Abstract
PurposeTo investigate the impact of blood-brain barrier (BBB) alterations induced by an experimental tumor and radiotherapy on MRI signal intensity (SI) in deep cerebellar nuclei (DCN) and the presence of gadolinium after repeated administration of a linear gadolinium-based contrast agent in rats.MethodsEighteen Fischer rats were divided into a tumor (gliosarcoma, GS9L model), a radiotherapy, and a control group. All animals received 5 daily injections (1.8 mmol/kg) of gadopentetate dimeglumine. For tumor-bearing animals, the BBB disruption was confirmed by contrast-enhanced MRI. Animals from the tumor and radiation group underwent radiotherapy in 6 fractions of 5 Gray. The SI ratio between DCN and brain stem was evaluated on T1-weigthed MRI at baseline and 1 week after the last administration. Subsequently, the brain was dissected for gadolinium quantification by inductively coupled plasma-mass spectrometry. Statistical analysis was done with the Kruskal-Wallis test.ResultsAn increased but similar DCN/brain stem SI ratio was found for all three groups (p = 0.14). The gadolinium tissue concentrations (median, nmol/g) were 6.7 (tumor), 6.3 (radiotherapy), and 6.8 (control) in the cerebellum (p = 0.64) and 17.8/14.6 (tumor), 20.0/18.9 (radiotherapy), and 17.8/15.9 (control) for the primary tumor (p = 0.98) and the contralateral hemisphere (p = 0.41) of the cerebrum, respectively.ConclusionAn experimental brain tumor treated by radiotherapy or radiotherapy alone did not alter DCN signal hyperintensity and gadolinium concentration in the rat brain 1 week after repeated administration of gadopentetate. This suggests that a local BBB disruption does not affect the amount of retained gadolinium in the brain.
Highlights
Gadolinium-based contrast agents (GBCAs) are frequently used in clinical MRI examination in particular for CNS imaging
It was demonstrated in healthy rats that small amounts of GBCASs can cross the blood-CSF barrier independent of their chemical structure or physicochemical properties [17]
For the other 5 rats, the presence of the tumor and the consequent local disruption of the blood-brain barrier (BBB) was confirmed by contrast-enhanced MRI 1 week after inoculation
Summary
Gadolinium-based contrast agents (GBCAs) are frequently used in clinical MRI examination in particular for CNS imaging. An increasing number of studies reported increased signal intensities (SIs) on unenhanced T1-weighted images in the dentate nucleus (DN) and the globus pallidus (GP) of patients that received repeated contrast-enhanced MRI examinations [1, 2]. These signal hyperintensities depend on the ligand type of the agent [3, 4] and has been primarily. It was demonstrated in healthy rats that small amounts of GBCASs can cross the blood-CSF barrier independent of their chemical structure or physicochemical properties [17] This was confirmed in a clinical study where Gd
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