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Technical Innovation |
1 Department of Radiology, Johns Hopkins University Medical School, JHOC 4223,
601 N Caroline St., Baltimore, MD 21287. Address correspondence to M.
Stuber.
2 Department of Electrical and Computer Engineering, Johns Hopkins University,
Baltimore, MD.
3 Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland,
OH.
4 Philips Medical Systems, Cleveland, OH.
5 Department of Medicine, Johns Hopkins University Medical School, Baltimore,
MD.
Received March 6, 2006;
accepted after revision August 1, 2006.
This work was supported by a biomedical engineering grant from the Whitaker
Foundation (RG-02-0745), a grant from the Donald W. Reynolds Foundation, and a
grant from the National Institutes of Health (HL61912).
Abstract
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CONCLUSION. Quantitative analysis of the moving phantom showed that dimension measurements approached those obtained in the static phantom when using FREEZE. In vitro, vessel sharpness, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were significantly improved when coronary MRA was performed during the software-prescribed period of minimal myocardial motion (p < 0.05). Consistent with these objective findings, image quality assessments by consensus review also improved significantly when using the automated prescription of the period of minimal myocardial motion. The use of FREEZE improves image quality of coronary MRA. Simultaneously, operator dependence can be minimized while the ease of use is improved.
Keywords: cardiac imaging • heart • MR angiography • MRI • MR technique
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On MRI, signal sampling during a period of rapid coronary motion leads to blurring that adversely affects the diagnostic quality of the images. The duration of the acquisition window can be abbreviated to minimize this effect. However, this change is associated with prolonged scanning times. Evidently, myocardial motion is not constant throughout the entire cardiac cycle. Therefore, careful selection of both the position and the duration [6] of the MRI acquisition window plays an important role in minimizing the effects of blurring on coronary MRA [7]. Furthermore, these rest periods must be determined on a per-subject basis [8]. Although visual assessment of this quiescent period on MR cine images is likely to be superior to empiric formulas [9], visual inspection is still subjective.
A powerful calibration scan based on navigator echoes was introduced by Wang et al. [9]. However, this approach necessitates meticulous geometric planning of the navigator position and has currently not found widespread use. As an alternative, automated image-based cross-correlation analysis for multi-heart phase images has recently been reported for the identification of the period of minimal myocardial motion [8]. Hereby, a frame-to-frame correlation method on a selected volume encompassing the heart was used. In these studies, the trigger delays found by visual assessment and those identified by an automated algorithm were compared. However, the effect of these strategies on coronary MR image quality was not ascertained to our knowledge.
In the present work, we tested the hypothesis that coronary MRA performed at a computer-identified time delay after the R wave of the ECG leads to better objective and subjective image quality when compared with that using a visually identified period of minimal myocardial motion. For the automated detection of that rest period, a computer algorithm, FREEZE, was developed; the name "FREEZE" is not an abbreviation or acronym. The adequacy of this algorithm to detect minimal motion was first tested in a moving phantom [10] at 1.5 T. Subsequently, 3-T in vivo coronary MRA images obtained using visual inspection of the period of minimal motion were compared with those obtained using FREEZE.
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Subsequently, a moving average displacement is calculated using these values in a user-specified time window (i.e., the acquisition window for coronary MRA), and the time point of minimal displacement is identified and transferred to the scanner. This FREEZE algorithm (Fig. 1) was implemented using interactive data language (IDL 6.0, RSI, Inc.) on a commercial PC running Windows XP (Microsoft) that is interfaced with the scanner. The scanner was programmed to automatically use this software-prescribed time point of minimal myocardial motion for coronary MRA scanning.
Phantom Experiments
To test the hypothesis that FREEZE can effectively identify periods of
minimal motion, phantom studies were conducted
[11]. An MR-compatible
sinusoidally moving phantom with ECG output and a maximum displacement of 1.4
cm (frequency, 72 cycles/min; maximum velocity, 10.2 cm/s) was developed, as
described in an earlier article
[10]. A curved silicone tube
with an internal diameter of 1.8 mm attached to a water bottle was mounted on
the moving phantom (Fig. 2A,
2B,
2C). The tube was filled with
mineral oil (Johnson's Baby Oil, Johnson & Johnson).
