Gadofosveset trisodium (Ablavar®, formerly Vasovist®) is the first intravas-cular contrast agent approved for clinical use in peripheral vascular disease.The purpose of this review is to illustrate the clinical uses of gadofosveset-enhanced magnetic resonance angiography in patients referred for assess-ment of arteriovenous disease.
Superior T1 shortening enables first pass renal and peripheral arteriographyof quality comparable with larger doses of extracellular agents. In applicationssuch as thoracic outlet syndrome, there may be other advantages such assuperior venous imaging and need for only one injection. Steady-statedelayed imaging provides high resolution mapping of both arterial and venoussystems and imaging of multiple territories. A combination of dynamic anddelayed steady-state imaging can provide detailed anatomy and flow char-acteristics of vascular malformations and mapping for percutaneous sclero-therapy at one investigation. The ability to image in the steady state canprovide minimally invasive imaging of thrombo-occlusive disease of centralveins.
Key words: angiography; blood pool agent; contrast; magnetic resonanceimaging; vascular imaging.
Introduction
Gadolinium-enhanced magnetic resonance angiography(MRA) of the abdomen was introduced in 1995.1 Contrast-enhanced MRA (CE-MRA) is conventionally performedwith extracellular gadolinium chelates. The pharmacoki-netics of these agents limits the temporal or spatialresolution and anatomical coverage that is possible.
Blood pool, or intravascular, contrast agents bind withalbumin prolonging intravascular half-life. This increasesthe temporal window for imaging and allows greatersignal or spatial resolution for arterial and venousimaging. Data acquisition with these agents is indepen-dent of timing of intravenous contrast administration.
Ablavar® (gadofosveset trisodium, Lantheus MedicalImaging, North Billerica, MA, USA), formerly Vasovist®(Bayer Schering Pharma AG, Berlin, Germany) is the firstlicensed compound for CE-MRA in peripheral vasculardisease (PVD). Eighty-five to ninety-five per cent of thisgadolinium-based compound binds strongly but revers-ibly to albumin in the blood.2 The blood plasma half-life in
the distribution phase is approximately 29 min.3 Steady-state imaging for up to 1 h after injection is possible.4 Thelarge molecular size of the chelate-albumin complex alsoresults in significantly shorter T1 relaxation times (19.0 L/mmol/sec at 37°C, 1.5 T), approximately five times thatof extracellular agents at 1.5 T.3 This results in greaterefficacy per unit gadolinium dose so that lower injectionvolumes and fewer injections are sufficient for diagnosticpurposes. The standard dose for MRA is 0.03 mmol/kg(0.12 mL/kg body weight).
The potential of angiography using gadofosveset tri-sodium has been documented.5 In this pictorial review,we demonstrate examples of the clinical applications.
Technique
Studies were performed on a Siemens 1.5 T Avanto unit(Siemens Medical Solutions, Erlangen, Germany). Aspoiled gradient echo 3D acquisition mask was obtainedand then repeated during or after infusion of 10 mL(2.44 g) of intravenous gadofosveset.
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Journal of Medical Imaging and Radiation Oncology 56 (2012) 187–191
Dynamic and steady-state acquisitions were per-formed as required with spoiled gradient echo 3D acqui-sition: Time to repetition 2.56–5.7 ms, time to echo1.07–1.92 ms, flip angle 20–30°, bandwidth 200–1000 Hz/pixel. Voxel size varied from 0.7 mm isotropic
to 1.7 ¥ 1.3 ¥ 1.0 mm depending on the territory imagedand requirement for breath-hold/dynamic imaging. Par-allel imaging factors up to three were used.
Applications of gadofosveset
Renal MRA
Renal MRA with extracellular agents is well described;6
however, concerns have been raised over the sensitivitycompared with conventional angiography (Fig. 1).7 Bloodpool contrast agents show greater sensitivity and speci-ficity,8 particularly in combination with steady-stateimaging.
Lower limb peripheral MRA
CE-MRA is an established diagnostic test in occlusivePVD,9 but is limited by vessel size, motion and venouscontamination (Fig. 2). Blood pool contrast agentsenable higher resolution in the first pass imaging as wellas clear differentiation of the arterial and venous struc-tures in an acceptable acquisition time.10
Peripheral arteriovenous fistula
Due to the longer half-life and greater relaxivity of bloodpool contrast agents, imaging of vascular malformationsappears improved compared with extracellular CE-MRA,allowing accurate visualisation of the feeding artery andcommunicating venous structures (Fig. 3).
Fig. 1. First pass coronal mean intensity projection (MIP) contrast-enhanced
magnetic resonance angiography (CE-MRA). A 69-year-old male presented
with refractory hypertension. CE-MRA was performed to exclude renal artery
stenosis. Coronal MIP demonstrates bilateral main and accessory renal arter-
ies with no evidence of renal artery narrowing.
a b c
Fig. 2. Peripheral magnetic resonance angiography (MRA) using thigh compression cuffs. An 87-year-old arteriopath presented with right leg swelling following a
right femoropopliteal bypass. Lower limb contrast-enhanced MRA with gadofosveset demonstrates a patent graft on the right with left femoral and run-off disease.
