Loading…

SlicerCBM: automatic framework for biomechanical analysis of the brain

Purpose Brain shift that occurs during neurosurgery disturbs the brain’s anatomy. Prediction of the brain shift is essential for accurate localisation of the surgical target. Biomechanical models have been envisaged as a possible tool for such predictions. In this study, we created a framework to au...

Full description

Saved in:
Bibliographic Details
Published in:International journal for computer assisted radiology and surgery 2023-10, Vol.18 (10), p.1925-1940
Main Authors: Safdar, Saima, Zwick, Benjamin F., Yu, Yue, Bourantas, George C., Joldes, Grand R., Warfield, Simon K., Hyde, Damon E., Frisken, Sarah, Kapur, Tina, Kikinis, Ron, Golby, Alexandra, Nabavi, Arya, Wittek, Adam, Miller, Karol
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-c475t-89929107d7bf24673129254e5904b3bbe7ac615f314de74f26c7e399d5189daa3
cites cdi_FETCH-LOGICAL-c475t-89929107d7bf24673129254e5904b3bbe7ac615f314de74f26c7e399d5189daa3
container_end_page 1940
container_issue 10
container_start_page 1925
container_title International journal for computer assisted radiology and surgery
container_volume 18
creator Safdar, Saima
Zwick, Benjamin F.
Yu, Yue
Bourantas, George C.
Joldes, Grand R.
Warfield, Simon K.
Hyde, Damon E.
Frisken, Sarah
Kapur, Tina
Kikinis, Ron
Golby, Alexandra
Nabavi, Arya
Wittek, Adam
Miller, Karol
description Purpose Brain shift that occurs during neurosurgery disturbs the brain’s anatomy. Prediction of the brain shift is essential for accurate localisation of the surgical target. Biomechanical models have been envisaged as a possible tool for such predictions. In this study, we created a framework to automate the workflow for predicting intra-operative brain deformations. Methods We created our framework by uniquely combining our meshless total Lagrangian explicit dynamics (MTLED) algorithm for computing soft tissue deformations, open-source software libraries and built-in functions within 3D Slicer, an open-source software package widely used for medical research. Our framework generates the biomechanical brain model from the pre-operative MRI, computes brain deformation using MTLED and outputs results in the form of predicted warped intra-operative MRI. Results Our framework is used to solve three different neurosurgical brain shift scenarios: craniotomy, tumour resection and electrode placement. We evaluated our framework using nine patients. The average time to construct a patient-specific brain biomechanical model was 3 min, and that to compute deformations ranged from 13 to 23 min. We performed a qualitative evaluation by comparing our predicted intra-operative MRI with the actual intra-operative MRI. For quantitative evaluation, we computed Hausdorff distances between predicted and actual intra-operative ventricle surfaces. For patients with craniotomy and tumour resection, approximately 95% of the nodes on the ventricle surfaces are within two times the original in-plane resolution of the actual surface determined from the intra-operative MRI. Conclusion Our framework provides a broader application of existing solution methods not only in research but also in clinics. We successfully demonstrated the application of our framework by predicting intra-operative deformations in nine patients undergoing neurosurgical procedures.
