Intrathecal Use of Gadobutrol for Glymphatic MR Imaging: Prospective Safety Study of 100 Patients

Abstract

BACKGROUND AND PURPOSE: Intrathecal contrast-enhanced glymphatic MR imaging has shown promise in assessing glymphatic function in patients with dementia. The purpose of this study was to determine the safety profile and feasibility of this new MR imaging technique. MATERIALS AND METHODS: A prospective safety and feasibility study was performed in 100 consecutive patients (58 women and 42 men, 51 Ϯ 19 years of age) undergoing glymphatic MR imaging from September 2015 to August 2018. Short-and long-term serious and nonserious adverse events were registered clinically and by interview after intrathecal administration of 0.5 mL of gadobutrol (1.0 mmol/mL) along with 3 mL of iodixanol (270 mg I/mL). Adverse events are presented as numbers and percentages. RESULTS: One serious adverse event (anaphylaxis) occurred in a patient with known allergy to iodine-containing contrast agents (1%). The main nonserious adverse events during the first 1-3 days after contrast injection included severe headache (28%) and severe nausea (34%), though the frequency depended heavily on the diagnosis. After 4 weeks, adverse events had resolved. CONCLUSIONS: Intrathecal administration of gadobutrol in conjunction with iodixanol for glymphatic MR imaging is safe and feasible. We cannot conclude whether short-duration symptoms such as headache and nausea were caused by gadobutrol, iodixanol, the lumbar puncture, or the diagnosis. The safety profile closely resembles that of iodixanol alone. ABBREVIATIONS: gMRI ϭ glymphatic MR imaging; iNPH ϭ idiopathic normal pressure hydrocephalus

In vivo assessment of cerebrospinal fluid efflux to nasal mucosa in humans

“…Concerns about gadolinium brain deposition have primarily been associated with linear contrast agents 43 . Recently published data showed the same safety profile for intrathecal administration of gadobutrol as for intrathecal administration of the CT contrast agent iodixanol 18 , and no signs of deposition in brain tissue have been detected after 4 weeks 19 .…”

Neurofluid Dynamics and the Glymphatic System: A Neuroimaging Perspective

“…The study clinically registered short- and long-term adverse events using patient interviews after the intrathecal administration of 0.5 mL of gadobutrol (1.0 mmol/mL) along with 3 mL of iodixanol (270 mg I/mL). In the series, serious anaphylaxis occurred in one patient with a known allergy to iodine-containing contrast agents (1%); other adverse events during the first 1–3 days after contrast injection included severe headache (28%) and severe nausea (34%) ( 29 ).…”

Noninvasive Ultrasonic Glymphatic Induction Enhances Intrathecal Drug Delivery

“…Overall, our results suggest that low-intensity noninvasive transcranial ultrasound may be used to increase the whole-brain delivery of a variety of off-the-shelf small or large therapeutic agents, following the same intrathecal administration that is used routinely in clinics worldwide to administer therapeutic agents into the CSF (Burch et al, 1988;Calias et al, 2014;Edeklev et al, 2019;Eide et al, 2018;Jain et al, 2019;Leal et al, 2011;Liu et al, 2004;Mack et al, 2016). Further, this method provides a means to directly upregulate glymphatic transport, which could be used for causative evaluation of the role of the glymphatic system in the variety of physiological and disease processes to which the glymphatic system has been correlated (Abbott et al, 2018;Ahn et al, 2019;Aspelund et al, 2015;Benveniste et al, 2019;Gaberel et al, 2014;Gakuba et al, 2018;Iliff et al, 2014;Kress et al, 2014;Lundgaard et al, 2017;Mader and Brimberg, 2019;Mendelsohn and Larrick, 2013;Peng et al, 2016;Plog and Nedergaard, 2018;Pu et al, 2019;Simon and Iliff, 2016).…”