Sonja Kinner^1,2, Tilman B Schubert^1,3, Susan Rebsamen¹, Richard Bruce¹, Scott B Reeder^1,4,5,6,7, and Howard A Rowley^1
1Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, ²Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany, ³Clinic for Radiology and Nuclear Medicine, Basel University Hospital, Basel, Switzerland, ⁴Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, ⁵Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, ⁶Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, ⁷Department of Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States

Recent studies report intrinsic T1 hyperintense signal in deep brain nuclei on MRI after multiple doses of gadolinium-based contrast agents in adults. We investigated whether similar T1 shortening was also found in children, and furthermore evaluated the influence of radiochemotherapy (RCTX) on its appearance. Signal increases were found in 2/60 children without RCTX and in 12/16 children with RCTX. Signal ratio changes were significantly different between the two groups and appeared with fewer doses in children with RCTX. 

Svein Are Vatnehol¹, Inge Rasmus Groote¹, Christopher Larsson¹, Magne Kleppestø¹, Jonas Vardal¹, and Atle Bjørnerud^1,2
1The Intervention Center, Oslo University Hospital, Oslo, Norway, ²Department of Physics, University of Oslo, Oslo, Norway

Recent publications have shown an increase in signal intensity on non-enhanced T1w-images for the Dentate Nucleus and Globus Pallidus. This effect seems to be linked to multiple administrations of linear gadolinium chelate. In this retrospective study we have analyzed the quantitative T1 values (qT1) and the normalized native T1 signal intensity (nSI) for the Globus Pallidus and the nSI for the Dentate Nucleus in patients with multiple injections of gadobutrol (Gadovist™). Our analysis suggest a significant change in the qT1 and nSI for the Globus Pallidus as well as in the nSI for the Dentate Nucleus

Hubertus Pietsch¹, Thomas Frenzel¹, Anna-Lena Frisk¹, Diana Constanze Lenhard², Gregor Jost¹, Martin Andrew Sieber¹, Astrid Zimmermann³, Volker Nischwitz³, and Jessica Lohrke^1
1Bayer Healthcare, Berlin, Germany, ²Charité, Humboldt University Berlin, Berlin, Germany, ³Forschungszentrum Jülich, Jülich, Germany

Recent publications reported increased T1-weighted signal intensities in the dentate nucleus of patients who received multiple contrast-enhanced MRI scans. In this animal study histopathological changes and gadolinium retention in the skin and brain of rats after twenty intravenous injections of linear and macrocyclic GBCAs at high doses (2.5mmol/kgbw) were systematically investigated. The Gd brain concentrations of linear GBCAs (gadodiamide, gadopentetate dimeglumine) were significantly higher than those of macrocyclic agents (gadobutrol, gadoteridol). Since no morphological changes could be detected by routine H&E microscopic examination, immunohistochemistry and special stains, these findings are considered be of no toxicological relevance in rats.

Gregor Jost¹, Diana Lenhard², Jessica Lohrke¹, Thomas Frenzel¹, and Hubertus Pietsch^1
1MR and CT Contrast Media Research, Bayer Healthcare, Berlin, Germany, ²Institute of Vegetative Physiology, Charité, Berlin, Germany

Recent publications reported increased T1-weighted (T1w) signal intensities (SI) in the dentate nucleus and globus pallidus after repeated administrations of gadolinium based contrast agents (GBCAs). In the present animal study the T1w SI of three linear and two macrocyclic GBCAs were systematically evaluated after ten administrations each with a dose of 2.5 mmol/kg. Increased cerebellar nuclei to pons SI ratios were found after administration of linear GBCAs (significantly increased for gadodiamide and gadobenate dimeglumine, and non-significantly increased for gadopentetate dimeglumine). In contrast no elevated SI ratios were observed after administration of the macrocyclic GBCAs gadobutrol and gadoterate meglumine or saline.

Daniel Calle¹, Irene Guadilla¹, Pilar López-Larrubia¹, and Sebastián Cerdán^1
1Instituto de Investigaciones Biomédicas "Alberto Sols", CSIC, Madrid, Spain

We report on the kinetics of uptake and clearance of Gd(III)DTPA from different brain structures to healthy mice. We fitted a biexponential  model to cerebral time courses of increase and decrease of T_1w MRI signal intensity, calculating rate constants for the uptake (k_abs) and elimination (k_el).  k_abs showed the rapid absorption in the ventricles and hypothalamus, slowing down significantly in the cortex, globus pallidus and dentante nucleus. These latter structures required 617 h. (cortex), 245 h. (globus pallidus) and approximately 100h (hypothalamus and dentate nucleus), to remove 99% of the administered agent, revealing very high cerebral residence times of Magnevist.

Shinji Naganawa¹ and Toshiaki Taoka^1
1Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

Perivascular spaces (PVS) have been described as non-enhancing structures with a fluid signal. In this study, we confirmed that PVS signals are enhanced in images obtained 4 hours after intravenous administration of gadolinium based contrast agent (GBCA) in human subjects without renal insufficiency. Contrast enhancement of CSF was also observed. It is possible that GBCA in the blood vessels might have permeated into the CSF space and PVS. This could be the route by which GBCA is distributed to brain parenchyma through the glymphatic system in subjects with a normal blood brain barrier.

Hirofumi Kuno¹, Hernan Jara¹, Karen Buch¹, Andrew Mills¹, Muhammad Mustafa Quresh¹, Neil Thayil ¹, Margaret N Chapman¹, and Osamu Sakai^1
1Radiology, Boston University, Boston Medical Center, Boston, MA, United States

To assess potential regional and global correlations between brain relaxation times and the number of prior administrations of linear gadolinium-based contrast agents (GBCA) using quantitative MRI. The subjects consisted of 40 patients (7 patients with multiple prior linear GBCA exposures and 33 patients with no prior GBCA exposures) with brain MRI using the mixed turbo spin-echo pulse sequence. T1 and T2 relaxation times were assessed in selected regions of brain parenchyma (GP, DN, thalamus, and pons) and the whole brain, and were demonstrated to be associated with the number of gadolinium administrations. A stronger relationship was demonstrated in gray matter.