Comparison of dynamic contrast-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for evaluation of the effects of sorafenib in a rat model of hepatocellular carcinoma
To compare the accuracy of contrast-enhanced ultrasound (CEUS) and Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the assessment of changes in tissue vascularization as result of sorafenib treatment in a rat model of hepatocellular carcinoma (HCC). Male Buffalo rats with orthot...
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| Veröffentlicht in: | Magnetic resonance imaging 2019-04, Vol.57, p.156-164 |
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| creator | Muñoz, Nina M. Minhaj, Adeeb A. Maldonado, Kiersten L. Kingsley, Charles V. Cortes, Andrea C. Taghavi, Houra Polak, Urszula Mitchell, Jennifer M. Ensor, Joe E. Bankson, James A. Rashid, Asif Avritscher, Rony |
| description | To compare the accuracy of contrast-enhanced ultrasound (CEUS) and Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the assessment of changes in tissue vascularization as result of sorafenib treatment in a rat model of hepatocellular carcinoma (HCC).
Male Buffalo rats with orthotopic liver tumors treated daily with 7.5 mg/kg sorafenib via oral gavage for 2 weeks (n = 9) were subject to DCE-MRI and CEUS 2 weeks after tumor implantation - right before treatment initiation - and also after treatment completion - right before tumor harvest. Untreated animals (n = 10) were used as control. Tumor tissue sections were stained for hematoxylin-eosin, pimonidazole, and CD34 for quantitative assessment of necrosis, hypoxia, and microvessel density (MVD), respectively.
Of all the DCE-MRI parameters that were evaluated, only volume transfer constant (Ktrans) measurements were significantly lower in sorafenib-treated tumors (0.18 vs 0.33 min−1, p |
| doi_str_mv | 10.1016/j.mri.2018.11.012 |
| format | Article |
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Male Buffalo rats with orthotopic liver tumors treated daily with 7.5 mg/kg sorafenib via oral gavage for 2 weeks (n = 9) were subject to DCE-MRI and CEUS 2 weeks after tumor implantation - right before treatment initiation - and also after treatment completion - right before tumor harvest. Untreated animals (n = 10) were used as control. Tumor tissue sections were stained for hematoxylin-eosin, pimonidazole, and CD34 for quantitative assessment of necrosis, hypoxia, and microvessel density (MVD), respectively.
Of all the DCE-MRI parameters that were evaluated, only volume transfer constant (Ktrans) measurements were significantly lower in sorafenib-treated tumors (0.18 vs 0.33 min−1, p < 0.01), indicating a substantial decrease in vascular permeability caused by the therapy. This reduction was associated with decreased MVD (3.9 vs 10.8% CD34+ cells, p < 0.01), higher tumor necrosis (31.9 vs 21.8%, p < 0.001) and hypoxia (19.7 vs 10.5% pimonidazole binding, p < 0.01). Moreover, statistical analysis demonstrate significant correlation of DCE-MRI Ktrans with histopathologic tissue necrosis (r = −0.537, p < 0.05) and MVD (r = 0.599, p < 0.05). Interestingly, none of the CEUS measurements were significantly different between the control and treatment groups, and did not show statistical correlation with any of the histopathological parameters assessed (p > 0.05).
