9
Optimization of Spiral-Based Pulse Sequences for First-Pass Myocardial Perfusion Imaging Michael Salerno, 1 * Christopher T. Sica, 2 Christopher M. Kramer, 1,3 and Craig H. Meyer 3,4 Although spiral trajectories have multiple attractive features such as their isotropic resolution, acquisition efficiency, and robust- ness to motion, there has been limited application of these tech- niques to first-pass perfusion imaging because of potential off- resonance and inconsistent data artifacts. Spiral trajectories may also be less sensitive to dark-rim artifacts that are caused, at least in part, by cardiac motion. By careful consideration of the spiral trajectory readout duration, flip angle strategy, and image reconstruction strategy, spiral artifacts can be abated to create high-quality first-pass myocardial perfusion images with high sig- nal-to-noise ratio. The goal of this article was to design inter- leaved spiral pulse sequences for first-pass myocardial perfusion imaging and to evaluate them clinically for image quality and the presence of dark-rim, blurring, and dropout artifacts. Magn Reson Med 65:1602–1610, 2011. V C 2011 Wiley-Liss, Inc. Key words: myocardial perfusion; spiral pulse sequences; saturation recovery It is estimated that 17.6 million Americans have coro- nary artery disease (CAD), and it is responsible for approximately one in six deaths (1). A recent retrospec- tive analysis of the National Cardiovascular Data Registry demonstrated that nearly 40% of the 398,987 patients without known CAD who underwent coronary angiogra- phy did not have significant CAD (2). Thus, improve- ments in the accuracy of noninvasive assessment of CAD could significantly reduce health care costs resulting from unnecessary and expensive invasive procedures. Cardiac magnetic resonance (CMR) stress perfusion imag- ing has multiple potential advantages over existing modalities, and its combination with wall motion analy- sis and late gadolinium enhancement can provide addi- tional important information to assess for the presence and extent of CAD (3). First-pass perfusion imaging using CMR has become clinically applicable, but has not yet gained widespread acceptance. One of the limitations has been the presence of dark-rim artifacts (DRAs) that may be mistaken for true perfusion abnormalities resulting in false-positive studies (4–7). Multiple factors have been hypothesized to contribute to the DRA including magnetic susceptibility differences between the myocardium and blood pool during first pass of contrast, ‘‘Gibbs ringing’’ resulting from the limitations in spatial resolution predominantly in the phase-encoding direction, and motion-induced phase shifts during data acquisition resulting from car- diac motion during the finite time of data acquisition (4,8–10). Efforts to combat this DRA have primarily focused on imaging the heart faster to minimize effects of myocar- dial motion during the imaging sequence and increasing spatial resolution to minimize the effects of ‘‘Gibbs’’ ring- ing. These have included the use of interleaved echo-pla- nar imaging (EPI) pulse sequences (11,12) and using par- allel imaging techniques (12,13). Investigators have not frequently examined alterna- tive acquisition strategies such as spiral imaging that may be less sensitive to motion artifacts. Spiral imag- ing has been applied to rapid real-time applications including imaging of the coronary arteries (14–16). However, there has been limited application of spiral trajectories to first-pass perfusion CMR (17,18). Spiral trajectories have other attractive features such as effi- ciency in traversing k-space, isotropic resolution and point-spread functions and the lack of discrete ghost- ing resulting from motion. Spiral techniques also lend themselves to parallel imaging that could further reduce imaging time and improve temporal resolution (19–21). Potential drawbacks include sensitivity to off- resonance and concomitant field gradients that can result in blurring and signal loss and to inconsistent data artifacts when the signal intensity varies between interleaves due to nonequilibrium magnetization. How- ever, by careful consideration of the spiral trajectory readout (RO) duration and flip angle strategy, we dem- onstrate that these effects can be abated to create high- quality first-pass myocardial perfusion images. The goal of this article was to design and evaluate inter- leaved spiral pulse sequences for first-pass myocardial perfusion imaging. MATERIALS AND METHODS Pulse Sequence Design Design Criteria To design an optimal spiral pulse sequence for perfusion imaging, specific goals for resolution, timing, and signal- 1 Cardiovascular Division, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA. 2 Department of Radiology, Pennsylvania State Hershey Medical Center, Hershey, Pennsylvania, USA. 3 Department of Radiology, University of Virginia Health System, Charlottesville, Virginia, USA. 4 Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA. Grant sponsor: AHA; Grant number: 10SDG2650038; Grant sponsor: NIH; Grant numbers: 5T32EB003841, R01 HL079110; Grant sponsor: Siemens Medical Solutions. *Correspondence to: Michael Salerno, MD, Ph D, Assistant Professor of Medicine and Radiology, Cardiovascular Division, University of Virginia Health System, Lee Street, Charlottesville, VA 22908. E-mail: [email protected] Received 20 June 2010; revised 26 October 2010; accepted 7 November 2010. DOI 10.1002/mrm.22746 Published online 10 January 2011 in Wiley Online Library (wileyonlinelibrary. com). Magnetic Resonance in Medicine 65:1602–1610 (2011) V C 2011 Wiley-Liss, Inc. 1602

