JOURNAL OF MAGNETIC RESONANCE IMAGING 41:1150–1156 (2015)
Technical Development
Nonenhanced Arterial Spin Labeled Carotid MR Angiography Using Three-Dimensional Radial Balanced Steady-State Free Precession Imaging Ioannis Koktzoglou, PhD,1,2* Joel R. Meyer, MD,1,2 William J. Ankenbrandt, MD,1,2 Shivraman Giri, PhD,3 Davide Piccini, PhD,4,5 Michael O. Zenge, PhD,6 Oisin Flanagan, MD,1,7 Tina Desai, MD,2,8 NavYash Gupta, MD,2,8 and Robert R. Edelman, MD1,7 Purpose: To optimize and preliminarily evaluate a threedimensional (3D) radial balanced steady-state free precession (bSSFP) arterial spin labeled (ASL) sequence for nonenhanced MR angiography (MRA) of the extracranial carotid arteries.
by eliminating RF energy during the pseudocontinuous control phase (P < 0.001). With higher levels of undersampling, the carotid arteries were displayed in 2 min. Conclusion: Nonenhanced MRA using hybridized ASL with a 3D radial bSSFP trajectory can display long lengths of the carotid arteries with 1 mm3 isotropic resolution.
Materials and Methods: The carotid arteries of 13 healthy subjects and 2 patients were imaged on a 1.5 Tesla MRI system using an undersampled 3D radial bSSFP sequence providing a scan time of 4 min and 1 mm3 isotropic resolution. A hybridized scheme that combined pseudocontinuous and pulsed ASL was used to maximize arterial coverage. The impact of a post label delay period, the sequence repetition time, and radiofrequency (RF) energy configuration of pseudocontinuous labeling on the display of the carotid arteries was assessed with contrast-to-noise ratio (CNR) measurements. Faster, higher undersampled 2 and 1 min scans were tested.
Key Words: carotid; angiography; arterial spin labeling; radial; nonenhanced J. Magn. Reson. Imaging 2015;41:1150–1156. C 2014 Wiley Periodicals, Inc. V
Results: Using hybridized ASL MRA and a 3D radial bSSFP trajectory, arterial CNR was maximized with a post label delay of 0.2 s, repetition times 2.5 s (P < 0.05), and 1 Department of Radiology, NorthShore University HealthSystem, Evanston, Illinois, USA. 2 The University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA. 3 Siemens Healthcare, Chicago, Illinois, USA. 4 Advanced Clinical Imaging Technology, Siemens Healthcare IM BM PI, Lausanne, Switzerland. 5 Department of Radiology, University Hospital (CHUV) and University of Lausanne (UNIL)/Center for Biomedical Imaging (CIBM), Lausanne, Switzerland. 6 MR Product Innovation and Definition, Healthcare Sector, Siemens AG, Erlangen, Germany. 7 Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 8 Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois, USA. Contract grant sponsor: American Heart Association; Contract grant number: 12GRNT12080013. *Address reprint requests to: I.K., NorthShore University HealthSystem, Walgreen Jr. Building, G507, 2650 Ridge Avenue, Evanston, IL 60201. E-mail: [email protected] Received January 11, 2014; Accepted March 26, 2014. DOI 10.1002/jmri.24640 View this article online at wileyonlinelibrary.com. C 2014 Wiley Periodicals, Inc. V
MR ANGIOGRAPHY (MRA) is often used in the screening and diagnosis of carotid artery stenosis. Conventional methods for nonenhanced MRA (NEMRA) of the carotid arteries include two-dimensional (2D) and 3D time of flight (TOF). TOF MRA methods are reasonably accurate (1), but artifacts and limitations in vascular coverage have rendered gadolinium based contrastenhanced MRA (CEMRA) the preferred approach (2–4). Due to the prevalence of renal insufficiency in patients with carotid artery stenosis (5) and the association of gadolinium based contrast with nephrogenic systemic fibrosis (6), however, there has been a spurt of interest in the development of more sophisticated NEMRA techniques (7,8). One method for high contrast NEMRA is to use arterial spin labeling (ASL) (9–11) in combination with a balanced steady-state free precession (bSSFP) readout (12). In performing ASL on commercial MRI systems with standard hardware, pulsed ASL (PASL) (11) or pseudocontinuous ASL (pCASL) (13) methods are typically used. For carotid NEMRA in particular, pCASL was recently found to provide better signal-to-noise ratio (SNR) than PASL (14). Shortcomings of this work, which used a 3D Cartesian bSSFP imaging sequence, included anisotropic spatial resolution, the need for signal averaging to reduce sensitivity to motion artifact, and limited anatomical coverage providing poor display of the proximal common carotid arteries.
1150
Carotid ASL MRA Using 3D Radial bSSFP
1151
Figure 1. a: The hASL MRA pulse sequence. Labeled and control data were interleaved and an optional PLD period was inserted before the 3D radial bSSFP imaging readout. b: Coronal maximum intensity projection hASL MRA image showing the positions of the pCASL labeling plane and pulsed inversion label. c: Locations where arterial-to-background CNR were measured: 1, common carotid artery origins; 2, mid common carotid arteries; 3, common carotid artery proximal to the bifurcation; 4, internal carotid arterial bulb; 5, mid-cervical internal carotid artery; 6, petrous internal carotid artery.
Recently, Robson et al (15) described the combination of pCASL and PASL, or “hybridized” ASL (hASL), for the purpose of maximizing arterial coverage and conspicuity in intracranial NEMRA using a quasi-projective Cartesian bSSFP readout. Using a similar labeling scheme, Wu and colleagues (16) used an undersampled 3D spoiled gradient-echo sequence for depicting the intracranial arteries with sub-millimeter isotropic spatial resolution. On the basis of these works, as well as the known robustness of radial imaging to motion artifact (17) and the high vascular signal provided by bSSFP imaging, we hypothesized that hASL coupled with undersampled 3D radial bSSFP imaging could be used to efficiently image long lengths of the extracranial carotid arteries with fine isotropic spatial resolution. The aim of this work was to test this hypothesis and determine a suitable set of sequence parameters for imaging the extracranial carotid arteries at 1.5 Tesla (T). MATERIALS AND METHODS This study was approved by our institutional review board. Written informed consent was obtained from all subjects before their participation in this study. MRI was performed on a 32-channel 1.5T system (MAGNETOM Avanto, Siemens AG Healthcare Sector, Erlangen, Germany). Six channel head and neck coils were used for signal reception. Arterial Spin Labeled MRA Sequence The investigational prototype hASL MRA pulse sequence used is shown in Figure 1a. The sequence
consists of pseudocontinuous ASL applied axially 5 cm below the carotid bifurcation for a labeling time (LT), a pulsed inversion radiofrequency (RF) pulse inferior to the pseudocontinuous labeling plane, a post label delay period (PLD), and a 3D radial bSSFP readout. Labeling regions are shown in Figure 1b. Pseudocontinuous labeling applied over a LT of 1s or longer allows for adequate inflow of labeled spins into the carotid arteries, while the pulsed inversion displays the proximal common carotid arteries. Pseudocontinuous ASL was applied in the gradient unbalanced configuration (13) with the following parameters: 500-ms-long sinc RF pulses; 1.5 ms RF spacing; 25 flip angle; 4.5 mT/m maximum and 0.50 mT/m average gradient strengths. Pulsed labeling was applied to an axial 10-cm-thick region using a frequency offset corrected inversion radiofrequency (RF) pulse (m ¼ 10, b ¼ 800). The 3D radial sampling trajectory of Nielles-Vallespin et al was used (18). The hASL MRA sequence was compared with a similar sequence acquired with pseudocontinuous labeling alone. Parameters common to all experiments were: 256 mm isotropic field of view, 1.0 mm isotropic resolution, nonselective 300-ms-long rectangular hard RF excitation pulses, 90 flip angle. Control and labeled bSSFP readouts were interleaved. Imaging Protocol for Experiment A Sequence optimization was performed in two experiments. In the first experiment (experiment A), the repetition time of the sequence was fixed at 2.0 s while the labeling duration and PLD times were varied to
1152
Koktzoglou et al.