Sorafenib-induced reduction in vascular permeability in this preclinical model of HCC is detected more accurately through DCE-MRI than CEUS, and DCE-MRI parameters strongly correlate with histopathological changes in tissue vascularization and tissue necrosis.]]></description><identifier>ISSN: 0730-725X</identifier><identifier>EISSN: 1873-5894</identifier><identifier>DOI: 10.1016/j.mri.2018.11.012</identifier><identifier>PMID: 30465870</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Animals ; Biomarkers, Tumor ; Capillary Permeability ; Carcinoma, Hepatocellular - diagnostic imaging ; Carcinoma, Hepatocellular - pathology ; Cell Line, Tumor ; Contrast Media - chemistry ; Contrast-enhanced functional imaging ; Disease Models, Animal ; Hepatocellular carcinoma ; Hypoxia ; Image Processing, Computer-Assisted ; Liver Neoplasms - diagnostic imaging ; Liver Neoplasms - pathology ; Magnetic Resonance Imaging ; Male ; Necrosis ; Neovascularization, Pathologic ; Permeability ; Rats ; Sorafenib ; Sorafenib - chemistry ; Tissue perfusion ; Vascular permeability</subject><ispartof>Magnetic resonance imaging, 2019-04, Vol.57, p.156-164</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-b626103633bc0d43c7535c00d2ab4c3c50eac8b0dd512812a2f22d92a5519b723</citedby><cites>FETCH-LOGICAL-c419t-b626103633bc0d43c7535c00d2ab4c3c50eac8b0dd512812a2f22d92a5519b723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mri.2018.11.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30465870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Muñoz, Nina M.</creatorcontrib><creatorcontrib>Minhaj, Adeeb A.</creatorcontrib><creatorcontrib>Maldonado, Kiersten L.</creatorcontrib><creatorcontrib>Kingsley, Charles V.</creatorcontrib><creatorcontrib>Cortes, Andrea C.</creatorcontrib><creatorcontrib>Taghavi, Houra</creatorcontrib><creatorcontrib>Polak, Urszula</creatorcontrib><creatorcontrib>Mitchell, Jennifer M.</creatorcontrib><creatorcontrib>Ensor, Joe E.</creatorcontrib><creatorcontrib>Bankson, James A.</creatorcontrib><creatorcontrib>Rashid, Asif</creatorcontrib><creatorcontrib>Avritscher, Rony</creatorcontrib><title>Comparison of dynamic contrast-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for evaluation of the effects of sorafenib in a rat model of hepatocellular carcinoma</title><title>Magnetic resonance imaging</title><addtitle>Magn Reson Imaging</addtitle><description><![CDATA[To compare the accuracy of contrast-enhanced ultrasound (CEUS) and Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the assessment of changes in tissue vascularization as result of sorafenib treatment in a rat model of hepatocellular carcinoma (HCC).
Male Buffalo rats with orthotopic liver tumors treated daily with 7.5 mg/kg sorafenib via oral gavage for 2 weeks (n = 9) were subject to DCE-MRI and CEUS 2 weeks after tumor implantation - right before treatment initiation - and also after treatment completion - right before tumor harvest. Untreated animals (n = 10) were used as control. Tumor tissue sections were stained for hematoxylin-eosin, pimonidazole, and CD34 for quantitative assessment of necrosis, hypoxia, and microvessel density (MVD), respectively.
Of all the DCE-MRI parameters that were evaluated, only volume transfer constant (Ktrans) measurements were significantly lower in sorafenib-treated tumors (0.18 vs 0.33 min−1, p < 0.01), indicating a substantial decrease in vascular permeability caused by the therapy. This reduction was associated with decreased MVD (3.9 vs 10.8% CD34+ cells, p < 0.01), higher tumor necrosis (31.9 vs 21.8%, p < 0.001) and hypoxia (19.7 vs 10.5% pimonidazole binding, p < 0.01). Moreover, statistical analysis demonstrate significant correlation of DCE-MRI Ktrans with histopathologic tissue necrosis (r = −0.537, p < 0.05) and MVD (r = 0.599, p < 0.05). Interestingly, none of the CEUS measurements were significantly different between the control and treatment groups, and did not show statistical correlation with any of the histopathological parameters assessed (p > 0.05).
