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Published online before print October 19, 2007, 10.1148/radiol.2452062067
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(Radiology 2007;245:761-769.)
© RSNA, 2007

Experimental Studies

Hind Limb Ischemia in Rabbit Model: T2-prepared versus Time-of-Flight MR Angiography at 3 T1

Grigorios Korosoglou, MD 2, Wesley D. Gilson, PhD, Michael Schär, PhD, Ali Ustun, MS, Lawrence V. Hofmann, MD, Dara L. Kraitchman, VMD, PhD, and Matthias Stuber, PhD

1 From the Russell H. Morgan Department of Radiology and Radiological Science, JHOC 4223, The Johns Hopkins University School of Medicine, 601 N Caroline St, Baltimore, MD, 21287 (G.K., W.D.G., M. Schär, A.U., D.L.K., M. Stuber); Philips Medical Systems, Cleveland, Ohio (M. Schär); and Department of Interventional Radiology, Stanford University Medical Center, Stanford, Calif (L.V.H.). Received December 5, 2006; revision requested February 5, 2007; revision received March 2; final version accepted April 16. Supported in part by National Institutes of Health grants 1 K08 EB004922-01 (L.V.H.), R01-HL073223 (D.L.K.), and R01-HL084186 (M. Stuber). Address correspondence to M. Stuber (e-mail: mstuber{at}mri.jhu.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Purpose: To prospectively compare various parameters of vessels imaged at 3 T by using time-of-flight (TOF) and T2-prepared magnetic resonance (MR) angiography in a rabbit model of hind limb ischemia.

Materials and Methods: Experiments were approved by the institutional animal care and use committee. Endovascular occlusion of the left superficial femoral artery was induced in 14 New Zealand white rabbits. After 2 weeks, MR angiography and conventional (x-ray) angiography were performed. Vessel sharpness was evaluated visually in the ischemic and nonischemic limbs, and the presence of small collateral vessels was evaluated in the ischemic limbs. Vessel sharpness was also quantified by evaluating the magnitude of signal intensity change at the vessel borders.

Results: The sharpness of vessels in the nonischemic limbs was similar between the TOF and the T2-prepared images. In the ischemic limbs, however, T2-prepared imaging, as compared with TOF imaging, generated higher vessel sharpness in arteries with diminished blood flow (mean vessel sharpness: 44% vs 30% for popliteal arteries, 45% vs 28% for saphenous arteries; P < .001 for both comparisons) and enabled better detection of small collateral vessels (93% vs 36% of vessels, P < .001).

Conclusion: T2-prepared imaging can facilitate high-spatial-resolution MR angiography of small vessels with low blood flow and thus has potential as a tool for noninvasive evaluation of arteriogenic therapies, without use of contrast material.

Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/2452062067/DC1

© RSNA, 2007


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Critical limb ischemia is one of the leading causes of amputation and death in patients with peripheral arterial occlusive disease (1,2). Currently, conventional (x-ray) angiography is considered the reference standard for the diagnosis of peripheral arterial occlusive disease (1,3,4). However, because angiography is invasive, noninvasive techniques such as magnetic resonance (MR) angiography may be valuable alternatives (1,3,4). Currently, arteriogenic therapies based on gene and cellular products are being evaluated in preclinical (5) and clinical (6) trials. MR imaging offers promise as a method of tracking and following up the development of the neovasculature and noninvasively assessing the effectiveness of arteriogenic therapies. However, the diminished blood flow and the small size of the neovasculature present a challenge at MR imaging.

Time-of-flight (TOF) MR angiography generates adequate signal intensity in the peripheral arteries (7–10). TOF MR angiography is based on the formation of contrast due to the inflow of unsaturated spins contained in moving blood into the saturated spins contained in surrounding tissues (7,9,11). Therefore, the contrast generated by using this technique is blood flow dependent, and this dependence may result in the inadequate delineation of segments that have diminished blood flow (11,12).

