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Intraarterial Versus IV Gadolinium Injections for MR Angiography: Quantitative and Qualitative Assessment of the Infrainguinal Arteries

¹ Biocenter, University of Basel, Basel, Switzerland.
² Institute of Diagnostic Radiology, University Hospital of Basel, Petersgraben 4, Basel, Switzerland 4031.
³ Department of Angiology, University Hospital of Basel, Basel, Switzerland.
⁴ Hochrheinklinik, Bad Saeckingen, Germany.

Received July 16, 2004; accepted after revision October 15, 2004.

 
Address correspondence to D. Bilecen (dbilecen{at}uhbs.ch).

Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
OBJECTIVE. Our purpose was to quantitatively and qualitatively compare 3D intraarterial (IA) gadolinium-enhanced MR angiography (IA MRA) versus the standard of reference of MR angiography, 3D IV gadolinium-enhanced MR angiography (IV MRA), in patients with peripheral arterial occlusive disease (PAOD) for use during catheter-based MR-guided endovascular interventions.

CONCLUSION. IA MRA provides image quality of the infrainguinal arteries in PAOD patients comparable to IV MRA with a significantly improved assessment of the infrapopliteal arteries due to reduced venous contamination. Further benefits of IA MRA include usage of only very low doses of gadolinium and simplified bolus timing.

Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Several properties of MRI encourage research on endovascular interventions under MR guidance. The major advantages of 3D contrast-enhanced MR angiography (MRA) over intraarterial (IA) digital subtraction angiography (DSA) include avoidance of ionizing radiation for patient and investigator, no use of nephrotoxic iodinated contrast material, high soft-tissue contrast, and 3D depiction of the arterial tree. These potential benefits have motivated investigators during the last few years to extend MR technology in the direction of MR-guided endovascular interventions. Techniques have been developed to visualize, track, and control catheters and guidewires [1-3]. Furthermore, animal studies have shown that some endovascular procedures, such as stent placement [4, 5] and embolization [6, 7], can be performed under MR guidance.

3D contrast-enhanced MRA with IV gadolinium has become a well-accepted diagnostic tool for noninvasive evaluation of the human macrovasculature and is presently the standard of reference in MRA of peripheral arteries. However, gadolinium-containing contrast agents can also be applied by IA injections. For catheter-based MR-guided interventions, this approach seems to be natural since the arterial access has already been established for the intervention and can be used for contrast media injection. Unlike IV MRA, IA gadolinium is not completely nonnephrotoxic, but it has a lower nephrotoxicity than iodinated contrast media [8]. IA 3D contrast-enhanced MRA is a field of growing interest and may play a key role in MR-guided endovascular interventions.

Phantom and animal studies have shown that IA MRA with substantially reduced gadolinium doses is feasible to provide angiograms for MR-guided endovascular procedures [9-13]. Furthermore, there is no need for complex timing procedures because the start of data acquisition and bolus injection can be performed simultaneously. Such timing schemes would not be feasible in an interventional setting, where the focus has to be on the intervention and not on imaging. A first IA MRA study in patients with peripheral arterial occlusive disease (PAOD) has shown good arterial signaling in the infrainguinal arteries using a low-dose injection protocol [14]. These primary results seem very promising for establishing IA MRA as a tool for MR-guided endovascular interventions in humans.

However, a detailed and direct comparison between the image quality of IA and IV MRA—which is considered the standard of reference in MRA [15, 16]—is required to estimate the diagnostic potential of catheter-directed IA injections. A recent animal study has shown that IA and IV MRA have a similar accuracy for detecting renal artery stenosis in swine [17]. However, until now, no quantitative or qualitative comparison between these contrast-enhanced MRA techniques in humans has been reported.

The objective of this patient study was to determine whether low-dose IA MR angiograms of the infrainguinal arteries are quantitatively and qualitatively comparable to IV MR angiograms.

Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Patients
Within a 12-week period, IA MRA and IV MRA were performed in 11 patients (10 men, one woman; age range, 48-86 years; mean age, 69.3 ± 12.1 years; body weight, 75.0 ± 7.6 kg) with angiographically documented PAOD (Fontaine grade IIa/b). Exclusion criteria were general contraindications for MRI such as pacemakers, ferromagnetic implants, and claustrophobia. Table 1 summarizes the characteristics of each patient. The study protocol was approved by our institutional review board. After providing a detailed explanation of the study, we obtained written informed consent from all patients before they entered the study.

All patients were referred to the department of radiology for radiographically guided percutaneous transluminal angioplasty (PTA) of the iliac or femoropopliteal artery. Transfemoral arterial access in either antegrade or retrograde direction was used. IA MRA was performed directly after PTA. For this reason, the 4-French/6-French introducer sheath remained either in the proximal superficial (antegrade) or in the common femoral artery (retrograde) position. To ensure optimal dispersion of the contrast agent in the bloodstream, side hole catheters—that is, a 4-French Royal Flush catheter (Merritt) in case of antegrade or a 4-French Omni Flush catheter (Merritt) in case of retrograde crossover access—were introduced via the percutaneous sheath. The connection of the catheter was extended by a plastic tube to enable comfortable IA gadolinium administration.

The patients were transferred from the DSA suite to the MR suite on a stretcher. A continuous infusion of saline solution at a flow rate of approximately 1 mL/min was applied to preserve the patency of the system during transportation. The overall time for patient transportation and repositioning within the magnet took approximately 15-25 min. IV MRA of the patient was performed 24-48 hr later. In all 11 patients, IA and IV MRA were performed postinterventionally on the ipsilateral side of the PTA (Table 1). None of the patients underwent additional interventions between IA and IV MRA.

MRI
All imaging was performed with a clinical 1.5-T MR system (Magnetom Sonata, Siemens Medical Solutions) equipped with high-performance gradients (amplitude, 40 mT/m; rise time, 200 µsec). A phased-array peripheral vascular coil was used for signal reception. Patients were examined in the supine position with feet first in the MR scanner.

Contrast-enhanced data sets of the infrainguinal arteries were acquired in the coronal plane using a fast spoiled 3D gradient-echo sequence with fat suppression. For IA MRA, a two-step nonautomated technique covering thigh and calf station was applied. For IV MRA, a standard three-step automated moving-table protocol covering pelvis, thigh, and calf station was used [18, 19]. Overlapping data sets of the two stations of the infrainguinal arteries were acquired with identical acquisition parameters for IA and IV MRA of the thigh/calf: TR, 2.8/3.5 msec; TE, 1.1/1.3 msec; flip angle, 20°/20°; field of view, 380 x 380/325.7 x 380 mm²; matrix, 448 x 314/448 x 307 interpolated by zero-filling to 448 x 448/448 x 384. One slab of 48/48 partitions interpolated by zero-filling to 64/80 (slab thickness, 80/80 mm; slice thickness, 1.7/1.7 mm interpolated to 1.3/1.0 mm) was acquired. Eighty percent partial Fourier was applied in both phase-encoding directions to reduce the acquisition time to 27/33 sec (2.8 msec x 314 x 0.8 x 48 x 0.8/3.5 msec x 307 x 0.8 x 48 x 0.8). Table stepping from one station to the next was performed within 5 sec, resulting in a cumulative acquisition time of 65 sec for the two stations.

