Loading…
Frequency‐dependent shear properties of annulus fibrosus and nucleus pulposus by magnetic resonance elastography
Aging and degeneration are associated with changes in mechanical properties in the intervertebral disc, generating interest in the establishment of mechanical properties as early biomarkers for the degenerative cascade. Magnetic resonance elastography (MRE) of the intervertebral disc is usually limi...
Saved in:
Published in: | NMR in biomedicine 2018-10, Vol.31 (10), p.e3918-n/a |
---|---|
Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c3498-3916faf49cb62c32a11e71aabc8dd917b21ac0d0ceb656ccf90cfd94c6fd69ad3 |
---|---|
cites | cdi_FETCH-LOGICAL-c3498-3916faf49cb62c32a11e71aabc8dd917b21ac0d0ceb656ccf90cfd94c6fd69ad3 |
container_end_page | n/a |
container_issue | 10 |
container_start_page | e3918 |
container_title | NMR in biomedicine |
container_volume | 31 |
creator | Beauchemin, P.F. Bayly, P.V. Garbow, J.R. Schmidt, J.L.S. Okamoto, R.J. Chériet, F. Périé, D. |
description | Aging and degeneration are associated with changes in mechanical properties in the intervertebral disc, generating interest in the establishment of mechanical properties as early biomarkers for the degenerative cascade. Magnetic resonance elastography (MRE) of the intervertebral disc is usually limited to the nucleus pulposus, as the annulus fibrosus is stiffer and less hydrated. The objective of this work was to adapt high‐frequency needle MRE to the characterization of the shear modulus of both the nucleus pulposus and annulus fibrosus. Bovine intervertebral discs were removed from fresh oxtails and characterized by needle MRE. The needle was inserted in the center of the disc and vibrations were generated by an amplified piezoelectric actuator. MRE acquisitions were performed on a 4.7‐T small‐animal MR scanner using a spin echo sequence with sinusoidal motion encoding gradients. Acquisitions were repeated over a frequency range of 1000–1800 Hz. The local frequency estimation inversion algorithm was used to compute the shear modulus. Stiffness maps allowed the visualization of the soft nucleus pulposus surrounded by the stiffer annulus fibrosus surrounded by the homogeneous gel. A significant difference in shear modulus between the nucleus pulposus and annulus fibrosus, and an increase in the shear modulus with excitation frequency, were observed, in agreement with the literature. This study demonstrates that global characterization of both the nucleus pulposus and annulus fibrosus of the intervertebral disc is possible with needle MRE using a preclinical magnetic resonance imaging (MRI) scanner. MRE can be a powerful method for the mapping of the complex properties of the intervertebral disc. The developed method could be adapted for in situ use by preserving adjacent vertebrae and puncturing the side of the intervertebral disc, thereby allowing an assessment of the contribution of osmotic pressure to the mechanical behavior of the intervertebral disc.
This study demonstrated that global characterization of the intervertebral disc was possible with needle Magnetic Resonance Elastography (MRE) using a preclinical MRI scanner. A significant difference in shear moduli between the nucleus pulposus and annulus fibrosus and an increase of shear modulus with excitation frequency were observed. MRE can be a powerful method for mapping the complex properties of the intervertebral disc without requiring multiple tests and biopsies. |
doi_str_mv | 10.1002/nbm.3918 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2035244990</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2035244990</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3498-3916faf49cb62c32a11e71aabc8dd917b21ac0d0ceb656ccf90cfd94c6fd69ad3</originalsourceid><addsrcrecordid>eNp1kctKxDAUhoMoOl7AJ5CAGzfV3KbTLHXwBl42ug5pcqKVNq1Ji3TnI_iMPokZxwsIrnIIHx_nPz9Cu5QcUkLYkS-bQy5psYImlEiZUSHZKpoQOWUZFwXZQJsxPhFCCsHZOtpgcsZmQhYTFM4CPA_gzfj--mahA2_B9zg-gg64C20Hoa8g4tZh7f1QDxG7qgxtTIP2FvvB1JDmbqi7z89yxI1-8NBXBgeIrdfeAIZax759CLp7HLfRmtN1hJ2vdwvdn53ezS-yq9vzy_nxVWZ4Wi1LeXKnnZCmzJnhTFMKM6p1aQprJZ2VjGpDLDFQ5tPcGCeJcVYKkzubS235FjpYelOMFDH2qqmigbrWHtohKkb4lAkhJUno_h_0qR2CT9spRomQORe8-BWalD8GcKoLVaPDqChRix5U6kEtekjo3pdwKBuwP-D34ROQLYGXqobxX5G6Obn-FH4A0P-Vtg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2104963438</pqid></control><display><type>article</type><title>Frequency‐dependent shear properties of annulus fibrosus and nucleus pulposus by magnetic resonance elastography</title><source>Wiley</source><creator>Beauchemin, P.F. ; Bayly, P.V. ; Garbow, J.R. ; Schmidt, J.L.S. ; Okamoto, R.J. ; Chériet, F. ; Périé, D.