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MRI Helps Detect pH Changes in Tumor Tissue

By MedImaging International staff writers
Posted on 31 May 2017

Image: Hyperpolarized ZA measurements compared to pH-values in a rat kidney (Photo courtesy of Franz Schilling / TUM).

A new study demonstrates how hyperpolarized 13C-labelled zymonic acid (ZA) can be used as a magnetic resonance imaging (MRI) pH imaging sensor.

Researchers at Munich Technical University developed the pH imaging sensor using ZA marked with carbon-13 in order to be visible in MRI images. In order to make pH values visible using ZA, the molecule is first hyperpolarized using microwaves at very low temperatures; a hot liquid is then used to quickly return the ZA to room temperature. The biosensor is then injected into the body, and the scan is performed immediately, as the hyperpolarization effect wears off in 60 seconds.

When inside the MRI, the magnetic field waves excite the nuclear spins of the ZA to oscillation. The reactions of the nuclei are then recorded, and the data is used to calculate frequency spectra, which in turn provide information about the chemical properties of the molecular surroundings of the nuclei. The pH value at any examined location in the tissue can be represented based on molecular changes in the ZA. The researchers have succeeded in showing that their method is sensitive enough to represent medically relevant pH value changes in the organism.

The researchers conducted studies in rat kidneys and subcutaneously inoculated tumors derived from a mammary adenocarcinoma cell line, generating in-vivo pH maps, and also successfully characterized ZA as a non-toxic compound predominantly present in the extracellular space. The researchers also suggest that in contrast to current optical methods, which are limited to superficial penetration into the body due to the low transparency of tissue, there are no limitations to the depth of penetration for MRI. The study was published on May 11, 2017, in Nature Communications.

“Areas surrounding tumors and inflammations are usually slightly more acidic than areas surrounding healthy tissue, a phenomenon possibly linked to the aggressiveness of tumors,” said senior author TUM physicist Franz Schilling, PhD. “pH values are also interesting when it comes to evaluating the efficacy of tumor treatments. Even before a successfully treated tumor starts to shrink, its metabolism and thus the pH value of the surrounding area could change. An appropriate pH imaging method would indicate at a much earlier stage whether or not the right approach has been selected.”

The hyperpolarized spin state exists at very low spin temperature that are not in a thermal equilibrium with the temperature of the tissue, which leads to high magnetization of the spin ensemble, resulting in very high nuclear magnetic resonance signal intensity. The hyperpolarized spin state eventually returns to the thermal equilibrium temperature by depolarization.

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69 (32.186508178711): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=212 ORDER BY `ordering`

70 (263.21411132812): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294769426 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (237.94174194336): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294769426 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (39.100646972656): 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`

73 (76.055526733398): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (44.107437133789): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (38.862228393555): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (46.014785766602): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (53.882598876953): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (80.108642578125): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294769426 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (43.869018554688): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294769426 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (36.954879760742): 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 (55.074691772461): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (31.948089599609): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (34.093856811523): 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 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (56.982040405273): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (90.837478637695): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

105 (59.843063354492): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

106 (54.121017456055): 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=294769426 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (466.10832214355): 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=294769426 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (101.08947753906): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

109 (60.081481933594): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

110 (47.922134399414): 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=294769426 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (564.0983581543): 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=294769426 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (777.9598236084): 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 (!!!!! 3134.01222229): 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 (89.883804321289): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

115 (64.13459777832): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

116 (66.041946411133): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

117 (41.961669921875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

118 (51.975250244141): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

119 (40.054321289062): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

120 (288.00964355469): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

121 (!!!!! 48671.007156372): 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 (93.936920166016): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

123 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

124 (496.14906311035): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294769426 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294769426 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 816925.04882812): ( 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 (85.830688476562): ( 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 (46.968460083008): 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 (37.908554077148): 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 (46.968460083008): 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 (37.908554077148): 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 (37.193298339844): 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 (36.001205444336): 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 (550.98533630371): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

134 (628.94821166992): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

135 (318.05038452148): SELECT name FROM jos_deeppockets WHERE id=212

136 (37.908554077148): SELECT name FROM jos_deeppockets WHERE id=212

137 (595.8080291748): 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

138 (524.04403686523): 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

139 (73.909759521484): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

140 (51.975250244141): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

141 (!!!!! 11434.078216553): TRUNCATE TABLE jos_trademed_module

142 (106.8115234375): 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=294769426 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

143 (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=294769426 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

144 (477.07557678223): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

145 (65.088272094727): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

146 (65.803527832031): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

147 (48.160552978516): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

148 (!!!!! 1466.9895172119): 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 (62.942504882812): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

150 (59.127807617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

151 (47.922134399414): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294769426 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294769426 AND type='deeppockets_item' AND published='1' LIMIT 1

152 (45.7763671875): 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)

153 (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=212 or channel_id is null)

154 (34.809112548828): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

155 (83.208084106445): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

156 (58.889389038086): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294769426 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294769426 AND published='1' LIMIT 1

157 (40.054321289062): select jos_twitters.link from jos_twitters where cat=10

158 (32.186508178711): select jos_facebook.link from jos_facebook where cat=10

159 (41.961669921875): select jos_google_plus.link from jos_google_plus where cat=10

160 (41.961669921875): select jos_linkedin.link from jos_linkedin where cat=10

161 (360.01205444336): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)

162 (!!!!! 1726.1505126953): insert into jos_banners_delta values (14615,'2025-06-19 15:08:00','216.73.216.120','view'),(14202,'2025-06-19 15:08:00','216.73.216.120','view'),(14203,'2025-06-19 15:08:00','216.73.216.120','view')

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