On the other hand, with T2 preparation, a flow-independent technique, one can suppress the muscles, veins, and fat, facilitating the delineation of arteries that contain oxygenated blood with a prolonged T2 (12,13). The feasibility of T2 preparation for enhancing coronary vessel sharpness has been previously demonstrated (13–15). However, the utility of this technique for imaging peripheral arteries has not been investigated. Thus, the purpose of our study was to prospectively compare various parameters of vessels imaged at 3 T by using TOF and T2-prepared MR angiography in a rabbit model of hind limb ischemia (16).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
One author (M. Stuber) is compensated as a consultant of Philips Medical Systems (Best, the Netherlands), the manufacturer of the equipment used in this study. Another author (M. Schär) is an employee of Philips Medical Systems (Cleveland, Ohio). All other authors had full control of the inclusion of any data or information that might have represented a conflict of interest for the authors who are a consultant or an employee of Philips Medical Systems. The terms of these agreements were approved by the Johns Hopkins University in accordance with its conflict of interest policies.

Animals and Endovascular Occlusion Procedure
The experiments were approved by the institutional animal care and use committee of The Johns Hopkins University School of Medicine. Fourteen New Zealand white rabbits weighing 2.5–3.2 kg were sedated with acepromazine (1 mg per kilogram of body weight) and ketamine (40 mg/kg), both of which were injected intramuscularly. General anesthesia was maintained with intravenous thiopental. Endovascular occlusions were performed by a single operator (L.V.H.), as described previously (16). Briefly, a carotid artery cutdown was performed, by using a sterile technique, to place a 3-F sheath (Cook, Bloomington, Ind). A 3-F catheter was advanced into the distal left superficial femoral artery (SFA), and five platinum endovascular coils (Boston Scientific, Newington, NH) were placed to occlude the vessel. Two weeks after coil placement, the rabbits were imaged by using TOF and T2-prepared techniques.

MR Imaging
The rabbits were imaged with a 3T Achieva system (Philips Medical Systems) equipped with dual quasar gradients (maximal amplitude, 80 mT/m; maximal slew rate, 200 [mT · m–1]/msec) by using a human six-element cardiac phased-array receiver coil. The heart rate of the rabbits varied between 180 and 220 beats per minute, resulting in a mean R-R interval of approximately 0.3 second, and vector electrocardiography was used in all examinations for R-wave triggering (17). A gradient-echo three-plane scout image was acquired to localize the abdominal aorta and the iliac arteries for high-spatial-resolution MR angiography.

T2-prepared MR angiography
T2 preparation (12–14) is a magnetization preparation scheme used to enhance the contrast between areas with different T2, such as blood and muscle. In short, with use of T2 preparation, the longitudinal magnetization is initially tipped into the transverse plane by using a non–section-selective 90° radiofrequency pulse. Subsequently, a series of non–section-selective 180° pulses keep the magnetization in the transverse plane, where it undergoes T2 decay. After the final 180° pulse, the transverse magnetization is fully refocused and a non–section-selective 90° tip-up pulse is used to restore the magnetization in the longitudinal direction. At this point, greater longitudinal magnetization is achieved in areas of longer T2 than in areas of shorter T2. If imaging is performed after T2 preparation, high signal intensity is achieved in areas of longer T2, while the signal intensity of areas with shorter T2 is attenuated. Thus, T2 preparation (12–14) results in the suppression of muscle (T2 = 50 msec) (13,14,18), veins with deoxygenated blood (T2 = 20 msec) (15), and fat, while the signal intensity of arterial blood with a relatively long T2 (100 msec) is only minimally suppressed. This phenomenon results in enhanced contrast between the oxygenated blood and the surrounding tissues. Although this magnetization preparation has been successfully applied at 1.5-T imaging, B1 inhomogeneity has occurred at higher magnetic field strengths (15). However, with the implementation of an adiabatic (19) version of the T2 preparation, the sensitivity of T2 preparation to B1 inhomogeneity can be successfully minimized and effective T2-dependent contrast can still be generated.

