NEUROTOXIC POTENTIAL OF GADODIAMIDE AFTER INJECTION INTO THE LATERAL CEREBRAL VENTRICLE OF RATS

PURPOSE: Results of a previous report showed that, if administered by intraventricular injection to access tissue normally protected by the blood-brain barrier, gadopentetate dimeglumine produced acute excitati on, persistent ataxia, and widespread brain lesions in rats at 5-mu mo l/g brain but not at 3.8-mu mol/g brain, The present study using gadod iamide was undertaken to see whether the effects were agent-specific, METHODS: Rats, surgically prepared with a lateral ventricular cannula, were administered a slow injection at 2 mu L/min of gadodiamide into the lateral ventricle, and behavioral and neuropathologic changes were noted, RESULTS: Both gadodiamide and gadopentetate dimeglumine produc ed focal and generalized myoclonus over several hours, Gadodiamide did not produce the medium-term tremor or persistent ataxia seen after tr eatment with gadopentetate dimeglumine. Neuropathologic changes develo ped over 1 to 3 days and took three distinct forms: vacuolated thalami c lesions closely resembling those produced by gadopentetate dimeglumi ne; small but similar vacuolated symmetrical caudate lesions not produ ced by gadopentetate dimeglumine; and severe swelling and astrocytic h ypertrophy and hyperplasia in the cerebellar vermis, again not produce d by gadopentetate dimeglumine. Unlike gadopentetate dimeglumine, gado diamide produced no spinal cord lesions, The cerebellar changes were s een at 1.25-mu mol/g brain and above, behavioral changes at 2.5-mu mol /g brain and above, and thalamic and caudate lesions at 10-mu mol/g br ain, the maximal dose used, Markedly reducing the rate of injecting th e same volume over 28 hours prevented the acute excitation but did not reduce the severity of the morphologic effects, CONCLUSION: The acute excitatory effects of high intraventricular doses of gadopentetate di meglumine and gadodiamide are similar and appear to be attributable to local action at the infusion site, but differences exist between the two agents in the character and topography of the distant morphologic changes, The cerebellum was the brain area most sensitive to gadodiami de in this experimental model, It is unlikely that gadodiamide would g ain access to the brain at these tissue doses when used intravenously for conventional clinical imaging, but our experimental model suggeste d that it had some unexpectedly specific neuropathologic potential.