Optimization of spiral-based pulse sequences for first-pass myocardial perfusion imaging

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Page 1: Optimization of spiral-based pulse sequences for first-pass myocardial perfusion imaging

Optimization of Spiral-Based Pulse Sequences forFirst-Pass Myocardial Perfusion Imaging

Michael Salerno,1* Christopher T. Sica,2 Christopher M. Kramer,1,3

and Craig H. Meyer3,4

Although spiral trajectories have multiple attractive features suchas their isotropic resolution, acquisition efficiency, and robust-ness to motion, there has been limited application of these tech-niques to first-pass perfusion imaging because of potential off-resonance and inconsistent data artifacts. Spiral trajectories mayalso be less sensitive to dark-rim artifacts that are caused, atleast in part, by cardiac motion. By careful consideration of thespiral trajectory readout duration, flip angle strategy, and imagereconstruction strategy, spiral artifacts can be abated to createhigh-quality first-pass myocardial perfusion images with high sig-nal-to-noise ratio. The goal of this article was to design inter-leaved spiral pulse sequences for first-pass myocardial perfusionimaging and to evaluate them clinically for image quality and thepresence of dark-rim, blurring, and dropout artifacts. MagnReson Med 65:1602–1610, 2011. VC 2011 Wiley-Liss, Inc.

Key words: myocardial perfusion; spiral pulse sequences;saturation recovery

It is estimated that 17.6 million Americans have coro-nary artery disease (CAD), and it is responsible forapproximately one in six deaths (1). A recent retrospec-tive analysis of the National Cardiovascular Data Registrydemonstrated that nearly 40% of the 398,987 patientswithout known CAD who underwent coronary angiogra-phy did not have significant CAD (2). Thus, improve-ments in the accuracy of noninvasive assessment of CADcould significantly reduce health care costs resultingfrom unnecessary and expensive invasive procedures.Cardiac magnetic resonance (CMR) stress perfusion imag-ing has multiple potential advantages over existingmodalities, and its combination with wall motion analy-sis and late gadolinium enhancement can provide addi-tional important information to assess for the presenceand extent of CAD (3).

First-pass perfusion imaging using CMR has becomeclinically applicable, but has not yet gained widespread

acceptance. One of the limitations has been the presenceof dark-rim artifacts (DRAs) that may be mistaken fortrue perfusion abnormalities resulting in false-positivestudies (4–7). Multiple factors have been hypothesized tocontribute to the DRA including magnetic susceptibilitydifferences between the myocardium and blood poolduring first pass of contrast, ‘‘Gibbs ringing’’ resultingfrom the limitations in spatial resolution predominantlyin the phase-encoding direction, and motion-inducedphase shifts during data acquisition resulting from car-diac motion during the finite time of data acquisition(4,8–10).

Efforts to combat this DRA have primarily focused onimaging the heart faster to minimize effects of myocar-dial motion during the imaging sequence and increasingspatial resolution to minimize the effects of ‘‘Gibbs’’ ring-ing. These have included the use of interleaved echo-pla-nar imaging (EPI) pulse sequences (11,12) and using par-allel imaging techniques (12,13).

Investigators have not frequently examined alterna-tive acquisition strategies such as spiral imaging thatmay be less sensitive to motion artifacts. Spiral imag-ing has been applied to rapid real-time applicationsincluding imaging of the coronary arteries (14–16).However, there has been limited application of spiraltrajectories to first-pass perfusion CMR (17,18). Spiraltrajectories have other attractive features such as effi-ciency in traversing k-space, isotropic resolution andpoint-spread functions and the lack of discrete ghost-ing resulting from motion. Spiral techniques also lendthemselves to parallel imaging that could furtherreduce imaging time and improve temporal resolution(19–21). Potential drawbacks include sensitivity to off-resonance and concomitant field gradients that canresult in blurring and signal loss and to inconsistentdata artifacts when the signal intensity varies betweeninterleaves due to nonequilibrium magnetization. How-ever, by careful consideration of the spiral trajectoryreadout (RO) duration and flip angle strategy, we dem-onstrate that these effects can be abated to create high-quality first-pass myocardial perfusion images. Thegoal of this article was to design and evaluate inter-leaved spiral pulse sequences for first-pass myocardialperfusion imaging.