For T2-prepared MR angiography, 30–44 coronal sections with a thickness of 1.5 mm were acquired during an 8.5–12.0-minute examination. Imaging parameters were as follows: 12 radiofrequency excitations with segmented k-space gradient-echo readouts per R-R interval, 14.0/3.8 (repetition time msec/echo time msec), a fractional echo, a 20° excitation angle, a 270 x 216-mm field of view, a 64.7 Hz/pixel bandwidth, a T2-prepared echo time of 50 msec, and an 800 x 800 image acquisition matrix reconstructed to 1024 x 1024 to result in a 0.34 x 0.35 x 1.5-mm acquired voxel size and a 0.26 x 0.26 x 0.75-mm reconstructed voxel size.

TOF MR angiography
For TOF MR angiography, 140 transverse sections with a thickness of 1 mm were acquired during a 4.5-minute examination. Imaging parameters were as follows: a sensitivity-encoding factor of two, 25/3.5, a 20° excitation angle, a 200 x 150-mm field of view, a partial echo, a 217 Hz/pixel bandwidth, radiofrequency spoiled acquisition, and a 496 x 496 acquired image matrix reconstructed to 512 x 512 to result in a 0.4 x 0.71 x 1.0-mm acquired voxel size and a 0.39 x 0.39 x 0.5-mm reconstructed voxel size. The TOF angiograms were subdivided into four subvolumes, with an ascending volume against the arterial flow direction to maximize inflow contrast. An inferior saturation band was used to suppress venous signal, and spectral spatial excitation was used to suppress fat.

Conventional Angiography
Conventional digital subtraction angiograms were obtained within 24 hours after the MR angiography examination, before the animals were euthanized, by an interventional radiologist (L.V.H.) with 8 years experience performing interventional procedures. Briefly, a 3-F pigtail catheter (Cook) was positioned in the distal abdominal aorta approximately 3 cm above the iliac bifurcation (Fig 1) (16), and anteroposterior digital subtraction angiograms of the pelvis and both hind limbs were acquired at a film rate of 15 frames per second by using an angiographic unit (Infinix-CCi Angiographic System; Toshiba, Tokyo, Japan). Diatrizoate meglumine (Hypaque, 300 mg of iodine per milliliter; Amersham Health, Buckinghamshire, England) was injected at a rate of 4 mL/sec (total of 16 mL administered) by using a power injector (Liebel-Flarsheim-Angiomat 3000; Liebel-Flarsheim, Cincinnati, Ohio). As a reference for quantitative measurements, a quarter (24.3 mm) was placed alongside each rabbit at approximately the same distance from the film as the rabbit's aorta.


Figure 1
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  		Figure 1: Anteroposterior conventional digital subtraction angiograms of peripheral vasculature in a rabbit show, A, a nonischemic limb divided into seven normal segments and, B, an ischemic limb with endovascular occlusion of the SFA. The small vessels in A, which originate from the profunda femoris artery, are normal secondary arteries that, in contrast to the collateral vessels (outlined by circle and oval in B) in the ischemic limb, do not show a re-entry zone in the distal branches.

 
Image Analyses
Visual assessment in nonischemic limbs.—An area of the nonischemic limb was divided into seven arterial segments: hypogastric artery, common femoral artery, profunda femoris artery, lateral circumflex artery, SFA, saphenous artery, and popliteal artery (Fig 1, A). The segments were visually evaluated for vessel sharpness on maximum intensity projection images generated from the three-dimensional TOF and T2-prepared MR angiography data sets by using the postprocessing software on the MR unit. For visual analysis, 60 maximum intensity projection images rotating about the craniocaudal axis were used. The images were scored by using a three-grade scale: Grade 0 indicated good vessel sharpness, which enabled delineation and judgment of vessel patency along the entire length of the segment; grade 1, moderate sharpness, with at least one discontinuity that confounded the evaluation of vessel patency; and grade 2, very low sharpness, with which the vessel was hardly detectable or not detectable on the image. The presence or absence of veins adjacent to the arterial segments (ie, venous contamination) was also evaluated in each of the seven normal segments.

