MRA With Feraheme in HHT

The safety of the use of gadolinium based contrast agents in MR is a concern for the FDA, with risks of development of nephrogenic systemic fibrosis and the more recent discovery of accumulation of gadolinium in the brain in patients who have received multiple prior MR scans.

Hereditary hemorrhagic telangiectasia (HHT) manifests with multiple vascular malformations (VMs) in the skin, mucous membranes and solid organs affecting the spine, brain, liver, gastrointestinal tract, pancreas, and lungs. The disease has an autosomal dominant inheritance and affects 1 in 5000 individuals.

Cerebral vascular malformations occur in 23 % of HHT patients, with a bleeding risk of 0.5% per year. Pulmonary AVMs occur in 15-50% of HHT patients, with a complication rate of 50% ranging from fatal hemoptysis or hemothorax to stroke or cerebral abscess. Liver vascular malformations are present in 32-78% of HHT patients.

The rationale for screening for vascular malformations is detection of a treatable lesion prior to the development of a fatal complication. The international guidelines currently recommend different first line screening tests in each organ: MRI for cerebral VMs, transthoracic echocardiography for pulmonary VMs, endoscopy for gastrointestinal VMs, Doppler US or CT for liver VMs.

Contrast enhanced magnetic resonance angiography (CE-MRA) may play an important role in the simultaneous whole body screening of vascular malformations. The advantages of CE-MRA include visualization of the entire body vasculature in one examination, high spatial resolution comparable to CT, no ionizing radiation and easy of multiplanar reconstructions.

Substituting a conventional gadolinium based contrast agent (GBCA) with an ultra small, super paramagnetic iron oxide agent (USPIO) e.g ferumoxytol, will eliminate any potential risk of developing nephrogenic systemic fibrosis. Since 2009, ferumoxytol ('Feraheme' Advanced Magnetics, Cambridge, MA) has been FDA approved for the treatment of iron deficiency anemia in adult patients with chronic kidney disease. The results of prior studies suggest that ferumoxytol is comparable to standard GBCAs for CE- MRA. Our experience with use of ferumoxytol to date suggests that it will be a superior agent for detection of vascular malformations in a range of vascular territories and that it will be uniquely capable of interrogating multiple territories in one sitting, due to its highly stable intravascular residence time.