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      Quantitative Assessment of Tissue Perfusion in Hepatocellular Carcinoma Using Perflubutane Dynamic Contrast-Enhanced Ultrasonography: A Preliminary Study

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          Abstract

          Our purpose in this study was to assess the relationship between contrast signal intensity (CI) and concentration of perflubutane microbubbles in a phantom experiment, and to examine the feasibility of this technique for quantitative analysis of vascularity in hepatocellular carcinoma (HCC). Microbubble solutions of the perflubutane contrast agent were prepared by mixing with purified water. We examined the relationship between CI in dB units and the concentration. Moreover, seven HCC patients were examined using real-time dynamic contrast imaging. The perfusion index was calculated from time-intensity curves generated for both HCC and surrounding liver parenchyma. We observed a linear relationship between the CI dB and the concentration in the phantom study and a higher perfusion index in the HCC lesions relative to the surrounding liver parenchyma. Dynamic contrast-enhanced ultrasonography with perflubutane microbubbles, which exhibit linear and temporally stable characteristics under continuous ultrasound exposure, allows the collection of quantitative hemodynamic information regarding HCC.

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          Management of Hepatocellular Carcinoma in Japan: Consensus-Based Clinical Practice Guidelines Proposed by the Japan Society of Hepatology (JSH) 2010 Updated Version

          Masatoshi Kudo, M Kudo, Namiki Izumi … (2011)
          Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death not only in Japan but also worldwide. Clinical practice guidelines for HCC were first published in 2001 by the European Society of Study of the Liver (EASL) followed by the American Association for the Study of Liver Disease (AASLD) published in 2005 and updated in 2010. However, these guidelines have proven to be somewhat unsuitable for Japanese patients. In 2005, supported by the Japanese Ministry of Health, Labour and Welfare, evidence-based clinical practice guidelines for HCC were compiled in Japan. In 2009, a revised version of evidence-based guidelines was published. Based on both ‘evidence-based’ guidelines and the consensus of an expert panel on HCC, the Japan Society of Hepatology (JSH) published the Consensus-Based Clinical Practice Manual in 2007 and updated in 2010. In this article, the 2010 updated version of this manual, especially issues on prevention, surveillance, pathology, diagnosis, staging, and treatment algorithm are summarized.
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            Efficacy of perflubutane microbubble-enhanced ultrasound in the characterization and detection of focal liver lesions: phase 3 multicenter clinical trial.

            Fuminori Moriyasu, Kouichi Itoh (2009)
            The purpose of this study was to assess the efficacy and safety of contrast-enhanced ultrasound performed with perflubutane microbubbles in comparison with unenhanced ultrasound and dynamic CT in the characterization of focal liver lesions during the vascular phase of imaging and in the detection of lesions during the Kupffer phase. A total of 196 patients were enrolled at 15 centers in Japan. Vascular phase images were obtained before contrast injection until 1 minute after injection. Kupffer phase images were obtained 10 minutes after injection. Dual-phase CT was performed as determined by standard clinical practice at each center. Unenhanced ultrasound, contrast-enhanced ultrasound, and CT images were read by blinded reviewers, and the results they reached regarding characterization and detection were compared with reference standard findings made by onsite investigators. The safety observation period was 72 hours after contrast administration. Among the 190 patients included in the characterization analysis, the accuracy of contrast-enhanced ultrasound (88.9%) was significantly greater than that of unenhanced ultrasound (68.4%) and dynamic CT (80.5%) (p < 0.001 and p = 0.008). Among the 191 patients in the detection analysis, the efficacy of contrast-enhanced ultrasound in detection of lesions was significantly higher than that of unenhanced ultrasound and dynamic CT (p < 0.001 and p = 0.008), predominantly because more metastatic lesions were detected (both p < 0.001). In particular, contrast-enhanced ultrasound was superior to dynamic CT in the detection of metastatic lesions measuring 1 cm or smaller. The incidence of adverse events was 49.2% and that of adverse drug reactions was 10.4%. All adverse drug reactions were mild. Compared with unenhanced ultrasound and dynamic CT, contrast-enhanced ultrasound with perflubutane microbubbles improved diagnostic efficacy in both characterization and detection of focal liver lesions with no serious adverse drug reactions.
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              Measurement of tissue perfusion by dynamic computed tomography.

              Lynden K. Miles (1991)
              A method for quantifying tissue perfusion by dynamic computed tomography (CT) is described. By applying a nuclear medicine data processing technique to time-density data from a single-location dynamic CT sequence, tissue perfusion can be determined from the maximum gradient of the tissue time-density curve divided by the peak enhancement of the aorta. Using this method, splenic perfusion was measured at 1.2 ml min-1 ml-1, normal renal cortical perfusion at 2.5 ml min-1 ml-1 and normal renal medullary perfusion at 1.1 ml min-1 ml-1. Changes in cortical and medullary perfusion in renal failure and hypertension were demonstrated. The ability of dynamic CT to provide quantitative functional information is not well recognized and is potentially of value when studying structures, such as the renal cortex and medulla, that cannot be anatomically resolved by standard functional imaging techniques.
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                Author and article information

                Contributors
                Philippe L. Pereira: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Diagnostics (Basel)
                Journal ID (iso-abbrev): Diagnostics (Basel)
                Journal ID (publisher-id): diagnostics
                Title: Diagnostics
                Publisher: MDPI
                ISSN (Electronic): 2075-4418
                Publication date (Electronic): 20 May 2015
                Publication date Collection: June 2015
                Volume: 5
                Issue: 2
                Pages: 210-218
                Affiliations
                [1 ]Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80, Kodatsuno, Kanazawa, Ishikawa 9200942, Japan; E-Mail: nohno@ 123456med.kanazawa-u.ac.jp
                [2 ]Department of Radiology, Tonami General Hospital, 16-1, Shintomicho, Tonami, Toyama 9391395, Japan; E-Mails: karkulaiset.0323@ 123456gmail.com (M.Y.); mayu.narikawa@ 123456med.tonami.toyama.jp (M.N.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: ramiyati@ 123456mhs.mp.kanazawa-u.ac.jp ; Tel./Fax: +81-76-265-2540.
                Article
                Publisher ID: diagnostics-05-00210
                DOI: 10.3390/diagnostics5020210
                PMC ID: 4665596
                SO-VID: 7c70e06c-cb56-49de-9179-d91575a17981
                Copyright © © 2015 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 19 January 2015
                Date accepted : 14 May 2015
                Categories
                Subject: Article

                Keywords: contrast-enhanced ultrasonography (ceus),perflubutane,low mechanical index,hepatocellular carcinoma (hcc),perfusion index
                Data availability:
                Keywords: contrast-enhanced ultrasonography (ceus), perflubutane, low mechanical index, hepatocellular carcinoma (hcc), perfusion index

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