In recent years, magnetic resonance angiography (MRA) of the peripheral vascular tree has evolved into a widely available and valuable technique in the diagnostic and pre-interventional work-up of patients with peripheral arterial disease. Numerous studies have demonstrated the diagnostic accuracy of MRA for the assessment of abdominal and peripheral arteries, and in many hospitals the technique is now solidly integrated into the clinical workflow.1–3 The recent introduction of the first high-relaxivity blood-pool agent, Vasovist, offers the opportunity for further improvements in image quality and expansion of the range of clinical indications for which MRA can be used. This article provides considerations on practical aspects of blood-pool- enhanced-MRA and current clinical indications, as well as examples of the added value of blood-pool imaging over conventional first-pass imaging.
Technical Principles and Practical Considerations
Background
Over the past few years, contrast-enhanced MRA (CE-MRA) has evolved as the preferred technique for evaluation of patients with different forms of peripheral arterial disease. The basic idea is to acquire an arterial luminogram during initial arterial passage (the ‘first pass’) of contrast material. First-pass CE-MRA essentially necessitates a compromise between the desire for high spatial resolution and large volumetric coverage (i.e. long acquisition duration), the desire to avoid disturbing venous enhancement (i.e. short acquisition duration) and high vessel-to-background contrast. Because of the higher relaxivity and prolonged intravascular residence time of Vasovist, the aforementioned trade-off is governed by much less stringent conditions.
Blood-pool Contrast Media
Blood-pool contrast agents can be used in exactly the same way as extracellular agents with regard to first-pass imaging. The advantage of using these agents for first-pass imaging lies in their much higher relaxivity (see Table 1).4 This means that a higher signal-to-noise ratio can be obtained when parameters are kept identical or, conversely, that spatial resolution can be increased while maintaining the same signal-to-noise ratio. The truly interesting property of blood-pool agents, however, is their much longer intravascular residence time. Equilibrium imaging is possible because – despite the fact that dilution of the injected contrast medium after first arterial passage leads to a T1 increase of the blood pool compared with the first pass – the value is still much lower than that of fat. Hartmann et al. estimate that T1 of blood in the equilibrium phase, 3–5 minutes after injection of 0.03mmol/kg Vasovist, is about 130ms, increasing to about 150ms after 10–15 minutes.5
This prolonged T1 reduction offers the opportunity to obtain images of the peripheral vascular tree up to about 45–60 minutes after injection. The extended imaging window can be used to acquire images with much higher spatial resolution without a significant loss of vessel-to-background contrast. In clinical practice this means that scan duration is no longer determined by the transient T1 shortening, but by the capacity of the patient to sustain a breathhold or to remain motionless. The apparent drawback of using a blood-pool agent is the simultaneous enhancement of venous structures close to arteries. This phenomenon is a well-known problem at first-pass imaging, often resulting in images that cannot be used for clinical decision-making. However, because equilibrium-phase images can be acquired at much higher spatial resolution – often with a 5–15-fold decrease in voxel size compared with first-pass protocols – arteries can be readily separated from accompanying veins.
Practical Aspects of Contrast-enhanced Magnetic Resonance Angiography with Blood-pool Agents
The use of a blood-pool contrast agent has reduced the deleterious consequences of missing the bolus in the first pass. If, for whatever reason, acquisition in the first pass fails, images can always be obtained in the equilibrium phase because of the prolonged intravascular retention. Although prolonged intravascular retention is highly advantageous, it is not recommended to perform a test bolus when using a blood-pool agent because of this property. If possible, it is better to acquire a dynamic series of acquisitions using a time-resolved MRA technique and to evaluate the data set with the best selective arterial opacification. The most commonly used format to display 3-D MR angiographic data is the maximum intensity projection (MIP). Although MIP is an elegant way to collapse a 3-D volumetric data set into a 2-D projection, review of cross-sectional images remains an integral part of the evaluation, especially for data acquired in the equilibrium phase. The MIP algorithm works best when using thin-slab or curved subvolume selections. In whole-volume MIPs, contrast-enhancing organs or other vascular structures may superimpose over smaller arteries when they have higher signal intensities along a particular viewing path. When working with equilibrium-phase images, the use of thin-slab sub-volume MIPs can be particularly useful. Another helpful technique for the precise evaluation of vessel morphology, especially when evaluating equilibrium phase data, is curved multiplanar reformation (cMPR) along the axis of the arterial segment of interest. Most post-processing workstations offer the ability to interactively generate a cMPR while scrolling through source images. This technique is particularly useful to obtain views of eccentric stenoses, and as a basis to generate views perpendicular to the central axis of the vessel to measure cross-sectional area reduction in stenoses.
