Assessment of microvascular dysfunction in acute limb ischemia‐reperfusion injury
Background Ischemia‐reperfusion (I/R) injury involves damage to the microvessel structure (eg, increased permeability) and function (blunted vasomodulation). While microstructural damage can be detected with dynamic contrast‐enhanced (DCE) MRI, there is no diagnostic to detect deficits in microvascu...
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| Veröffentlicht in: | Journal of magnetic resonance imaging 2019-04, Vol.49 (4), p.1174-1185 |
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| creator | Ganesh, Tameshwar Zakher, Eric Estrada, Marvin Cheng, Hai‐Ling Margaret |
| description | Background
Ischemia‐reperfusion (I/R) injury involves damage to the microvessel structure (eg, increased permeability) and function (blunted vasomodulation). While microstructural damage can be detected with dynamic contrast‐enhanced (DCE) MRI, there is no diagnostic to detect deficits in microvascular function.
Purpose
To apply a novel MRI method for evaluating dynamic vasomodulation to assess microvascular dysfunction in skeletal muscle following I/R injury.
Study Type
Prospective, longitudinal.
Animal Model
Twenty‐three healthy male adult Sprague–Dawley rats.
Field Strength/Sequence
Dynamic T1 fast field echo imaging at 3.0T with preinjection T1 mapping.
Assessment
Injury in the left hindlimb was induced using a 3‐hour I/R procedure. Longitudinal MRI scanning was performed up to 74 days, with animals completing assessment at different intervals for histological and laser Doppler perfusion validation. Pharmacokinetic parameters Ktrans and ve were determined following i.v. injection of gadovist (0.1 mmol/kg). Vasomodulatory response was probed on gadofosveset (0.3 mmol/kg) using hypercapnic gases delivered through a controlled gas‐mixing circuit to induce vasoconstriction and vasodilation in ventilated rats. Heart rate and blood oxygen saturation were monitored.
Statistical Tests
Two‐way analysis of variance with Tukey–Kramer post‐hoc analysis was used to determine significant changes in vasomodulatory response, Ktrans, and ve.
Results
This new MRI technique revealed impaired vasomodulation in the injured hindlimb. Vasoconstriction was maintained, but vasodilation was blunted up to 21 days postinjury (P |
| doi_str_mv | 10.1002/jmri.26308 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2117820630</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2190830431</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3578-a076abf1f30c5cd2a3306781b6557847a1198d63057374dfc4d0030d5ce4f0a33</originalsourceid><addsrcrecordid>eNp90MtKAzEYBeAgiq3VjQ8gA25EGP2TTGbSZSleKhXBy3rIZBLMMJeaNEp3PoLP6JOYOtWFC1cJ5ONwchA6xHCGAch51VhzRlIKfAsNMSMkJoyn2-EOjMaYQzZAe85VADAeJ2wXDShQIJwlQ_QwcU4516h2GXU6aoy03atw0tfCRuXKad_KpenayLSRkH6poto0RWScfFaNEZ_vH1YtlNXe9ajydrWPdrSonTrYnCP0dHnxOL2O53dXs-lkHkvKMh4LyFJRaKwpSCZLIiiFNOO4SFl4TjKB8ZiX4Vsso1lSapmUEHqXTKpEQ9AjdNLnLmz34pVb5k3opepatKrzLicYZ5xASAj0-A-tOm_b0C6oMXAKCcVBnfYqjOCcVTpfWNMIu8ox5Oup8_XU-ffUAR9tIn3RqPKX_mwbAO7Bm6nV6p-o_Ob2ftaHfgEN14m9</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2190830431</pqid></control><display><type>article</type><title>Assessment of microvascular dysfunction in acute limb ischemia‐reperfusion injury</title><source>Wiley Free Content</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Ganesh, Tameshwar ; Zakher, Eric ; Estrada, Marvin ; Cheng, Hai‐Ling Margaret</creator><creatorcontrib>Ganesh, Tameshwar ; Zakher, Eric ; Estrada, Marvin ; Cheng, Hai‐Ling Margaret</creatorcontrib><description>Background
Ischemia‐reperfusion (I/R) injury involves damage to the microvessel structure (eg, increased permeability) and function (blunted vasomodulation). While microstructural damage can be detected with dynamic contrast‐enhanced (DCE) MRI, there is no diagnostic to detect deficits in microvascular function.
Purpose
To apply a novel MRI method for evaluating dynamic vasomodulation to assess microvascular dysfunction in skeletal muscle following I/R injury.
