Changes in Signal Intensity of the Dentate Nucleus and Globus Pallidus in Pediatric Patients: Impact of Brain Irradiation and Presence of Primary Brain Tumors Independent of Linear Gadolinium-based Contrast Agent Administration

Tamrazi, Benita; Nguyen, Binh; Liu, Chia-Shang J.; Azen, Colleen; Nelson, Mary Baron; Dhall, Girish; Nelson, Marvin D.

doi:10.1148/radiol.2017171850

Cited by 31 publications

(34 citation statements)

References 33 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the results of our study demonstrated concordance with the results of Tamrazi et al (20) and Kinner et al (21) with regard to changes in signal intensity on T1-weighted images secondary to treatment, there does not appear to be a relationship between dose and signal intensity changes when treatment effects are accounted for, as was seen with a linear GBCA. This suggests that macrocyclic GBCAs have potentially different retention mechanisms in brain tissue than do linear GBCAs.…”

Section: Figuresupporting

confidence: 90%

“…In our study, we found that the signal intensity in the DN on T1-weighted images was higher in children who had undergone brain irradiation than in those who had not received radiology.rsna.org n Radiology: Volume 289: Number 1-October 2018 ous study by Tamrazi et al (20), in which similar changes in pediatric patients with brain tumors with exposure to a linear GBCA were investigated, again suggesting that changes in T1-weighted signal intensity from radiation therapy exposure are independent of the type of GBCA-that is, a linear agent or, as in our current study, a macrocyclic agent. The results of our study also showed that the signal intensity on T1weighted images of the DN did not appear to have a dosedependent relationship with the gadobutrol administered.…”

Section: Discussionsupporting

confidence: 47%

“…However, our findings are discordant with those from the recent study by Bjørnerud et al (34), who reported increased signal intensity of the DN on unenhanced T1weighted images in patients with repeated administration of the macrocyclic GBCA gadobutrol. The discordance with the findings of Bjørnerud et al may be due to the fact that their study was composed entirely of patients with high-grade glioma brain tumor who had received chemotherapy and radiation therapy, a factor that has been shown to result in T1-weighted signal intensity changes independent of gadolinium administration (20,21). When we evaluated the DN-to-pons ratios of our patients who had undergone radiation therapy, our confounded results would appear to agree with those of Bjørnerud et al, with an apparent dose-dependent relationship of the DN-topons ratio when the results of all of the treatment groups are pooled.…”

Section: Figurementioning

confidence: 62%

See 2 more Smart Citations

Brain Irradiation and Gadobutrol Administration in Pediatric Patients with Brain Tumors: Effect on MRI Brain Signal Intensity

et al. 2018

Self Cite

View full text Add to dashboard Cite

Purpose To determine whether treatment affects MRI signal intensity in pediatric patients with primary brain tumors independent of the administration of macrocyclic gadolinium-based contrast agents (GBCAs). Materials and Methods This retrospective, single-center study included 78 patients (mean age, 7.7 years ± 5.4) with primary brain tumors who underwent macrocyclic GBCA-enhanced MRI from 2015 to 2018. Three groups were compared: (a) patients who had undergone radiation therapy (37 patients, 26 of whom had undergone concurrent chemotherapy), (b) patients who had undergone chemotherapy only (17 patients), and (c) patients who had received no treatment ("no-treatment group," 24 patients). The signal intensity in the globus pallidus (GP), thalamus, dentate nucleus (DN), and pons was measured on unenhanced T1-weighted images. GP-to-thalamus and DN-to-pons signal intensity ratios were compared among groups with analysis of variance by using the Kruskal-Wallis test, followed by post hoc pairwise tests with Tukey adjustment, and were analyzed relative to group, total cumulative doses of GBCA, age, and sex with multivariable linear models. Results The mean number of GBCA-enhanced MRI examinations in the radiation therapy, chemotherapy-only, and no-treatment groups was 7.11, 7.29, and 4.96, respectively (P < .01 for the radiation therapy and chemotherapy groups compared with the no-treatment group). The DN-to-pons ratio in the radiation therapy group was higher than that in both the no-treatment group and the chemotherapy-only group (P < .01 for both). There was no significant difference in the DN-to-pons ratios between the chemotherapy-only group and the no-treatment group (P = .99). The GP-to-thalamus ratios did not differ among all three groups (P = .09). There was no dose-dependent effect of GBCA on the DN-to-pons and GP-to-thalamus ratios when adjusting for the effects of treatment (P = .21 and P = .38, respectively). Conclusion Brain irradiation contributes to a higher dentate nucleus signal intensity in pediatric patients with brain tumor independent of the administration of macrocyclic gadolinium-based contrast agents. © RSNA, 2018.

show abstract

Section: Figuresupporting

confidence: 90%

Section: Discussionsupporting

confidence: 47%

Section: Figurementioning

confidence: 62%

See 1 more Smart Citation

Brain Irradiation and Gadobutrol Administration in Pediatric Patients with Brain Tumors: Effect on MRI Brain Signal Intensity

