title: To see or not to see: non-invasive imaging for improved readout of drug treatment trials in the murine model of secondary alveolar echinococcosis.
abstract: Alveolar echinococcosis (AE) is an emerging zoonotic disease caused by the cestode Echinococcus multilocularis. The secondary infection model of AE is based on intraperitoneal injection of disease-causing metacestodes into the peritoneal cavity of mice, which allows investigations on novel drugs or immunotherapeutical treatment options in vivo. So far, such in vivo studies assessed exclusively the parasite weight at the endpoint of a given treatment period. We here developed an ultrasound (US)-based scoring system that allows to follow-up parasite development in the living animal, and provides insights into parasite growth during the treatment phase. By this method a statistically significant difference between untreated and medicated mice with E. multilocularis infection was observed at 2 months post-infection, and the growth curve of the parasite load was described by a linear mixed model. High correlation and similar levels of variation were observed for the standard method based on parasite weight measurement, the novel US-based scoring system, as well volume segmentation by post-mortem magnetic resonance imaging. Thus, US-based scoring in the live animal has the potential to assist the 3R concept by contributing to the refinement and reduction of animal use in experimental echinococcosis.
authors.affiliation: Division of Clinical Radiology, Vetsuisse-Faculty,Länggassstrasse 128, 3012 Berne,Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Gorgas
authors.affiliation: Centre for Fish and Wildlife Health,Vetsuisse-Faculty, Länggassstrasse 122,3012 Berne,Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Marreros
authors.affiliation: Vetsuisse-Faculty,Institute of Parasitology,Länggassstrasse 122, 3012 Berne,Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Rufener
authors.affiliation: Vetsuisse-Faculty,Institute of Parasitology,Länggassstrasse 122, 3012 Berne,Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Hemphill
authors.affiliation: Vetsuisse-Faculty,Institute of Parasitology,Länggassstrasse 122, 3012 Berne,Switzerland.
authors.forename: B
authors.identifier: http://orcid.org/0000-0003-2672-5766
authors.initials: B
authors.lastname: Lundström-Stadelmann
mesh_terms: D015766:Albendazole / Q000494:pharmacology; D000818:Animals; D000923:Anticestodal Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004443:Echinococcosis / Q000000981:diagnostic imaging*; D048210:Echinococcus multilocularis / Q000187:drug effects*; D005260:Female; D008279:Magnetic Resonance Imaging; D015767:Mefloquine / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D059208:Parasite Load / Q000379:methods*; D014463:Ultrasonography
chemical_list: D000923:Anticestodal Agents; D015766:Albendazole; D015767:Mefloquine
keywords: 
                 Echinococcus multilocularis
              ; 3R; magnetic resonance imaging; refinement; ultrasound scoring