MATERIALS AND METHODS

Pulse Sequence Design

Design Criteria

To design an optimal spiral pulse sequence for perfusionimaging, specific goals for resolution, timing, and signal-

1Cardiovascular Division, Department of Medicine, University of VirginiaHealth System, Charlottesville, Virginia, USA.2Department of Radiology, Pennsylvania State Hershey Medical Center,Hershey, Pennsylvania, USA.3Department of Radiology, University of Virginia Health System,Charlottesville, Virginia, USA.4Department of Biomedical Engineering, University of Virginia, Charlottesville,Virginia, USA.

Grant sponsor: AHA; Grant number: 10SDG2650038; Grant sponsor: NIH;Grant numbers: 5T32EB003841, R01 HL079110; Grant sponsor: SiemensMedical Solutions.

*Correspondence to: Michael Salerno, MD, Ph D, Assistant Professor ofMedicine and Radiology, Cardiovascular Division, University of VirginiaHealth System, Lee Street, Charlottesville, VA 22908.E-mail: [email protected]

Received 20 June 2010; revised 26 October 2010; accepted 7 November2010.

DOI 10.1002/mrm.22746Published online 10 January 2011 in Wiley Online Library (wileyonlinelibrary.com).

Magnetic Resonance in Medicine 65:1602–1610 (2011)

VC 2011 Wiley-Liss, Inc. 1602

Page 2: Optimization of spiral-based pulse sequences for first-pass myocardial perfusion imaging

to-noise ratio (SNR) must be clearly defined. To haveadequate spatial coverage to describe myocardial perfu-sion in the modified 16-segment American Heart Associ-ation model of the left ventricle (LV) (17-segment modelwith the apical cap excluded), data must be acquired ata minimum of three short-axis slices. These slices areideally imaged each heart beat due to the rapidity of thefirst pass of gadolinium (22). Increases in heart rate dur-ing adenosine infusion, which are typically 20% of rest-ing heart rate, must also be taken into account. For thesereasons, our goal was to image rapidly enough to imagethree slice locations every heart beat at heart rates up to110 BPM. At this rate, the RR interval is 546 msec, and,thus, the time to acquire each image must be less than182 msec for three-slice locations.

For clinical first-pass perfusion sequences, in-planespatial resolutions (Dx) generally range from 1.8 to 2.8mm in the RO direction and 2.8–3.4 mm in the phase-encoding direction (6). A rectangular field of view anddecreased resolution in the phase-encoding direction aretypically used for Cartesian sampling to minimize thetotal number of lines of raw data that are needed. In spi-ral imaging, the field of view is inherently isotropic, asis the spatial resolution. Isotropic in-plane resolutions of2.2–3.1 mm2 (with resolution defined as 1/2kmax) corre-spond to the same voxel volumes as in the aforemen-tioned Cartesian case with the same slice thickness. Ourminimum goal was to have spatial resolution that issuperior to current Cartesian pulse sequences.

Spiral Gradient Trajectory Design

Slew-limited spiral gradient trajectories were created usingthe optimal spiral design of Meyer and Hu (21). Briefly,the process consists of specifying the desired number of

interleaves, sampling time, number of points per trajectory,field of view, and maximum gradient and slew rate param-eters to determine the desired k-space trajectory k(t) ¼At(t)e�iwt(t). An algorithm that maximizes t, and arbitraryfunction of time, for each subsequent k-space step subjectto the above constraints is repeated until a desired numberof gradient points are achieved. The actual spatial resolu-tion of the trajectory is then determined by integrating thegradient trajectory to determine the maximal k-space loca-tion sampled. The same gradient trajectory design tech-nique was used to create single-shot spiral trajectories togenerate a field map with each image acquisition for thesemiautomatic reconstruction.

There are two competing issues when considering theoptimal sampling time for each interleaf for interleavedspiral pulse sequences. Longer RO times are more efficientand require fewer spiral interleaves to collect the k-spacedata, but they are more sensitive to off-resonance blurringand signal losses. To balance between these competingfactors, while achieving the desired temporal and spatialresolution described above, spiral trajectories with ROdurations between 4 and 12 msec per interleaf were con-sidered, yielding between 6 and 16 interleaves per image.

