (1) or twice refocused (2) spin echo in DWI sequences. Shorter T2 values for brain tissue at 7T (45–50 ms as compared to 56–69 ms at 3T (3)) further affect the achievable SNR gain. Parallel transmit (PTx) systems, which exploit the added degree of freedom afforded by multiple transmit coils, may be employed to achieve uniform transmit B1 profiles (4–6). However, safety limits currently restrict PTx to the use small flip angles in vivo because the heterogeneous SAR profiles resulting from parallel transmission are difficult to model. Given the high flip angles required for refocusing, PTx is not readily translatable to diffusion MRI. Additionally, such an approach requires additional specialized hardware. Dielectric pads are valuable to improve B1 homogeneity and alter the transmit profile in a given region of the brain, but optimum placement around the subject’s head is difficult to predict. The effects of B1 inhomogeneity can also be alleviated by using adiabatic RF pulses, which operate over a wider range of B1 values. In previous preclinical and human studies a pair of adiabatic refocusing pulses in a twice-refocused adiabatic spin-echo (TRASE) DWI acquisition achieved more uniform signal intensity in the presence of B1 variation at high magnetic fields when compared to a conventional twice-refocused spin-echo (TRSE) approach (7,8). However the relatively long echo time (TE) of the TRSE and TRASE DWI sequences limit the SNR gain that may be achieved at 7T. In addition, using two refocusing pulses substantially increases RF power deposition as measured by the specific absorption rate (SAR), which reduces volume coverage or results in a longer acquisition time at 7T. Given these limitations, our goal is to use a single-refocused DWI preparation (1) that offers reduced TE and SAR, combined with an adiabatic 180° RF pulse to reduce the effect of inhomogeneous B1.
Although adiabatic refocusing pulses are typically used in a paired configuration in order to refocus the nonlinear phase deposited across the slice, investigators have also developed single-refocused adiabatic spin-echo sequences, using “matched-phase” 90° RF pulses that are designed to compensate the nonlinear phase induced by a single adiabatic refocusing pulse (9,10). Such methods allow the implementation of a matched-phase adiabatic spin echo (MASE) sequence, which can then be utilized to perform single-refocused DWI with adiabatic refocusing pulses. The purpose of this study is to develop a single-refocused MASE DWI sequence using an optimized slice-selective semi-adiabatic refocusing pulse coupled with a matched-phase excitation pulse, and to compare its performance to conventional DWI using linear-phase RF pulses and to the twice-refocused techniques TRSE and TRASE at 7T.
Semi-adiabatic pulses, which are a class of quadratic phase pulses allowing to trade-off adiabaticity, pulse length and deposited power, were designed using the adiabatic Shinnar-Le Roux (SLR) algorithm that has been previously described in detail (11). Here we briefly give the design steps leading to the refocusing pulses used in this work. First, a filter was generated using the firls function in Matlab (R2014a, The Mathworks, Natick, MA, USA), with inputs as follows:
With N = 355 samples; F = [0, 0.007, 0.017, 1] and A = [1, 1, 0, 0], which represent the relative low-pass filter frequency band edges and amplitude values; and W= [0.1/8, sqrt(0.01/2)], which contains the relative ripple amplitudes in the pass-band and stop-band respectively. Before SLR inversion, quadratic phase was applied using k=3000 cycles, in order to induce adiabatic behavior and distribute RF energy more uniformly, reducing peak B1 amplitude. After SLR inversion, the pulse was truncated, resulting in a 4 ms duration, 1.32 kHz bandwidth and 12.4 μT peak amplitude at adiabatic threshold putting the peak amplitude well below the 24 μT maximum amplitude allowed on our head transmit coil at 7T. Matched-phase excitation pulse: In a second step, a 90° excitation RF pulse was created in order to compensate the phase of the 180° adiabatic refocusing pulse. To achieve this, the beta polynomial of the 90° pulse was derived from that of the 180° pulse, such that:
The corresponding minimum-phase alpha polynomial α90 was then generated, and the pulse envelope was derived using the inverse SLR transform. The resulting 90° pulse had an 8 ms duration, 1.43 kHz bandwidth and 3.9 μT peak amplitude. RF pulse waveforms are shown in Fig. 1.