doi_str_mv 10.1007/s11548-023-02881-7
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10497672</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2864240164</sourcerecordid><originalsourceid>FETCH-LOGICAL-c475t-89929107d7bf24673129254e5904b3bbe7ac615f314de74f26c7e399d5189daa3</originalsourceid><addsrcrecordid>eNp9kblOxDAQhi0EguV4AQoUiYYm4Cs-aBCsuKRFFEBtOY7DeknixU5AvD2G5S4oRjPSfPOPxz8A2wjuIwj5QUSooCKHmKQQAuV8CYyQYChnFMvlH_UaWI9xBiEtOClWwRrhqWaUjcDZTeOMDeOTq8NMD71vde9MVgfd2mcfHrLah6x0vrVmqjtndJPpTjcv0cXM11k_tVkZtOs2wUqtm2i3PvIGuDs7vR1f5JPr88vx8SQ3lBd9LqTEEkFe8bLGlHGCsMQFtYWEtCRlabk2DBU1QbSynNaYGW6JlFWBhKy0JhvgaKE7H8rWVsZ2fdCNmgfX6vCivHbqd6dzU3XvnxSCVHLGcVLY-1AI_nGwsVeti8Y2je6sH6LCXFImJGEiobt_0JkfQjo_USJ9K4WI0UThBWWCjzHY-us1CKo3n9TCJ5V8Uu8-KZ6Gdn7e8TXyaUwCyAKIqdXd2_C9-x_ZV2ajnT0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2864240164</pqid></control><display><type>article</type><title>SlicerCBM: automatic framework for biomechanical analysis of the brain</title><source>Springer Nature</source><creator>Safdar, Saima ; Zwick, Benjamin F. ; Yu, Yue ; Bourantas, George C. ; Joldes, Grand R. ; Warfield, Simon K. ; Hyde, Damon E. ; Frisken, Sarah ; Kapur, Tina ; Kikinis, Ron ; Golby, Alexandra ; Nabavi, Arya ; Wittek, Adam ; Miller, Karol</creator><creatorcontrib>Safdar, Saima ; Zwick, Benjamin F. ; Yu, Yue ; Bourantas, George C. ; Joldes, Grand R. ; Warfield, Simon K. ; Hyde, Damon E. ; Frisken, Sarah ; Kapur, Tina ; Kikinis, Ron ; Golby, Alexandra ; Nabavi, Arya ; Wittek, Adam ; Miller, Karol</creatorcontrib><description>Purpose Brain shift that occurs during neurosurgery disturbs the brain’s anatomy. Prediction of the brain shift is essential for accurate localisation of the surgical target. Biomechanical models have been envisaged as a possible tool for such predictions. In this study, we created a framework to automate the workflow for predicting intra-operative brain deformations. Methods We created our framework by uniquely combining our meshless total Lagrangian explicit dynamics (MTLED) algorithm for computing soft tissue deformations, open-source software libraries and built-in functions within 3D Slicer, an open-source software package widely used for medical research. Our framework generates the biomechanical brain model from the pre-operative MRI, computes brain deformation using MTLED and outputs results in the form of predicted warped intra-operative MRI. Results Our framework is used to solve three different neurosurgical brain shift scenarios: craniotomy, tumour resection and electrode placement. We evaluated our framework using nine patients. The average time to construct a patient-specific brain biomechanical model was 3 min, and that to compute deformations ranged from 13 to 23 min. We performed a qualitative evaluation by comparing our predicted intra-operative MRI with the actual intra-operative MRI. For quantitative evaluation, we computed Hausdorff distances between predicted and actual intra-operative ventricle surfaces. For patients with craniotomy and tumour resection, approximately 95% of the nodes on the ventricle surfaces are within two times the original in-plane resolution of the actual surface determined from the intra-operative MRI. Conclusion Our framework provides a broader application of existing solution methods not only in research but also in clinics. We successfully demonstrated the application of our framework by predicting intra-operative deformations in nine patients undergoing neurosurgical procedures.</description><identifier>ISSN: 1861-6429</identifier><identifier>ISSN: 1861-6410</identifier><identifier>EISSN: 1861-6429</identifier><identifier>DOI: 10.1007/s11548-023-02881-7</identifier><identifier>PMID: 37004646</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Algorithms ; Biomechanical engineering ; Biomechanics ; Brain ; Brain - diagnostic imaging ; Brain - pathology ; Brain - surgery ; Brain Neoplasms - diagnostic imaging ; Brain Neoplasms - pathology ; Brain Neoplasms - surgery ; Brain research ; Computer Imaging ; Computer Science ; Craniotomy ; Health Informatics ; Humans ; Imaging ; Magnetic resonance imaging ; Magnetic Resonance Imaging - methods ; Medical research ; Medicine ; Medicine &amp; Public Health ; Neurosurgical Procedures ; Open source software ; Original ; Original Article ; Pattern Recognition and Graphics ; Public domain ; Radiology ; Soft tissues ; Software packages ; Surgery ; Tumors ; Vision ; Workflow</subject><ispartof>International journal for computer assisted radiology and surgery, 2023-10, Vol.18 (10), p.1925-1940</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-89929107d7bf24673129254e5904b3bbe7ac615f314de74f26c7e399d5189daa3</citedby><cites>FETCH-LOGICAL-c475t-89929107d7bf24673129254e5904b3bbe7ac615f314de74f26c7e399d5189daa3</cites><orcidid>0000-0001-5994-061X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37004646$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Safdar, Saima</creatorcontrib><creatorcontrib>Zwick, Benjamin F.</creatorcontrib><creatorcontrib>Yu, Yue</creatorcontrib><creatorcontrib>Bourantas, George C.</creatorcontrib><creatorcontrib>Joldes, Grand R.</creatorcontrib><creatorcontrib>Warfield, Simon K.</creatorcontrib><creatorcontrib>Hyde, Damon E.</creatorcontrib><creatorcontrib>Frisken, Sarah</creatorcontrib><creatorcontrib>Kapur, Tina</creatorcontrib><creatorcontrib>Kikinis, Ron</creatorcontrib><creatorcontrib>Golby, Alexandra</creatorcontrib><creatorcontrib>Nabavi, Arya</creatorcontrib><creatorcontrib>Wittek, Adam</creatorcontrib><creatorcontrib>Miller, Karol</creatorcontrib><title>SlicerCBM: automatic framework for biomechanical analysis of the brain</title><title>International journal for computer assisted radiology and surgery</title><addtitle>Int J CARS</addtitle><addtitle>Int J Comput Assist Radiol Surg</addtitle><description>Purpose Brain shift that occurs during neurosurgery disturbs the brain’s anatomy. Prediction of the brain shift is essential for accurate localisation of the surgical target. Biomechanical models have been envisaged as a possible tool for such predictions. In this study, we created a framework to automate the workflow for predicting intra-operative brain deformations. Methods We created our framework by uniquely combining our meshless total Lagrangian explicit dynamics (MTLED) algorithm for computing soft tissue deformations, open-source software libraries and built-in functions within 3D Slicer, an open-source software package widely used for medical research. Our framework generates the biomechanical brain model from the pre-operative MRI, computes brain deformation using MTLED and outputs results in the form of predicted warped intra-operative MRI. Results Our framework is used to solve three different neurosurgical brain shift scenarios: craniotomy, tumour resection and electrode placement. We evaluated our framework using nine patients. The average time to construct a patient-specific brain biomechanical model was 3 min, and that to compute deformations ranged from 13 to 23 min. We performed a qualitative evaluation by comparing our predicted intra-operative MRI with the actual intra-operative MRI. For quantitative evaluation, we computed Hausdorff distances between predicted and actual intra-operative ventricle surfaces. For patients with craniotomy and tumour resection, approximately 95% of the nodes on the ventricle surfaces are within two times the original in-plane resolution of the actual surface determined from the intra-operative MRI. Conclusion Our framework provides a broader application of existing solution methods not only in research but also in clinics. We successfully demonstrated the application of our framework by predicting intra-operative deformations in nine patients undergoing neurosurgical procedures.</description><subject>Algorithms</subject><subject>Biomechanical engineering</subject><subject>Biomechanics</subject><subject>Brain</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - pathology</subject><subject>Brain - surgery</subject><subject>Brain Neoplasms - diagnostic imaging</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain Neoplasms - surgery</subject><subject>Brain research</subject><subject>Computer Imaging</subject><subject>Computer Science</subject><subject>Craniotomy</subject><subject>Health Informatics</subject><subject>Humans</subject><subject>Imaging</subject><subject>Magnetic resonance imaging</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Neurosurgical Procedures</subject><subject>Open source software</subject><subject>Original</subject><subject>Original Article</subject><subject>Pattern Recognition