Muldoon LL, Tratnyek PG, Jacobs PM, et al. Imaging and Nanomedicine for Diagnosis and Therapy in the Central Nervous System: Report of the Eleventh Annual Blood-Brain Barrier Disruption Consortium Meeting. AJNR Am J Neuroradiol 2006;27:715–21
Csanád Várallyay
The Annual Blood-Brain Barrier Consortium Meeting takes place in the Pacific Northwest every March. Besides novel therapeutic approaches to brain tumor therapy, CNS imaging has become an important topic of discussion. In particular, studies using ferumoxytol iron oxide nanoparticles as a contrast agent for brain tumor imaging have been extensively discussed. This article, published in AJNR in 2006, reports on the 11th annual meeting, the first conference in which results using ferumoxytol in patients with brain tumor were presented.
At the time I joined Dr. Neuwelt’s working group in 2005, clinical studies using ferumoxytol were just getting started; less than 10 MRI studies of patients were completed. Over the years, new MRI systems were installed, including 3T and 7T human scanners, and a 12T animal MRI unit, all hosted by the Advanced Imaging Research Center at Oregon Health & Science University (where most of our patients have been scanned). Currently, the number of clinical research MRI cases using ferumoxytol is over 500.
The first imaging protocols studied the potential of ferumoxytol-enhanced anatomic imaging; later the focus shifted toward metabolic and physiologic imaging. Unlike low-molecular-weight gadolinium-containing contrast agents (GBCA), the macromolecular agent ferumoxytol has 2 unique features: lack of early extravasation and strong susceptibility effect. Therefore, ferumoxytol seemed to be a good candidate for dynamic susceptibility contrast perfusion imaging, which was successfully performed using doses of 1 mg or 2 mg ferumoxytol/kg body weight. The lack of extravasation and absence of T1 effect showed a clear improvement compared to GBCA.
Because the dynamic perfusion parameters (such as blood flow and mean transit time) are rarely used in the assessment of brain tumors, we aimed to improve of cerebral blood volume maps by substantially eliminating image distortion and increasing resolution. We added high-resolution T2*-weighted 3D sequences to the clinical imaging protocols acquired before and after ferumoxytol injection. The changes in transverse relaxation rate caused by the blood pool agent could be used as a steady-state (SS)-CBV map.
The steady-state blood volume MRI technique is straightforward and has been previously tested in animal models, including CBV-based functional imaging. The only question was whether good quality, high-resolution CBV maps can be achieved using clinically applicable ferumoxytol doses in patients. The aim of our recent study was to test the feasibility of SS-CBV measurement using ferumoxytol at clinically applicable doses and compare it with DSC-CBV using gadoteridol (Figure 1). After testing doses between 2mg/kg to 10mg/kg we found that, at a dose of ferumoxytol above 6mg/kg, good quality images could be obtained using a voxel size of 0.6 x 0.5 x 1.2 mm3. Figure 2 shows a comparison of SS-CBV and DSC-rCBV measurements, indicating significantly better resolution of tumor vasculature and areas of active tumor growth. There are disadvantages to the high resolution. Steady-state imaging requires a higher dose of ferumoxytol (>6mg/kg) compared with dynamic perfusion (<2mg/kg), and the scan time is also longer than required for dynamic MR scanning (~10 minutes vs. 2 minutes).
