Gadolinium retention in gliomas and adjacent normal brain tissue: association with tumor contrast enhancement and linear/macrocyclic agents

Abstract

Purpose To quantitate gadolinium deposits in gliomas and adjacent normal brain specimens, and to evaluate their association with tumor contrast enhancement and the type of gadolinium-based contrast agent (GBCA) used. Methods A total of 69 patients with primary glioma who underwent contrast-enhanced magnetic resonance imaging (MRI) prior to surgery were included in this retrospective study. Gadolinium was measured from histologically viable tumor, normal brain, and necrosis within the sample, when available, using inductively coupled plasma mass spectrometry (ICP-MS). Tumor contrast enhancement was categorized as none, minimal, or noticeable. Differences in gadolinium deposits by contrast enhancement and GBCA type were assessed. Results Seven patients received linear GBCA and 62 macrocyclic, respectively. At the time of surgery, gadolinium deposits were detected in 39 out of 69 (57%) tumor samples, 8 out of 13 (62%) normal brain, and 12 out of 14 (86%) necrotic specimens. Gadolinium was detected in both enhancing and non-enhancing tumors, but was greatest in gliomas with noticeable enhancement (p = 0.02). Administration of linear agents gadodiamide and gadopentetate dimeglumine resulted in significantly higher tumor gadolinium relative to macrocyclic gadoterate meglumine (p < 0.01 and p < 0.05, respectively). Normal brain and necrosis also showed higher gadolinium after exposure to linear gadodiamide (both p < 0.05). In multivariate regression, GBCA type (linear/ macrocyclic) was the most powerful predictor of tumor gadolinium retention (p < 0.001). Conclusion Gadolinium can be detected in both enhancing and non-enhancing gliomas, neighboring normal brain, and necrosis. Gadolinium retention is higher after exposure to linear GBCAs compared with the macrocyclic gadoterate meglumine.

Feasibility of intravoxel incoherent motion in the assessment of tumor microvasculature and blood–brain barrier integrity: a case-based evaluation of gliomas

“…In this region, an enhanced signal in post-contrast T1-weighted images represents a viable hyperproliferative tumor whose increased demand for blood supply led to neovascularization and BBB breakdown. BBB disruption becomes evident by the extravasation of gadolinium from the intravascular compartment into tumoral tissues, perceived as areas of contrast enhancement [28]. In such regions, DSC-CBF was sensitive to increased perfusion, as well as IVIM maps, which agrees with previous studies [12,14].…”

Gadolinium deposition in the brain of dogs after multiple intravenous administrations of linear gadolinium based contrast agents

“…[25] We assessed between 1.5 to 2.5 μg gadolinium/g tissue in the DCN of the research beagle dog, which would have caused a signal intensity change in MRI. Currently published case reports and research studies describe LA-ICP-MS as a useful tool to measure the quantities of retained gadolinium in human [19,58,59] and rodent tissues [47,60]. Potential risk factors with effect on Gd retention described are ongoing neuroinflammation [60] or primary gliomas [59].…”

“…Currently published case reports and research studies describe LA-ICP-MS as a useful tool to measure the quantities of retained gadolinium in human [19,58,59] and rodent tissues [47,60]. Potential risk factors with effect on Gd retention described are ongoing neuroinflammation [60] or primary gliomas [59]. Additionally, any type of inflammation can negatively influence the blood brain barrier permeability [61] and therefore could be potential risk factor for gadolinium retention.…”

Nanotechnology‐Based Strategies for Early Diagnosis of Central Nervous System Disorders

“…[80] Copyright 2018, Wiley-VCH Verlag. 1,4,7-triazacyclononane-N,N 0 ,N 00 -triacetic acid (NOTA)-modified truncated evans blue (NEB) coordinated with manganese ion (MnNEB) and conjugating with bovine serum albumin (Mn-NEB þ BSA) [91] ; Gadolinium-based contrast agent (GBCA) [225] High spatial resolution Unlimited penetration Explore the 3D amideproton-transfer (APT) imaging along with rampand spin-echo information Fast magnetic resonance fingerprinting (MRF) for quantitative CEST imitates the metabolic proteins of the metastatic brain in early and the prognosis diagnosis Manganese oxide NPs [226] (MONs, such as MnO, MnO2, Mn3O4, and MnOx) MN-MPAP-Cy5.5 probe [227] Gadolinium oxide (Gd 2 O 3 ) [228] Magnetic NPs (Polymers, micelles, nanoshells, QDs, and IONPs)…”