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MRI Sensor Provides Molecular View of the Brain

By MedImaging International staff writers
Posted on 02 Apr 2010
Neuroscientists have designed a new magnetic resonance imaging (MRI) sensor that responds to the neurotransmitter dopamine, an accomplishment that may significantly improve the specificity and resolution of future brain imaging procedures.

Although functional magnetic resonance imaging (fMRI) has enhanced the understanding of brain function since it was first introduced about 20 years ago, the technology in fact measures blood flow, which is a slow and indirect readout of neural activity. When a brain region becomes active, blood vessels in that region dilate, causing increased blood flow to the site. Iron found in the blood's hemoglobin mediates a magnetic change that is detected by MRI.

But MRI sensors that directly and rapidly respond to chemicals involved in the brain's data processing would provide a much more precise measurement of brain activity. This technology has not been available until now. "We have designed an artificial molecular probe that changes its magnetic properties in response to the neurotransmitter dopamine,” explained Dr. Alan Jasanoff, an associate professor of biological engineering at the Massachusetts of Technology (MIT; Cambridge, MA, USAu) and senior author of the article describing the study, published February 28, 2010, is the journal Nature Biotechnology. "This new tool connects molecular phenomena in the nervous system with whole-brain imaging techniques, allowing us to probe very precise processes and relate them to the overall function of the brain and of the organism. With molecular fMRI, we can say something much more specific about the brain's activity and circuitry than we could using conventional blood-related fMRI.”

Measuring dopamine in the living brain is of particular interest to neuroscientists because this neurotransmitter plays a role in motivation, reward, addiction, and several neurodegenerative conditions, including Parkinson's disease. To design a molecular probe that binds to dopamine, Dr. Jasanoff''s group, in collaboration with MIT Institute Prof. Robert Langer and the laboratory of Frances Arnold at the California Institute of Technology (Caltech; Pasadena, USA), borrowed an evolutionary gimmick. Beginning with a magnetically active protein similar to hemoglobin, the researchers demonstrated that it could be visualized by MRI, and then "evolved” the protein--through rounds of artificial mutation and selection--to bind specifically to dopamine.

"By harnessing the power of protein engineering we now have the ability to advance neuroscience through more precise noninvasive imaging of the brain,” said Dr. Mikhail Shapiro, joint first author of the study and a former graduate student supervised by Dr. Jasanoff and Prof. Langer. Dr. Shapiro devised the directed evolution approach used to make MRI sensors in the study.

After validating that the protein responded to dopamine produced by cells in test tubes, the researchers tested whether it could detect dopamine in the living brain. They found a change in the MRI intensity precisely when they artificially triggered dopamine release in the presence of the sensor. "This means that we can see signal changes in the brain due to the modulation of dopamine,” explained Dr. Gil Westmeyer, joint first author of the study and a postdoctoral fellow in Dr. Jasanoff's lab who directed the in vivo research. "This novel MRI sensor will enable us to study the spatial and temporal patterns of dopamine transmission over the vast and heterogeneous dopamine network in the brain.”

Dr. Jasanoff's team will now use the new MRI sensor to study how the spatial and temporal patterns of dopamine release relate to an animal's experience of reward, learning, and reinforcement. They hope to develop a related suite of new tools to detect different molecular events across the whole brain, and they expect to see additional gains in sensitivity through improved experimental paradigms and further molecular engineering.

While synthetic molecules are typically introduced into the brain with external devices, Dr. Jasanoff's new sensor is based on a protein, which means that researchers may also have the ability to encode genetically the sensor to express on its own. The new dopamine sensor is an important tool for animal research, but the researchers also hope one day to develop agents that can measure neural activity in the human brain.

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89 (33.140182495117): 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 (56.982040405273): SELECT show_live FROM jos_com_show_setting LIMIT 1
91 (29.802322387695): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (26.941299438477): 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 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (33.140182495117): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (37.193298339844): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (82.015991210938): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
105 (43.869018554688): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
106 (51.975250244141): 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=294728764 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (59.127807617188): 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=294728764 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (66.995620727539): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
109 (42.915344238281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
110 (49.114227294922): 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=294728764 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (531.91184997559): 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=294728764 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (546.93222045898): 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 (348.09112548828): 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 (78.916549682617): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
115 (53.167343139648): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
116 (51.021575927734): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
117 (39.100646972656): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
118 (46.014785766602): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
119 (35.04753112793): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
120 (41.007995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
121 (47.922134399414): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
122 (299.93057250977): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 37765.026092529): 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 (460.86311340332): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294728764 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294728764 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 21208.047866821): ( 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 (!!!!! 1781.9404602051): ( 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 (42.200088500977): 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 (33.140182495117): 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 (38.862228393555): 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 (30.994415283203): 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 (336.88545227051): 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 (38.862228393555): 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 (33.855438232422): 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 (40.054321289062): 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 (505.92422485352): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (405.78842163086): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (42.915344238281): SELECT name FROM jos_deeppockets WHERE id=212
138 (29.087066650391): SELECT name FROM jos_deeppockets WHERE id=212
139 (635.14709472656): 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((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (483.98971557617): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (85.115432739258): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
142 (52.928924560547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
143 (!!!!! 8476.0189056396): TRUNCATE TABLE jos_trademed_module
144 (93.936920166016): 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=294728764 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (56.982040405273): 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=294728764 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (928.16352844238): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (82.969665527344): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (66.995620727539): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
149 (41.007995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
150 (!!!!! 1177.0725250244): 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 (86.069107055664): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
152 (53.167343139648): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
153 (43.153762817383): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294728764 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294728764 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (30.040740966797): 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 (27.179718017578): 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 (33.855438232422): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (151.15737915039): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
158 (54.121017456055): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294728764 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294728764 AND published='1' LIMIT 1
159 (41.961669921875): select jos_twitters.link from jos_twitters where cat=10
160 (30.994415283203): select jos_facebook.link from jos_facebook where cat=10
161 (34.093856811523): select jos_google_plus.link from jos_google_plus where cat=10
162 (30.994415283203): select jos_linkedin.link from jos_linkedin where cat=10
163 (275.1350402832): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)
164 (!!!!! 1092.9107666016): insert into jos_banners_delta values (14615,'2025-06-28 11:35:20','216.73.216.249','view'),(14202,'2025-06-28 11:35:20','216.73.216.249','view'),(14203,'2025-06-28 11:35:20','216.73.216.249','view')