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The Journal of Clinical Investigation Mar 2013The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates...
The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain.
Topics: Alzheimer Disease; Animals; Brain; Cluster Analysis; Contrast Media; Extracellular Fluid; Extravasation of Diagnostic and Therapeutic Materials; Female; Gadolinium DTPA; Humans; Injections, Spinal; Magnetic Resonance Imaging; Neuroimaging; Rats; Rats, Sprague-Dawley; Tissue Distribution
PubMed: 23434588
DOI: 10.1172/JCI67677 -
AJNR. American Journal of Neuroradiology Jul 2018
Topics: Animals; Crush Injuries; Gadolinium DTPA; Rats; Sciatic Nerve
PubMed: 29700050
DOI: 10.3174/ajnr.A5661 -
Investigative Radiology Oct 2022Using a murine model of multiple sclerosis, we previously showed that repeated administration of gadopentetate dimeglumine led to retention of gadolinium (Gd) within...
OBJECTIVES
Using a murine model of multiple sclerosis, we previously showed that repeated administration of gadopentetate dimeglumine led to retention of gadolinium (Gd) within cerebellar structures and that this process was enhanced with inflammation. This study aimed to compare the kinetics and retention profiles of Gd in inflamed and healthy brains after application of the macrocyclic Gd-based contrast agent (GBCA) gadobutrol or the linear GBCA gadopentetate. Moreover, potential Gd-induced neurotoxicity was investigated in living hippocampal slices ex vivo.
MATERIALS AND METHODS
Mice at peak of experimental autoimmune encephalomyelitis (EAE; n = 29) and healthy control mice (HC; n = 24) were exposed to a cumulative dose of 20 mmol/kg bodyweight of either gadopentetate dimeglumine or gadobutrol (8 injections of 2.5 mmol/kg over 10 days). Magnetic resonance imaging (7 T) was performed at baseline as well as at day 1, 10, and 40 post final injection (pfi) of GBCAs. Mice were sacrificed after magnetic resonance imaging and brain and blood Gd content was assessed by laser ablation-inductively coupled plasma (ICP)-mass spectrometry (MS) and ICP-MS, respectively. In addition, using chronic organotypic hippocampal slice cultures, Gd-induced neurotoxicity was addressed in living brain tissue ex vivo, both under control or inflammatory (tumor necrosis factor α [TNF-α] at 50 ng/μL) conditions.
RESULTS
Neuroinflammation promoted a significant decrease in T1 relaxation times after multiple injections of both GBCAs as shown by quantitative T1 mapping of EAE brains compared with HC. This corresponded to higher Gd retention within the EAE brains at 1, 10, and 40 days pfi as determined by laser ablation-ICP-MS. In inflamed cerebellum, in particular in the deep cerebellar nuclei (CN), elevated Gd retention was observed until day 40 after last gadopentetate application (CN: EAE vs HC, 55.06 ± 0.16 μM vs 30.44 ± 4.43 μM). In contrast, gadobutrol application led to a rather diffuse Gd content in the inflamed brains, which strongly diminished until day 40 (CN: EAE vs HC, 0.38 ± 0.08 μM vs 0.17 ± 0.03 μM). The analysis of cytotoxic effects of both GBCAs using living brain tissue revealed an elevated cell death rate after incubation with gadopentetate but not gadobutrol at 50 mM. The cytotoxic effect due to gadopentetate increased in the presence of the inflammatory mediator TNF-α (with vs without TNF-α, 3.15% ± 1.18% vs 2.17% ± 1.14%; P = 0.0345).
CONCLUSIONS
In the EAE model, neuroinflammation promoted increased Gd retention in the brain for both GBCAs. Whereas in the inflamed brains, efficient clearance of macrocyclic gadobutrol during the investigated time period was observed, the Gd retention after application of linear gadopentetate persisted over the entire observational period. Gadopentetate but not gadubutrol appeared to be neurotoxic in an ex vivo paradigm of neuronal inflammation.
