title: Tumor vessel compression hinders perfusion of ultrasonographic contrast agents.
abstract: Contrast-enhanced ultrasound (CEUS) is an advanced approach to in vivo assessment of tumor vascularity and is being increasingly adopted in clinical oncology. It is based on 1- to 10 microm-sized gas microbubbles, which can cross the capillary beds of the lungs and are effective echo enhancers. It is known that high cell density, high transendothelial fluid exchange, and poorly functioning lymphatic circulation all provoke solid stress, which compresses vessels and drastically reduces tumor blood flow. Given their size, we supposed that the perfusion of microbubbles is affected by anatomic features of tumor vessels more than are contrast agents traditionally used in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Here, we compared dynamic information obtained from CEUS and DCE-MRI on two experimental tumor models exhibiting notable differences in vessel anatomy. We found that tumors with small, flattened vessels show a much higher resistance to microbubble perfusion than to MRI contrast agents, and appear scarcely vascularized at CEUS examination, despite vessel volume adequate for normal function. Thus, whereas CEUS alone could induce incorrect diagnosis when tumors have small or collapsed vessels, integrated analysis using CEUS and DCE-MRI allows in vivo identification of tumors with a vascular profile frequently associated with malignant phenotypes.
authors.affiliation: Section of Anatomy and Histology, Department of Morphological and Biomedical Sciences, University of Verona, Verona (VR), Italy. mirco@anatomy.univr.it
authors.forename: Mirco
authors.initials: M
authors.lastname: Galiè
authors.forename: Mirko
authors.initials: M
authors.lastname: D'Onofrio
authors.forename: Maura
authors.initials: M
authors.lastname: Montani
authors.forename: Augusto
authors.initials: A
authors.lastname: Amici
authors.forename: Laura
authors.initials: L
authors.lastname: Calderan
authors.forename: Pasquina
authors.initials: P
authors.lastname: Marzola
authors.forename: Donatella
authors.initials: D
authors.lastname: Benati
authors.forename: Flavia
authors.initials: F
authors.lastname: Merigo
authors.forename: Cristina
authors.initials: C
authors.lastname: Marchini
authors.forename: Andrea
authors.initials: A
authors.lastname: Sbarbati
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D002196:Capillaries / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003287:Contrast Media / Q000494:pharmacology; D019786:Gadolinium DTPA / Q000494:pharmacology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D015674:Mammary Neoplasms, Animal / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D045423:Microbubbles; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic; D010477:Perfusion; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D051381:Rats; D013997:Time Factors; D014463:Ultrasonography / Q000295:instrumentation* / Q000379:methods*
chemical_list: D000418:Albumins; D003287:Contrast Media; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019786:Gadolinium DTPA