Table 1 ASL Protocols Used in Experiment A Sequence
TA (min:s)
TR (s)
LT (s)
PLD (s)
Views per shot
Total views
4:30 4:30 4:30 4:30 4:30
2.0 2.0 2.0 2.0 2.0
1.5 1.5 1.3 1.1 0.9
0.0 0.0 0.2 0.4 0.6
128 128 128 128 128
8704 8704 8704 8704 8704
pCASL* hASL hASL hASL hASL
Protocols were acquired in a random order. *Obtained by omitting the pulsed inversion and post label delay time of Figure 1a.
assess their impact on vascular signal intensity. Seven healthy volunteers (six male, age 34.7 6 11.4 years, weight 77.3 6 9.5 kg) were imaged in experiment A. Imaging parameters common to the ASL sequences in this experiment were: 128 radial views per shot, 8704 total views (undersampling factor of 11.8 compared with the Nyquist rate), bSSFP TR/TE of 3.4 ms/1.7 ms, receiver bandwidth of 673 Hz/ pixel, 4 min 30 s acquisition time. Table 1 lists the sequences run in experiment A.
Imaging Protocol for Experiment B In a second experiment, the labeling configuration and PLD times providing the largest contrast-to-noise ratio (CNR) in experiment A were used, while the repetition time (TR) of the sequence was varied from 2.0 s to 3.0 s in increments of 0.5 s. Six healthy volunteers (four male, age 35.7 6 13.8 years, weight 80.5 6 17.2 kg) were imaged in experiment B. For the three sequence configurations (TRs of 2.0 s, 2.5 s, and 3.0 s) to acquire an equivalent number of radial views in the same scan time, the total number of views acquired in this experiment was fixed at 7680 (undersampling factor of 13.4) and the number of views acquired in each shot was proportional to the TR: 128, 160 and 192 views per shot for TRs of 2.0 s, 2.5 s and 3.0 s, respectively. Remaining parameters for experiment B were: bSSFP TR/TE of 3.7 ms/1.8 ms, receiver bandwidth of 558 Hz/pixel, 4 min scan time. This experiment also evaluated whether applying RF energy during the pCASL control phase to better equalize magnetization transfer effects between labeled and control readouts (the standard implementation of pCASL) affected arterial CNR. No additional measures were taken to exactly null the RF energy in both readouts. Table 2 lists the ASL sequences acquired in experiment B.
Patient Imaging Two male patients (82 and 68 years of age, mean weight 82.8 6 8.0 kg) with sonographically documented 70% carotid arterial stenosis were imaged. The optimal ASL MRA configuration determined in experiment B was acquired along with 2D and 3D TOF MRA, first-pass CEMRA, and steady-state CEMRA. Nonenhanced scans were acquired in a random order and with equivalent spatial resolution. Parameters for 2D TOF MRA were: TR/TE/flip of 25.0 ms/6.6 ms/60 , 1.0 mm 1.0 mm spatial resolution, 256 mm 164 mm field of view, 100 1.5-mm-thick slices with 0.5 mm overlap, receiver bandwidth of 100 Hz/pixel, parallel imaging (GRAPPA) factor of 2, scan time of 4 min 7 s. Parameters for 3D TOF were: TR/ TE/flip of 25.0 ms/7.2 ms/25 , 1.0 mm 1.0 mm spatial resolution, 256 mm 180 mm field of view, 2 overlapping slabs acquiring forty 1.0-mm-thick slices (12 mm slab overlap), receiver bandwidth of 102 Hz/ pixel, tilt optimized nonsaturated excitation RF pulses with 70% ramp (19), scan time of 4 min 5 s. After the 4-min-long ASL and TOF scans were acquired and before CEMRA, we tested highly undersampled implementations of 3D radial ASL MRA to achieve scan times of 2 and 1 min (these scans acquired 3840 and 1920 views, respectively). Fluoroscopically triggered CEMRA was performed with administration of 0.03 mmol/kg of gadofosveset trisodium (AblavarV, Lantheus Medical Imaging, North Billerica, MA) in an antecubical vein at a rate of 2 cm3/ s. Imaging parameters for first-pass CEMRA were: TR/ TE/flip of 2.8 ms/1.2 ms/25 , 0.80 mm 0.89 mm spatial resolution, 410 mm 308 mm field of view, one hundred twenty 0.9-mm-thick slices interpolated from ninety-six 1.125-mm-thick slices, receiver bandwidth of 440 Hz/pixel, 6/8th partial Fourier in the phase and slice directions, GRAPPA factor of 3, scan time 24 s. Steady-state CEMRA was acquired 5 min after contrast R
Table 2 ASL Protocols Used in Experiment B* Sequence hASL hASL hASL hASL hASL hASL
TA (min:s)
TR (s)
LT (s)
PLD (s)
Views per shot
Total views
RF energy during pCASL control phase
4:00 4:00 4:00 4:00 4:00 4:00
2.0 2.0 2.5 2.5 3.0 3.0
1.30 1.30 1.69 1.69 2.07 2.07
0.2 0.2 0.2 0.2 0.2 0.2
128 128 160 160 192 192
7680 7680 7680 7680 7680 7680
on off on off on off
*Protocols were acquired in a random order.