Topics: Animals; Brain; Chelating Agents; Contrast Media; Gadolinium; Gadolinium DTPA; Inflammation; Magnetic Resonance Imaging; Mice; Organometallic Compounds; Tumor Necrosis Factor-alpha
PubMed: 35467573
DOI: 10.1097/RLI.0000000000000884 -
Asian Pacific Journal of Cancer... 2014As a common and essential contrast medium at present, gadobenate dimeglumine has shown better performance than some other agents when applied to Breast Magnetic... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
As a common and essential contrast medium at present, gadobenate dimeglumine has shown better performance than some other agents when applied to Breast Magnetic Resonance Imaging Screening (Breast MRI Screening). Nevertheless, reports on the diagnostic performance of these two mediums (gadobenate dimeglumine and gadopentetate dimeglumine) are not completely consistent.
OBJECTIVE
To assess the diagnostic value of gadobenate dimeglumine and gadopentetate dimeglumine for Breast MRI Screening in patients suffering from breast cancer and to provide more convinced evidence to guide clinical practice in terms of appropriate contrast agents.
DATA SOURCES AND REVIEW METHODS
Original articles in English and Chinese published before January 2013 were selected from available databases (The Cochrane Library, PUBMED, EMBASE, Chinese Biomedical Literature Database, Chinese Scientific Journals Full-text Database, Chinese Journal Full-text). The criteria for inclusion and exclusion were based on the standard for diagnosis tests. Meta-Disc software (Version 1.4) was used for data analysis. Then, the area under curve (AUC) of SROC and the spearman rank correlation of sensitivity against (1-specificity) were calculated.
RESULTS
Total of 17 researches involving 1934 patients were included. The pooled sensitivity of gadobenate dimeglumine and gadopentetate dimeglumine were 0.99 (0.97, 1.00) and 0.93 (0.88, 1.00) respectively. The pooled specificity for these two contrast agents were 0.924 (0.902, 0.943) and 0.838 (0.817, 0.858) respectively, and the AUC of SROC curve were 0.9781 and 0.9215 respectively.
CONCLUSIONS
Gadobenate dimeglumine can be regarded as a more effective and feasible contrast medium for Breast MRI Screening. At least 5% differences in diagnostic performance are usually considered as clinically relevant.
Topics: Breast Neoplasms; Contrast Media; Early Detection of Cancer; Female; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Meglumine; Organometallic Compounds; Prognosis
PubMed: 24998534
DOI: 10.7314/apjcp.2014.15.12.5089 -
Korean Journal of Radiology Jan 2019Gadolinium-based contrast agents (GBCAs) are commonly used for enhancement in MR imaging and have long been considered safe when administered at recommended doses.... (Review)
Review
Gadolinium-based contrast agents (GBCAs) are commonly used for enhancement in MR imaging and have long been considered safe when administered at recommended doses. However, since the report that nephrogenic systemic fibrosis is linked to the use of GBCAs in subjects with severe renal diseases, accumulating evidence has suggested that GBCAs are not cleared entirely from our bodies; some GBCAs are deposited in our tissues, including the brain. GBCA deposition in the brain is mostly linked to the specific chelate structure of the GBCA: linear GBCAs were responsible for brain deposition in almost all reported studies. This review aimed to summarize the current knowledge about GBCA brain deposition and discuss its clinical implications.
