Blood Pool Contrast-enhanced Magnetic Resonance Angiography with Correlation to Digital Subtraction Angiography: A Pictorial Review

MRA and contrast agents

Non-contrast MRA sequences are currently being developed;[4] however, in daily practice, CE-MRA still provides a higher contrast-to-noise ratio, higher spatial resolution, more rapid speed of acquisition, less artifacts, and higher diagnostic accuracy compared to non-CE-MRA techniques. Therefore, CE-MRA is heavily favored in clinical practice. These contrast agents are formed by chelation of the gadolinium (Gd) ion to prevent cellular uptake and decrease acute toxicity. Free Gd has an ionic radius similar to calcium and acts as an inorganic blocker of many types of voltage-gated calcium channels, inhibiting many calcium-dependent physiological processes. Therefore, ligands are utilized to encapsulate the Gd ion in order to increase thermodynamic stability allowing the contrast agents to be excreted intact. Different agents contain different ligands which create compounds that have varying pharmacokinetic properties and biodistributions. These differences are the basis for the classification and target of Gd-contrast agents (Gd-CA).[56]

The first approved agents are classified as conventional extracellular fluid (ECF) agents. After intravenous injection, these agents occupy the intravascular and interstitial space which is collectively known as the ECF. The volume of distribution (V_D) of these agents ranges from 0.21 l/kg to 0.28 l/kg, which is consistent with the V_D of ECF agents. Blood pool contrast agents (BPCAs) which largely remain in the vasculature were recently introduced. The V_D of these agents is 0.148 l/kg ± 0.016 l/kg, which is lower than that of ECF agents, but also indicates these agents are not 100% confined to the vasculature (V_D of pure intravascular agents is 0.07 l/kg). BPCAs contain a lipophilic biphenylcyclohexyl group that reversibly binds human serum albumin. This bond does not allow the BPCA to rapidly extravasate from the vessel into the interstitial space, as occurs with unbounded conventional ECF agents. BPCAs exhibit a prolonged plasma half-life and, therefore, a longer imaging window unlike conventional agents which are restricted to a short imaging window during the first pass.[6] BPCA also allows for steady-state imaging from 5 min up to 60 min post injection, if needed.[7]

The mechanism of action for all Gd-CA can be explained by the difference in T1 relaxation times of blood and surrounding tissue when the contrast is injected intravenously. In general, these agents also shorten T1, T2, and T2* relaxation time constants of adjacent water molecules. The shortened T1 generates a high intravascular signal-to-noise ratio. The binding of albumin by BPCA further increases the relaxivity compared to conventional agents, and thus further improves the image resolution and vascular enhancement. These properties allow for a lower dose of BPCA needed for quality image acquisition.[58] The recommended dose for gadofosveset is 0.03 mmol/kg compared to a dose of 0.1 mmol/kg for all other conventional agents. This could potentially decrease the risk of nephrogenic systemic fibrosis (NSF). There are several indications for using MRA in clinical practices, including known or suspected vascular pathology, cardiac congenital anomalies, treatment planning, and postoperative follow-up of vascular pathology or cardiac congenital anomalies. All of these indications could benefit from the improved image resolution, increased vascular enhancement, and decreased dose of contrast needed when utilizing BPCA.

Gadofosveset trisodium

Gadofosveset trisodium, marketed as Ablavar^® (Lantheus Medical Imaging, N. Billerica, MA, USA) is the first clinically approved BPCA available in the United States for use in aortoiliac occlusive disease (AIOD). Phase III trials showed a reduced rate of non-interpretable imaging and improved diagnostic confidence compared to unenhanced two-dimensional time-of-flight MRA. The agent was proven safe with low incidence of severe and serious adverse events. Therefore, overall, gadofosveset was determined to be safe and effective for the MR evaluation of patients with AIOD.[7] An additional phase III trial of 145 patients with known or suspected renal artery stenosis demonstrated an increased specificity (23–29%), sensitivity (25–42%), and accuracy of diagnosis (23–29%) of gadofosveset-enhanced MRA compared to non–CE-MRA. The same study demonstrated a decrease of uninterpretable images from 30% to less than 2% when utilizing gadofosveset.[9] Gadofosveset has also been shown to decrease the number of uninterpretable images when evaluating peripheral arterial disease affecting the pedal arteries. Bosch et al., showed a decrease in uninterpretable images from 16% to 2% when utilizing the BPCA.[10]

Interventional radiology and pre-procedural planning

The use of pre-treatment imaging is becoming increasingly important to reduce procedure time, decrease exposure to ionizing radiation, and decrease the time the patient is sedated. The Trans-Atlantic Intersociety Consensus Group (TASC) concluded that CE-MRA is the ideal imaging modality in predicting which patients require conservative management versus interventions such as angioplasty or surgical revascularization,[11] leaving angioplasty for use in targeted therapy. CE-MRA has been shown to adequately demonstrate vascular anatomy and identify the lesions responsible for patient symptoms, making it sufficient for planning and therapy in many cases.[8] Pre-procedural MR images can be reconstructed in any plane and can be viewed from many angles creating a “roadmap” of potentially complicated vasculature. The use of BPCA can further enhance the detail of these roadmaps. In this article, we illustrate through case presentations the clinical and promising future applications for gadofosveset-enhanced MRA in the evaluation of peripheral vascular disease and abdominal and pelvic pathology.