Contrast Agent Administration
For all MRA examinations, commercially available gadopentetate dimeglumine (Magnevist, Schering) distributed with a full-strength concentration of 500 mmol/L was used. For IA MRA, the contrast agent was diluted with physiologic saline solution to obtain a gadolinium concentration of 50 mmol/L. A bolus volume of 20 mL corresponding to a dose of 1 mmol (gadolinium concentration x bolus volume) was applied for each station of the two-step MRA. The bolus was injected manually at a flow rate of approximately 1 mL/sec and was flushed with 10 mL of saline injected at the same flow rate. IA gadolinium injection and MR data acquisition started simultaneously. The MR scanner was triggered by a foot switch next to the scanner. Before each of the two contrast agent injections, an unenhanced image of the respective station was acquired, serving as mask for digital subtraction of the contrast-enhanced data sets.

For IV MRA, gadolinium was injected through an IV catheter placed in the antecubital fossa using a computer-controlled power injector (Spectris, Medrad). Patients with less than 75 kg body weight received 20 mL of undiluted gadolinium, whereas patients weighing more than 75 kg received 30 mL gadolinium, corresponding to a dose of 10 mmol and 15 mmol, respectively. Gadolinium was injected using a biphasic protocol: The first half was administered at a rate of 1 mL/sec, and the second half was administered at a rate of 0.5 mL/sec followed by a flush of 30 mL of saline solution at a rate of 0.5 mL/sec. Before contrast agent administration, unenhanced mask images of the three stations were acquired. Bolus timing was performed using MR fluoroscopic real-time monitoring of the pelvic station. When the contrast agent reached the distal part of the abdominal aorta, acquisition of the 3D contrast-enhanced MRA data set was started manually.

Image Analysis
Comparison between IA and IV MRA was based on a quantitative and qualitative analysis. For each patient, the infrainguinal arterial vasculature was divided into four segments: proximal superficial femoral artery, distal superficial femoral artery, popliteal artery, and infrapopliteal arteries. Data sets of the first station (pelvis) available only in the IV MRA examinations were excluded from further evaluation.

View larger version (15K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —Anteroposterior maximum intensity projection images of left thigh and calf station obtained with fast spoiled 3D contrast-enhanced gradient-echo sequence in 69-year-old man after left antegrade percutaneous transluminal angioplasty of superficial femoral artery. Intraarterial angiogram. Gadolinium was administered intraarterially at a dose of 1 mmol/station.

View larger version (24K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —Anteroposterior maximum intensity projection images of left thigh and calf station obtained with fast spoiled 3D contrast-enhanced gradient-echo sequence in 69-year-old man after left antegrade percutaneous transluminal angioplasty of superficial femoral artery. Conventional IV angiogram obtained with identical acquisition parameters as A. Dose of 15 mmol of gadolinium was administered IV. At thigh level, optimal image quality was achieved with both injection modes, whereas at calf level of IV angiogram, disturbing venous overlay is observed.

IA and IV MR angiograms were subjected to a prospective qualitative analysis based on a segment-by-segment review. The MRA data sets were available on a workstation that allowed viewing of source images, MIPs, and multiplanar reconstructions. Two board-certified radiologists and one board-certified physician who specialized in angiology assessed the image quality with concern for venous contamination and arterial visualization. These reviewers were blinded to the mode of contrast agent injection and patient identity and clinical history. The MR angiograms were interpreted twice, once by the three observers independently and then by consensus of all three reviewers. The arterial visualization was rated on a 3-point scale: 1, good (all arteries of interest evaluable); 2, moderate (arteries incompletely evaluable); 3, poor (arteries minimally evaluable to inaccessible). The assessment of venous contamination was also based on a 3-point rating scale: 1, good (no venous signal); 2, moderate (minor to considerable venous contamination); 3, poor (major to severe venous contamination). Mean arterial visualization (AVS_mean) and venous contamination scores (VCS_mean) were calculated for each segment and each MR examination. A Student's t test (paired, two-sided) was performed to determine statistically significant differences between the IA and IV MR angiograms.

Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
IA and IV MRA provided good image quality of the thigh and calf vasculature in all 11 patients with PAOD (Figs. 1A, 1B, 2A, and 2B). Both the IA and the IV injection protocols were well tolerated, and no side effects were noted by any of the patients.