Pulse Sequence Design

The pulse sequence is shown schematically in Fig. 1. Acomposite saturation pulse, consisting of a combination ofthree radiofrequency (RF) pulses and crusher gradients,was used (23). Although spectral-spatial excitation pulsesare often used for spiral imaging to only excite the waterresonance, at 1.5 T these pulses require at least 8 msecand are time prohibitive for this application, given theachievable number of spiral interleaves for the desiredtemporal and spatial resolution requirements. Instead,before data acquisition, a spectrally selective fat-saturationpulse is applied. Then, two single-shot spiral images withdifferent echo times (TEs) are acquired that are used toobtain a field map for the semiautomatic off-resonancecorrection performed as part of the fast conjugate phaseimage reconstruction (20,24). The pulse repetition time(TR) for these single-shot spirals was kept similar to thatof the spiral interleaves used for data collection. Next,Nint spiral interleaves are obtained in successive TRs tocreate the perfusion image. The collection of the fieldmap results in two additional TRs plus the DTE (typically1 msec) between the field map acquisitions. Thus, thetime to collect a single data set is (Nint þ 2)*TR þ DTE.Figure 2 shows the minimum time for a single imageincluding the time necessary for the fat-saturation pulsefor slew-limited spiral trajectories with varying numbersof interleaves. When the total sampling time for eachimage is kept constant and the TR is minimized given theRO time per interleaf, the total imaging time for a perfu-sion image is a nonlinear function of the number of inter-leaves. Given our spatial and temporal resolution require-ments, the optimal number of interleaves is �6.

Saturation Recovery Time Considerations

The total time needed for data collection and the desiredtime to image each slice set a limit on the possible

FIG. 1. Pulse sequence schematic for the SR spiral perfusionpulse sequence. Following the SR pulse, a single fat-saturation

pulse is applied followed by two single-spiral images for field mapdetermination and then the interleaved spiral readout module.

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saturation recovery time (TS) that can be used. We defineTS as the time from the saturation preparation to the firstimaging RF pulse. The TS is the major determinant of thedegree of T1 weighting and, thus, both the contrast andSNR of the resulting perfusion images. Assuming that theconcentrations of gadolinium in the myocardium are 0.5–2.0 mmol/L, the expected T1s should range between 100and 300 msec (25). Given this range of T1s as well as ourtiming constraints, our TS must be in the range of 60–80msec. As a point of reference, the time to the first RFpulse for fast low angle shot (FLASH) and steady-statefree precession (SSFP) is generally 40 msec and for EPI istypically 50 msec (6). This increase in TS should providean SNR gain for spiral imaging.

Flip Angle Considerations

Among the potential problems with spiral perfusionimaging are inconsistent data artifacts if similar trans-verse magnetization is not available on each interleaf, asthis could lead to periodic modulation of k-space, mani-festing as swirling artifacts in image space. Ideally, thetransverse magnetization would be the same for each spi-ral interleaf. To minimize this issue, we derived an opti-mal constant flip angle (hc) that exactly balances the lossin magnetization from each RF pulse to the T1 recoveryof magnetization during each TR for a given TR, TS, and

T1 to ensure similar transverse magnetization for eachspiral interleaf. This flip angle is given by:

hc ¼ cos�1 E1 � ES

E1ð1� ESÞ� �

; ½1�

where E1 ¼ exp(�TR/T1) and Es ¼ exp(�TS/T1). Table 1shows the optimal constant flip angles as a function ofthe gadolinium concentration and TS for a TR of 12msec. Notably, this flip angle strongly depends on thechosen TS, but is considerably less sensitive to the gado-linium concentration. This results in reasonably constantsignal evolution over a wide range of T1 values as shownin Fig. 3. As a point of reference, FLASH, EPI, and SSFPtypically have FA of 12, 25, and 50, respectively.

SNR Considerations

When the optimized flip angle for a given TS, TR, andT1 is used for the spiral pulse sequence, the actual trans-verse magnetization (Mxy) following each RF pulse isMxy ¼ Mzsin(hc), where Mz is the transverse magnetiza-tion that recovers during TS. For a TR of 12 msec, a gad-olinium concentration of 2 mmol (corresponding to a T1

of 176 msec), and TSs of 60–80 msec, the Mxy is�0.25M0. For a gadolinium concentration of 2 mmol, theFLASH sequence will have an Mxy � 0.05M0, the EPIsequence will have an Mxy of �0.15 M0, and the SSFPsequence will have a magnetization of roughly 0.23M0(6). Thus, the available transverse magnetization isgreater for the spiral pulse than that of FLASH or EPIand should be comparable to that available with SSFP.