Carotid ASL MRA Using 3D Radial bSSFP
1153
Figure 2. Coronal maximum intensity projection images (40 mm thickness) depicting the carotid arteries as obtained in experiment A: pCASL MRA (LT ¼ 1.5 s) (a), hASL MRA (LT ¼ 1.5 s, PLD ¼ 0.0 s) (b), hASL MRA (LT ¼ 1.3 s, PLD ¼ 0.2 s) (c), hASL MRA (LT ¼ 1.1 s, PLD ¼ 0.4 s) (d), and hASL MRA (LT ¼ 0.9 s, PLD ¼ 0.6 s) (e). Hybridized ASL (b–e) improved the display of the common carotid origins. Long PLDs reduced the conspicuity of the proximal common carotid arteries, while short PLDs increased the appearance of nonvascular background signal in the upper chest. f: CNR values obtained in experiment A. Mean CNR values across the 6 locations are shown at right. Hybridized ASL with a 0.2 s PLD maximized mean CNR within the carotid arteries. Error bars show the standard error. Dashed arrows indicate statistically significant trends for increasing CNR across the four hASL acquisitions: *P < 0.001; #P < 0.01; yP < 0.05.
injection with the following parameters: TR/TE/flip of 3.6 ms/1.6 ms/15 , 0.60 mm isotropic spatial resolution, 300 mm 253 mm field of view, 176 slices, receiver bandwidth of 350 Hz/pixel, 7/8th partial Fourier in the phase and slice directions, GRAPPA factor of 2, fat saturation, 2 averages, scan time 4 min 15 s.
and matched pairs t-tests. Linear regression analysis was used to identify trends in CNR data with respect to PLD. Statistical tests were performed in commercial software (SPSS Statistics 17.0, SPSS Inc., Chicago, IL).
Quantitative Analysis in Experiments A and B
RESULTS
For each acquisition, signal within the carotid arteries was measured at the six locations shown in Figure 1c. Corresponding signal measurements in the left and right carotid arteries were averaged to yield one measurement (SA) at each location. At each location, the signal of nonvascular background tissue (SB) was measured as the mean signal in a circular region between the carotid arteries, and noise (N) was measured as the standard deviation of a region containing air signal. Arterial CNR at each location was computed as (SA-SB)/N. Signal measurements were made using ImageJ software (v1.47i, National Institutes of Health, Bethesda, MA). Data and Statistical Analysis Differences in CNR data were assessed using repeated measures analysis of variance with post hoc testing
Experiment A: Impact of Labeling Technique and Timing Figure 2a–e shows the typical image appearance observed in this experiment. Arterial-to-background CNR measurements obtained are shown in Figure 2f. With hASL MRA, shorter PLD times increased the CNR of the common carotid origins (P < 0.001), mid common carotid arteries (P < 0.001), and distal common carotid arteries (P < 0.01). Conversely, the CNR of the petrous internal carotid artery increased as the PLD was lengthened (P < 0.05). With hASL MRA, flowindependent enhancement of vascular and nonvascular tissue was observed in the upper chest where the axial pulsed RF inversion was applied. The use of hASL MRA with a short PLD of 0.2 s provided the largest mean CNR across the six locations evaluated. This PLD was considered optimal and used in
1154
Koktzoglou et al.
Experiment B: Impact of Sequence Repetition Time and pCASL Configuration
Figure 3. Plots of CNR data showing the impact of the sequence repetition time and RF energy in the pseudocontinuous control phase. a: Sequence TRs of 2.5 s and 3.0 s provided larger arterial CNR values than a TR of 2.0 s (P ¼ 0.006 and P ¼ 0.012, respectively). b: Eliminating RF energy during the pseudocontinuous control phase improved CNR by 5.4% (P < 0.001).
experiment B. Compared with pseudocontinuous labeling alone, hybridized labeling with a PLD of 0.2 s improved arterial CNR by 73% over the length of the extracranial carotid arteries, and by 87% at the carotid bifurcation.
Compared with a TR of 2.0 s, longer TRs of 2.5 s and 3.0 s improved arterial-to-background CNR by approximately 6.5% (P ¼ 0.006 and P ¼ 0.012, respectively) (Fig. 3a). As compared to applying RF energy during the pseudocontinuous control phase, elimination of RF energy during this phase improved arterial CNR by 5.4% (P < 0.001) (Fig. 3b). The optimal hASL protocol at the conclusion of this experiment was one using a repetition time of 2.5 s and applying no RF energy during the pseudocontinuous control phase; this protocol was used in the subsequent patient studies. Preliminary Results in Patients with Carotid Stenosis The image quality obtained with the optimized hASL MRA protocol in two patients with sonographically documented carotid artery severe stenosis is shown in Figure 4. Clear display of the carotid stenosis and correspondence with first-pass and steady-state CEMRA was observed. Compared with TOF MRA, 3D radial hASL MRA provided larger vascular coverage
Figure 4. Comparison of nonenhanced 3D radial hASL MRA (TR 2.5s, PLD 0.2 s, no RF energy during pCASL control phase) (a), first-pass CEMRA (b), steady-state CEMRA (c), nonenhanced 2D TOF MRA (d), and nonenhanced 3D TOF MRA (e) in an 82-year-old male (top panel) and a 68-year-old male (bottom panel) with ultrasound documented severe (70%) carotid artery stenoses. The 3D radial hASL angiograms clearly display the arterial stenoses (arrows) and show excellent correlation with firstpass and high spatial resolution steady-state CEMRA. In comparison with TOF MRA, improved display of the stenosis is observed with 3D radial hASL MRA. Steady-state CEMRA images are 1-mmthick maximum intensity projections; remaining images are 30-mm-thick maximum intensity projections.
Carotid ASL MRA Using 3D Radial bSSFP
Figure 5. Nonenhanced 3D radial hASL MRA in the 68-yearold patient of Figure 4 using the standard 4 min protocol (corresponding to a radial undersampling factor of 13.4) (a), and accelerated scans acquired in 2 (b) and 1 (c) min (undersampling factors of 26.8 and 53.6, respectively). Despite the reduced CNR, the highly undersampled 3D radial hASL protocols displayed the carotid stenosis (arrows).
and better display of the diseased carotid bifurcation. Figure 5 shows the results of the 2 and 1 min hASL MRA protocols in the second patient. Despite the reduced CNR associated with aggressive radial undersampling, the carotid artery stenosis was readily visualized.
