Friday, October 19, 2012


As a follow-up on MR angiography with contrast (10/18/12)... if the gadolinium ion is necessary for contrast, how can we deliver it to the blood stream?  A salt solution of Gd-ions in buffered water? 

No... that would be bad. Naked gadolinium (III) ions are toxic to the body, but can be safely transported through the bloodstream as a chelate.  This actually works to the benefit of imaging, because, similar to principles in nuclear medicine, engineering the chelate can be useful in affecting its biodistribution.  For example, using a chelate with a molecule which would be taken up by hepatocytes (Eovist), allows selective liver imaging.

So how could this be useful for MR angiography?

Since we want to image the vascular structures, it would be nice if we could keep the contrast in the vessels.  For a conventional chelate, it pumps through the blood pool and is excreted out at a rate of 20% of cardiac output per pass through the kidneys.  Multihance is generally used as an MRA contrast agent because a small % of it binds to the plasma proteins, which (hopefully most of the time) aren't excreted, thus prolonging its time in the blood pool.

Gadofosveset ("Ablavar")
A relatively-recently approved new chelate -- Ablavar -- improves on Multihance for contrast-enhanced MRA.  Instead of a few % plasma protein binding, Ablavar binds at approximately 50%. Most extracellular agents have a half life of about 100 minutes... Ablavar lasts 15.5 hours.

Not only that, but the relaxivity of Ablavar is much higher than traditional extracellular agents -- about 4x higher.

Why is this a good thing? Well... contrast-enhanced MRA is very dependent on timing of the contrast bolus. Conventional agents "leak" out into the blood pool of the tissues and getting a good sequence is critically dependent on good bolus timing (and good centering of k-space)... but the extended acquisition time and increased relaxivity of Ablavar allows for longer steady-state acquisition times, and potentially submillimeter voxels.  If you can get voxels this small without worsening of signal to noise, and thereby increasing the spatial resolution of the MR angiogram... then the overlay of veins in a steady-state MRA would not be a problem with multiplanar reformats. This is particularly promising for evaluation of the peripheral vasculature, which previously was difficult to assess due to "the inability to differentiate arteries from veins with a resolution of 1 mm3 that is typically acquired at standard-resolution first-pass MR angiography with gadolinium chelate contrast agent." Ablavar has the potential to open up MRA for evaluation of small vessels, such as those in the lower extremities and in the mesenteric circulation. Some early studies show that it may be as good as contrast-enhanced CT for the evaluation of many vascular pathologies.

Coronal image from an Ablavar-enhanced evaluation of the aorta

Downsides?  The spectre of NSF is always looming around gadolinium contrast agents, and though Ablavar's track record has no blemishes, it's still not totally proven.  The fact that the increased relaxivity allows for smaller doses to be used is promising.

As a side note, although it can be used for a wide-variety of angiographic purposes, Ablavar is officially only FDA-approved for use in aorto-iliac disease, with the other uses being off-label.  The suggest dose is 0.03 mmol/kg and the smaller dose that than of other extracellular contrast agents such as Multihance, result in a different bolus profile... and a decrease in the usual rate to about half has been found to be useful.

As another side note... the equilibrium phase for Ablavar imaging seems to work better with a decreased flip angle.  Lowering the angle to around 20 degrees seems to provide a better image.

1. "Duke Review of MRI Principles: Case Review Series" Mangrum, et al. (2012).
2. Hadizadeh DR, Gieseke J, Lohmaier SH, et al. "Peripheral MR Angiography with Blood Pool Contrast Agent: Prospective Intraindividual Comparative Study of High-Spatial-Resolution Steady-State MR Angiography versus Standard-Resolution First-Pass MR Angiography and DSA"  November 2008 Radiology, 249, 701-711.
3. Goyen M. "Gadofosveset-enhanced magnetic resonance angiography" Vascular Health and Risk Management 2008:4(1) 1–9