When comparing the SNR of interleaved spiral pulsesequences with the same total sampling time and spatialresolution, as a smaller number of interleaves is used,the TR must be increased because of the increased ROtime per interleaf. This increased TR results in a higheroptimal constant flip angle and thus a higher SNR. Forinterleaved spiral pulse sequences with total RO dura-tion of 65 msec and a spatial resolution of 2.18 mm2, thetheoretical SNR of a four interleaf pulse sequence wouldbe 27% higher than the eight interleaf pulse sequence,and the theoretical SNR for 16 interleaf pulse sequencewould be 20% lower than the eight interleaf pulsesequence. Thus, from a SNR perspective, a smaller num-ber of spiral interleaves is advantageous.

Overall, these considerations indicate that spiral pulsesequences should have SNR that is higher than thatavailable with conventional Cartesian pulse sequences.This improved signal can be used to shorten acquisitiontime, improve off-resonance performance, or increasespatial resolution.

FIG. 2. Minimum time to image one slice with a resolution of 2.16

mm, using an interleaved spiral pulse sequence with an additionaltwo interleaves for field map acquisition, as a function of the num-

ber of interleaves. For a given total sampling time, there is an opti-mal number of interleaves in terms of minimizing the time toacquire data for each perfusion image due to the field map

acquisition.

Table 1Optimal Constant Flip Angles for Constant Signal Evolution

[Gado] T1 post TS, 40 msec TS, 60 msec TS, 80 msec TS, 100 msec

0 mmol 850 msec 45� 36� 31� 27�

0.5 mmol 292 msec 44� 35� 30� 26�

1 mmol 176 msec 44� 34� 29� 25�

2 mmol 98 msec 42� 32� 27� 22�

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Imaging Studies

All imaging studies were conducted on a 1.5-T Magne-tom Avanto (Siemens Healthcare, Erlangen, Germany).Resting spiral perfusion imaging was performed in 32patients who were undergoing clinically ordered CMRstudies with and without contrast under an IRB-approved protocol. All patients signed informed con-sent. All of the patients had low likelihood of CAD,and none of the patients had wall motion abnormal-

ities or evidence of myocardial scarring or fibrosis bydelayed enhancement imaging. These subjects werechosen so that artifacts could be evaluated without in-terference from true perfusion abnormalities. Imageswere obtained at three slice locations during injectionof 0.1 mmol/kg of gadolinium contrast agent via a pe-ripheral IV at a rate of 4 mL/sec. Fifty images wereobtained at each slice position during first pass of thecontrast agent.

Multiple interleaved spiral pulse sequences wereimplemented and evaluated. Common sequence parame-ters included TS of 80 msec, TE 1.0 msec, slice thickness10 mm, and field of view 320–340 mm depending onpatient size. Twelve patients were imaged with a spiralpulse sequence with eight interleaves with a RO time of8.1 msec and a spatial resolution of 2.18 mm2, whichserved as the reference pulse sequence. To evaluate theeffects of RO duration on image quality, eight subjectswere imaged with pulse sequences with the same spatialresolution but shorter (6.5 msec, 10 interleaves, N ¼ 4)or longer (10.8 msec, six interleaves, N ¼ 4) RO times.For these experiments, the spatial resolution and totaldata collection time were held constant between pulsesequences. To evaluate the effects of image resolutionwith a fixed RO time, 10 subjects were imaged with aspatial resolution of 2.63 mm2 with a spiral pulsesequence with six interleaves. In this experiment, the ROduration was matched to that of the eight-interleavedpulse sequence so that off-resonance performance wouldbe similar. As the six interleaf sequence has a lower spa-tial resolution, it should have a higher SNR, but thiseffect is partially offset by the decreased total data sam-pling time. The RO duration for the field map wasmatched to that of the corresponding pulse sequence.This yielded field map resolutions of 10 mm for the 10-

FIG. 3. Simulated transverse magnetization curves as a function

of RF pulse number for TS 80 msec, TR 12 msec, and expectedT1 of 175 msec (corresponding to 1 mmol concentration of Gd-

DTPA) using the optimal constant flip angle of 29� for these pa-rameters. The signal evolution is nearly constant over theexpected range of Gd-DTPA concentrations (0.5–2 mmol) corre-

sponding to T1s of 100–300 msec.

FIG. 4. First-pass perfusion images using the eight-interleaved spiral pulse sequence (every fifth image shown through first pass). Theimages have minimal artifacts and high SNR.

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interleaved pulse sequence, 8.7 mm for the eight-inter-leaved pulse sequence (and low-resolution six interleavepulse sequence), and 7.2 mm for the six-interleavedpulse sequence.