Visual assessment in ischemic limbs.—The ischemic limbs were visually evaluated for depiction of the collateral vessels and distal branches. For evaluation of the collateral vessels, images were assigned a score of 0, indicating that no collateral vessels were detectable, or 1, indicating that at least one collateral vessel was detectable. This evaluation was performed for each perfusion territory of the lateral circumflex and profunda femoris arteries (20) (Fig 1, B). For evaluation of the distal branches, including the saphenous and popliteal arteries, the images were assigned a score of 0, indicating that the distal branch was not detectable, or 1, indicating that the distal branch was detectable (Fig 1, B).

Visual evaluation of vessel sharpness was performed independently by two observers (G.K., L.V.H., with 6 and 8 years experience in cardiovascular imaging, respectively). One of these observers (G.K.) evaluated the presence of collateral vessels and distal branches in the ischemic limbs. This same observer counted the number of detectable secondary branches originating from normal segments in each nonischemic limb and divided this value by the number of primary segments. In this way, a ratio that reflected the mean number of detectable small branches per primary segment was created.

Quantitative Analyses
Transverse diameters.—Vessel diameters were measured (G.K.) for TOF and T2 preparation on the MIP images at specific anatomic points (at the branching of the lateral circumflex artery; at the bifurcation of the SFA into the popliteal and saphenous arteries; and 2, 4, 6, and 8 mm proximal to the bifurcation) and compared with the same anatomic points on the conventional angiograms. All transverse diameters were measured by using the Deriche edge detection algorithm (15,21). In brief, a signal intensity profile was used perpendicular to the centerline of the vessel. This profile was evaluated on a Deriche image, where the magnitude is proportional to the local change in signal intensity (first-order derivative of the image). On a signal intensity profile perpendicular to the vessel, this magnitude results in two peaks, which are indicative of the left and right vessel boundaries. For diameter quantification, the distance between these two peaks was calculated.

Vessel sharpness.—Vessel sharpness was measured (G.K.) in all seven arterial segments in the nonischemic limb and in the popliteal and saphenous branches distal to the SFA occlusion. The vessel sharpness was also quantified by evaluating the magnitude of signal intensity change at the vessel borders on the Deriche image (15,21). A vessel sharpness of 100% indicates the maximal difference in signal intensity (full dynamic range) between two adjacent pixels. In the present analysis—and dependent on the anatomic region—the average vessel sharpness (expressed as a percentage) for a 1–5-cm contiguous vessel segment was quantified. Vessel sharpness was measured in multiple equidistant steps of 0.2 mm and was plotted against the length of the arterial segment (Fig 2) by using automatic vessel tracking (21).


Figure 2A
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  		Figure 2a: (a–c) Maximum intensity projections of normal SFA obtained (a) with coronal T2-prepared MR angiography (14.0/3.8, 20° flip angle), (b) with the artery reconstructed by using multiplanar reformatting, and (c) with vessel sharpness measured at multiple anatomic points. (d) SFA vessel sharpness (measured in c) versus arterial segment length is plotted by using automatic vessel tracking. The inferior margin of this vessel exhibits lower signal intensity along the margins, which may be attributed to veins that run parallel to the arteries, Gibbs ringing, or flow artifacts.

 

Figure 2B
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  		Figure 2b: (a–c) Maximum intensity projections of normal SFA obtained (a) with coronal T2-prepared MR angiography (14.0/3.8, 20° flip angle), (b) with the artery reconstructed by using multiplanar reformatting, and (c) with vessel sharpness measured at multiple anatomic points. (d) SFA vessel sharpness (measured in c) versus arterial segment length is plotted by using automatic vessel tracking. The inferior margin of this vessel exhibits lower signal intensity along the margins, which may be attributed to veins that run parallel to the arteries, Gibbs ringing, or flow artifacts.

