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Optical Imaging System Brings Molecular Diagnostics to the OR

By MedImaging International staff writers
Posted on 03 Jan 2019
Image: Label-free imaging of the tumor microenvironment can provides real-time visualization of structural and molecular features, including EVs (Photo courtesy of UIUC).
Image: Label-free imaging of the tumor microenvironment can provides real-time visualization of structural and molecular features, including EVs (Photo courtesy of UIUC).
A novel portable optical imaging system can successfully visualize the tumor microenvironment of excised human breast tissue, according to a new study.

Developed at the University of Illinois at Urbana-Champaign (UIUC; USA) and Carle Foundation Hospital (Urbana, IL, USA), the nonlinear imaging system uses precise light pulses to simultaneously image tissue in four modalities, showing concurrent molecular processes within cells and tissue in the tumor microenvironment. For example, collagen fibers appear in green; elastin fibers and Flavin-based cell cytoplasm appear in yellow; cell membranes, lipid boundaries, and extracellular vesicles (EVs) appear in magenta; and nicotinamide adenine dinucleotide in the cells and lipids appears in cyan.

To demonstrate the viability of the imaging system in the OR, the researchers intraoperatively imaged untreated human breast tissues from 29 patients with breast cancer using label-free optical contrasts, correlated with histological findings, which enabled point-of-procedure characterization of the tumor microenvironment within 30 minutes of diseased tissue extraction. EV densities were found to increase with higher histologic grade and shorter tumor-to-margin distance, and were significantly higher than those from seven cancer-free patients undergoing breast reduction surgery. The study was published on December 19, 2018, in Science Advances.

“EVs do play an essential role in cancer progression. Quantifying EV densities may be developed as a potential biomarker for future cancer diagnoses,” said lead author graduate student Yi Sun, MSc. “What we observed about the extracellular vesicles is significant, but it could only be accurately determined with our new system. Our imaging technique works well with current cancer treatment routines and is free of any form of perturbation.”

“We believe that capturing the dynamic cellular and molecular features in freshly removed or biopsied tissue specimens contains valuable diagnostic and prognostic information that is currently lost when specimens are placed in a fixative and essentially killed quickly in order to preserve structure,” said senior author Professor Stephen Boppart, PhD, of the UIUC Beckman Institute for Advanced Science and Technology. “Our imaging platform and methodology allow us to extract this new information in real-time, at the point-of-procedure.”

Tumor-associated EVs play important roles in intercellular communication, both inside and outside of the tumor microenvironment, promoting tumor progression by directing cancer-associated events and changes. Various EV detection methods have been proposed and investigated, such as flow cytometry performed on circulating exosomes, immuno-based detection, and fluorescence label-based approaches for visualization, but none are label-free. Few attempts have been made to study human EVs using label-free imaging of fresh untreated or unstained human tumor tissues.

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97 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (25.033950805664): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (25.98762512207): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (!!!!! 1863.0027770996): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
105 (66.041946411133): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
106 (79.870223999023): 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=294776363 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (66.995620727539): 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=294776363 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (565.0520324707): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
109 (65.088272094727): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
110 (132.79914855957): 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=294776363 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (512.12310791016): 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=294776363 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (798.94065856934): 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 (486.13548278809): 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 (122.0703125): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
115 (82.015991210938): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
116 (73.909759521484): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
117 (52.928924560547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
118 (52.928924560547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
119 (72.002410888672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
120 (388.14544677734): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
121 (!!!!! 117558.00247192): 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
122 (156.87942504883): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
123 (68.902969360352): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
124 (!!!!! 1960.0391387939): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294776363 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294776363 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 1291646.9573975): ( 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 (70.810317993164): ( 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 (39.100646972656): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800513 LIMIT 1
128 (29.802322387695): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800513 LIMIT 1
129 (36.001205444336): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800359 LIMIT 1
130 (27.894973754883): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800359 LIMIT 1
131 (32.901763916016): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800361 LIMIT 1
132 (41.007995605469): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294800361 LIMIT 1
133 (718.83201599121): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
134 (425.10032653809): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
135 (38.862228393555): SELECT name FROM jos_deeppockets WHERE id=215
136 (29.087066650391): SELECT name FROM jos_deeppockets WHERE id=215
137 (536.91864013672): 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((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
138 (441.7896270752): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))215((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
139 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
140 (50.067901611328): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
141 (!!!!! 9865.9992218018): TRUNCATE TABLE jos_trademed_module
142 (103.95050048828): 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=294776363 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
143 (72.956085205078): 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=294776363 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
144 (835.18028259277): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
145 (68.902969360352): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
146 (75.101852416992): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
147 (45.061111450195): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
148 (!!!!! 2090.9309387207): 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
149 (827.07405090332): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
150 (58.889389038086): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
151 (910.04371643066): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294776363 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294776363 AND type='deeppockets_item' AND published='1' LIMIT 1
152 (44.107437133789): 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)
153 (43.869018554688): 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)
154 (46.014785766602): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
155 (82.969665527344): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
156 (50.067901611328): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294776363 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294776363 AND published='1' LIMIT 1
157 (!!!!! 4239.0823364258): select jos_twitters.link from jos_twitters where cat=10
158 (!!!!! 3316.8792724609): select jos_facebook.link from jos_facebook where cat=10
159 (91.075897216797): select jos_google_plus.link from jos_google_plus where cat=10
160 (41.007995605469): select jos_linkedin.link from jos_linkedin where cat=10
161 (322.10350036621): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)
162 (!!!!! 1400.9475708008): insert into jos_banners_delta values (14615,'2025-06-20 00:05:08','216.73.216.120','view'),(14202,'2025-06-20 00:05:08','216.73.216.120','view'),(14203,'2025-06-20 00:05:08','216.73.216.120','view')