Perfusion CT Assessment of Tissue Hemodynamics Following Hepatic Arterial Infusion of Increasing Doses of Angiotensin II in a Rabbit Liver Tumor Model
To investigate the effects of increasing doses of angiotensin II on hepatic hemodynamics in the normal rabbit liver and in hepatic VX2 tumors by using dynamic contrast material-enhanced perfusion computed tomography (CT). This study was approved by the institutional animal care and use committee. So...
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| Veröffentlicht in: | Radiology 2011-09, Vol.260 (3), p.718-726 |
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| creator | WRIGHT, Kenneth C RAVOORI, Murali K DIXON, Katherine A LIN HAN SINGH, Sheela P PING LIU GUPTA, Sanjay JOHNSON, Valen E ZUXING KAN KUNDRA, Vikas |
| description | To investigate the effects of increasing doses of angiotensin II on hepatic hemodynamics in the normal rabbit liver and in hepatic VX2 tumors by using dynamic contrast material-enhanced perfusion computed tomography (CT).
This study was approved by the institutional animal care and use committee. Solitary hepatic VX2 tumors were implanted into 12 rabbits. In each animal, perfusion CT of the liver was performed before (at baseline) and after hepatic arterial infusion of varying doses (0.1-50.0 μg/mL) of angiotensin II. Images were acquired continuously for 80 seconds after the start of the intravenous contrast material administration. Blood flow (BF), blood volume (BV), mean transit time (MTT), and capillary permeability-surface area product were calculated for the tumor and the adjacent and distant normal liver tissue. Generalized linear mixed models were used to estimate the effects of angiotensin II dose on outcome measures.
Angiotensin II infusion increased contrast enhancement of the tumor and distal liver vessels. Tumor BF increased in a dose-dependent manner after administration of 0.5-25.0 μg/mL angiotensin II, but only the 2.5 μg/mL dose induced a significant increase in tumor BF compared with BF in the adjacent (68.0 vs 26.3 mL/min/100 g, P < .0001) and distant (68.0 vs 28.3 mL/min/100 g, P = .02) normal liver tissue. Tumor BV varied with angiotensin II dose but was greater than the BV of the adjacent and distant liver tissue at only the 2.5 μg/mL (4.8 vs 3.5 mL/100 g for adjacent liver [P < .0001], 4.8 vs 3.3 mL/100 g for distant liver [P = .0006]) and 10.0 μg/mL (4.9 vs 4.4 mL/100 g for adjacent liver [P = .007], 4.9 vs 4.3 mL/100 g for distant liver [P = .04]) doses. Tumor MTT was significantly shorter than the adjacent liver tissue MTT at angiotensin II doses of 2.5 μg/mL (9.7 vs 15.8 sec, P = .001) and 10.0 μg/mL (5.1 vs 13.2 sec, P = .007) and significantly shorter than the distant liver tissue MTT at 2.5 μg/mL only (9.7 vs 15.3 sec, P = .0006). The capillary permeability-surface area product for the tumor was higher than that for the adjacent liver tissue at the 2.5 μg/mL angiotensin II dose only (11.5 vs 8.1 mL/min/100 g, P = .01).
Perfusion CT enables a mechanistic understanding of angiotensin II infusion in the liver and derivation of the optimal effective dose. The 2.5 μg/mL angiotensin II dose increases perfusion in hepatic VX2 tumors versus that in adjacent and distant normal liver tissue primarily by constricting normal distal liver |
| doi_str_mv | 10.1148/radiol.11101868 |
| format | Article |
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This study was approved by the institutional animal care and use committee. Solitary hepatic VX2 tumors were implanted into 12 rabbits. In each animal, perfusion CT of the liver was performed before (at baseline) and after hepatic arterial infusion of varying doses (0.1-50.0 μg/mL) of angiotensin II. Images were acquired continuously for 80 seconds after the start of the intravenous contrast material administration. Blood flow (BF), blood volume (BV), mean transit time (MTT), and capillary permeability-surface area product were calculated for the tumor and the adjacent and distant normal liver tissue. Generalized linear mixed models were used to estimate the effects of angiotensin II dose on outcome measures.
