Traumatic axonal injury: is the prognostic information produced by conventional MRI and DTI complementary or supplementary?
A traumatic axonal injury (TAI) diagnosis has traditionally been based on conventional MRI, especially on those sequences with a higher sensitivity to edema and blood degradation products. A more recent technique, diffusion tensor imaging (DTI), can infer the microstructure of white matter (WM) due...
Gespeichert in:
Veröffentlicht in: | Journal of neurosurgery 2022-01, Vol.136 (1), p.242-256 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 256 |
---|---|
container_issue | 1 |
container_start_page | 242 |
container_title | Journal of neurosurgery |
container_volume | 136 |
creator | Castaño-Leon, Ana M Cicuendez, Marta Navarro-Main, Blanca Paredes, Igor Munarriz, Pablo M Hilario, Amaya Ramos, Ana Gomez, Pedro A Lagares, Alfonso |
description | A traumatic axonal injury (TAI) diagnosis has traditionally been based on conventional MRI, especially on those sequences with a higher sensitivity to edema and blood degradation products. A more recent technique, diffusion tensor imaging (DTI), can infer the microstructure of white matter (WM) due to the restricted diffusion of water in organized tissues. However, there is little information regarding the correlation of the findings obtained by both methods and their use for outcome prognosis. The main objectives of this study were threefold: 1) study the correlation between DTI metrics and conventional MRI findings; 2) evaluate whether the prognostic information provided by the two techniques is supplementary or complementary; and 3) determine the incremental value of the addition of these variables compared to a traditional prognostic model.
The authors studied 185 patients with moderate to severe traumatic brain injury (TBI) who underwent MRI with DTI study during the subacute stage. The number and volume of lesions in hemispheric subcortical WM, corpus callosum (CC), basal ganglia, thalamus, and brainstem in at least four conventional MRI sequences (T1-weighted, T2-weighted, FLAIR, T2* gradient recalled echo, susceptibility-weighted imaging, and diffusion-weighted imaging) were determined. Fractional anisotropy (FA) was measured in 28 WM bundles using the region of interest method. Nonparametric tests were used to evaluate the colocalization of macroscopic lesions and FA. A multivariate logistic regression analysis was performed to assess the independent prognostic value of each neuroimaging modality after adjustment for relevant clinical covariates, and the internal validation of the model was evaluated in a contemporary cohort of 92 patients.
Differences in the lesion load between patients according to their severity and outcome were found. Colocalization of macroscopic nonhemorrhagic TAI lesions (not microbleeds) and lower FA was limited to the internal and external capsule, corona radiata, inferior frontooccipital fasciculus, CC, and brainstem. However, a significant association between the FA value and the identification of macroscopic lesions in distant brain regions was also detected. Specifically, lower values of FA of some hemispheric WM bundles and the splenium of the CC were related to a higher number and volume of hyperintensities in the brainstem. The regression analysis revealed that age, motor score, hypoxia, FA of the genu of the CC, c |