and Graphics</subject><subject>Public domain</subject><subject>Radiology</subject><subject>Soft tissues</subject><subject>Software packages</subject><subject>Surgery</subject><subject>Tumors</subject><subject>Vision</subject><subject>Workflow</subject><issn>1861-6429</issn><issn>1861-6410</issn><issn>1861-6429</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kblOxDAQhi0EguV4AQoUiYYm4Cs-aBCsuKRFFEBtOY7DeknixU5AvD2G5S4oRjPSfPOPxz8A2wjuIwj5QUSooCKHmKQQAuV8CYyQYChnFMvlH_UaWI9xBiEtOClWwRrhqWaUjcDZTeOMDeOTq8NMD71vde9MVgfd2mcfHrLah6x0vrVmqjtndJPpTjcv0cXM11k_tVkZtOs2wUqtm2i3PvIGuDs7vR1f5JPr88vx8SQ3lBd9LqTEEkFe8bLGlHGCsMQFtYWEtCRlabk2DBU1QbSynNaYGW6JlFWBhKy0JhvgaKE7H8rWVsZ2fdCNmgfX6vCivHbqd6dzU3XvnxSCVHLGcVLY-1AI_nGwsVeti8Y2je6sH6LCXFImJGEiobt_0JkfQjo_USJ9K4WI0UThBWWCjzHY-us1CKo3n9TCJ5V8Uu8-KZ6Gdn7e8TXyaUwCyAKIqdXd2_C9-x_ZV2ajnT0</recordid><startdate>20231001</startdate><enddate>20231001</enddate><creator>Safdar, Saima</creator><creator>Zwick, Benjamin F.</creator><creator>Yu, Yue</creator><creator>Bourantas, George C.</creator><creator>Joldes, Grand R.</creator><creator>Warfield, Simon K.</creator><creator>Hyde, Damon E.</creator><creator>Frisken, Sarah</creator><creator>Kapur, Tina</creator><creator>Kikinis, Ron</creator><creator>Golby, Alexandra</creator><creator>Nabavi, Arya</creator><creator>Wittek, Adam</creator><creator>Miller, Karol</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</scope><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><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5994-061X</orcidid></search><sort><creationdate>20231001</creationdate><title>SlicerCBM: automatic framework for biomechanical analysis of the brain</title><author>Safdar, Saima ; Zwick, Benjamin F. ; Yu, Yue ; Bourantas, George C. ; Joldes, Grand R. ; Warfield, Simon K. ; Hyde, Damon E. ; Frisken, Sarah ; Kapur, Tina ; Kikinis, Ron ; Golby, Alexandra ; Nabavi, Arya ; Wittek, Adam ; Miller, Karol</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-89929107d7bf24673129254e5904b3bbe7ac615f314de74f26c7e399d5189daa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Algorithms</topic><topic>Biomechanical engineering</topic><topic>Biomechanics</topic><topic>Brain</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - pathology</topic><topic>Brain - surgery</topic><topic>Brain Neoplasms - diagnostic imaging</topic><topic>Brain Neoplasms - pathology</topic><topic>Brain Neoplasms - surgery</topic><topic>Brain research</topic><topic>Computer Imaging</topic><topic>Computer Science</topic><topic>Craniotomy</topic><topic>Health Informatics</topic><topic>Humans</topic><topic>Imaging</topic><topic>Magnetic resonance imaging</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Neurosurgical Procedures</topic><topic>Open source software</topic><topic>Original</topic><topic>Original Article</topic><topic>Pattern Recognition and Graphics</topic><topic>Public domain</topic><topic>Radiology</topic><topic>Soft tissues</topic><topic>Software packages</topic><topic>Surgery</topic><topic>Tumors</topic><topic>Vision</topic><topic>Workflow</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Safdar, Saima</creatorcontrib><creatorcontrib>Zwick, Benjamin F.</creatorcontrib><creatorcontrib>Yu, Yue</creatorcontrib><creatorcontrib>Bourantas, George C.</creatorcontrib><creatorcontrib>Joldes, Grand R.</creatorcontrib><creatorcontrib>Warfield, Simon K.</creatorcontrib><creatorcontrib>Hyde, Damon E.</creatorcontrib><creatorcontrib>Frisken, Sarah</creatorcontrib><creatorcontrib>Kapur, Tina</creatorcontrib><creatorcontrib>Kikinis, Ron</creatorcontrib><creatorcontrib>Golby, Alexandra</creatorcontrib><creatorcontrib>Nabavi, Arya</creatorcontrib><creatorcontrib>Wittek, Adam</creatorcontrib><creatorcontrib>Miller, Karol</creatorcontrib><collection>SpringerOpen</collection><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal for computer assisted radiology and surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Safdar, Saima</au><au>Zwick, Benjamin F.</au><au>Yu, Yue</au><au>Bourantas, George C.</au><au>Joldes, Grand R.</au><au>Warfield, Simon K.</au><au>Hyde, Damon E.