 

Figure 2C
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  		Figure 2c: (a–c) Maximum intensity projections of normal SFA obtained (a) with coronal T2-prepared MR angiography (14.0/3.8, 20° flip angle), (b) with the artery reconstructed by using multiplanar reformatting, and (c) with vessel sharpness measured at multiple anatomic points. (d) SFA vessel sharpness (measured in c) versus arterial segment length is plotted by using automatic vessel tracking. The inferior margin of this vessel exhibits lower signal intensity along the margins, which may be attributed to veins that run parallel to the arteries, Gibbs ringing, or flow artifacts.

 

Figure 2D
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  		Figure 2d: (a–c) Maximum intensity projections of normal SFA obtained (a) with coronal T2-prepared MR angiography (14.0/3.8, 20° flip angle), (b) with the artery reconstructed by using multiplanar reformatting, and (c) with vessel sharpness measured at multiple anatomic points. (d) SFA vessel sharpness (measured in c) versus arterial segment length is plotted by using automatic vessel tracking. The inferior margin of this vessel exhibits lower signal intensity along the margins, which may be attributed to veins that run parallel to the arteries, Gibbs ringing, or flow artifacts.

 
Statistical Analyses
Quantitative data are presented as means ± standard deviations, and categorical variable data are presented as percentages. On the basis of protocols in previous studies of coronary arteries (15), we estimated the number of animals that would be sufficient to achieve a statistical power of greater than 80% for the detection of relevant differences in vessel sharpness. Paired Student t tests were performed to compare quantitative vessel sharpness between TOF and T2-prepared MR angiography. Differences in visual assessment were tested by using McNemar {chi}2 statistics (22). A clustered regression approach was used to compare the transverse diameter measurements obtained at TOF or T2-prepared MR angiography with those obtained at conventional angiography, and Bland-Altman analysis (23) was performed to determine whether there was any systematic bias in favor of either MR angiography technique. Agreement between the observers in the evaluation of vessel sharpness according to visual criteria was assessed by using {kappa} statistics. Intraobserver variability in measurements was assessed by using repeated analysis of 20 representative vessel segments. To minimize recall bias, the readings were performed 2 months apart. Differences were considered significant at P < .05. All calculations, except those used for clustered regression analysis, were performed by using SPSS 11.5 for Windows software (SPSS, Chicago, Ill). Clustered regression analysis was performed by using the Stata 9.2 software package (StataCorp, College Station, Tex).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Visual Assessments
Visually assessed vessel sharpness and venous suppression in the nonischemic limbs were similar between TOF and T2-prepared imaging. However, T2-prepared imaging was superior to TOF imaging for the detection of small secondary branches (mean number of detectable branches per primary segment: 1.2 branches ± 0.5 [standard deviation] with T2 preparation vs 0.5 branch ± 0.3 with TOF, P < .001) in the nonischemic limbs and for the identification of small collateral vessels (93% of vessels detectable with T2 preparation vs 36% of vessels detectable with TOF, P < .001) and distal branches (96% of branches detectable with T2 preparation vs 29% of branches detectable with TOF, P < .001) in the ischemic limbs (Table). Analysis of 92 segments that were examinable with both techniques was performed; in three of 14 rabbits, the common femoral and lateral circumflex arteries were not visible in the imaging volume acquired with TOF.


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  		Visual Assessment of Normal and Collateral Vessels after Endovascular Coil Placement

 
For the nonischemic segments, we observed similar vessel sharpness between TOF (Fig 3, A) and T2-prepared (Fig 3, B) MR angiography. The discontinuities seen in the hypogastric and profunda femoris arteries at TOF and T2-prepared imaging were not attributed to true luminal narrowing but rather to compromised vessel sharpness. Secondary branches were detectable to a greater extent on the T2-prepared images. The presence of these smaller branches and the patency of all the arterial segments were confirmed on the conventional angiograms (Fig 3, C).