Clinical Indications for Blood-pool Imaging of Peripheral Arteries
Clinically, blood pool imaging is indicated: 1) whenever the spatial resolution of first-pass imaging is insufficient to answer the clinical question; 2) when depiction of both the arterial and venous systems is desired; and 3) when the venous system is of primary interest. Furthermore, there are a number of indications – which are still considered to be experimental at present – such as perfusion imaging, plaque imaging and imaging of tumours. The latter indication is beyond the scope of this article and will not be discussed any further.
Atherosclerotic Peripheral Arterial Occlusive Disease
The most common cause of peripheral arterial occlusive disease is atherosclerosis of the infrarenal aorta and lower extremity arteries. Patients with chronic occlusive disease are generally excellent candidates for imaging with CE-MRA. The aorta and iliac arteries are also referred to as ‘inflow’ arteries in the context of peripheral arterial disease of the lower extremities. CE-MRA acquisitions are performed in the coronal plane, and a parallel imaging, capable phased-array surface coil should be used whenever possible. Truly acquired slice thickness in the first pass should not exceed 2.0–2.5mm if possible. In cases where additional coverage is needed in the anteroposterior direction – for instance in the presence of an abdominal aortic aneurysm or a femorofemoral cross-over bypass graft, or when the LeRiche syndrome is suspected – the number of slices should be increased to cover all the relevant anatomy. Preliminary experience indicates that small collateral vessels are better depicted in the first pass (see Figure 1), because of the higher relaxivity of the contrast medium, than with conventional extracellular contrast agents.6 In the steady state, acquisitions should be acquired during cessation of breathing. The key differentiation the radiologist must make when evaluating the upper-leg vasculature is whether there is a relatively short, focal stenosis or a complete occlusion over a long segment. This differentiation is particularly important in the setting of intermittent claudication, as patients and their vascular surgeons may be interested only in invasive treatment in case endovascular options can be considered. There can be substantial added value in acquiring equilibrium-phase images when establishing whether a lesion is an occlusion or merely a high-grade stenosis (see Figure 2).
Lower Leg and Pedal Arteries
Although depiction of the infragenicular arterial system in patients with intermittent claudication is important, it is usually not the location of the lesions that causes symptoms, nor the target for invasive intervention, except in patients with diabetes mellitus.7 This is opposed to the group of patients with chronic critical ischemia, i.e. rest pain and/or tissue loss. The angiographic hallmark of chronic critical ischemia is bilateral, multiple stenoses and occlusions at different levels in the peripheral arterial tree.
Patients with diabetes are a well-recognised subgroup with primarily distal atherosclerotic occlusive disease and preservation of normal inflow. Obtaining a full anatomical study from the infrarenal aorta down to the lower leg and pedal arteries is essential in the pre-interventional work-up of distal peripheral arterial disease. Equilibrium-phase imaging is especially well suited to characterising the distal lower-extremity vasculature. The diameter of the lower leg arteries gradually decreases from approximately 5–6mm in the distal popliteal artery to about 2–3mm in the foot. To reliably diagnose arterial occlusive disease, the spatial resolution should be in the order of 1.0 x 1.0 x 1.0mm3 or better. On modern 1.5T and 3.0T MR scanners equipped with state-of-the-art gradient systems, this resolution is certainly feasible. At this resolution, the higher signal-to-noise ratio with blood-pool agents in the first pass allows for routine high-quality imaging. In fact, Nikolaou et al. have already demonstrated the feasibility of imaging the lower legs with a 0.4 x 0.4 x 0.4 mm3 (64 microns) resolution.8 This represents an almost 16-fold decrease in voxel size compared with imaging at 1.0 x 1.0 x 1.0mm3. In the opinion of this author, 0.5 x 0.5 x 0.5mm3 (125 microns) represents a good compromise between spatial resolution and acquisition duration (see Figure 3).
Evaluation of Peripheral Arterial Bypass Grafts
Considering the chronic nature of the atherosclerotic disease process, many patients will ultimately present with renewed complaints after having been treated successfully for intermittent claudication or chronic critical ischemia. Equilibrium-phase imaging may also confer substantial added value over first-pass imaging in patients with bypass grafts. Ultra-high spatial resolution imaging may actually evolve into an important adjunct to first-pass imaging in these patients for two main reasons: first, steady-state imaging is better suited to characterising the exact degree of stenosis at the sites of proximal and distal anastomosis; and second, because of the ability to perform multiple subsequent ultra-high spatial resolution acquisitions, the field of view becomes virtually unlimited, thus in effect greatly extending anatomic coverage compared with what can be imaged during first arterial passage of contrast medium.
