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{"id":10326,"date":"2016-10-14T11:30:34","date_gmt":"2016-10-14T15:30:34","guid":{"rendered":"http:\/\/circulatingnow.nlm.nih.gov\/?p=10326"},"modified":"2022-12-07T11:33:44","modified_gmt":"2022-12-07T16:33:44","slug":"truly-translational-louis-sokoloff-and-pet-brain-imaging","status":"publish","type":"post","link":"https:\/\/circulatingnow.nlm.nih.gov\/2016\/10\/14\/truly-translational-louis-sokoloff-and-pet-brain-imaging\/","title":{"rendered":"Truly Translational: Louis Sokoloff and PET Brain Imaging"},"content":{"rendered":"<p><em>By Susan Speaker<\/em><\/p>\n<figure id=\"attachment_10345\" aria-describedby=\"caption-attachment-10345\" style=\"width: 190px\" class=\"wp-caption alignright\"><a href=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgd.png?ssl=1\"><img data-recalc-dims=\"1\" loading=\"lazy\" decoding=\"async\" data-attachment-id=\"10345\" data-permalink=\"https:\/\/circulatingnow.nlm.nih.gov\/2016\/10\/14\/truly-translational-louis-sokoloff-and-pet-brain-imaging\/nlbbgd\/\" data-orig-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgd.png?fit=832%2C1200&ssl=1\" data-orig-size=\"832,1200\" data-comments-opened=\"1\" data-image-meta=\"{"aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}\" data-image-title=\"Autoradiograph of Brain Crossections\" data-image-description=\"<p>https:\/\/profiles.nlm.nih.gov\/ps\/retrieve\/ResourceMetadata\/NLBBGD<br \/>\nThis image accompanied one of the early publications demonstrating the DG method (Kennedy, et al., PNAS 73 (1976): 4230-4234) and was also used by Sokoloff to illustrate his Schmitt lecture in 1980. The caption reads, “Autoradiographs of coronal brain sections from rhesus monkeys at the level of the striate cortex. A: Animal with normal binocular vision. Note the laminar distribution of the density; the dark band corresponds to layer IV. B: Animal with bilateral visual deprivation. Note the almost uniform and reduced relative density, especially the virtual disappearance of the dark band corresponding to layer IV. C: Animal with right eye occluded. The half-brain on the left side of the photograph represents the left hemisphere contralateral to the occluded eye. Note the alternate dark and light striations, each approximately 0.3 to 0.4 mm in width, that represent the ocular dominance columns. These columns are most apparent in the dark band corresponding to layer IV, but extend through the entire thickness of the cortex. The arrows point to regions of bilateral asymmetry where the ocular dominance columns are absent. These are presumably areas with normally only monocular input. The one on the left, contralateral to occluded eye, has a continuous dark lamina corresponding to layer IV which is completely absent on the side ipsilateral to the occluded eye. These regions are believed to be the loci of the cortical representations of the blind spots.” <\/p>\n\" data-image-caption=\"<p>Autoradiograph of brain sections from rhesus monkeys showing effects of visual occlusion, ca. 1975<br \/>\nProfiles in Science<\/p>\n\" data-medium-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgd.png?fit=208%2C300&ssl=1\" data-large-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgd.png?fit=710%2C1024&ssl=1\" class=\"wp-image-10345 \" title=\"Autoradiograph of Brain Sections\" src=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgd.png?resize=190%2C274&ssl=1\" alt=\"Three images of brain crossections, one light, one dark and one banded.