The complete pulse sequence diagram, showing the matched-phase spin echo inserted into a diffusion-weighted echo planar imaging (EPI) sequence, is provided in Fig. 2. In order to correct for Nyquist ghosting occurring in EPI readouts, phase correction needs to be performed using additional calibration scans (12). In our implementation, 3 calibration lines are acquired in the fast readout direction at the center of k-space. In conventional diffusion-weighted EPI these lines are typically placed after the initial 90° pulse. For a matched-phase spin echo, doing so would result in nonlinear phase present in the calibration lines, which would affect ghosting reduction techniques. To address this issue, the calibration lines were acquired outside the DWI acquisition by playing a low flip angle (5°) linear-phase RF pulse before the 90° pulse. This allows the acquisition of high fidelity calibration data while negligibly affecting the signal available for DWI acquisition.
The magnetization response to different RF pulses was modeled using the Cayley-Klein polynomials α and β of the respective pulses (13), neglecting the effect of transverse and longitudinal relaxation. With this formalism, an inversion or refocusing pulse transforms the magnetization as follows:
where M(−) and M(+) represent the magnetization before and after the pulse respectively, and (*) stands for the complex conjugate. Given an initial magnetization M0, the transverse magnetization after the 90° excitation pulse is
Finally, the magnetization at the echo time for a single spin echo sequence is:
For each pulse, the frequency-dependent parameters α and β were computed as a function of the applied B1 field, ranging from 0.5 to 2.5 times the optimal B1 value (defined as the B1 necessary to achieve a given rotation for linear pulses, or B1 at adiabatic threshold for adiabatic pulses). The resulting frequency (or slice) profiles were then integrated to yield the total spin echo signal as a function of B1.
7T imaging was performed on an actively-shielded, whole-body Siemens Magnetom 7T scanner (Siemens Healthcare, Erlangen, Germany) equipped with a 32-channel receive / 1 channel transmit head coil (Nova Medical, Wilmington, MA, USA) and 70 mT/m maximum gradient (200 mT/m/ms slew rate). B0-shimming was performed to the 2nd order on a manually-adjusted volume. Transmitter voltage was adjusted as follows: average flip angle was measured using the Bloch-Siegert shift technique (11) over a 5 cm × 5cm region located in a central part of the brain. The voltage was then adjusted to calibrate the average flip angle value in this region, resulting in transmitter voltages of order 200V. Figure 4A shows a Bloch-Siegert acquisition in a volunteer. Calibration of the adiabatic pulses was experimentally performed on a spherical phantom containing a 0.011 g/L solution of MACROLEX Blue (Fig. 4B). First the refocusing pulse was calibrated using the TRASE sequence by increasing the amplitude of the adiabatic pulses (keeping the excitation pulse amplitude constant) until a plateau was reached for signal intensity. The matched-phase excitation pulse of MASE was then adjusted to match the previously-calibrated adiabatic refocusing pulse. The excitation pulse amplitude was varied until a maximum in signal intensity was reached (Fig. 4B).
Anatomical T1-weighted images were acquired in a sagittal orientation using a 3D MP-RAGE sequence (14,15). The following diffusion acquisitions were performed in this order: ST, MASE, TRSE and TRASE. 30 slices were sampled in axial direction with anterior-posterior phase encoding and a partial Fourier ratio of 6/8. Parallel imaging was applied using GRAPPA (16) with acceleration factor R=3. Each sequence was run at the maximum SAR, within limits set by the Food and Drug Administration regulations (12 W/kg average SAR for local head exposure). Increased RF power that resulted when using adiabatic pulses or twice-refocused acquisitions was balanced with an increase in TR in order to maintain similar average SAR. TE/TR were 51/9700 ms for ST, 53/13500 ms for MASE, 65/15200 ms for TRSE and 65/20500 ms for TRASE.
