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Diffraction-Enhanced Imaging Developed for Early Alzheimer's Disease Diagnosis

By MedImaging International staff writers
Posted on 27 Jul 2009
Researchers have demonstrated a new, highly detailed X-ray imaging technique that could be developed into an application for early diagnosis of Alzheimer's disease (AD). The technique has previously been used to look at tumors in breast tissue and cartilage in the human knee and ankle joints, but a new study is first to assess its ability to visualize a class of miniscule plaques that are a hallmark feature of AD.

The scientists, from the U.S. Department of Energy's (DOE) Brookhaven National Laboratory (Upton, NY, USA), published their findings in the July 2009 issue of the journal NeuroImage. Researchers have long known that Alzheimer's disease is associated with plaques, areas of dense built-up proteins, in the affected brain. Many also believe that these plaques, called amyloid beta (Aß) plaques after the protein they contain, actually cause the disease. A major goal is to develop a drug that removes the plaques from the brain. However, before drug therapies can be tested, researchers need a noninvasive, safe, and cost-effective way to track the plaques' number and size.

That is no simple task: Aß plaques are extremely small--on the micrometer scale, or one millionth of a meter. Moreover, conventional techniques such as computed tomography (CT) poorly distinguish between the plaques and other soft tissue such as cartilage or blood vessels. "These plaques are very difficult to see, no matter how you try to image them,” said Dr. Dean Connor, a former postdoctoral researcher at Brookhaven Lab now working for the University of North Carolina (Chapel Hill). "Certain methods can visualize the plaque load, or overall number of plaques, which plays a role in clinical assessment and analysis of drug efficacy. But these methods cannot provide the resolution needed to show us the properties of individual Aß plaques.”

A technique developed at Brookhaven, called diffraction-enhanced imaging (DEI), might provide the extra imaging power researchers need. DEI, which makes use of extremely bright beams of X-rays available at synchrotron sources such as Brookhaven's National Synchrotron Light Source, is used to visualize not only bone, but also soft tissue in a manner that is not possible using standard X-rays. In contrast to conventional sources, synchrotron X-ray beams are thousands of times more intense and extremely concentrated into a narrow beam. The result is typically a lower X-ray dose with a higher image quality.

In this study, researchers from Brookhaven and Stony Brook University utilized DEI in a high-resolution mode called microcomputed tomography to visualize individual plaques in a mouse-brain model of Alzheimer's disease. The results not only revealed detailed images of the plaques, but also proved that DEI can be used on whole brains to visualize a wide range of anatomic structures without the use of a contrast agent.

The images are similar to those produced by high-resolution magnetic resonance imaging (MRI), with the potential to even exceed MRI pictures in resolution, according to Dr. Connor. "The contrast and resolution we achieved in comparison to other types of imaging really is amazing,” he said. "When DEI is used, everything just lights up.”

The radiation dose used for this study is too high to safely image individual Aß plaques in humans--the ultimate goal--but the results provide researchers with promising clues. "Now that we know we can actually see these plaques, the hope is to develop an imaging modality that will work in living humans,” Dr. Connor said. "We've also now shown that we can see these plaques in a full brain, which means we can produce images from a live animal and learn how these plaques grow.”

To make a diffraction-enhanced image, X-rays from the synchrotron are first tuned to one wavelength before being beamed at an anatomic structure or slide. As the monochromatic (single wavelength) beam passes through the tissue, the X-rays scatter and refract, or bend, at different angles depending on the characteristics of the tissue. The subtle scattering and refraction are detected by what is called an analyzer crystal, which diffracts (alters the intensity) of the X-rays by different amounts according to their scattering angles.

The diffracted beam is passed onto a radiographic plate or digital recorder, which documents the differences in intensity to show the interior structural details.

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90 (66.995620727539): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294724584 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
91 (45.061111450195): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294724584 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
92 (46.014785766602): 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 (74.148178100586): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (39.100646972656): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (33.855438232422): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (39.100646972656): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
105 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1
106 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1
107 (106.0962677002): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
108 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
109 (88.930130004883): 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=294724584 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
110 (216.96090698242): 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=294724584 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (297.06954956055): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
112 (82.969665527344): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
113 (68.902969360352): 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=294724584 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
114 (633.00132751465): 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=294724584 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
115 (541.92543029785): 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 (336.88545227051): 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 (82.969665527344): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
118 (60.081481933594): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
119 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
120 (39.815902709961): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
121 (98.943710327148): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
122 (40.054321289062): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
123 (57.93571472168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
124 (37.193298339844): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
125 (264.88304138184): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
126 (!!!!! 19340.038299561): 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 (523.09036254883): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294724584 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294724584 AND type='deeppockets_item' AND published='1' LIMIT 1
128 (!!!!! 7225.0366210938): ( 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 (77.962875366211): ( 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 (45.061111450195): 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 (30.040740966797): 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 (33.855438232422): 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 (27.894973754883): 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 (314.95094299316): 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 (57.93571472168): 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 (35.04753112793): 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 (27.894973754883): 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 (576.01928710938): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
139 (407.93418884277): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
140 (262.02201843262): SELECT name FROM jos_deeppockets WHERE id=211
141 (50.067901611328): SELECT name FROM jos_deeppockets WHERE id=211
142 (761.03210449219): 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 '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
143 (684.97657775879): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
144 (110.14938354492): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
145 (80.82389831543): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
146 (!!!!! 11168.956756592): TRUNCATE TABLE jos_trademed_module
147 (113.96408081055): 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=294724584 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
148 (89.168548583984): 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=294724584 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
149 (!!!!! 1144.8860168457): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
150 (94.890594482422): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
151 (155.92575073242): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
152 (55.074691772461): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
153 (!!!!! 1400.2323150635): 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 (99.897384643555): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
155 (70.095062255859): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
156 (71.048736572266): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294724584 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294724584 AND type='deeppockets_item' AND published='1' LIMIT 1
157 (697.13592529297): 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=211 or channel_id is null)
158 (57.93571472168): 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=211 or channel_id is null)
159 (66.041946411133): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
160 (112.05673217773): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
161 (76.055526733398): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294724584 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294724584 AND published='1' LIMIT 1
162 (73.19450378418): select jos_twitters.link from jos_twitters where cat=10
163 (46.014785766602): select jos_facebook.link from jos_facebook where cat=10
164 (50.067901611328): select jos_google_plus.link from jos_google_plus where cat=10
165 (44.107437133789): select jos_linkedin.link from jos_linkedin where cat=10