Angiotensin II infusion increased contrast enhancement of the tumor and distal liver vessels. Tumor BF increased in a dose-dependent manner after administration of 0.5-25.0 μg/mL angiotensin II, but only the 2.5 μg/mL dose induced a significant increase in tumor BF compared with BF in the adjacent (68.0 vs 26.3 mL/min/100 g, P < .0001) and distant (68.0 vs 28.3 mL/min/100 g, P = .02) normal liver tissue. Tumor BV varied with angiotensin II dose but was greater than the BV of the adjacent and distant liver tissue at only the 2.5 μg/mL (4.8 vs 3.5 mL/100 g for adjacent liver [P < .0001], 4.8 vs 3.3 mL/100 g for distant liver [P = .0006]) and 10.0 μg/mL (4.9 vs 4.4 mL/100 g for adjacent liver [P = .007], 4.9 vs 4.3 mL/100 g for distant liver [P = .04]) doses. Tumor MTT was significantly shorter than the adjacent liver tissue MTT at angiotensin II doses of 2.5 μg/mL (9.7 vs 15.8 sec, P = .001) and 10.0 μg/mL (5.1 vs 13.2 sec, P = .007) and significantly shorter than the distant liver tissue MTT at 2.5 μg/mL only (9.7 vs 15.3 sec, P = .0006). The capillary permeability-surface area product for the tumor was higher than that for the adjacent liver tissue at the 2.5 μg/mL angiotensin II dose only (11.5 vs 8.1 mL/min/100 g, P = .01).
Perfusion CT enables a mechanistic understanding of angiotensin II infusion in the liver and derivation of the optimal effective dose. The 2.5 μg/mL angiotensin II dose increases perfusion in hepatic VX2 tumors versus that in adjacent and distant normal liver tissue primarily by constricting normal distal liver vessels and in turn increasing tumor BF and BV.</description><identifier>ISSN: 0033-8419</identifier><identifier>EISSN: 1527-1315</identifier><identifier>DOI: 10.1148/radiol.11101868</identifier><identifier>PMID: 21633050</identifier><identifier>CODEN: RADLAX</identifier><language>eng</language><publisher>Oak Brook, IL: Radiological Society of North America</publisher><subject>Angiotensin II - administration & dosage ; Animals ; Biological and medical sciences ; Blood Flow Velocity ; Contrast Media - administration & dosage ; Gastroenterology. Liver. Pancreas. Abdomen ; Image Enhancement - methods ; Infusions, Intralesional ; Liver Circulation ; Liver Neoplasms, Experimental - diagnostic imaging ; Liver Neoplasms, Experimental - physiopathology ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Original Research ; Perfusion Imaging - methods ; Rabbits ; Reproducibility of Results ; Sensitivity and Specificity ; Tomography, X-Ray Computed - methods ; Tumors ; Vasoconstrictor Agents - administration & dosage</subject><ispartof>Radiology, 2011-09, Vol.260 (3), p.718-726</ispartof><rights>2015 INIST-CNRS</rights><rights>RSNA, 2011 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-241f6e64e2abe2cd59be36ad79e26e2d0f71009e81baddced52aa1671378b8c03</citedby><cites>FETCH-LOGICAL-c422t-241f6e64e2abe2cd59be36ad79e26e2d0f71009e81baddced52aa1671378b8c03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24407241$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21633050$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WRIGHT, Kenneth C</creatorcontrib><creatorcontrib>RAVOORI, Murali K</creatorcontrib><creatorcontrib>DIXON, Katherine A</creatorcontrib><creatorcontrib>LIN HAN</creatorcontrib><creatorcontrib>SINGH, Sheela P</creatorcontrib><creatorcontrib>PING LIU</creatorcontrib><creatorcontrib>GUPTA, Sanjay</creatorcontrib><creatorcontrib>JOHNSON, Valen E</creatorcontrib><creatorcontrib>ZUXING KAN</creatorcontrib><creatorcontrib>KUNDRA, Vikas</creatorcontrib><title>Perfusion CT Assessment of Tissue Hemodynamics Following Hepatic Arterial Infusion of Increasing Doses of Angiotensin II in a Rabbit Liver Tumor Model</title><title>Radiology</title><addtitle>Radiology</addtitle><description>To investigate the effects of increasing doses of angiotensin II on hepatic hemodynamics in the normal rabbit liver and in hepatic VX2 tumors by using dynamic contrast material-enhanced perfusion computed tomography (CT).
