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Photoacoustic Tomography Technique Developed for Earlier Detection of Melanoma

By MedImaging International staff writers
Posted on 08 Sep 2010
Two new applications devised by two researchers have resulted in an imaging technique and a contrast agent that produce images of melanoma with remarkable three-dimensional (3D) clarity.

The five-year survival rate for early stage melanoma is very high (98%), but the rate drops precipitously if the cancer is detected late or there is recurrence. So a great deal rides on the accuracy of the initial surgery, where the goal is to remove as little tissue as possible while obtaining "clean margins" all around the tumor. So far, no imaging technique has been able to define the melanoma's boundaries accurately enough to guide surgery. Instead, surgeons tend to cut well beyond the visible margins of the lesion in order to be certain they remove all the malignant tissue.

Two scientists at Washington University in St. Louis (MO, USA) have developed technologies that together promise to solve this difficult problem. Their solution, described in the July 2010 issue of the journal ACS [American Chemical Society] Nano, combines an imaging technique developed by Lihong Wang, Ph.D., a professor of biomedical engineering, and a contrast agent developed by Younan Xia, Ph.D., a professor of biomedical engineering.

The imaging technique is based on the photoacoustic effect discovered by Alexander Graham Bell 100 years ago. Bell exploited the effect in what he considered his greatest invention ever, the photophone, which converted sound to light, transmitted the light, and then converted it back to sound at the receiver. In Bell's effect, the absorption of light heats a material slightly, typically by a matter of millikelvins, and the temperature rise causes thermoelastic expansion. "Much the same thing happens," said Dr. Wang "when you heat a balloon and it expands."

If the light is pulsed at the right frequency, the material will expand and contract, generating a sound wave. "We detect the sound signal outside the tissue, and from there on, it's a mathematical problem," noted Dr. Wang. "We use a computer to reconstruct an image. We're essentially listening to a structure instead of looking at it. Using pure optical imaging, it is hard to look deep into tissues because light is absorbed and scattered. The useful photons run out of juice within 1 mm."

Photoacoustic tomography (PAT) can detect deep structures that strongly absorb light because sound scatters much less than light in tissue. "PAT improves tissue transparency by two to three orders of magnitude," remarked Dr. Wang. Moreover, it is a lot safer than other means of deep imaging. It utilizes photons whose energy is only a couple of electron-volts, whereas X-rays have energies in the thousands of electron-volts. Positron emission tomography (PET) also requires high-energy photons, according to Dr. Wang.

Photoacoustic images of biologic tissue can be made without the use of contrast agents, particularly if tissues are pigmented by molecules such as hemoglobin or melanin. However, photoacoustic images of melanomas are fuzzy and vague around the edges. To improve the contrast between the malignant and normal tissue, Dr. Xia loads the malignant tissue with gold. "Gold is much better at scattering and absorbing light than biological materials," Dr. Xia stated. "One gold nanocage absorbs as much light as a million melanin molecules."

Dr. Xia's contrast agent consists of hollow gold cages, so small they can only be seen through the color they collectively lend to the liquid in which they float. By altering the size and geometry of the particles, they can be tuned to absorb or scatter light over a wide range of wavelengths. In this way, the nanoparticles behave quite differently than bulk gold.

For photoacoustic imaging, Dr. Xia's team tunes the nanocages to absorb strongly at 780 nm, a wavelength that falls within a thin window of tissue transparency in the near-infrared. Light in this sweet spot can penetrate as deep as several inches in the body. Once injected, the gold particles naturally tend to accumulate in tumors because the cells that line a tumor's blood vessels are jumbled and leaky.

However, Dr. Xia has dramatically increased the uptake rate by embellishing the nanoparticles with a hormone that binds to hormone receptors on the melanoma's cells. The molecule is alpha-melanocyte-stimulating hormone, slightly modified to make it more stable in the body. This hormone normally stimulates the production and release of the brown pigment melanin in the skin and hair.

As is the case in many types of cancers, this hormone seems to trigger the growth of cancerous cells, which produce more hormone receptors than normal cells. In experiments with mice, melanomas took up four times as many "functionalized" nanocages than nanocages coated with an inert chemical. With the contrast agent, the photoacoustic signal from the melanoma was 36% stronger. Subcutaneous mouse melanomas barely visible to the unaided eye show up distinctly in the photoacoustic images, their areas of malignancy starkly revealed.

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85 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1
86 (38.862228393555): SELECT show_live FROM jos_com_show_setting LIMIT 1
87 (38.14697265625): SELECT show_live FROM jos_com_show_setting LIMIT 1
88 (39.100646972656): SELECT show_live FROM jos_com_show_setting LIMIT 1
89 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1
90 (72.002410888672): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294731051 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
91 (42.200088500977): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294731051 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
92 (51.975250244141): 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`
93 (77.009201049805): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (39.100646972656): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (48.87580871582): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (42.915344238281): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (78.916549682617): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (41.961669921875): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (69.141387939453): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1
105 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1
106 (42.915344238281): SELECT show_live FROM jos_com_show_setting LIMIT 1
107 (123.97766113281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
108 (101.80473327637): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
109 (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=294731051 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
110 (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=294731051 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (127.07710266113): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
112 (106.0962677002): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
113 (70.095062255859): 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=294731051 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
114 (934.12399291992): 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=294731051 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
115 (800.13275146484): 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
116 (537.87231445312): 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
117 (123.97766113281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
118 (69.141387939453): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
119 (93.936920166016): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
120 (56.028366088867): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
121 (94.175338745117): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
122 (59.127807617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
123 (60.081481933594): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
124 (41.007995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
125 (228.1665802002): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
126 (!!!!! 26386.976242065): 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
127 (555.03845214844): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294731051 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294731051 AND type='deeppockets_item' AND published='1' LIMIT 1
128 (!!!!! 8414.9837493896): ( 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
129 (76.055526733398): ( 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
130 (101.08947753906): 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
131 (41.007995605469): 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
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 = 294803276 LIMIT 1
133 (29.802322387695): 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
134 (287.05596923828): 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
135 (62.942504882812): 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
136 (34.809112548828): 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
137 (29.087066650391): 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
138 (384.80758666992): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
139 (344.99168395996): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
140 (174.99923706055): SELECT name FROM jos_deeppockets WHERE id=215
141 (36.001205444336): SELECT name FROM jos_deeppockets WHERE id=215
142 (723.83880615234): 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((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
143 (755.07164001465): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))215((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
144 (89.883804321289): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
145 (72.956085205078): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
146 (!!!!! 11201.143264771): TRUNCATE TABLE jos_trademed_module
147 (131.84547424316): 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=294731051 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
148 (72.002410888672): 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=294731051 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
149 (!!!!! 7014.0361785889): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
150 (84.877014160156): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
151 (118.97087097168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
152 (61.03515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
153 (!!!!! 1418.1137084961): 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
154 (70.095062255859): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
155 (50.067901611328): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
156 (37.908554077148): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294731051 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294731051 AND type='deeppockets_item' AND published='1' LIMIT 1
157 (41.961669921875): 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)
158 (120.16296386719): 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)
159 (49.114227294922): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
160 (180.00602722168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
161 (78.916549682617): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294731051 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294731051 AND published='1' LIMIT 1
162 (61.988830566406): select jos_twitters.link from jos_twitters where cat=10
163 (34.809112548828): select jos_facebook.link from jos_facebook where cat=10
164 (61.988830566406): select jos_google_plus.link from jos_google_plus where cat=10
165 (34.093856811523): select jos_linkedin.link from jos_linkedin where cat=10