DISCUSSION We optimized nonenhanced arterial spin labeled MR angiography of the extracranial carotid arteries using a 3D radial bSSFP imaging sequence at 1.5T. The use of hybridized arterial spin labeling applying both pseudocontinuous and pulsed elements better displayed long lengths of the extracranial carotid arteries with larger CNR than pseudocontinuous labeling alone. With hASL, a short PLD on the order of 0.2 s was found to optimize CNR. We also observed that use of sequence repetition times 2.5 s and elimination of RF energy during the pseudocontinuous control phase maximized arterial-to-background CNR. With hybridized labeling, a short PLD of 0.2 s was found to optimize CNR over the full lengths of the extracranial carotid arteries. This finding is somewhat counterintuitive because it would seem, on a cursory level, that use of no delay would optimize arterial SNR and therefore arterial-to-background CNR. The lower CNR observed with no PLD (as compared to a PLD of 0.2 s) is likely due to an amplification of undersampling-related streak artifacts from the high
1155
signal in the upper chest where the pulsed inversion was applied. Elimination of RF energy during the pseudocontinuous control phase led to a small but significant increase in arterial-to-background CNR. This increase in CNR is likely due to partial saturation of magnetization that occurs when RF energy is applied during the pseudocontinuous control phase. This strategy, which reduces applied RF energy may be useful in extensions of the technique at 3T where specific absorption rates are more of a concern. The T1 of arterial blood is approximately 1.2 s at 1.5T (20). The small but significant improvement of CNR at sequence repetition times of 2.5 s (as compared to 2.0 s) suggests that use of a TR at least on the order of twice the T1 of blood is recommended for optimizing arterial CNR. Initial testing of the optimized 3D radial hASL MRA sequence in two patients with carotid atherosclerosis demonstrated that the method can depict severe carotid stenoses with good correlation with CEMRA. Increased vascular coverage and improved image quality was observed compared with TOF MRA. We also observed that substantial reductions in scan time can be obtained by further undersampling the 3D radial trajectory, enabling 3D NEMRA in 2 min of less. With respect to TOF MRA, we found that 3D radial hASL MRA improves arterial coverage. Potential drawbacks of 3D radial hASL MRA with respect to TOF include increased sensitivity to off-resonance due to the use of pseudocontinuous labeling, radial sampling, and the use of a bSSFP readout. Unlike CEMRA, nonenhanced hASL MRA can be repeated in case of technical error or gross motion during the scan. On the other hand, hybridized ASL MRA is expected to be more flow dependent than CEMRA which may result in poorer display of vascular locations containing slow or stagnant blood flow. Limitations of this study include the finite number of experimental configurations of 3D radial hASL MRA that could be tested, reduced CNR for displaying the common carotid origins, and the small patient sample size. It is possible that other configurations of hASL MRA, for instance, by adding a short delay after each imaging readout, may improve the CNR efficiency of the sequence by reducing the saturation of inflowing arterial spins. Improved CNR of the carotid origins may be possible by placing an additional surface coil over the upper chest or by acquiring a second station inferiorly. Further testing in additional patients with carotid artery stenosis is required to assess the strengths, weaknesses, and reproducibility of 3D radial bSSFP hASL MRA and determine whether it could replace or supplement TOF MRA and CEMRA. In conclusion, hybridized arterial spin labeling of the extracranial carotid arteries using a 3D radial bSSFP imaging sequence can display long lengths of the extracranial carotid arteries with fine isotropic spatial resolution in volunteers and patients. The use of a short post label delay, a repetition time 2.5 s, and elimination of RF energy during the pCASL control phase is advised to maximize the CNR of the
1156
extracranial carotid arteries. With use of more aggressive radial undersampling, scan times as short as 1 min are possible. ACKNOWLEDGMENT We thank Dr. Matthias Guenther for his help with implementing the frequency offset corrected inversion radiofrequency pulses. REFERENCES 1. Debrey SM, Yu H, Lynch JK, et al. Diagnostic accuracy of magnetic resonance angiography for internal carotid artery disease: a systematic review and meta-analysis. Stroke 2008;39:2237–2248. 2. Huston J III, Fain SB, Riederer SJ, Wilman AH, Bernstein MA, Busse RF. Carotid arteries: maximizing arterial to venous contrast in fluoroscopically triggered contrast-enhanced MR angiography with elliptic centric view ordering. Radiology 1999;211:265–273. 3. Nederkoorn PJ, van der Graaf Y, Eikelboom BC, van der Lugt A, Bartels LW, Mali WP. Time-of-flight MR angiography of carotid artery stenosis: does a flow void represent severe stenosis? AJNR Am J Neuroradiol 2002;23:1779–1784. 4. Etesami M, Hoi Y, Steinman DA, et al. Comparison of carotid plaque ulcer detection using contrast-enhanced and time-of-flight MRA Techniques. AJNR Am J Neuroradiol 2013;34:177–184. 5. Kuroda S, Nishida N, Uzu T, et al. Prevalence of renal artery stenosis in autopsy patients with stroke. Stroke 2000;31:61–65. 6. Kuo PH, Kanal E, Abu-Alfa AK, Cowper SE. Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis. Radiology 2007;242:647–649. 7. Takei N, Miyoshi M, Kabasawa H. Noncontrast MR angiography for supraaortic arteries using inflow enhanced inversion recovery fast spin echo imaging. J Magn Reson Imaging 2012;35:957–962. 8. Kramer H, Runge VM, Morelli JN, et al. Magnetic resonance angiography of the carotid arteries: comparison of unenhanced and contrast enhanced techniques. Eur Radiol 2011;21:1667–1676. 9. Dixon WT, Du LN, Faul DD, Gado M, Rossnick S. Projection angiograms of blood labeled by adiabatic fast passage. Magn Reson Med 1986;3:454–462.
Koktzoglou et al. 10. Nishimura DG, Macovski A, Pauly JM, Conolly SM. MR angiography by selective inversion recovery. Magn Reson Med 1987;4: 193–202. 11. Edelman RR, Siewert B, Adamis M, Gaa J, Laub G, Wielopolski P. Signal targeting with alternating radiofrequency (STAR) sequences: application to MR angiography. Magn Reson Med 1994;31: 233–238. 12. Koktzoglou I, Edelman RR. STAR and STARFIRE for flowdependent and flow-independent noncontrast carotid angiography. Magn Reson Med 2009;61:117–124. 13. Dai W, Garcia D, de Bazelaire C, Alsop DC. Continuous flowdriven inversion for arterial spin labeling using pulsed radio frequency and gradient fields. Magn Reson Med 2008;60:1488– 1497. 14. Koktzoglou I, Gupta N, Edelman RR. Nonenhanced extracranial carotid MR angiography using arterial spin labeling: improved performance with pseudocontinuous tagging. J Magn Reson Imaging 2011;34:384–394. 15. Robson PM, Dai W, Shankaranarayanan A, Rofsky NM, Alsop DC. Time-resolved vessel-selective digital subtraction MR angiography of the cerebral vasculature with arterial spin labeling. Radiology 2010;257:507–515. 16. Wu H, Block WF, Turski PA, Mistretta CA, Johnson KM. Noncontrast-enhanced three-dimensional (3D) intracranial MR angiography using pseudocontinuous arterial spin labeling and accelerated 3D radial acquisition. Magn Reson Med 2013;69:708– 715. 17. Glover GH, Pauly JM. Projection reconstruction techniques for reduction of motion effects in MRI. Magn Reson Med 1992;28: 275–289. 18. Nielles-Vallespin S, Weber MA, Bock M, et al. 3D radial projection technique with ultrashort echo times for sodium MRI: clinical applications in human brain and skeletal muscle. Magn Reson Med 2007;57:74–81. 19. Nagele T, Klose U, Grodd W, Petersen D, Tintera J. The effects of linearly increasing flip angles on 3D inflow MR angiography. Magn Reson Med 1994;31:561–566. 20. Simonetti OP, Finn JP, White RD, Laub G, Henry DA. “Black blood” T2-weighted inversion-recovery MR imaging of the heart. Radiology 1996;199:49–57.