doi_str_mv | 10.3171/2020.11.JNS203124 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2548406793</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2548406793</sourcerecordid><originalsourceid>FETCH-LOGICAL-c301t-4dfec1c429e619971bdcc86448d0624af74b01e6b9e687dffd55f31dcc9797cc3</originalsourceid><addsrcrecordid>eNpFkMlOwzAQhi0EoqXwAFyQj1xSPLabhQtCZStikaCcI8d2IFViFztBVLw8jlrKaaR_Gc18CB0DGTNI4IwSSsYA4_unV0oYUL6DhpAxFpE4Y7toSAilESPpZIAOvF8QAjGP6T4aME6BZ0k2RD9zJ7pGtJXE4tsaUePKLDq3OseVx-2Hxktn3431faAypXV91ppeVp3UChcrLK350qaXQ_3xZYaFUfhqPgtGs6x1EzzhVtg67Lvlv3BxiPZKUXt9tJkj9HZzPZ_eRQ_Pt7Pp5UMkGYE24qrUEiSnmY4hyxIolJRpzHmqSEy5KBNeENBxEfw0UWWpJpOSQQiFDxMp2QidrveGoz877du8qbzUdS2Mtp3P6YSnnMRJIDdCsI5KZ713usyXrmrCsTmQvGee98xzgHzLPHRONuu7otFq2_iDzH4BhQt_Vg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2548406793</pqid></control><display><type>article</type><title>Traumatic axonal injury: is the prognostic information produced by conventional MRI and DTI complementary or supplementary?</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Castaño-Leon, Ana M ; Cicuendez, Marta ; Navarro-Main, Blanca ; Paredes, Igor ; Munarriz, Pablo M ; Hilario, Amaya ; Ramos, Ana ; Gomez, Pedro A ; Lagares, Alfonso</creator><creatorcontrib>Castaño-Leon, Ana M ; Cicuendez, Marta ; Navarro-Main, Blanca ; Paredes, Igor ; Munarriz, Pablo M ; Hilario, Amaya ; Ramos, Ana ; Gomez, Pedro A ; Lagares, Alfonso</creatorcontrib><description>A traumatic axonal injury (TAI) diagnosis has traditionally been based on conventional MRI, especially on those sequences with a higher sensitivity to edema and blood degradation products. A more recent technique, diffusion tensor imaging (DTI), can infer the microstructure of white matter (WM) due to the restricted diffusion of water in organized tissues. However, there is little information regarding the correlation of the findings obtained by both methods and their use for outcome prognosis. The main objectives of this study were threefold: 1) study the correlation between DTI metrics and conventional MRI findings; 2) evaluate whether the prognostic information provided by the two techniques is supplementary or complementary; and 3) determine the incremental value of the addition of these variables compared to a traditional prognostic model.
The authors studied 185 patients with moderate to severe traumatic brain injury (TBI) who underwent MRI with DTI study during the subacute stage. The number and volume of lesions in hemispheric subcortical WM, corpus callosum (CC), basal ganglia, thalamus, and brainstem in at least four conventional MRI sequences (T1-weighted, T2-weighted, FLAIR, T2* gradient recalled echo, susceptibility-weighted imaging, and diffusion-weighted imaging) were determined. Fractional anisotropy (FA) was measured in 28 WM bundles using the region of interest method. Nonparametric tests were used to evaluate the colocalization of macroscopic lesions and FA. A multivariate logistic regression analysis was performed to assess the independent prognostic value of each neuroimaging modality after adjustment for relevant clinical covariates, and the internal validation of the model was evaluated in a contemporary cohort of 92 patients.
Differences in the lesion load between patients according to their severity and outcome were found. Colocalization of macroscopic nonhemorrhagic TAI lesions (not microbleeds) and lower FA was limited to the internal and external capsule, corona radiata, inferior frontooccipital fasciculus, CC, and brainstem. However, a significant association between the FA value and the identification of macroscopic lesions in distant brain regions was also detected. Specifically, lower values of FA of some hemispheric WM bundles and the splenium of the CC were related to a higher number and volume of hyperintensities in the brainstem. The regression analysis revealed that age, motor score, hypoxia, FA of the genu of the CC, characterization of TAI lesions in the CC, and the presence of thalamic/basal ganglia lesions were independent prognostic factors. The performance of the proposed model was higher than that of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in TBI) model in the validation cohort.
