Intravenous GBCA exposure is associated with neuronal tissue deposition in the setting of relatively normal renal function. Additional studies are needed to investigate the clinical significance of these findings and the generalizability to other GBCAs. Online supplemental material is available for this article.

Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings challenge current understanding of the biodistribution of these contrast agents and their safety. RSNA, 2017.

Purpose To compare gadolinium tissue concentrations of multiple linear and macrocyclic chelates in a rat model to better understand the scope and extent of tissue deposition following multiple intravenous doses of gadolinium-based contrast agent (GBCA). Materials and Methods In this Institutional Animal Care and Use Committee-approved study, healthy rats received 20 intravenous injections of 2.5 mmol gadolinium per kilogram (gadolinium-exposed group) or saline (control group) over a 26-day period. Unenhanced T1 signal intensities of the dentate nucleus were measured from magnetic resonance (MR) images obtained prior to GBCA injection and 3 days after final injection. Rat brain and renal, hepatic, and splenic tissues were harvested 7 days after final injection and subjected to inductively coupled plasma mass spectrometry and transmission electron microscopy for quantification and characterization of gadolinium deposits. Results Gadolinium deposition in brain tissue significantly varied with GBCA type (F = 31.2; P < .0001), with median concentrations of 0 μg gadolinium per gram of tissue (95% confidence interval [CI]: 0, 0.2) in gadoteridol-injected rats, 1.6 μg gadolinium per gram of tissue (95% CI: 0.9, 4.7) in gadobutrol-injected rats, 4.7 μg gadolinium per gram of tissue (95% CI: 3.5, 6.1) in gadobenate dimeglumine-injected rats, and 6.9 μg gadolinium per gram of tissue (95% CI: 6.2, 7.0) in gadodiamide-injected rats; a significant positive dose-signal intensity correlation was identified (ρ = 0.93; P < .0001). No detectable neural tissue deposition or MR imaging signal was observed in control rats (n = 6). Similar relative differences in gadolinium deposition were observed in renal, hepatic, and splenic tissues at much higher tissue concentrations (P < .0001). Gadolinium deposits were visualized directly in the endothelial capillary walls and neural interstitium in GBCA-injected rats, but not in control rats. Conclusion Tissue deposition of gadolinium was two- to fourfold higher following administration of the linear agents gadodiamide and gadobenate dimeglumine compared with the macrocyclic agents gadobutrol and gadoteridol. These findings suggest that organ tissue deposition is reduced but not eliminated following administration of macrocyclic GBCA chelates in lieu of linear chelates. RSNA, 2017 Online supplemental material is available for this article.

Objective: To determine the safety of intrathecal autologous adipose-derived mesenchymal stromal cell treatment for amyotrophic lateral sclerosis (ALS).Methods: Participants with ALS were enrolled and treated in this phase I dose-escalation safety trial, ranging from 1 3 10 7 (single dose) to 1 3 10 8 cells (2 monthly doses). After intrathecal treatments, participants underwent standardized follow-up, which included clinical examinations, revised ALS Functional Rating Scale (ALSFRS-R) questionnaire, blood and CSF sampling, and MRI of the neuroaxis.Results: Twenty-seven patients with ALS were enrolled and treated in this study. The safety profile was positive, with the most common side effects reported being temporary low back and radicular leg pain at the highest dose level. These clinical findings were associated with elevated CSF protein and nucleated cells with MRI of thickened lumbosacral nerve roots. Autopsies from 4 treated patients did not show evidence of tumor formation. Longitudinal ALSFRS-R questionnaires confirmed continued progression of disease in all treated patients.Conclusions: Intrathecal treatment of autologous adipose-derived mesenchymal stromal cells appears safe at the tested doses in ALS. These results warrant further exploration of efficacy in phase II trials. Classification of evidence:This phase I study provides Class IV evidence that in patient with ALS, intrathecal autologous adipose-derived mesenchymal stromal cell therapy is safe.

These findings document a key mechanism of tumor resistance to oncolytic MV therapy and describe for the first time the development of a prediction algorithm to preselect for oncolytic treatment or combinatorial strategies.