Phantom experiments were performed on a 170 mm-diameter sphere containing saline solution (with concentrations [NaOH] = 56 mM, [KH2PO4] = 50 mM) and used as a model for the human head.
In vivo experiments were performed on healthy volunteers. In one experiment, all four DWI acquisitions (ST, MASE, TRSE and TRASE) were performed on the same subject using 20 diffusion directions (b = 1000 s/mm2), with spatial resolution 1.9 × 1.9 × 3 mm3. In a second scan, 68 diffusion directions were acquired (b = 1000 s/mm2) with higher spatial resolution (1.4 × 1.4 × 2 mm3). For the second in vivo acquisition, only the single-refocused DWI acquisitions (ST and MASE) were acquired in order to determine the benefit of MASE for tractography and track density imaging within a reasonable total exam time. Acquisition times for the 68-directions scans were 10:51 min for ST (TR 8.8 s) and 15:10 min for MASE (TR 12.3 s).
Adiabatic acquisitions were compared to conventional acquisitions in terms of signal intensity, which was measured on reconstructed diffusion trace images instead of individual diffusion directions to avoid anisotropic effects. Signal intensity could be directly compared because the receive gains and subject position relative to receive coils were identical between the DWI scans. Pixel-by-pixel division was performed between adiabatic and conventional acquisitions, as well as between single and twice refocused acquisitions, to derive maps showing signal enhancement. A signal intensity profile was extracted along a horizontal line placed on signal enhancement maps, using custom-built analysis software designed with Matlab (R2014a, Mathworks, Natick, MA, USA).
In addition to signal intensity comparison, we compared the performance of different diffusion acquisitions in terms of the derived diffusion metrics. Diffusion-weighted volumes were registered to anatomical MP-RAGE images and corrected for eddy current-induced bias using the FMRIB Software Library (FSL) (17). Further DWI processing was achieved using MRtrix (18,19). Fractional anisotropy (FA) was derived from the intensity-masked DW images for both 20 and 68-direction acquisitions. White matter tractography and track density imaging (TDI) (20) were performed on the 68-direction datasets, using the constrained spherical deconvolution method (21).
Next, the effect of the adiabatic RF pulses on fiber tractography was evaluated on the 68-direction datasets. Tracks were generated using a hand-drawn seed region of interest (ROI), and were constrained to include hand-drawn target ROIs. For exact technique comparison, all tracking parameters and ROIs were the same for ST and MASE datasets. We evaluated tractography performance on a group of fibers that passes through the region most severely affected by B1 inhomogeneity, running from the ventral tegmental area (VTA) to the frontal cortex via the anterior limb of the internal capsule (ALIC). Tracks were generated from a seed ROI placed in the midbrain-VTA region, and an include ROI in the ALIC, in both the left and right hemispheres. For the left and right side pathways probabilistic tractography was performed, generating 10000 tracks from the seed region and accepting only tracks passing through the include region. Finally, track density imaging (TDI) was derived from whole brain fiber tracking using 106 tracks and an isotropic spatial resolution of 1.5 mm.
Figure 3 shows the magnetization and signal as a function of the frequency and applied B1, for individual pulses as well as full spin echoes. For both MASE and TRASE, the spin echo signal integrated over the slice is higher than for conventional ST and TRSE in a wide range of B1 values. This is because, for any B1 over the adiabatic threshold, the profile of the adiabatic refocusing pulse (Fig. 3A, right panel) remains almost unchanged, while the conventional refocusing pulse profile demonstrates severe variations. The deleterious effects of the conventional refocusing pulse also result in worse behavior for TRSE when compared to ST, because TRSE uses two refocusing pulses, compounding their effects. Significant differences are also observed between conventional and matched-phase excitation pulses. Because a conventional excitation pulse suffers from severe signal loss at 1.5–2 B1 overdrive, while a matched-phase excitation pulse offers an improved slice profile over this range, the MASE technique yields higher spin echo signal than TRASE over a large B1 range (Fig. 3B,C).