\" width=\"190\" height=\"274\" \/><\/a><figcaption id=\"caption-attachment-10345\" class=\"wp-caption-text\">Autoradiograph of brain sections from rhesus monkeys showing effects of visual occlusion, ca. 1975<br \/><a href=\"https:\/\/profiles.nlm.nih.gov\/101743402X86\"><em>Profiles in Science<\/em><\/a><\/figcaption><\/figure>\n<p>Twenty-first century medical practitioners have many ways of making images of the inside of the body, including x-rays, ultrasound, magnetic resonance imaging (MRI), computerized axial tomography (CT scan), and positron emission tomography (PET). These technologies allow physicians to \u201csee\u201d structural abnormalities, and in the case of functional MRI and PET, can show which tissues are active, by showing their level of blood flow or energy consumption (metabolism). This is very useful if you want to see, for example, what specific area of the brain is stimulated by a certain drug, or track a tumor\u2019s response to chemotherapy. We\u2019re familiar with these images, especially the colorful CT and PET brain scans, and it\u2019s easy to think of them as just pretty color photos taken with a giant camera. In truth, the pictures are the product of a complex system that includes the scanner, sophisticated computer programs, and radioactive tracer substances (in the case of PET). The accurate clinical information conveyed by these images derives from decades of painstaking basic research by scientists such as Louis Sokoloff, who was born 95 years ago today.<\/p>\n<figure id=\"attachment_10342\" aria-describedby=\"caption-attachment-10342\" style=\"width: 218px\" class=\"wp-caption alignleft\"><a href=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbby.png?ssl=1\"><img data-recalc-dims=\"1\" loading=\"lazy\" decoding=\"async\" data-attachment-id=\"10342\" data-permalink=\"https:\/\/circulatingnow.nlm.nih.gov\/2016\/10\/14\/truly-translational-louis-sokoloff-and-pet-brain-imaging\/nlbbby\/\" data-orig-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbby.png?fit=872%2C1200&ssl=1\" data-orig-size=\"872,1200\" data-comments-opened=\"1\" data-image-meta=\"{"aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}\" data-image-title=\"Louis Sokoloff\" data-image-description=\"<p>https:\/\/profiles.nlm.nih.gov\/ps\/retrieve\/ResourceMetadata\/NLBBBY<\/p>\n\" data-image-caption=\"<p>Louis Sokoloff, 1991<br \/>\nCourtesy of Ann Sokoloff<br \/>\nProfiles in Science<\/p>\n\" data-medium-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbby.png?fit=218%2C300&ssl=1\" data-large-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbby.png?fit=744%2C1024&ssl=1\" class=\"wp-image-10342 size-medium\" title=\"Louis Sokoloff, 1991\" src=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbby.png?resize=218%2C300&ssl=1\" alt=\"Formal portrait of Louis Sokoloff\" width=\"218\" height=\"300\" \/><\/a><figcaption id=\"caption-attachment-10342\" class=\"wp-caption-text\">Louis Sokoloff, 1991<br \/><em>Courtesy of Ann Sokoloff<\/em><br \/><a href=\"https:\/\/profiles.nlm.nih.gov\/101743402X20\"><em>Profiles in Science<\/em><\/a><\/figcaption><\/figure>\n<p>Dr. Sokoloff (1921\u20132015), the focus of NLM’s newest <a href=\"https:\/\/profiles.nlm.nih.gov\/spotlight\/nl\"><em>Profiles in Science<\/em><\/a> collection, worked in the Laboratory of Cerebral Metabolism at the National Institute of Mental Health from 1953 until his retirement in 2004. During that time, he used his extensive knowledge of medicine, biochemistry, physiology, neuroscience, mathematics, and kinetic modeling to transform the study of brain structure and function. And he was able to \u201ctranslate\u201d his laboratory discoveries into a clinical technology\u2014PET scanning\u2014that could show the human brain working in real time.<\/p>\n<p>When Sokoloff began his research career, one of the central problems in neuroscience was how to find out when things are happening in the brain, and <em>where<\/em> they\u2019re happening\u2014initiation of movement, response to stimuli, thought, emotion, and so on. It was a difficult problem\u2014after all, how can one watch the brain at work, when a) it\u2019s hidden inside the skull, and b) even if it were visible, it doesn\u2019t actually <em>move<\/em>? One of Sokoloff\u2019s mentors, Seymour Kety, had developed a technique using nitrous oxide (N<sub>2<\/sub>O) to measure blood flow in the brain, and used this and blood oxygen levels as indirect measures of activity. But many brain phenomena couldn\u2019t be detected with such a general method.