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Sci Rep. 2017 May 26;7(1):2452. doi: 10.1038/s41598-017-02706-z.

Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging.

Author information

1
Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
2
Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
3
Sorbonne Universités, UPMC, Department of Radiology, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
4
Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
5
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
6
Oncological Science, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
7
Department of Medicine/Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
8
Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States. bachir.taouli@mountsinai.org.
9
Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. bachir.taouli@mountsinai.org.

Abstract

Tumour heterogeneity poses a significant challenge for treatment stratification. The goals of this study were to quantify heterogeneity in hepatocellular carcinoma (HCC) using multiparametric magnetic resonance imaging (mpMRI), and to report preliminary data correlating quantitative MRI parameters with advanced histopathology and gene expression in a patient subset. Thirty-two HCC patients with 39 HCC lesions underwent mpMRI including diffusion-weighted imaging (DWI), blood-oxygenation-level-dependent (BOLD), tissue-oxygenation-level-dependent (TOLD) and dynamic contrast-enhanced (DCE)-MRI. Histogram characteristics [central tendency (mean, median) and heterogeneity (standard deviation, kurtosis, skewness) MRI parameters] in HCC and liver parenchyma were compared using Wilcoxon signed-rank tests. Histogram data was correlated between MRI methods in all patients and with histopathology and gene expression in 14 patients. HCCs exhibited significantly higher intra-tissue heterogeneity vs. liver with all MRI methods (P < 0.030). Although central tendency parameters showed significant correlations between MRI methods and with each of histopathology and gene expression, heterogeneity parameters exhibited additional complementary correlations between BOLD and DCE-MRI and with histopathologic hypoxia marker HIF1α and gene expression of Wnt target GLUL, pharmacological target FGFR4, stemness markers EPCAM and KRT19 and immune checkpoint PDCD1. Histogram analysis combining central tendency and heterogeneity mpMRI features is promising for non-invasive HCC characterization on the imaging, histologic and genomics levels.

PMID:
28550313
PMCID:
PMC5446396
DOI:
10.1038/s41598-017-02706-z
[Indexed for MEDLINE]
Free PMC Article

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