Monitoring Liver Tumor Ablation with MR Spectroscopy of Extracellular pH.

Abstract

HomeRadiology: Imaging CancerVol. 2, No. 2 PreviousNext Research HighlightsFree AccessMonitoring Liver Tumor Ablation with MR Spectroscopy of Extracellular pHGary D. LukerGary D. LukerGary D. LukerPublished Online:Mar 27 2020https://doi.org/10.1148/rycan.2020204007MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked InEmail Take-Away Points■ Major Focus: To monitor response of hepatocellular carcinoma to chemoembolization therapy using MR spectroscopy of extracellular pH.■ Key Result: Successful therapy reversed acidosis in liver tumors.■ Impact: Recovery of extracellular pH toward normal may provide a functional readout of treatment efficacy in hepatocellular carcinoma.Many patients with hepatocellular carcinoma cannot undergo surgical resection because of tumor size or concurrent medical problems. Transarterial chemoembolizaton (TACE) and other interventional ablation techniques offer alternatives for local control of disease, extending survival and potentially enabling surgical resection or liver transplantation. TACE alone typically fails to cause complete necrosis of hepatocellular carcinoma tumor nodules, motivating efforts to develop new imaging approaches to monitor response to therapy. Savic et al applied MR spectroscopy to noninvasively measure extracellular pH in liver tumors, using an established rabbit model of hepatocellular carcinoma. Hepatocellular carcinomas commonly utilize glycolysis to generate energy and a protumorigenic, immunosuppressive local environment. Glycolytic metabolism releases protons and lactate into the extracellular space, leading to reduced extracellular pH relative to adjacent normal liver tissue. As quantified by MR spectroscopy, TACE progressively reversed acidosis in the tumor environment, although values did not return completely to normal even in tumors with no pathologic evidence of residual disease. MR spectroscopy showed heterogeneous pH maps in incompletely treated tumors with areas of persistent acidic pH correlating with remaining viable tumor cells. The research team complemented MR spectroscopic data with multimodal MRI methods for cellularity (diffusion) and perfusion (contrast-enhanced T1-weighted images) combined with CT for distribution of lipiodol, a component of the TACE solution, in liver. Coregistered images showed similarities of lipiodol distribution, loss of cellularity, diminished perfusion, and reversal of acidic pH. Histologic analysis confirmed imaging data for tumor cellularity versus necrosis, vasculature, and reductions in markers of glycolytic metabolism. While the study included only preclinical animal models of therapy, the imaging methods could translate readily to clinical trials and applications. Combining MR spectroscopic mapping of extracellular pH as a marker of tumor metabolism with multimodal MRI and CT methods offers a highly promising, clinically translatable approach to monitor local ablation therapies used for hepatocellular carcinoma and likely other solid tumors.Highlighted ArticleSavic LJ, Schobert IT, Peters D, et al. Molecular imaging of extracellular tumor pH to reveal effects of locoregional therapy on liver cancer microenvironment. Clin Cancer Res 2020;26:428-438. doi: 10.1158/1078-0432.CCR-19-1702Highlighted ArticleSavic LJ, Schobert IT, Peters D, et al. Molecular imaging of extracellular tumor pH to reveal effects of locoregional therapy on liver cancer microenvironment. Clin Cancer Res 2020;26:428-438. doi: 10.1158/1078-0432.CCR-19-1702 Crossref, Medline, Google ScholarArticle HistoryPublished online: Mar 27 2020 FiguresReferencesRelatedDetailsRecommended Articles TACE Treatment in Patients with Sorafenib-treated Unresectable Hepatocellular Carcinoma in Clinical Practice: Final Analysis of GIDEONRadiology2016Volume: 279Issue: 2pp. 630-640Ablative Chemoembolization for Hepatocellular Carcinoma: A Prospective Phase I Case-Control Comparison with Conventional ChemoembolizationRadiology2017Volume: 287Issue: 1pp. 340-348Lack of Response to Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma: Abandon or Repeat?Radiology2021Volume: 298Issue: 3pp. 680-692Ischemia Induces Quiescence and Autophagy Dependence in Hepatocellular CarcinomaRadiology2017Volume: 283Issue: 3pp. 702-710MRI Assessment of Hepatocellular Carcinoma after Local-Regional Therapy: A Comprehensive ReviewRadiology: Imaging Cancer2020Volume: 2Issue: 1See More RSNA Education Exhibits Common Patterns of Change in ADC Histogram of Hepatocellular Carcinoma Lesions Following Transarterial Chemoembolization and Their Relationship with Patients’ PrognosisDigital Posters2019The Fast and the Furious: Rapid Progression of HCC After Locoregional Therapy — A Tri-Institutional Collaboration on Imaging PatternsDigital Posters2018A Practical Guide of Locoregional Treatment for Patients with Hepatocellular CarcinomaDigital Posters2019 RSNA Case Collection Hepatic AdenomatosisRSNA Case Collection2021Radioembolization of Liver Metastasis RSNA Case Collection2020Hepatic AngiosarcomaRSNA Case Collection2021 Vol. 2, No. 2 Metrics Downloaded 259 times Altmetric Score