View larger version (26K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —Comparison of anteroposterior maximum intensity projection images of right infrainguinal arteries obtained with fast spoiled 3D contrast-enhanced gradient-echo sequence in 75-year-old man after right antegrade percutaneous transluminal angioplasty of superficial femoral artery. Image obtained with intraarterial injection of low dose of gadolinium.

View larger version (16K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —Comparison of anteroposterior maximum intensity projection images of right infrainguinal arteries obtained with fast spoiled 3D contrast-enhanced gradient-echo sequence in 75-year-old man after right antegrade percutaneous transluminal angioplasty of superficial femoral artery. Image obtained with conventional IV injection of standard dose of gadolinium. Note purely arterial filling of all arteries of interest in intraarterial angiogram. Although in IV angiogram, all arteries are fully evaluable at thigh level showing precise bolus timing, assessment of infrapopliteal arteries is complicated due to considerable venous contamination and background tissue enhancement.

View larger version (22K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3 —Comparison of contrast-to-noise ratio (CNR) values between intraarterial MR angiography (gray bars) and IV MR angiography (black bars). CNR ± SD of four arterial segments from thigh and calf station are averaged over all 11 patients.

Qualitative analysis of the four arterial segments seen in both MRA examinations revealed an overall good correlation between IA and IV MRA regarding venous contamination and arterial visualization (Table 2). The proximal, distal superficial femoral, and popliteal arteries were rated as similar in quality without significant differences. For the infrapopliteal arteries, the analysis showed significantly higher venous contamination and poorer arterial visualization for IV MRA (p < 0.02)—2.0 ± 0.9 and 1.8 ± 0.8 for IV MRA versus 1.2 ± 0.6 and 1.2 ± 0.6 for IA MRA, respectively.

Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
In this study, a quantitative and qualitative comparison between IA and IV MRA of the infrainguinal arteries of patients suffering from PAOD has been performed. The low-dose injection protocol applied for IA MRA has been recently proposed and has been shown to generate good image quality and high arterial enhancement in the infrainguinal arteries [14].

The major finding of this study was that IA MRA provided image quality regarding CNR of the infrainguinal arteries similar to that of IV MRA, the standard of reference for MRA (p > 0.05). Qualitative assessment of thigh and calf arteries revealed a significant reduction of venous overlay in IA MRA at the infrapopliteal level (p < 0.02), which was accompanied by improved arterial visualization.

One of the most important requirements for MR-guided interventions is the repetitive and rapid acquisition of high-spatial-resolution MR angiograms. These are mandatory to document the vascular state before intervention, localize devices and show advances during intervention, and finally visualize therapeutic changes achieved by the interventional procedure. Because of the short half-life of gadolinium in blood, repetitive gadolinium injections are needed to visualize the arteries of interest during an endovascular intervention. Therefore, the U.S. Food and Drug Administration (FDA)-approved total dose of 0.3 mmol/kg is not to be exceeded. In our study, the IV MRAs were obtained with a dose of 10-15 mmol—slightly less than the FDA-approved daily limit. A dose of only 2 mmol was applied for the IA MRAs of the entire infrainguinal arteries—that is, 1 mmol for each of the two stations. Assuming a body weight of 75 kg—which was the average body weight in this study—only 4-5% of the total permissible dose was applied per station. Therefore, IA MRA will allow more than 20 intraarterial injections, which might be sufficient during an MR-guided endovascular intervention.

The CNR of IA MRA cannot be increased infinitely by applying higher injected gadolinium doses. Because of the paramagnetic properties of gadolinium, there is an optimal range for the injected dose [20, 21]. Higher gadolinium doses will lead to a signal decrease because the T2/T2^*-dependent signal loss will reduce or even overcompensate for the T1-dependent signal gain.