Technical Development
Nonenhanced Arterial Spin Labeled Carotid MR Angiography Using Three-Dimensional Radial Balanced Steady-State Free Precession Imaging Ioannis Koktzoglou, PhD,1,2* Joel R. Meyer, MD,1,2 William J. Ankenbrandt, MD,1,2 Shivraman Giri, PhD,3 Davide Piccini, PhD,4,5 Michael O. Zenge, PhD,6 Oisin Flanagan, MD,1,7 Tina Desai, MD,2,8 NavYash Gupta, MD,2,8 and Robert R. Edelman, MD1,7 Purpose: To optimize and preliminarily evaluate a threedimensional (3D) radial balanced steady-state free precession (bSSFP) arterial spin labeled (ASL) sequence for nonenhanced MR angiography (MRA) of the extracranial carotid arteries.
by eliminating RF energy during the pseudocontinuous control phase (P < 0.001). With higher levels of undersampling, the carotid arteries were displayed in 2 min. Conclusion: Nonenhanced MRA using hybridized ASL with a 3D radial bSSFP trajectory can display long lengths of the carotid arteries with 1 mm3 isotropic resolution.
Materials and Methods: The carotid arteries of 13 healthy subjects and 2 patients were imaged on a 1.5 Tesla MRI system using an undersampled 3D radial bSSFP sequence providing a scan time of 4 min and 1 mm3 isotropic resolution. A hybridized scheme that combined pseudocontinuous and pulsed ASL was used to maximize arterial coverage. The impact of a post label delay period, the sequence repetition time, and radiofrequency (RF) energy configuration of pseudocontinuous labeling on the display of the carotid arteries was assessed with contrast-to-noise ratio (CNR) measurements. Faster, higher undersampled 2 and 1 min scans were tested.
Key Words: carotid; angiography; arterial spin labeling; radial; nonenhanced J. Magn. Reson. Imaging 2015;41:1150–1156. C 2014 Wiley Periodicals, Inc. V
Results: Using hybridized ASL MRA and a 3D radial bSSFP trajectory, arterial CNR was maximized with a post label delay of 0.2 s, repetition times 2.5 s (P < 0.05), and 1 Department of Radiology, NorthShore University HealthSystem, Evanston, Illinois, USA. 2 The University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA. 3 Siemens Healthcare, Chicago, Illinois, USA. 4 Advanced Clinical Imaging Technology, Siemens Healthcare IM BM PI, Lausanne, Switzerland. 5 Department of Radiology, University Hospital (CHUV) and University of Lausanne (UNIL)/Center for Biomedical Imaging (CIBM), Lausanne, Switzerland. 6 MR Product Innovation and Definition, Healthcare Sector, Siemens AG, Erlangen, Germany. 7 Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 8 Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois, USA. Contract grant sponsor: American Heart Association; Contract grant number: 12GRNT12080013. *Address reprint requests to: I.K., NorthShore University HealthSystem, Walgreen Jr. Building, G507, 2650 Ridge Avenue, Evanston, IL 60201. E-mail: [email protected] Received January 11, 2014; Accepted March 26, 2014. DOI 10.1002/jmri.24640 View this article online at wileyonlinelibrary.com. C 2014 Wiley Periodicals, Inc. V
MR ANGIOGRAPHY (MRA) is often used in the screening and diagnosis of carotid artery stenosis. Conventional methods for nonenhanced MRA (NEMRA) of the carotid arteries include two-dimensional (2D) and 3D time of flight (TOF). TOF MRA methods are reasonably accurate (1), but artifacts and limitations in vascular coverage have rendered gadolinium based contrastenhanced MRA (CEMRA) the preferred approach (2–4). Due to the prevalence of renal insufficiency in patients with carotid artery stenosis (5) and the association of gadolinium based contrast with nephrogenic systemic fibrosis (6), however, there has been a spurt of interest in the development of more sophisticated NEMRA techniques (7,8). One method for high contrast NEMRA is to use arterial spin labeling (ASL) (9–11) in combination with a balanced steady-state free precession (bSSFP) readout (12). In performing ASL on commercial MRI systems with standard hardware, pulsed ASL (PASL) (11) or pseudocontinuous ASL (pCASL) (13) methods are typically used. For carotid NEMRA in particular, pCASL was recently found to provide better signal-to-noise ratio (SNR) than PASL (14). Shortcomings of this work, which used a 3D Cartesian bSSFP imaging sequence, included anisotropic spatial resolution, the need for signal averaging to reduce sensitivity to motion artifact, and limited anatomical coverage providing poor display of the proximal common carotid arteries.
1150
Carotid ASL MRA Using 3D Radial bSSFP
1151
Figure 1. a: The hASL MRA pulse sequence. Labeled and control data were interleaved and an optional PLD period was inserted before the 3D radial bSSFP imaging readout. b: Coronal maximum intensity projection hASL MRA image showing the positions of the pCASL labeling plane and pulsed inversion label. c: Locations where arterial-to-background CNR were measured: 1, common carotid artery origins; 2, mid common carotid arteries; 3, common carotid artery proximal to the bifurcation; 4, internal carotid arterial bulb; 5, mid-cervical internal carotid artery; 6, petrous internal carotid artery.
Recently, Robson et al (15) described the combination of pCASL and PASL, or “hybridized” ASL (hASL), for the purpose of maximizing arterial coverage and conspicuity in intracranial NEMRA using a quasi-projective Cartesian bSSFP readout. Using a similar labeling scheme, Wu and colleagues (16) used an undersampled 3D spoiled gradient-echo sequence for depicting the intracranial arteries with sub-millimeter isotropic spatial resolution. On the basis of these works, as well as the known robustness of radial imaging to motion artifact (17) and the high vascular signal provided by bSSFP imaging, we hypothesized that hASL coupled with undersampled 3D radial bSSFP imaging could be used to efficiently image long lengths of the extracranial carotid arteries with fine isotropic spatial resolution. The aim of this work was to test this hypothesis and determine a suitable set of sequence parameters for imaging the extracranial carotid arteries at 1.5 Tesla (T). MATERIALS AND METHODS This study was approved by our institutional review board. Written informed consent was obtained from all subjects before their participation in this study. MRI was performed on a 32-channel 1.5T system (MAGNETOM Avanto, Siemens AG Healthcare Sector, Erlangen, Germany). Six channel head and neck coils were used for signal reception. Arterial Spin Labeled MRA Sequence The investigational prototype hASL MRA pulse sequence used is shown in Figure 1a. The sequence
consists of pseudocontinuous ASL applied axially 5 cm below the carotid bifurcation for a labeling time (LT), a pulsed inversion radiofrequency (RF) pulse inferior to the pseudocontinuous labeling plane, a post label delay period (PLD), and a 3D radial bSSFP readout. Labeling regions are shown in Figure 1b. Pseudocontinuous labeling applied over a LT of 1s or longer allows for adequate inflow of labeled spins into the carotid arteries, while the pulsed inversion displays the proximal common carotid arteries. Pseudocontinuous ASL was applied in the gradient unbalanced configuration (13) with the following parameters: 500-ms-long sinc RF pulses; 1.5 ms RF spacing; 25 flip angle; 4.5 mT/m maximum and 0.50 mT/m average gradient strengths. Pulsed labeling was applied to an axial 10-cm-thick region using a frequency offset corrected inversion radiofrequency (RF) pulse (m ¼ 10, b ¼ 800). The 3D radial sampling trajectory of Nielles-Vallespin et al was used (18). The hASL MRA sequence was compared with a similar sequence acquired with pseudocontinuous labeling alone. Parameters common to all experiments were: 256 mm isotropic field of view, 1.0 mm isotropic resolution, nonselective 300-ms-long rectangular hard RF excitation pulses, 90 flip angle. Control and labeled bSSFP readouts were interleaved. Imaging Protocol for Experiment A Sequence optimization was performed in two experiments. In the first experiment (experiment A), the repetition time of the sequence was fixed at 2.0 s while the labeling duration and PLD times were varied to
1152
Koktzoglou et al.
