title: Multiparametric human hepatocellular carcinoma characterization and therapy response evaluation by hyperpolarized (13) C MRSI.
abstract: Individual tumor characterization and treatment response monitoring based on current medical imaging methods remain challenging. This work investigates hyperpolarized (13) C compounds in an orthotopic rat hepatocellular carcinoma (HCC) model system before and after transcatheter arterial embolization (TAE). HCC ranks amongst the top six most common cancer types in humans and accounts for one-third of cancer-related deaths worldwide. Early therapy response monitoring could aid in the development of personalized therapy approaches and novel therapeutic concepts. Measurements with selectively (13) C-labeled and hyperpolarized urea, pyruvate and fumarate were performed in tumor-bearing rats before and after TAE. Two-dimensional, slice-selective MRSI was used to obtain spatially resolved maps of tumor perfusion, cell energy metabolic conversion rates and necrosis, which were additionally correlated with immunohistochemistry. All three injected compounds, taken together with their respective metabolites, exhibited similar signal distributions. TAE induced a decrease in blood flow into the tumor and thus a decrease in tumor to muscle and tumor to liver ratios of urea, pyruvate and its metabolites, alanine and lactate, whereas conversion rates remained stable or increased on TAE in tumor, muscle and liver tissue. Conversion from fumarate to malate successfully indicated individual levels of necrosis, and global malate signals after TAE suggested the washout of fumarase or malate itself on necrosis. This study presents a combination of three (13) C compounds as novel candidate biomarkers for a comprehensive characterization of genetically and molecularly diverse HCC using hyperpolarized MRSI, enabling the simultaneous detection of differences in tumor perfusion, metabolism and necrosis. If, as in this study, bolus dynamics are not required and qualitative perfusion information is sufficient, the desired information could be extracted from hyperpolarized fumarate and pyruvate alone, acquired at higher fields with better spectral separation. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Institute of Medical Engineering, Technische Universität München, Garching, Germany.|Department of Chemistry, Technische Universität München, Garching, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Düwel
authors.affiliation: Institute of Medical Engineering, Technische Universität München, Garching, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Durst
authors.affiliation: Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Concetta V
authors.initials: CV
authors.lastname: Gringeri
authors.affiliation: Institute of Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kosanke
authors.affiliation: Institute of Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gross
authors.affiliation: GE Global Research, Garching, Germany.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Janich
authors.affiliation: Institute of Medical Engineering, Technische Universität München, Garching, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haase
authors.affiliation: Department of Chemistry, Technische Universität München, Garching, Germany.
authors.forename: Steffen J
authors.initials: SJ
authors.lastname: Glaser
authors.affiliation: Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.affiliation: GE Global Research, Garching, Germany.
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Schulte
authors.affiliation: Institute of Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Rickmer
authors.initials: R
authors.lastname: Braren
authors.affiliation: GE Global Research, Garching, Germany.
authors.forename: Marion I
authors.initials: MI
authors.lastname: Menzel
mesh_terms: D000818:Animals; D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000379:methods*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy*; D045744:Cell Line, Tumor; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods; D057054:Molecular Imaging / Q000379:methods*; D009930:Organic Chemicals / Q000378:metabolism*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D009930:Organic Chemicals
keywords: cancer therapy responses; hepatobiliary cancers; hyperpolarized 13C; spectroscopic imaging