<\/p>\n<figure id=\"attachment_10344\" aria-describedby=\"caption-attachment-10344\" style=\"width: 300px\" class=\"wp-caption alignright\"><a href=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgc.png?ssl=1\"><img data-recalc-dims=\"1\" loading=\"lazy\" decoding=\"async\" data-attachment-id=\"10344\" data-permalink=\"https:\/\/circulatingnow.nlm.nih.gov\/2016\/10\/14\/truly-translational-louis-sokoloff-and-pet-brain-imaging\/nlbbgc\/\" data-orig-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgc.png?fit=1246%2C1200&ssl=1\" data-orig-size=\"1246,1200\" data-comments-opened=\"1\" data-image-meta=\"{"aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}\" data-image-title=\"Effect of L-DOPA treatment on brain metabolism in the monkey\" data-image-description=\"<p>https:\/\/profiles.nlm.nih.gov\/ps\/retrieve\/ResourceMetadata\/NLBBGC<br \/>\nSokoloff’s group used the deoxyglucose method to study many brain phenomena, including the effects of various drugs on cerebral metabolism. A series of studies in the mid-1980s explored the effects of l-dopa in the brains of monkeys with parkinsonism induced by MPTP. This is one of the slides used for presentations. It’s a color-coded autoradiograph of a coronal section. It shows clearly that l-dopa increases metabolism in the brains of monkeys with induced parkinsonism, though not much in normal brains. See, e.g., LG Porrino, et al., “Changes in local cerebral glucose utilization associated with Parkinson’s syndrome induced by 1-methyl-phenyl-1,2,3,6-tetrohydropyridine (MPTP) in the primate,” Life Sciences 40 (1987): 1657-1664. <\/p>\n\" data-image-caption=\"<p>A color-coded autoradiograph of a coronal section, ca. 1985. It shows clearly that l-dopa increases metabolism in the brains of monkeys with induced parkinsonism, though not much in normal brains.<br \/>\nProfiles in Science<\/p>\n\" data-medium-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgc.png?fit=300%2C289&ssl=1\" data-large-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgc.png?fit=840%2C809&ssl=1\" class=\"wp-image-10344 size-medium\" title=\"L-Dopa levels show on an autoradiograph, ca. 1985\" src=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgc.png?resize=300%2C289&ssl=1\" alt=\"A comparison of a normal and drugged brain showing higher l-dopa in the treated brain.\" width=\"300\" height=\"289\" \/><\/a><figcaption id=\"caption-attachment-10344\" class=\"wp-caption-text\">A color-coded autoradiograph of a coronal section, ca. 1985. It shows clearly that l-dopa increases metabolism in the brains of monkeys with induced parkinsonism, though not much in normal brains.<br \/><a href=\"https:\/\/profiles.nlm.nih.gov\/101743402X85\"><em>Profiles in Science<\/em><\/a><\/figcaption><\/figure>\n<p>In the 1950s, Sokoloff and his NIMH team began using radioactive tracers to track blood flow in specific parts of the brain, using experimental animals. For these studies, they infused a tracer solution into a living animal\u2019s vein for about one minute, continuously sampling the arterial blood to monitor the tracer concentration in the blood. To measure the concentrations of the tracer in particular parts of the brain at a particular moment, the animal was humanely killed and its head frozen in liquid nitrogen. The frozen brain was cut into thin cross-sections, and the sections placed on x-ray film. When the film was developed, the image (called an autoradiogram) showed the distribution of the radioactive tracer in the structures of the brain. The darker the film, the greater the concentration of the tracer in the tissue. The investigators could then use a densitometer (an instrument that measures the degree of darkness in film) to relate the darkness in a given region of the film image to the concentration of the tracer in the tissues shown. The autoradiograms clearly showed the anatomical components of the brain, and demonstrated significant differences in blood flow rates to them. Because the concentrations of tracer in the various tissues were closely related to the rates of blood flow to them, the autoradiograms were essentially pictures of the relative rates of blood flow in those tissues at a given moment. The group\u2019s <a href=\"https:\/\/profiles.nlm.nih.gov\/101743402X29\">1955 report<\/a>, which described images obtained from the brains of cats with eyes open or closed or stimulated with light flashes, was the first published demonstration of functional brain imaging.