Imaging of aortoiliac occlusive disease

Precise anatomic arterial mapping is essential for endovascular treatment of patients with peripheral arterial disease. Although DSA has been considered the Gold Standard, its invasiveness can lead to significant morbidity and mortality. The steady-state imaging that is possible with gadofosveset allows for greater spatial resolution at the cost of acquisition time; this, in turn, allows for detailed visualization of the degree of stenosis and mural abnormalities [Figure 1a–d]. Hadizeh et al., compared the accuracy of steady-state imaging with first-pass gadofosveset MRA against DSA that included a subset of patients with known peripheral arterial disease. Their results found 100% concordance of stenosis grade between the steady-state images and the DSA images. This improved accuracy was attributed to the higher spatial resolution which can be obtained because of the longer intravascular contrast time of the steady-state images.[12]

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Figure 1

64-year-old woman with 2-year history of progressive bilateral lower extremity claudication presented with bilateral leg rest pain and was diagnosed with localized atherosclerotic disease of the infrarenal abdominal aorta. Gadofosveset contrast-enhanced magnetic resonance angiography (CE-MRA) (a) First-pass MRA images show high-grade stenosis of right common iliac and long segment stenosis of the left common iliac artery (white arrow). There is also associated post-stenotic dilatation as indicated by the asterisks (A = aorta). (b) High-resolution steady-state image provides further detail of the atherosclerotic plaque (white solid arrows), which is significantly worse on the left (I = inferior vena cava, A = aorta). (c) Digital subtraction angiography performed prior to endovascular intervention reveals 100% correlation to the stenosis identified on MRA as shown by the black arrows, with post-stenotic dilatation as indicated by the asterisks (A = aorta). (d) Covered stents were placed in a kissing fashion at the common iliac arteries extending to the distal aorta with improved patency. The black arrows demonstrate the area of previous bilateral stenosis (A = aorta).

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A 64-year-old woman with a 2-year history of progressive bilateral lower extremity claudication presented with bilateral leg rest pain. Gadofosveset CE-MRA was performed to confirm the diagnosis of AIOD, grade the stenosis, and determine appropriate treatment plan. First-pass MRA revealed localized atherosclerotic disease of the infrarenal abdominal aorta [Figure 1a–d].

Imaging of venous thrombosis

Gadofosveset is also effectively applied to venous imaging. Hansch et al., demonstrated an increased detection of thrombus in the pelvic region, upper leg, and lower leg when utilizing gadofosveset-enhanced MRA over Doppler ultrasound.[13] Its high signal intensity venous enhancement relative to non-vascular structures during steady-state imaging allows for a broad coverage and high contrast evaluation of deep venous structures. This difference in signal is attributed to the higher signal intensity of contrast-enhanced venous blood compared to extracellular agents.

A 44-year-old man with a history of recurrent deep venous thrombosis (DVT) and pulmonary embolisms (PEs) status post inferior vena cava (IVC) filter placement at an outside hospital presented to the emergency room (ER) with chest pain. Computed tomography (CT) scan for work-up of PE revealed two small possible chronic PEs in the right lower lobe and apical right upper lobe. Lower extremity duplex ultrasound revealed a subacute DVT of the right distal external iliac and common femoral veins and chronic DVT of the left distal external iliac, left common femoral, left profunda femoris, bilateral femoral, right popliteal, right gastrocnemius, right posterior tibial, and right peroneal veins. Gadofosveset CE-MRA of the abdomen and pelvis was performed to further assess the venous system. The scan showed a metallic artifact secondary to IVC filter with associated thrombus. The thrombus was noted to extend superiorly to the level of the renal vein inflows [Figure 2a–c].

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Figure 2

44-year-old man with history of recurrent deep venous thrombosis (DVT) and pulmonary embolisms (PEs) post inferior vena cava (IVC) filter placement presented to the emergency room (ER) with chest pain. Gadofosveset contrast-enhanced magnetic resonance angiography (CE-MRA) of the abdomen and pelvis, coronal MR venograms: (a) shows a metallic artifact secondary to IVC filter with associated thrombus (*) and (b) shows the thrombus extends superiorly to the level of the renal vein inflows (dotted white arrow) (white solid arrow denotes the IVC, A = aorta). (c) Transcatheter IVC venogram prior to therapeutic thrombolysis demonstrates IVC filter (dotted white arrow) within the infrarenal IVC and filling defects (white solid arrows) consistent with thrombus extending superiorly to the level of the renal inflows (*) (V = IVC).