This study was approved by the institutional animal care and use committee. Solitary hepatic VX2 tumors were implanted into 12 rabbits. In each animal, perfusion CT of the liver was performed before (at baseline) and after hepatic arterial infusion of varying doses (0.1-50.0 μg/mL) of angiotensin II. Images were acquired continuously for 80 seconds after the start of the intravenous contrast material administration. Blood flow (BF), blood volume (BV), mean transit time (MTT), and capillary permeability-surface area product were calculated for the tumor and the adjacent and distant normal liver tissue. Generalized linear mixed models were used to estimate the effects of angiotensin II dose on outcome measures.
Angiotensin II infusion increased contrast enhancement of the tumor and distal liver vessels. Tumor BF increased in a dose-dependent manner after administration of 0.5-25.0 μg/mL angiotensin II, but only the 2.5 μg/mL dose induced a significant increase in tumor BF compared with BF in the adjacent (68.0 vs 26.3 mL/min/100 g, P < .0001) and distant (68.0 vs 28.3 mL/min/100 g, P = .02) normal liver tissue. Tumor BV varied with angiotensin II dose but was greater than the BV of the adjacent and distant liver tissue at only the 2.5 μg/mL (4.8 vs 3.5 mL/100 g for adjacent liver [P < .0001], 4.8 vs 3.3 mL/100 g for distant liver [P = .0006]) and 10.0 μg/mL (4.9 vs 4.4 mL/100 g for adjacent liver [P = .007], 4.9 vs 4.3 mL/100 g for distant liver [P = .04]) doses. Tumor MTT was significantly shorter than the adjacent liver tissue MTT at angiotensin II doses of 2.5 μg/mL (9.7 vs 15.8 sec, P = .001) and 10.0 μg/mL (5.1 vs 13.2 sec, P = .007) and significantly shorter than the distant liver tissue MTT at 2.5 μg/mL only (9.7 vs 15.3 sec, P = .0006). The capillary permeability-surface area product for the tumor was higher than that for the adjacent liver tissue at the 2.5 μg/mL angiotensin II dose only (11.5 vs 8.1 mL/min/100 g, P = .01).
Perfusion CT enables a mechanistic understanding of angiotensin II infusion in the liver and derivation of the optimal effective dose. The 2.5 μg/mL angiotensin II dose increases perfusion in hepatic VX2 tumors versus that in adjacent and distant normal liver tissue primarily by constricting normal distal liver vessels and in turn increasing tumor BF and BV.</description><subject>Angiotensin II - administration & dosage</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Flow Velocity</subject><subject>Contrast Media - administration & dosage</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Image Enhancement - methods</subject><subject>Infusions, Intralesional</subject><subject>Liver Circulation</subject><subject>Liver Neoplasms, Experimental - diagnostic imaging</subject><subject>Liver Neoplasms, Experimental - physiopathology</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Original Research</subject><subject>Perfusion Imaging - methods</subject><subject>Rabbits</subject><subject>Reproducibility of Results</subject><subject>Sensitivity and Specificity</subject><subject>Tomography, X-Ray Computed - methods</subject><subject>Tumors</subject><subject>Vasoconstrictor Agents - administration & dosage</subject><issn>0033-8419</issn><issn>1527-1315</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU2P0zAQhi0EYsvCmRvyBXEK6498OBekqrBspCIQKmdr4kyKkWMXO1m0f4Tfi6t2F7h4rHeeeW3NS8hLzt5yXqqrCIMNLt8546pWj8iKV6IpuOTVY7JiTMpClby9IM9S-sEYLyvVPCUXgtdSsoqtyO8vGMcl2eDpZkfXKWFKE_qZhpHubEoL0hucwnDnYbIm0evgXPhl_T7LB5itoes4Y7TgaOfPRnm08yYipCP3PmTPo7b2extm9FmlXUfzCfQr9L2d6dbeYqS7ZQqRfgoDuufkyQgu4YtzvSTfrj_sNjfF9vPHbrPeFqYUYi5Eycca6xIF9CjMULU9yhqGpkVRoxjY2HDGWlS8h2EwOFQCgNcNl43qlWHykrw7-R6WfsJM-DmC04doJ4h3OoDV_3e8_a734VbnBTeMHQ3enA1i-LlgmvVkk0HnwGNYklaqFHUrWZPJqxNpYkgp4vjwCmf6GKY-hanvw8wTr_793AN_n14GXp8BSAbcGMEbm_5yZcmavCL5B2FIrFg</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>WRIGHT, Kenneth