Elsevier

Magnetic Resonance Imaging

Volume 34, Issue 10, December 2016, Pages 1355-1358
Magnetic Resonance Imaging

MRI Finding
Technical aspects of MRI signal change quantification after gadolinium-based contrast agents' administration

https://doi.org/10.1016/j.mri.2016.09.004Get rights and content

Abstract

Over the last 2 years several studies have been published regarding gadolinium deposition in brain structures in patients with normal renal function after repeated administrations of gadolinium-based contrast agents (GBCAs). Most of the publications are magnetic resonance imaging (MRI) based retrospective studies, where gadolinium deposition may be indirectly measured by evaluating changes in T1 signal intensity (SI) in brain tissue, particularly in the dentate nucleus (DN) and/or globus pallidi (GP). The direct correlation between T1 signal changes and gadolinium deposition was validated by human pathology studies. However, the variability of the MR equipment and parameters used across different publications, along with the inherent limitations of MRI to assess gadolinium in human tissues should be acknowledged when interpreting those studies. Nevertheless, MRI studies remain essential regarding gadolinium bio-distribution knowledge. The aim of this paper is to overview current knowledge of technical aspects of T1 signal intensity evaluation by MRI and describe confounding factors, with the intention to achieve higher accuracy and maximize reproducibility.

Introduction

In the past 2 years several magnetic imaging (MRI) studies reported high T1 signal intensity in the dentate nucleus (DN) and/or globus pallidi (GP) in patients with normal renal function after multiple administrations of gadolinium-based contrast agents (GBCAs) suggesting gadolinium deposition [1], [2], [3], [4], [5], [6], [7], [8], [9]. The agent most commonly implicated was gadodiamide (Omniscan®) a non-ionic linear agent, classified according to its stability as a weak agent [10], followed by gadopentetate dimeglumine (Magnevist®) and gadobenate dimeglumine (MultiHance®), both ionic linear agents, classified as agents with intermediate stability [10]. The more stable macrocyclic compounds: gadoteridol (ProHance®), gadoterate meglumine (Dotarem®), and gadobutrol (Gadavist®) have not been associated with substantial MR imaging changes, suggesting that the molecular structure of the GBCA, whether linear or macrocyclic, is a crucial factor for the increase in signal intensity.

Gadolinium deposition in brain tissue and its relation to T1 signal intensity changes was confirmed by histopathological human studies [10], [11], [12], [13]. However, these studies found that gadolinium deposits were present in all evaluated brain tissues (with higher concentration in DN followed by GP) after the administration of either linear or macrocyclic agents, suggesting that MRI has a relative limited sensitivity to detect gadolinium deposition in brain tissue. This limitation should have been expected, as bone deposition, which has been recognized for a decade [14], occurs at much higher levels compared to brain tissue [13], and yet is not detected by MRI. Despite limited sensitivity, MRI remains the best available tool to evaluate gadolinium deposition in basal ganglia, which appears to correlate well and proportionately with the higher deposition in bone [13].

Recent peer-reviewed papers have been published in high impact factor radiology journals and represent similar experience reported by experts from all over the world. Some critical methodological issues have not been adequately standardized in a number of these studies including the sequences used to evaluate T1 signal intensity changes overtime, whether signal measurements between sequences can be correlated, the ratios used and which are optimal, the potential effect of field strength; the reliability of excluding previous gadolinium expositions; number of doses and volume of doses administered, the diseases of subjects and possible differences of retention between different disease types, and the age range of the studied population. Thus, the aim of this review is to evaluate and recommend imaging strategies to improve data accuracy, and identify potential confounding factors in assessing gadolinium deposition in MRI-studies.

Section snippets

MRI quantification of signal changes after (GBCAs) administration: basic principles

One major limitation of MRI human studies reporting gadolinium deposition is its retrospective nature. This unavoidable study design explains in part the variability of the MR imaging protocols used, which may change according to the pathology that is being studied and among different institutions. Quantitative and qualitative analysis have been described. Quantitative signal intensity ratios are favored and recommended for scientific research; however, it is difficult to apply in clinical

Field strength and types of T1-weighted sequences

The influence of MR field strength in quantitative and qualitative evaluation of T1 signal intensity of DN or other brain structures is presently unknown. It seems reasonable to assume that signal intensity will differ between 1.5 T and 3 T, but so far no studies have addressed this question. Therefore, we suggest analyzing data obtained from different field strength scans separately, i.e., for a given patient, the first (baseline) MRI and subsequent MRIs should be performed on the same field

Quantitative ratios measurements

Different ratios have been used for quantitative measurements including DN-to-pons, DN-to-middle cerebellar peduncle, DN-to-cerebellar white matter, DN-to-CSF, DN-to-corpus callosum genu (CC), GP-to-Th, GP-to-CSF, GP-to-CC, Th-to-CC, and Caudate nucleus-to-CC [1], [2], [3], [4], [5], [6], [7], [8], [9], [17], [18], [19], [20]. In a study with healthy volunteers, T1 SI of DN, pons, GP, white matter, and gray matter were all evaluated and normalized with CSF [21].

Up to the present time, no

GBCA related concerns

Essentially all reported studies describe the number of GBCA administrations in order to evaluate the increased T1 signal over time. Some authors suggested that 6 or more contrast enhanced MRI were needed to evaluate T1 signal changes over time [1], [2], while others evaluate the effect of only one high dose GBCA [21]. Provided that the number of doses were all accounted for, including brain and other contrast enhanced MRI, the critical factor is that only one GBCA should be evaluated for each

Population variability

Population demographics and diagnosis vary among studies. Some critical inclusion and exclusion criteria have been used to define the investigated patient populations. First, patients with brain lesions in the deep cerebellar nuclei unrelated to GBCA administration were excluded from analysis. In addition, patient populations were controlled for pre-existing diseases that are known to affect SI in the dentate nucleus or globus pallidus such as Langerhans cell histiocytosis and multiple

MRI limitations

As stated above, MRI does not detect all the gadolinium deposits present in human tissues following repeated administration of GBCA. To date, bone deposition, which is likely the largest repository for gadolinium, is not demonstrable with MRI, and only the DN and GP exhibit MR visible deposition in the brain despite the gadolinium presence in essentially all brain tissue. This limitation may result from low sensitivity to lower gadolinium concentration, but it could also be explained by the

Summary

In most MRI studies evaluating potential gadolinium deposition in brain tissue, researchers evaluated the SI ratios between the DN and GP compared to control regions, usually the pons and thalamus, respectively. Retrospective in nature, the analyses were performed on whichever T1-weighted MRI sequences that were performed at each institution including T1 SE, 3D MPRAGE, FLAIR, and FLASH; which account for an undesirable variability among the results. The amount and type of GBCA used in each

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