</creator><creatorcontrib>Beauchemin, P.F. ; Bayly, P.V. ; Garbow, J.R. ; Schmidt, J.L.S. ; Okamoto, R.J. ; Chériet, F. ; Périé, D.</creatorcontrib><description>Aging and degeneration are associated with changes in mechanical properties in the intervertebral disc, generating interest in the establishment of mechanical properties as early biomarkers for the degenerative cascade. Magnetic resonance elastography (MRE) of the intervertebral disc is usually limited to the nucleus pulposus, as the annulus fibrosus is stiffer and less hydrated. The objective of this work was to adapt high‐frequency needle MRE to the characterization of the shear modulus of both the nucleus pulposus and annulus fibrosus. Bovine intervertebral discs were removed from fresh oxtails and characterized by needle MRE. The needle was inserted in the center of the disc and vibrations were generated by an amplified piezoelectric actuator. MRE acquisitions were performed on a 4.7‐T small‐animal MR scanner using a spin echo sequence with sinusoidal motion encoding gradients. Acquisitions were repeated over a frequency range of 1000–1800 Hz. The local frequency estimation inversion algorithm was used to compute the shear modulus. Stiffness maps allowed the visualization of the soft nucleus pulposus surrounded by the stiffer annulus fibrosus surrounded by the homogeneous gel. A significant difference in shear modulus between the nucleus pulposus and annulus fibrosus, and an increase in the shear modulus with excitation frequency, were observed, in agreement with the literature. This study demonstrates that global characterization of both the nucleus pulposus and annulus fibrosus of the intervertebral disc is possible with needle MRE using a preclinical magnetic resonance imaging (MRI) scanner. MRE can be a powerful method for the mapping of the complex properties of the intervertebral disc. The developed method could be adapted for in situ use by preserving adjacent vertebrae and puncturing the side of the intervertebral disc, thereby allowing an assessment of the contribution of osmotic pressure to the mechanical behavior of the intervertebral disc.
This study demonstrated that global characterization of the intervertebral disc was possible with needle Magnetic Resonance Elastography (MRE) using a preclinical MRI scanner. A significant difference in shear moduli between the nucleus pulposus and annulus fibrosus and an increase of shear modulus with excitation frequency were observed. MRE can be a powerful method for mapping the complex properties of the intervertebral disc without requiring multiple tests and biopsies.</description><identifier>ISSN: 0952-3480</identifier><identifier>EISSN: 1099-1492</identifier><identifier>DOI: 10.1002/nbm.3918</identifier><identifier>PMID: 29727498</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Aging ; Animals ; Annuli ; annulus fibrosus ; Annulus Fibrosus - physiology ; Biological products ; Biomarkers ; Biomechanical Phenomena ; Cattle ; Degeneration ; Elasticity Imaging Techniques ; Frequency ranges ; Humans ; intervertebral disc ; Intervertebral discs ; Magnetic properties ; magnetic resonance elastography ; Magnetic Resonance Imaging ; Mapping ; Mechanical properties ; NMR ; Nuclear magnetic resonance ; Nucleus pulposus ; Nucleus Pulposus - physiology ; Osmosis ; Osmotic pressure ; Piercing ; Piezoelectric actuators ; Piezoelectricity ; Regression Analysis ; Resonance ; Shear modulus ; Shear properties ; Shear Strength ; Spine ; Stiffness ; Vertebrae ; Vibrations</subject><ispartof>NMR in biomedicine, 2018-10, Vol.31 (10), p.e3918-n/a</ispartof><rights>Copyright © 2018 John Wiley & Sons, Ltd.