Gadofluorine M enhancement allows more sensitive detection of inflammatory CNS lesions than T2-w imaging: a quantitative MRI study

Abstract

Magnetic resonance imaging plays a pivotal role in the diagnosis and treatment monitoring of multiple sclerosis. Currently available magnetic resonance-techniques only partly reflect the extent of tissue inflammation and damage. In the present study, application of the experimental magnetic resonance-contrast agent Gadofluorine M significantly increased the sensitivity of lesion detection in myelin-oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. Gadofluorine M-enhancement on T(1)-weighted (T(1)-w) images utilizing a clinical 1.5 T magnetic resonance unit showed numerous lesions in optic nerve, spinal cord and brain, the majority of which were not detectable on standard T(2)-weighted (T(2)-w) and Gd-DTPA enhanced T(1)-w sequences. Quantitative assessment by pixel counts revealed highly significant differences in sensitivity in favour of Gadofluorine M. Gadofluorine uptake closely corresponded to inflammation and demyelination on tissue sections. These unique features of Gadofluorine M in visualizing inflammatory CNS lesions hold promise for future clinical development in multiple sclerosis.

Magnetic resonance microimaging of the spinal cord in the SOD1 mouse model of amyotrophic lateral sclerosis detects motor nerve root degeneration

“…It is unclear if the presence of the gadolinium contrast agent increases the intensity changes beyond a general improvement in signal-to-noise. Huang et al (2009) (Bendszus et al, 2008).…”

“…Paramagnetic contrast agents are of benefit as they shorten T1, enabling greater signal-to-noise per unit time. These agents can also improve tissue contrast by selection of the contrast agent and use of targeted contrast agents (Bendszus et al, 2008;Blackwell et al, 2009;Huang et al, 2009;Ullmann et al, 2010b contrast and the ability to acquire a single 3D data set also lend themselves to both manual and automatic segmentation. Automated segmentation has been exploited for the generation of anatomic atlases such as the mouse brain (Ali et al, 2005;Johnson et al, 2007;Ma et al, 2005;Ma et al, 2008;Scheenstra et al, 2009;Sharief et al, 2008), rat brain (Schwarz et al, 2006), rhesus monkey (Wisco et al, 2008) and zebrafish (Ullmann et al, 2010a).…”

Gadofluorine M enhanced MRI in experimental glioma: Superior and persistent intracellular tumor enhancement compared with conventional MRI

“…Recently, the new MR-contrast agent Gadofluorine M (GfM) demonstrated an almost 10-fold higher load of inflammatory lesions compared with standard MR-techniques in experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis. GfM uptake closely corresponded with inflammation and demyelination on tissue sections (4). The mechanism of contrast enhancement was identified as a persistent binding of GfM to proteins of the extracellular matrix (ECM) as fibronectin, proteoglycan, tenascin, and collagen I and IV in neuroinflammation (7).…”

“…GfM was applied by tail vein injection at a dose of 0.1 mmol/kg body weight (BW). Due to its longer plasma half-life MRI was always performed 24 h after application of the contrast agent (4,10).…”

“…Commonly, contrast enhancement on T1-w images is regarded as indicator for tumor malignancy. However, biologically this only reflects an unspecific leakage of the bloodbrain barrier (BBB) for a particular molecule size (4). Moreover, the tumor size on Gd-DTPA-enhanced MRimages does not reflect the histopathological extent of the lesion (5).…”