Images were reconstructed on-line on the scanner witha semiautomatic reconstruction based on Chebyshevapproximation of the off-resonance phase term deter-mined from the low-resolution field map collected witheach perfusion image (20). This reconstruction method iscomputationally efficient and simultaneously corrects forB0 inhomogeneity and concomitant gradient field effects.

For all studies, the SNR was measured on each imagein a region of interest placed in the LV cavity, septalmyocardium, and background noise. The SNRs at maxi-mal LV and myocardial enhancement were recorded foreach slice and averaged over the three slice positions.The mean SNRs of the LV cavity and myocardium foreach of the above pulse sequences were compared usingone-way ANOVA. The contrast-to-noise ratio (CNR) ofthe myocardium for the above pulse sequences was com-pared using one-way ANOVA.

For the reference pulse sequence (eight interleaves),normalized upslope of the myocardial time intensitycurves was determined by measuring difference in signalintensity before contrast arrival in the myocardium andthe peak signal intensity in the myocardium and divid-

ing by the baseline myocardial signal. This was then di-vided by the number of frames from the beginning of theupslope to the peak myocardial signal intensity.

All image series were evaluated for blurring, DRA, andsignal dropout artifacts (graded as 1, mild; 2, moderate;3, severe). Image quality was graded on a five-point scale(1, excellent; 5, poor) independently by two cardiolo-gists. The image quality scores were compared usingone-way ANOVA. The proportion of image series cor-rupted with blurring, dark-rim, and signal dropoutwas compared using t-tests corrected for multiplecomparisons.

RESULTS

Figure 4 demonstrates first-pass perfusion images at threeslice positions from one subject using the eight interleafpulse sequence; the images have high SNR and minimalDRA or off-resonance artifact. Figure 5 shows time-inten-sity curves normalized to the baseline signal from the LVcavity and the myocardium of the mid-ventricular imagesin this subject. The SNR of the LV cavity and myocar-dium for the 6, 8, and 10 interleaf pulse sequences with2.18-mm resolution was 54.7 6 13.6 and 22.0 6 5.6, 52.66 13.7 and 21.3 6 4.2, and 38.5 6 6.2 and 13.6 6 3.5,respectively. There was no difference between the pulsesequences in peak SNR in the LV cavity (P ¼ 0.16) ormyocardium (P ¼ 0.13). However, the SNR on the 10interleaf pulse sequence had lower point estimates ofSNR in the LV cavity and myocardium as expected fromthe theoretical predictions. The contrast to noise ratios forthe myocardium for the 6, 8, and 10 interleaf pulsesequences were 13.9 6 3.7, 14.3 6 3.2, and 10.3 6 4.0,respectively. There was no significant difference in CNRbetween these pulse sequences (P ¼ 0.11). The averageupslope normalized to the baseline signal intensity for theeight interleaf pulse sequence was 15% 6 3% per frame.The average image quality scores for the 6, 8, and 10interleaf pulse sequences (Table 2) were 1.57, 1.31, and1.67, respectively (P ¼ 0.40). The six interleaf pulsesequences had the least DRAs (10% of images with mildDRA), but 23% of the images had mild blurring, and 40%of the studies had some signal dropout because of thereduced off-resonance performance of this pulse sequence(10.8 msec RO per interleaf). Dropout artifacts occurredprimarily in the inferolateral wall where there are largesusceptibility differences due to the proximity of the heartto the lung and liver in this region. The 10 interleaf pulsesequence had the least blurring (6% of images) and few

FIG. 5. Time intensity curves from six segments of the mid-ven-tricular slice of the subject in Fig. 4. These curves have been nor-malized to the baseline signal intensity as a proton density map

was not collected for intensity normalization.

Table 2

Image Artifact Comparison

Score % DRA % Blurring % Dropout

Six leaves (high res) N ¼ 5 1.5 6 0.4 10% mild 23% mild 20% mild0% mod 0% mod 20% mod

Eight leaves (high res) N ¼ 12 1.3 6 0.5 17% mild 13% mild 6% mild

13% mod 1% mod 0% modTen leaves (high res) N ¼ 5 1.7 6 0.6 20% mild 10% mild 3% mild

20% mod 0% mod 3% modSix leaves (low res) N ¼ 10 1.6 6 0.4 35% mild 7% mild 17% mild

12% mod 5% mod 3% mod

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dropout artifacts (6% of images). However, the 10 inter-leaf pulse sequence had a greater number of images (40%)with at least mild DRA. The eight interleaf pulsesequence had less dropout artifact and blurring than thesix interleaf sequence, likely because of the reduced ROduration, but had more studies with DRA. The proportionof image slices with dropout artifacts was significantlylower for the 8 (P < 0.05) and 10 (P ¼ 0.05) interleafpulse sequences when compared with the six interleafpulse sequence. Figure 6 shows typical images from dif-ferent subjects from the 6, 8, and 10 interleaf pulsesequences, respectively.

