title: Longitudinal, in vivo assessment of invasive pulmonary aspergillosis in mice by computed tomography and magnetic resonance imaging.
abstract: Invasive aspergillosis is an emerging threat to public health due to the increasing use of immune suppressive drugs and the emergence of resistance against antifungal drugs. To deal with this threat, research on experimental disease models provides insight into the pathogenesis of infections caused by susceptible and resistant Aspergillus strains and by assessing their response to antifungal drugs. However, standard techniques used to evaluate infection in a preclinical setting are severely limited by their invasive character, thereby precluding evaluation of disease extent and therapy effects in the same animal. To enable non-invasive, longitudinal monitoring of invasive pulmonary aspergillosis in mice, we optimized computed tomography (CT) and magnetic resonance imaging (MRI) techniques for daily follow-up of neutropenic BALB/c mice intranasally infected with A. fumigatus spores. Based on the images, lung parameters (signal intensity, lung tissue volume and total lung volume) were quantified to obtain objective information on disease onset, progression and extent for each animal individually. Fungal lung lesions present in infected animals were successfully visualized and quantified by both CT and MRI. By using an advanced MR pulse sequence with ultrashort echo times, pathological changes within the infected lung became visually and quantitatively detectable at earlier disease stages, thereby providing valuable information on disease onset and progression with high sensitivity. In conclusion, these non-invasive imaging techniques prove to be valuable tools for the longitudinal evaluation of dynamic disease-related changes and differences in disease severity in individual animals that might be readily applied for rapid and cost-efficient drug screening in preclinical models in vivo.
authors.affiliation: Biomedical MRI Unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Poelmans
authors.affiliation: Biomedical MRI Unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Amy
authors.initials: A
authors.lastname: Hillen
authors.affiliation: Biomedical MRI Unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Vanherp
authors.affiliation: Biomedical MRI Unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Kristof
authors.initials: K
authors.lastname: Govaerts
authors.affiliation: Hematology, Department of Immunology and Biology, KU Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.affiliation: Biomedical MRI Unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.|Radiology, Department of Imaging and Pathology, UZ Leuven, Leuven, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Dresselaers
authors.affiliation: Biomedical MRI Unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.affiliation: Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Lagrou
authors.affiliation: Biomedical MRI Unit/ MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Greetje
authors.identifier: 0000-0002-5633-3993
authors.initials: G
authors.lastname: Vande Velde
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000302:isolation & purification / Q000472:pathogenicity; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D018450:Disease Progression; D005690:Galactose / Q000031:analogs & derivatives; D055744:Invasive Pulmonary Aspergillosis / Q000000981:diagnostic imaging* / Q000382:microbiology; D008137:Longitudinal Studies; D008168:Lung / Q000000981:diagnostic imaging / Q000382:microbiology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008351:Mannans / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013172:Spores, Fungal / Q000302:isolation & purification / Q000472:pathogenicity; D014057:Tomography, X-Ray Computed
chemical_list: D008351:Mannans; C012990:galactomannan; D005690:Galactose