ICUS Weekly News Monitor 2-6-2015

1.  Journal of Ultrasound in Medicine,  Feb 1, 2015,  Dynamic Contrast-Enhanced Ultrasound for Quantification of Tissue Perfusion     Authors: Eckhart Fröhlich, MD et al
 
2.  Journal of Ultrasound in Medicine,  Feb 1, 2015,  Antivascular Ultrasound Therapy: Magnetic Resonance Imaging Validation and Activation of the Immune Response in Murine Melanoma     Authors: Stephen J. Hunt, MD, PhD, et al
 
3.  International Journal of Pharmaceutics,  Jan 1, 2015,  Development of an ultrasound sensitive oxygen carrier for oxygen delivery to hypoxic tissue     Authors: John R. Eisenbrey, et al
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Journal of Ultrasound in Medicine
doi: 10.7863/ultra.34.2.179   JUM February 1, 2015   vol. 34  no. 2  179-196
Feb 1, 2015
 
Dynamic Contrast-Enhanced Ultrasound for Quantification of Tissue Perfusion
 
Eckhart Fröhlich, MD, Reinhold Muller, PhD, Xin-Wu Cui, PhD, Dagmar Schreiber-Dietrich, MD and Christoph F. Dietrich, MD, PhD⇑
 
+ Author Affiliations
Department of Internal Medicine I, Karl-Olga-Krankenhaus Stuttgart, Academic Teaching Hospital of the University of Ulm, Germany (E.F.); Tropical Health Solutions Pty, Ltd, and Anton-Breinl Center, James Cook University, Townsville City, Queensland, Australia (R.M.); Sino-German Research Center of Ultrasound in Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, and Department of Internal Medicine II, Caritas-Krankenhaus Bad Mergentheim, Academic Teaching Hospital of the University of Würzburg, Bad Mergentheim, Germany (X.-W.C., D.S.-D., C.F.D.).
 
Address correspondence to Christoph F. Dietrich, MD, PhD, Sino-German Research Center of Ultrasound in Medicine, First Affiliated Hospital of Zhengzhou University, Jianshe East Rd 1, 450052 Zhengzhou, China. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
 
Abstract
 
Dynamic contrast-enhanced ultrasound (US) imaging, a technique that uses microbubble contrast agents with diagnostic US, has recently been technically summarized and reviewed by a European Federation of Societies for Ultrasound in Medicine and Biology position paper. However, the practical applications of this imaging technique were not included. This article reviews and discusses the published literature on the clinical use of dynamic contrast-enhanced US. This review finds that dynamic contrast-enhanced US imaging is the most sensitive cross-sectional real-time method for measuring the perfusion of parenchymatous organs noninvasively. It can measure parenchymal perfusion and therefore can differentiate between benign and malignant tumors. The most important routine clinical role of dynamic contrast-enhanced US is the prediction of tumor responses to chemotherapy within a very short time, shorter than using Response Evaluation Criteria in Solid Tumors criteria. Other applications found include quantifying the hepatic transit time, diabetic kidneys, transplant grafts, and Crohn disease. In addition, the problems involved in using dynamic contrast-enhanced US are discussed.
 
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Journal of Ultrasound in Medicine
doi: 10.7863/ultra.34.2.275   JUM February 1, 2015   vol. 34  no. 2  275-287
Feb 1, 2015
 
Antivascular Ultrasound Therapy
Magnetic Resonance Imaging Validation and Activation of the Immune Response in Murine Melanoma
 
Authors: Stephen J. Hunt, MD, PhD⇑, Terence Gade, MD, PhD,; Michael C. Soulen, MD, Stephen Pickup, PhD and Chandra M. Sehgal, PhD
 
+ Author Affiliations
 
Department of Radiology (S.J.H., T.G., M.C.S., S.P., C.M.S.), Penn Image-Guided Interventions Laboratory (S.J.H., T.G.), and Penn Ultrasound Research Laboratory (S.J.H., C.M.S.), Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania USA.
 