For the resolution experiment, the SNR of the LV cav-ity and myocardium for the six interleaf pulse sequencewith 2.63-mm2 resolution was 61.4 6 17.6 and 22.0 65.6, respectively, which was not different from that ofthe reference pulse sequence. Furthermore, the averageimage quality score was 1.57, which was worse than thatof the reference pulse sequence primarily because of ahigh number of images with DRAs. The increased num-ber of images with at least some DRA supports the con-cept that some of the DRA is likely explained by Gibbsringing due to the lower image resolution of this perfu-sion imaging pulse sequence. Figure 7 shows typicalimages from the low-resolution six interleaf pulsesequence and the eight interleaf pulse sequence with thesame RO duration.

To look at the effect of the bolus passage on the off-resonance frequency, the low-resolution field maps fromthe eight-interleaved pulse sequences were recon-structed. Large shifts in the mean off-resonance fre-quency occurred primarily when the bolus was passingthrough the right and left ventricular cavities. For theleft ventricular cavity, these shifts were typically around20 Hz over the 3–5 images of the peak bolus passagethrough the LV. The mean field shift in a region of inter-est placed over the ventricular cavity from all slices ana-lyzed was �22 6 4 Hz; however, there was a clear spa-tial variation over the region of interest. Given theresolution of the field maps, region of interest analysiswas not feasible within the myocardium.

DISCUSSION

We demonstrate that optimized slew-limited spiral tra-jectories are capable of producing high-quality first-passperfusion images. To the best of our knowledge, this isthe first full application of spirals to CMR perfusionimaging. These images have superior spatial resolutioncompared with current clinical perfusion protocols withadequate SNR. The temporal resolution of these pulsesequences, even without the use of parallel imaging,would enable imaging of three slice positions at heart

FIG. 6. Example images frombase, mid, and apex from (a) 6-,(b) 8-, and (c) 10-interleavedpulse sequences. There is mildsignal dropout on the six interleaf

pulse sequence and a mild DRAon the 10 interleaf pulse

sequence images.

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rates up to 110 BMP that may be encountered duringadenosine or regadenoson stress testing.

Through careful design, potential spiral artifacts havebeen largely eliminated. To minimize off-resonance arti-facts, short RO durations per interleaf were used. Off-res-onance artifacts increased with increasing RO times inthe range of 6–11 msec. To minimize dropout and blur-ring artifacts, particularly in the inferolateral wall, theRO duration per interleaf should be kept to less than 8msec. Artifacts in this region could potentially be less-ened by performing a localized shim before the perfusionimaging study. In some cases, there appears to be mildblurring artifacts during contrast passage through theright ventricle, but this was not evident when the con-trast bolus traverses the left ventricular cavity. Analysisof the field maps demonstrated significant shifts in off-resonance frequency within the LV particularly duringfirst pass of the bolus through the left ventricular cavity,which was consistent with those seen by Ferreira et al.who measured field maps during first-pass perfusionusing a conventional gradient-echo pulse sequence (26).As the off-resonance frequency is a function of the con-trast dose, and the angle of the left ventricular cavitywith respect to the main magnetic field, as well aspatient-specific anatomic factors, image quality willlikely be improved by correcting off-resonance with fieldmaps acquired during first pass of the contrast agent.Potential spiral artifacts may have also been mitigated bythe use of a reconstruction that corrects for both off-reso-nance and concomitant gradient fields that can result inimage blurring.

To minimize inconsistent data artifacts caused byvarying magnitude of transverse magnetization, wederived and applied a novel expression for a constantflip angle that should theoretically result in nearly con-stant transverse magnetization between interleaves for asaturation recovery pulse sequence. However, this flipangle will underestimate the flip angle needed for con-

stant evolution of magnetization when inflow effects areconsidered. Assuming a normal myocardial perfusion of1 mL/min g tissue, only 0.02% of the voxel volume isreplenished per TR and, thus, inflow effects are negligi-ble. However, for the LV cavity assuming a mid-cavityvelocity of 25 cm/sec, 30% of the voxel volume isreplenished each TR and inflow effects will be signifi-cant. We simulated the evolution of the transverse mag-netization in the LV cavity for a T1 of 100 msec for theoptimal flip angle and for a 15� flip angle and measuredthe percent increase in signal between the first RF pulseand the fifth RF pulse (half of the eight interleaf acquisi-tion). For the optimal flip angle, there was a 13% differ-ence in Mxy, whereas for the 15� flip angle there was a26% difference. Thus, even though the evolution is notcompletely flat with the optimized flip angle, there isless variation in Mxy and then there would be for a smallflip angle. Additionally, the mean Mxy (over 10 RFpulses) was 68% higher in the case of the optimal flipangle. This strategy appeared to work well for spiral per-fusion imaging; however, other factors such as the inter-leaf order may also play a role in reducing inconsistentdata artifacts (27).