Study Type
Prospective, longitudinal.
Animal Model
Twenty‐three healthy male adult Sprague–Dawley rats.
Field Strength/Sequence
Dynamic T1 fast field echo imaging at 3.0T with preinjection T1 mapping.
Assessment
Injury in the left hindlimb was induced using a 3‐hour I/R procedure. Longitudinal MRI scanning was performed up to 74 days, with animals completing assessment at different intervals for histological and laser Doppler perfusion validation. Pharmacokinetic parameters Ktrans and ve were determined following i.v. injection of gadovist (0.1 mmol/kg). Vasomodulatory response was probed on gadofosveset (0.3 mmol/kg) using hypercapnic gases delivered through a controlled gas‐mixing circuit to induce vasoconstriction and vasodilation in ventilated rats. Heart rate and blood oxygen saturation were monitored.
Statistical Tests
Two‐way analysis of variance with Tukey–Kramer post‐hoc analysis was used to determine significant changes in vasomodulatory response, Ktrans, and ve.
Results
This new MRI technique revealed impaired vasomodulation in the injured hindlimb. Vasoconstriction was maintained, but vasodilation was blunted up to 21 days postinjury (P < 0.05). However, DCE‐MRI measured Ktrans and ve were significantly (P < 0.05) different from baseline only during acute inflammation (Day 3), with severe inflammation noted on histology.
Data Conclusion
While conventional DCE‐MRI shows normalization after the acute phase, our new approach reveals sustained functional impairment in muscle microvasculature following I/R injury, with compromised response in vasomotor tone present for at least 21 days.
Level of Evidence: 4
Technical Efficacy: Stage 1
J. Magn. Reson. Imaging 2019;49:1174–1185.</description><identifier>ISSN: 1053-1807</identifier><identifier>EISSN: 1522-2586</identifier><identifier>DOI: 10.1002/jmri.26308</identifier><identifier>PMID: 30302854</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Animal models ; Damage detection ; Diagnostic systems ; Field strength ; Gases ; Heart rate ; Histology ; hypercapnia ; Injuries ; Ischemia ; ischemia‐reperfusion injury ; Magnetic resonance imaging ; Mapping ; Medical imaging ; microvascular dysfunction ; Microvasculature ; Mixer circuits ; Muscles ; Oxygen content ; Perfusion ; Permeability ; Pharmacology ; Reperfusion ; Rodents ; Skeletal muscle ; Statistical analysis ; Statistical tests ; Variance analysis ; vascular reactivity ; Vasoconstriction ; Vasodilation ; vasomodulation</subject><ispartof>Journal of magnetic resonance imaging, 2019-04, Vol.49 (4), p.1174-1185</ispartof><rights>2018 International Society for Magnetic Resonance in Medicine</rights><rights>2018 International Society for Magnetic Resonance in Medicine.</rights><rights>2019 International Society for Magnetic Resonance in Medicine</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3578-a076abf1f30c5cd2a3306781b6557847a1198d63057374dfc4d0030d5ce4f0a33</citedby><cites>FETCH-LOGICAL-c3578-a076abf1f30c5cd2a3306781b6557847a1198d63057374dfc4d0030d5ce4f0a33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmri.26308$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmri.26308$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30302854$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ganesh, Tameshwar</creatorcontrib><creatorcontrib>Zakher, Eric</creatorcontrib><creatorcontrib>Estrada, Marvin</creatorcontrib><creatorcontrib>Cheng, Hai‐Ling Margaret</creatorcontrib><title>Assessment of microvascular dysfunction in acute limb ischemia‐reperfusion injury</title><title>Journal of magnetic resonance imaging</title><addtitle>J Magn Reson Imaging</addtitle><description>Background
Ischemia‐reperfusion (I/R) injury involves damage to the microvessel structure (eg, increased permeability) and function (blunted vasomodulation). While microstructural damage can be detected with dynamic contrast‐enhanced (DCE) MRI, there is no diagnostic to detect deficits in microvascular function.
Purpose
To apply a novel MRI method for evaluating dynamic vasomodulation to assess microvascular dysfunction in skeletal muscle following I/R injury.
Study Type
Prospective, longitudinal.
Animal Model
Twenty‐three healthy male adult Sprague–Dawley rats.
Field Strength/Sequence
Dynamic T1 fast field echo imaging at 3.0T with preinjection T1 mapping.
