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Published on: July 22, 2014
Gadofluorine M-enhanced magnetic resonance nerve imaging: comparison between acute inflammatory and chronic
Carsten Wessig1, Leonie Jestaedt, Michael W Sereda
1Department of Neurology, University of Würzburg, Josef-Schneider-Strasse 11, Würzburg, Germany. wessig_c@klinik.uni-wuerzburg.de
Abstract:
Nerve imaging by magnetic resonance imaging (MRI) is an emerging tool for the diagnostic work-up of patients with PNS disorders. We have recently shown that the experimental MR contrast agent gadofluorine M (Gf, Bayer Schering Pharma AG, Berlin) accumulates in nerves undergoing Wallerian degeneration and in areas of acute focal demyelination allowing in-vivo assessment of nerve pathology. The exact pathomechanism underlying Gf accumulation in peripheral nerve disorders is unknown so far. In the present study we compared nerve signal alterations on T2-w and Gf-enhanced T1-w MRI in two different models of acute inflammatory and chronic degenerative demyelination: experimental autoimmune neuritis (EAN) induced by immunization with PNS myelin and experimental Charcot-Marie-Tooth (CMT) disease in rats overexpressing the myelin protein PMP22. During the acute stage of inflammation and demyelination, strong Gf enhancement on T1-w MRI was seen in nerve roots and peripheral nerves in EAN, which resolved with completed remyelination. Similarly, Gf accumulation was seen in CMT rats during early stages with active demyelination at 6 weeks while at chronic stages (9 months) Gf enhancement decreased despite numerous demyelinated axons and onion bulb formation. At all disease stages no signal alterations were seen on T2-w MRI. In conclusion, our data show that the novel MR contrast agent Gf, but not Gadolinium (Gd)-DTPA, facilitates detection of ongoing demyelination by MR neurography independent from the underlying pathology. It appears that the extent of Gf enhancement depends on the acuity of demyelination and is probably related to a transient disturbance of the blood-nerve barrier. Clinical development of Gf may help to further improve the sensitivity of nerve lesion assessment by MRI in patients with peripheral neuropathies.
Insights
The experimental contrast agent gadofluorine M (Gf) aids in detecting nerve demyelination using MRI. Gf shows promise for diagnosing peripheral nerve disorders by highlighting active nerve damage.
Area of Science:
- Neuroimaging
- Peripheral Nerve Disorders
- Magnetic Resonance Imaging (MRI)
Background:
- Magnetic resonance imaging (MRI) is an emerging diagnostic tool for peripheral nerve disorders.
- The experimental MR contrast agent gadofluorine M (Gf) accumulates in nerves with Wallerian degeneration and acute focal demyelination.
- The precise mechanism of Gf accumulation in peripheral nerve disorders remains unclear.
Purpose of the Study:
- To investigate the pathomechanism of gadofluorine M (Gf) accumulation in peripheral nerve disorders.
- To compare nerve signal alterations using T2-weighted and Gf-enhanced T1-weighted MRI in models of demyelination.
- To assess the utility of Gf in detecting active demyelination in peripheral nerves.
Main Methods:
- Two rat models were used: experimental autoimmune neuritis (EAN) for acute inflammatory demyelination and experimental Charcot-Marie-Tooth (CMT) disease for chronic degenerative demyelination.
- Nerve signal alterations were compared on T2-weighted and Gf-enhanced T1-weighted MRI.
- Gadolinium (Gd)-DTPA was used as a comparative contrast agent.
Main Results:
- Strong Gf enhancement was observed in EAN during acute inflammation and demyelination, resolving with remyelination.
- Gf accumulation occurred in CMT rats during early active demyelination but decreased in chronic stages.
- No signal alterations were detected on T2-weighted MRI at any disease stage; Gf enhancement correlated with active demyelination.
Conclusions:
- Gadofluorine M (Gf), unlike Gd-DTPA, effectively detects ongoing demyelination in MR neurography, irrespective of the underlying pathology.
- Gf enhancement appears dependent on the acuity of demyelination, likely linked to transient blood-nerve barrier disturbances.
- Gf holds potential for improving the sensitivity of MRI-based assessment of nerve lesions in peripheral neuropathies.
