Gadolinium Deposition in the Brain: Current Updates

Choi, Jin Woo; Moon, Won-Jin

doi:10.3348/kjr.2018.0356

Cited by 139 publications

(124 citation statements)

References 102 publications

(224 reference statements)

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“…Most preclinical studies also fail to acknowledge the delay between the identification of symptoms of stroke and the start of treatment, which is typically a couple of hours for most stroke patients. Also concerning the post-stroke assessment of BBB integrity as well as in other conditions where the integrity of the barrier might be compromised, gadolinium-based studies of microvascular integrity performed have shown limited sensitivity to detect low levels of extravasations across the BBB [69]. The facts discussed above highlight the urgent need to utilize technology that would better represent the disease conditions in humans.…”

Section: Strokementioning

confidence: 99%

In vitro modeling of the neurovascular unit: advances in the field

Bhalerao

Sivandzade

Archie

et al. 2020

Fluids Barriers CNS

115

103

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The blood-brain barrier (BBB) is a fundamental component of the central nervous system. Its functional and structural integrity is vital in maintaining the homeostasis of the brain microenvironment. On the other hand, the BBB is also a major hindering obstacle for the delivery of effective therapies to treat disorders of the Central Nervous System (CNS). Over time, various model systems have been established to simulate the complexities of the BBB. The development of realistic in vitro BBB models that accurately mimic the physiological characteristics of the brain microcapillaries in situ is of fundamental importance not only in CNS drug discovery but also in translational research. Successful modeling of the Neurovascular Unit (NVU) would provide an invaluable tool that would aid in dissecting out the pathological factors, mechanisms of action, and corresponding targets prodromal to the onset of CNS disorders. The field of BBB in vitro modeling has seen many fundamental changes in the last few years with the introduction of novel tools and methods to improve existing models and enable new ones. The development of CNS organoids, organ-on-chip, spheroids, 3D printed microfluidics, and other innovative technologies have the potential to advance the field of BBB and NVU modeling. Therefore, in this review, summarize the advances and progress in the design and application of functional in vitro BBB platforms with a focus on rapidly advancing technologies.The BBB consists of highly specialized vascular endothelial cells (EC) lining the brain microvessels in juxtaposition with closely associated pericytes [1], extracellular matrix components, and astrocytic end-feet processes [2]. Along with other cells such as neurons and microglia, this cellular milieu modulates the BBB properties, supports its viability and functions [3]. At the brain microvascular level, the BBB functions as a highly dynamic and active interface between the systemic circulation and the CNS. The BBB maintains a stable brain environment to protect the CNS from unsolicited cells, bacteria, viruses, and potentially harmful substances (either endogenous or exogenous) apart from protecting against systemic fluctuations. The BBB also regulates the transport of essential molecules and nutrients necessary to maintain the optimal CNS environment and support neuronal activities [4]. The BBB responds to many physiological and pathological cues, including rheological changes [5], inflammatory stimuli, oxidative stress [6], diabetes, and hypercholesterolemia [7-10], acute brain injury [3], etc. The intrinsically unique and utmost complex functional interaction between the BBB endothelium and the surrounding cellular milieu (including astrocytes, pericytes, neurons, microglia, myocytes as well as specialized cellular compartments such as endothelial glycocalyx [11,12] has been termed "neurovascular unit (NVU)" [2,13]. In addition, the basement membrane, which exerts essential functions in cellular support and signal transduction,

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Section: Strokementioning

confidence: 99%

In vitro modeling of the neurovascular unit: advances in the field

Bhalerao

Sivandzade

Archie

et al. 2020

Fluids Barriers CNS

115

103

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“…Particularly, the concern emerges by the presence of gadolinium in the brain of patients that received repeated administration of chelated gadolinium contrast agents for MRI . The dechelation of free Gd(III) ions from unstable contrast agents is considered the main cause for the observed accumulation . Also, it was reported a relation between the onset of nephrogenic systemic fibrosis (NSF) and the administration of gadolinium contrast agents in patients suffering from severe renal disease .…”