Lower limb pressure cuffs were used to limit venous contamination. Despite the small volume of chelate and the extended anatomical coverage, good signal to noise
is obtained even in the foot arteries at first pass.
Anatomical areas subject to respiratory movement aresubject to more artefacts than other anatomical areas(Fig. 4). In combination with gated steady-state imaging,diagnostic images can be acquired in these regions.
Venography
Intravascular agents may be particularly useful inpatients with venous occlusion where conventional tech-niques do not well demonstrate the anatomy and obviatethe need for multiple injections (Fig. 5).
a b c
Fig. 3. Lower limb 3D contrast-enhanced magnetic resonance angiography (CE-MRA). Early (a) and late dynamic (b), and steady state (c). A 61-year-old man had a
painful varicosity along the lateral aspect of his left thigh. Following duplex studies, CE-MRA was undertaken to assess suitability for percutaneous sclerotherapy.
mean intensity projections (MIPs) showed filling of an arteriovenous fistula in the lateral thigh (arrowhead), communicating with multiple superficial varicosities on
delayed images. First pass imaging shows high flow and early venous filling (a, arrowhead). Late dynamic and delayed high resolution MIPs show communications
with the superficial varicosities (b,c).
a
b
Fig. 4. A 37-year-old female with a painful congenital naevus of her left chest
wall underwent gadofosveset-enhanced magnetic resonance angiography
(MRA) to assess suitability for coil embolisation. MRA shows a large chest-wall
arteriovenous malformation (AVM), the AVM filling on delayed images (a). A
large draining intercostal vein (arrow) communicates with the hemiazygous
and lumbar veins (b).
Fig. 5. A 32-year old male had a history of repeated childhood femoral venous
cannulation and recurrent thrombosis. Duplex imaging was poor. Gadofos-
veset venography shows absence of the inferior vena cava with enlarged hemi-
While not a typical indication for MRA, blood pool agentscan be used to demonstrate complex vascular anatomyand occlusions, including regions normally avoided dueto excessive artefact and poor image quality (Fig. 6).
Thoracic outlet syndrome
The prolonged intravascular half-life enables imagingwith a single bolus of gadofosveset without reliance ontiming first pass imaging (Fig. 7). The greater T1 short-ening available with gadofosveset improves both arterialand venous imaging. Imaging of the thoracic outletvessels with extracellular contrast agents in our experi-ence is poor. To date, no studies have been publishedcomparing these two types of contrast agent for imagingof the thoracic outlet.
Discussion
Gadofosveset-enhanced angiography provides excellentdynamic-phase imaging because of increased T1 short-ening, as well as acquisition of steady-state images ofarteries and veins with high spatial resolution. The ability
to achieve isotropic imaging enables reformatting in anyplane and overcomes the drawback of superimposedarterial and venous structures on mean intensity projec-tions. Multiple territories can be assessed with a singleinjection, including at the thoracic inlet. The persistentvascular enhancement with these agents allows repeatedimaging of vascular territories and assessment of throm-bosis or venous occlusion. The combination of dynamicand delayed imaging can demonstrate anatomical andflow characteristics of arteriovenous malformations.Further applications, such as coronary artery imaging,have been proposed.11
In clinical trials, gadofosveset-enhanced MRA wasfound to be safe and well tolerated,12,13 including inpatients with severe (CKD 4) renal disease. Toxicity andimmunogenic side effects of gadolinium are thought tobe related to gadolinium dose and as such, many inves-tigators have focused attention on dose-reducingimaging strategies. Lower doses of gadofosveset can beused as a result of its higher relaxivity in human bloodcompared with other gadolinium chelates.13
Although the advantages of blood pool agentsappear straightforward, large prospective clinicaltrials are needed to demonstrate their benefit to allpopulations.
1. Prince MR, Narasimham DL, Stanley JC et al.Breath-hold gadolinium-enhanced MR angiography ofthe abdominal aorta and its major branches.Radiology 1995; 197: 785–92.
2. Parmelee DJ, Walovitch RC, Ouellet HS, Lauffer RB.Preclinical evaluation of the pharmacokinetics,biodistribution, and elimination of MS-325, a bloodpool agent for magnetic resonance imaging. InvestRadiol 1997; 32: 741–7.
13. Shamsi K, Yucel EK, Chamberlin P. A summary ofsafety of gadofosveset (MS-325) at 0.03 mmol/kgbody weight dose: Phase II and Phase III clinicaltrials data. Invest Radiol 2006; 41: 822–30.
a
b
c
Fig. 7. A 40-year-old male presented with clinical features of thoracic outlet
obstruction. Magnetic resonance angiography with gadofosveset shows
indentation of the left subclavian artery with the arms elevated (dynamic mean
intensity projection, a, arrow; high resolution base data, b, arrow). High reso-
lution delayed imaging showed normal subclavian arteries with the arms