Acquired Conditions Presenting with Symptoms of Peripheral Arterial Disease
Fibromuscular Dysplasia
Arterial fibrodysplasia encompassess a heterogeneous group of vascular occlusive and aneurysmal disorders that can affect virtually any large artery in the body. Most often, the renal, extracranial and intracranial cerebral, and proximal upper extremity arteries are involved. Four principal forms of fibrodysplasia exist: intimal fibroplasia; medial hyperplasia; medial fibroplasia; and perimedial fibroplasia.9
In 85% of cases, the renal arteries are affected by medial fibrodysplasia, producing the characteristic ‘string-of-beads’ appearance due to a series of stenoses interspersed with aneurysmal outpouchings.10 It is notoriously difficult to make this diagnosis with high confidence on first-pass images due to the limited spatial resolution. Equilibrium-phase ultra-high-resolution imaging, however, can readily demonstrate the characteristic ‘string-of-beads’ narrowing at the site of involvement and even the fibrous septae lining the arterial lumen (see Figure 4).
Popliteal Artery Entrapment
Popliteal artery entrapment results from an anatomic variant in which the popliteal artery passes medial to and underneath the medial head of the gastrocnemius muscle or a slip of that muscle, with consequent compression of the artery.11 There are five slightly different anatomical variants, and a sixth, ‘functional’ type in which the popliteal artery becomes occluded with plantar flexion but no anatomic abnormality exists.12 Popliteal entrapment is a disease of young men (male to female ratio is 9:1), and presents with calf or foot claudication. In up to 25% of cases, the abnormality is bilateral.12 Angiographically, the diagnosis is suggested when there is medial deviation of the proximal popliteal artery (P1 segment) in combination with segmental occlusion or post-stenotic dilatation.11 If no abnormality is seen, additional ‘stress’ views should be obtained during dorsiflexion (with contracted gastrocnemius muscles).13 Because of the prolonged intravascular retention of Vasovist, this contrast medium is ideally suited to this indication. The relationship of the popliteal artery to the surrounding soft tissues can be easily demonstrated by reviewing the source images.
Thoracic Outlet Syndrome
The thoracic outlet includes three compartments – the interscalene triangle, the costoclavicular space and the retropectoralis minor space – which extend from the cervical spine and mediastinum to the lower border of the pectoralis minor muscle. Dynamically induced compression of the neural, arterial or venous structures crossing these compartments leads to thoracic outlet syndrome (TOS). The diagnosis of TOS is based on the results of clinical evaluation, particularly if symptoms can be reproduced with various dynamic manoeuvres, including elevation of the arm. Imaging is required to demonstrate neurovascular compression and to determine the nature and location of the structure undergoing compression and the structure producing the compression.14
As in patients suspected of popliteal entrapment, the added value of equilibrium imaging lies in the possibility of visualising both arteries and veins in various positions, allowing the diagnosis to be made with a high degree of certainty in a non-invasive fashion (see Figure 5).
Venous Imaging
Vasovist-enhanced MR imaging of the venous system is ideally suited to the detection of venous thromboembolic disease and its long-term sequelae. In fact, it is the personal opinion of this author that blood-pool-enhanced imaging is the current gold standard for imaging peripheral veins. Deep venous thrombi, even below the knee, are readily detected (see Figure 6).15 Furthermore, in patients with massive thromboembolic occlusion of central veins, the collateral pathways can readily be visualised in a fashion that is superior to conventional X-ray-based venography (see Figure 7).
Conclusions
CE-MRA of the peripheral vasculature has evolved over the past few years from an experimental imaging modality to a technique that is now widely applied in clinical practice. The recent introduction of the higher relaxivity blood-pool agent Vasovist expands the diagnostic armamentarium of the radiologist by opening up new opportunities in the field of peripheral MRA. The higher relaxivity and prolonged intravascular residence time of Vasovist yield better first-pass image quality, as well as the possibility of obtaining additional steady-state MRA data. The latter property will lead to a fundamental paradigm shift in MR imaging of the vasculature, enabling the migration to equilibrium-phase ultra-high spatial resolution imaging sequences. In combination with current hard- and software, equilibrium-phase ultra-high spatial resolution images of the abdominal aorta and lower extremity vasculature, including the venous circulation, can be obtained that yield the necessary diagnostic and pre-interventional information in the vast majority of patients.