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t] = 14 milliseconds, n = 60 frames per
R-R interval) of the moving phantom was then acquired and further processed by
the FREEZE software. The duration of the time window in which FREEZE should
identify minimal motion was set to approximately 70 milliseconds, as
previously reported for coronary MRA
[12]. In this phantom
experiment, Tds is the time delay between the R wave and imaging for which
minimal motion is found.
Images of the moving phantom were then obtained using a conventional
navigator-gated and navigator-corrected 3D high-resolution segmented k-space
imaging sequence (TR/TE = 7.0/2.4, 
= 35°, resolution = 0.7 x
1 x 3 mm, 10 k-space lines per cardiac cycle, acquisition time window
[Tacq] = 70 milliseconds, field of view = 280 x 350 mm, 160
x 240 matrix). The trigger delay between the phantom-generated R wave
and the imaging sequence was then adjusted from 100 to 800 milliseconds in
increments of 100 milliseconds. For comparison, one static scan without motion
of the phantom was acquired and another scan with the trigger delay prescribed
by the software was acquired as well. Vessel diameter and sharpness were then
analyzed using Soap-Bubble software
[13].
All the phantom scans were obtained on a commercial 1.5-T system (Gyroscan Intera, Philips Medical Systems) equipped with a PowerTrak 6000 gradient system (Philips Medical Systems) (23 mT/m, 219-µsec rise time). The vessel diameter was calculated as the average value found perpendicular to a 3-cm segment of the plastic tube oriented perpendicular to the direction of motion (segments I and II in Fig. 2C). The vessel sharpness values were calculated for the same segment using the Deriche algorithm [14]. This analysis was then repeated for another 3-cm segment of the tube in parallel to the readout direction (segments III and IV in Fig. 2C).
In Vivo Experiments
Subjects—Ten healthy human subjects (nine men, one woman;
mean age, 24.9 years; age range, 21-32 years) who did not have contradictions
to MRI were examined. Written informed consent was obtained from all
participants, and the research protocol was approved by the hospital committee
on clinical investigation. The study was compliant with the Health Insurance
Portability and Accountability Act.
MR technique—All the in vivo MR scans were obtained on a commercial 3-T system (Gyroscan Achieva, Philips Medical Systems) equipped with a Dual Quasar gradient system (Philips Medical Systems) (80 mT/m, 200-µsec rise time, 16-channel parallel receiver architecture). All subjects were imaged in the supine position using a six-element cardiac phased-array coil for signal reception and vector ECG triggering [15].
To test the hypothesis that the use of FREEZE leads to improved coronary
MRA image quality when compared with images obtained using visual inspection
of the period of minimal myocardial motion, the following coronary MRA
protocol was used. To localize the heart, a low-resolution 2D free-breathing
segmented k-space gradientecho imaging scan was obtained in the transverse,
coronal, and sagittal orientations (3.8/1.8, = 20°). The scanning
duration for the scan was 12 seconds. The navigator for subsequent coronary
MRA was localized at the dome of the right hemidiaphragm as identified on the
transverse and coronal views of this first scout scan. The navigator was
localized one third above the lung-liver interface and two thirds below with a
5-mm navigator-gating window.
Subsequently, low-resolution free-breathing navigator-gated and
navigator-corrected 3D segmented k-space gradient-echo imaging (2.5/1.29,
= 15°, resolution = 2.11 x 2.11 x 4.0 mm, field of
view = 270 x 270 mm, 128 x 128 matrix) was performed in the
transverse orientation to accurately localize the left and right coronary
arterial systems. Twenty-five radiofrequency excitations were performed per
R-R interval (Tacq = 63 milliseconds), and the total scanning
duration for this scan was approximately 2 minutes during free breathing. On
these images, volume targeting parallel to the right and left coronary
arterial systems was obtained using a 3-point plan scan tool
[16].