Figure 3
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  		Figure 3: A, B, Representative maximum intensity projections obtained at, A, transverse TOF (25/3.5, 20° flip angle) and, B, coronal T2-prepared (14.0/3.8, 20° flip angle) MR angiography of a nonischemic limb in a rabbit. Secondary branches (arrowheads) originating from the lateral circumflex and profunda femoris arteries are appreciated to a larger extent in B. C, Anteroposterior digital subtraction angiogram findings confirm the presence of the smaller branches. Note that the discontinuities (arrows) seen in the hypogastric and profunda femoris arteries in both A and B are not attributed to true luminal narrowing but rather to compromised vessel sharpness.

 
The detection of collateral vessels after SFA occlusion with TOF imaging (Fig 4, A) was inferior to that with T2-prepared imaging (Fig 4, B). The origins of the small collateral vessels and the distal branching of the SFA into popliteal and saphenous arteries could be appreciated on the T2-prepared images but not on the TOF images. Conventional angiographic findings confirmed the presence of the collateral vessels and the distal branches seen on the T2-prepared images (Fig 4, C) (Movie, http://radiology.rsnajnls.org/cgi/content/full/2452062067/DC1).


Figure 4
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  		Figure 4: A, B, Representative MIP images of an ischemic limb. A, Transverse TOF MR angiogram (25/3.5, 20° flip angle) was inferior to, B, coronal T2-prepared MR angiogram (14.0/3.8, 20° flip angle) for depiction of collateral vessels. Small collateral vessels (hatched arrows) originating from the profunda femoris artery and distal branches (solid arrows) can be appreciated in B. C, Anteroposterior digital subtraction angiogram findings confirm the presence of the collateral vessels (hatched arrows) and the distal branches (solid arrows). Note that the decreased signal intensity of the popliteal vessel (topmost solid arrow in C) in the ischemic limb is not caused by true luminal narrowing of this vessel but rather by slow filling of this vessel from the collateral circulation of the lateral circumflex territory (Movie, http://radiology.rsnajnls.org/cgi/content/full/2452062067/DC1).

 
Quantitative Analyses
Vessel sharpness.—According to previous study protocols (15), we calculated that 14 animals would be sufficient to achieve a statistical power of 90% with an {alpha} of .05 for the detection of relevant differences in vessel sharpness between T2-prepared and TOF MR angiography. Quantitative vessel sharpness was similar between TOF and T2-prepared imaging for all normal arteries except the SFA, where TOF imaging yielded significantly higher sharpness (mean sharpness: 59% vs 50%, P < .001) (Fig 5). For the ischemic limbs, however, the use of T2 preparation resulted in significantly higher vessel sharpness for the branches with low blood flow distal to the occluded SFA (mean sharpness: 44% vs 30% for popliteal arteries, 45% vs 28% for saphenous arteries; P < .001 for both comparisons).


Figure 5
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  		Figure 5: Bar graph illustrates vessel sharpness in seven nonischemic limb arteries and two ischemic limb arteries with TOF and T2-prepared MR angiography. The two techniques generated similar sharpness in most segments of the nonischemic limbs. However, T2-prepared imaging yielded significantly higher sharpness in the ischemic limbs (mean sharpness: 44% vs 30% for popliteal arteries, 45% vs 28% for saphenous arteries; P < .001 [*] for both comparisons).

 
Vessel diameters.—At clustered regression analysis, a significant linear relationship between the vessel diameter measured with T2-prepared or TOF MR angiography and that measured with conventional angiography, our reference standard, was observed (mean correlation coefficient, 0.81 ± 0.09 [standard error of mean]; 95% confidence interval: 0.62, 1.00 [P < .001] for T2 preparation and 0.81 ± 0.06; 95% confidence interval: 0.69, 0.94 [P < .001] for TOF) (Fig 6a, 6b). Bland-Altman plots demonstrate that there was no systematic bias in favor of either T2-prepared or TOF MR angiography (Fig 6c, 6d).


Figure 6A
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  		Figure 6a: (a, b) Graphs show that transverse diameters of normal vessels measured at (a) T2-prepared and (b) TOF MR angiography were significantly correlated with diameters measured at conventional angiography (r = 0.81 for both techniques, P < .001 for both comparisons). (c, d) Bland-Altman plots demonstrate that there was no systematic bias in favor of either (c) T2-prepared or (d) TOF MR angiography.