Very limited colocalization of hyperintensities (none for microbleeds) with FA values was discovered. DTI and conventional MRI provide complementary prognostic information, and their combination can improve the performance of traditional prognostic models.</description><identifier>ISSN: 0022-3085</identifier><identifier>EISSN: 1933-0693</identifier><identifier>DOI: 10.3171/2020.11.JNS203124</identifier><identifier>PMID: 34214979</identifier><language>eng</language><publisher>United States</publisher><subject>Adolescent ; Adult ; Aged ; Anisotropy ; Brain Injuries, Traumatic - diagnostic imaging ; Brain Injuries, Traumatic - surgery ; Brain Mapping ; Diffuse Axonal Injury - diagnostic imaging ; Diffuse Axonal Injury - surgery ; Diffusion Tensor Imaging ; Female ; Glasgow Outcome Scale ; Healthy Volunteers ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuroimaging - methods ; Neurosurgical Procedures ; Predictive Value of Tests ; Prognosis ; Treatment Outcome ; White Matter - diagnostic imaging ; White Matter - surgery ; Young Adult</subject><ispartof>Journal of neurosurgery, 2022-01, Vol.136 (1), p.242-256</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c301t-4dfec1c429e619971bdcc86448d0624af74b01e6b9e687dffd55f31dcc9797cc3</citedby><cites>FETCH-LOGICAL-c301t-4dfec1c429e619971bdcc86448d0624af74b01e6b9e687dffd55f31dcc9797cc3</cites></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/34214979$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Castaño-Leon, Ana M</creatorcontrib><creatorcontrib>Cicuendez, Marta</creatorcontrib><creatorcontrib>Navarro-Main, Blanca</creatorcontrib><creatorcontrib>Paredes, Igor</creatorcontrib><creatorcontrib>Munarriz, Pablo M</creatorcontrib><creatorcontrib>Hilario, Amaya</creatorcontrib><creatorcontrib>Ramos, Ana</creatorcontrib><creatorcontrib>Gomez, Pedro A</creatorcontrib><creatorcontrib>Lagares, Alfonso</creatorcontrib><title>Traumatic axonal injury: is the prognostic information produced by conventional MRI and DTI complementary or supplementary?</title><title>Journal of neurosurgery</title><addtitle>J Neurosurg</addtitle><description>A traumatic axonal injury (TAI) diagnosis has traditionally been based on conventional MRI, especially on those sequences with a higher sensitivity to edema and blood degradation products. A more recent technique, diffusion tensor imaging (DTI), can infer the microstructure of white matter (WM) due to the restricted diffusion of water in organized tissues. However, there is little information regarding the correlation of the findings obtained by both methods and their use for outcome prognosis. The main objectives of this study were threefold: 1) study the correlation between DTI metrics and conventional MRI findings; 2) evaluate whether the prognostic information provided by the two techniques is supplementary or complementary; and 3) determine the incremental value of the addition of these variables compared to a traditional prognostic model.
The authors studied 185 patients with moderate to severe traumatic brain injury (TBI) who underwent MRI with DTI study during the subacute stage. The number and volume of lesions in hemispheric subcortical WM, corpus callosum (CC), basal ganglia, thalamus, and brainstem in at least four conventional MRI sequences (T1-weighted, T2-weighted, FLAIR, T2* gradient recalled echo, susceptibility-weighted imaging, and diffusion-weighted imaging) were determined. Fractional anisotropy (FA) was measured in 28 WM bundles using the region of interest method. Nonparametric tests were used to evaluate the colocalization of macroscopic lesions and FA. A multivariate logistic regression analysis was performed to assess the independent prognostic value of each neuroimaging modality after adjustment for relevant clinical covariates, and the internal validation of the model was evaluated in a contemporary cohort of 92 patients.
Differences in the lesion load between patients according to their severity and outcome were found. Colocalization of macroscopic nonhemorrhagic TAI lesions (not microbleeds) and lower FA was limited to the internal and external capsule, corona radiata, inferior frontooccipital fasciculus, CC, and brainstem. However, a significant association between the FA value and the identification of macroscopic lesions in distant brain regions was also detected. Specifically, lower values of FA of some hemispheric WM bundles and the splenium of the CC were related to a higher number and volume of hyperintensities in the brainstem. The regression analysis revealed that age, motor score, hypoxia, FA of the genu of the CC, characterization of TAI lesions in the CC, and the presence of thalamic/basal ganglia lesions were independent prognostic factors. The performance of the proposed model was higher than that of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in TBI) model in the validation cohort.