In Figure 5 central axial slices from the trace-weighted (b=1000 s/mm2) volume acquired in the water phantom using ST (Fig. 5A1), MASE (Fig. 5A2), TRSE (Fig. 5B1) and TRASE (Fig. 5B2) are compared. Both of the non-adiabatic preparations (Fig. 5A1,B1) have lower signal in the center of the image than their adiabatic counterparts (Fig. 5A2,B2), demonstrating the enhanced uniformity of the adiabatic pulses. In an image of the ratio of the image acquired with each adiabatic pulse to the image acquired with its non-adiabatic counterpart it can been appreciated that the signal uniformity is primarily improved in the center of the image (Fig. 5C1,D1) with little change in the periphery of the image. A horizontal profile across the ratio images is plotted in Fig. 5C2,D2 to show the shape and magnitude of the improvement obtained with adiabatic preparations. The signal in the center of the image up to 90 % higher for MASE vs. ST, up to 130 % higher for TRASE vs. TRSE. Finally the image ratio between MASE and TRASE in Fig. 5E1,E2 shows that adiabatic acquisitions yield similar signal in a saline phantom.
In Figure 6 signal intensities on the trace-weighted images acquired in vivo with each of the preparations are compared. The images from left to right are the trace-weighted image acquired with the non-adiabatic sequence (Fig. 6 first column), the trace-weighted image acquired with the adiabatic sequence (Fig. 6 second column), the ratio of the image acquired with the adiabatic sequence to the image acquired in the non-adiabatic sequence (Fig. 6 third column), and a central horizontal profile across the ratio image (Fig. 6 last column).
20-directions brain DWI: In vivo signal intensity comparisons of all 4 sequences using 20-direction DWI acquisitions are shown in Fig. 6(A–B). Similar to the phantom experiment, higher signal intensity was observed in central regions of the brain when comparing MASE to ST or TRASE to TRSE. The gain in signal intensity was found to be higher when comparing twice-refocused acquisitions (up to 140 %) than for single refocused ones (up to 64 %), because using 2 conventional refocusing pulses lead to more severe signal loss, as demonstrated in Fig. 3. Finally, RF power deposition was lowest for ST, followed by MASE, TRSE and TRASE, as reflected by their respective TRs (9.7, 13.5, 15.2 and 20.5 s) necessary to operate within SAR limits. The use of adiabatic pulses led to increased deposited power (39 % for MASE vs. ST and 35 % for TRASE vs. TRSE) as expected.
68-directions brain DWI: Signal intensity comparisons of the trace-weighted images acquired in MASE and ST are shown in Fig. 6C; note that twice refocused sequences were not acquired in this subject. In this dataset, gains up to 50 % signal intensity were observed in central regions, which included portions of the thalamus as well as the splenium of the corpus callosum.
In Figure 7, signal intensities between MASE and TRASE are compared for the 20-direction dataset, to evaluate the advantage of lower echo time achievable with MASE. In the signal intensity ratio image between MASE and TRASE, shown in Fig. 7C, globally higher signal of MASE acquisition is observed. The line profile (Fig. 7D) shows that in white matter regions the MASE signal intensity is 20 to 40% higher than that of TRASE.
In Figure 8, axial slices of the principle eigenvector image weighted by FA (color FA) and fiber tractography from the data acquired using the 68-direction protocol with MASE and ST are compared. In the zoom-in of the color FA the better depiction of the ALIC on MASE compared to ST is apparent (Fig. 8A,B zoom box). This is the result of low SNR in the ST acquisition; noise propagates through the calculation of the tensor resulting in changes in the derived parametric maps such as the color FA. The effect of this reduced SNR on the fiber tractography of the group of fibers which passes through the ALIC (Fig. 8C,D) is a reduction in the number of tracks found in the ST data compared to the MASE data, especially apparent on the left side. The tracks obtained from the MASE data, by contrast, are symmetric in appearance as expected in this healthy subject.