 

Figure 6B
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  		Figure 6b: (a, b) Graphs show that transverse diameters of normal vessels measured at (a) T2-prepared and (b) TOF MR angiography were significantly correlated with diameters measured at conventional angiography (r = 0.81 for both techniques, P < .001 for both comparisons). (c, d) Bland-Altman plots demonstrate that there was no systematic bias in favor of either (c) T2-prepared or (d) TOF MR angiography.

 

Figure 6C
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  		Figure 6c: (a, b) Graphs show that transverse diameters of normal vessels measured at (a) T2-prepared and (b) TOF MR angiography were significantly correlated with diameters measured at conventional angiography (r = 0.81 for both techniques, P < .001 for both comparisons). (c, d) Bland-Altman plots demonstrate that there was no systematic bias in favor of either (c) T2-prepared or (d) TOF MR angiography.

 

Figure 6D
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  		Figure 6d: (a, b) Graphs show that transverse diameters of normal vessels measured at (a) T2-prepared and (b) TOF MR angiography were significantly correlated with diameters measured at conventional angiography (r = 0.81 for both techniques, P < .001 for both comparisons). (c, d) Bland-Altman plots demonstrate that there was no systematic bias in favor of either (c) T2-prepared or (d) TOF MR angiography.

 
Observer variability in visual and quantitative assessments.—For visual assessment, there was 80% interobserver agreement (for 148 of 184 segments, {kappa} = 0.68) and 90% intraobserver agreement (for 166 of 184 segments, {kappa} = 0.76). In terms of quantitative assessment, there was 3.4% intraobserver variation in the determination of vessel sharpness and 6.5% intraobserver variation in the determination of vessel diameters.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
The central findings of our study were that (a) both TOF and T2-prepared techniques are feasible for MR angiography of the peripheral vessels, without contrast agent administration, and (b) T2-prepared imaging is superior to TOF imaging in the identification of small and collateral vessels with low blood flow.

In the described experimental model, TOF imaging yielded high vessel sharpness in arterial segments with normal blood flow. However, consistent with the theoretic limitations of this technique (9,11,12), TOF imaging yielded reduced vessel sharpness for segments with low blood flow. Thus, with use of TOF imaging, segments distal to occluded vessels were not detectable in 10 of the 14 rabbits, although the corresponding nonischemic branches in the contralateral limb were visible. Similarly, only 36% of the collateral vessels generated after SFA occlusion could be detected at TOF imaging compared with 93% of the collateral vessels that could be detected at T2-prepared imaging.

In our study, T2 preparation enabled excellent anatomic definition of arteries with inherently low blood flow. The average size of the small vessels evaluated by using T2-prepared imaging in this rabbit model varied between 1.0 and 2.5 mm, which is similar to the range of sizes of the distal coronary arteries in humans (24) and to the range of sizes of collateral arteries in patients with peripheral arterial occlusive disease of the lower extremities (25). T2-prepared imaging also yielded high sharpness of small vessels with low blood flow distal to the occluded SFA and accurately depicted small collateral vessels in the ischemic limbs. Furthermore, in the normal arteries, secondary branches with lower blood flow could be detected more readily with T2-prepared imaging than with TOF imaging.

