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Dose Optimization for Dynamic Time-Resolved Contrast-Enhanced 3D MR Angiography of Pulmonary Circulation

¹ Department of Radiology, University Hospitals Basel, Petersgraben 4, CH-4053 Basel, Switzerland.
² Department of Radiology, Section of Medical Physics, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany.

Received March 24, 2003; accepted after revision June 17, 2003.

 
Address correspondence to S. Sonnet.

Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
OBJECTIVE. The aim of this study was to optimize contrast media dose for assessment of pulmonary circulation with dynamic time-resolved contrast-enhanced 3D MR angiography.

SUBJECTS AND METHODS. Twenty healthy volunteers (20–38 years old; mean [± SD], 27.2 ± 4.5 years) were examined prospectively using turbo fast low-angle shot MR angiography (TR/TE, 2.4/1.04). Ten consecutive coronal 3D slabs with a frame rate of 3.2-sec duration were acquired during injection of contrast media at a rate of 4 mL/sec. Signal intensities were measured in various vessels and pulmonary parenchyma. Maximum signal-intensity enhancement (SI_max) and time to peak enhancement were calculated. Depiction of pulmonary vessels and pulmonary parenchyma was scored according to an image quality score.

RESULTS. Central pulmonary arteries were well visualized at all tested doses. Segmental arteries, however, were blurry with 0.025 or 0.05 mmol/kg; image quality was improved at 0.1 mmol/kg of gadoterate meglumine (p < 0.05). Image quality did not further improve at 0.2 mmol/kg (p = not significant). Values for SI_max in the pulmonary trunk were 38.9 ± 9.7, 64.1 ± 9.1, 79.7 ± 12.2, and 96 ± 6.0 at 0.025, 0.5, 0.1, and 0.2 mmol/kg of gadoterate meglumine, respectively. Pulmonary parenchyma showed almost no enhancement at 0.025 and 0.5 mmol/kg of gadoterate meglumine (SI_max = 1.6 ± 1.1 and 1.6 ± 1.2, respectively), but better visualization was shown with 0.1 and 0.2 mmol/kg of gadoterate meglumine (SI_max = 2.9 ± 0.8 and 6.7 ± 2.1, respectively). Time from peak enhancement in pulmonary arteries to peak enhancement in veins was independent of dose.

CONCLUSION. A dose of 0.1 mmol/kg of gadolinium chelate allows depiction of pulmonary arteries and qualitative assessment of pulmonary parenchyma. Thus, 0.1 mmol/kg can be recommended for dynamic contrast-enhanced 3D MR angiography.

Introduction

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Dynamic angiography of the heart and pulmonary circulation can be useful in complex congenital heart disease before and after surgical repair or when arteriovenous malformations are suspected. The gold standard for dynamic imaging of the cardiopulmonary circulation is invasive catheter angiography, which has excellent temporal and anatomic resolution. Invasive angiography, however, is associated with morbidity and mortality rates of 6% and 0.5%, respectively [1]. Thus, a noninvasive technique for dynamic angiography would be desirable.

Echocardiography allows assessment of morphology and flow pattern in central pulmonary vessels, but its use in peripheral vessels is limited because it depends on acoustic windows. Helical CT is an excellent tool for pulmonary artery imaging up to the segmental level [2] but provides little information on pulmonary circulation dynamics.

Dynamic contrast-enhanced 2D MR angiography has been used for dynamic assessment of the pulmonary circulation in diseases such as partial anomalous pulmonary venous return, pulmonary arteriovenous malformation, and vasculitis [3]. This technique was proposed for various clinical applications by Wang et al. [4] in 1996 and for pulmonary abnormalities by Hennig et al. [5] in 1997. Its application in arterial occlusive disease of cervical and intracranial arteries was evaluated in various studies [6, 7]. Although dynamic contrast-enhanced 2D MR angiography provides good temporal resolution, it is hampered by poor spatial resolution because data contain no 3D information, lack of which is a potential problem in the assessment of small vascular structures. Thus, a 3D technique would be helpful.

Three-dimensional dynamic contrast-enhanced MR angiography was described by Korosec et al. [8] in 1996 and by Mistretta et al. [9] in 1998. Initial results evaluating the pulmonary arteries in eight patients with suspected pulmonary embolism and three healthy volunteers have been presented by Goyen et al. [10]. These researchers used a flow rate of 3 mL/sec for a total volume of 20 mL of gadoterate meglumine (Guerbet, Aulnay-sous-Bois, France) flushed with 20 mL of normal saline. Another case with pulmonary arteriovenous malformation has been described by Goyen et al. [11]. Various contrast media flow rates and doses have been used for dynamic contrast-enhanced 3D MR angiography. To our knowledge, the appropriate contrast media dose, however, has not yet been established.

