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MRI Used to Track Neuronal Stem Cells

By MedImaging International staff writers
Posted on 18 Oct 2011
Biologists have developed a magnetic resonance imaging (MRI)-based technique that allows researchers to monitor neural stem cells noninvasively in vivo.

The recently patented technology could be used to further the study of neural stem cells and inform the development of new treatments for brain injury caused by trauma, stroke, Parkinson’s disease, and other neurologic disorders. The study, conducted by Carnegie Mellon University (Pittsburg, PA, USA), associate professor of biological sciences Dr. Eric Ahrens and biological Sciences postdoctoral student Dr. Bistra Iordanova, were published online October 2011 in the journal NeuroImage.

Scientists have long believed that once a brain cell dies, it is lost forever. Neuroscientists now know that this is purely myth, having proved that the brain is constantly producing new neurons. These neural stem cells are born deep in an area of the brain called the subventricular zone. As time goes on, the cells, also called neuroblasts, make their way to other regions of the brain where they mature into functioning neurons. The brain’s ability to regenerate its cells is of great significance to scientists.

“If we could better understand the molecular migratory signals that guide neuroblasts, we could try to redirect these cells to areas of the brain harmed by stroke or traumatic brain injury. With this information, scientists might be able to one day repair the brain,” said Dr. Ahrens, who also is a member of the Pittsburgh NMR Center for Biomedical Research.

Studying cells in a living brain is problematic. Common forms of in vivo cell imaging like fluorescence and bioluminescence rely on light to generate images, making them unsuitable for viewing neuroblasts buried deep beneath the skull and layers of opaque tissue. Until now, scientists had only been able to examine neuronal stem cells by looking at slices of the brain under a microscope. Dr. Ahrens was able to overcome this hurdle using MRI technology.

Instead of light, MRI uses magnets to create high-resolution images. A typical MRI scan uses a magnetic field and radio frequency pulses to cause the hydrogen protons found in the body’s water molecules to give off signals. Those signals are converted into a high-resolution image.

At the basis of this core is a technology Dr. Ahrens developed. As reported in a 2005 issue of the journal Nature Medicine, Dr. Ahrens devised a method that causes cells to produce their own contrast agent allowing them to be imaged with MRI. Using a viral vector, Dr. Ahrens integrated the gene that produces the naturally occurring metalloprotein ferritin into living cells. Ferritin, which is present in all biologic cells, harvests and stores naturally occurring iron. When the cells tagged with ferritin began to produce increased amounts of the protein, they draw in additional iron, turning themselves into nanomagnets. This disrupts the magnetic field surrounding the tagged cells, altering the signal given off by adjacent water molecules. This change appears as dark spots on the MRI image indicating the cells’ presence. Since then, Dr. Ahrens’ team has improved on the process, developing an engineered form of ferritin that is a more effective MRI reporter than naturally occurring ferritin.

In the current study, Drs. Iordanova and Ahrens used the same technique as in the first study, this time tagging neuroblasts with the engineered ferritin. They incorporated the DNA sequence for the modified metalloprotein into an adenovirus vector, which they then injected into the subventricular zone of a rat brain. The adenovirus infected the neural stem cells giving the cells the genetic instructions to begin producing the ferritin reporter. Dr. Iordanova then imaged the brain with MRI and found that she was able to track--in real time--the neuroblasts as they moved toward the olfactory bulb and ultimately formed new inhibitory neurons. These results mirrored what had been observed in histology studies.

Recently, Carnegie Mellon received a patent for the reporter. Dr. Ahrens hopes to continue to develop the technology in order to allow researchers to better understand neuronal stem cells and how neurons regenerate. Dr. Ahrens also plans to use the reporters to improve clinical trials of cell-based therapies. By integrating the reporter into the cells before implantation, researchers would be able to find the solution to a host of vital questions.

“Where do these cells go, days, weeks, and months later? How do we know that they’ve grafted to the right cells? Or have they grafted in the wrong place? Or died?” Dr. Ahrens asked. “The reporter can show us the answers.”

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87 (86.069107055664): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294737634 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
88 (29.802322387695): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294737634 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
89 (31.948089599609): 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 (54.121017456055): SELECT show_live FROM jos_com_show_setting LIMIT 1
91 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (31.948089599609): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (97.036361694336): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
105 (56.028366088867): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
106 (64.13459777832): 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=294737634 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (59.843063354492): 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=294737634 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (78.916549682617): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
109 (57.220458984375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
110 (62.942504882812): 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=294737634 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (633.95500183105): 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=294737634 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (509.02366638184): 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 (332.11708068848): 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 (72.002410888672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
115 (48.160552978516): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
116 (82.015991210938): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
117 (41.961669921875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
118 (64.849853515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
119 (66.041946411133): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
120 (42.915344238281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
121 (37.908554077148): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
122 (246.04797363281): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 56016.206741333): 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 (658.03527832031): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294737634 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294737634 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 23247.957229614): ( 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 (200.03318786621): ( 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 (368.83354187012): 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 (931.0245513916): 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 (!!!!! 1175.1651763916): 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 (51.021575927734): 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 (459.90943908691): 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 (82.015991210938): 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 (44.822692871094): 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 (31.948089599609): 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 (!!!!! 3134.9658966064): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (597.95379638672): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (77.962875366211): SELECT name FROM jos_deeppockets WHERE id=212
138 (45.061111450195): SELECT name FROM jos_deeppockets WHERE id=212
139 (849.96223449707): 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((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (566.00570678711): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (!!!!! 5294.0845489502): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
142 (71.048736572266): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
143 (!!!!! 17712.116241455): TRUNCATE TABLE jos_trademed_module
144 (!!!!! 5454.0634155273): 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=294737634 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (!!!!! 1219.0341949463): 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=294737634 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (479.22134399414): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (87.976455688477): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (118.97087097168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
149 (62.942504882812): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
150 (!!!!! 1384.0198516846): 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 (81.062316894531): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
152 (68.902969360352): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
153 (681.87713623047): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294737634 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294737634 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (61.03515625): 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 (40.054321289062): 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 (68.187713623047): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (244.140625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
158 (94.890594482422): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737634 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737634 AND published='1' LIMIT 1
159 (!!!!! 2324.8195648193): select jos_twitters.link from jos_twitters where cat=10
160 (85.115432739258): select jos_facebook.link from jos_facebook where cat=10
161 (49.114227294922): select jos_google_plus.link from jos_google_plus where cat=10
162 (72.956085205078): select jos_linkedin.link from jos_linkedin where cat=10
163 (439.16702270508): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)
164 (!!!!! 9296.8940734863): insert into jos_banners_delta values (14615,'2025-06-26 19:44:08','216.73.216.249','view'),(14202,'2025-06-26 19:44:08','216.73.216.249','view'),(14203,'2025-06-26 19:44:08','216.73.216.249','view')