<\/p>\n<figure id=\"attachment_10343\" aria-describedby=\"caption-attachment-10343\" style=\"width: 263px\" class=\"wp-caption alignleft\"><a href=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgb.png?ssl=1\"><img data-recalc-dims=\"1\" loading=\"lazy\" decoding=\"async\" data-attachment-id=\"10343\" data-permalink=\"https:\/\/circulatingnow.nlm.nih.gov\/2016\/10\/14\/truly-translational-louis-sokoloff-and-pet-brain-imaging\/nlbbgb\/\" data-orig-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgb.png?fit=1053%2C1200&ssl=1\" data-orig-size=\"1053,1200\" data-comments-opened=\"1\" data-image-meta=\"{"aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}\" data-image-title=\"Functional Anatomy of the Operational Equation of the [14C]Deoxyglucose Method\" data-image-description=\"<p>https:\/\/profiles.nlm.nih.gov\/ps\/retrieve\/ResourceMetadata\/NLBBGB<\/p>\n\" data-image-caption=\"<p>This diagram was frequently used in presentations and publications after Sokoloff did the initial work on the DG method, ca. 1975<br \/>\nProfiles in Science<\/p>\n\" data-medium-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgb.png?fit=263%2C300&ssl=1\" data-large-file=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgb.png?fit=840%2C957&ssl=1\" class=\"wp-image-10343 size-medium\" style=\"border: 2px solid #000000;\" title=\"Explaining a Complex Equation\" src=\"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgb.png?resize=263%2C300&ssl=1\" alt=\"A page explaining the complex equation describing the reaction rates for chemicals needed to interpret measured levels of chemicals.\" width=\"263\" height=\"300\" \/><\/a><figcaption id=\"caption-attachment-10343\" class=\"wp-caption-text\">This diagram was frequently used in presentations and publications after Sokoloff did the initial work on the DG method, ca. 1975<br \/><a href=\"https:\/\/profiles.nlm.nih.gov\/101743402X84\"><em>Profiles in Science<\/em><\/a><\/figcaption><\/figure>\n<p>Images of blood flow to specific brain regions helped researchers learn much more about brain structure and function, but blood flow was still an indirect measure. Sokoloff believed that measuring the brain\u2019s use of glucose\u2014its metabolism\u2014would be a better way to track its activity. During the 1960s and \u201870s, he developed a technique using radio-labeled 2-deoxyglucose (2-DG), a glucose analog that is taken up by brain tissue in the first step of glucose metabolism, and then retained there so that it can be detected in autoradiograms. As in the blood flow studies, the images were analyzed with densitometers to determine the relative concentrations of tracer in the tissues. Doing this manually was tedious and time-consuming, so the team collaborated with several computer scientists at NIMH to develop an image-processing program that could scan and reconstruct the radiographic images, and assign different colors to the different levels of metabolic activity. With the 2-DG method, Sokoloff and his team proved that functional activity levels in specific brain regions were linked to metabolic levels in those areas.\u00a0 Their work sparked a rapid expansion in brain mapping research.<\/p>\n<p>The final step of the bench-to-bedside process was to adapt the 2-DG method for use with human patients. This required only a non-invasive scanning device and a 2-DG tracer modified so that the device could detect it. Positron emission tomography (PET) technology was newly available by the late 1970s, and Sokoloff worked with a team at UCLA to finish the translation. This achievement earned Sokoloff a Lasker Award in 1981.