Address correspondence to Stephen J. Hunt, MD, PhD, Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce St, 1 Silverstein, Philadelphia, PA 19104 USA. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
 
 
Abstract
 
Objectives—The purpose of this study was to investigate the treatment effects of antivascular ultrasound (US) with dynamic contrast-enhanced magnetic resonance imaging (MRI), contrast-enhanced sonography, and histopathologic analysis in a murine melanoma model.
 
Methods—Subcutaneous K1735 murine melanoma tumors were grown in syngeneic C3H/HeN mice. Quantitative tumor perfusion characteristics were measured before antivascular US treatment with both dynamic contrast-enhanced MRI and high-resolution contrast-enhanced sonography. Tumors were subsequently treated with 1 or 3 minutes of continuous low-intensity US after intravenous administration of a US contrast agent. Treatment effects were assessed by quantitative dynamic contrast-enhanced MRI, contrast-enhanced sonography, histopathologic analysis, and immunohistochemistry.
 
Results—Low-intensity antivascular US treatment resulted in approximately a doubling and tripling of the time to peak enhancement on dynamic contrast-enhanced MRI in the 1- and 3-minute treatment groups, respectively, along with a significant decrease in contrast wash-out (P < .01). There was a potent reduction in tumor perfusion on contrast-enhanced sonography, with approximately 40% and 70% reductions in the tumor area perfused as assessed by contrast-enhanced sonography after 1 (P < .05) and 3 (P < .01) minutes of antivascular US. The pathologic and histologic changes spatially correlated with the regions of diminished perfusion seen on contrast-enhanced sonography and dynamic contrast-enhanced MRI. Antivascular US therapy resulted in a significant increase in the number of hypoxia-inducible factor 1A+ cells, indicating tumor hypoxia (P < .01), and of CD45+/CD3+ cells in tumors after treatment, in keeping with increased T-cell infiltration (P < .01).
 
Conclusions—Antivascular US treatment effects extend beyond direct cytotoxicity from hemorrhagic necrosis to include ischemia-mediated cytotoxicity, enhanced small molecule retention, and intratumoral immune activation.
 
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International Journal of Pharmaceutics
478 (2015) 361–367
Jan 1, 2015
 
Development of an ultrasound sensitive oxygen carrier for oxygen delivery to hypoxic tissue
 
Authors: John R. Eisenbrey a,*, Lorenzo Albala b, Michael R. Kramer a,c, Nick Daroshefski b, David Brownb, Ji-Bin Liu a, Maria Stanczak a, Patrick O’Kane a, Flemming Forsberg a, Margaret A. Wheatley b
 
a. Department of Radiology, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA 19107, USA
b. School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA
c. Temple University School of Medicine, Temple University, Philadelphia, PA 19140, USA
 
Abstract
Radiation therapy is frequently used in the treatment of malignancies, but tumors are often more resistant than the surrounding normal tissue to radiation effects, because the tumor microenvironment is hypoxic. This manuscript details the fabrication and characterization of an ultrasound-sensitive,injectable oxygen microbubble platform (SE61O2) for overcoming tumor hypoxia. SE61O2 was fabricated by first sonicating a mixture of Span 60 and water-soluble vitamin E purged with perfluorocarbon gas.SE61O2 microbubbles were separated from the foam by flotation, then freeze dried under vacuum to remove all perfluorocarbon, and reconstituted with oxygen. Visually, SE61O2 microbubbles were smooth, spherical, with an average diameter of 3.1 mm and were reconstituted to a concentration of 6.5 E7 microbubbles/ml. Oxygen-filled SE61O2 provides 16.9 1.0 dB of enhancement at a dose of 880 ml/l (5.7 E7 microbubbles/l) with a half-life under insonation of approximately 15 min. In in vitro release experiments, 2 ml of SE61O2 (1.3 E8 microbubbles) triggered with ultrasound was found to elevate oxygen partial pressures of 100 ml of degassed saline 13.8 mmHg more than untriggered bubbles and 20.6 mmHg more than ultrasound triggered nitrogen-filled bubbles. In preliminary in vivo delivery experiments, triggered SE61O2 resulted in a 30.4 mmHg and 27.4 mmHg increase in oxygen partial pressures in two breast tumor mouse xenografts.

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