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Raman Technique Visualizes Details Almost to a Trillionth of a Meter

By MedImaging staff writers
Posted on 05 May 2008
A team of researchers has developed a new type of imaging system that can illuminate tumors in living subjects--obtaining images with a precision of nearly one-trillionth of a meter.

This technique, called Raman spectroscopy, expands the existing range of tools for the field of molecular imaging, according to team leader Sanjiv Sam Gambhir, M.D., Ph.D., professor of radiology at Stanford University School of Medicine (Stanford, CA, USA). He is the senior author of a study describing the application that was published in the March 31, 2008, advance online issue of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS).

"This is an entirely new way of imaging living subjects, not based on anything previously used,” said Dr. Gambhir, who directs the Molecular Imaging Program at Stanford. He reported that signals from Raman spectroscopy are stronger and longer lived than other available techniques, and the type of particles used in this method can transmit information about multiple types of molecular targets simultaneously. "Usually we can measure one or two things at a time,” he said. "With this, we can now likely see 10, 20, 30 things at once.

Dr. Gambhir reported that he believes this is the first time Raman spectroscopy has been used to image deep within the body, using tiny nanoparticles injected into the body to serve as beacons. When laser light is beamed from a source outside the body, these specialized particles emit signals that can be measured and translated into a visible indicator of their location in the body.

Postdoctoral scholars Shay Keren, Ph.D., and Cristina Zavaleta, Ph.D., co-first authors of the study, found a way to make Raman spectroscopy a medical application. To accomplish this, they used two types of engineered Raman nanoparticles: gold nanoparticles and single-wall carbon nanotubes. First, they injected mice with the some of the nanoparticles. To see the nanoparticles, they used a special microscope that the group had adapted to view anesthetized mice exposed to laser light. The researchers could see that the nanoparticles migrated to the liver, where they were processed for excretion.

To be able to detect molecular events, according to Dr. Zavaleta, they labeled separate batches of spectrally unique Raman nanoparticles with different "tags” (peptides or antibodies) and then injected them into the body simultaneously to see where they went. For example, if each type of particle migrated to a different tumor site, the newly developed Raman microscope would enable the researchers to separate the signals from each batch of particles.

As part of this proof-of-principle work, Dr. Gambhir's team tagged the gold nanoparticles with different bits of proteins that homed in on different tumor molecules. "We could attach pretty much anything,” said Dr. Gambhir. The Raman effect also lasts indefinitely, so the particles do not lose effectiveness as indicators as long as they stay in the body.

Using a microscope they modified to detect Raman nanoparticles, the researchers were able to visualize targets on a scale 1,000 times smaller than what is now obtainable by the most precise fluorescence imaging using quantum dots. When modified for human use, they researchers reported, the technique has the potential to be useful during surgery, for example, in the removal of cancerous tissue. The extreme sensitivity of the imager could enable detection of even the smalltest malignant tissues.

A clinical trial is planned to test the gold nanoparticles in humans for possible use in conjunction with a colonoscopy to indicate early-stage colorectal cancer.


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88 (38.14697265625): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=280370000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
89 (39.815902709961): 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 (76.055526733398): SELECT show_live FROM jos_com_show_setting LIMIT 1
91 (38.14697265625): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (33.855438232422): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (33.140182495117): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (47.922134399414): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (41.961669921875): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (99.897384643555): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
105 (59.127807617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
106 (82.969665527344): 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=280370000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (67.949295043945): 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=280370000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (102.99682617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
109 (86.069107055664): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
110 (73.909759521484): 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=280370000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (644.92225646973): 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=280370000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (866.17469787598): 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 (650.88272094727): 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 (173.09188842773): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
115 (76.055526733398): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
116 (96.08268737793): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
117 (65.803527832031): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
118 (70.095062255859): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
119 (56.028366088867): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
120 (69.856643676758): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
121 (50.067901611328): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
122 (375.98609924316): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 28427.839279175): 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 (696.18225097656): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=280370000 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=280370000 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 10334.968566895): ( 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 (181.91337585449): ( 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 (61.03515625): 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 (38.14697265625): 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 (55.074691772461): 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 (38.14697265625): 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 (385.99967956543): 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 (60.081481933594): 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 (52.928924560547): 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 (50.067901611328): 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 (555.99212646484): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (447.98851013184): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (50.067901611328): SELECT name FROM jos_deeppockets WHERE id=215
138 (37.193298339844): SELECT name FROM jos_deeppockets WHERE id=215
139 (715.97099304199): 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 '((;)|(^))215((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (694.03648376465): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))215((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (87.02278137207): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
142 (69.856643676758): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
143 (!!!!! 9588.9568328857): TRUNCATE TABLE jos_trademed_module
144 (134.94491577148): 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=280370000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (94.890594482422): 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=280370000 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (519.99092102051): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (63.896179199219): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (69.141387939453): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
149 (56.982040405273): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
150 (!!!!! 1616.0011291504): 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 (108.95729064941): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
152 (78.916549682617): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
153 (55.074691772461): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=280370000 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=280370000 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (41.007995605469): 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=215 or channel_id is null)
155 (37.908554077148): 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=215 or channel_id is null)
156 (56.982040405273): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (83.92333984375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
158 (58.889389038086): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=280370000 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=280370000 AND published='1' LIMIT 1
159 (49.114227294922): select jos_twitters.link from jos_twitters where cat=10
160 (36.001205444336): select jos_facebook.link from jos_facebook where cat=10
161 (36.001205444336): select jos_google_plus.link from jos_google_plus where cat=10
162 (38.14697265625): select jos_linkedin.link from jos_linkedin where cat=10
163 (557.89947509766): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14202,14203)
164 (!!!!! 1147.0317840576): insert into jos_banners_delta values (14202,'2025-08-24 02:44:09','216.73.216.171','view'),(14203,'2025-08-24 02:44:09','216.73.216.171','view')