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

Nina M. Muñoz, Adeeb A. Minhaj, Kiersten L. Maldonado, Charles V. Kingsley, Andrea C. Cortes, Houra Taghavi, Urszula Polak, Jennifer Mitchell, Joe E. Ensor, James A Bankson, Asif Rashid, Rony Avritscher

Research output: Contribution to journalArticle

Abstract

Objectives: 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). Methods: 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. Results: Of all the DCE-MRI parameters that were evaluated, only volume transfer constant (K trans ) 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 K trans 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)156-164
Number of pages9
JournalMagnetic Resonance Imaging
Volume57
DOIs
StatePublished - Apr 1 2019

Fingerprint

Magnetic resonance
Rats
Tumors
Hepatocellular Carcinoma
Ultrasonics
Magnetic Resonance Imaging
Imaging techniques
Tissue
Necrosis
Neoplasms
Capillary Permeability
Microvessels
Buffaloes
Hematoxylin
Eosine Yellowish-(YS)
Liver
sorafenib
Statistical methods
Animals

Keywords

  • Contrast-enhanced functional imaging
  • Hepatocellular carcinoma
  • Sorafenib
  • Tissue perfusion
  • Vascular permeability

ASJC Scopus subject areas

  • Biophysics
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging

Cite this

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. / Muñoz, Nina M.; Minhaj, Adeeb A.; Maldonado, Kiersten L.; Kingsley, Charles V.; Cortes, Andrea C.; Taghavi, Houra; Polak, Urszula; Mitchell, Jennifer; Ensor, Joe E.; Bankson, James A; Rashid, Asif; Avritscher, Rony.

In: Magnetic Resonance Imaging, Vol. 57, 01.04.2019, p. 156-164.

Research output: Contribution to journalArticle

Muñoz, Nina M. ; Minhaj, Adeeb A. ; Maldonado, Kiersten L. ; Kingsley, Charles V. ; Cortes, Andrea C. ; Taghavi, Houra ; Polak, Urszula ; Mitchell, Jennifer ; Ensor, Joe E. ; Bankson, James A ; Rashid, Asif ; Avritscher, Rony. / 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. In: Magnetic Resonance Imaging. 2019 ; Vol. 57. pp. 156-164.
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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",
abstract = "Objectives: 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). Methods: 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. Results: Of all the DCE-MRI parameters that were evaluated, only volume transfer constant (K trans ) 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 K trans 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). Conclusions: 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.",
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author = "Mu{\~n}oz, {Nina M.} and Minhaj, {Adeeb A.} and Maldonado, {Kiersten L.} and Kingsley, {Charles V.} and Cortes, {Andrea C.} and Houra Taghavi and Urszula Polak and Jennifer Mitchell and Ensor, {Joe E.} and Bankson, {James A} and Asif Rashid and Rony Avritscher",
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T1 - 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

AU - Muñoz, Nina M.

AU - Minhaj, Adeeb A.

AU - Maldonado, Kiersten L.

AU - Kingsley, Charles V.

AU - Cortes, Andrea C.

AU - Taghavi, Houra

AU - Polak, Urszula

AU - Mitchell, Jennifer

AU - Ensor, Joe E.

AU - Bankson, James A

AU - Rashid, Asif

AU - Avritscher, Rony

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Objectives: 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). Methods: 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. Results: Of all the DCE-MRI parameters that were evaluated, only volume transfer constant (K trans ) 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 K trans 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). Conclusions: 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.

AB - Objectives: 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). Methods: 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. Results: Of all the DCE-MRI parameters that were evaluated, only volume transfer constant (K trans ) 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 K trans 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). Conclusions: 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.

KW - Contrast-enhanced functional imaging

KW - Hepatocellular carcinoma

KW - Sorafenib

KW - Tissue perfusion

KW - Vascular permeability

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