C</creator><creator>RAVOORI, Murali K</creator><creator>DIXON, Katherine A</creator><creator>LIN HAN</creator><creator>SINGH, Sheela P</creator><creator>PING LIU</creator><creator>GUPTA, Sanjay</creator><creator>JOHNSON, Valen E</creator><creator>ZUXING KAN</creator><creator>KUNDRA, Vikas</creator><general>Radiological Society of North America</general><general>Radiological Society of North America, Inc</general><scope>IQODW</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></search><sort><creationdate>20110901</creationdate><title>Perfusion CT Assessment of Tissue Hemodynamics Following Hepatic Arterial Infusion of Increasing Doses of Angiotensin II in a Rabbit Liver Tumor Model</title><author>WRIGHT, Kenneth C ; RAVOORI, Murali K ; DIXON, Katherine A ; LIN HAN ; SINGH, Sheela P ; PING LIU ; GUPTA, Sanjay ; JOHNSON, Valen E ; ZUXING KAN ; KUNDRA, Vikas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-241f6e64e2abe2cd59be36ad79e26e2d0f71009e81baddced52aa1671378b8c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Angiotensin II - administration & dosage</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Flow Velocity</topic><topic>Contrast Media - administration & dosage</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Image Enhancement - methods</topic><topic>Infusions, Intralesional</topic><topic>Liver Circulation</topic><topic>Liver Neoplasms, Experimental - diagnostic imaging</topic><topic>Liver Neoplasms, Experimental - physiopathology</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Original Research</topic><topic>Perfusion Imaging - methods</topic><topic>Rabbits</topic><topic>Reproducibility of Results</topic><topic>Sensitivity and Specificity</topic><topic>Tomography, X-Ray Computed - methods</topic><topic>Tumors</topic><topic>Vasoconstrictor Agents - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WRIGHT, Kenneth C</creatorcontrib><creatorcontrib>RAVOORI, Murali K</creatorcontrib><creatorcontrib>DIXON, Katherine A</creatorcontrib><creatorcontrib>LIN HAN</creatorcontrib><creatorcontrib>SINGH, Sheela P</creatorcontrib><creatorcontrib>PING LIU</creatorcontrib><creatorcontrib>GUPTA, Sanjay</creatorcontrib><creatorcontrib>JOHNSON, Valen E</creatorcontrib><creatorcontrib>ZUXING KAN</creatorcontrib><creatorcontrib>KUNDRA, Vikas</creatorcontrib><collection>Pascal-Francis</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>Radiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WRIGHT, Kenneth C</au><au>RAVOORI, Murali K</au><au>DIXON, Katherine A</au><au>LIN HAN</au><au>SINGH, Sheela P</au><au>PING LIU</au><au>GUPTA, Sanjay</au><au>JOHNSON, Valen E</au><au>ZUXING KAN</au><au>KUNDRA, Vikas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Perfusion CT Assessment of Tissue Hemodynamics Following Hepatic Arterial Infusion of Increasing Doses of Angiotensin II in a Rabbit Liver Tumor Model</atitle><jtitle>Radiology</jtitle><addtitle>Radiology</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>260</volume><issue>3</issue><spage>718</spage><epage>726</epage><pages>718-726</pages><issn>0033-8419</issn><eissn>1527-1315</eissn><coden>RADLAX</coden><abstract>To investigate the effects of increasing doses of angiotensin II on hepatic hemodynamics in the normal rabbit liver and in hepatic VX2 tumors by using dynamic contrast material-enhanced perfusion computed tomography (CT).
