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Imaging Probe Allows Noninvasive Detection of Heart-Valve Infection

By MedImaging International staff writers
Posted on 29 Aug 2011
An innovative imaging probe may make it possible to diagnose accurately a dangerous infection of the heart valves. The investigators revealed how the presence of Staphylococcus aureus-associated endocarditis in a mouse model was revealed by positron emission tomography (PET) imaging with a radiolabeled version of a protein involved in a process that typically conceals infecting bacteria from the immune system.

“Our probe was able to sense whether S. aureus was present in abnormal growths that hinder the normal function of heart valves,” said Matthias Nahrendorf, MD, PhD, of the Massachusetts General Hospital (MGH; Boston, MA, USA) Center for Systems Biology, a co-lead author of the study, which was published August 2011 in advance online edition of the journal Nature Medicine. “It has been very difficult to identify the bacteria involved in endocarditis, but a precise diagnosis is important to steering well-adjusted antibiotic therapy.”

An infection of the tissue lining the heart valves, endocarditis is characterized by growths called vegetations comprised of clotting components such as platelets and fibrin along with infecting microorganisms. Endocarditis caused by S. aureus is the most dangerous, with a mortality rate of from 25 to nearly 50%, but diagnosis can be difficult since symptoms such as fever and heart murmur are vague and blood tests may not detect the involved bacteria. Without appropriate antibiotic therapy, S. aureus endocarditis can progress rapidly, damaging or destroying heart valves.

S. aureus bacteria initiate the growth of vegetations by secreting staphylocoagulase, an enzyme that sets off the clotting cascade. This process involves a protein called prothrombin, which is part of a pathway leading to the deposition of fibrin, a primary component of blood clots. The clotting process enlarges the vegetation, anchors it to the heart valve, and serves to conceal the bacteria from immune cells in the bloodstream.

To develop an imaging-based approach to diagnosing S. aureus endocarditis, the MGH investigators first investigated the molecular process by which staphylocoagulase sets off the clotting cascade, finding that one staphylocoagulase molecule interacts with at least four molecules of fibrin or its predecessor molecule fibrinogen in a complex that binds to a growing vegetation. Because prothrombin is an essential intermediary in the staphylocoagulase/fibrin interaction, the researchers investigated whether labeled versions of prothrombin could accurately detect S. aureus endocarditis in mice.

After initial experiments confirmed that an optical imaging technology called fluorescence molecular tomography -computed tomography (FMT-CT) could detect a fluorescence-labeled version of prothombin deposited into S. aureus-induced vegetations, the researchers showed that a radiolabeled version of prothombin enabled the detection of S. aureus vegetations with combined PET-CT imaging, an approach that could be used in human patients after additional development and FDA approval.

“An approach like this could help clinicians detect the presence of endocarditis, determine its severity and whether it is caused by S. aureus, and track the effectiveness of antibiotics or other treatments,” said Dr. Nahrendorf, also a co-corresponding author of the Nature Medicine article and an assistant professor of radiology at Harvard Medical School (Boston, MA, USA). “We are working to improve the PET reporter probe with streamlined chemistry and a more mainstream PET isotope to make it a better candidate for eventual testing in patients.”

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92 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (63.180923461914): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
105 (55.789947509766): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
106 (55.074691772461): 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=294736797 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (48.87580871582): 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=294736797 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (70.095062255859): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
109 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
110 (46.014785766602): 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=294736797 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (504.0168762207): 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=294736797 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (643.01490783691): 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 (319.9577331543): 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 (89.168548583984): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
115 (84.877014160156): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
116 (388.14544677734): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
117 (424.14665222168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
118 (303.98368835449): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
119 (!!!!! 2505.0640106201): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
120 (99.897384643555): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
121 (61.03515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
122 (174.99923706055): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 23147.106170654): 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 (481.84394836426): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294736797 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294736797 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 7243.1564331055): ( 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 (80.82389831543): ( 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 (53.167343139648): 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 (30.994415283203): 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 (36.001205444336): 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 (30.040740966797): 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 (288.00964355469): 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 (93.936920166016): 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 (30.994415283203): 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 (56.028366088867): 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 (489.95018005371): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (366.2109375): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (271.79718017578): SELECT name FROM jos_deeppockets WHERE id=213
138 (34.093856811523): SELECT name FROM jos_deeppockets WHERE id=213
139 (556.23054504395): 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 '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (455.85632324219): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))213((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (65.803527832031): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
142 (50.067901611328): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
143 (!!!!! 8207.7980041504): TRUNCATE TABLE jos_trademed_module
144 (129.93812561035): 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=294736797 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=294736797 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (801.80168151855): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (52.928924560547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (61.03515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
149 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
150 (!!!!! 1101.9706726074): 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 (53.882598876953): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
152 (47.206878662109): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
153 (104.90417480469): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294736797 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294736797 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (31.948089599609): 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=213 or channel_id is null)
155 (33.855438232422): 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=213 or channel_id is null)
156 (29.087066650391): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (61.03515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
158 (44.107437133789): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294736797 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294736797 AND published='1' LIMIT 1
159 (46.968460083008): select jos_twitters.link from jos_twitters where cat=10
160 (31.948089599609): 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 (32.901763916016): select jos_linkedin.link from jos_linkedin where cat=10
163 (205.99365234375): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)
164 (921.96464538574): insert into jos_banners_delta values (14615,'2025-06-22 00:45:51','216.73.216.120','view'),(14202,'2025-06-22 00:45:51','216.73.216.120','view'),(14203,'2025-06-22 00:45:51','216.73.216.120','view')