In terms of DRAs, fewer interleaves and higher resolu-tion resulted in fewer DRAs. All of the DRAs noted weresubendocardial at all phases of the cardiac cycle. Wehave previously demonstrated that for Cartesian pulsesequences motion-induced DRA typically appears as dif-ferent locations within the myocardium at differentphases of the cardiac cycle (28). Although this study didnot enable us to separate the effects of motion and Gibbsringing, the increased number of DRA in the low-resolu-tion experiment is consistent with a contribution ofGibbs ringing to the DRA.

In our pulse sequence, we had adequate fat saturationusing a single spectral saturation before the spiral RO. Aprevious study of spiral coronary artery imaging demon-strated a similar performance of a single spectral fat-

FIG. 7. Example images frombase, mid, and apex obtainedwith (a) the six interleaf pulse

sequence (resolution 2.63 mm2)and (b) the eight interleaf pulse

sequence (resolution 2.18 mm2)with the same readout duration(8.1 msec per interleaf). The six

interleaf pulse sequence shows amild DRA in the basal slice, and

the eight interleaf sequenceshows a mild DRA in the mid-slice.

1608 Salerno et al.

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saturation pulse and spectral-spatial excitation (29).Given the time constraints for perfusion imaging and ourcurrent number of spiral interleaves, spectral-spatial ex-citation would be time prohibitive. However, spectral-spatial pulses may be feasible with parallel imagingwhere a fewer number of excitations would be needed.

This study has a few limitations. As this study wasperformed during a routine clinical examination, only asingle perfusion study could be obtained in each subject.This precluded direct comparison of spiral and Cartesianpulse sequences in the same patient. For the same rea-son, only rest perfusion images could be obtained. How-ever, the goal of this study was to evaluate potential arti-facts that could be mistaken for true perfusionabnormalities. We only enrolled patients with a very lowlikelihood of having CAD and performed resting perfu-sion studies so that any abnormalities seen in the imageswould be a result of artifact rather than resulting fromperfusion abnormalities. Furthermore, clinical validationwill be essential to determine how sensitive and specificthese pulse sequences will be for detecting perfusionabnormalities. We are planning a more comprehensivestudy where these pulse sequences will be evaluatedusing cardiac catheterization as the gold standard. Wedid not perform a comprehensive evaluation of differentoff-resonance reconstruction methods, and it is possiblethat a different reconstruction may further improve off-resonance performance. T2/T2* effects resulting fromcompartmentalization of gadolinium within the myocar-dium were not considered; however, the relatively shortTE should minimize these effects. These effects, how-ever, may be significant for quantification of myocardialperfusion especially given the high doses of contrastused in this study.

This is a preliminary study in the development of spi-ral-based perfusion pulse sequences; the sequencescould easily be extended to parallel imaging using bothspatial and/or temporal acceleration techniques. Variabledensity spirals may enable further shortening of the ROduration, thus further improving off-resonance perform-ance, and can be used for apodization of the data withcareful consideration of the density compensation func-tion (30). This could further reduce the appearance ofDRAs.

CONCLUSIONS

High-quality perfusion images can be obtained usingoptimized interleaved spiral pulse sequences. Theadvantages of spiral trajectories for myocardial perfusionimaging include its data-collection efficiency and robust-ness to motion that enable the rapid collection of high-spatial resolution and high SNR images with minimalmotion-induced artifacts. Multiple strategies were usedto overcome the inherent off-resonance limitations of spi-ral trajectories including minimizing RO duration perinterleaf, fat-saturation, and off-resonance deblurringusing field maps collected with each perfusion image.Although the focus of this manuscript was to optimizesequences from the perspective of mitigating artifacts,additional studies will be needed to determine the con-spicuity of perfusion abnormalities on spiral perfusion

images. Validation studies in patients with known CADwill be essential to further assess and optimize the off-resonance performance of these sequences. Furtherdevelopments such as the implementation of parallelimaging techniques may make this an ideal pulsesequences for stress myocardial perfusion imaging.

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