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Skin lesions associated with GBCA administration have been reported both in animal models and in human subjects is no explicit evidence of gadolinium directly transgressing the intact BBB. The mechanisms of transit across the blood-CSF barrier, retention in neural tissues, potential role of concomitant radiation or chemotherapy (94,95), and clearance via the glymphatic tissues are currently poorly understood.…”

Section: Retention Of Gadolinium In Non-cns Tissuesmentioning

confidence: 99%

Gadolinium Retention: A Research Roadmap from the 2018 NIH/ACR/RSNA Workshop on Gadolinium Chelates

et al. 2018

View full text Add to dashboard Cite

Gadolinium-based contrast agents (GBCAs) have revolutionized MRI, enabling physicians to obtain crucial life-saving medical information that often cannot be obtained with other imaging modalities. Since initial approval in 1988, over 450 million intravenous GBCA doses have been administered worldwide, with an extremely favorable pharmacologic safety profile; however, recent information has raised new concerns over the safety of GBCAs. Mounting evidence has shown there is long-term retention of gadolinium in human tissues. Further, a small subset of patients have attributed a constellation of symptoms to GBCA exposure, although the association of these symptoms with GBCA administration or gadolinium retention has not been proven by scientific investigation. Despite evidence that macrocyclic GBCAs show less gadolinium retention than linear GBCAs, the safety implications of gadolinium retention are unknown. The mechanism and chemical forms of gadolinium retention, as well as the biologic activity and clinical importance of these retained gadolinium species, remain poorly understood and underscore the need for additional research. In February 2018, an international meeting was held in Bethesda, Md, at the National Institutes of Health to discuss the current literature and knowledge gaps about gadolinium retention, to prioritize future research initiatives to better understand this phenomenon, and to foster collaborative standardized studies. The greatest priorities are to determine (a) if gadolinium retention adversely affects the function of human tissues, (b) if retention is causally associated with short- or long-term clinical manifestations of disease, and (c) if vulnerable populations, such as children, are at greater risk for experiencing clinical disease. The purpose of the research roadmap is to highlight important information that is not known and to identify and prioritize needed research. ©RSNA, 2018 Online supplemental material is available for this article .

show abstract

“…In studies that report a SI increase, it is mandatory to consider the confounders of conditions that increase the concentration of manganese in the deep gray matter (parenteral feeding, exposure to manganese, portosystemic shunt) or certain disorders associated with an increase of the SI of the basal ganglia (neurofibromatosis type I, metabolic disorders, hypoxic-ischemic encephalopathy, etc.). The influence of radiation as a confounder is still a topic under investigation [52].…”

Section: -Assess Exclusively Si Differences/changes Measured With Commentioning

confidence: 99%

Standardized assessment of the signal intensity increase on unenhanced T1-weighted images in the brain: the European Gadolinium Retention Evaluation Consortium (GREC) Task Force position statement

et al. 2018

View full text Add to dashboard Cite

After the initial report in 2014 on T1-weighted (T1w) hyperintensity of deep brain nuclei following serial injections of linear gadolinium-based contrast agents (GBCAs), a multitude of studies on the potential of the marketed GBCAs to cause T1w hyperintensity in the brain have been published. The vast majority of these studies found a signal intensity (SI) increase for linear GBCAs in the brain-first and foremost in the dentate nucleus-while no SI increase was found for macrocyclic GBCAs. However, the scientific debate about this finding is kept alive by the fact that SI differences do not unequivocally represent the amount of gadolinium retained. Since the study design of the SI measurement in various brain structures is relatively simple, MRI studies investigating gadolinium-dependent T1w hyperintensity are currently conducted at multiple institutions worldwide. However, methodological mistakes may result in flawed conclusions. In this position statement, we assess the methodological basis of the published retrospective studies and define quality standards for future studies to give guidance to the scientific community and to help identify studies with potentially flawed methodology and misleading results. Key Points • A multitude of studies has been published on the potential of the marketed GBCAs to cause T1w hyperintensity in the brain.• The gadolinium-dependent T1w hyperintensity in the brain depends on patient's history, types of GBCAs used (i.e., linear vs.macrocyclic GBCAs) and MR imaging setup and protocols. • Quality standards for the design of future studies are needed to standardize methodology and avoid potentially misleading results from retrospective studies.

show abstract

Changes in Signal Intensity of the Dentate Nucleus and Globus Pallidus in Pediatric Patients: Impact of Brain Irradiation and Presence of Primary Brain Tumors Independent of Linear Gadolinium-based Contrast Agent Administration

Cited by 31 publications

References 33 publications

Brain Irradiation and Gadobutrol Administration in Pediatric Patients with Brain Tumors: Effect on MRI Brain Signal Intensity

Brain Irradiation and Gadobutrol Administration in Pediatric Patients with Brain Tumors: Effect on MRI Brain Signal Intensity

Gadolinium Retention: A Research Roadmap from the 2018 NIH/ACR/RSNA Workshop on Gadolinium Chelates

Standardized assessment of the signal intensity increase on unenhanced T1-weighted images in the brain: the European Gadolinium Retention Evaluation Consortium (GREC) Task Force position statement

Contact Info

Product

Resources

About