Section: In Vitro and Animal Model Safety Assessmentsmentioning

confidence: 99%

Gadolinium‐containing carbon nanomaterials for magnetic resonance imaging: Trends and challenges

Rodríguez-Galván

Rivera

Garcı́a-López

et al. 2020

J Cellular Molecular Medi

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Gadolinium-containing carbon nanomaterials are a new class of contrast agent for magnetic resonance imaging. They are characterized by a superior proton relaxivity to any current commercial gadolinium contrast agent and offer the possibility to design multifunctional contrasts. Intense efforts have been made to develop these nanomaterials because of their potential for better results than the available gadolinium contrast agents. The aim of the present work is to provide a review of the advances in research on gadolinium-containing carbon nanomaterials and their advantages over conventional gadolinium contrast agents. Due to their enhanced proton relaxivity, they can provide a reliable imaging contrast for cells, tissues or organs with much smaller doses than currently used in clinical practice, thus leading to reduced toxicity (as shown by cytotoxicity and biodistribution studies). Their active targeting capability allows for improved MRI of molecular or cellular targets, overcoming the limited labelling capability of available contrast agents (restricted to physiological irregularities during pathological conditions). Their potential of multifunctionality encompasses multimodal imaging and the combination of imaging and therapy. K E Y W O R D S biodistribution, carbon nanomaterials, cell labelling, gadolinium contrast agent, magnetic resonance imaging, multifunctional contrast agent, toxicity

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“…In musculoskeletal applications, CEUS represents a complementary investigative approach, which offers certain advantages in comparison to conventionally used diagnostic instruments such as DCE-MRI or DCE-CT. 34 Contrary to MRI, CT and X-ray examinations, the costeffective CEUS can be safely used in patients with renal impairment, without ionizing radiation or deposition of contrast agents in human body and fear of claustrophobia. 15,[35][36][37] Considering, among other things, the resolution and frame rate of CEUS, whose detail accuracy is superior to conventional MRI, CEUS may soon be able to support other time-consuming and cost-intensive medical investigations for various indications. 36…”

Section: Discussionmentioning

confidence: 99%

<p>Safety Profile of Musculoskeletal Contrast-Enhanced Ultrasound with Sulfur Hexafluoride Contrast Agent</p>

Fischer¹,

Kamtchouing²,

Strauch³

et al. 2020

TCRM

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These authors contributed equally to this workPurpose: Muscle, bone and tendon regeneration depend on the microperfusion of the corresponding tissue which can be quantified with contrast-enhanced ultrasound (CEUS) using sulfur hexafluoride contrast agent (SonoVue ® ). This study investigated the incidence of adverse events (AEs) in musculoskeletal patients and gives an overview of musculoskeletal CEUS applications. Patients and Methods: Based on 13 studies in a standardized monocentric setting, a total of 2268 CEUS examinations in 764 patients were performed and AEs due to the administration of sulfur hexafluoride contrast agent were classified as either mild, moderate or severe. Results: No fatal events occurred. AEs were reported in three cases, of which only one was classified as severe and two as mild. The total rate of all AEs was 0.13% and 0.04% for severe AEs. Conclusion: The present analysis confirms the safety of musculoskeletal CEUS using sulfur hexafluoride contrast agent with a lower rate of AEs than that reported for other contrast agents even in elderly patients with concomitant diseases.

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Gadolinium Deposition in the Brain: Current Updates

Cited by 139 publications

References 102 publications

In vitro modeling of the neurovascular unit: advances in the field

In vitro modeling of the neurovascular unit: advances in the field

Gadolinium‐containing carbon nanomaterials for magnetic resonance imaging: Trends and challenges

<p>Safety Profile of Musculoskeletal Contrast-Enhanced Ultrasound with Sulfur Hexafluoride Contrast Agent</p>

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