Thus, we sought to determine the best contrast media dose for dynamic contrast-enhanced 3D MR angiography of the pulmonary circulation with respect to depiction of pulmonary artery branches; depiction of pulmonary parenchyma, which can reflect pulmonary perfusion; and differentiation of pulmonary arteries from veins.

Subjects and Methods

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In this prospective study, 20 young healthy volunteers (nine men and 11 women; age range, 20–38 years; mean [± SD], 27.2 ± 4.5 years) were evaluated. All volunteers gave informed consent to participate in the study.

MRI was performed on a 1.5-T scanner (Magnetom Symphony, Siemens, Erlangen, Germany) equipped with Quantum gradients (amplitude, 30 mT/m; slew rate, 125 T/m per second, Siemens) and a 4-element (circular polarized) phased array body coil. Slabs for contrast-enhanced 3D MR angiography were oriented in the coronal direction and acquired using a turbo fast low-angle shot sequence (TR/TE, 2.4/1.04; flip angle, 20°; slice thickness, 5 mm; minimal field of view, 400 x 400 mm; matrix, 120 x 256. Ten consecutive 3D slices were prescribed with an acquisition time of 3.2 sec each; thus, the total imaging time for contrast-enhanced 3D MR angiography was 32 sec. The imaging sequence was started simultaneously with the injection of the contrast agent bolus by means of a power injector (Spectris, Medrad, Indianola, PA). The first 3D slab was used for image subtraction. The volunteers were requested to breath-hold; shallow breathing was allowed at the end of the data-acquisition period. Gadoterate meglumine was injected at doses of 0.025, 0.05, 0.1, or 0.2 mmol/kg (four groups of five volunteers each in random order) followed by a saline flush of 30 mL at a flow rate of 4 mL/sec via a large-gauge cannula placed in an antecubital vein.

Data were analyzed in a qualitative and quantitative fashion. For qualitative analysis, contrast-enhanced 3D MR angiograms were reviewed in consensus by two radiologists experienced in cardiovascular imaging. Image quality with respect to depiction of various pulmonary vessels and parenchyma was evaluated according to the imagequality score. The images received the following scores: 1, structure not seen; 2, poor visibility; 3, structure visible but blurry; 4, good visibility and delineation possible; 5, excellent visibility and clear delineation of structure. An image-quality score was applied to right, left, lobar, segmental, and subsegmental arteries and lung parenchyma. Image-quality criteria for lung parenchyma were visibility of parenchymal enhancement and delineation from adjacent chest wall and pulmonary vessels. Image-quality scores were ranked and plotted as mean ± SD. Results were compared using the nonparametric Kruskal-Wallis test [12]; a p value of less than 0.05 was considered to be statistically significant. In this exploratory study, we did not adjust the p values for multiple comparisons.

For quantitative analysis, the signal intensity was measured in five different regions of interest (ROIs) in each volunteer in all consecutive contrast-enhanced 3D MR angiography slabs. The ROIs were set in the pulmonary trunk, the pulmonary parenchyma, the left atrium, the aorta, and the inferior vena cava (Fig. 1). The position of the ROI was verified in all consecutive 3D slabs to control for motion of anatomic structures and to minimize partial volume effects. In the pulmonary trunk, the left atrium, the aorta, and the inferior vena cava, ROIs contained at least 40 pixels; in pulmonary parenchyma, they contained at least 320 pixels. Maximum signal-intensity enhancement (SI_max) was calculated as signal intensity (SI) in the respective slab minus SI in first slab in identical locations. Differences among various doses and anatomic structures were analyzed by means of a linear mixed-effect analysis of variance, in which subjects were treated as a random factor. A p value of less than 0.05 was considered significant (Fig. 2A, 2B, 2C).

View larger version (171K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1. —29-year-old healthy male volunteer. Contrast-enhanced 3D MR angiogram shows signal intensity measurements. Regions of interest are set in five different anatomic regions to measure signal intensities in 1, pulmonary trunk; 2, pulmonary parenchyma; 3, left atrium; 4, aorta; and 5, inferior vena cava. Repeated measurements in consecutive 3D slabs in identical locations provide time-course data of signal intensity changes.

View larger version (12K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A. —Graphs show signal-intensity enhancement in arbitrary units (SI) with 0.025 (), 0.05 (), 0.1 (), and 0.2 l (•) mmol/kg of gadoterate meglumine plotted over time. Graphs show main pulmonary artery (A).

View larger version (11K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B. —Graphs show signal-intensity enhancement in arbitrary units (SI) with 0.025 (), 0.05 (), 0.1 (), and 0.2 l (•) mmol/kg of gadoterate meglumine plotted over time. left atrium (B).

