Volume 46, Issue 1 pp. 248-256

Original Research

Multiparametric MR diffusion-weighted imaging for monitoring the ultra-early treatment effect of sorafenib in human hepatocellular carcinoma xenografts

Xin Chen MD,

Xin Chen MD

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

Department of Radiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China

The first two authors contributed equally to this work.

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Zelan Ma MD,

Zelan Ma MD

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

The first two authors contributed equally to this work.

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Yanqi Huang MD,

Yanqi Huang MD

orcid.org/0000-0002-0286-3964

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

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Lan He MPhil,

Lan He MPhil

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

School of Medicine, South China University of Technology, Guangzhou, China

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Cuishan Liang MD,

Cuishan Liang MD

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

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Changzheng Shi MD,

Changzheng Shi MD

Medical Imaging Center, First Affiliated Hospital, Jinan University, Guangzhou, China

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Zhongping Zhang MPhil,

Zhongping Zhang MPhil

GE Healthcare China, Guangzhou, China

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Changhong Liang MD,

Changhong Liang MD

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

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Zaiyi Liu MD,

Corresponding Author

Zaiyi Liu MD

[email protected]

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

Address reprint requests to: Z.L., Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou 510080, China. E-mail: [email protected]Search for more papers by this author

Xin Chen MD,

Xin Chen MD

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

Department of Radiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China

The first two authors contributed equally to this work.

Search for more papers by this author

Zelan Ma MD,

Zelan Ma MD

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

The first two authors contributed equally to this work.

Search for more papers by this author

Yanqi Huang MD,

Yanqi Huang MD

orcid.org/0000-0002-0286-3964

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

Search for more papers by this author

Lan He MPhil,

Lan He MPhil

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

School of Medicine, South China University of Technology, Guangzhou, China

Search for more papers by this author

Cuishan Liang MD,

Cuishan Liang MD

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

Search for more papers by this author

Changzheng Shi MD,

Changzheng Shi MD

Medical Imaging Center, First Affiliated Hospital, Jinan University, Guangzhou, China

Search for more papers by this author

Zhongping Zhang MPhil,

Zhongping Zhang MPhil

GE Healthcare China, Guangzhou, China

Search for more papers by this author

Changhong Liang MD,

Changhong Liang MD

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

Search for more papers by this author

Zaiyi Liu MD,

Corresponding Author

Zaiyi Liu MD

[email protected]

Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

First published: 26 October 2016

https://doi.org/10.1002/jmri.25527

Citations: 8

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Abstract

Purpose

To investigate the value of multiparametric magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) for monitoring the ultra-early (within 24 hours) treatment effect of sorafenib in human hepatocellular carcinoma (HCC) xenografts.

Materials and Methods

With institutional Animal Care and Use Committee approval, 16 BALB/c nude mice bearing subcutaneous HCC xenografts underwent serial Gaussian and non-Gaussian DWI at baseline and 1, 3, 6, 12, and 24 hours posttreatment using a 1.5T whole-body MRI system. Gaussian-DWI-derived apparent diffusion coefficient (ADC), D, D*, and f, and non-Gaussian-DWI-derived MD, MK, DDC, and α were calculated and compared between the control (n = 6) and sorafenib-treated groups (n = 10) with respect to each timepoint using Mann–Whitney or Wilcoxon signed-rank test. Results were validated by pathology.

Results

Compared to baseline, ADC and D at 1 hour posttreatment (P = 0.005 and P = 0.013, respectively) and MD and DDC at 3 hours posttreatment (P = 0.009 and P = 0.005, respectively) significantly decreased and remained lower through 12 hours of follow-up (P = 0.005–0.022), followed by recovery to baseline levels at 24 hours posttreatment (P = 0.139–0.646). MK significantly increased at 1 hour posttreatment (P = 0.013) and remained higher through 24 hours of follow-up (P = 0.009–0.028). No significant differences were found in D*, f, and α at different timepoints (P = 0.188–0.714). Light microscopy did not reveal abnormal findings until 3 hours posttreatment, when central patchy necrosis was observed; more prominent diffuse necrosis was observed at 24 hours. Electron microscopy revealed swollen mitochondria at 1 hour posttreatment and accumulation of intracellular autophagosomes from 3 to 24 hours posttreatment.

Conclusion

Multiparametric DWI might evaluate therapeutic effects of sorafenib in HCC, where metrics of ADC, D, and MK could potentially serve as imaging biomarkers for monitoring therapeutic effects as early as 1 hour after treatment.

Level of Evidence 1

Technical Efficacy: Stage 4

J. MAGN. RESON. IMAGING 2017;46:248–256

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Volume46, Issue1

July 2017

Pages 248-256

Multiparametric MR diffusion-weighted imaging for monitoring the ultra-early treatment effect of sorafenib in human hepatocellular carcinoma xenografts

Abstract

Purpose

Materials and Methods

Results

Conclusion

References

Citing Literature

References

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Multiparametric MR diffusion-weighted imaging for monitoring the ultra-early treatment effect of sorafenib in human hepatocellular carcinoma xenografts

Abstract

Purpose

Materials and Methods

Results

Conclusion

References

Citing Literature

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