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      Gadolinium-based Contrast Agent Accumulates in the Brain Even in Subjects without Severe Renal Dysfunction: Evaluation of Autopsy Brain Specimens with Inductively Coupled Plasma Mass Spectroscopy

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          Abstract

          To use inductively coupled plasma mass spectroscopy (ICP-MS) to evaluate gadolinium accumulation in brain tissues, including the dentate nucleus (DN) and globus pallidus (GP), in subjects who received a gadolinium-based contrast agent (GBCA).

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          Most cited references14

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          High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material.

          To explore any correlation between the number of previous gadolinium-based contrast material administrations and high signal intensity (SI) in the dentate nucleus and globus pallidus on unenhanced T1-weighted magnetic resonance (MR) images. The institutional review board approved this study, waiving the requirement to obtain written informed consent. A group of 381 consecutive patients who had undergone brain MR imaging was identified for cross-sectional analysis. For longitudinal analysis, 19 patients who had undergone at least six contrast-enhanced examinations were compared with 16 patients who had undergone at least six unenhanced examinations. The mean SIs of the dentate nucleus, pons, globus pallidus, and thalamus were measured on unenhanced T1-weighted images. The dentate nucleus-to-pons SI ratio was calculated by dividing the SI in the dentate nucleus by that in the pons, and the globus pallidus-to-thalamus SI ratio was calculated by dividing the SI in the globus pallidus by that in the thalamus. Stepwise regression analysis was undertaken in the consecutive patient group to detect any relationship between the dentate nucleus-to-pons or globus pallidus-to-thalamus SI ratio and previous gadolinium-based contrast material administration or other factors. A random coefficient model was used to evaluate for longitudinal analysis. The dentate nucleus-to-pons SI ratio showed a significant correlation with the number of previous gadolinium-based contrast material administrations (P < .001; regression coefficient, 0.010; 95% confidence interval [CI]: 0.009, 0.011; standardized regression coefficient, 0.695). The globus pallidus-to-thalamus SI ratio showed a significant correlation with the number of previous gadolinium-based contrast material administrations (P < .001; regression coefficient, 0.004; 95% CI: 0.002, 0.006; standardized regression coefficient, 0.288), radiation therapy (P = .009; regression coefficient, -0.014; 95% CI: -0.025, -0.004; standardized regression coefficient, -0.151), and liver function (P = .031; regression coefficient, 0.023; 95% CI: 0.002, 0.044; standardized regression coefficient, 0.107). The dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios in patients who had undergone contrast-enhanced examinations were significantly greater than those of patients who had undergone unenhanced examinations (P < .001 for both). High SI in the dentate nucleus and globus pallidus on unenhanced T1-weighted images may be a consequence of the number of previous gadolinium-based contrast material administrations. RSNA, 2013
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            Progressive increase of T1 signal intensity of the dentate nucleus on unenhanced magnetic resonance images is associated with cumulative doses of intravenously administered gadodiamide in patients with normal renal function, suggesting dechelation.

            The purpose of this study was to assess the association between the serial number of gadolinium-enhanced magnetic resonance imaging (MRI) examinations and the signal hyperintensity of the dentate nucleus on unenhanced T1-weighted images in patients with multiple sclerosis (MS) and those with brain metastases (BMs).
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              Comparison of Gd(DTPA-BMA) (Omniscan) versus Gd(HP-DO3A) (ProHance) relative to gadolinium retention in human bone tissue by inductively coupled plasma mass spectroscopy.

              The objective of this study was to determine the gadolinium (Gd) concentration remaining in human bone tissue after administration of standard clinical doses of 2 Gd-based contrast agents: ProHance and Omniscan. After administration of 0.1 mmol/kg of Gd chelate to patients undergoing hip replacement surgery, bone specimens were collected and analyzed, and compared with an age-matched control population without a history of Gd chelate administration. Bone specimens were collected fresh, refrigerated, and subsequently frozen. After grinding and freeze-drying, tissue digestion was performed using Teflon bombs and concentrated nitric acid. A method for analysis of Gd in bone specimens was developed and validated using inductively coupled plasma mass spectroscopy (ICP-MS). Results were compared with a previous study using a different technique for analysis of the same tissue specimens. Tissue retention was 1.77+/-0.704 microg Gd/g bone (n=9) for Omniscan and 0.477+/-0.271 microg Gd/g bone (n=10) for ProHance measured by ICP-MS. These findings confirmed results from the previous ICP-AES study. Omniscan (Gd[DTPA-BMA]) left approximately 4 times (previous study 2.5 times) more Gd behind in bone than did ProHance (Gd[HP-DO3A]).
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                Author and article information

                Journal
                Radiology
                Radiology
                Radiological Society of North America (RSNA)
                0033-8419
                1527-1315
                July 2015
                July 2015
                : 276
                : 1
                : 228-232
                Article
                10.1148/radiol.2015142690
                25942417
                b90ba86d-b361-4841-977d-c12c84d9cb9d
                © 2015
                History

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