Stephen J Hunt1, Terence Gade2, Michael C Soulen2, Stephen Pickup2, Chandra M Sehgal2. 1. 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. stephen.hunt@uphs.upenn.edu. 2. 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.
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.
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 murinemelanoma model. METHODS: Subcutaneous K1735 murinemelanoma 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.
Authors: Brett Z Fite; Azadeh Kheirolomoom; Josquin L Foiret; Jai W Seo; Lisa M Mahakian; Elizabeth S Ingham; Sarah M Tam; Alexander D Borowsky; Fitz-Roy E Curry; Katherine W Ferrara Journal: J Control Release Date: 2017-04-07 Impact factor: 9.776
Authors: Laith R Sultan; Julia C D'Souza; Mrigendra B Karmacharya; Stephen J Hunt; Angela K Brice; Terence Gade; Andrew Kw Wood; Chandra M Sehgal Journal: IEEE Int Ultrason Symp Date: 2020-11-17
Authors: Klazina Kooiman; Silke Roovers; Simone A G Langeveld; Robert T Kleven; Heleen Dewitte; Meaghan A O'Reilly; Jean-Michel Escoffre; Ayache Bouakaz; Martin D Verweij; Kullervo Hynynen; Ine Lentacker; Eleanor Stride; Christy K Holland Journal: Ultrasound Med Biol Date: 2020-03-10 Impact factor: 2.998