TY - JOUR
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 M.
AU - Ensor, Joe E.
AU - Bankson, James A.
AU - Rashid, Asif
AU - Avritscher, Rony
N1 - Funding Information:
This research was funded through the generous support of the John S. Dunn Foundation via the Distinguished Chair in Diagnostic Imaging; the CPRIT Individual Investigator Award RP160229 (R.A.), and the NIH / NCI through M. D. Anderson's Cancer Center Support Grant CA016672 used by the Small Animal Imaging and the Flow Cytometry & Cellular Imaging Core Facilities.
Funding Information:
This research was funded through the generous support of the John S. Dunn Foundation via the Distinguished Chair in Diagnostic Imaging; the CPRIT Individual Investigator Award RP160229 (R.A.), and the NIH/NCI through M. D. Anderson's Cancer Center Support Grant CA016672 used by the Small Animal Imaging and the Flow Cytometry & Cellular Imaging Core Facilities.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/4
Y1 - 2019/4
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 (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). 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 (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). 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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U2 - 10.1016/j.mri.2018.11.012
DO - 10.1016/j.mri.2018.11.012
M3 - Article
C2 - 30465870
AN - SCOPUS:85057474071
SN - 0730-725X
VL - 57
SP - 156
EP - 164
JO - Magnetic Resonance Imaging
JF - Magnetic Resonance Imaging
ER -