Sorafenib-induced reduction in vascular permeability in this preclinical model of HCC is detected more accurately through DCE-MRI than CEUS, and DCE-MRI parameters strongly correlate with histopathological changes in tissue vascularization and tissue necrosis.]]></description><subject>Animals</subject><subject>Biomarkers, Tumor</subject><subject>Capillary Permeability</subject><subject>Carcinoma, Hepatocellular - diagnostic imaging</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell Line, Tumor</subject><subject>Contrast Media - chemistry</subject><subject>Contrast-enhanced functional imaging</subject><subject>Disease Models, Animal</subject><subject>Hepatocellular carcinoma</subject><subject>Hypoxia</subject><subject>Image Processing, Computer-Assisted</subject><subject>Liver Neoplasms - diagnostic imaging</subject><subject>Liver Neoplasms - pathology</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Necrosis</subject><subject>Neovascularization, Pathologic</subject><subject>Permeability</subject><subject>Rats</subject><subject>Sorafenib</subject><subject>Sorafenib - chemistry</subject><subject>Tissue perfusion</subject><subject>Vascular permeability</subject><issn>0730-725X</issn><issn>1873-5894</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UcuO1DAQtBCIHRY-gAvykUtC246TjDih0fKQVuICEjerY3d2PErswU5W2k_j73A0CyfEyXLXo-0qxl4LqAWI9t2pnpOvJYi-FqIGIZ-wneg7Vel-3zxlO-gUVJ3UP67Yi5xPAKCl0s_ZlYKm1X0HO_brEOczJp9j4HHk7iHg7C23MSwJ81JROGKw5PiMd4GWAiUq3G3GfZn5cMcxuH8I1mkbxLWAY0yc7nFacfGXPcuROI0j2SVv1xwTjhT8wH3gyBMufI6Opg070hmXaGma1gkTt5isD3HGl-zZiFOmV4_nNfv-8ebb4XN1-_XTl8OH28o2Yr9UQytbAapVarDgGmU7rbQFcBKHxiqrgdD2AzinheyFRDlK6fYStRb7oZPqmr29-J5T_LlSXszs8_YcDBTXbKRQXdNK2UGhigvVpphzotGcUwkpPRgBZmvMnExpzGyNGSFMaaxo3jzar8NM7q_iT0WF8P5CoPLJe0_JZOtpi9inkp9x0f_H_jdwdKsc</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>Muñoz, Nina M.</creator><creator>Minhaj, Adeeb A.</creator><creator>Maldonado, Kiersten L.</creator><creator>Kingsley, Charles V.</creator><creator>Cortes, Andrea C.</creator><creator>Taghavi, Houra</creator><creator>Polak, Urszula</creator><creator>Mitchell, Jennifer M.</creator><creator>Ensor, Joe E.</creator><creator>Bankson, James A.</creator><creator>Rashid, Asif</creator><creator>Avritscher, Rony</creator><general>Elsevier 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>7X8</scope></search><sort><creationdate>201904</creationdate><title>Comparison of dynamic contrast-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for evaluation of the effects of sorafenib in a rat model of hepatocellular carcinoma</title><author>Muñoz, Nina M. ; Minhaj, Adeeb A. ; Maldonado, Kiersten L. ; Kingsley, Charles V. ; Cortes, Andrea C. ; Taghavi, Houra ; Polak, Urszula ; Mitchell, Jennifer M. ; Ensor, Joe E. ; Bankson, James A. ; Rashid, Asif ; Avritscher, Rony</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-b626103633bc0d43c7535c00d2ab4c3c50eac8b0dd512812a2f22d92a5519b723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Biomarkers, Tumor</topic><topic>Capillary Permeability</topic><topic>Carcinoma, Hepatocellular - diagnostic imaging</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell Line, Tumor</topic><topic>Contrast Media - chemistry</topic><topic>Contrast-enhanced functional imaging</topic><topic>Disease Models, Animal</topic><topic>Hepatocellular carcinoma</topic><topic>Hypoxia</topic><topic>Image Processing, Computer-Assisted</topic><topic>Liver Neoplasms - diagnostic imaging</topic><topic>Liver Neoplasms - pathology</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Necrosis</topic><topic>Neovascularization, Pathologic</topic><topic>Permeability</topic><topic>Rats</topic><topic>Sorafenib</topic><topic>Sorafenib - chemistry</topic><topic>Tissue perfusion</topic><topic>Vascular permeability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Muñoz, Nina M.</creatorcontrib><creatorcontrib>Minhaj, Adeeb A.</creatorcontrib><creatorcontrib>Maldonado, Kiersten L.</creatorcontrib><creatorcontrib>Kingsley, Charles V.</creatorcontrib><creatorcontrib>Cortes, Andrea C.