</rights><rights>2018 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3498-3916faf49cb62c32a11e71aabc8dd917b21ac0d0ceb656ccf90cfd94c6fd69ad3</citedby><cites>FETCH-LOGICAL-c3498-3916faf49cb62c32a11e71aabc8dd917b21ac0d0ceb656ccf90cfd94c6fd69ad3</cites><orcidid>0000-0002-9113-4738</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29727498$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beauchemin, P.F.</creatorcontrib><creatorcontrib>Bayly, P.V.</creatorcontrib><creatorcontrib>Garbow, J.R.</creatorcontrib><creatorcontrib>Schmidt, J.L.S.</creatorcontrib><creatorcontrib>Okamoto, R.J.</creatorcontrib><creatorcontrib>Chériet, F.</creatorcontrib><creatorcontrib>Périé, D.</creatorcontrib><title>Frequency‐dependent shear properties of annulus fibrosus and nucleus pulposus by magnetic resonance elastography</title><title>NMR in biomedicine</title><addtitle>NMR Biomed</addtitle><description>Aging and degeneration are associated with changes in mechanical properties in the intervertebral disc, generating interest in the establishment of mechanical properties as early biomarkers for the degenerative cascade. Magnetic resonance elastography (MRE) of the intervertebral disc is usually limited to the nucleus pulposus, as the annulus fibrosus is stiffer and less hydrated. The objective of this work was to adapt high‐frequency needle MRE to the characterization of the shear modulus of both the nucleus pulposus and annulus fibrosus. Bovine intervertebral discs were removed from fresh oxtails and characterized by needle MRE. The needle was inserted in the center of the disc and vibrations were generated by an amplified piezoelectric actuator. MRE acquisitions were performed on a 4.7‐T small‐animal MR scanner using a spin echo sequence with sinusoidal motion encoding gradients. Acquisitions were repeated over a frequency range of 1000–1800 Hz. The local frequency estimation inversion algorithm was used to compute the shear modulus. Stiffness maps allowed the visualization of the soft nucleus pulposus surrounded by the stiffer annulus fibrosus surrounded by the homogeneous gel. A significant difference in shear modulus between the nucleus pulposus and annulus fibrosus, and an increase in the shear modulus with excitation frequency, were observed, in agreement with the literature. This study demonstrates that global characterization of both the nucleus pulposus and annulus fibrosus of the intervertebral disc is possible with needle MRE using a preclinical magnetic resonance imaging (MRI) scanner. MRE can be a powerful method for the mapping of the complex properties of the intervertebral disc. The developed method could be adapted for in situ use by preserving adjacent vertebrae and puncturing the side of the intervertebral disc, thereby allowing an assessment of the contribution of osmotic pressure to the mechanical behavior of the intervertebral disc.
This study demonstrated that global characterization of the intervertebral disc was possible with needle Magnetic Resonance Elastography (MRE) using a preclinical MRI scanner. A significant difference in shear moduli between the nucleus pulposus and annulus fibrosus and an increase of shear modulus with excitation frequency were observed. MRE can be a powerful method for mapping the complex properties of the intervertebral disc without requiring multiple tests and biopsies.</description><subject>Aging</subject><subject>Animals</subject><subject>Annuli</subject><subject>annulus fibrosus</subject><subject>Annulus Fibrosus - physiology</subject><subject>Biological products</subject><subject>Biomarkers</subject><subject>Biomechanical Phenomena</subject><subject>Cattle</subject><subject>Degeneration</subject><subject>Elasticity Imaging Techniques</subject><subject>Frequency ranges</subject><subject>Humans</subject><subject>intervertebral disc</subject><subject>Intervertebral discs</subject><subject>Magnetic properties</subject><subject>magnetic resonance elastography</subject><subject>Magnetic Resonance Imaging</subject><subject>Mapping</subject><subject>Mechanical properties</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Nucleus pulposus</subject><subject>Nucleus Pulposus - physiology</subject><subject>Osmosis</subject><subject>Osmotic pressure</subject><subject>Piercing</subject><subject>Piezoelectric actuators</subject><subject>Piezoelectricity</subject><subject>Regression Analysis</subject><subject>Resonance</subject><subject>Shear modulus</subject><subject>Shear properties</subject><subject>Shear Strength</subject><subject>Spine</subject><subject>Stiffness</subject><subject>Vertebrae</subject><subject>Vibrations</subject><issn>0952-3480</issn><issn>1099-1492</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kctKxDAUhoMoOl7AJ5CAGzfV3KbTLHXwBl42ug5pcqKVNq1Ji3TnI_iMPokZxwsIrnIIHx_nPz9Cu5QcUkLYkS-bQy5psYImlEiZUSHZKpoQOWUZFwXZQJsxPhFCCsHZOtpgcsZmQhYTFM4CPA_gzfj--mahA2_B9zg-gg64C20Hoa8g4tZh7f1QDxG7qgxtTIP2FvvB1JDmbqi7z89yxI1-8NBXBgeIrdfeAIZax759CLp7HLfRmtN1hJ2vdwvdn53ezS-yq9vzy_nxVWZ4Wi1LeXKnnZCmzJnhTFMKM6p1aQprJZ2VjGpDLDFQ5tPcGCeJcVYKkzubS235FjpYelOMFDH2qqmigbrWHtohKkb4lAkhJUno_h_0qR2CT9spRomQORe8-BWalD8GcKoLVaPDqChRix5U6kEtekjo3pdwKBuwP-D34ROQLYGXqobxX5G6Obn-FH4A0P-Vtg</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Beauchemin, P.F.</creator><creator>Bayly, P.V.</creator><creator>Garbow, J.R.</creator><creator>Schmidt, J.L.S.</creator><creator>Okamoto, R.J.</creator><creator>Chériet, F.</creator><creator>Périé, D.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9113-4738</orcidid></search><sort><creationdate>201810</creationdate><title>Frequency‐dependent shear properties of annulus fibrosus and nucleus pulposus by magnetic resonance elastography</title><author>Beauchemin, P.F. ; Bayly, P.V. ; Garbow, J.R. ; Schmidt, J.L.S. ; Okamoto, R.J. ; Chériet, F. ; Périé, D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3498-3916faf49cb62c32a11e71aabc8dd917b21ac0d0ceb656ccf90cfd94c6fd69ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aging</topic><topic>Animals</topic><topic>Annuli</topic><topic>annulus fibrosus</topic><topic>Annulus Fibrosus - physiology</topic><topic>Biological products</topic><topic>Biomarkers</topic><topic>Biomechanical Phenomena</topic><topic>Cattle</topic><topic>Degeneration</topic><topic>Elasticity Imaging Techniques</topic><topic>Frequency ranges</topic><topic>Humans</topic><topic>intervertebral disc</topic><topic>Intervertebral discs</topic><topic>Magnetic properties</topic><topic>magnetic resonance elastography</topic><topic>Magnetic Resonance Imaging</topic><topic>Mapping</topic><topic>Mechanical properties</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Nucleus pulposus</topic><topic>Nucleus Pulposus - physiology</topic><topic>Osmosis</topic><topic>Osmotic pressure</topic><topic>Piercing</topic><topic>Piezoelectric actuators</topic><topic>Piezoelectricity</topic><topic>Regression Analysis</topic><topic>Resonance</topic><topic>Shear modulus</topic><topic>Shear properties</topic><topic>Shear Strength</topic><topic>Spine</topic><topic>Stiffness</topic><topic>Vertebrae</topic><topic>Vibrations</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beauchemin, P.F.</creatorcontrib><creatorcontrib>Bayly, P.V.</creatorcontrib><creatorcontrib>Garbow, J.R.</creatorcontrib><creatorcontrib>Schmidt, J.L.S.</creatorcontrib><creatorcontrib>Okamoto, R.J.</creatorcontrib><creatorcontrib>Chériet, F.</creatorcontrib><creatorcontrib>Périé, D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>NMR in biomedicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beauchemin, P.F.</au><au>Bayly, P.V.</au><au>Garbow, J.R.</au><au>Schmidt, J.L.S.</au><au>Okamoto, R.J.</au><au>Chériet, F.</au><au>Périé, D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Frequency‐dependent shear properties of annulus fibrosus and nucleus pulposus by magnetic resonance elastography</atitle><jtitle>NMR in biomedicine</jtitle><addtitle>NMR Biomed</addtitle><date>2018-10</date><risdate>2018</risdate><volume>31</volume><issue>10</issue><spage>e3918</spage><epage>n/a</epage><pages>e3918-n/a</pages><issn>0952-3480</issn><eissn>1099-1492</eissn><abstract>Aging and degeneration are associated with changes in mechanical properties in the intervertebral disc, generating interest in the establishment of mechanical properties as early biomarkers for the degenerative