This study was approved by the institutional animal care and use committee. Solitary hepatic VX2 tumors were implanted into 12 rabbits. In each animal, perfusion CT of the liver was performed before (at baseline) and after hepatic arterial infusion of varying doses (0.1-50.0 μg/mL) of angiotensin II. Images were acquired continuously for 80 seconds after the start of the intravenous contrast material administration. Blood flow (BF), blood volume (BV), mean transit time (MTT), and capillary permeability-surface area product were calculated for the tumor and the adjacent and distant normal liver tissue. Generalized linear mixed models were used to estimate the effects of angiotensin II dose on outcome measures.
Angiotensin II infusion increased contrast enhancement of the tumor and distal liver vessels. Tumor BF increased in a dose-dependent manner after administration of 0.5-25.0 μg/mL angiotensin II, but only the 2.5 μg/mL dose induced a significant increase in tumor BF compared with BF in the adjacent (68.0 vs 26.3 mL/min/100 g, P < .0001) and distant (68.0 vs 28.3 mL/min/100 g, P = .02) normal liver tissue. Tumor BV varied with angiotensin II dose but was greater than the BV of the adjacent and distant liver tissue at only the 2.5 μg/mL (4.8 vs 3.5 mL/100 g for adjacent liver [P < .0001], 4.8 vs 3.3 mL/100 g for distant liver [P = .0006]) and 10.0 μg/mL (4.9 vs 4.4 mL/100 g for adjacent liver [P = .007], 4.9 vs 4.3 mL/100 g for distant liver [P = .04]) doses. Tumor MTT was significantly shorter than the adjacent liver tissue MTT at angiotensin II doses of 2.5 μg/mL (9.7 vs 15.8 sec, P = .001) and 10.0 μg/mL (5.1 vs 13.2 sec, P = .007) and significantly shorter than the distant liver tissue MTT at 2.5 μg/mL only (9.7 vs 15.3 sec, P = .0006). The capillary permeability-surface area product for the tumor was higher than that for the adjacent liver tissue at the 2.5 μg/mL angiotensin II dose only (11.5 vs 8.1 mL/min/100 g, P = .01).
Perfusion CT enables a mechanistic understanding of angiotensin II infusion in the liver and derivation of the optimal effective dose. The 2.5 μg/mL angiotensin II dose increases perfusion in hepatic VX2 tumors versus that in adjacent and distant normal liver tissue primarily by constricting normal distal liver vessels and in turn increasing tumor BF and BV.</abstract><cop>Oak Brook, IL</cop><pub>Radiological Society of North America</pub><pmid>21633050</pmid><doi>10.1148/radiol.11101868</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Angiotensin II - administration & dosage Animals Biological and medical sciences Blood Flow Velocity Contrast Media - administration & dosage Gastroenterology. Liver. Pancreas. Abdomen Image Enhancement - methods Infusions, Intralesional Liver Circulation Liver Neoplasms, Experimental - diagnostic imaging Liver Neoplasms, Experimental - physiopathology Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Original Research Perfusion Imaging - methods Rabbits Reproducibility of Results Sensitivity and Specificity Tomography, X-Ray Computed - methods Tumors Vasoconstrictor Agents - administration & dosage |
| title | Perfusion CT Assessment of Tissue Hemodynamics Following Hepatic Arterial Infusion of Increasing Doses of Angiotensin II in a Rabbit Liver Tumor Model |
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