Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks

Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery 1 . The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive 2 , 3 . Moreover, interpretation of intraoperativ...

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Veröffentlicht in:Nature medicine 2020-01, Vol.26 (1), p.52-58
Hauptverfasser: Hollon, Todd C., Pandian, Balaji, Adapa, Arjun R., Urias, Esteban, Save, Akshay V., Khalsa, Siri Sahib S., Eichberg, Daniel G., D’Amico, Randy S., Farooq, Zia U., Lewis, Spencer, Petridis, Petros D., Marie, Tamara, Shah, Ashish H., Garton, Hugh J. L., Maher, Cormac O., Heth, Jason A., McKean, Erin L., Sullivan, Stephen E., Hervey-Jumper, Shawn L., Patil, Parag G., Thompson, B. Gregory, Sagher, Oren, McKhann, Guy M., Komotar, Ricardo J., Ivan, Michael E., Snuderl, Matija, Otten, Marc L., Johnson, Timothy D., Sisti, Michael B., Bruce, Jeffrey N., Muraszko, Karin M., Trautman, Jay, Freudiger, Christian W., Canoll, Peter, Lee, Honglak, Camelo-Piragua, Sandra, Orringer, Daniel A.
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container_end_page 58
container_issue 1
container_start_page 52
container_title Nature medicine
container_volume 26
creator Hollon, Todd C.
Pandian, Balaji
Adapa, Arjun R.
Urias, Esteban
Save, Akshay V.
Khalsa, Siri Sahib S.
Eichberg, Daniel G.
D’Amico, Randy S.
Farooq, Zia U.
Lewis, Spencer
Petridis, Petros D.
Marie, Tamara
Shah, Ashish H.
Garton, Hugh J. L.
Maher, Cormac O.
Heth, Jason A.
McKean, Erin L.
Sullivan, Stephen E.
Hervey-Jumper, Shawn L.
Patil, Parag G.
Thompson, B. Gregory
Sagher, Oren
McKhann, Guy M.
Komotar, Ricardo J.
Ivan, Michael E.
Snuderl, Matija
Otten, Marc L.
Johnson, Timothy D.
Sisti, Michael B.
Bruce, Jeffrey N.
Muraszko, Karin M.
Trautman, Jay
Freudiger, Christian W.
Canoll, Peter
Lee, Honglak
Camelo-Piragua, Sandra
Orringer, Daniel A.
description Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery 1 . The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive 2 , 3 . Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce 4 . In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH) 5 – 7 , a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20–30 min) 2 . In a multicenter, prospective clinical trial ( n  = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory. A prospective, multicenter, case–control clinical trial evaluates the potential of artificial intelligence for providing accurate bedside diagnosis of patients with brain tumors.
doi_str_mv 10.1038/s41591-019-0715-9
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In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH) 5 – 7 , a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20–30 min) 2 . In a multicenter, prospective clinical trial ( n  = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory. 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The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive 2 , 3 . Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce 4 . In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH) 5 – 7 , a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20–30 min) 2 . In a multicenter, prospective clinical trial ( n  = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory. 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Gregory ; Sagher, Oren ; McKhann, Guy M. ; Komotar, Ricardo J. ; Ivan, Michael E. ; Snuderl, Matija ; Otten, Marc L. ; Johnson, Timothy D. ; Sisti, Michael B. ; Bruce, Jeffrey N. ; Muraszko, Karin M. ; Trautman, Jay ; Freudiger, Christian W. ; Canoll, Peter ; Lee, Honglak ; Camelo-Piragua, Sandra ; Orringer, Daniel A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c740t-2e3d1ec3bd07b5ae0dccf65f6a686b29f777998b32f732b60b56bf240caf6f2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/114/1305</topic><topic>631/1647/527/1821</topic><topic>631/67/2321</topic><topic>692/308/575</topic><topic>Algorithms</topic><topic>Artificial intelligence</topic><topic>Artificial neural networks</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - diagnosis</topic><topic>Brain Neoplasms - diagnostic imaging</topic><topic>Brain tumors</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Clinical trials</topic><topic>Clinical Trials as Topic</topic><topic>Computer Systems</topic><topic>Deep Learning</topic><topic>Diagnosis</topic><topic>Diagnostic systems</topic><topic>Feature recognition</topic><topic>Health aspects</topic><topic>Histology</topic><topic>Humans</topic><topic>Image Processing, Computer-Assisted</topic><topic>Image segmentation</topic><topic>Infectious Diseases</topic><topic>Letter</topic><topic>Medical imaging</topic><topic>Metabolic Diseases</topic><topic>Molecular Medicine</topic><topic>Monitoring, Intraoperative</topic><topic>Neural networks</topic><topic>Neural Networks, Computer</topic><topic>Neuroimaging</topic><topic>Neurosciences</topic><topic>Pathology</topic><topic>Probability</topic><topic>Raman spectroscopy</topic><topic>Real time</topic><topic>Spectrum Analysis, Raman</topic><topic>Tumors</topic><topic>Workflow</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hollon, Todd C.