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Link Between Brain Abnormalities and Gadolinium-Based Contrast Agent

By MedImaging International staff writers
Posted on 08 Jan 2014
Image: A new study raises the possibility that a toxic component of the contrast agent may remain in the body long after administration (Photo courtesy of Radiology).
Image: A new study raises the possibility that a toxic component of the contrast agent may remain in the body long after administration (Photo courtesy of Radiology).
Researchers for the first time have confirmed an association between a common magnetic resonance imaging (MRI) contrast agent and abnormalities seen on brain MRI scans.

The new findings were published online December 2013 in the journal Radiology, and reveals the possibility that a toxic component of the contrast agent may stay in the body a long time after administration.

Brain MRI scans are frequently performed with a gadolinium-based contrast medium (Gd-CM). Gadolinium’s paramagnetic properties make it useful for MRI scanning, however, because of the toxicity of the gadolinium ion, it must be chemically bonded with nonmetal ions so that it can be moved through the kidneys and out of the body before the ion is released in tissue. Gd-CM is believed to be safe in patients with normal kidney function.

However, in recently, Japanese clinicians noticed that patients with a history of multiple administrations of Gd-CM showed areas of high intensity (hyperintensity) on MRI in two brain areas: the dentate nucleus (DN) and globus pallidus (GP). The specific clinical implications of hyperintensity are not known, but hyperintensity in the DN has been linked with multiple sclerosis, while hyperintensity of the GP is associated with hepatic dysfunction and several disorders.

The investigators compared unenhanced T1-weighted MR images (T1WI) of 19 patients who had undergone six or more contrast-enhanced MR brain scanning with 16 patients who had received six or fewer unenhanced scans. The hyperintensity of both the DN and the GP correlated with the number of Gd-CM administrations.

“Hyperintensity in the DN and GP on unenhanced MRI may be a consequence of the number of previous Gd-CM administrations,” said lead author Tomonori Kanda, MD, PhD, from Teikyo University School of Medicine (Tokyo, Japan) and the Hyogo Cancer Center (Akashi, Japan). “Because gadolinium has a high signal intensity in the body, our data may suggest that the toxic gadolinium component remains in the body even in patients with normal renal function.”

Dr. Kanda noted that because patients with multiple sclerosis tend to undergo numerous contrast-enhanced brain MRI scans, the hyperintensity of the DN seen in these patients may have more to do with the large cumulative gadolinium dose than the disease itself.

The processes by which Gd-CM administration causes hyperintensity of the DN and GP remain not known, according to Dr. Kanda. Earlier research on animals and humans has demonstrated that the ion can be kept in bone and tissue for several days or longer after administration. “The hyperintensity of DN and GP on unenhanced T1WI may be due to gadolinium deposition in the brain independent of renal function, and the deposition may remain in the brain for a long time,” Dr. Kanda suggested.

Dr. Kanda emphasized that there is currently no evidence that gadolinium is responsible for hyperintensity on brain MRI scans. Additional studies gleaned from autopsy specimens and animal experiments will be needed to illuminate the relationship and determine if the patients with MRI hyperintensity in their brains have symptoms. “Because patients who have multiple contrast material injections tend to have severe diseases, a slight symptom from the gadolinium ion may be obscured,” Dr. Kanda said.

There are two types of Gd-CM, macrocyclic and linear, with distinct chemical configurations. Because the patients in the study received only the linear type, additional research is needed to see if the macrocyclic type can prevent MRI hyperintensity, according to Dr. Kanda.

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Teikyo University School of Medicine


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88 (31.948089599609): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294750040 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
89 (36.001205444336): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`
90 (51.021575927734): SELECT show_live FROM jos_com_show_setting LIMIT 1
91 (29.802322387695): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (33.855438232422): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (66.041946411133): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
105 (108.95729064941): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
106 (55.074691772461): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294750040 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (47.922134399414): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294750040 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (72.002410888672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
109 (41.007995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
110 (45.061111450195): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294750040 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (477.07557678223): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294750040 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (523.09036254883): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
113 (315.18936157227): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
114 (72.956085205078): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
115 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
116 (50.067901611328): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
117 (38.862228393555): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
118 (49.114227294922): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
119 (85.115432739258): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
120 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
121 (36.954879760742): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
122 (292.06275939941): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 20750.999450684): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
124 (567.91305541992): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294750040 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294750040 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 7406.9499969482): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
126 (66.041946411133): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
127 (296.11587524414): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
128 (39.815902709961): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
129 (249.14741516113): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
130 (34.809112548828): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
131 (210.04676818848): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
132 (36.954879760742): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
133 (201.94053649902): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
134 (34.093856811523): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
135 (439.88227844238): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (319.9577331543): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (190.97328186035): SELECT name FROM jos_deeppockets WHERE id=212
138 (30.994415283203): SELECT name FROM jos_deeppockets WHERE id=212
139 (556.94580078125): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (482.08236694336): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
142 (42.915344238281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
143 (!!!!! 7245.0637817383): TRUNCATE TABLE jos_trademed_module
144 (97.990036010742): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294750040 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (80.82389831543): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294750040 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (907.89794921875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (55.074691772461): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (64.13459777832): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
149 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
150 (!!!!! 1084.0892791748): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
151 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
152 (60.081481933594): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
153 (41.007995605469): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294750040 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294750040 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (35.04753112793): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)
155 (32.186508178711): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)
156 (34.093856811523): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (144.00482177734): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
158 (54.121017456055): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294750040 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294750040 AND published='1' LIMIT 1
159 (136.13700866699): select jos_twitters.link from jos_twitters where cat=10
160 (30.040740966797): select jos_facebook.link from jos_facebook where cat=10
161 (26.941299438477): select jos_google_plus.link from jos_google_plus where cat=10
162 (29.087066650391): select jos_linkedin.link from jos_linkedin where cat=10
163 (242.94853210449): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)
164 (948.90594482422): insert into jos_banners_delta values (14615,'2025-06-24 09:35:22','216.73.216.120','view'),(14202,'2025-06-24 09:35:22','216.73.216.120','view'),(14203,'2025-06-24 09:35:22','216.73.216.120','view')