In Figure 9, a trace-weighted central slice and coronal reformat (Fig. 9A,C) of the 68-direction acquisitions and corresponding TDI (Fig. 9B,D) from the ST and MASE acquisitions are compared. As noted previously, the image acquired with the ST acquisition has lower signal in the center part of the image than the image acquired with the MASE acquisition. The consequences of this reduction in signal on the tractography can be seen in the TDI (Fig. 9B,D). The most obvious differences are in the regions affected by the signal loss, with higher densities of tracks in the central region of the brain and the ALIC (Fig. 9 arrows) in the TDI generated from the MASE data compared to the TDI generated from the ST data. However, because tractography uses data from multiple regions to generate tracks, differences are also visible in regions not directly affected by the signal intensity loss such as the right frontal region indicated in Fig. 9D in the upper left corner.
In this study, we have developed a new single-refocused DWI acquisition which utilizes a Matched-phase Adiabatic Spin Echo (MASE) to achieve reduced sensitivity to B1 variations at ultra-high field. By comparing adiabatic and conventional single- and twice-refocused DWI acquisitions, we found that adiabatic sequences (MASE and TRASE) led to increased signal in a large range of B1 when compared to conventional ones (ST and TRSE), as shown by simulations as well as in vivo experiments. This resulted in recovered signal in important areas of the brain and improved calculation of diffusion metrics. Furthermore, white matter tractography performed with a MASE acquisition showed improved, more symmetric track visualization compared to conventional single-refocused ST. Due to a lack of a “gold standard”, typical of tractography experiments in vivo, the improvement in tractography in MASE versus ST was inferred from a more symmetric visualization of tracks in a healthy subject.
MASE yielded higher signal than twice-refocused TRASE because of shorter achievable minimum echo time. In addition, simulations showed that the matched-phase excitation pulse of MASE has a different slice profile than a conventional excitation pulse, decreasing slowly in efficiency when B1 increases. This results in slightly improved immunity to B1 compared to TRASE, up to about 2.3 overdrive factor. Finally, using MASE results in significant SAR reduction compared to TRASE. For these reasons, we believe that MASE is a better option than TRASE to reduce the effect of B1 inhomogeneity at ultra-high field, allowing for higher signal and reduced RF power deposition.
In order to assert the efficiency of the MASE approach against conventional DWI, the increase in scan time imposed by larger SAR deposition needs to be balanced against the gains in signal. With MASE, we observed signal intensity gains ranging from 50 – 63 % in the center of the brain, where B1 values are the highest. A comparable gain could be achieved with signal averaging, requiring in the best case 2 to 3 averages. Thus signal averaging would lead to longer scan time when compared to the 40 % increase in scan time imposed by SAR may improve the diagnostic performance of DWI at high b value.
Tractography based on images acquired with MASE resulted in more fibers compared to ST for a group of fibers passing through the ALIC, as well as a more symmetric left-right representation of the tracks. Furthermore the TDI results show that this trend holds in other regions, especially in the central region encompassing the thalamus. This has implications for structural connectivity analyses such as those proposed in human connectome projects (22). Because connectivity is based on the tractography, differences in tracking can have profound effects on the derived connectivity matrices, especially in massively connected “hub” regions like the thalamus (23–25). The tractography results shown here indicate that more uniform B1 provided by MASE may be important in obtaining accurate connectivity measures in areas most affected by B1 inhomogeneity such as the thalamus and the internal capsule.
The pulse pair used in MASE is very amenable to conversion into a simultaneous multi-slice (SMS) pulse pair. Feldman et al. have already published a SEAMS pulse pair (26) that achieves this exact purpose. Future work includes evaluating MASE in a larger cohort of subjects undergoing diffusion-weighted tractography, developing a SMS version of MASE by utilizing a SEAMS pulse pair in a single refocused diffusion sequence, as well as combining improved readout options, such as segmented EPI (27), with adiabatic RF pulses to provide a diffusion sequence robust to both B0 and B1 inhomogeneity.
Funding Sources: NIH-NINDS R00 NS070821, Icahn School of Medicine Capital Campaign, Translational and Molecular Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, Siemens Healthcare.