Assessment
Injury in the left hindlimb was induced using a 3‐hour I/R procedure. Longitudinal MRI scanning was performed up to 74 days, with animals completing assessment at different intervals for histological and laser Doppler perfusion validation. Pharmacokinetic parameters Ktrans and ve were determined following i.v. injection of gadovist (0.1 mmol/kg). Vasomodulatory response was probed on gadofosveset (0.3 mmol/kg) using hypercapnic gases delivered through a controlled gas‐mixing circuit to induce vasoconstriction and vasodilation in ventilated rats. Heart rate and blood oxygen saturation were monitored.
Statistical Tests
Two‐way analysis of variance with Tukey–Kramer post‐hoc analysis was used to determine significant changes in vasomodulatory response, Ktrans, and ve.
Results
This new MRI technique revealed impaired vasomodulation in the injured hindlimb. Vasoconstriction was maintained, but vasodilation was blunted up to 21 days postinjury (P < 0.05). However, DCE‐MRI measured Ktrans and ve were significantly (P < 0.05) different from baseline only during acute inflammation (Day 3), with severe inflammation noted on histology.
Data Conclusion
While conventional DCE‐MRI shows normalization after the acute phase, our new approach reveals sustained functional impairment in muscle microvasculature following I/R injury, with compromised response in vasomotor tone present for at least 21 days.
Level of Evidence: 4
Technical Efficacy: Stage 1
J. Magn. Reson. Imaging 2019;49:1174–1185.</description><subject>Animal models</subject><subject>Damage detection</subject><subject>Diagnostic systems</subject><subject>Field strength</subject><subject>Gases</subject><subject>Heart rate</subject><subject>Histology</subject><subject>hypercapnia</subject><subject>Injuries</subject><subject>Ischemia</subject><subject>ischemia‐reperfusion injury</subject><subject>Magnetic resonance imaging</subject><subject>Mapping</subject><subject>Medical imaging</subject><subject>microvascular dysfunction</subject><subject>Microvasculature</subject><subject>Mixer circuits</subject><subject>Muscles</subject><subject>Oxygen content</subject><subject>Perfusion</subject><subject>Permeability</subject><subject>Pharmacology</subject><subject>Reperfusion</subject><subject>Rodents</subject><subject>Skeletal muscle</subject><subject>Statistical analysis</subject><subject>Statistical tests</subject><subject>Variance analysis</subject><subject>vascular reactivity</subject><subject>Vasoconstriction</subject><subject>Vasodilation</subject><subject>vasomodulation</subject><issn>1053-1807</issn><issn>1522-2586</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp90MtKAzEYBeAgiq3VjQ8gA25EGP2TTGbSZSleKhXBy3rIZBLMMJeaNEp3PoLP6JOYOtWFC1cJ5ONwchA6xHCGAch51VhzRlIKfAsNMSMkJoyn2-EOjMaYQzZAe85VADAeJ2wXDShQIJwlQ_QwcU4516h2GXU6aoy03atw0tfCRuXKad_KpenayLSRkH6poto0RWScfFaNEZ_vH1YtlNXe9ajydrWPdrSonTrYnCP0dHnxOL2O53dXs-lkHkvKMh4LyFJRaKwpSCZLIiiFNOO4SFl4TjKB8ZiX4Vsso1lSapmUEHqXTKpEQ9AjdNLnLmz34pVb5k3opepatKrzLicYZ5xASAj0-A-tOm_b0C6oMXAKCcVBnfYqjOCcVTpfWNMIu8ox5Oup8_XU-ffUAR9tIn3RqPKX_mwbAO7Bm6nV6p-o_Ob2ftaHfgEN14m9</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>Ganesh, Tameshwar</creator><creator>Zakher, Eric</creator><creator>Estrada, Marvin</creator><creator>Cheng, Hai‐Ling Margaret</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201904</creationdate><title>Assessment of microvascular dysfunction in acute limb ischemia‐reperfusion injury</title><author>Ganesh, Tameshwar ; Zakher, Eric ; Estrada, Marvin ; Cheng, Hai‐Ling Margaret</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3578-a076abf1f30c5cd2a3306781b6557847a1198d63057374dfc4d0030d5ce4f0a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animal models</topic><topic>Damage detection</topic><topic>Diagnostic systems</topic><topic>Field strength</topic><topic>Gases</topic><topic>Heart rate</topic><topic>Histology</topic><topic>hypercapnia</topic><topic>Injuries</topic><topic>Ischemia</topic><topic>ischemia‐reperfusion injury</topic><topic>Magnetic resonance imaging</topic><topic>Mapping</topic><topic>Medical imaging</topic><topic>microvascular dysfunction</topic><topic>Microvasculature</topic><topic>Mixer circuits</topic><topic>Muscles</topic><topic>Oxygen content</topic><topic>Perfusion</topic><topic>Permeability</topic><topic>Pharmacology</topic><topic>Reperfusion</topic><topic>Rodents</topic><topic>Skeletal