Table 1 ASL Protocols Used in Experiment A Sequence
TA (min:s)
TR (s)
LT (s)
PLD (s)
Views per shot
Total views
4:30 4:30 4:30 4:30 4:30
2.0 2.0 2.0 2.0 2.0
1.5 1.5 1.3 1.1 0.9
0.0 0.0 0.2 0.4 0.6
128 128 128 128 128
8704 8704 8704 8704 8704
pCASL* hASL hASL hASL hASL
Protocols were acquired in a random order. *Obtained by omitting the pulsed inversion and post label delay time of Figure 1a.
assess their impact on vascular signal intensity. Seven healthy volunteers (six male, age 34.7 6 11.4 years, weight 77.3 6 9.5 kg) were imaged in experiment A. Imaging parameters common to the ASL sequences in this experiment were: 128 radial views per shot, 8704 total views (undersampling factor of 11.8 compared with the Nyquist rate), bSSFP TR/TE of 3.4 ms/1.7 ms, receiver bandwidth of 673 Hz/ pixel, 4 min 30 s acquisition time. Table 1 lists the sequences run in experiment A.
Imaging Protocol for Experiment B In a second experiment, the labeling configuration and PLD times providing the largest contrast-to-noise ratio (CNR) in experiment A were used, while the repetition time (TR) of the sequence was varied from 2.0 s to 3.0 s in increments of 0.5 s. Six healthy volunteers (four male, age 35.7 6 13.8 years, weight 80.5 6 17.2 kg) were imaged in experiment B. For the three sequence configurations (TRs of 2.0 s, 2.5 s, and 3.0 s) to acquire an equivalent number of radial views in the same scan time, the total number of views acquired in this experiment was fixed at 7680 (undersampling factor of 13.4) and the number of views acquired in each shot was proportional to the TR: 128, 160 and 192 views per shot for TRs of 2.0 s, 2.5 s and 3.0 s, respectively. Remaining parameters for experiment B were: bSSFP TR/TE of 3.7 ms/1.8 ms, receiver bandwidth of 558 Hz/pixel, 4 min scan time. This experiment also evaluated whether applying RF energy during the pCASL control phase to better equalize magnetization transfer effects between labeled and control readouts (the standard implementation of pCASL) affected arterial CNR. No additional measures were taken to exactly null the RF energy in both readouts. Table 2 lists the ASL sequences acquired in experiment B.
Patient Imaging Two male patients (82 and 68 years of age, mean weight 82.8 6 8.0 kg) with sonographically documented 70% carotid arterial stenosis were imaged. The optimal ASL MRA configuration determined in experiment B was acquired along with 2D and 3D TOF MRA, first-pass CEMRA, and steady-state CEMRA. Nonenhanced scans were acquired in a random order and with equivalent spatial resolution. Parameters for 2D TOF MRA were: TR/TE/flip of 25.0 ms/6.6 ms/60 , 1.0 mm 1.0 mm spatial resolution, 256 mm 164 mm field of view, 100 1.5-mm-thick slices with 0.5 mm overlap, receiver bandwidth of 100 Hz/pixel, parallel imaging (GRAPPA) factor of 2, scan time of 4 min 7 s. Parameters for 3D TOF were: TR/ TE/flip of 25.0 ms/7.2 ms/25 , 1.0 mm 1.0 mm spatial resolution, 256 mm 180 mm field of view, 2 overlapping slabs acquiring forty 1.0-mm-thick slices (12 mm slab overlap), receiver bandwidth of 102 Hz/ pixel, tilt optimized nonsaturated excitation RF pulses with 70% ramp (19), scan time of 4 min 5 s. After the 4-min-long ASL and TOF scans were acquired and before CEMRA, we tested highly undersampled implementations of 3D radial ASL MRA to achieve scan times of 2 and 1 min (these scans acquired 3840 and 1920 views, respectively). Fluoroscopically triggered CEMRA was performed with administration of 0.03 mmol/kg of gadofosveset trisodium (AblavarV, Lantheus Medical Imaging, North Billerica, MA) in an antecubical vein at a rate of 2 cm3/ s. Imaging parameters for first-pass CEMRA were: TR/ TE/flip of 2.8 ms/1.2 ms/25 , 0.80 mm 0.89 mm spatial resolution, 410 mm 308 mm field of view, one hundred twenty 0.9-mm-thick slices interpolated from ninety-six 1.125-mm-thick slices, receiver bandwidth of 440 Hz/pixel, 6/8th partial Fourier in the phase and slice directions, GRAPPA factor of 3, scan time 24 s. Steady-state CEMRA was acquired 5 min after contrast R
Table 2 ASL Protocols Used in Experiment B* Sequence hASL hASL hASL hASL hASL hASL
TA (min:s)
TR (s)
LT (s)
PLD (s)
Views per shot
Total views
RF energy during pCASL control phase
4:00 4:00 4:00 4:00 4:00 4:00
2.0 2.0 2.5 2.5 3.0 3.0
1.30 1.30 1.69 1.69 2.07 2.07
0.2 0.2 0.2 0.2 0.2 0.2
128 128 160 160 192 192
7680 7680 7680 7680 7680 7680
on off on off on off
*Protocols were acquired in a random order.