View larger version (11K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C. —Graphs show signal-intensity enhancement in arbitrary units (SI) with 0.025 (), 0.05 (), 0.1 (), and 0.2 l (•) mmol/kg of gadoterate meglumine plotted over time. aorta (C).

Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
MRI and contrast media injections were well tolerated. Contrast-enhanced 3D MR angiography was easy to perform and successful in all volunteers. Neither test bolus calculation nor real-time bolus visualization was necessary. The total room time in the MRI unit was less than 20 min for each volunteer.

Right and left pulmonary arteries were well visualized in all volunteers with good to excellent image quality (score, 4–5), regardless of dose (Fig. 3A). SI measurements in the pulmonary trunk showed strong SI at all tested doses. Lobar pulmonary arteries were well visualized but blurry with 0.025 and 0.05 mmol/kg of gadoterate meglumine. With 0.1 mmol/kg, image quality and visibility of lobar pulmonary arteries improved significantly to a score of 4–5 (p < 0.05). Further dose increase to 0.2 mmol/kg, however, yielded no further improvement of image-quality score. Similarly, segmental arteries were poorly visualized and blurry (score, 2–3) with 0.025 and 0.05 mmol/kg, but significantly better (p < 0.05) visualized with 0.1 mmol/kg. A further dose increase to 0.2 mmol/kg did not improve the image-quality score. Subsegmental arteries were visualized poorly or not at all for all doses (score, 1–2).

View larger version (16K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A. —Visibility and delineation of pulmonary structures at various doses of contrast media. Light gray bars = 0.025 mmol/kg of gadoterate meglumine, dark gray bars = 0.05 mmol/kg of gadoterate meglumine, black bars = 0.1 mmol/kg of gadoterate meglumine, and white bars = 0.2 mmol/kg of gadoterate meglumine. Graph shows that image-quality score for right and left pulmonary arteries (r/l PA) was 4 or better, regardless of dose. Lobar (Lobar PA) and segmental arteries (Segm PA) were scored below 4 with 0.025 and 0.05 mmol/kg of gadoterate meglumine; significantly better score was achieved with 0.1 of mmol/kg. Dose increase to 0.2 of mmol/kg of gadoterate meglumine did not further improve score. Subsegmental arteries (Subsegm PA) were scored below 2 at all tested doses (p < 0.5).

Visibility of pulmonary parenchyma was poor with 0.025 and 0.05 mmol/kg of gadoterate meglumine (SI_max = 1.6 ± 1.1 and 1.6 ± 1.2 arbitrary units) and improved with an increased dose. Pulmonary parenchyma was visible but blurry with 0.1 and 0.2 mmol/kg (SI_max = 2.9 ± 0.8 and 6.7 ± 2.1 arbitrary units) of gadoterate meglumine (Fig. 3B). Thus dynamic time-resolved contrast-enhanced 3D MR angiography may be useful for qualitative assessment of pulmonary perfusion but not for depiction of anatomic details of the lungs. A representative example, seen in Figure 4A, 4B, 4C, 4D, shows contrast-enhanced 3D MR angiography with 0.1 mmol/kg of gadoterate meglumine during early and late pulmonary arterial phase, pulmonary venous phase, and systemic arterial phase.

View larger version (11K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B. —Visibility and delineation of pulmonary structures at various doses of contrast media. Light gray bars = 0.025 mmol/kg of gadoterate meglumine, dark gray bars = 0.05 mmol/kg of gadoterate meglumine, black bars = 0.1 mmol/kg of gadoterate meglumine, and white bars = 0.2 mmol/kg of gadoterate meglumine. Graph shows that pulmonary parenchyma was visible, but score did not exceed 3 at all tested doses.

View larger version (122K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4A. —29-year-old healthy male volunteer. Contrast-enhanced maximum-intensity-projection 3D MR angiogram obtained with 0.1 mmol/kg of gadoterate meglumine during early pulmonary arterial phase shows clear depiction of pulmonary trunk and left and right (arrow) pulmonary arteries.

View larger version (140K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4B. —29-year-old healthy male volunteer. Contrast-enhanced maximum-intensity-projection 3D MR angiogram was obtained with 0.1 mmol/kg of gadoterate meglumine during late pulmonary arterial phase. Note pulmonary arteries up to segmental level and parenchymal blush (arrows).

View larger version (143K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4C. —29-year-old healthy male volunteer. Contrast-enhanced 3D MR angiogram obtained during pulmonary venous phase shows central pulmonary veins (arrows).

View larger version (157K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4D. —29-year-old healthy male volunteer. Contrast-enhanced 3D MR angiogram obtained during systemic arterial phase shows aorta (arrows) and proximal brachiocephalic arteries.