Very limited colocalization of hyperintensities (none for microbleeds) with FA values was discovered. DTI and conventional MRI provide complementary prognostic information, and their combination can improve the performance of traditional prognostic models.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Anisotropy</subject><subject>Brain Injuries, Traumatic - diagnostic imaging</subject><subject>Brain Injuries, Traumatic - surgery</subject><subject>Brain Mapping</subject><subject>Diffuse Axonal Injury - diagnostic imaging</subject><subject>Diffuse Axonal Injury - surgery</subject><subject>Diffusion Tensor Imaging</subject><subject>Female</subject><subject>Glasgow Outcome Scale</subject><subject>Healthy Volunteers</subject><subject>Humans</subject><subject>Image Processing, Computer-Assisted</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neuroimaging - methods</subject><subject>Neurosurgical Procedures</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Treatment Outcome</subject><subject>White Matter - diagnostic imaging</subject><subject>White Matter - surgery</subject><subject>Young Adult</subject><issn>0022-3085</issn><issn>1933-0693</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMlOwzAQhi0EoqXwAFyQj1xSPLabhQtCZStikaCcI8d2IFViFztBVLw8jlrKaaR_Gc18CB0DGTNI4IwSSsYA4_unV0oYUL6DhpAxFpE4Y7toSAilESPpZIAOvF8QAjGP6T4aME6BZ0k2RD9zJ7pGtJXE4tsaUePKLDq3OseVx-2Hxktn3431faAypXV91ppeVp3UChcrLK350qaXQ_3xZYaFUfhqPgtGs6x1EzzhVtg67Lvlv3BxiPZKUXt9tJkj9HZzPZ_eRQ_Pt7Pp5UMkGYE24qrUEiSnmY4hyxIolJRpzHmqSEy5KBNeENBxEfw0UWWpJpOSQQiFDxMp2QidrveGoz877du8qbzUdS2Mtp3P6YSnnMRJIDdCsI5KZ713usyXrmrCsTmQvGee98xzgHzLPHRONuu7otFq2_iDzH4BhQt_Vg</recordid><startdate>20220101</startdate><enddate>20220101</enddate><creator>Castaño-Leon, Ana M</creator><creator>Cicuendez, Marta</creator><creator>Navarro-Main, Blanca</creator><creator>Paredes, Igor</creator><creator>Munarriz, Pablo M</creator><creator>Hilario, Amaya</creator><creator>Ramos, Ana</creator><creator>Gomez, Pedro A</creator><creator>Lagares, Alfonso</creator><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>7X8</scope></search><sort><creationdate>20220101</creationdate><title>Traumatic axonal injury: is the prognostic information produced by conventional MRI and DTI complementary or supplementary?</title><author>Castaño-Leon, Ana M ; Cicuendez, Marta ; Navarro-Main, Blanca ; Paredes, Igor ; Munarriz, Pablo M ; Hilario, Amaya ; Ramos, Ana ; Gomez, Pedro A ; Lagares, Alfonso</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c301t-4dfec1c429e619971bdcc86448d0624af74b01e6b9e687dffd55f31dcc9797cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Anisotropy</topic><topic>Brain Injuries, Traumatic - diagnostic imaging</topic><topic>Brain Injuries, Traumatic - surgery</topic><topic>Brain Mapping</topic><topic>Diffuse Axonal Injury - diagnostic imaging</topic><topic>Diffuse Axonal Injury - surgery</topic><topic>Diffusion Tensor Imaging</topic><topic>Female</topic><topic>Glasgow Outcome Scale</topic><topic>Healthy Volunteers</topic><topic>Humans</topic><topic>Image Processing, Computer-Assisted</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neuroimaging - methods</topic><topic>Neurosurgical Procedures</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Treatment Outcome</topic><topic>White Matter - diagnostic imaging</topic><topic>White Matter - surgery</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Castaño-Leon, Ana M</creatorcontrib><creatorcontrib>Cicuendez, Marta</creatorcontrib><creatorcontrib>Navarro-Main, Blanca</creatorcontrib><creatorcontrib>Paredes, Igor</creatorcontrib><creatorcontrib>Munarriz, Pablo M</creatorcontrib><creatorcontrib>Hilario, Amaya</creatorcontrib><creatorcontrib>Ramos, Ana</creatorcontrib><creatorcontrib>Gomez, Pedro A</creatorcontrib><creatorcontrib>Lagares, Alfonso</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurosurgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Castaño-Leon, Ana M</au><au>Cicuendez, Marta</au><au>Navarro-Main, Blanca</au><au>Paredes, Igor</au><au>Munarriz, Pablo M</au><au>Hilario, Amaya</au><au>Ramos, Ana</au><au>Gomez, Pedro A</au><au>Lagares, Alfonso</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Traumatic axonal injury: is the prognostic information produced by conventional MRI and DTI complementary or supplementary?</atitle><jtitle>Journal of neurosurgery</jtitle><addtitle>J Neurosurg</addtitle><date>2022-01-01</date><risdate>2022</risdate><volume>136</volume><issue>1</issue><spage>242</spage><epage>256</epage><pages>242-256</pages><issn>0022-3085</issn><eissn>1933-0693</eissn><abstract>A traumatic axonal injury (TAI) diagnosis has traditionally been based on conventional MRI, especially on those sequences with a higher sensitivity to edema and blood degradation products. A more recent technique, diffusion tensor imaging (DTI), can infer the microstructure of white matter (WM) due to the restricted diffusion of water in organized tissues. However, there is little information regarding the correlation of the findings obtained by both methods and their use for outcome prognosis. The main objectives of this study were threefold: 1) study the correlation between DTI metrics and conventional MRI findings; 2) evaluate whether the prognostic information provided by the two techniques is supplementary or complementary; and 3) determine the incremental value of the addition of these variables compared to a traditional prognostic model.