<\/p>\n<p>PET imaging made it possible to map all kinds of activity in the human brain with greater certainty, from the processes of thinking, sleeping, dreaming, and physical movement, to the actions of drugs and hormones. It also proved useful in clinical diagnosis, e.g., for Alzheimer\u2019s disease, Huntington\u2019s disease, and seizure disorders, and later, for identifying and tracking the treatment of many types of tumors.<\/p>\n<p>We invite you to explore the <a href=\"https:\/\/profiles.nlm.nih.gov\/spotlight\/nl\">Louis Sokoloff papers on <em>Profiles in Science<\/em><\/a> and learn more about Sokoloff’s story through a selection of digitized photos from his childhood and early career, correspondence with colleagues and students, and experimental brain images produced with the tracers he developed.\u00a0 The full collection of NLM’s Louis Sokoloff Papers is described in the collection <a href=\"https:\/\/findingaids.nlm.nih.gov\/repositories\/4\/resources\/956\">finding aid<\/a> and available to onsite researchers. \u00a0 NLM is giving special attention to this and all of the Library’s archives and manuscript collections in a <a href=\"https:\/\/circulatingnow.nlm.nih.gov\/2016\/10\/04\/celebrating-american-archives-month\/\">number of activities<\/a> this month in honor of American Archives Month.<\/p>\n<p><em>Susan Speaker, PhD, is Historian for the Digital Manuscripts Program of the History of Medicine Division at the National Library of Medicine.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>By Susan Speaker Twenty-first century medical practitioners have many ways of making images of the inside of the body, including<\/p>\n","protected":false},"author":53041628,"featured_media":10354,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_coblocks_attr":"","_coblocks_dimensions":"","_coblocks_responsive_height":"","_coblocks_accordion_ie_support":"","advanced_seo_description":"","jetpack_seo_html_title":"","jetpack_seo_noindex":false,"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"Truly Translational: Louis Sokoloff and PET Brain Imaging - NLM announces a new Profiles in Science collection","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":false,"jetpack_social_options":{"image_generator_settings":{"template":"highway","enabled":false},"version":2}},"categories":[42333869,12763,103],"tags":[490,12080,16283,382263396,134383,631875,5535849],"class_list":["post-10326","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-archives-manuscripts","category-collections","category-news","tag-animals","tag-archives","tag-brain","tag-louis-sokoloff","tag-neurophysiology","tag-nih","tag-profiles-in-science"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/circulatingnow.nlm.nih.gov\/wp-content\/uploads\/2016\/10\/nlbbgc_feature2.png?fit=932%2C365&ssl=1","jetpack_likes_enabled":true,"jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p3xcDk-2Gy","jetpack-related-posts":[],"amp_enabled":true,"_links":{"self":[{"href":"https:\/\/circulatingnow.nlm.nih.gov\/wp-json\/wp\/v2\/posts\/10326","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/circulatingnow.nlm.nih.gov\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/circulatingnow.nlm.nih.gov\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/circulatingnow.nlm.nih.gov\/wp-json\/wp\/v2\/users\/53041628"}],"replies":[{"embeddable":true,"href":"https:\/\/circulatingnow.nlm.nih.gov\/wp-json\/wp\/v2\/comments?post=10326"}],"version-history":[{"count":26,"href":"https:\/\/circulatingnow.nlm.nih.gov\/wp-json\/wp\/v2\/posts\/10326\/revisions"}],"predecessor-version":[{"id":25577,"href":"https:\/\/circulatingnow.nlm.nih.gov\/wp-json\/wp\/v2\/posts\/10326\/revisions\/25577"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/circulatingnow.nlm.nih.gov\/wp-json\/wp\/v2\/media\/10354"}],"wp:attachment":[{"href":"https:\/\/circulatingnow.nlm.nih.gov\/wp-json\/wp\/v2\/media?parent=10326"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/circulatingnow.nlm.nih.gov\/wp-json\/wp\/v2\/categories?post=10326"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/circulatingnow.nlm.nih.gov\/wp-json\/wp\/v2\/tags?post=10326"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}} |