Carotid ASL MRA Using 3D Radial bSSFP
1153
Figure 2. Coronal maximum intensity projection images (40 mm thickness) depicting the carotid arteries as obtained in experiment A: pCASL MRA (LT ¼ 1.5 s) (a), hASL MRA (LT ¼ 1.5 s, PLD ¼ 0.0 s) (b), hASL MRA (LT ¼ 1.3 s, PLD ¼ 0.2 s) (c), hASL MRA (LT ¼ 1.1 s, PLD ¼ 0.4 s) (d), and hASL MRA (LT ¼ 0.9 s, PLD ¼ 0.6 s) (e). Hybridized ASL (b–e) improved the display of the common carotid origins. Long PLDs reduced the conspicuity of the proximal common carotid arteries, while short PLDs increased the appearance of nonvascular background signal in the upper chest. f: CNR values obtained in experiment A. Mean CNR values across the 6 locations are shown at right. Hybridized ASL with a 0.2 s PLD maximized mean CNR within the carotid arteries. Error bars show the standard error. Dashed arrows indicate statistically significant trends for increasing CNR across the four hASL acquisitions: *P < 0.001; #P < 0.01; yP < 0.05.
injection with the following parameters: TR/TE/flip of 3.6 ms/1.6 ms/15 , 0.60 mm isotropic spatial resolution, 300 mm 253 mm field of view, 176 slices, receiver bandwidth of 350 Hz/pixel, 7/8th partial Fourier in the phase and slice directions, GRAPPA factor of 2, fat saturation, 2 averages, scan time 4 min 15 s.
and matched pairs t-tests. Linear regression analysis was used to identify trends in CNR data with respect to PLD. Statistical tests were performed in commercial software (SPSS Statistics 17.0, SPSS Inc., Chicago, IL).
Quantitative Analysis in Experiments A and B
RESULTS
For each acquisition, signal within the carotid arteries was measured at the six locations shown in Figure 1c. Corresponding signal measurements in the left and right carotid arteries were averaged to yield one measurement (SA) at each location. At each location, the signal of nonvascular background tissue (SB) was measured as the mean signal in a circular region between the carotid arteries, and noise (N) was measured as the standard deviation of a region containing air signal. Arterial CNR at each location was computed as (SA-SB)/N. Signal measurements were made using ImageJ software (v1.47i, National Institutes of Health, Bethesda, MA). Data and Statistical Analysis Differences in CNR data were assessed using repeated measures analysis of variance with post hoc testing
Experiment A: Impact of Labeling Technique and Timing Figure 2a–e shows the typical image appearance observed in this experiment. Arterial-to-background CNR measurements obtained are shown in Figure 2f. With hASL MRA, shorter PLD times increased the CNR of the common carotid origins (P < 0.001), mid common carotid arteries (P < 0.001), and distal common carotid arteries (P < 0.01). Conversely, the CNR of the petrous internal carotid artery increased as the PLD was lengthened (P < 0.05). With hASL MRA, flowindependent enhancement of vascular and nonvascular tissue was observed in the upper chest where the axial pulsed RF inversion was applied. The use of hASL MRA with a short PLD of 0.2 s provided the largest mean CNR across the six locations evaluated. This PLD was considered optimal and used in
1154
Koktzoglou et al.
Experiment B: Impact of Sequence Repetition Time and pCASL Configuration
Figure 3. Plots of CNR data showing the impact of the sequence repetition time and RF energy in the pseudocontinuous control phase. a: Sequence TRs of 2.5 s and 3.0 s provided larger arterial CNR values than a TR of 2.0 s (P ¼ 0.006 and P ¼ 0.012, respectively). b: Eliminating RF energy during the pseudocontinuous control phase improved CNR by 5.4% (P < 0.001).
experiment B. Compared with pseudocontinuous labeling alone, hybridized labeling with a PLD of 0.2 s improved arterial CNR by 73% over the length of the extracranial carotid arteries, and by 87% at the carotid bifurcation.
Compared with a TR of 2.0 s, longer TRs of 2.5 s and 3.0 s improved arterial-to-background CNR by approximately 6.5% (P ¼ 0.006 and P ¼ 0.012, respectively) (Fig. 3a). As compared to applying RF energy during the pseudocontinuous control phase, elimination of RF energy during this phase improved arterial CNR by 5.4% (P < 0.001) (Fig. 3b). The optimal hASL protocol at the conclusion of this experiment was one using a repetition time of 2.5 s and applying no RF energy during the pseudocontinuous control phase; this protocol was used in the subsequent patient studies. Preliminary Results in Patients with Carotid Stenosis The image quality obtained with the optimized hASL MRA protocol in two patients with sonographically documented carotid artery severe stenosis is shown in Figure 4. Clear display of the carotid stenosis and correspondence with first-pass and steady-state CEMRA was observed. Compared with TOF MRA, 3D radial hASL MRA provided larger vascular coverage
Figure 4. Comparison of nonenhanced 3D radial hASL MRA (TR 2.5s, PLD 0.2 s, no RF energy during pCASL control phase) (a), first-pass CEMRA (b), steady-state CEMRA (c), nonenhanced 2D TOF MRA (d), and nonenhanced 3D TOF MRA (e) in an 82-year-old male (top panel) and a 68-year-old male (bottom panel) with ultrasound documented severe (70%) carotid artery stenoses. The 3D radial hASL angiograms clearly display the arterial stenoses (arrows) and show excellent correlation with firstpass and high spatial resolution steady-state CEMRA. In comparison with TOF MRA, improved display of the stenosis is observed with 3D radial hASL MRA. Steady-state CEMRA images are 1-mmthick maximum intensity projections; remaining images are 30-mm-thick maximum intensity projections.
Carotid ASL MRA Using 3D Radial bSSFP
Figure 5. Nonenhanced 3D radial hASL MRA in the 68-yearold patient of Figure 4 using the standard 4 min protocol (corresponding to a radial undersampling factor of 13.4) (a), and accelerated scans acquired in 2 (b) and 1 (c) min (undersampling factors of 26.8 and 53.6, respectively). Despite the reduced CNR, the highly undersampled 3D radial hASL protocols displayed the carotid stenosis (arrows).
and better display of the diseased carotid bifurcation. Figure 5 shows the results of the 2 and 1 min hASL MRA protocols in the second patient. Despite the reduced CNR associated with aggressive radial undersampling, the carotid artery stenosis was readily visualized.