Topics: Brain; Contrast Media; Gadolinium; Gadolinium DTPA; Humans; Magnetic Resonance Imaging
PubMed: 30627029
DOI: 10.3348/kjr.2018.0356 -
The Neuroradiology Journal Dec 2017Background and purpose The facial nerve is unique among cranial nerves in demonstrating normal enhancement of particular segments. The effect of varying T1 relaxivities... (Comparative Study)
Comparative Study
Background and purpose The facial nerve is unique among cranial nerves in demonstrating normal enhancement of particular segments. The effect of varying T1 relaxivities of gadolinium-based contrast agents on facial nerve enhancement is unclear. In this study, we assess differences in normal facial nerve enhancement with two different gadolinium-based contrast agents, gadobutrol and gadopentetate dimeglumine. In addition, we evaluate differences in facial nerve enhancement with spin-echo (SE) T1 versus 3D inversion recovery prepared fast spoiled gradient-echo (FSPGR) post-contrast sequences. Methods A total of 140 facial nerves in 70 individuals were evaluated (70 with gadobutrol and 70 with gadopentetate dimeglumine) by two blinded reviewers. Differences in enhancement of facial nerve segments between the two agents were analyzed. Differences in enhancement between SE T1 and FSPGR imaging were also evaluated. Results There was no significant difference in facial nerve enhancement between gadobutrol and gadopentetate dimeglumine. Enhancement was commonly observed in the geniculate, tympanic and mastoid segments (98%-100%) with either contrast agent; enhancement was less common in the labyrinthine segments (9%-14%) and lateral canalicular segment (2%-5%). There was a smaller enhancing proportion of labyrinthine and tympanic segments with FSPGR as compared to SE T1 images with gadobutrol. Conclusion There is no significant difference in overall enhancement of the facial nerve between gadobutrol and gadopentetate dimeglumine. Mild enhancement of the lateral canalicular portion of the facial nerve may be a normal finding. With FSPGR sequence, there is lesser perceived enhancement of the labyrinthine and tympanic segments of the facial nerve with gadobutrol.
Topics: Contrast Media; Facial Nerve; Female; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Male; Organometallic Compounds; Reference Values; Retrospective Studies
PubMed: 28696161
DOI: 10.1177/1971400917719714 -
NMR in Biomedicine Nov 2008MRI has long been applied to clinical medical and neurological cases for the structural assessment of tissues as well as their physiological and functional needs and... (Review)
Review
MRI has long been applied to clinical medical and neurological cases for the structural assessment of tissues as well as their physiological and functional needs and processes. These uses are at a variety of developmental stages in ophthalmology, from common use of clinical structural assessment for neuro-ophthalmology and evaluation of space-occupying lesions to the beginning stages of experimentally measuring functional activation of specific layers within the retina and measurement of physiological oxygen responses. New MRI methodologies, such as the use of orbital coils and Gd-DTPA image enhancement, have been researched, developed, and validated in the eye, opening new possibilities for this technology to enter the clinic. This review aims to summarize the clinical ophthalmological uses of MRI, focusing on the current use of the technology and future applications.
Topics: Contrast Media; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Ophthalmology
PubMed: 18384176
DOI: 10.1002/nbm.1247 -
RoFo : Fortschritte Auf Dem Gebiete Der... Jan 2018Gadoxetate disodium is an intracellular contrast agent for magnetic resonance imaging (MRI) of the liver. Recent publications revealed that injection of gadoxetate... (Review)
Review
BACKGROUND
Gadoxetate disodium is an intracellular contrast agent for magnetic resonance imaging (MRI) of the liver. Recent publications revealed that injection of gadoxetate disodium can lead to imaging artifacts due to transient severe motion (TSM) in the arterial phase of contrast-enhanced liver MRI. In this review we present and discuss published frequencies of TSM, contrast injection and image acquisition protocols, potential risk factors, and proposed strategies to avoid or minimize the effects of TSM.
METHOD
Two reviewers independently searched the PubMed search engine for "transient severe motion artifact" and related terms. Reference lists of retrieved articles were also searched. The two reviewers selected in consensus nine studies that reported both frequencies of TSM and potential risk factors. Study data were extracted by both reviewers, and disagreement was resolved by consensus.
RESULTS AND CONCLUSION
TSM is caused by impaired breath-hold ability after gadoxetate disodium injection and occurs in 5 - 22 % of patients. The dose of applied contrast agent, repeated exposure to gadoxetate disodium, high BMI and pulmonary disease have been described as potential risk factors for TSM. However, there are only few concordant results on this topic and the pathophysiology of TSM has not been identified. Proposed strategies for the prevention of TSM are slow injection rates and low doses of diluted gadoxetate disodium. Accelerated and free-breathing MRI sequence protocols and breath-hold training may minimize the effects of TSM. Further prospective studies are needed to confirm these strategies and to identify the underlying mechanism of TSM.