</creatorcontrib><creatorcontrib>Taghavi, Houra</creatorcontrib><creatorcontrib>Polak, Urszula</creatorcontrib><creatorcontrib>Mitchell, Jennifer M.</creatorcontrib><creatorcontrib>Ensor, Joe E.</creatorcontrib><creatorcontrib>Bankson, James A.</creatorcontrib><creatorcontrib>Rashid, Asif</creatorcontrib><creatorcontrib>Avritscher, Rony</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>Magnetic resonance imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Muñoz, Nina M.</au><au>Minhaj, Adeeb A.</au><au>Maldonado, Kiersten L.</au><au>Kingsley, Charles V.</au><au>Cortes, Andrea C.</au><au>Taghavi, Houra</au><au>Polak, Urszula</au><au>Mitchell, Jennifer M.</au><au>Ensor, Joe E.</au><au>Bankson, James A.</au><au>Rashid, Asif</au><au>Avritscher, Rony</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of dynamic contrast-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for evaluation of the effects of sorafenib in a rat model of hepatocellular carcinoma</atitle><jtitle>Magnetic resonance imaging</jtitle><addtitle>Magn Reson Imaging</addtitle><date>2019-04</date><risdate>2019</risdate><volume>57</volume><spage>156</spage><epage>164</epage><pages>156-164</pages><issn>0730-725X</issn><eissn>1873-5894</eissn><abstract><![CDATA[To compare the accuracy of contrast-enhanced ultrasound (CEUS) and Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the assessment of changes in tissue vascularization as result of sorafenib treatment in a rat model of hepatocellular carcinoma (HCC).
Male Buffalo rats with orthotopic liver tumors treated daily with 7.5 mg/kg sorafenib via oral gavage for 2 weeks (n = 9) were subject to DCE-MRI and CEUS 2 weeks after tumor implantation - right before treatment initiation - and also after treatment completion - right before tumor harvest. Untreated animals (n = 10) were used as control. Tumor tissue sections were stained for hematoxylin-eosin, pimonidazole, and CD34 for quantitative assessment of necrosis, hypoxia, and microvessel density (MVD), respectively.
Of all the DCE-MRI parameters that were evaluated, only volume transfer constant (Ktrans) measurements were significantly lower in sorafenib-treated tumors (0.18 vs 0.33 min−1, p < 0.01), indicating a substantial decrease in vascular permeability caused by the therapy. This reduction was associated with decreased MVD (3.9 vs 10.8% CD34+ cells, p < 0.01), higher tumor necrosis (31.9 vs 21.8%, p < 0.001) and hypoxia (19.7 vs 10.5% pimonidazole binding, p < 0.01). Moreover, statistical analysis demonstrate significant correlation of DCE-MRI Ktrans with histopathologic tissue necrosis (r = −0.537, p < 0.05) and MVD (r = 0.599, p < 0.05). Interestingly, none of the CEUS measurements were significantly different between the control and treatment groups, and did not show statistical correlation with any of the histopathological parameters assessed (p > 0.05).
Sorafenib-induced reduction in vascular permeability in this preclinical model of HCC is detected more accurately through DCE-MRI than CEUS, and DCE-MRI parameters strongly correlate with histopathological changes in tissue vascularization and tissue necrosis.]]></abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>30465870</pmid><doi>10.1016/j.mri.2018.11.012</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Biomarkers, Tumor Capillary Permeability Carcinoma, Hepatocellular - diagnostic imaging Carcinoma, Hepatocellular - pathology Cell Line, Tumor Contrast Media - chemistry Contrast-enhanced functional imaging Disease Models, Animal Hepatocellular carcinoma Hypoxia Image Processing, Computer-Assisted Liver Neoplasms - diagnostic imaging Liver Neoplasms - pathology Magnetic Resonance Imaging Male Necrosis Neovascularization, Pathologic Permeability Rats Sorafenib Sorafenib - chemistry Tissue perfusion Vascular permeability |
| title | Comparison of dynamic contrast-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for evaluation of the effects of sorafenib in a rat model of hepatocellular carcinoma |
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