Next, an axial free-breathing 2D segmented k-space gradient-echo cine
sequence with 4 signal averages (2.7/1.37, =25°,
resolution=2x2x8 mm, field of view = 320 x 320 mm, 160
x 160 matrix, scan duration = 15 seconds, 50 frames/s) was used for
imaging at a midventricular level. This scan was used to determine the time
point (after the R wave of the ECG) of the onset of the period of minimal
myocardial motion for both visual assessment (Tdsv) and FREEZE
(Tdsf). To determine Tdsf, an ROI of approximately 100
x 75 pixels that included both the left and right ventricles was
manually selected on an end-diastolic frame of the axial cine images.
To image the coronary arteries with a high spatial resolution at
Tdsv and Tdsf, volume-targeted navigator-gated and
navigator-corrected double oblique 3D segmented k-space gradient-echo imaging
was performed for the left and right coronary arterial systems (4.3/1.47,
=20°, resolution=0.7x1x3 mm, field of view = 360
x 270 mm, 512 x 268 matrix, 16 radiofrequency excitations per R-R
interval, Tacq = 69 milliseconds, bandwidth = 362 Hz/pixel, scan
duration = 145-259 seconds depending on the navigator efficiency and heart
rate, 10 slices [acquired], 20 slices [reconstructed using zero filling], fat
saturation, adiabatic T2 prepulse, [TE = 50 milliseconds])
[17]. In one volunteer study,
free-breathing coronary MRA using Tdsf was performed with a voxel
size of 0.35 x 0.35 x 1.5 mm (7.5/2.3, = 20°, field of
view = 270 x 216 mm, 800 x 610 matrix, scan duration = 906
seconds, 12 radiofrequency excitations per R-R interval, Tacq = 90
milliseconds, 10 slices [acquired], 20 slices [reconstructed], fat
saturation).
Image Analysis
Quantitative analysis of coronary MRA was performed using the Soap-Bubble
tool [13] by one reviewer who
was blinded to the scanning method (Tdsv or Tdsf).
Images obtained at Tdsv and Tdsf were compared for
length of visible vessel, vessel sharpness, vessel diameter, signal-to-noise
ratio (SNR), and contrast-to-noise ratio (CNR). Length measurements were
performed for both the right coronary artery (RCA) and the left anterior
descending (LAD) coronary artery. Vessel sharpness and vessel diameter were
measured in the proximal 4 cm of both the RCA and LAD. As described in depth
in a related article by Etienne et al.
[13], a Deriche algorithm was
applied on the multiplanar reformatted coronary Soap-Bubble image. The local
value in a Deriche image represents the magnitude of local change in signal
intensity (derivative), which allows the user to map the vessel sharpness
along the diameter of a selected vessel.
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In a similar manner, CNR was determined using three ROIs: ROIA and ROIB were identical to those used for the SNR assessment, and the third ROI was positioned on the myocardium (ROIC). The difference between the signal intensities in ROIA and ROIC was then divided by the SD in ROIB to calculate CNR.
The qualitative analysis of coronary MRA was first performed individually by two reviewers blinded to how images were obtained (i.e., with Tdsv or Tdsf). This was followed by a consensus review by the same reviewers using a previously reported 1- to 4-point scale to assess image quality: 1, coronary artery not visible or visible with markedly blurred borders or edges; 2, coronary artery visible with moderately blurred borders or edges; 3, coronary artery visible with mildly blurred borders or edges; and 4, coronary artery visible with sharply defined borders or edges [18].
Statistical Analysis
Quantitative and qualitative results from evaluation of images obtained
using visual assessment and FREEZE were compared using the paired Student's
t test. A p value of < 0.05 was considered statistically
significant. The correlation between grades assigned by two blinded readers
was tested using the Pearson's correlation coefficient method. According to
that method, for a two-tailed test with a significance level of 0.01 to be
statistically important, the rxy value—that is, the Pearson's
method result—must be above 0.606. This was taken into consideration for
the interpretation of reviewer consensus. For statistical comparison of image
quality grading, Wilcoxon's rank sum test was used.