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Imaging of malformations

When assessing for vascular malformations and deciding on appropriate interventional therapies, magnetic resonance imaging (MRI) is essential for differentiating between high-flow vascular malformations and low-flow venous malformations. Utilization of the time-resolved first-pass effect of gadofosveset allows for this distinction, and can effectively be a roadmap for interventional treatment. This time-resolved first-pass effect can assess arteriolar feeders, and/or venous drainage, while the steady-state high-resolution imaging can assess the surrounding vascular structures.[14]

A 37-year-old woman with history of trauma to left knee in 2000 underwent three surgeries to help with swelling and pain presented with continued left lower extremity pain and swelling which was significantly limiting her lifestyle. On examination, a bruit was appreciated over the left patellar area. Previous MR imaging in 2008 revealed arteriovenous malformation (AVM). Gadofosveset CE-MRA was performed to re-evaluate the extent of her AVM and determine appropriate treatment plan. MRA showed a large AVM with dominant arterial feeders from the left superficial femoral artery. This was confirmed by DSA [Figure 3a–g]. Endovascular treatment of AVM was performed with Onyx resulting in decreased flow through treated portions of the AVM [Figure 3h–j].

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Figure 3

37-year-old woman with history of trauma to left knee presented with continued left lower extremity pain and swelling with a bruit over the left patellar area. Gadofosveset contrast-enhanced magnetic resonance angiography (CE-MRA) (a) First-pass and (b) steady-state MRA images demonstrate large AVM (white solid arrows) with dominant arterial feeders (white dotted arrow) from the left superficial femoral artery (SFA, * = SFA). Steady-state (c) magnetic resonance imaging (MRI) and (d) MRA high-resolution images demonstrate the vasculature in more detail. (AVM is denoted by white solid arrows.) Corresponding digital subtraction angiography (e and f) arterial and (g) venous phase images demonstrate a large AVM (black solid arrows) with a predominant arterial feeder (black dotted arrow) arising from the SFA confirms the MRA findings. Early venous filling is demonstrated by the solid gray arrows (* = SFA). (h-i) Fluoroscopic images show staged endovascular treatment of AVM performed with Onyx (solid black arrow denotes the Onyx placed first, dashed black arrow is the Onyx placed second). (j) Digital subtraction angiogram (DSA) image shows decreased flow through treated portions of the AVM (Onyx is subtracted out in DSA image, but is still faintly visible). (k) Final angiographic result reveals significant decrease in flow to the AVM (* = SFA).

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Imaging of pelvic pathology

Chronic pelvic pain is a common health problem that affects millions of women worldwide, but can be a difficult condition to address. Pelvic congestion syndrome (PCS) is a diagnosis that should be considered in many women after other pelvic pathologies have been ruled out. Given its vague symptomatology, PCS is often underdiagnosed. Many of these patients undergo an MRI which offers improved diagnosis and allows for more precise pre-procedural treatment planning.

The incompetent ovarian veins in this syndrome can be identified with gadofosveset imaging. Specifically, the steady-state imaging can allow a clear depiction of the ovarian veins at high resolution. Furthermore, the time-resolved first-pass images are equivalent to a Gold Standard transcatheter venogram in depicting retrograde flow within the ovarian veins.[15]

A 41-year-old woman presented with worsening intermittent pelvic pain that had persisted for several years. Gadofosveset CE-MRA of her abdomen and pelvis was performed to assess underlying pathology. MRA revealed a dilated left gonadal vein (white solid arrow) coursing inferiorly to the pelvic area. The patient was treated with coil embolization of left gonadal vein [Figure 4a–e].

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Figure 4

41-year-old woman presented with worsening intermittent pelvic pain over several years. Gadofosveset contrast-enhanced magnetic resonance angiography (CE-MRA) performed of her abdomen and pelvis to assess for underlying pathology. (a) Venous phase image shows a dilated left gonadal vein (white solid arrow) coursing inferiorly to the pelvic area. (b) Maximum intensity projection (MIP) image demonstrates enlarged gonadal vein (white solid arrows) supplying several pelvic collaterals confirming the presence of pelvic venous insufficiency. (c and d) Conventional transcatheter venography following catheterization of the left renal vein demonstrate the dilated left gonadal vein (V) supplying several pelvic collaterals (*), confirming MR findings. (e) Post-therapeutic venography demonstrates coil embolization of left gonadal vein (black solid arrows).

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