DISCUSSION We optimized nonenhanced arterial spin labeled MR angiography of the extracranial carotid arteries using a 3D radial bSSFP imaging sequence at 1.5T. The use of hybridized arterial spin labeling applying both pseudocontinuous and pulsed elements better displayed long lengths of the extracranial carotid arteries with larger CNR than pseudocontinuous labeling alone. With hASL, a short PLD on the order of 0.2 s was found to optimize CNR. We also observed that use of sequence repetition times 2.5 s and elimination of RF energy during the pseudocontinuous control phase maximized arterial-to-background CNR. With hybridized labeling, a short PLD of 0.2 s was found to optimize CNR over the full lengths of the extracranial carotid arteries. This finding is somewhat counterintuitive because it would seem, on a cursory level, that use of no delay would optimize arterial SNR and therefore arterial-to-background CNR. The lower CNR observed with no PLD (as compared to a PLD of 0.2 s) is likely due to an amplification of undersampling-related streak artifacts from the high
1155
signal in the upper chest where the pulsed inversion was applied. Elimination of RF energy during the pseudocontinuous control phase led to a small but significant increase in arterial-to-background CNR. This increase in CNR is likely due to partial saturation of magnetization that occurs when RF energy is applied during the pseudocontinuous control phase. This strategy, which reduces applied RF energy may be useful in extensions of the technique at 3T where specific absorption rates are more of a concern. The T1 of arterial blood is approximately 1.2 s at 1.5T (20). The small but significant improvement of CNR at sequence repetition times of 2.5 s (as compared to 2.0 s) suggests that use of a TR at least on the order of twice the T1 of blood is recommended for optimizing arterial CNR. Initial testing of the optimized 3D radial hASL MRA sequence in two patients with carotid atherosclerosis demonstrated that the method can depict severe carotid stenoses with good correlation with CEMRA. Increased vascular coverage and improved image quality was observed compared with TOF MRA. We also observed that substantial reductions in scan time can be obtained by further undersampling the 3D radial trajectory, enabling 3D NEMRA in 2 min of less. With respect to TOF MRA, we found that 3D radial hASL MRA improves arterial coverage. Potential drawbacks of 3D radial hASL MRA with respect to TOF include increased sensitivity to off-resonance due to the use of pseudocontinuous labeling, radial sampling, and the use of a bSSFP readout. Unlike CEMRA, nonenhanced hASL MRA can be repeated in case of technical error or gross motion during the scan. On the other hand, hybridized ASL MRA is expected to be more flow dependent than CEMRA which may result in poorer display of vascular locations containing slow or stagnant blood flow. Limitations of this study include the finite number of experimental configurations of 3D radial hASL MRA that could be tested, reduced CNR for displaying the common carotid origins, and the small patient sample size. It is possible that other configurations of hASL MRA, for instance, by adding a short delay after each imaging readout, may improve the CNR efficiency of the sequence by reducing the saturation of inflowing arterial spins. Improved CNR of the carotid origins may be possible by placing an additional surface coil over the upper chest or by acquiring a second station inferiorly. Further testing in additional patients with carotid artery stenosis is required to assess the strengths, weaknesses, and reproducibility of 3D radial bSSFP hASL MRA and determine whether it could replace or supplement TOF MRA and CEMRA. In conclusion, hybridized arterial spin labeling of the extracranial carotid arteries using a 3D radial bSSFP imaging sequence can display long lengths of the extracranial carotid arteries with fine isotropic spatial resolution in volunteers and patients. The use of a short post label delay, a repetition time 2.5 s, and elimination of RF energy during the pCASL control phase is advised to maximize the CNR of the
1156
extracranial carotid arteries. With use of more aggressive radial undersampling, scan times as short as 1 min are possible. ACKNOWLEDGMENT We thank Dr. Matthias Guenther for his help with implementing the frequency offset corrected inversion radiofrequency pulses. REFERENCES 1. Debrey SM, Yu H, Lynch JK, et al. Diagnostic accuracy of magnetic resonance angiography for internal carotid artery disease: a systematic review and meta-analysis. Stroke 2008;39:2237–2248. 2. Huston J III, Fain SB, Riederer SJ, Wilman AH, Bernstein MA, Busse RF. Carotid arteries: maximizing arterial to venous contrast in fluoroscopically triggered contrast-enhanced MR angiography with elliptic centric view ordering. Radiology 1999;211:265–273. 3. Nederkoorn PJ, van der Graaf Y, Eikelboom BC, van der Lugt A, Bartels LW, Mali WP. Time-of-flight MR angiography of carotid artery stenosis: does a flow void represent severe stenosis? AJNR Am J Neuroradiol 2002;23:1779–1784. 4. Etesami M, Hoi Y, Steinman DA, et al. Comparison of carotid plaque ulcer detection using contrast-enhanced and time-of-flight MRA Techniques. AJNR Am J Neuroradiol 2013;34:177–184. 5. Kuroda S, Nishida N, Uzu T, et al. Prevalence of renal artery stenosis in autopsy patients with stroke. Stroke 2000;31:61–65. 6. Kuo PH, Kanal E, Abu-Alfa AK, Cowper SE. Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis. Radiology 2007;242:647–649. 7. Takei N, Miyoshi M, Kabasawa H. Noncontrast MR angiography for supraaortic arteries using inflow enhanced inversion recovery fast spin echo imaging. J Magn Reson Imaging 2012;35:957–962. 8. Kramer H, Runge VM, Morelli JN, et al. Magnetic resonance angiography of the carotid arteries: comparison of unenhanced and contrast enhanced techniques. Eur Radiol 2011;21:1667–1676. 9. Dixon WT, Du LN, Faul DD, Gado M, Rossnick S. Projection angiograms of blood labeled by adiabatic fast passage. Magn Reson Med 1986;3:454–462.
Koktzoglou et al. 10. Nishimura DG, Macovski A, Pauly JM, Conolly SM. MR angiography by selective inversion recovery. Magn Reson Med 1987;4: 193–202. 11. Edelman RR, Siewert B, Adamis M, Gaa J, Laub G, Wielopolski P. Signal targeting with alternating radiofrequency (STAR) sequences: application to MR angiography. Magn Reson Med 1994;31: 233–238. 12. Koktzoglou I, Edelman RR. STAR and STARFIRE for flowdependent and flow-independent noncontrast carotid angiography. Magn Reson Med 2009;61:117–124. 13. Dai W, Garcia D, de Bazelaire C, Alsop DC. Continuous flowdriven inversion for arterial spin labeling using pulsed radio frequency and gradient fields. Magn Reson Med 2008;60:1488– 1497. 14. Koktzoglou I, Gupta N, Edelman RR. Nonenhanced extracranial carotid MR angiography using arterial spin labeling: improved performance with pseudocontinuous tagging. J Magn Reson Imaging 2011;34:384–394. 15. Robson PM, Dai W, Shankaranarayanan A, Rofsky NM, Alsop DC. Time-resolved vessel-selective digital subtraction MR angiography of the cerebral vasculature with arterial spin labeling. Radiology 2010;257:507–515. 16. Wu H, Block WF, Turski PA, Mistretta CA, Johnson KM. Noncontrast-enhanced three-dimensional (3D) intracranial MR angiography using pseudocontinuous arterial spin labeling and accelerated 3D radial acquisition. Magn Reson Med 2013;69:708– 715. 17. Glover GH, Pauly JM. Projection reconstruction techniques for reduction of motion effects in MRI. Magn Reson Med 1992;28: 275–289. 18. Nielles-Vallespin S, Weber MA, Bock M, et al. 3D radial projection technique with ultrashort echo times for sodium MRI: clinical applications in human brain and skeletal muscle. Magn Reson Med 2007;57:74–81. 19. Nagele T, Klose U, Grodd W, Petersen D, Tintera J. The effects of linearly increasing flip angles on 3D inflow MR angiography. Magn Reson Med 1994;31:561–566. 20. Simonetti OP, Finn JP, White RD, Laub G, Henry DA. “Black blood” T2-weighted inversion-recovery MR imaging of the heart. Radiology 1996;199:49–57.