muscle</topic><topic>Statistical analysis</topic><topic>Statistical tests</topic><topic>Variance analysis</topic><topic>vascular reactivity</topic><topic>Vasoconstriction</topic><topic>Vasodilation</topic><topic>vasomodulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ganesh, Tameshwar</creatorcontrib><creatorcontrib>Zakher, Eric</creatorcontrib><creatorcontrib>Estrada, Marvin</creatorcontrib><creatorcontrib>Cheng, Hai‐Ling Margaret</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of magnetic resonance imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ganesh, Tameshwar</au><au>Zakher, Eric</au><au>Estrada, Marvin</au><au>Cheng, Hai‐Ling Margaret</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessment of microvascular dysfunction in acute limb ischemia‐reperfusion injury</atitle><jtitle>Journal of magnetic resonance imaging</jtitle><addtitle>J Magn Reson Imaging</addtitle><date>2019-04</date><risdate>2019</risdate><volume>49</volume><issue>4</issue><spage>1174</spage><epage>1185</epage><pages>1174-1185</pages><issn>1053-1807</issn><eissn>1522-2586</eissn><abstract>Background
Ischemia‐reperfusion (I/R) injury involves damage to the microvessel structure (eg, increased permeability) and function (blunted vasomodulation). While microstructural damage can be detected with dynamic contrast‐enhanced (DCE) MRI, there is no diagnostic to detect deficits in microvascular function.
Purpose
To apply a novel MRI method for evaluating dynamic vasomodulation to assess microvascular dysfunction in skeletal muscle following I/R injury.
Study Type
Prospective, longitudinal.
Animal Model
Twenty‐three healthy male adult Sprague–Dawley rats.
Field Strength/Sequence
Dynamic T1 fast field echo imaging at 3.0T with preinjection T1 mapping.
Assessment
Injury in the left hindlimb was induced using a 3‐hour I/R procedure. Longitudinal MRI scanning was performed up to 74 days, with animals completing assessment at different intervals for histological and laser Doppler perfusion validation. Pharmacokinetic parameters Ktrans and ve were determined following i.v. injection of gadovist (0.1 mmol/kg). Vasomodulatory response was probed on gadofosveset (0.3 mmol/kg) using hypercapnic gases delivered through a controlled gas‐mixing circuit to induce vasoconstriction and vasodilation in ventilated rats. Heart rate and blood oxygen saturation were monitored.
Statistical Tests
Two‐way analysis of variance with Tukey–Kramer post‐hoc analysis was used to determine significant changes in vasomodulatory response, Ktrans, and ve.
Results
This new MRI technique revealed impaired vasomodulation in the injured hindlimb. Vasoconstriction was maintained, but vasodilation was blunted up to 21 days postinjury (P < 0.05). However, DCE‐MRI measured Ktrans and ve were significantly (P < 0.05) different from baseline only during acute inflammation (Day 3), with severe inflammation noted on histology.
Data Conclusion
While conventional DCE‐MRI shows normalization after the acute phase, our new approach reveals sustained functional impairment in muscle microvasculature following I/R injury, with compromised response in vasomotor tone present for at least 21 days.
Level of Evidence: 4
Technical Efficacy: Stage 1
J. Magn. Reson. Imaging 2019;49:1174–1185.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30302854</pmid><doi>10.1002/jmri.26308</doi><tpages>12</tpages></addata></record> |
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| ispartof | Journal of magnetic resonance imaging, 2019-04, Vol.49 (4), p.1174-1185 |
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| source | Wiley Free Content; Wiley Online Library Journals Frontfile Complete |
| subjects | Animal models Damage detection Diagnostic systems Field strength Gases Heart rate Histology hypercapnia Injuries Ischemia ischemia‐reperfusion injury Magnetic resonance imaging Mapping Medical imaging microvascular dysfunction Microvasculature Mixer circuits Muscles Oxygen content Perfusion Permeability Pharmacology Reperfusion Rodents Skeletal muscle Statistical analysis Statistical tests Variance analysis vascular reactivity Vasoconstriction Vasodilation vasomodulation |
| title | Assessment of microvascular dysfunction in acute limb ischemia‐reperfusion injury |
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