Insufficient arterial enhancement or disturbing venous overlay was not observed at all in IA MRA—neither at thigh nor at calf level—but was occasionally found in IV MRA mainly at the calf level (Figs. 1A, 1B, 2A, and 2B). The resulting significantly more pronounced venous contamination and poorer arterial visualization scores for the infrapopliteal arteries in IV MRA might be explained by variations in the precision of bolus timing. In bolus chase IV MRA, exact synchronization of contrast agent arrival and data acquisition is difficult to achieve and may easily lead to an inconsistent image quality [22]. On the other hand, IA MRA does not rely on complicated timing strategies because acquisition of MRA data and bolus injection start simultaneously. Thus, timing errors are virtually excluded.

For diagnostic purposes, IA MRA is not a competitor to IV MRA because IV injections are minimally invasive and thus safer. However, for therapeutic MR-guided interventional procedures in the future, IA MRA would be recommended because a catheter has already been placed within the lumen of the vessel of interest and contrast agent application can be performed directly. Furthermore, as has been demonstrated in this study, IA MRA will be more advantageous for MR-guided endovascular interventions than IV MRA because of the substantially reduced gadolinium dose, no need for bolus timing, and minimal venous contamination. In summary, there is promise that IA MRA will become the method of choice for the acquisition of high-spatial-resolution MR angiograms for MR-guided interventional procedures. This may support the development of MR-guided endovascular interventions in humans as a possible alternative to IA DSA, which would allow the replacement of radiographic monitoring by MRI and of iodinated contrast agents by gadolinium injections.

This study has a number of limitations. First, our experiments were limited to the infrainguinal arteries. The applied low-dose injection protocol used for IA MRA has only been validated for the flow condition of the human femoral artery and may not be appropriate for the delineation of major vessels with higher blood flow rates such as the aorta. However, it can be expected that a comparison between IA and IV MRA in vascular territories with similar blood flow rates as the femoral artery will yield results analogous to those obtained in our study.

Second, the comparison of IA MRA versus IV MRA was restricted to a single MRA examination. The image quality after multiple injections of gadolinium over a time period typical for an interventional procedure still needs to be evaluated. It may be hypothesized that a gradually increased dose of gadolinium might be necessary to overcome the increasing amount of accumulated contrast agent in the soft tissue with each injection. On the other hand, the mask strategy applied for IA MRA—that is, acquisition of a new mask image immediately before each injection, might facilitate to reduce the growing amount of background tissue enhancement.

Third, IA application of gadolinium-containing contrast agents is an off-label route, which has not yet been approved by the FDA. However, IA injections of gadolinium have been safely used for diagnostic or therapeutic IA DSA in the past [23, 24].

Finally, we have only compared the image quality of IA and IV MRA (that is, CNR, venous contamination, arterial visualization), not their diagnostic value. However, from the equivalent image quality and the results of an animal study demonstrating no significant differences between IA and IV MRA in detecting stenosis [17], it may be hypothesized that IA MRA will have the same diagnostic potential as IV MRA. Nevertheless, a direct comparison between IA MRA and IA DSA—as the standard of reference for endovascular interventions—will be required to evaluate the sensitivity, specificity, and accuracy of IA MRA for the depiction of stenosis and occlusions in humans. In one of our clinical studies, we are investigating the diagnostic value of IA MRA.

In conclusion, quantitative and qualitative assessment of the infrainguinal arteries in PAOD patients after PTA demonstrated that IA and IV MRA yield comparable image quality, except for significantly reduced venous overlay at the infrapopliteal level in IA MRA. MRA with IA injections of gadolinium allows the use of substantially lower doses. This may enable more than 20 injections during an MR-guided endovascular intervention before the FDA-approved maximum dose is reached. The use of IA MRA may facilitate the development of MR-guided endovascular interventional procedures in humans, which eventually will become a potential competitor to DSA.

Acknowledgments
 
We thank Tanja Haas and Phillip Madoerin for their assistance in data acquisition and processing.

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