To see or not to see: non-invasive imaging for improved readout of drug treatment trials in the murine model of secondary alveolar echinococcosis

• Published in: Parasitology Vol. 144; no. 7; pp. 937 - 944
• Main Authors: GORGAS, D., MARREROS, N., RUFENER, R., HEMPHILL, A., LUNDSTRÖM-STADELMANN, B.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.06.2017
• Subjects: Abdomen; Albendazole - pharmacology; Alveoli; Animal models; Animals; Anticestodal Agents - pharmacology; Chemotherapy; Disease; Disease Models, Animal; Drugs; Echinococcosis; Echinococcosis - diagnostic imaging; Echinococcus multilocularis - drug effects; Female; Image processing; Image segmentation; In vivo methods and tests; Infections; Laboratory animals; Liver; Magnetic Resonance Imaging; Medical imaging; Mefloquine - pharmacology; Metastasis; Mice; Mice, Inbred BALB C; NMR; Nuclear magnetic resonance; Parasite Load - methods; Parasites; Parasitic diseases; Peritoneum; Principal components analysis; Rodents; Secondary infection; Statistical analysis; Substance abuse treatment; Tropical diseases; Ultrasonic imaging; Ultrasonography; Ultrasound; Weight measurement; Zoonoses; Echinococcus multilocularis; ultrasound scoring; magnetic resonance imaging; refinement; 3R
• ISSN: 0031-1820; 1469-8161
• DOI: 10.1017/S0031182017000051

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.