</au><au>Frisken, Sarah</au><au>Kapur, Tina</au><au>Kikinis, Ron</au><au>Golby, Alexandra</au><au>Nabavi, Arya</au><au>Wittek, Adam</au><au>Miller, Karol</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SlicerCBM: automatic framework for biomechanical analysis of the brain</atitle><jtitle>International journal for computer assisted radiology and surgery</jtitle><stitle>Int J CARS</stitle><addtitle>Int J Comput Assist Radiol Surg</addtitle><date>2023-10-01</date><risdate>2023</risdate><volume>18</volume><issue>10</issue><spage>1925</spage><epage>1940</epage><pages>1925-1940</pages><issn>1861-6429</issn><issn>1861-6410</issn><eissn>1861-6429</eissn><abstract>Purpose Brain shift that occurs during neurosurgery disturbs the brain’s anatomy. Prediction of the brain shift is essential for accurate localisation of the surgical target. Biomechanical models have been envisaged as a possible tool for such predictions. In this study, we created a framework to automate the workflow for predicting intra-operative brain deformations. Methods We created our framework by uniquely combining our meshless total Lagrangian explicit dynamics (MTLED) algorithm for computing soft tissue deformations, open-source software libraries and built-in functions within 3D Slicer, an open-source software package widely used for medical research. Our framework generates the biomechanical brain model from the pre-operative MRI, computes brain deformation using MTLED and outputs results in the form of predicted warped intra-operative MRI. Results Our framework is used to solve three different neurosurgical brain shift scenarios: craniotomy, tumour resection and electrode placement. We evaluated our framework using nine patients. The average time to construct a patient-specific brain biomechanical model was 3 min, and that to compute deformations ranged from 13 to 23 min. We performed a qualitative evaluation by comparing our predicted intra-operative MRI with the actual intra-operative MRI. For quantitative evaluation, we computed Hausdorff distances between predicted and actual intra-operative ventricle surfaces. For patients with craniotomy and tumour resection, approximately 95% of the nodes on the ventricle surfaces are within two times the original in-plane resolution of the actual surface determined from the intra-operative MRI. Conclusion Our framework provides a broader application of existing solution methods not only in research but also in clinics. We successfully demonstrated the application of our framework by predicting intra-operative deformations in nine patients undergoing neurosurgical procedures.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>37004646</pmid><doi>10.1007/s11548-023-02881-7</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-5994-061X</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1861-6429
ispartof International journal for computer assisted radiology and surgery, 2023-10, Vol.18 (10), p.1925-1940
issn 1861-6429
1861-6410
1861-6429
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10497672
source Springer Nature
subjects Algorithms
Biomechanical engineering
Biomechanics
Brain
Brain - diagnostic imaging
Brain - pathology
Brain - surgery
Brain Neoplasms - diagnostic imaging
Brain Neoplasms - pathology
Brain Neoplasms - surgery
Brain research
Computer Imaging
Computer Science
Craniotomy
Health Informatics
Humans
Imaging
Magnetic resonance imaging
Magnetic Resonance Imaging - methods
Medical research
Medicine
Medicine & Public Health
Neurosurgical Procedures
Open source software
Original
Original Article
Pattern Recognition and Graphics
Public domain
Radiology
Soft tissues
Software packages
Surgery
Tumors
Vision
Workflow
title SlicerCBM: automatic framework for biomechanical analysis of the brain
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T23%3A54%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=SlicerCBM:%20automatic%20framework%20for%20biomechanical%20analysis%20of%20the%20brain&rft.jtitle=International%20journal%20for%20computer%20assisted%20radiology%20and%20surgery&rft.au=Safdar,%20Saima&rft.date=2023-10-01&rft.volume=18&rft.issue=10&rft.spage=1925&rft.epage=1940&rft.pages=1925-1940&rft.issn=1861-6429&rft.eissn=1861-6429&rft_id=info:doi/10.1007/s11548-023-02881-7&rft_dat=%3Cproquest_pubme%3E2864240164%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c475t-89929107d7bf24673129254e5904b3bbe7ac615f314de74f26c7e399d5189daa3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2864240164&rft_id=info:pmid/37004646&rfr_iscdi=true