For contrast material—enhanced MR angiography, gadolinium-based MR contrast agents are used, and these agents increase vascular conspicuity by decreasing the T1 relaxation time of blood. However, the vascular half-life of these agents in the vasculature of interest, which is limited, governs the maximal spatial resolution that can be obtained (26,27). Therefore, multiple contrast agent doses, complex stepping-table techniques, and sophisticated algorithms to calculate the optimal time delay are required to solve these problems (26,28). Furthermore, the use of contrast agents also results in venous enhancement, which further hampers the assessment of arterial segments (9,28). Because of these limitations, contrast agents might not be optimally suited for the prolonged imaging times that are currently necessary for high-spatial-resolution approaches. In our study, a high spatial resolution of 0.18 mm3 was achieved with T2-prepared imaging by using a human cardiac receiver coil array. This spatial resolution was markedly higher than those in previous studies involving the use of contrast-enhanced MR angiography: 5–8 mm3 in humans (26,29) and 3 mm3 in rabbits (30). Also, a small voxel size is required for the identification of small collateral vessels in studies of arteriogenic therapies (27). However, the use of intravascular contrast agents that do not extravasate into the extracellular space (31) and of parallel imaging with high acceleration factors may facilitate high-spatial-resolution contrast-enhanced MR angiography in future studies. Finally and of importance, the administration of gadolinium-based contrast material has been reported to have a role in the development of nephrogenic systemic fibrosis in patients who have impaired renal function (32). Therefore, the availability of MR angiography techniques that do not rely on exogenous contrast enhancement with gadolinium-based contrast agents may be important.

Our study had limitations. The spatial resolutions of TOF imaging (0.4 x 0.71 x 1.0 mm) and T2-prepared imaging (0.34 x 0.35 x 1.5 mm) were not identical. However, all imaging parameters, including sensitivity encoding, total imaging time, imaging volume, and spatial resolution, were optimized experimentally to achieve optimal image quality with each technique. During this developmental phase, we sought to optimize both vessel conspicuity and spatial resolution for adequate visualization of the femoral arteries above and below the platinum coil. TOF MR angiography was performed by using a sensitivity-encoding factor of two. Because the noise statistics become non-Gaussian when parallel imaging techniques such as sensitivity encoding are used, the conventional signal-to-noise and contrast-to-noise ratio measurements obtained at TOF imaging cannot be accurately compared with those obtained at T2-prepared imaging. For this reason, we chose to quantify vessel sharpness to compare TOF and T2-prepared MR angiography (15,21).

The six-element coil array used for signal reception was a commercially available human cardiac coil. However, several factors, such as a larger distance between the coil and the vessels of interest, a larger field of view, time constraints, and limited coverage of the vasculature of interest, may cause reduced spatial resolution for certain human applications compared with the spatial resolution achieved in rabbits. In addition, dedicated smaller-diameter animal surface coils are needed to further optimize the technique. Finally, while T2-prepared imaging was superior to TOF imaging in the delineation and assessment of small-diameter vessels, the discontinuities observed in the more proximal segments on both the T2-prepared and the TOF images may have been attributable to "Venetian blind" artifacts (33) or to pulsatile or turbulent flow, despite electrocardiographic triggering (34). Thus, shortening the echo time might have to be considered in future studies.

In conclusion, our study results demonstrate the utility of T2 preparation for nonenhanced MR angiography of the peripheral arteries in a preclinical model of hind limb ischemia imaged at a high magnetic field strength. Use of this technique with a commercially available human MR imaging system can facilitate high spatial resolution, which enables superior delineation of small arteries with low blood flow.

Practical application: T2-prepared MR angiography appears to be promising for studying arteriogenesis. Further evaluation is necessary to assess the value of this technique in clinical practice. The emerging field of therapeutic arteriogenesis may benefit from T2 preparation because it enables serial assessment of small and collateral vessels with low blood flow noninvasively and without x-ray exposure.


   ADVANCE IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
IMPLICATION FOR PATIENT CARE
 References
 


   IMPLICATION FOR PATIENT CARE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
References
 


   FOOTNOTES
 

Abbreviations: SFA = superficial femoral artery • TOF = time of flight

2 Current address: Department of Cardiology, University of Heidelberg, Heidelberg, Germany. Back

Author contributions: Guarantors of integrity of entire study, G.K., M. Stuber; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, G.K., W.D.G., L.V.H., M. Stuber; experimental studies, G.K., W.D.G., A.U., L.V.H., D.L.K., M. Stuber; statistical analysis, G.K.; and manuscript editing, G.K., W.D.G., M. Schär, L.V.H., D.L.K., M. Stuber

See Materials and Methods for pertinent disclosures.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 

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