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Orthogonal to the direction of motion, a constant diameter of 2.2 mm (22% overestimation) was found for all time points, the static condition, and Tds.
For tube interface definition (i.e., sharpness), the highest values were found for the nonmoving (i.e., static) phantom (72%) and for the software-prescribed trigger delay in the moving phantom (73%). The lowest sharpness value (40%) was found during the highest velocity in temporal coincidence with the maximum overestimation of the tube diameter (Figs. 2B and 3B).
Perpendicular to the readout direction, 60% sharpness was found independent of the phantom velocity (Fig. 3B).
In Vivo Experiments
Using FREEZE, the identification of the period of minimal myocardial
motion, including data transfer from and to the scanner was less than 1
minute.
The mean vessel length obtained from images acquired with Tdsv was 65.2 mm. The mean vessel length measured on the images that were acquired using FREEZE was 83.2 mm (Table 1). The mean vessel sharpness for the proximal coronary arteries was 43.8% using Tdsv, whereas it amounted to 46.3% with FREEZE (Table 1). In the same segments, the vessel diameter on the images obtained using Tdsv was 2.9 mm compared with 3.0 mm using FREEZE (p < 0.04) (Table 1). The average SNR measured on images acquired at Tdsv was 29.5 arbitrary units (AU) in comparison with 32.0 AU obtained from the images acquired using FREEZE. Simultaneously, the average CNR was 21.0 and 23.0 AU (Table 1), respectively.
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Using Pearson's correlation coefficient, there was certain reviewer consensus for the qualitative grading of the images obtained using visual assessment and FREEZE (rxy = 0.76). The median quality grade of the images obtained with visual assessment and those obtained with FREEZE was 3 on the scale described earlier, which ranges from 1 to 4. The results of the Wilcoxon's rank sum test suggest that there is a significant difference in image quality grades between images obtained with Tdsf and those obtained with Tdsv (p < 0.02), with the Tdsf images being superior.
In Figure 4A, 4B, 4C, 4D, 4E, 4F, three sets of images—each set composed of one image obtained using visual identification and the other, FREEZE—are compared for image quality, sharpness, and vessel length. In Figure 4B, the left coronary system obtained using Tdsf has both higher visual vessel definition and contrast in comparison with the image in Figure 4A that was obtained with Tdsv. In another subject shown in Figure 4D, a longer contiguous segment of the RCA is observed with Tdsv. Finally, Figures 4E and 4F show one of the cases in which a strong disagreement between Tds and Tdsv was found.
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To minimize the adverse effects of B0 inhomogeneity on image quality, we used local volume shimming in conjunction with segmented k-space gradient-echo imaging rather than SSFP imaging. To remove artifacts originating from B1 inhomogeneity, we used an adiabatic T2 prepulse for contrast generation between the coronary blood pool and the myocardium [17].
To avoid signal loss due to a prolonged T1, we lowered the radiofrequency excitation angle to 20° for coronary MRA (30° at 1.5 T). Reliable R wave triggering at a higher field strength was ensured using vector ECG technology [15]. In all of our subjects, ECG triggering was reliable and repositioning of electrodes was never necessary. However, once the 3 T-specific challenges were addressed, residual myocardial motion had to be further constrained to support better vessel conspicuity and, ultimately, imaging at a higher spatial resolution. Therefore, FREEZE was developed, and its utility was tested in the present study.
In Figure 3A, a variable diameter measurement is a result of different phantom velocities during the acquisition interval. Imaging during increased phantom velocity leads to an overestimation of the diameter measurements of structures that are oriented perpendicular to the direction of motion. However, for structures that are oriented parallel to the direction of motion, no such oscillations are visible, but an overestimation of the diameter measurements occurs. This can be attributed to the anisotropic in-plane spatial resolution of 0.7 x 1.0 mm. Similar findings can be reported for vessel sharpness, which is adversely affected if imaging is performed during high phantom velocities. Together with the variable diameter measurements as a function of phantom velocity, this emphasizes the strong need for approaches that minimize motion during the signal readout.