The mean contrast media travel time from peak enhancement of the pulmonary trunk to the left atrium was 2.76 sec (p < 0.01) without evidence of dose effect (p = not significant).

Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Our results show that depiction of central pulmonary vessels improves as the dose increases from 0.025 to 0.1 mmol/kg. Further dose increase, however, does not provide better image quality. These findings are in agreement with data of Lentschig et al. [13], who compared various doses of gadoterate meglumine (0.1, 0.2, and 0.3 mmol/kg) for MR angiography of the aorta. These investigators found no significant differences in contrast-enhanced 3D MR angiography of the aorta with respect to quantitative signal enhancement analysis and qualitative interpretation. These authors applied a test bolus followed by a contrast-enhanced 3D MR angiography sequence of 20-sec duration. Enhancement of pulmonary parenchyma was visible but did not allow detailed depiction of pulmonary anatomy at any of the tested doses. Pulmonary enhancement, however, was visible with doses of 0.1 mmol/kg or higher, which may allow qualitative assessment and detection of perfusion defects. The feasibility of pulmonary perfusion imaging with contrast-enhanced 3D MRI has been reported with a dose of 0.2 mmol/kg [14] or with specific sequences at a dose of 0.1 mmol/kg [15]. It appears that the appropriate dose for contrast-enhanced 3D perfusion MRI remains to be determined. The injection rate for gadolinium does not significantly change maximal enhancement in contrast-enhanced 3D pulmonary perfusion MRI, as was recently shown for rates of 1, 3, and 5 mL/sec [16].

Contrast media travel times to pulmonary arteries and veins were significantly different, evident as different times to peak enhancement. The measured times to peak enhancement in pulmonary arteries and veins were similar to those in data reported from Barger et al. [17]. We found no relationship between dose and contrast media travel time. Thus, the current single-phase bolus injection technique does not provide reliable differential enhancement of pulmonary arteries and veins. An interesting approach for differential enhancement of pulmonary arteries and veins has been reported by Schoenberg et al. [18]. These investigators used a dynamic time-resolved contrast-enhanced 3D MR angiography with a temporal resolution of 6.28 sec and two injections of gadolinium chelate boluses synchronized with the first and third data sets. This infusion strategy created two anticorrelated data sets with predominantly pulmonary arterial or venous signal enhancement. Further separation of arteries and veins by means of correlation analysis resulted in high-resolution pulmonary arteriograms and venograms.

Dynamic time-resolved contrast-enhanced 3D MR angiography remains a balance between high temporal and high spatial resolution. Further improvements can be achieved with stronger gradient systems. In our study, we used a gradient system with an amplitude of 30 mT/m and a slew rate of 125 mT/m per millisecond allowing for a TR/TE of 2.4/1.0, respectively. Stronger gradient systems with an amplitude of 40 mT/m and a slew rate of 125 T/m per second can realize 1.6/0.6 and thus provide higher spatial resolution with a similar scan time of 3.74 sec [10]. Even stronger gradient systems might further improve resolution, but physiologic limits with stimulation of muscle and nerve tissues may be reached [19, 20]. View-sharing of central k-space data with sequences such as contrast-enhanced 3D time-resolved imaging of contrast kinetics can enhance the frame rate [8]. Increasing the sampling rate of central k-space lines defining lower spatial frequencies and temporal interpolation of k-space views results in a frame rate of one 3D volume every 2 sec [8]. Even higher frame rates and temporal resolution can be achieved with 2D projection MR angiography with up to four images per second [3]. This sequence, however, has a poor spatial resolution with marked voxel anisotropy (2 x 2 x 200 mm³) and no 3D information; thus, small structures may not be visible. Blood pool agents may also be used for 3D MR angiography of the pulmonary circulation with strong signal enhancement and good detail depiction, but distinguishing arteries from veins can be difficult [21].

Our study had the following limitations: We examined only 20 healthy volunteers and analyzed the visibility of pulmonary vessels and parenchyma. We are assuming that the current imaging protocol can also be applied in patients to detect circulation abnormalities (e.g., arteriovenous malformation and partial anomalous pulmonary venous return). In patients with cardiopulmonary or pulmonary disease, however, circulation time may vary substantially, thus affecting vascular enhancement.

In conclusion, dynamic time-resolved contrast enhanced 3D MR angiography is easy to apply because it requires no bolus-timing scan and it can be readily implemented on most clinical scanners. For assessment of pulmonary vessels, a dose of 0.1 mmol/kg of gadolinium chelates can be recommended.

Acknowledgments
 
We thank T. Haas and the entire team of MRI technologists for their valuable help in the examinations and data handling.

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