Multiple sclerosis (MS) is an autoimmune inflammatory disease of the nervous system due to a still unknown antigen.1 While the diagnosis of MS relies primarily on a combination of typical clinical symptoms and paraclinical findings (cerebrospinal fluid [CSF] findings from lumbar puncture), neuroimaging plays an important role in its management.2 While plaques can sometimes be seen on computed tomography (CT), nowadays CT plays no role whatsoever except as a rule-out method in patients with acute symptoms in whom haemorrhage or stroke must be diagnosed/excluded; instead, imaging today relies entirely on magnetic resonance imaging (MRI).
As diagnosis using imaging relies on counting the number of demyelinating lesions in the white matter, the presence of enhancing lesions will increase the diagnostic yield of the method. As a result, contrast-enhanced imaging is mandatory in the assessment of patients with known or suspected MS.3–6
Neuroimaging plays an important role not only in the diagnosis but also in the management of these diseases: indeed, imaging and contrast enhancement can demonstrate disease activity and thus be used not just to monitor the natural history of the disease, but also to look at the impact of treatment.
Multiplanar fluid-attenuated inversion recovery (FLAIR) and T2 sequences (usually axial T2 and FLAIR and sagittal FLAIR) together with axial pre-contrast T1 and post-contrast T1 in all three planes constitutes the traditional approach to the patient with MS. It must be stressed that imaging of the orbits (with coronal T2 and axial and coronal fat-saturated T1-weighted post-contrast images) can often be performed in addition to imaging the whole spinal cord. Additionally, techniques such as diffusion tensor imaging, diffusion-weighted imaging, spectroscopy and magnetisation transfer have been used with success in this disease.
In addition to clinical and laboratory criteria, classifications such as those proposed by MacDonald or Barkhof are usually used in order to make the diagnosis of MS more precise. These classifications include a count of the number of lesions visible on T2-weighted images in the white matter, as well as of lesions that enhance.
Rationale for Gadovist
One-molar Contrast Material
Gadovist (gadobutrol) is a one-molar gadolinium chelate that has found wide acceptance in applications in the central nervous system (CNS). It has been used for applications in the brain relating to imaging of primary brain tumours and metastases, as well as for optimising brain perfusion in stroke.7–11 Besides its uniquely high concentration, Gadovist has been found to have a higher relaxivity than other macrocycle contrast media (see Figure 1), which leads to the highest available T1-shortening per volume and should also allow increased contrast at the same concentration.12
Delayed Magnetic Resonance Images
Due to its higher T1-shortening and relaxivity, which seem to increase with time, there is an apparent advantage to the use of Gadovist together with late images: indeed, the conspicuousness of lesions increases with time after injection with Gadovist. This has been nicely demonstrated in the paper by Uysal et al.,13 who found that the use of 1.0mol/l gadolinium chelate enabled them to detect an increased number of enhancing lesions and patients with active disease. They also found that a delay of five minutes after the injection of the gadolinium chelate might be sufficient to detect active lesions in patients with MS. We have also found that performing late imaging with Gadovist with sequential images being performed up to 12 minutes after administration enhances the capacitiy of Gadovist to detect MS lesions (see Figures 2 and 3).
Gadovist was the first commercially available MR contrast agent at a concentration of 1.0mol/l. This means that it is available at a higher concentration at the same dose: this can allow a double dose at the same injected volume, or allow the volume to be reduced by half while retaining the same effect as another (half-molar) compound.
Safety Concerns and Nephrogenic Systemic Fibrosis
Recently, an association has been found between the administration of gadolinium compounds and the occurrence of nephrogenic systemic fibrosis (NSF).14 Gadovist, which is a macrocyclic compound, seems more stable and much less susceptible to causing such complications. However, NSF does tend to occur in a more elderly population with co-morbidities that are often not present in the younger MS population. Indeed, NSF is mostly associated with cases of renal failure and patients who have received multiple doses of linear Gd-chelates. However, caution still needs to be exercised, and renal function should be tested.
Gadovist is a safe gadolinium chelate compound that has been used successfully for neuroimaging with MRI of the nervous system for many years. Its advantages are a higher concentration and a higher relaxivity. This allows higher contrast at the same dosage, or lower injected volumes with maintained or even improved contrast effect. Due to the fact that it is a more stable compound that can be used at half volume, it should also be a safer molecule, which is important in the context of growing concern regarding NSF. ■