KEY POINTS
· TSM occurs in 5 - 22 % of patients after gadoxetate disodium injection.. · Potential risk factors of TSM are dose, repeated exposure, BMI, pulmonary disease.. · The underlying mechanism for TSM has not been identified.. · Slow injection rates and diluted gadoxetate disodium may prevent TSM.. · Accelerated image acquisition or free-breathing sequences may mitigate the effects of TSM..
CITATION FORMAT
· Well L, Weinrich JM, Adam G et al. Transient Severe Respiratory Motion Artifacts After Application of Gadoxetate Disodium: What We Currently Know. Fortschr Röntgenstr 2018; 190: 20 - 30.
Topics: Artifacts; Body Mass Index; Breath Holding; Contrast Media; Dose-Response Relationship, Drug; Gadolinium DTPA; Humans; Liver; Lung Diseases; Magnetic Resonance Imaging; Respiration; Risk Factors
PubMed: 29156475
DOI: 10.1055/s-0043-120116 -
Molecules (Basel, Switzerland) Dec 2021The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the... (Review)
Review
The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.
Topics: Animals; Chemical Phenomena; Contrast Media; Gadolinium; Gadolinium DTPA; Humans; Kinetics; Magnetic Resonance Imaging; Molecular Structure; Thermodynamics
PubMed: 35011290
DOI: 10.3390/molecules27010058 -
Journal of Magnetic Resonance Imaging :... Sep 2012To evaluate the influence of contrast agents with different relaxivity on the partition coefficient (λ) and timing of equilibration using a modified Look-Locker... (Comparative Study)
Comparative Study Randomized Controlled Trial
PURPOSE
To evaluate the influence of contrast agents with different relaxivity on the partition coefficient (λ) and timing of equilibration using a modified Look-Locker inversion recovery (MOLLI) sequence in cardiac magnetic resonance imaging (MRI).
MATERIALS AND METHODS
MOLLI was acquired in 20 healthy subjects (1.5T) at the mid-ventricular short axis precontrast and 5, 10, 20, 25, and 30 minutes after administration of a bolus of 0.15 mmol/kg gadobenate dimeglumine (Gd-BOPTA) (n = 10) or gadopentetate dimeglumine (Gd-DTPA) (n = 10). T1 times were measured in myocardium and blood pool. λ was approximated by ΔR1(myocardium) /ΔR1(blood) . Values for Gd-BOPTA and Gd-DTPA were compared. Interobserver agreement was evaluated (intraclass correlation coefficient [ICC]).
RESULTS
T1 times of myocardium and blood pool (P < 0.001) and λ (0.42 ± 0.03 and 0.47 ± 0.04, respectively, P < 0.001; excluding 5 minutes for Gd-BOPTA) were significantly lower for Gd-BOPTA than Gd-DTPA. The λ((Gd-DTPA)) showed no significant variation between 5 and 30 minutes. The λ((Gd-BOPTA)) values were significantly lower at 5 minutes compared to other times (0.38 vs. 0.42; P < 0.05). Interobserver agreement for λ values was excellent with Gd-BOPTA (ICC = 0.818) and good for Gd-DTPA (ICC = 0.631).
CONCLUSION
The λ((Gd-BOPTA)) values were significantly lower compared to λ((Gd-DTPA)) at the same administered dose. Using Gd-BOPTA, the equilibrium between myocardium and blood pool was not achieved at 5 minutes postcontrast.
Topics: Adult; Chelating Agents; Computer Simulation; Contrast Media; Gadolinium DTPA; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Meglumine; Metabolic Clearance Rate; Models, Cardiovascular; Myocardium; Organometallic Compounds; Reproducibility of Results; Sensitivity and Specificity
PubMed: 22488770
DOI: 10.1002/jmri.23651