The authors studied 185 patients with moderate to severe traumatic brain injury (TBI) who underwent MRI with DTI study during the subacute stage. The number and volume of lesions in hemispheric subcortical WM, corpus callosum (CC), basal ganglia, thalamus, and brainstem in at least four conventional MRI sequences (T1-weighted, T2-weighted, FLAIR, T2* gradient recalled echo, susceptibility-weighted imaging, and diffusion-weighted imaging) were determined. Fractional anisotropy (FA) was measured in 28 WM bundles using the region of interest method. Nonparametric tests were used to evaluate the colocalization of macroscopic lesions and FA. A multivariate logistic regression analysis was performed to assess the independent prognostic value of each neuroimaging modality after adjustment for relevant clinical covariates, and the internal validation of the model was evaluated in a contemporary cohort of 92 patients.
Differences in the lesion load between patients according to their severity and outcome were found. Colocalization of macroscopic nonhemorrhagic TAI lesions (not microbleeds) and lower FA was limited to the internal and external capsule, corona radiata, inferior frontooccipital fasciculus, CC, and brainstem. However, a significant association between the FA value and the identification of macroscopic lesions in distant brain regions was also detected. Specifically, lower values of FA of some hemispheric WM bundles and the splenium of the CC were related to a higher number and volume of hyperintensities in the brainstem. The regression analysis revealed that age, motor score, hypoxia, FA of the genu of the CC, characterization of TAI lesions in the CC, and the presence of thalamic/basal ganglia lesions were independent prognostic factors. The performance of the proposed model was higher than that of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in TBI) model in the validation cohort.
Very limited colocalization of hyperintensities (none for microbleeds) with FA values was discovered. DTI and conventional MRI provide complementary prognostic information, and their combination can improve the performance of traditional prognostic models.</abstract><cop>United States</cop><pmid>34214979</pmid><doi>10.3171/2020.11.JNS203124</doi><tpages>15</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0022-3085 |
ispartof | Journal of neurosurgery, 2022-01, Vol.136 (1), p.242-256 |
issn | 0022-3085 1933-0693 |
language | eng |
recordid | cdi_proquest_miscellaneous_2548406793 |
source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
subjects | Adolescent Adult Aged Anisotropy Brain Injuries, Traumatic - diagnostic imaging Brain Injuries, Traumatic - surgery Brain Mapping Diffuse Axonal Injury - diagnostic imaging Diffuse Axonal Injury - surgery Diffusion Tensor Imaging Female Glasgow Outcome Scale Healthy Volunteers Humans Image Processing, Computer-Assisted Magnetic Resonance Imaging Male Middle Aged Neuroimaging - methods Neurosurgical Procedures Predictive Value of Tests Prognosis Treatment Outcome White Matter - diagnostic imaging White Matter - surgery Young Adult |
title | Traumatic axonal injury: is the prognostic information produced by conventional MRI and DTI complementary or supplementary? |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T08%3A30%3A58IST&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=Traumatic%20axonal%20injury:%20is%20the%20prognostic%20information%20produced%20by%20conventional%20MRI%20and%20DTI%20complementary%20or%20supplementary?&rft.jtitle=Journal%20of%20neurosurgery&rft.au=Casta%C3%B1o-Leon,%20Ana%20M&rft.date=2022-01-01&rft.volume=136&rft.issue=1&rft.spage=242&rft.epage=256&rft.pages=242-256&rft.issn=0022-3085&rft.eissn=1933-0693&rft_id=info:doi/10.3171/2020.11.JNS203124&rft_dat=%3Cproquest_cross%3E2548406793%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2548406793&rft_id=info:pmid/34214979&rfr_iscdi=true |