cascade. Magnetic resonance elastography (MRE) of the intervertebral disc is usually limited to the nucleus pulposus, as the annulus fibrosus is stiffer and less hydrated. The objective of this work was to adapt high‐frequency needle MRE to the characterization of the shear modulus of both the nucleus pulposus and annulus fibrosus. Bovine intervertebral discs were removed from fresh oxtails and characterized by needle MRE. The needle was inserted in the center of the disc and vibrations were generated by an amplified piezoelectric actuator. MRE acquisitions were performed on a 4.7‐T small‐animal MR scanner using a spin echo sequence with sinusoidal motion encoding gradients. Acquisitions were repeated over a frequency range of 1000–1800 Hz. The local frequency estimation inversion algorithm was used to compute the shear modulus. Stiffness maps allowed the visualization of the soft nucleus pulposus surrounded by the stiffer annulus fibrosus surrounded by the homogeneous gel. A significant difference in shear modulus between the nucleus pulposus and annulus fibrosus, and an increase in the shear modulus with excitation frequency, were observed, in agreement with the literature. This study demonstrates that global characterization of both the nucleus pulposus and annulus fibrosus of the intervertebral disc is possible with needle MRE using a preclinical magnetic resonance imaging (MRI) scanner. MRE can be a powerful method for the mapping of the complex properties of the intervertebral disc. The developed method could be adapted for in situ use by preserving adjacent vertebrae and puncturing the side of the intervertebral disc, thereby allowing an assessment of the contribution of osmotic pressure to the mechanical behavior of the intervertebral disc.
This study demonstrated that global characterization of the intervertebral disc was possible with needle Magnetic Resonance Elastography (MRE) using a preclinical MRI scanner. A significant difference in shear moduli between the nucleus pulposus and annulus fibrosus and an increase of shear modulus with excitation frequency were observed. MRE can be a powerful method for mapping the complex properties of the intervertebral disc without requiring multiple tests and biopsies.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29727498</pmid><doi>10.1002/nbm.3918</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-9113-4738</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0952-3480 |
ispartof | NMR in biomedicine, 2018-10, Vol.31 (10), p.e3918-n/a |
issn | 0952-3480 1099-1492 |
language | eng |
recordid | cdi_proquest_miscellaneous_2035244990 |
source | Wiley |
subjects | Aging Animals Annuli annulus fibrosus Annulus Fibrosus - physiology Biological products Biomarkers Biomechanical Phenomena Cattle Degeneration Elasticity Imaging Techniques Frequency ranges Humans intervertebral disc Intervertebral discs Magnetic properties magnetic resonance elastography Magnetic Resonance Imaging Mapping Mechanical properties NMR Nuclear magnetic resonance Nucleus pulposus Nucleus Pulposus - physiology Osmosis Osmotic pressure Piercing Piezoelectric actuators Piezoelectricity Regression Analysis Resonance Shear modulus Shear properties Shear Strength Spine Stiffness Vertebrae Vibrations |
title | Frequency‐dependent shear properties of annulus fibrosus and nucleus pulposus by magnetic resonance elastography |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T16%3A17%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Frequency%E2%80%90dependent%20shear%20properties%20of%20annulus%20fibrosus%20and%20nucleus%20pulposus%20by%20magnetic%20resonance%20elastography&rft.jtitle=NMR%20in%20biomedicine&rft.au=Beauchemin,%20P.F.&rft.date=2018-10&rft.volume=31&rft.issue=10&rft.spage=e3918&rft.epage=n/a&rft.pages=e3918-n/a&rft.issn=0952-3480&rft.eissn=1099-1492&rft_id=info:doi/10.1002/nbm.3918&rft_dat=%3Cproquest_cross%3E2035244990%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c3498-3916faf49cb62c32a11e71aabc8dd917b21ac0d0ceb656ccf90cfd94c6fd69ad3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2104963438&rft_id=info:pmid/29727498&rfr_iscdi=true |