</creatorcontrib><creatorcontrib>Pandian, Balaji</creatorcontrib><creatorcontrib>Adapa, Arjun R.</creatorcontrib><creatorcontrib>Urias, Esteban</creatorcontrib><creatorcontrib>Save, Akshay V.</creatorcontrib><creatorcontrib>Khalsa, Siri Sahib S.</creatorcontrib><creatorcontrib>Eichberg, Daniel G.</creatorcontrib><creatorcontrib>D’Amico, Randy S.</creatorcontrib><creatorcontrib>Farooq, Zia U.</creatorcontrib><creatorcontrib>Lewis, Spencer</creatorcontrib><creatorcontrib>Petridis, Petros D.</creatorcontrib><creatorcontrib>Marie, Tamara</creatorcontrib><creatorcontrib>Shah, Ashish H.</creatorcontrib><creatorcontrib>Garton, Hugh J. 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Gregory</creatorcontrib><creatorcontrib>Sagher, Oren</creatorcontrib><creatorcontrib>McKhann, Guy M.</creatorcontrib><creatorcontrib>Komotar, Ricardo J.</creatorcontrib><creatorcontrib>Ivan, Michael E.</creatorcontrib><creatorcontrib>Snuderl, Matija</creatorcontrib><creatorcontrib>Otten, Marc L.</creatorcontrib><creatorcontrib>Johnson, Timothy D.</creatorcontrib><creatorcontrib>Sisti, Michael B.</creatorcontrib><creatorcontrib>Bruce, Jeffrey N.</creatorcontrib><creatorcontrib>Muraszko, Karin M.</creatorcontrib><creatorcontrib>Trautman, Jay</creatorcontrib><creatorcontrib>Freudiger, Christian W.</creatorcontrib><creatorcontrib>Canoll, Peter</creatorcontrib><creatorcontrib>Lee, Honglak</creatorcontrib><creatorcontrib>Camelo-Piragua, Sandra</creatorcontrib><creatorcontrib>Orringer, Daniel A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hollon, Todd C.</au><au>Pandian, Balaji</au><au>Adapa, Arjun R.</au><au>Urias, Esteban</au><au>Save, Akshay V.</au><au>Khalsa, Siri Sahib S.</au><au>Eichberg, Daniel G.</au><au>D’Amico, Randy S.</au><au>Farooq, Zia U.</au><au>Lewis, Spencer</au><au>Petridis, Petros D.</au><au>Marie, Tamara</au><au>Shah, Ashish H.</au><au>Garton, Hugh J. L.</au><au>Maher, Cormac O.</au><au>Heth, Jason A.</au><au>McKean, Erin L.</au><au>Sullivan, Stephen E.</au><au>Hervey-Jumper, Shawn L.</au><au>Patil, Parag G.</au><au>Thompson, B. Gregory</au><au>Sagher, Oren</au><au>McKhann, Guy M.</au><au>Komotar, Ricardo J.</au><au>Ivan, Michael E.</au><au>Snuderl, Matija</au><au>Otten, Marc L.</au><au>Johnson, Timothy D.</au><au>Sisti, Michael B.</au><au>Bruce, Jeffrey N.</au><au>Muraszko, Karin M.</au><au>Trautman, Jay</au><au>Freudiger, Christian W.</au><au>Canoll, Peter</au><au>Lee, Honglak</au><au>Camelo-Piragua, Sandra</au><au>Orringer, Daniel A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks</atitle><jtitle>Nature medicine</jtitle><stitle>Nat Med</stitle><addtitle>Nat Med</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>26</volume><issue>1</issue><spage>52</spage><epage>58</epage><pages>52-58</pages><issn>1078-8956</issn><eissn>1546-170X</eissn><abstract>Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery 1 . The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive 2 , 3 . Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce 4 . In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH) 5 – 7 , a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20–30 min) 2 . In a multicenter, prospective clinical trial ( n  = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory. A prospective, multicenter, case–control clinical trial evaluates the potential of artificial intelligence for providing accurate bedside diagnosis of patients with brain tumors.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>31907460</pmid><doi>10.1038/s41591-019-0715-9</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-2300-6136</orcidid><orcidid>https://orcid.org/0000-0001-7608-5723</orcidid><orcidid>https://orcid.org/0000-0002-4798-4989</orcidid><orcidid>https://orcid.org/0000-0001-5987-6531</orcidid><orcidid>https://orcid.org/0000-0001-6427-8376</orcidid><orcidid>https://orcid.org/0000-0003-0800-3866</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1078-8956
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issn 1078-8956
1546-170X
language eng
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source MEDLINE; Nature; Alma/SFX Local Collection
subjects 631/114/1305
631/1647/527/1821
631/67/2321
692/308/575
Algorithms
Artificial intelligence
Artificial neural networks
Biomedical and Life Sciences
Biomedicine
Brain
Brain cancer
Brain Neoplasms - diagnosis
Brain Neoplasms - diagnostic imaging
Brain tumors
Cancer
Cancer Research
Clinical trials
Clinical Trials as Topic
Computer Systems
Deep Learning
Diagnosis
Diagnostic systems
Feature recognition
Health aspects
Histology
Humans
Image Processing, Computer-Assisted
Image segmentation
Infectious Diseases
Letter
Medical imaging
Metabolic Diseases
Molecular Medicine
Monitoring, Intraoperative
Neural networks
Neural Networks, Computer
Neuroimaging
Neurosciences
Pathology
Probability
Raman spectroscopy
Real time
Spectrum Analysis, Raman
Tumors
Workflow
title Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks
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