In vivo, the use of FREEZE led to objective and subjective improvements in image quality. The SNR, CNR, vessel sharpness, and vessel length values for images obtained using FREEZE were superior to those for images obtained using visual assessment of the rest period. Consistent with these findings, visual grading also showed an improvement in image quality when FREEZE was used. A minor discrepancy was also observed between phantom and in vivo studies. Whereas the diameter measurement in the phantom was slightly reduced by the use of FREEZE, FREEZE led to a diameter increase of 0.1 mm in the in vivo study. Although this effect reached only borderline statistical significance, it may be attributed to coronary blood flow that was present in the in vivo but not in the in vitro part of the study.
Interestingly, the correlation between Tdsv and Tdsf was not outstanding, suggesting that visual inspection may not have allowed correct identification of the period of minimal myocardial motion in all cases. We found two examples in which the visually identified trigger delay and the FREEZE-prescribed trigger delay were in strong disagreement. In these cases, end-systolic rather than late diastolic windows of minimal myocardial motion were identified by the software. In both cases, image quality was substantially improved when FREEZE was used. These findings suggests that FREEZE may be more objective than reviewers in identifying the period of minimal myocardial motion.
A 2D segmented k-space gradient-echo cine sequence acquired at a midventricular level was used to determine the onset of the period of minimal myocardial motion using FREEZE. During the cardiac cycle, the displacement and velocity of the different coronary segments are not identical. However, using biplanar angiography, Johnson et al. [11] identified a period of relative quiescence during mid diastole in which proximal, mid, and distal segments of both the left and right coronary arterial systems are at rest simultaneously. This finding suggests that cine images from an axial midventricular level are adequate for determining the optimal trigger delay for coronary MRA.
In the present study, we used a fixed acquisition window. However, previous studies have shown that periods of minimal myocardial motion vary among individuals and can be as long as 200 milliseconds if a patient's heart rate is lower than 60 beats per minute. This allows the duration of the acquisition window to be adjusted for abbreviated scanning times [5-7]. Although this was not part of the present study, the FREEZE software could be modified to prescribe not only the onset of the period of minimal myocardial motion, but also its relative duration.
Even though an in-depth study about the selection of the ROI for the identification of the period of minimal myocardial motion was not performed, experimental repeated assessments of the period of minimal cardiac motion using FREEZE on the same volunteer resulted in no or very minor variations of the trigger delay. We expect that the use of smaller ROIs may lead to larger variations in the trigger delay.
By increasing the magnetic field strength from 1.5 to 3 T, the increased SNR can theoretically be traded for enhanced spatial resolution. However, this necessitates sufficiently constrained residual myocardial motion, as already mentioned. Encouraged by the results obtained with FREEZE, we tried to reduce the voxel size in one subject to 0.35 x 0.35 x 1.5 mm (Fig. 6) toward the end of our study. Although these preliminary data show this approach is feasible and promising, more experience with that protocol in both adult patients and healthy adult subjects is now needed.
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To our knowledge, this study is the first that shows that the automated identification of the period of minimal myocardial motion results in improved image quality for free-breathing 3D coronary MRA. However, there are still some challenges that remain to be addressed.
Heart rate variability is an important reason for the change of both temporal position and the duration of the period of minimal myocardial motion. FREEZE needs to be applied before coronary MRA to achieve the highest precision in the identification of this rest period. However, FREEZE cannot accommodate real-time changes due to heart rate variability during scanning. Therefore, real-time identification of this rest period is the next step to elaborate.
Although we have not studied the effect of using this software tool to evaluate patients with coronary artery disease, the results obtained in a phantom and in healthy adult subjects suggest an improvement in image quality. Improvement in image quality is likely to support improved characterization of coronary artery disease.
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The FREEZE tool may easily be adapted for use on multiple vendors' systems. In addition, this method may have the potential to improve coronary CT angiography as well.
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